Special Issue "Recent Advances and Clinical Outcomes of Kidney Transplantation"

A special issue of Journal of Clinical Medicine (ISSN 2077-0383). This special issue belongs to the section "Nephrology & Urology".

Deadline for manuscript submissions: closed (31 December 2019).

Special Issue Editors

Dr. Charat Thongprayoon
Website
Guest Editor
Dr. Wisit Cheungpasitporn
Website
Guest Editor
Dr. Napat Leeaphorn
Website
Guest Editor
Department of Nephrology, Department of Medicine, Saint Luke's Health System, Kansas City, MO, USA
Interests: kidney transplantation; observational studies; statistical analysis; epidemiology

Special Issue Information

Dear Colleagues,

Advances in immunosuppression and kidney transplant techniques have led to significant improvements in the short-term survival of the renal allograft. Long-term graft survival, however, has relatively lagged behind and has now become one of the main problems in kidney transplantation.

In this Special Issue, we are making a call to action to stimulate researchers and clinicians to submit their invaluable studies on kidney transplantation, including works on issues related to donors, allograft, and patient survival following transplantation that will provide additional knowledge and skills in the field of transplantation research, ultimately to improve outcomes after kidney transplantation. Original investigations, review articles, and short communications are especially welcome.

Potential topics include, but are not limited to, the following:

ABO-Incompatible Kidney Transplant Outcomes
Advances in Renal Transplant Immunosuppression
Advances in Kidney Procurement and Transplantation  
Antibody-Mediated Rejection: New Approaches to Prevention and Management
APOL1 Genotype and Kidney Transplantation Outcomes
BK Virus Nephropathy and Kidney Transplantation
Bone Disease after Renal Transplantation
Cardiovascular complications after renal transplantation
Cell-Free DNA and Active Rejection in Renal Allografts
Clinical outcomes of kidney transplantation in older end-stage renal disease patients
Donor-specific Antibody and Graft Outcomes in Kidney Transplant Recipients.
Evaluation of the living kidney donor candidate
Infectious complications after kidney transplantation
Combined Liver–Kidney Transplantation
Management of acute rejection of kidney allograft
Pancreas and Kidney Transplants: New Lease on Life
Pediatric kidney transplantation in the New Era
Post-transplantation diabetes in kidney transplant recipients
Post-Transplant Lymphoproliferative Disorder in Kidney Transplant Recipients
Recent Advances in Perioperative Management for Kidney Transplantation
Recurrent glomerulonephritis after kidney transplantation
Risks and complications in living kidney donors
Role of Procurement Biopsies in Acceptance Decisions for Kidneys Retrieved for Transplantation
Treatment of Chronic Antibody-Mediated Rejection after Kidney Transplantation

Dr. Charat Thongprayoon
Dr. Wisit Cheungpasitporn
Dr. Napat Leeaphorn
Guest Editor
s

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Journal of Clinical Medicine is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2000 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • acute rejection
  • BK virus nephropathy
  • donor-specific antibody
  • immunosuppression
  • kidney donor
  • kidney transplantation
  • organ procurement
  • renal transplantation
  • post-transplant lymphoproliferative disorder
  • transplantation

Published Papers (43 papers)

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Editorial

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Open AccessEditorial
Recent Advances and Clinical Outcomes of Kidney Transplantation
J. Clin. Med. 2020, 9(4), 1193; https://doi.org/10.3390/jcm9041193 - 22 Apr 2020
Cited by 1
Abstract
Recent advances in surgical, immunosuppressive and monitoring protocols have led to the significant improvement of overall one-year kidney allograft outcomes. Nonetheless, there has not been a significant change in long-term kidney allograft outcomes. In fact, chronic and acute antibody-mediated rejection (ABMR) and non-immunological [...] Read more.
Recent advances in surgical, immunosuppressive and monitoring protocols have led to the significant improvement of overall one-year kidney allograft outcomes. Nonetheless, there has not been a significant change in long-term kidney allograft outcomes. In fact, chronic and acute antibody-mediated rejection (ABMR) and non-immunological complications following kidney transplantation, including multiple incidences of primary kidney disease, as well as complications such as cardiovascular diseases, infections, and malignancy are the major factors that have contributed to the failure of kidney allografts. The use of molecular techniques to enhance histological diagnostics and noninvasive surveillance are what the latest studies in the field of clinical kidney transplant seem to mainly focus upon. Increasingly innovative approaches are being used to discover immunosuppressive methods to overcome critical sensitization, prevent the development of anti-human leukocyte antigen (HLA) antibodies, treat chronic active ABMR, and reduce non-immunological complications following kidney transplantation, such as the recurrence of primary kidney disease and other complications, such as cardiovascular diseases, infections, and malignancy. In the present era of utilizing electronic health records (EHRs), it is strongly believed that big data and artificial intelligence will reshape the research done on kidney transplantation in the near future. In addition, the utilization of telemedicine is increasing, providing benefits such as reaching out to kidney transplant patients in remote areas and helping to make scarce healthcare resources more accessible for kidney transplantation. In this article, we discuss the recent research developments in kidney transplants that may affect long-term allografts, as well as the survival of the patient. The latest developments in living kidney donation are also explored. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Research

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Open AccessArticle
The Preliminary Results of Bortezomib Used as A Primary Treatment for An Early Acute Antibody-Mediated Rejection after Kidney Transplantation—A Single-Center Case Series
J. Clin. Med. 2020, 9(2), 529; https://doi.org/10.3390/jcm9020529 - 15 Feb 2020
Cited by 2
Abstract
Proteasome inhibitor bortezomib has been used in the treatment of refractory cases of acute and chronic antibody-mediated rejection (AMR) in kidney transplant recipients. However, its efficacy and safety as a primary treatment for early AMR has been scarcely investigated. We herein present our [...] Read more.
Proteasome inhibitor bortezomib has been used in the treatment of refractory cases of acute and chronic antibody-mediated rejection (AMR) in kidney transplant recipients. However, its efficacy and safety as a primary treatment for early AMR has been scarcely investigated. We herein present our preliminary experience with bortezomib- and plasmapheresis-based primary treatment for early AMR. Thirteen patients transplanted between October 2015 and September 2019 were treated (starting at median 19th post-transplant day) with bortezomib/plasmapheresis protocol for early biopsy-proven AMR. Twelve out of thirteen patients received 4 doses and one patient recieved 3 doses of bortezomib (1.3 mg/m2 per dose). In 11/13 patients, 4–7 concomitant plasmapheresis sessions were performed, with or without intravenous immunoglobulin (IVIG). Of note, rituximab was not used in all study patients. The kidney graft and patient survival were 100%. The mean 3-month estimated glomerular filtration rate (eGFR) was 55.3 (95%CI: 44.9–65.8) mL/min/1.73m2, 8/13 patients completed 12-month follow-up with mean eGFR 60.4 (45.4–75.4) mL/min/1.73m2, and 6/13 patients completed a 24-month follow-up period with mean eGFR 73.9 (56.7–91.1) mL/min/1.73m2. Neutropenia < 1 G/L was observed in one patient, third or fourth grade thrombocytopenia in two patients, and eleven patients needed a blood transfusion (median: 2 units/patient). The mid-term results of a primary bortezomib-based treatment for kidney AMR showed its non-inferiority as compared to preceding regimens and acceptable safety. However, our data should be validated in a multicenter randomized trial. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Altered Gut Microbial Fermentation and Colonization with Methanobrevibacter smithii in Renal Transplant Recipients
J. Clin. Med. 2020, 9(2), 518; https://doi.org/10.3390/jcm9020518 - 14 Feb 2020
Cited by 1
Abstract
Renal transplant recipients (RTRs) often suffer from posttransplant diarrhea. The observed dysbiosis in RTR may influence the fermentation processes in the gut. In this study, we aimed to investigate whether fermentation differs between RTRs and healthy controls (HCs), by measuring breath H2 [...] Read more.
Renal transplant recipients (RTRs) often suffer from posttransplant diarrhea. The observed dysbiosis in RTR may influence the fermentation processes in the gut. In this study, we aimed to investigate whether fermentation differs between RTRs and healthy controls (HCs), by measuring breath H2 and CH4 concentrations. Additionally, we determined the fecal presence of the methanogen Methanobrevibacter smithii (M. smithii), which plays a main role in the process of methanogenesis. Data from the TransplantLines Biobank and Cohort Study (NCT03272841) was used. A total of 142 RTRs and 77 HCs were included. Breath H2 concentrations in RTRs were not significantly different from HCs. Breath CH4 concentrations in RTRs were significantly lower compared with HCs (median [interquartile range (IQR)] 7.5 [3.9–10.6] ppm vs. 16.0 [8.0–45.5] ppm, p < 0.001). M. smithii was less frequently present in the feces of RTRs compared to HCs (28.6% vs. 86.4% resp., p < 0.001). Our findings regarding the altered methanogenesis in the gut of RTRs show similarities with previous results in inflammatory bowel disease patients. These findings provide novel insight into the alterations of fermentation after renal transplantation, which may contribute to understanding the occurrence of posttransplant diarrhea. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
High Plasma Branched-Chain Amino Acids Are Associated with Higher Risk of Post-Transplant Diabetes Mellitus in Renal Transplant Recipients
J. Clin. Med. 2020, 9(2), 511; https://doi.org/10.3390/jcm9020511 - 13 Feb 2020
Cited by 2
Abstract
Post-transplant diabetes mellitus (PTDM) is a serious complication in renal transplant recipients. Branched-chain amino acids (BCAAs) are involved in the pathogenesis of insulin resistance. We determined the association of plasma BCAAs with PTDM and included adult renal transplant recipients (≥18 y) with a [...] Read more.
Post-transplant diabetes mellitus (PTDM) is a serious complication in renal transplant recipients. Branched-chain amino acids (BCAAs) are involved in the pathogenesis of insulin resistance. We determined the association of plasma BCAAs with PTDM and included adult renal transplant recipients (≥18 y) with a functioning graft for ≥1 year in this cross-sectional cohort study with prospective follow-up. Plasma BCAAs were measured in 518 subjects using nuclear magnetic resonance spectroscopy. We excluded subjects with a history of diabetes, leaving 368 non-diabetic renal transplant recipients eligible for analyses. Cox proportional hazards analyses were used to assess the association of BCAAs with the development of PTDM. Mean age was 51.1 ± 13.6 y (53.6% men) and plasma BCAA was 377.6 ± 82.5 µM. During median follow-up of 5.3 (IQR, 4.2–6.0) y, 38 (9.8%) patients developed PTDM. BCAAs were associated with a higher risk of developing PTDM (HR: 1.43, 95% CI 1.08–1.89) per SD change (p = 0.01), independent of age and sex. Adjustment for other potential confounders did not significantly change this association, although adjustment for HbA1c eliminated it. The association was mediated to a considerable extent (53%) by HbA1c. The association was also modified by HbA1c; BCAAs were only associated with renal transplant recipients without prediabetes (HbA1c < 5.7%). In conclusion, high concentrations of plasma BCAAs are associated with developing PTDM in renal transplant recipients. Alterations in BCAAs may represent an early predictive biomarker for PTDM. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Urinary Excretion of N1-methyl-2-pyridone-5-carboxamide and N1-methylnicotinamide in Renal Transplant Recipients and Donors
J. Clin. Med. 2020, 9(2), 437; https://doi.org/10.3390/jcm9020437 - 06 Feb 2020
Cited by 1
Abstract
N1-methylnicotinamide (N1-MN) and N1-methyl-2-pyridone-5-carboxamide (2Py) are successive end products of NAD+ catabolism. N1-MN excretion in 24-h urine is the established biomarker of niacin nutritional status, and recently shown to be reduced in renal [...] Read more.
N1-methylnicotinamide (N1-MN) and N1-methyl-2-pyridone-5-carboxamide (2Py) are successive end products of NAD+ catabolism. N1-MN excretion in 24-h urine is the established biomarker of niacin nutritional status, and recently shown to be reduced in renal transplant recipients (RTR). However, it is unclear whether 2Py excretion is increased in this population, and, if so, whether a shift in excretion of N1-MN to 2Py can be attributed to kidney function. Hence, we assessed the 24-h urinary excretion of 2Py and N1-MN in RTR and kidney donors before and after kidney donation, and investigated associations of the urinary ratio of 2Py to N1-MN (2Py/N1-MN) with kidney function, and independent determinants of urinary 2Py/N1-MN in RTR. The urinary excretion of 2Py and N1-MN was measured in a cross-sectional cohort of 660 RTR and 275 healthy kidney donors with liquid chromatography-tandem mass spectrometry (LC-MS/MS). Linear regression analyses were used to investigate associations and determinants of urinary 2Py/N1-MN. Median 2Py excretion was 178.1 (130.3–242.8) μmol/day in RTR, compared to 155.6 (119.6–217.6) μmol/day in kidney donors (p < 0.001). In kidney donors, urinary 2Py/N1-MN increased significantly after kidney donation (4.0 ± 1.4 to 5.2 ± 1.5, respectively; p < 0.001). Smoking, alcohol consumption, diabetes, high-density lipoprotein (HDL), high-sensitivity C-reactive protein (hs-CRP) and estimated glomerular filtration rate (eGFR) were identified as independent determinants of urinary 2Py/N1-MN in RTR. In conclusion, the 24-h urinary excretion of 2Py is higher in RTR than in kidney donors, and urinary 2Py/N1-MN increases after kidney donation. As our data furthermore reveal strong associations of urinary 2Py/N1-MN with kidney function, interpretation of both N1-MN and 2Py excretion may be recommended for assessment of niacin nutritional status in conditions of impaired kidney function. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Circulating Arsenic is Associated with Long-Term Risk of Graft Failure in Kidney Transplant Recipients: A Prospective Cohort Study
J. Clin. Med. 2020, 9(2), 417; https://doi.org/10.3390/jcm9020417 - 03 Feb 2020
Cited by 1
Abstract
Arsenic is toxic to many organ systems, the kidney being the most sensitive target organ. We aimed to investigate whether, in kidney transplant recipients (KTRs), the nephrotoxic exposure to arsenic could represent an overlooked hazard for graft survival. We performed a prospective cohort [...] Read more.
Arsenic is toxic to many organ systems, the kidney being the most sensitive target organ. We aimed to investigate whether, in kidney transplant recipients (KTRs), the nephrotoxic exposure to arsenic could represent an overlooked hazard for graft survival. We performed a prospective cohort study of 665 KTRs with a functional graft ≥1 year, recruited in a university setting (2008‒2011), in The Netherlands. Plasma arsenic was measured by ICP-MS, and dietary intake was comprehensively assessed using a validated 177-item food-frequency questionnaire. The endpoint graft failure was defined as restart of dialysis or re-transplantation. Median arsenic concentration was 1.26 (IQR, 1.04‒2.04) µg/L. In backwards linear regression analyses we found that fish consumption (std β = 0.26; p < 0.001) was the major independent determinant of plasma arsenic. During 5 years of follow-up, 72 KTRs developed graft failure. In Cox proportional-hazards regression analyses, we found that arsenic was associated with increased risk of graft failure (HR 1.80; 95% CI 1.28–2.53; p = 0.001). This association remained materially unaltered after adjustment for donor and recipient characteristics, immunosuppressive therapy, eGFR, primary renal disease, and proteinuria. In conclusion, in KTRs, plasma arsenic is independently associated with increased risk of late graft failure. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Physical Activity and the Development of Post-Transplant Diabetes Mellitus, and Cardiovascular- and All-Cause Mortality in Renal Transplant Recipients
J. Clin. Med. 2020, 9(2), 415; https://doi.org/10.3390/jcm9020415 - 03 Feb 2020
Cited by 1
Abstract
(1) Background: Little is currently known about the health impacts of daily-life moderate-to-vigorous physical activity (MVPA) in relation to the development of post-transplant diabetes mellitus (PTDM) and the long-term survival of renal transplant recipients (RTRs). (2) Methods: We analyzed self-reported data on MVPA [...] Read more.
(1) Background: Little is currently known about the health impacts of daily-life moderate-to-vigorous physical activity (MVPA) in relation to the development of post-transplant diabetes mellitus (PTDM) and the long-term survival of renal transplant recipients (RTRs). (2) Methods: We analyzed self-reported data on MVPA within non-occupational and occupational domains, estimated with the SQUASH questionnaire, from a prospective cohort study of RTRs (n = 650) with a functioning graft exceeding 1 year. PTDM diagnoses were based on plasma glucose levels (≥126 mg/dL), HbA1c (≥6.5%), and the use of antidiabetic medication. Mortality data were retrieved from patient files up to the end of September 2015. (3) Results: During a median follow-up period of 5.3 years, 50 patients (10%) developed PTDM and 129 (19.8%) died. Of these deaths, 53 (8.9%) were caused by cardiovascular disease. Cox regression analyses showed that higher MVPA levels among patients were associated with a lower risk of PTDM (hazard ratio (HR); 95% confidence interval (95%CI) = 0.49; 0.25–0.96, p = 0.04), cardiovascular- (0.34; 0.15–0.77, p = 0.01), and all-cause mortality (0.37; 0.24–0.58, p < 0.001) compared with No-MVPA patients, independently of age, sex, and kidney function parameters. Associations of MVPA with cardiovascular and all-cause mortality remained significant and materially unchanged following further adjustments made for transplant characteristics, lifestyle factors, metabolic parameters, medication use, and creatinine excretion (muscle mass). However, the association between MVPA and PTDM was no longer significant after we adjusted for metabolic confounders and glucose levels. (4) Conclusion: Higher MVPA levels are associated with long-term health outcomes in RTRs. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
C3d-Positive Preformed DSAs Tend to Persist and Result in a Higher Risk of AMR after Kidney Transplants
J. Clin. Med. 2020, 9(2), 375; https://doi.org/10.3390/jcm9020375 - 30 Jan 2020
Cited by 1
Abstract
C3d-binding assays have been introduced as methods for the prediction of the presence of complement-binding functional antibodies; however, the prognostic value of C3d-positive preformed donor-specific antibodies (pDSAs) has not been fully evaluated. In this study, we performed a retrospective investigation of the association [...] Read more.
C3d-binding assays have been introduced as methods for the prediction of the presence of complement-binding functional antibodies; however, the prognostic value of C3d-positive preformed donor-specific antibodies (pDSAs) has not been fully evaluated. In this study, we performed a retrospective investigation of the association of pDSAs and their C3d-binding capacity with one-year clinical outcomes. pDSAs were defined as donor-specific antibodies (DSAs) that were produced before kidney transplants (KTs) (pre-pDSAs) or within the first four weeks after KTs, owing to rebound immune response (post-pDSAs). Of 455 adult KT recipients, pre-pDSAs and post-pDSAs were found in 56 (12.3%) and 56 (12.3%) recipients, respectively, and C3d-positive post-pDSAs were found in 13 recipients (2.9%) in total. Approximately half of the C3d-negative pre-pDSAs (37/73, 50.7%) disappeared after transplantation; however, all C3d-positive pre-pDSAs (8/8, 100%) persisted after transplantation despite desensitization (p = 0.008). C3d-positive pDSAs were significantly associated with a higher incidence and risk of AMR (p < 0.001, OR 94.467–188.934). Identification of the C3d-binding activity of pDSAs before and early after KT is important for predicting the persistence of pDSAs and the risk of AMR induced by the presence of pDSAs. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Female Specific Association of Low Insulin-Like Growth Factor 1 (IGF1) Levels with Increased Risk of Premature Mortality in Renal Transplant Recipients
J. Clin. Med. 2020, 9(2), 293; https://doi.org/10.3390/jcm9020293 - 21 Jan 2020
Cited by 2
Abstract
Associations between insulin-like growth factor 1 (IGF1) and mortality have been reported to be female specific in mice and in human nonagenarians. Intervention in the growth hormone (GH)-IGF1 axis may particularly benefit patients with high risk of losing muscle mass, including renal transplant [...] Read more.
Associations between insulin-like growth factor 1 (IGF1) and mortality have been reported to be female specific in mice and in human nonagenarians. Intervention in the growth hormone (GH)-IGF1 axis may particularly benefit patients with high risk of losing muscle mass, including renal transplant recipients (RTR). We investigated whether a potential association of circulating IGF1 with all-cause mortality in stable RTR could be female specific and mediated by variation in muscle mass. To this end, plasma IGF1 levels were measured in 277 female and 343 male RTR by mass spectrometry, and their association with mortality was assessed by Cox regression. During a median follow-up time of 5.4 years, 56 female and 77 male RTR died. In females, IGF1 was inversely associated with risk (hazard ratio (HR) per 1-unit increment in log2-transformed (doubling of) IGF1 levels, 95% confidence interval (CI)) of mortality (0.40, 0.24–0.65; p < 0.001), independent of age and the estimated Glomerular filtration rate (eGFR). In equivalent analyses, no significant association was observed for males (0.85, 0.56–1.29; p = 0.44), for which it should be noted that in males, age was negatively and strongly associated with IGF1 levels. The association for females remained materially unchanged upon adjustment for potential confounders and was furthermore found to be mediated for 39% by 24 h urinary creatinine excretion. In conclusion, low IGF1 levels associate with an increased risk of all-cause mortality in female RTR, which may link to conditions of low muscle mass that are known to be associated with poor outcomes in transplantation patients. For males, the strongly negative association of age with IGF1 levels may explain why low IGF1 levels were not found to be associated with an increased risk of all-cause mortality. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
The Effect of Proton Pump Inhibitor Use on Renal Function in Kidney Transplanted Patients
J. Clin. Med. 2020, 9(1), 258; https://doi.org/10.3390/jcm9010258 - 18 Jan 2020
Cited by 1
Abstract
Recently, proton pump inhibitor (PPI) intake has been linked to acute kidney injury and chronic kidney disease. The objective of this study was to assess the effect of PPIs on renal function and rejection rate in kidney transplant patients. We performed a single [...] Read more.
Recently, proton pump inhibitor (PPI) intake has been linked to acute kidney injury and chronic kidney disease. The objective of this study was to assess the effect of PPIs on renal function and rejection rate in kidney transplant patients. We performed a single center, retrospective analysis of 455 patients who received a kidney transplant between May 2010 and July 2015. Median follow-up time was 3.3 years. PPI prescription was assessed in half-year intervals. Primary outcome parameters were the estimated glomerular filtration rate (eGFR), change in the eGFR, and >30% and >50% eGFR decline for different time periods (up to four years post-transplantation). Our secondary outcome parameter was occurrence of biopsy proven acute rejection (BPAR) in the first two years after transplantation. Except for >30% eGFR decline from half a year to two years post-transplantation (p = 0.044) and change in the eGFR, >30% and >50% eGFR decline showed no association with PPI intake in our patient cohort (p > 0.05). Similarly, by analyzing 158 rejection episodes, BPAR showed no correspondence with mean daily PPI intake. We conclude that prolonged PPI intake has no relevant adverse effect on kidney transplant function or rejection rates. Polypharmacy, however, remains a problem in renal transplant recipients and it is thus advisable to question the necessity of PPI prescriptions when clear indications are missing. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Beliefs of UK Transplant Recipients about Living Kidney Donation and Transplantation: Findings from a Multicentre Questionnaire-Based Case–Control Study
J. Clin. Med. 2020, 9(1), 31; https://doi.org/10.3390/jcm9010031 - 21 Dec 2019
Cited by 1
Abstract
Differing beliefs about the acceptability of living-donor kidney transplants (LDKTs) have been proposed as explaining age, ethnic and socioeconomic disparities in their uptake. We investigated whether certain patient groups hold beliefs incompatible with LDKTs. This questionnaire-based case–control study was based at 14 hospitals [...] Read more.
Differing beliefs about the acceptability of living-donor kidney transplants (LDKTs) have been proposed as explaining age, ethnic and socioeconomic disparities in their uptake. We investigated whether certain patient groups hold beliefs incompatible with LDKTs. This questionnaire-based case–control study was based at 14 hospitals in the United Kingdom. Participants were adults transplanted between 1 April 2013 and 31 March 2017. LDKT recipients were compared to deceased-donor kidney transplant (DDKT) recipients. Beliefs were determined by the direction and strength of agreement with ten statements. Multivariable logistic regression was used to investigate the association between beliefs and LDKT versus DDKT. Sex, age, ethnicity, religion, and education were investigated as predictors of beliefs. A total of 1240 questionnaires were returned (40% response). DDKT and LDKT recipients responded in the same direction for 9/10 statements. A greater strength of agreement with statements concerning the ‘positive psychosocial effects’ of living kidney donation predicted having an LDKT over a DDKT. Older age, Black, Asian and Minority Ethnic (BAME) group ethnicity, and having a religion other than Christianity were associated with greater degree of uncertainty regarding a number of statements, but there was no evidence that individuals in these groups hold strong beliefs against living kidney donation and transplantation. Interventions should address uncertainty, to increase LDKT activity in these groups. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
Open AccessArticle
Management of Immunosuppression in Kidney Transplant Recipients Who Develop Malignancy
J. Clin. Med. 2019, 8(12), 2189; https://doi.org/10.3390/jcm8122189 - 11 Dec 2019
Cited by 1
Abstract
The risk of cancer increases after transplantation. However, the consensus on immunosuppression (IS) adjustment after diagnosis of malignancy is lacking. Our study aims to assess the impact of IS adjustment on mortality of post-kidney transplant patients and allograft outcomes. We retrospectively reviewed the [...] Read more.
The risk of cancer increases after transplantation. However, the consensus on immunosuppression (IS) adjustment after diagnosis of malignancy is lacking. Our study aims to assess the impact of IS adjustment on mortality of post-kidney transplant patients and allograft outcomes. We retrospectively reviewed the data in our center of 110 subjects. Our results showed IS dose adjustment was not statistically associated with mortality risk (HR 1.94, 95%CI 0.85–4.41, p = 0.12), and chemotherapy was the only factor that was significantly related to mortality (HR 2.3, 95%CI 1.21–4.35, p = 0.01). IS reduction was not statistically associated with worsening graft function (OR 3.8, 95%CI 0.77–18.71, p = 0.10), nor with graft survival (SHR 4.46, 95%CI 0.58–34.48, p = 0.15) after variables adjustment. Creatinine at cancer diagnosis and history of rejection were both negatively associated with graft survival (SHR 1.72, 95%CI 1.28–2.30, p < 0.01 and SHR 3.44, 95%CI 1.25–9.49, p = 0.02). Reduction of both mycophenolate and calcineurin inhibitors was associated with worsening graft function and lower graft survival in subgroup analysis (OR 6.14, 95%CI 1.14–33.15, p = 0.04; HR 17.97, 95%CI 1.81–178.78, p = 0.01). In summary, cancer causes high mortality and morbidity in kidney transplant recipients; the importance of cancer screening should be emphasized. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Proton-Pump Inhibitors and Hypomagnesaemia in Kidney Transplant Recipients
J. Clin. Med. 2019, 8(12), 2162; https://doi.org/10.3390/jcm8122162 - 06 Dec 2019
Cited by 2
Abstract
Proton-pump inhibitors (PPIs) are commonly used after kidney transplantation and there is rarely an incentive to discontinue treatment. In the general population, PPI use has been associated with hypomagnesaemia. We aimed to investigate whether PPI use is associated with plasma magnesium, 24-h urinary [...] Read more.
Proton-pump inhibitors (PPIs) are commonly used after kidney transplantation and there is rarely an incentive to discontinue treatment. In the general population, PPI use has been associated with hypomagnesaemia. We aimed to investigate whether PPI use is associated with plasma magnesium, 24-h urinary magnesium excretion and hypomagnesaemia, in kidney transplant recipients (KTR). Plasma magnesium and 24-h urinary magnesium excretion were measured in 686 stable outpatient KTR with a functioning allograft for ≥1 year from the TransplantLines Food and Nutrition Biobank and Cohort-Study (NCT02811835). PPIs were used by 389 KTR (56.6%). In multivariable linear regression analyses, PPI use was associated with lower plasma magnesium (β: −0.02, P = 0.02) and lower 24-h urinary magnesium excretion (β: −0.82, P < 0.001). Moreover, PPI users had a higher risk of hypomagnesaemia (plasma magnesium <0.70 mmol/L), compared with non-users (Odds Ratio (OR): 2.12; 95% confidence interval (CI) 1.43–3.15, P < 0.001). This risk tended to be highest among KTR taking high PPI dosages (>20 mg omeprazole Eq/day) and was independent of adjustment for potential confounders (OR: 2.46; 95% CI 1.32–4.57, P < 0.005). No interaction was observed between PPI use and the use of loop diuretics, thiazide diuretics, tacrolimus, or diabetes (Pinteraction > 0.05). These results demonstrate that PPI use is independently associated with lower magnesium status and hypomagnesaemia in KTR. The concomitant decrease in urinary magnesium excretion indicates that this likely is the consequence of reduced intestinal magnesium absorption. Based on these results, it might be of benefit to monitor magnesium status periodically in KTR on chronic PPI therapy. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Urinary Oxalate Excretion and Long-Term Outcomes in Kidney Transplant Recipients
J. Clin. Med. 2019, 8(12), 2104; https://doi.org/10.3390/jcm8122104 - 02 Dec 2019
Cited by 3
Abstract
Epidemiologic studies have linked urinary oxalate excretion to risk of chronic kidney disease (CKD) progression and end-stage renal disease. We aimed to investigate whether urinary oxalate, in stable kidney transplant recipients (KTR), is prospectively associated with risk of graft failure. In secondary analyses [...] Read more.
Epidemiologic studies have linked urinary oxalate excretion to risk of chronic kidney disease (CKD) progression and end-stage renal disease. We aimed to investigate whether urinary oxalate, in stable kidney transplant recipients (KTR), is prospectively associated with risk of graft failure. In secondary analyses we evaluated the association with post-transplantation diabetes mellitus, all-cause mortality and specific causes of death. Oxalate excretion was measured in 24-h urine collection samples in a cohort of 683 KTR with a functioning allograft ≥1 year. Mean eGFR was 52 ± 20 mL/min/1.73 m2. Median (interquartile range) urinary oxalate excretion was 505 (347–732) µmol/24-h in women and 519 (396–736) µmol/24-h in men (p = 0.08), with 302 patients (44% of the study population) above normal limits (hyperoxaluria). A consistent and independent inverse association was found with all-cause mortality (HR 0.77, 95% CI 0.63–0.94, p = 0.01). Cause-specific survival analyses showed that this association was mainly driven by an inverse association with mortality due to infection (HR 0.56, 95% CI 0.38–0.83, p = 0.004), which remained materially unchanged after performing sensitivity analyses. Twenty-four-hour urinary oxalate excretion did not associate with risk of graft failure, post-transplant diabetes mellitus, cardiovascular mortality, mortality due to malignancies or mortality due to miscellaneous causes. In conclusion, in KTR, 24-h urinary oxalate excretion is elevated in 44% of KTR and inversely associated with mortality due to infectious causes. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Plasmapheresis Reduces Mycophenolic Acid Concentration: A Study of Full AUC0–12 in Kidney Transplant Recipients
J. Clin. Med. 2019, 8(12), 2084; https://doi.org/10.3390/jcm8122084 - 01 Dec 2019
Cited by 1
Abstract
Background: Mycophenolic acid (MPA), a crucial immunosuppressive drug, and plasmapheresis, an effective immunoreduction method, are simultaneously used for the management of various immune-related diseases, including kidney transplantation. While plasmapheresis has been proven efficient in removing many substances from the blood, its effect on [...] Read more.
Background: Mycophenolic acid (MPA), a crucial immunosuppressive drug, and plasmapheresis, an effective immunoreduction method, are simultaneously used for the management of various immune-related diseases, including kidney transplantation. While plasmapheresis has been proven efficient in removing many substances from the blood, its effect on MPA plasma levels remains unestablished. Objectives: To evaluate the full pharmacokinetics of MPA by measuring the area under the time–concentration curve (AUC0–12), which is the best indicator for MPA treatment monitoring after each plasmapheresis session, and to compare the AUC0–12 measurements on the day with and on the day without plasmapheresis. Methods: A cross-sectional study was conducted in kidney transplantation recipients who were taking a twice-daily oral dose of mycophenolate mofetil (MMF, Cellcept®) and undergoing plasmapheresis at King Chulalongkorn Memorial Hospital, Bangkok, Thailand, during January 2018 and January 2019. The MPA levels were measured by an enzymatic method (Roche diagnostic®) 0, 1/2, 1, 2, 3, 4, 6, 8, and 12 h after MMF administration, for AUC0–12 calculation on the day with and on the day without plasmapheresis sessions. Plasmapheresis was started within 4 h after administering the oral morning dose of MMF. Our primary outcome was the difference of AUC0–12 between the day with and the day without plasmapheresis. Results: Forty complete AUC measurements included 20 measurements on the plasmapheresis day and other 20 measurements on the day without plasmapheresis in six kidney transplant patients. The mean age of the patients was 56.2 ± 20.7 years. All patients had received 1000 mg/day of MMF for at least 72 h before undergoing 3.5 ± 1.2 plasmapheresis sessions. The mean AUC on the day with plasmapheresis was lower than that on the day without plasmapheresis (28.22 ± 8.21 vs. 36.79 ± 10.29 mg × h/L, p = 0.001), and the percentage of AUC reduction was 19.49 ± 24.83%. This was mainly the result of a decrease in AUC0–4 of MPA (23.96 ± 28.12% reduction). Conclusions: Plasmapheresis significantly reduces the level of full AUC0–12 of MPA. The present study is the first to measure the full AUC0–12 in MPA-treated patients undergoing plasmapheresis. Our study suggests that a supplementary dose of MPA is necessary for patients undergoing plasmapheresis. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Plasma Vitamin C and Cancer Mortality in Kidney Transplant Recipients
J. Clin. Med. 2019, 8(12), 2064; https://doi.org/10.3390/jcm8122064 - 23 Nov 2019
Cited by 1
Abstract
There is a changing trend in mortality causes in kidney transplant recipients (KTR), with a decline in deaths due to cardiovascular causes along with a relative increase in cancer mortality rates. Vitamin C, a well-known antioxidant with anti-inflammatory and immune system enhancement properties, [...] Read more.
There is a changing trend in mortality causes in kidney transplant recipients (KTR), with a decline in deaths due to cardiovascular causes along with a relative increase in cancer mortality rates. Vitamin C, a well-known antioxidant with anti-inflammatory and immune system enhancement properties, could offer protection against cancer. We aimed to investigate the association of plasma vitamin C with long-term cancer mortality in a cohort of stable outpatient KTR without history of malignancies other than cured skin cancer. Primary and secondary endpoints were cancer and cardiovascular mortality, respectively. We included 598 KTR (mean age 51 ± 12 years old, 55% male). Mean (SD) plasma vitamin C was 44 ± 20 μmol/L. At a median follow-up of 7.0 (IQR, 6.2–7.5) years, 131 patients died, of which 24% deaths were due to cancer. In Cox proportional hazards regression analyses, vitamin C was inversely associated with cancer mortality (HR 0.50; 95%CI 0.34–0.74; p < 0.001), independent of potential confounders, including age, smoking status and immunosuppressive therapy. In secondary analyses, vitamin C was not associated with cardiovascular mortality (HR 1.16; 95%CI 0.83–1.62; p = 0.40). In conclusion, plasma vitamin C is inversely associated with cancer mortality risk in KTR. These findings underscore that relatively low circulating plasma vitamin C may be a meaningful as yet overlooked modifiable risk factor of cancer mortality in KTR. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Urinary Excretion of N1-Methylnicotinamide, as a Biomarker of Niacin Status, and Mortality in Renal Transplant Recipients
J. Clin. Med. 2019, 8(11), 1948; https://doi.org/10.3390/jcm8111948 - 12 Nov 2019
Cited by 2
Abstract
Renal transplant recipients (RTR) commonly suffer from vitamin B6 deficiency and its functional consequences add to an association with poor long-term outcome. It is unknown whether niacin status is affected in RTR and, if so, whether this affects clinical outcomes, as vitamin [...] Read more.
Renal transplant recipients (RTR) commonly suffer from vitamin B6 deficiency and its functional consequences add to an association with poor long-term outcome. It is unknown whether niacin status is affected in RTR and, if so, whether this affects clinical outcomes, as vitamin B6 is a cofactor in nicotinamide biosynthesis. We compared 24-h urinary excretion of N1-methylnicotinamide (N1-MN) as a biomarker of niacin status in RTR with that in healthy controls, in relation to dietary intake of tryptophan and niacin as well as vitamin B6 status, and investigated whether niacin status is associated with the risk of premature all-cause mortality in RTR. In a prospective cohort of 660 stable RTR with a median follow-up of 5.4 (4.7–6.1) years and 275 healthy kidney donors, 24-h urinary excretion of N1-MN was measured with liquid chromatography-tandem mass spectrometry LC-MS/MS. Dietary intake was assessed by food frequency questionnaires. Prospective associations of N1-MN excretion with mortality were investigated by Cox regression analyses. Median N1-MN excretion was 22.0 (15.8–31.8) μmol/day in RTR, compared to 41.1 (31.6–57.2) μmol/day in healthy kidney donors (p < 0.001). This difference was independent of dietary intake of tryptophan (1059 ± 271 and 1089 ± 308 mg/day; p = 0.19), niacin (17.9 ± 5.2 and 19.2 ± 6.2 mg/day; p < 0.001), plasma vitamin B6 (29.0 (17.5–49.5), and 42.0 (29.8–60.3) nmol/L; p < 0.001), respectively. N1-MN excretion was inversely associated with the risk of all-cause mortality in RTR (HR 0.57; 95% CI 0.45–0.71; p < 0.001), independent of potential confounders. RTR excrete less N1-MN in 24-h urine than healthy controls, and our data suggest that this difference cannot be attributed to lower dietary intake of tryptophan and niacin, nor vitamin B6 status. Importantly, lower 24-h urinary excretion of N1-MN is independently associated with a higher risk of premature all-cause mortality in RTR. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Urinary Biomarkers α-GST and π-GST for Evaluation and Monitoring in Living and Deceased Donor Kidney Grafts
J. Clin. Med. 2019, 8(11), 1899; https://doi.org/10.3390/jcm8111899 - 07 Nov 2019
Cited by 1
Abstract
The aim of this study was to analyze the value of urine α- and π-GST in monitoring and predicting kidney graft function following transplantation. In addition, urine samples from corresponding organ donors was analyzed and compared with graft function after organ donation from [...] Read more.
The aim of this study was to analyze the value of urine α- and π-GST in monitoring and predicting kidney graft function following transplantation. In addition, urine samples from corresponding organ donors was analyzed and compared with graft function after organ donation from brain-dead and living donors. Urine samples from brain-dead (n = 30) and living related (n = 50) donors and their corresponding recipients were analyzed before and after kidney transplantation. Urine α- and π-GST values were measured. Kidney recipients were grouped into patients with acute graft rejection (AGR), calcineurin inhibitor toxicity (CNI), and delayed graft function (DGF), and compared to those with unimpaired graft function. Urinary π-GST revealed significant differences in deceased kidney donor recipients with episodes of AGR or DGF at day one after transplantation (p = 0.0023 and p = 0.036, respectively). High π-GST values at postoperative day 1 (cutoff: >21.4 ng/mg urine creatinine (uCrea) or >18.3 ng/mg uCrea for AGR or DGF, respectively) distinguished between rejection and no rejection (sensitivity, 100%; specificity, 66.6%) as well as between DGF and normal-functioning grafts (sensitivity, 100%; specificity, 62.6%). In living donor recipients, urine levels of α- and π-GST were about 10 times lower than in deceased donor recipients. In deceased donors with impaired graft function in corresponding recipients, urinary α- and π-GST were elevated. α-GST values >33.97 ng/mg uCrea were indicative of AGR with a sensitivity and specificity of 77.7% and 100%, respectively. In deceased donor kidney transplantation, evaluation of urinary α- and π-GST seems to predict different events that deteriorate graft function. To elucidate the potential advantages of such biomarkers, further analysis is warranted. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Validation of Identified Susceptible Gene Variants for New-Onset Diabetes in Renal Transplant Recipients
J. Clin. Med. 2019, 8(10), 1696; https://doi.org/10.3390/jcm8101696 - 16 Oct 2019
Cited by 1
Abstract
Genome-wide association studies (GWAS) and candidate gene approaches have identified single nucleotide polymorphisms (SNPs) associated with new-onset diabetes after renal transplantation (NODAT). We evaluated associations between NODAT and SNPs identified in previous studies. We genotyped 1102 renal transplant recipients from the Korean Organ [...] Read more.
Genome-wide association studies (GWAS) and candidate gene approaches have identified single nucleotide polymorphisms (SNPs) associated with new-onset diabetes after renal transplantation (NODAT). We evaluated associations between NODAT and SNPs identified in previous studies. We genotyped 1102 renal transplant recipients from the Korean Organ Transplantation Registry (KOTRY) database; 13 SNPs were assessed for associations with NODAT (occurring in 254 patients; 23.0%), within one year after transplantation. The frequency of the T allele at KCNQ1 rs2237892 was significantly lower in patients with NODAT compared to control patients (0.30 vs. 0.39; p = 8.5 × 10−5). The T allele at rs2237892 was significantly associated with decreased risk of NODAT after adjusting for multiple variables, compared to the C allele (OR 0.63, 95% CI 0.51–0.79; p = 5.5 × 10−5). Dominant inheritance modeling showed that CT/TT genotypes were associated with a lower risk for development of NODAT (OR 0.56, 95% CI 0.42–0.76; p = 2.0 × 10−4) compared to the CC genotype. No other SNPs were associated with NODAT. Our study validated the protective effect of T allele at KCNQ1 rs2237892 on the development of NODAT in a large cohort of renal transplant recipients. Our findings on susceptibility variants might be a useful tool to predict NODAT development after renal transplantation. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
Open AccessArticle
Urinary Epidermal Growth Factor/Creatinine Ratio and Graft Failure in Renal Transplant Recipients: A Prospective Cohort Study
J. Clin. Med. 2019, 8(10), 1673; https://doi.org/10.3390/jcm8101673 - 13 Oct 2019
Cited by 2
Abstract
Graft failure (GF) remains a significant limitation to improve long-term outcomes in renal transplant recipients (RTR). Urinary epidermal growth factor (uEGF) is involved in kidney tissue integrity, with a reduction of its urinary excretion being associated with fibrotic processes and a wide range [...] Read more.
Graft failure (GF) remains a significant limitation to improve long-term outcomes in renal transplant recipients (RTR). Urinary epidermal growth factor (uEGF) is involved in kidney tissue integrity, with a reduction of its urinary excretion being associated with fibrotic processes and a wide range of renal pathologies. We aimed to investigate whether, in RTR, uEGF is prospectively associated with GF. In this prospective cohort study, RTR with a functioning allograft ≥1-year were recruited and followed-up for three years. uEGF was measured in 24-hours urine samples and normalized by urinary creatinine (Cr). Its association with risk of GF was assessed by Cox-regression analyses and its predictive ability by C-statistic. In 706 patients, uEGF/Cr at enrollment was 6.43 [IQR 4.07–10.77] ng/mg. During follow-up, 41(6%) RTR developed GF. uEGF/Cr was inversely associated with the risk of GF (HR 0.68 [95% CI 0.59–0.78]; P < 0.001), which remained significant after adjustment for immunosuppressive therapy, estimated Glomerular Filtration Rate, and proteinuria. C-statistic of uEGF/Cr for GF was 0.81 (P < 0.001). We concluded that uEGF/Cr is independently and inversely associated with the risk of GF and depicts strong prediction ability for this outcome. Further studies seem warranted to elucidate whether uEGF might be a promising marker for use in clinical practice. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Native Nephrectomy before and after Renal Transplantation in Patients with Autosomal Dominant Polycystic Kidney Disease (ADPKD)
J. Clin. Med. 2019, 8(10), 1622; https://doi.org/10.3390/jcm8101622 - 04 Oct 2019
Cited by 1
Abstract
The aim of this study was 1) to evaluate and compare pre-, peri-, and post-operative data of Autosomal Dominant Polycystic Kidney Disease (ADPKD) patients undergoing native nephrectomy (NN) either before or after renal transplantation and 2) to identify advantages of optimal surgical timing, [...] Read more.
The aim of this study was 1) to evaluate and compare pre-, peri-, and post-operative data of Autosomal Dominant Polycystic Kidney Disease (ADPKD) patients undergoing native nephrectomy (NN) either before or after renal transplantation and 2) to identify advantages of optimal surgical timing, postoperative outcomes, and economical aspects in a tertiary transplant centre. This retrospective analysis included 121 patients divided into two groups—group 1: patients who underwent NN prior to receiving a kidney transplant (n = 89) and group 2: patients who underwent NN post-transplant (n = 32). Data analysis was performed according to demographic patient details, surgical indication, laboratory parameters, perioperative complications, underlying pathology, and associated mortality. There was no significant difference in patient demographics between the groups, however right-sided nephrectomy was performed predominantly within group 1. The main indication in both groups undergoing a nephrectomy was pain. Patients among group 2 had no postoperative kidney failure and a significantly shorter hospital stay. Higher rates of more severe complications were observed in group 1, even though this was not statistically significant. Even though the differences between both groups were substantial, the time of NN prior or post-transplant does not seem to affect short-term and long-term transplantation outcomes. Retroperitoneal NN remains a low risk treatment option in patients with symptomatic ADPKD and can be performed either pre- or post-kidney transplantation depending on patients’ symptom severity. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Intraoperative Fluid Restriction is Associated with Functional Delayed Graft Function in Living Donor Kidney Transplantation: A Retrospective Cohort Analysis
J. Clin. Med. 2019, 8(10), 1587; https://doi.org/10.3390/jcm8101587 - 02 Oct 2019
Cited by 2
Abstract
Background: In 2016 we observed a marked increase in functional delayed graft function (fDGF) in our living donor kidney transplantation (LDKT) recipients from 8.5% in 2014 and 8.8% in 2015 to 23.0% in 2016. This increase coincided with the introduction of a goal-directed [...] Read more.
Background: In 2016 we observed a marked increase in functional delayed graft function (fDGF) in our living donor kidney transplantation (LDKT) recipients from 8.5% in 2014 and 8.8% in 2015 to 23.0% in 2016. This increase coincided with the introduction of a goal-directed fluid therapy (GDFT) protocol in our kidney transplant recipients. Hereupon, we changed our intraoperative fluid regimen to a fixed amount of 50 mL/kg body weight (BW) and questioned whether the intraoperative fluid regimen was related to this increase in fDGF. Methods: a retrospective cohort analysis of all donors and recipients in our LDKT program between January 2014–February 2017 (n = 275 pairs). Results: Univariate analysis detected various risk factors for fDGF. Dialysis dependent recipients were more likely to develop fDGF compared to pre-emptively transplanted patients (p < 0.001). Recipients developing fDGF received less intraoperative fluid (36 (25.9–50.0) mL/kg BW vs. 47 (37.3–55.6) mL/kg BW (p = 0.007)). The GDFT protocol resulted in a reduction of intraoperative fluid administration on average by 850 mL in total volume and 21% in mL/kg BW compared to our old protocol (p < 0.001). In the unadjusted analysis, a higher intraoperative fluid volume in mL/kg BW was associated with a lower risk for the developing fDGF (OR 0.967, CI (0.941–0.993)). After adjustment for the confounders, prior dialysis and the use of intraoperative noradrenaline, the relationship of fDGF with fluid volume was still apparent (OR 0.970, CI (0.943–0.998)). Conclusion: Implementation of a GDFT protocol led to reduced intraoperative fluid administration in the LDKT recipients. This intraoperative fluid restriction was associated with the development of fDGF. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
A Low Tacrolimus Concentration/Dose Ratio Increases the Risk for the Development of Acute Calcineurin Inhibitor-Induced Nephrotoxicity
J. Clin. Med. 2019, 8(10), 1586; https://doi.org/10.3390/jcm8101586 - 02 Oct 2019
Cited by 3
Abstract
Fast tacrolimus metabolism is linked to inferior outcomes such as rejection and lower renal function after kidney transplantation. Renal calcineurin-inhibitor toxicity is a common adverse effect of tacrolimus therapy. The present contribution hypothesized that tacrolimus-induced nephrotoxicity is related to a low concentration/dose (C/D) [...] Read more.
Fast tacrolimus metabolism is linked to inferior outcomes such as rejection and lower renal function after kidney transplantation. Renal calcineurin-inhibitor toxicity is a common adverse effect of tacrolimus therapy. The present contribution hypothesized that tacrolimus-induced nephrotoxicity is related to a low concentration/dose (C/D) ratio. We analyzed renal tubular epithelial cell cultures and 55 consecutive kidney transplant biopsy samples with tacrolimus-induced toxicity, the C/D ratio, C0, C2, and C4 Tac levels, pulse wave velocity analyses, and sublingual endothelial glycocalyx dimensions in the selected kidney transplant patients. A low C/D ratio (C/D ratio < 1.05 ng/mL×1/mg) was linked with higher C2 tacrolimus blood concentrations (19.2 ± 8.7 µg/L vs. 12.2 ± 5.2 µg/L respectively; p = 0.001) and higher degrees of nephrotoxicity despite comparable trough levels (6.3 ± 2.4 µg/L vs. 6.6 ± 2.2 µg/L respectively; p = 0.669). However, the tacrolimus metabolism rate did not affect the pulse wave velocity or glycocalyx in patients. In renal tubular epithelial cells exposed to tacrolimus according to a fast metabolism pharmacokinetic profile it led to reduced viability and increased Fn14 expression. We conclude from our data that the C/D ratio may be an appropriate tool for identifying patients at risk of developing calcineurin-inhibitor toxicity. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Chronic Use of Proton-Pump Inhibitors and Iron Status in Renal Transplant Recipients
J. Clin. Med. 2019, 8(9), 1382; https://doi.org/10.3390/jcm8091382 - 03 Sep 2019
Cited by 4
Abstract
Proton-pump inhibitor (PPI) use may influence intestinal iron absorption. Low iron status and iron deficiency (ID) are frequent medical problems in renal transplant recipients (RTR). We hypothesized that chronic PPI use is associated with lower iron status and ID in RTR. Serum iron, [...] Read more.
Proton-pump inhibitor (PPI) use may influence intestinal iron absorption. Low iron status and iron deficiency (ID) are frequent medical problems in renal transplant recipients (RTR). We hypothesized that chronic PPI use is associated with lower iron status and ID in RTR. Serum iron, ferritin, transferrin saturation (TSAT), and hemoglobin were measured in 646 stable outpatient RTR with a functioning allograft for ≥ 1 year from the “TransplantLines Food and Nutrition Biobank and Cohort Study” (NCT02811835). Median time since transplantation was 5.3 (1.8–12.0) years, mean age was 53 ± 13 years, and 56.2% used PPI. In multivariable linear regression analyses, PPI use was inversely associated with serum iron (β = −1.61, p = 0.001), natural log transformed serum ferritin (β = −0.31, p < 0.001), TSAT (β = −2.85, p = 0.001), and hemoglobin levels (β = −0.35, p = 0.007), independent of potential confounders. Moreover, PPI use was independently associated with increased risk of ID (Odds Ratio (OR): 1.57; 95% Confidence Interval (CI) 1.07–2.31, p = 0.02). Additionally, the odds ratio in RTR taking a high PPI dose as compared to RTR taking no PPIs (OR 2.30; 95% CI 1.46–3.62, p < 0.001) was higher than in RTR taking a low PPI dose (OR:1.78; 95% CI 1.21–2.62, p = 0.004). We demonstrated that PPI use is associated with lower iron status and ID, suggesting impaired intestinal absorption of iron. Moreover, we found a stronger association with ID in RTR taking high PPI dosages. Use of PPIs should, therefore, be considered as a modifiable cause of ID in RTR. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Efficacy and Safety of Belatacept Treatment in Renal Allograft Recipients at High Cardiovascular Risk—A Single Center Experience
J. Clin. Med. 2019, 8(8), 1164; https://doi.org/10.3390/jcm8081164 - 03 Aug 2019
Cited by 1
Abstract
Belatacept is an attractive option for immunosuppression after renal transplantation. Renal allograft function is superior when compared to calcineurin inhibitor (CNI) based therapy in “de novo” treated patients and it has also been proposed that individuals at high cardiovascular (CV) risk may benefit [...] Read more.
Belatacept is an attractive option for immunosuppression after renal transplantation. Renal allograft function is superior when compared to calcineurin inhibitor (CNI) based therapy in “de novo” treated patients and it has also been proposed that individuals at high cardiovascular (CV) risk may benefit most. In this retrospective cohort study, we assessed the efficacy and safety of treating patients at high cardiovascular risk with Belatacept (n = 34, for 1194 observation months) when compared to a matched control group of 150 individuals under CNI immunosuppression (for 7309 months of observation). The estimated glomerular filtration rate (eGFR) increased for patients taking Belatacept but decreased during CNI-based therapy (+2.60 vs. −0.89 mL/min/1.73 m2/year, p = 0.006). In a multivariate Cox regression model, Belatacept remained the only significant factor associated with the improvement of eGFR (HR 4.35, 95%CI 2.39–7.93). Belatacept treatment was not a significant risk factor for renal allograft rejection or graft loss. In terms of safety, the only significant risk factor for de novo cardiovascular events was a pre-existing cerebrovascular disease, but Belatacept was not associated with a significant risk reduction. Belatacept treatment was not associated with an increased risk of severe infections, cytomegalo virus (CMV) or BK-virus reactivation, malignancy or death in the multivariate Cox regression analysis. Belatacept is an efficient and safe option for patients after renal transplantation at high cardiovascular risk. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
CD45RC Expression of Circulating CD8+ T Cells Predicts Acute Allograft Rejection: A Cohort Study of 128 Kidney Transplant Patients
J. Clin. Med. 2019, 8(8), 1147; https://doi.org/10.3390/jcm8081147 - 01 Aug 2019
Cited by 2
Abstract
Predictive biomarkers of acute rejection (AR) are lacking. Pre-transplant expression of CD45RC on blood CD8+ T cells has been shown to predict AR in kidney transplant (KT) patients. The objective of the present study was to study CD45RC expression in a large [...] Read more.
Predictive biomarkers of acute rejection (AR) are lacking. Pre-transplant expression of CD45RC on blood CD8+ T cells has been shown to predict AR in kidney transplant (KT) patients. The objective of the present study was to study CD45RC expression in a large cohort of KT recipients exposed to modern immunosuppressive regimens. CD45RC expression on T cells was analyzed in 128 KT patients, where 31 patients developed AR, of which 24 were found to be T-cell mediated (TCMR). Pre-transplant CD4+ and CD8+ CR45RChigh T cell proportions were significantly higher in patients with AR. The frequency of CD45RChigh T cells was significantly associated with age at transplantation but was not significantly different according to gender, history of transplantation, pre-transplant immunization, and de novo donor specific anti-Human Leucocyte Antigen (HLA) antibody. Survival-free AR was significantly better in patients with CD8+ CD45RChigh T cells below 58.4% (p = 0.0005), but not different according to CD4+ T cells (p = 0.073). According to multivariate analysis, CD8+ CD45RChigh T cells above 58.4% increased the risk of AR 4-fold (HR 3.96, p = 0.003). Thus, pre-transplant CD45RC expression on CD8+ T cells predicted AR, mainly TCMR, in KT patients under modern immunosuppressive therapies. We suggest that CD45RC expression should be evaluated in a prospective study to validate its usefulness to quantify the pre-transplant risk of AR. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Analysis of the Effects of Day-Time vs. Night-Time Surgery on Renal Transplant Patient Outcomes
J. Clin. Med. 2019, 8(7), 1051; https://doi.org/10.3390/jcm8071051 - 18 Jul 2019
Cited by 1
Abstract
Sleep deprivation and disruption of the circadian rhythms could impair individual surgical performance and decision making. For this purpose, this study identified potential confounding factors on surgical renal transplant patient outcomes during day and night. Our retrospective cohort study of 215 adult renal [...] Read more.
Sleep deprivation and disruption of the circadian rhythms could impair individual surgical performance and decision making. For this purpose, this study identified potential confounding factors on surgical renal transplant patient outcomes during day and night. Our retrospective cohort study of 215 adult renal cadaver transplant recipients, of which 132 recipients were allocated in the “day-time” group and 83 recipients in the “night-time” group, primarily stratified the patients into two cohorts, depending on the start time. Within a 24 h operational system, “day-time” was considered as being from 8 a.m. to 8 p.m. and “night-time” from 8 p.m. to 8 a.m.. Primary outcomes examined patient and graft survival after three months and one year. Secondary outcomes included the presence of acute rejection (AR) and delayed graft function (DGF), as well as the rate of postoperative complications. In log-rank testing, “day-time” surgery was associated with a significantly higher risk of patient death (p = 0.003), whereas long-term graft survival was unaffected by the operative time of day. The mean cold ischemia time (CIT), which was 12.4 ± 5.3 h in the “night-time” group, was significantly longer compared to 10.7 ± 3.6 for those during the day (p = 0.01). We observed that “night-time” kidney recipients experienced more wound complications. From our single-centre data, we conclude that night-time kidney transplantation does not increase the risk of adverse events or predispose the patient to a worse outcome. Nevertheless, further research is required to explore the effect of fatigue on nocturnal surgical performance. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Phenotypic and Genotypic Characterization of Escherichia coli Causing Urinary Tract Infections in Kidney-Transplanted Patients
J. Clin. Med. 2019, 8(7), 988; https://doi.org/10.3390/jcm8070988 - 07 Jul 2019
Cited by 2
Abstract
Urinary tract infection (UTI), frequently caused by uropathogenic Escherichia coli (UPEC), is the most common infection after kidney transplantation (KTx). Untreated, it can lead to urosepsis and impairment of the graft function. We questioned whether the UPEC isolated from KTx patients differed from [...] Read more.
Urinary tract infection (UTI), frequently caused by uropathogenic Escherichia coli (UPEC), is the most common infection after kidney transplantation (KTx). Untreated, it can lead to urosepsis and impairment of the graft function. We questioned whether the UPEC isolated from KTx patients differed from the UPEC of non-KTx patients. Therefore, we determined the genome sequences of 182 UPEC isolates from KTx and control patients in a large German university clinic and pheno- and genotypically compared these two isolated groups. Resistance to the β-lactams, trimethoprim or trimethoprim/sulfamethoxazole was significantly higher among UPEC from KTx than from control patients, whereas both the isolated groups were highly susceptible to fosfomycin. Accordingly, the gene content conferring resistance to β-lactams or trimethoprim, but also to aminoglycosides, was significantly higher in KTx than in control UPEC isolates. E. coli isolates from KTx patients more frequently presented with uncommon UPEC phylogroups expressing higher numbers of plasmid replicons, but interestingly, less UPEC virulence-associated genes than the control group. We conclude that there is no defining subset of virulence traits for UPEC from KTx patients. The clinical history and immunocompromised status of KTx patients enables E. coli strains with low uropathogenic potential, but with increased antibiotic resistance to cause UTIs. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Exposure to Hyperchloremia Is Associated with Poor Early Recovery of Kidney Graft Function after Living-Donor Kidney Transplantation: A Propensity Score-Matching Analysis
J. Clin. Med. 2019, 8(7), 955; https://doi.org/10.3390/jcm8070955 - 02 Jul 2019
Cited by 2
Abstract
The effects of hyperchloremia on kidney grafts have not been investigated in patients undergoing living-donor kidney transplantation (LDKT). In this study, data from 200 adult patients undergoing elective LDKT between January 2016 and December 2017 were analyzed after propensity score (PS) matching. The [...] Read more.
The effects of hyperchloremia on kidney grafts have not been investigated in patients undergoing living-donor kidney transplantation (LDKT). In this study, data from 200 adult patients undergoing elective LDKT between January 2016 and December 2017 were analyzed after propensity score (PS) matching. The patients were allocated to hyperchloremia and non-hyperchloremia groups according to the occurrence of hyperchloremia (i.e., ≥110 mEq/L) immediately after surgery. Poor early graft recovery was defined as estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2 during the first 48 hours after surgery. After PS matching, no significant differences in perioperative recipient or donor graft parameters were observed between groups. Although the total amount of crystalloid fluid infused during surgery did not differ between groups, the proportions of main crystalloid fluid type used (i.e., 0.9% normal saline vs. Plasma Solution-A) did. The eGFR increased gradually during postoperative day (POD) 2 in both groups. However, the proportion of patients with eGFR > 60 mL/min/1.73 m2 on POD 2 was higher in the non-hyperchloremia group than in the hyperchloremia group. In this PS-adjusted analysis, hyperchloremia was significantly associated with poor graft recovery on POD 2. In conclusion, exposure to hyperchloremia may have a negative impact on early graft recovery in LDKT. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
Open AccessArticle
Comparison of Glucose Tolerance between Kidney Transplant Recipients and Healthy Controls
J. Clin. Med. 2019, 8(7), 920; https://doi.org/10.3390/jcm8070920 - 27 Jun 2019
Cited by 1
Abstract
Post-transplant hyperglycemia and new-onset diabetes mellitus after transplantation (NODAT) are common and important metabolic complications. Decreased insulin secretion and increased insulin resistance are important to the pathophysiologic mechanism behind NODAT. However, the progression of glucose intolerance diagnosed late after kidney transplantation remains clearly [...] Read more.
Post-transplant hyperglycemia and new-onset diabetes mellitus after transplantation (NODAT) are common and important metabolic complications. Decreased insulin secretion and increased insulin resistance are important to the pathophysiologic mechanism behind NODAT. However, the progression of glucose intolerance diagnosed late after kidney transplantation remains clearly unknown. Enrolled in this study were 94 kidney transplant recipients and 134 kidney transplant donors, as the healthy controls, who were treated at our institution. The 75 g-oral glucose tolerance test (OGTT) was performed in the recipients, and the healthy controls received an OGTT before donor nephrectomy. We assessed the prevalence of glucose intolerance including impaired fasting glucose and/or impaired glucose tolerance, as well as insulin secretion and insulin resistance using the homeostasis model assessment, and compared the results between the two groups. Multivariate analysis after adjustment for age, gender, body mass index, estimated glomerular filtration rate, and systolic blood pressure showed that the prevalence of glucose intolerance, insulin resistance, insulin secretion, and 2 h plasma glucose levels were significantly higher in the kidney transplant recipients compared to the healthy controls. Elevation of insulin secretion in kidney transplant recipients may be compensatory for increase of insulin resistance. Impaired compensatory pancreas β cell function may lead to glucose intolerance and NODAT in the future. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
Open AccessArticle
Outcomes of Kidney Transplant Patients with Atypical Hemolytic Uremic Syndrome Treated with Eculizumab: A Systematic Review and Meta-Analysis
J. Clin. Med. 2019, 8(7), 919; https://doi.org/10.3390/jcm8070919 - 27 Jun 2019
Cited by 4
Abstract
Background: Kidney transplantation in patients with atypical hemolytic uremic syndrome (aHUS) is frequently complicated by recurrence, resulting in thrombotic microangiopathy in the renal allograft and graft loss. We aimed to assess the use of eculizumab in the prevention and treatment of aHUS recurrence [...] Read more.
Background: Kidney transplantation in patients with atypical hemolytic uremic syndrome (aHUS) is frequently complicated by recurrence, resulting in thrombotic microangiopathy in the renal allograft and graft loss. We aimed to assess the use of eculizumab in the prevention and treatment of aHUS recurrence after kidney transplantation. Methods: Databases (MEDLINE, EMBASE and Cochrane Database) were searched through February 2019. Studies that reported outcomes of adult kidney transplant recipients with aHUS treated with eculizumab were included. Estimated incidence rates from the individual studies were extracted and combined using random-effects, generic inverse variance method of DerSimonian and Laird. Protocol for this systematic review has been registered with PROSPERO (International Prospective Register of Systematic Reviews; no. CRD42018089438). Results: Eighteen studies (13 cohort studies and five case series) consisting of 380 adult kidney transplant patients with aHUS who received eculizumab for prevention and treatment of post-transplant aHUS recurrence were included in the analysis. Among patients who received prophylactic eculizumab, the pooled estimated incidence rates of recurrent thrombotic microangiopathy (TMA) after transplantation and allograft loss due to TMA were 6.3% (95%CI: 2.8–13.4%, I2 = 0%) and 5.5% (95%CI: 2.9–10.0%, I2 = 0%), respectively. Among those who received eculizumab for treatment of post-transplant aHUS recurrence, the pooled estimated rates of allograft loss due to TMA was 22.5% (95%CI: 13.6–34.8%, I2 = 6%). When the meta-analysis was restricted to only cohort studies with data on genetic mutations associated with aHUS, the pooled estimated incidence of allograft loss due to TMA was 22.6% (95%CI: 13.2–36.0%, I2 = 10%). We found no significant publication bias assessed by the funnel plots and Egger’s regression asymmetry test (p > 0.05 for all analyses). Conclusions: This study summarizes the outcomes observed with use of eculizumab for prevention and treatment of aHUS recurrence in kidney transplantation. Our results suggest a possible role for anti-C5 antibody therapy in the prevention and management of recurrent aHUS. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
The Effect of Donors’ Demographic Characteristics in Renal Function Post-Living Kidney Donation. Analysis of a UK Single Centre Cohort
J. Clin. Med. 2019, 8(6), 883; https://doi.org/10.3390/jcm8060883 - 20 Jun 2019
Cited by 5
Abstract
Introduction: There is a great need to increase the organ donor pool, particularly for living donors. This study analyses the difference in post-living donation kidney function according to pre-donation characteristics of age, genetic relationship with the recipient, sex, ethnicity, and Body Mass Index [...] Read more.
Introduction: There is a great need to increase the organ donor pool, particularly for living donors. This study analyses the difference in post-living donation kidney function according to pre-donation characteristics of age, genetic relationship with the recipient, sex, ethnicity, and Body Mass Index (BMI). Methods: Retrospective single centre analysis of the trajectory of estimated Glomerular Filtration Rate (eGFR) post-living kidney donation, as a measure of kidney function. Mean eGFR of the different groups was compared at 6 months and during the 60 months follow up. Results: Mean age was 46 ± 13 years, 57% were female, and 60% Caucasian. Mean BMI was 27 ± 5 kg/m2, with more than a quarter of the cohort having a BMI > 30 (26%), and the majority of the donors genetically related to their recipients (56%). The higher decline rate in eGFR was at 6 months after donation, with female sex, non-Caucasian ethnicity, and age lower than 60 years being independently associated with higher recovery in kidney function (p < 0.05). In the 60 months follow up, older age, genetic relationship with the recipient, and male sex led to higher percentual difference in eGFR post-donation. Conclusion: In this study, with a high proportion of high BMI living kidney donors, female sex, age lower than 60 years, and non-genetic relationship with recipient were persistently associated with higher increase in post-donation kidney function. Ethnicity and BMI, per se, should not be a barrier to increasing the living donor kidney pool. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Epidemiology, Risk Factors, and Outcomes of Opportunistic Infections after Kidney Allograft Transplantation in the Era of Modern Immunosuppression: A Monocentric Cohort Study
J. Clin. Med. 2019, 8(5), 594; https://doi.org/10.3390/jcm8050594 - 30 Apr 2019
Cited by 1
Abstract
Epidemiology of opportunistic infections (OI) after kidney allograft transplantation in the modern era of immunosuppression and the use of OI prevention strategies are poorly described. We retrospectively analyzed a single-center cohort on kidney allograft adult recipients transplanted between January 2008 and December 2013. [...] Read more.
Epidemiology of opportunistic infections (OI) after kidney allograft transplantation in the modern era of immunosuppression and the use of OI prevention strategies are poorly described. We retrospectively analyzed a single-center cohort on kidney allograft adult recipients transplanted between January 2008 and December 2013. The control group included all kidney recipients transplanted in the same period, but with no OI. We analyzed 538 kidney transplantations (538 patients). The proportion of OI was 15% (80 and 72 patients). OI occurred 12.8 (6.0–31.2) months after transplantation. Viruses were the leading cause (n = 54, (10%)), followed by fungal (n = 15 (3%)), parasitic (n = 6 (1%)), and bacterial (n = 5 (0.9%)) infections. Independent risk factors for OI were extended criteria donor (2.53 (1.48–4.31), p = 0.0007) and BK viremia (6.38 (3.62–11.23), p < 0.0001). High blood lymphocyte count at the time of transplantation was an independent protective factor (0.60 (0.38–0.94), p = 0.026). OI was an independent risk factor for allograft loss (2.53 (1.29–4.95), p = 0.007) but not for patient survival. Post-kidney transplantation OIs were mostly viral and occurred beyond one year after transplantation. Pre-transplantation lymphopenia and extended criteria donor are independent risk factors for OI, unlike induction therapy, hence the need to adjust immunosuppressive regimens to such transplant candidates. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Fast Tac Metabolizers at Risk—It is Time for a C/D Ratio Calculation
J. Clin. Med. 2019, 8(5), 587; https://doi.org/10.3390/jcm8050587 - 28 Apr 2019
Cited by 9Correction
Abstract
Tacrolimus (Tac) is a part of the standard immunosuppressive regimen after renal transplantation (RTx). However, its metabolism rate is highly variable. A fast Tac metabolism rate, defined by the Tac blood trough concentration (C) divided by the daily dose (D), is associated with [...] Read more.
Tacrolimus (Tac) is a part of the standard immunosuppressive regimen after renal transplantation (RTx). However, its metabolism rate is highly variable. A fast Tac metabolism rate, defined by the Tac blood trough concentration (C) divided by the daily dose (D), is associated with inferior renal function after RTx. Therefore, we hypothesize that the Tac metabolism rate impacts patient and graft survival after RTx. We analyzed all patients who received a RTx between January 2007 and December 2012 and were initially treated with an immunosuppressive regimen containing Tac (Prograf®), mycophenolate mofetil, prednisolone and induction therapy. Patients with a Tac C/D ratio <1.05 ng/mL × 1/mg at three months after RTx were characterized as fast metabolizers and those with a C/D ratio ≥1.05 ng/mL × 1/mg as slow metabolizers. Five-year patient and overall graft survival were noticeably reduced in fast metabolizers. Further, fast metabolizers showed a faster decline of eGFR (estimated glomerular filtration rate) within five years after RTx and a higher rejection rate compared to slow metabolizers. Calculation of the Tac C/D ratio three months after RTx may assist physicians in their daily clinical routine to identify Tac-treated patients at risk for the development of inferior graft function, acute rejections, or even higher mortality. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Incidence and Mortality of Renal Cell Carcinoma after Kidney Transplantation: A Meta-Analysis
J. Clin. Med. 2019, 8(4), 530; https://doi.org/10.3390/jcm8040530 - 17 Apr 2019
Cited by 4
Abstract
Background: The incidence and mortality of renal cell carcinoma (RCC) after kidney transplantation (KTx) remain unclear. This study’s aims were (1) to investigate the pooled incidence/incidence trends, and (2) to assess the mortality/mortality trends in KTx patients with RCC. Methods: A literature search [...] Read more.
Background: The incidence and mortality of renal cell carcinoma (RCC) after kidney transplantation (KTx) remain unclear. This study’s aims were (1) to investigate the pooled incidence/incidence trends, and (2) to assess the mortality/mortality trends in KTx patients with RCC. Methods: A literature search was conducted using the MEDLINE, EMBASE and Cochrane databases from inception through October 2018. Studies that reported the incidence or mortality of RCC among kidney transplant recipients were included. The pooled incidence and 95% CI were calculated using a random-effect model. The protocol for this meta-analysis is registered with PROSPERO; no. CRD42018108994. Results: A total of 22 observational studies with a total of 320,190 KTx patients were enrolled. Overall, the pooled estimated incidence of RCC after KTx was 0.7% (95% CI: 0.5–0.8%, I2 = 93%). While the pooled estimated incidence of de novo RCC in the native kidney was 0.7% (95% CI: 0.6–0.9%, I2 = 88%), the pooled estimated incidence of RCC in the allograft kidney was 0.2% (95% CI: 0.1–0.4%, I2 = 64%). The pooled estimated mortality rate in KTx recipients with RCC was 15.0% (95% CI: 7.4–28.1%, I2 = 80%) at a mean follow-up time of 42 months after RCC diagnosis. While meta-regression analysis showed a significant negative correlation between year of study and incidence of de novo RCC post-KTx (slopes = −0.05, p = 0.01), there were no significant correlations between the year of study and mortality of patients with RCC (p = 0.50). Egger’s regression asymmetry test was performed and showed no publication bias in all analyses. Conclusions: The overall estimated incidence of RCC after KTX was 0.7%. Although there has been a potential decrease in the incidence of RCC post-KTx, mortality in KTx patients with RCC has not decreased over time. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Subarachnoid Hemorrhage in Hospitalized Renal Transplant Recipients with Autosomal Dominant Polycystic Kidney Disease: A Nationwide Analysis
J. Clin. Med. 2019, 8(4), 524; https://doi.org/10.3390/jcm8040524 - 17 Apr 2019
Cited by 2
Abstract
Background: This study aimed to evaluate the hospitalization rates for subarachnoid hemorrhage (SAH) among renal transplant patients with adult polycystic kidney disease (ADPKD) and its outcomes, when compared to non-ADPKD renal transplant patients. Methods: The 2005–2014 National Inpatient Sample databases were used to [...] Read more.
Background: This study aimed to evaluate the hospitalization rates for subarachnoid hemorrhage (SAH) among renal transplant patients with adult polycystic kidney disease (ADPKD) and its outcomes, when compared to non-ADPKD renal transplant patients. Methods: The 2005–2014 National Inpatient Sample databases were used to identify all hospitalized renal transplant patients. The inpatient prevalence of SAH as a discharge diagnosis between ADPKD and non-ADPKD renal transplant patients was compared. Among SAH patients, the in-hospital mortality, use of aneurysm clipping, hospital length of stay, total hospitalization cost and charges between ADPKD and non-ADPKD patients were compared, adjusting for potential confounders. Results: The inpatient prevalence of SAH in ADPKD was 3.8/1000 admissions, compared to 0.9/1000 admissions in non-ADPKD patients (p < 0.01). Of 833 renal transplant patients with a diagnosis of SAH, 30 had ADPKD. Five (17%) ADPKD renal patients with SAH died in hospitals compared to 188 (23.4%) non-ADPKD renal patients (p = 0.70). In adjusted analysis, there was no statistically significant difference in mortality, use of aneurysm clipping, hospital length of stay, or total hospitalization costs and charges between ADPKD and non-ADPKD patients with SAH. Conclusion: Renal transplant patients with ADPKD had a 4-fold higher inpatient prevalence of SAH than those without ADPKD. Further studies are needed to compare the incidence of overall admissions in ADPKD and non-ADPKD patients. When renal transplant patients developed SAH, inpatient mortality rates were high regardless of ADPKD status. The outcomes, as well as resource utilization, were comparable between the two groups. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
Open AccessArticle
Higher Incidence of BK Virus Nephropathy in Pediatric Kidney Allograft Recipients with Alport Syndrome
J. Clin. Med. 2019, 8(4), 491; https://doi.org/10.3390/jcm8040491 - 11 Apr 2019
Cited by 2
Abstract
A retrospective review was performed to assess the risk factors and outcomes of BK virus infection and nephropathy (BKVN), an early complication in pediatric kidney allograft recipients. The study investigated the incidence, risk factors, and clinical outcomes of BK viremia and BKVN in [...] Read more.
A retrospective review was performed to assess the risk factors and outcomes of BK virus infection and nephropathy (BKVN), an early complication in pediatric kidney allograft recipients. The study investigated the incidence, risk factors, and clinical outcomes of BK viremia and BKVN in a Korean population of pediatric patients who received renal transplantation from 2001–2015 at the Seoul National University Hospital. BKVN was defined as biopsy-proven BKVN or plasma BK viral loads >10,000 copies/mL for >3 weeks. BK viremia was defined as a BK viral load >100 copies/mL in blood. Among 168 patients assessed for BK virus status, 30 patients (17.9%) tested positive for BK viremia at a median of 12.6 months after transplantation. BKVN was diagnosed in six patients (3.6%) at a median of 13.4 months after transplantation. Three of the six BKVN patients had Alport syndrome (p = 0.003), despite this disease comprising only 6% of the study population. Every patient with BK viremia and Alport syndrome developed BKVN, while only 11.1% of patients with BK viremia progressed to BKVN in the absence of Alport syndrome. Multivariate analysis revealed that Alport syndrome was associated with BKVN development (hazard ratio 13.2, p = 0.002). BKVN treatment included the reduction of immunosuppression, leflunomide, and intravenous immunoglobulin. No allografts were lost in the two years following the diagnosis of BKVN. In summary, the incidence of BKVN in pediatric kidney allograft recipients was similar to findings in previous reports, but was higher in patients with underlying Alport syndrome. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessArticle
Plasma Malondialdehyde and Risk of New-Onset Diabetes after Transplantation in Renal Transplant Recipients: A Prospective Cohort Study
J. Clin. Med. 2019, 8(4), 453; https://doi.org/10.3390/jcm8040453 - 04 Apr 2019
Cited by 2
Abstract
New-onset diabetes after transplantation (NODAT) is a frequent complication in renal transplant recipients (RTR). Although oxidative stress has been associated with diabetes mellitus, data regarding NODAT are limited. We aimed to prospectively investigate the long-term association between the oxidative stress biomarker malondialdehyde (measured [...] Read more.
New-onset diabetes after transplantation (NODAT) is a frequent complication in renal transplant recipients (RTR). Although oxidative stress has been associated with diabetes mellitus, data regarding NODAT are limited. We aimed to prospectively investigate the long-term association between the oxidative stress biomarker malondialdehyde (measured by high-performance liquid chromatography) and NODAT in an extensively phenotyped cohort of non-diabetic RTR with a functioning graft ≥1 year. We included 516 RTR (51 ± 13 years-old, 57% male). Median plasma malondialdehyde (MDA) was 2.55 (IQR, 1.92–3.66) µmol/L. During a median follow-up of 5.3 (IQR, 4.6–6.0) years, 56 (11%) RTR developed NODAT. In Cox proportional-hazards regression analyses, MDA was inversely associated with NODAT, independent of immunosuppressive therapy, transplant-specific covariates, lifestyle, inflammation, and metabolism parameters (HR, 0.55; 95% CI, 0.36–0.83 per 1-SD increase; p < 0.01). Dietary antioxidants intake (e.g., vitamin E, α-lipoic acid, and linoleic acid) were effect-modifiers of the association between MDA and NODAT, with particularly strong inverse associations within the subgroup of RTR with relatively higher dietary antioxidants intake. In conclusion, plasma MDA concentration is inversely and independently associated with long-term risk of NODAT in RTR. Our findings support a potential underrecognized role of oxidative stress in post-transplantation glucose homeostasis. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessReview
Ischemia and Reperfusion Injury in Kidney Transplantation: Relevant Mechanisms in Injury and Repair
J. Clin. Med. 2020, 9(1), 253; https://doi.org/10.3390/jcm9010253 - 17 Jan 2020
Cited by 3
Abstract
Ischemia and reperfusion injury (IRI) is a complex pathophysiological phenomenon, inevitable in kidney transplantation and one of the most important mechanisms for non- or delayed function immediately after transplantation. Long term, it is associated with acute rejection and chronic graft dysfunction due to [...] Read more.
Ischemia and reperfusion injury (IRI) is a complex pathophysiological phenomenon, inevitable in kidney transplantation and one of the most important mechanisms for non- or delayed function immediately after transplantation. Long term, it is associated with acute rejection and chronic graft dysfunction due to interstitial fibrosis and tubular atrophy. Recently, more insight has been gained in the underlying molecular pathways and signalling cascades involved, which opens the door to new therapeutic opportunities aiming to reduce IRI and improve graft survival. This review systemically discusses the specific molecular pathways involved in the pathophysiology of IRI and highlights new therapeutic strategies targeting these pathways. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessReview
BK Polyomavirus Virus Glomerular Tropism: Implications for Virus Reactivation from Latency and Amplification during Immunosuppression
J. Clin. Med. 2019, 8(9), 1477; https://doi.org/10.3390/jcm8091477 - 17 Sep 2019
Cited by 2
Abstract
BK polyomavirus (BKPyV), or BKV infection, is ubiquitous and usually non-pathogenic, with subclinical infections in 80–90% of adults worldwide. BKV infection is often associated with pathology in immunocompromised individuals. BKV infection often is associated with renal impairment, including ureteral stenosis, hemorrhagic cystitis, and [...] Read more.
BK polyomavirus (BKPyV), or BKV infection, is ubiquitous and usually non-pathogenic, with subclinical infections in 80–90% of adults worldwide. BKV infection is often associated with pathology in immunocompromised individuals. BKV infection often is associated with renal impairment, including ureteral stenosis, hemorrhagic cystitis, and nephropathy. BKV infection is less commonly associated with pneumonitis, retinitis, liver disease, and meningoencephalitis. BKV is known to replicate, establish latency, undergo reactivation, and induce clinical pathology in renal tubular epithelial cells. However, recent in vitro studies support the notion that BKV has expanded tropism-targeting glomerular parenchymal cells of the human kidney, which could impact glomerular function, enhance inflammation, and serve as viral reservoirs for reactivation from latency during immunosuppression. The implications of BKV expanded tropism in the glomerulus, and how specific host and viral factors that would contribute to glomerular inflammation, cytolysis, and renal fibrosis are related to BKV associated nephropathy (BKVAN), have not been explored. The pathogenesis of BKV in human glomerular parenchymal cells is poorly understood. In this review, I examine target cell populations for BKV infectivity in the human glomerulus. Specifically, I explore the implications of BKV expanded tropism in the glomerulus with regard viral entry, replication, and dissemination via cell types exposed to BKV trafficking in glomerulus. I also describe cellular targets shown to be permissive in vitro and in vivo for BKV infection and lytic replication, the potential role that glomerular parenchymal cells play in BKV latency and/or reactivation after immunosuppression, and the rare occurrence of BKV pathology in glomerular parenchymal cells in patients with BKVAN. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessReview
Machine Perfusion for Abdominal Organ Preservation: A Systematic Review of Kidney and Liver Human Grafts
J. Clin. Med. 2019, 8(8), 1221; https://doi.org/10.3390/jcm8081221 - 15 Aug 2019
Cited by 4
Abstract
Introduction: To match the current organ demand with organ availability from the donor pool, there has been a shift towards acceptance of extended criteria donors (ECD), often associated with longer ischemic times. Novel dynamic preservation techniques as hypothermic or normothermic machine perfusion (MP) [...] Read more.
Introduction: To match the current organ demand with organ availability from the donor pool, there has been a shift towards acceptance of extended criteria donors (ECD), often associated with longer ischemic times. Novel dynamic preservation techniques as hypothermic or normothermic machine perfusion (MP) are increasingly adopted, particularly for organs from ECDs. In this study, we compared the viability and incidence of reperfusion injury in kidneys and livers preserved with MP versus Static Cold Storage (SCS). Methods: Systematic review and meta-analysis with a search performed between February and March 2019. MEDLINE, EMBASE and Transplant Library were searched via OvidSP. The Cochrane Library and The Cochrane Central Register of Controlled Trials (CENTRAL) were also searched. English language filter was applied. Results: the systematic search generated 10,585 studies, finally leading to a total of 30 papers for meta-analysis of kidneys and livers. Hypothermic MP (HMP) statistically significantly lowered the incidence of primary nonfunction (PMN, p = 0.003) and delayed graft function (DGF, p < 0.00001) in kidneys compared to SCS, but not its duration. No difference was also noted for serum creatinine or eGFR post-transplantation, but overall kidneys preserved with HMP had a significantly longer one-year graft survival (OR: 1.61 95% CI: 1.02 to 2.53, p = 0.04). Differently from kidneys where the graft survival was affected, there was no significant difference in primary non function (PNF) for livers stored using SCS for those preserved by HMP and NMP. Machine perfusion demonstrated superior outcomes in early allograft dysfunction and post transplantation AST levels compared to SCS, but however, only HMP was able to significantly decrease serum bilirubin and biliary stricture incidence compared to SCS. Conclusions: MP improves DGF and one-year graft survival in kidney transplantation; it appears to mitigate early allograft dysfunction in livers, but more studies are needed to prove its potential superiority in relation to PNF in livers. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessReview
Timing of Ureteric Stent Removal and Occurrence of Urological Complications after Kidney Transplantation: A Systematic Review and Meta-Analysis
J. Clin. Med. 2019, 8(5), 689; https://doi.org/10.3390/jcm8050689 - 16 May 2019
Cited by 4
Abstract
Implanting a ureteric stent during ureteroneocystostomy reduces the risk of leakage and ureteral stenosis after kidney transplantation (KTx), but it may also predispose to urinary tract infections (UTIs). The aim of this study is to determine the optimal timing for ureteric stent removal [...] Read more.
Implanting a ureteric stent during ureteroneocystostomy reduces the risk of leakage and ureteral stenosis after kidney transplantation (KTx), but it may also predispose to urinary tract infections (UTIs). The aim of this study is to determine the optimal timing for ureteric stent removal after KTx. Searches were performed in EMBASE, MEDLINE Ovid, Cochrane CENTRAL, Web of Science, and Google Scholar (until November 2017). For this systematic review, all aspects of the Cochrane Handbook for Interventional Systematic Reviews were followed and it was written based on the PRISMA-statement. Articles discussing JJ-stents (double-J stents) and their time of removal in relation to outcomes, UTIs, urinary leakage, ureteral stenosis or reintervention were included. One-thousand-and-forty-three articles were identified, of which fourteen articles (three randomised controlled trials, nine retrospective cohort studies, and two prospective cohort studies) were included (describing in total n = 3612 patients). Meta-analysis using random effect models showed a significant reduction of UTIs when stents were removed earlier than three weeks (OR 0.49, CI 95%, 0.33 to 0.75, p = 0.0009). Regarding incidence of urinary leakage, there was no significant difference between early (<3 weeks) and late stent removal (>3 weeks) (OR 0.60, CI 95%, 0.29 to 1.23, p = 0.16). Based on our results, earlier stent removal (<3 weeks) was associated with a decreased incidence of UTIs and did not show a higher incidence of urinary leakage compared to later removal (>3 weeks). We recommend that the routine removal of ureteric stents implanted during KTx should be performed around three weeks post-operatively. Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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Open AccessCorrection
Correction: Fast Tac Metabolizers at Risk—It is Time for a C/D Ratio Calculation. J. Clin. Med. 2019, 8, 587
J. Clin. Med. 2019, 8(11), 1870; https://doi.org/10.3390/jcm8111870 - 04 Nov 2019
Cited by 2
Abstract
The authors wish to make the following corrections to this paper [...] Full article
(This article belongs to the Special Issue Recent Advances and Clinical Outcomes of Kidney Transplantation)
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