Special Issue "Infectious Complications in Chronic Kidney Disease and Renal Transplant Patients: Prevention, Diagnosis, Management, and Emerging Trends"

A special issue of Pathogens (ISSN 2076-0817). This special issue belongs to the section "Immunological Responses and Immune Defense Mechanisms".

Deadline for manuscript submissions: 30 November 2022 | Viewed by 4278

Special Issue Editors

Dr. Carlo Alfieri
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Guest Editor
Department of Nephrology, Dialysis and Renal Transplantation, Fondazione IRCCS Ca’Granda Ospedale Maggiore Policlinico, Milan, Italy
Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
Interests: Renal transplantation; chronic kidney disease; mineral bone disorders in CKD and renal transplanted patients; Markers of CKD progression
Dr. Evaldo Favi
E-Mail Website
Guest Editor
1. Renal Transplantation, Fondazione IRCCS Ca’ Granda Ospedale Maggiore Policlinico, Milan, Italy
2. Department of Clinical Sciences and Community Health, University of Milan, Milan, Italy
Interests: kidney transplantation; organ donation; immunosuppression; vascular access; polyomavirus
Special Issues, Collections and Topics in MDPI journals
Prof. Dr. Serena Delbue
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Guest Editor
Department of Biomedical, Surgical and Dental Sciences, University of Milan, Milan, Italy
Interests: human polyomaviruses epidemiology and replication in the immunocompromised hosts; viral infections in renal transplantation recipients
Special Issues, Collections and Topics in MDPI journals
Dr. Roberto Antonio Simone CACCIOLA
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Guest Editor
Department of Surgical Sciences, Università di Tor Vergata, 00133 Rome, Italy
Interests: kidney transplantation; living donor transplantation; governance and outcome analysis; health economics; infectious disease in transplantation

Special Issue Information

Dear Colleagues,

Chronic kidney disease (CKD) and renal transplantation (RTx) are associated with a higher risk of all-cause mortality and morbidity than the general population. Apart from cardiovascular disease, infectious complications actually represent the most relevant and perhaps preventable cause of death among these specific groups of patients. The increased susceptibility to infections observed in CKD and RTx recognizes several predisposing factors such as uremia, impaired primary host immunity, sustained exposure to microbiological agents during dialysis, and, especially in RTx patients, chronic immunosuppression.

In this Special Issue of Pathogens, we will provide an updated representation of the current prevention, diagnosis, and management strategies of common and rare infections in CKD and RTx patients. In addition, we will offer further insight into future directions and emerging trends in basic, clinical, and translational science relevant to the topic.

With those aims, we invite researchers to submit high-quality works for consideration. Original articles, as well as narrative reviews of particular interest and case reports of exceptional didactical value, will be considered.

“Infectious Complications in Chronic Kidney Disease and Renal Transplant Patients: Prevention, Diagnosis, Management, and Emerging Trends” will give specialists and scientists involved in the care of renal patients the opportunity to share their experience or point of view on several critical issues, with the primary objective of improving global knowledge and patients outcome.

Dr. Carlo Alfieri
Dr. Evaldo Favi
Prof. Dr. Serena Delbue
Dr. Roberto Antonio Simone CACCIOLA
Guest Editors

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Keywords

  • infectious diseases
  • renal transplantation
  • chronic kidney disease
  • end stage renal disease

Published Papers (4 papers)

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Research

Article
Cryptococcal Meningitis in Kidney Transplant Recipients: A Two-Decade Cohort Study in France
Pathogens 2022, 11(6), 699; https://doi.org/10.3390/pathogens11060699 - 17 Jun 2022
Viewed by 328
Abstract
Cryptococcosis is the third most common cause of invasive fungal infection in solid organ transplant recipients and cryptococcal meningitis (CM) its main clinical presentation. CM outcomes, as well as its clinical features and radiological characteristics, have not yet been considered on a large [...] Read more.
Cryptococcosis is the third most common cause of invasive fungal infection in solid organ transplant recipients and cryptococcal meningitis (CM) its main clinical presentation. CM outcomes, as well as its clinical features and radiological characteristics, have not yet been considered on a large scale in the context of kidney transplantation (KT). We performed a nationwide retrospective study of adult patients diagnosed with cryptococcosis after KT between 2002 and 2020 across 30 clinical centers in France. We sought to describe overall and graft survival based on whether KT patients with cryptococcosis developed CM or not. Clinical indicators of CNS involvement and brain radiological characteristics were assessed. Eighty-eight cases of cryptococcosis were diagnosed during the study period, with 61 (69.3%) cases of CM. Mortality was high (32.8%) at 12 months (M12) but not significantly different whether or not patients presented with CM. Baseline hyponatremia and at least one neurological symptom were independently associated with CM (p < 0.001). Positive serum cryptococcal antigen at diagnosis was also significantly associated with CM (p < 0.001). On magnetic resonance imaging (MRI), three patterns of brain injury were identified: parenchymal, meningeal, and vascular lesions. Although CM does not affect graft function directly, it entails a grim prognosis. Full article
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Article
High Mortality and Graft Loss after Infective Endocarditis in Kidney Transplant Recipients: A Case-Controlled Study from Two Centers
Pathogens 2021, 10(8), 1023; https://doi.org/10.3390/pathogens10081023 - 13 Aug 2021
Viewed by 761
Abstract
Kidney transplant recipients (KTRs) tend to develop infections with characteristic epidemiology, presentation, and outcome. While infective endocarditis (IE) is among such complications in KTRs, the literature is scarce. We describe the presentation, epidemiology, and factors associated with IE in KTRs. We performed a [...] Read more.
Kidney transplant recipients (KTRs) tend to develop infections with characteristic epidemiology, presentation, and outcome. While infective endocarditis (IE) is among such complications in KTRs, the literature is scarce. We describe the presentation, epidemiology, and factors associated with IE in KTRs. We performed a retrospective case/control study which included patients from two centers. First episodes of definite or possible IE (Duke criteria) in adult KTRs from January 2010 to December 2018 were included, as well as two controls per case, and followed until 31 December 2019. Clinical, biological, and microbiological data and the outcome were collected. Survival was studied using the Kaplan–Meier method. Finally, we searched for factors associated with the onset of IE in KTRs by the comparison of cases and controls. Seventeen cases and 34 controls were included. IE was diagnosed after a mean delay of 78 months after KT, mostly on native valves of the left heart only. Pathogens of digestive origin were most frequently involved (six Enterococcus spp, three Streptococcus gallolyticus, and one Escherichia coli), followed by Staphylococci (three cases of S. aureus and S. epidermidis each). Among the risk factors evaluated, age, vascular nephropathy, and elevated calcineurin inhibitor through levels were significantly associated with the occurrence of IE in our study. Patient and death-censored graft survival were greatly diminished five years after IE, compared to controls being 50.3% vs. 80.6% (p < 0.003) and 29.7% vs. 87.5% (p < 0.002), respectively. IE in KTRs is a disease that carries significant risks both for the survival of the patient and the transplant. Full article
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Article
COVID-19 Infection in Kidney Transplant Patients: An Italian One Year Single Centre Experience
Pathogens 2021, 10(8), 964; https://doi.org/10.3390/pathogens10080964 - 30 Jul 2021
Cited by 2 | Viewed by 1050
Abstract
COVID-19 is a life-threatening infection among elderly patients, comorbid patients, or transplanted patients. Lombardy (region of Italy), accounts for 786,324 cases as of 21 April 2021. We retrospectively describe our single Centre experience in 82 adult kidney-transplant patients with COVID-19 infection during two [...] Read more.
COVID-19 is a life-threatening infection among elderly patients, comorbid patients, or transplanted patients. Lombardy (region of Italy), accounts for 786,324 cases as of 21 April 2021. We retrospectively describe our single Centre experience in 82 adult kidney-transplant patients with COVID-19 infection during two pandemic outbreaks: 27 (first outbreak) and 65 (second outbreak). Thirty-seven patients were hospitalized (HP) and sixty-five were home managed (HM). Infection presented with fever (80%), cough (51%), and dyspnea (33%). HP were older (60 ± 11 vs. 50 ± 14 years, p = 0.001), had more severe respiratory symptoms (dyspnea 62.1%, p < 0.0001–cough 67% p = 0.008), and a longer length of disease (30 ± 28 vs. 21 ± 10, p = 0.04). The incidence of acute kidney injury (AKI) was 29.7% (p < 0.0001). Steroid dosage was increased in 66% of patients (p = 0.0003), while calcineurin inhibitors were reduced by up to one third in 45% of cases, p < 0.0001. Eleven patients died (13%). HM patients recovered completely without sequelae. In the overall cohort, AKI development (p = 0.006 OR 50.4 CI 95% 3.0–836) and age (p = 0.04 OR 1.1 CI 95% 1.0–1.2) were the most important factors influencing the probability of death during the infection. Although we report a relatively low incidence of infection (5.1%) the incidence of death is almost four times higher than it is in the general population. Full article
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Article
Cytomegalovirus Disease in Renal Transplanted Patients: Prevalence, Determining Factors, and Influence on Graft and Patients Outcomes
Pathogens 2021, 10(4), 473; https://doi.org/10.3390/pathogens10040473 - 14 Apr 2021
Cited by 1 | Viewed by 1262
Abstract
The prevalence and the factors related to cytomegalovirus (CMV) disease (CMVd) during the 1st year of renal transplantation (RTx) and the relationship between CMVd and early and long-term graft and RTx-patient (RTx-p) survival were evaluated. In 505 RTx-p, followed up for 8(5–11) years, [...] Read more.
The prevalence and the factors related to cytomegalovirus (CMV) disease (CMVd) during the 1st year of renal transplantation (RTx) and the relationship between CMVd and early and long-term graft and RTx-patient (RTx-p) survival were evaluated. In 505 RTx-p, followed up for 8(5–11) years, data were recorded after 1-(T1) and 12-(T12) months of RTx. CMVd was defined either by CMV replication without clinical signs of disease (CMVr, 43%), or CMV replication with signs of disease (CMVs, 57%). During the 1st year of RTx, 45% of RTx-p had CMVd (CMVd+). CMVd+ patients were older than CMVd− patients. Female gender and Donor CMV-IgG+ (CMV IgG−D+)/recipient IgG- (CMV IgG−R-) status were more prevalent in CMVd+. At T1, CMVd+ had lower albumin, haemoglobin, and higher uric-acid and reactive C-protein than CMVd− and, at T1 and T12, received more steroids. Albumin-T1 was the unique factor in determining CMVd+, maintaining its significance also after the inclusion of IgG−D+/IgG−R− status to the model. CMVs had higher prevalence of CMV IgG-D+/IgG-R- than CMVr. CMVd, CMVr, and CMVs had no impact on graft loss (11% of RTx-p) and RTx-p death (8% of RTx-p). CMVd is highly prevalent during the 1st year of RTx. Albumin-T1 influences CMVd insurgence. CMVd did not impact on RTx and RTx-p loss. Full article
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Pre-transplant and early infectious complications in the kidney transplant recipient
Authors: Beje Thomas, MD; Hector M. Madariaga, MD; Edgar V. Lerma, MD
Affiliation: (1) MedStart Georgetown University Hospital, Washington, DC, USA, (2) Good Samaritan Medical Center, Brockton, MA, USA (3)UIC/Advocate Christ Medical Center, Oak Lawn, IL, USA

Title: Central Nervous System Cryptococcosis In Kidney Transplant Recipients: Who, When, How, and Why?
Authors: Laurène Tardieu; Gillian Divard; Olivier Lortholary; Anne Scemla; Nassim Kamar; Eric Rondeau; Hannah Kaminsky; Moglie Le Quintrec Donnette; Valérie Moal; Christophe Legendre; Cécile Vig
Affiliation: Service des Urgences Néphrologiques et Transplantation rénale, Hôpital Tenon, Paris, France
Abstract: Cryptococcosis ranks as the third cause of fungal infection in solid organ transplant recipients (1). Central nervous system involvement (CNS) varies greatly in this setting with rates ranging from 25% to 72% (2–4) and has been recognized to portend an increased risk of mortality (2–4). Whether these results holds true in the context of kidney transplantation (KT) has never been verified (5). Furthermore, clinical features, radiological characteristics, laboratory findings and cerebrospinal fluid analysis had yet to be scrutinized in this specific population with cryptococcal meningitidis (CM). We performed a retrospective cohort study of adult patients diagnosed with cryptococcosis after kidney transplantation between 2002 and 2019 in France. Patients’ outcomes were compared according to CM. From 2002 and 2019, 88 cases of cryptococcosis were diagnosed in France in the setting of KT and included. CNS disease was the most common organ involvement in patients with cryptococcosis (n=61, 69.3%) and in 60.7% of cases, the CNS was the only site of infection. Of these 61 patients, only 2 did not yield fungemia. When considering patients with CM, 10% (n=6) disclosed no neurological symptoms at diagnosis. , Brain imaging (MRI and / or CT) was performed in 91.7% (n=77) of the cases of CM. The predominant injury patterns consisted in vascular damage (n=13, 15.5%), parenchymal lesions (n=12) and meningeal (pachymeningeal and leptomeningeal) lesions (n=11). Patient with CM were more likely to display higher serum cryptococcosis antigen titer and were more frequently fungemic than those without CM (48.3%, p=0.029). Fever was not associated with CM (61%, p=0.27). The time between transplantation and the onset of cryptococcosis did not differ whether patients presented with CM (35.7 [14.4-72.9] months) or not (36.4 [12.3-114.8], (p = 0.8497). CM was not significantly associated with a worst survival (p=0.409). Graft survival was not significantly altered whether CM was demonstrated or not (p=0.298). CM represents the prevailing organ involvement, consistent with previous studies indicating that non-HIV patients are more prone to developing CNS disease than HIV-related cryptococcosis (6–8). Brain imaging displayed 3 main types of injury patterns with a relative predominance of vascular involvement. Prior studies have produced conflicting results with respect to the type of CNS lesion upon imaging : Singh's study (5) did not describe cerebrovascular lesions in organ transplant recipients. Conversely, recent reports (9,10) highlighted the relative importance of vascular involvement with cerebral ischemia detected in 15-43% of non-HIV patients. Fungemia is closely associated with CM and should therefore encourage clinicians to perform CSF analysis and imaging to document CM. At odds with results stemming from previous studies in other settings, we failed to demonstrate that cryptococcosis-related CNS disease conferred a worst overall survival or kidney graft survival

Title: OUTCOMES OF PATIENTS RECEIVING A KIDNEY TRANSPLANT OR REMAINING ON DIALYSIS AT THE EPICENTRUM OF THE COVID-19 PANDEMIC: AN OBSERVATIONAL COMPARATIVE STUDY.
Authors: Evaldo Favi 1,2, Marta Perego 1, Samuele Iesari 1, Maria Teresa Gandolfo 3, Carlo Alfieri 2,3, Serena Delbue 4, Roberto Cacciola 5,6, Mariano Ferraresso 1,2
Affiliation: 1 Kidney Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy 2 Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Milan, Italy 3 Nephrology, Dialysis and Transplantation, Fondazione IRCCS Ca' Granda Ospedale Maggiore Policlinico, Milan, Italy 4 Department of Biomedical, Surgical and Dental Sciences, Università degli Studi di Milano, Milan, Italy 5 Surgery, King Salman Armed Forces Hospital, Tabuk, Kingdom of Saudi Arabia 6 HPB Surgery and Transplantation, Fondazione PTV, Rome, Italy
Abstract: Background. Since the declaration of the first wave COVID-19 pandemic, we have witnessed a dramatic reduction in the number of solid organ transplants performed worldwide. Besides the generalized healthcare crisis, this unprecedented drop of the kidney transplant (KT) rate recognizes multiple reasons such as the risk of direct viral transmission through the allograft, the perceived increase in SARS-CoV-2-related mortality and morbidity in immunocompromised hosts, and the possibility to safely remain on dialysis while waiting for an effective antiviral treatment. As a leading national healthcare service hospital operating at the epi-centrum of the COVID-19 pandemic (Milan, Italy), our institution continued the adult KT program without prespecified restrictions or limitations. We herein report our experience offering an in-depth evaluation of the outcomes of the patients transplanted or remaining on the transplant waiting list, before and during the pandemic. Methods. In this single-centre retrospective observational study with a median follow-up of 1 year, we analysed baseline characteristics and outcomes of four groups of patients: 1) subjects transplanted during the pandemic (COV-KT, n=123); 2) subjects transplanted before the pandemic (pre-COV-KT, n=122); 3) subjects awaiting a KT during the pandemic (COV-WL, n=396); and 4) subjects awaiting a KT before the pandemic (pre-COV-WL, n=427). Donors, recipients and patients in the WL were regularly screened for SARS-CoV-2 infection by PCR assay on nasal swab, BAS and/or BAL as appropriate. Results. Main demographic and clinical characteristics of the patients in the WL (pre-COV-WL or COV-WL) were equivalent whereas there was a significant difference in the prevalence of diabetes mellitus between pre-COV-KT and COV-KT (15.6% vs 4.1%; P<0.05). We observed that the pandemic did not affect post-transplant mortality or allograft loss as the number of events for each group was substantially similar (death: n=1 in pre-COV-KT vs n=2 in COV-KT; graft loss: n=6 in pre-COV-KT vs n=8 in COV-KT). On the contrary, there was an excess in mortality among COV-WL patients compared to pre-COV-WL (n=19 vs n=10). This discrepancy was primarily caused by SARS-CoV-2 infection (7/19). Patients transplanted during the pandemic exhibited slightly higher DGF rate (28% vs 22%; P=ns) and incidence of rejection (n=14 vs n=11). After 1-year follow-up, recipients in the COV-KT group showed significantly higher median serum creatinine than those in pre-COV-KT group. Median tacrolimus levels, MMF and steroid daily doses were not significantly different at any time point of the study, reflecting the fact that we did not change our immunosuppressive strategy after the onset of the pandemic. Overall, we recorded 22 COVID-19 infections in COV-KT (asymptomatic: n=5; moderate: n=13; severe: n=4), 19 in pre-COV-KT (asymptomatic: n=2: moderate: n=10; severe: n=7; and fatal: n=3), and 43 in COV-WL (asymptomatic: n=13; moderate: n=13; severe: n=15; and fatal: n=7). Infections were mostly acquired during in-centre haemodialysis or while attending outpatient clinics. Conclusions. Our study demonstrates that KT performed during the COVID-19 pandemic were not associated with increased mortality or inferior transplant-related outcomes compared to KT carried out before the pandemic. The observation that overall survivals in transplant recipients and patients remaining in the WL were substantially similar, might reassure transplant centres willing to continue their programs and might offer some reliable data for patient counselling. The perceived increase in the risk of death from SARS-CoV-2 among those awaiting a KT further supports this point of view provided that strict infection control strategies and aggressive follow-up monitoring are adopted. National multicentre studies with wider populations and different logistics are warranted.

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