Submit to JCM Review for JCM Propose a Special Issue

Journal Browser

Optimizing Drug Therapy and Developing Novel Therapeutic Interventions in Nephrology

Print Special Issue Flyer
Special Issue Editors
Special Issue Information
Keywords
Published Papers

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 (1 October 2021) | Viewed by 27710

Share This Special Issue

Special Issue Editors

Dr. Smaragdi Marinaki

E-Mail Website
Guest Editor

Department of Nephrology and Renal Transplantation, Laiko Hospital, Medical School, National & Kapodistrian University of Athens, 11527 Athens, Greece
Interests: glomerular disease; lupus nephritis; kidney transplantation; nephrotic syndrome
Special Issues, Collections and Topics in MDPI journals

Dr. Sophia Lionaki

E-Mail Website
Guest Editor

Department of Nephrology, Attikon University Hospital, National and Kapodistrian University of Athens, Athens, Greece
Interests: glomerular disease; IgA nephropathy; ANCA vasculitis and glomerulonephritis; membranous nephropathy; lupus nephritis; complement-mediated glomerular diseases
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Novel therapeutic agents have been widely used in the field of nephrology, primarily in immune-mediated glomerular diseases and renal transplantation and to a lesser extend in AKI, CKD, and inherited kidney diseases such as APDKD.

Immunosuppressive agents are the mainstay of therapy; they were first introduced in the early ‘60s with non-specific immunosuppressants such as azathioprine and corticosteroids. In the ‘80s, the introduction of the first of the two calcineurin inhibitors, ciclosporin, produced a revolutionary improvement in outcomes of renal transplantation. The ‘90s were the period of the most significant immunosuppressive drug development. Toxicities of early immunosuppressants and a better understanding of the mechanisms of auto- and alloimmunity have led to the introduction of therapeutic agents, with many of them being monoclonal antibodies, that selectively target humoral and cellular immunity pathways such as B-cell and plasma cell depleting agents, T-cell targeted therapies blocking the three signals of T-cell activation and proliferation, complement inhibitors, cytokine inhibitors, etc, as well as modalities for removing circulating factors such as plasmapheresis and immunoadsorption.

Besides immunosuppressants, investigational agents that slow down fibrosis such as senolytic drugs, the vasopressin V2-receptor antagonist that delays cyst development in APDKD, and SGLT2 inhibitors (gliflozins) in DM type II have all been used with promising results.

The purpose of this Special Issue is to place these agents into a context together with a brief discussion of unique features of their development and their use that will be of interest to many specialists of internal medicine.

Dr. Smaragdi Marinaki
Dr. Sophia Lionaki
Guest Editors

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 submissions that pass pre-check are 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 semimonthly 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 2600 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

B-cell depleting therapies
T-cell therapies
complement inhibition
vasopressin antagonists
antidiabetics
plasmapheresis
cytokine inhibition

Published Papers (13 papers)

Download All Papers

Research

Jump to: Review

13 pages, 4263 KiB

Open AccessArticle

Single, Double and Triple Blockade of RAAS in Alport Syndrome: Different Tools to Freeze the Evolution of the Disease

by Antonio Mastrangelo, Marta Brambilla, Giorgia Romano, Jessica Serafinelli, Giuseppe Puccio, Marisa Giani and Giovanni Montini

J. Clin. Med. 2021, 10(21), 4946; https://doi.org/10.3390/jcm10214946 - 26 Oct 2021

Cited by 6 | Viewed by 1570

Abstract

Background: The goal of the treatment of Alport syndrome (AS) is to delay the progression of kidney damage. The current standard of care is the use of Renin Angiotensin Aldosterone System (RAAS) blockers: angiotensin-converting enzyme inhibition (ACEi), angiotensin receptor blockade, and, recently, spironolactone (SP). Aim of the study: the purpose of this retrospective study is to evaluate the efficacy (reduction of proteinuria and changes of glomerular function) and safety of a sequential introduction of RAAS blockers up to a triple RAAS blockade in pediatric proteinuric patients with AS. Methods: in this retrospective study (1995 to 2019), we evaluated proteinuria values in AS patients, during the 12 months following the beginning of a new RAAS blocker, up to a triple blockade. ACEi was always the first line of treatment; then ARB and SP were sequentially added if uPCR increased by 50% from the basal level in 2 consecutive samples during a 3-months observation period, or when uPCR ratio was >2 mg/mg. Results: 26 patients (mean age at treatment onset was 10.55 ± 5.02 years) were enrolled. All patients were on ACEi, 14/26 were started on a second drug (6/14 ARB, 8/14 SP) after a mean time of 2.2 ± 1.7 years, 7/26 were on triple RAAS blockade after a further period of 5.5 ± 2.3 years from the introduction of a second drug. Repeated Measure Anova analysis of log-transformed data shows that the reduction of uPCR values after Time 0 from the introduction of the first, second and third drug is highly significant in all three cases (p values = 0.0016, 0.003, and 0.014, respectively). No significant changes in eGFR were recorded in any group, apart from a 15-year-old boy with X-linked AS, who developed kidney failure. One patient developed mild hyperkaliemia, and one gynecomastia and symptomatic hypotension. No life-threatening events were recorded. Conclusions: double and triple RAAS blockade is an effective and safe strategy to reduce proteinuria in children with AS. Nevertheless, we suggest monitoring eGFR and Kaliemia during follow-up. Full article

(This article belongs to the Special Issue Optimizing Drug Therapy and Developing Novel Therapeutic Interventions in Nephrology)

► Show Figures

Figure 1

11 pages, 581 KiB

Open AccessArticle

Assessment of Hyperglycemia, Hypoglycemia and Inter-Day Glucose Variability Using Continuous Glucose Monitoring among Diabetic Patients on Chronic Hemodialysis

by Maria Divani, Panagiotis I. Georgianos, Triantafyllos Didangelos, Vassilios Liakopoulos, Kali Makedou, Fotios Iliadis, Christos Savopoulos and Dimitrios M. Grekas

J. Clin. Med. 2021, 10(18), 4116; https://doi.org/10.3390/jcm10184116 - 12 Sep 2021

Cited by 6 | Viewed by 1823

Abstract

Continuous glucose monitoring (CGM) facilitates the assessment of short-term glucose variability and identification of acute excursions of hyper- and hypo-glycemia. Among 37 diabetic hemodialysis patients who underwent 7-day CGM with the iPRO2 device (Medtronic Diabetes, Northridge, CA, USA), we explored the accuracy of glycated albumin (GA) and hemoglobin A1c (HbA1c) in assessing glycemic control, using CGM-derived metrics as the reference standard. In receiver operating characteristic (ROC) analysis, the area under the curve (AUC) in diagnosing a time in the target glucose range of 70–180 mg/dL (TIR^70–180) in <50% of readings was higher for GA (AUC: 0.878; 95% confidence interval (CI): 0.728–0.962) as compared to HbA1c (AUC: 0.682; 95% CI: 0.508–0.825) (p < 0.01). The accuracy of GA (AUC: 0.939; 95% CI: 0.808–0.991) in detecting a time above the target glucose range > 250 mg/dL (TAR^>250) in >10% of readings did not differ from that of HbA1c (AUC: 0.854; 95% CI: 0.699–0.948) (p = 0.16). GA (AUC: 0.712; 95% CI: 0.539–0.848) and HbA1c (AUC: 0.740; 95% CI: 0.570–0.870) had a similarly lower efficiency in detecting a time below target glucose range < 70 mg/dL (TBR^<70) in >1% of readings (p = 0.71). Although the mean glucose levels were similar, the coefficient of variation of glucose recordings (39.2 ± 17.3% vs. 32.0 ± 7.8%, p < 0.001) and TBR^<70 (median (range): 5.6% (0, 25.8) vs. 2.8% (0, 17.9)) were higher during the dialysis-on than during the dialysis-off day. In conclusion, the present study shows that among diabetic hemodialysis patients, GA had higher accuracy than HbA1c in detecting a 7-day CGM-derived TIR^70–180 < 50%. However, both biomarkers provided an imprecise reflection of acute excursions of hypoglycemia and inter-day glucose variability. Full article

(This article belongs to the Special Issue Optimizing Drug Therapy and Developing Novel Therapeutic Interventions in Nephrology)

► Show Figures

Figure 1

9 pages, 1578 KiB

Open AccessArticle

Survival of Peritoneal Membrane Function on Biocompatible Dialysis Solutions in a Peritoneal Dialysis Cohort Assessed by a Novel Test

by Olga Balafa, Anila Duni, Paraskevi Tseke, Karolos Rapsomanikis, Paraskevi Pavlakou, Margarita Ikonomou, Vasileios Tatsis and Evangelia Dounousi

J. Clin. Med. 2021, 10(16), 3650; https://doi.org/10.3390/jcm10163650 - 18 Aug 2021

Cited by 1 | Viewed by 1440

Abstract

Background: Longitudinal surveillance of peritoneal membrane function is crucial in defining patients with a risk of ultrafiltration failure. Long PD is associated with increased low molecular weight solute transport and decreased ultrafiltration and free water transport. Classic PET test only provides information about low molecular solute transport, and the vast majority of longitudinal studies are based on this test and include patients using conventional dialysates. Our aim was to prospectively analyze longitudinal data on peritoneal function in patients on biocompatible solutions using a novel test. Methods: Membrane function data were collected based on uni-PET (a combination of modified and mini PET). A total of 85 patients (age 61.1 ± 15.1 years) with at least one test/year were included. Results: The median follow up was 36 months (21.3, 67.2). A total of 219 PETs were performed. One-way repeated measures ANOVA showed that there were no statistically significant differences over time in ultrafiltration, free water transport, ultrafiltration through small pores, sodium removal, D/D0 and D/PCre in repeated PET-tests. Twenty-three tests revealed ultrafiltration failure in 16 (18.8%) patients. Those patients were longer on PD, had higher D/P creatinine ratios, lower ultrafiltration at one hour with lower free water transport and higher urine volume at baseline. Multivariate analysis revealed that the variation of ultrafiltration over repeated PET-tests independently correlated only with D/Pcreatinine, free water transport and ultrafiltration through small pores. Conclusions. Uni-PET is a combination of two tests that provides more information on the function of the membrane compared with PET. Our study on a PD cohort using only biocompatible solutions revealed that function membrane parameters remained stable over a long time. Ultrafiltration failure was correlated with increased D/P creatinine and decreased free water transport and ultrafiltration through small pores. Full article

(This article belongs to the Special Issue Optimizing Drug Therapy and Developing Novel Therapeutic Interventions in Nephrology)

► Show Figures

Figure 1

13 pages, 1031 KiB

Open AccessArticle

Clinical Characteristics and Outcomes of Adults with Nephrotic Syndrome Due to Minimal Change Disease

by Sophia Lionaki, Evangelos Mantios, Ioanna Tsoumbou, Smaragdi Marinaki, George Makris, George Liapis, Chrysovalantis Vergandis and Ioannis Boletis

J. Clin. Med. 2021, 10(16), 3632; https://doi.org/10.3390/jcm10163632 - 17 Aug 2021

Cited by 5 | Viewed by 2926

Abstract

Purpose: Minimal change disease (MCD) is considered a relatively benign glomerulopathy, as it rarely progresses to end-stage kidney disease. The aim of this study was to describe the characteristics and outcomes of adults with MCD and identify potential risk factors for relapse. Patients & Methods: We retrospectively studied a cohort of adults with biopsy-proven MCD in terms of clinical features and treatment outcomes. Baseline characteristics and outcomes were recorded and predictors of relapse were analyzed using logistic regression multivariate analysis. Results: 59 patients with adult-onset primary MCD with nephrotic syndrome were included. Mean serum creatinine at diagnosis was 0.8 mg/dL (±2.5) and estimated GFR (eGFR) was 87 mL/min/1.73 m² (±29.5). Mean serum albumin was 2.5 g/dL (±0.8) and 24 h proteinuria 6.8 g (±3.7). Microscopic hematuria was detected in 35 (58.5%) patients. 42 patients received prednisone alone, six patients received prednisone plus cyclophosphamide, five patients received prednisone plus cyclosporine, one patient received prednisone plus rituximab and five patients did not receive immunosuppression at all since they achieved spontaneous remission. During a mean follow up time of 34.7(22.1) months, 46.1% of patients experienced at least one episode of relapse. The mean age of patients who did not experience a relapse was significantly higher than that of patients who relapsed while relapsers had a significantly longer duration of 24 h proteinuria prior to biopsy compared to non-relapsers. Overall, 10% of patients experienced acute kidney injury while the mean eGFR at the end was 82 mL/min/1.73 m² (±29.1) and one patient ended up in chronic dialysis. Overall, the proportion of non-relapsers, who experienced acute kidney injury (17%) was significantly higher than the one recorded among relapsers (0%).Conclusion: In this series of patients, almost 46% of adult-onset nephrotic MCD patients experienced a relapse, although their renal progression was rare. Younger onset age was an independent risk factor for relapse in adult-onset MCD patients. Full article

(This article belongs to the Special Issue Optimizing Drug Therapy and Developing Novel Therapeutic Interventions in Nephrology)

► Show Figures

Figure 1

12 pages, 4528 KiB

Open AccessArticle

Organoprotective Effects of Spironolactone on Top of Ramipril Therapy in a Mouse Model for Alport Syndrome

by Diana Rubel, Yanqin Zhang, Nenja Sowa, Rainer Girgert and Oliver Gross

J. Clin. Med. 2021, 10(13), 2958; https://doi.org/10.3390/jcm10132958 - 30 Jun 2021

Cited by 7 | Viewed by 2126

Abstract

Angiotensin-converting enzyme inhibitors (ACEi) delay progression of the inherited renal disease Alport syndrome. However, the effect of ACEis weakens gradually due to an “aldosterone escape”. Here, we investigate if an aldosterone antagonist can counteract loss of ACEi-efficacy. COL4A3-/- mice were treated with ramipril (ACEi), starting at 4.5 weeks of age, and spironolactone was added at 7 weeks of age. Lifespan until renal failure, as well as kidney function parameters, were investigated. Dual therapy decreased proteinuria levels compared to ACEi monotherapy. Matrix accumulation, as well as tubulointerstitial and glomerular scar-tissue formation, were significantly reduced compared to untreated mice and ACEi-monotherapy at 75 and 100 days. Lifespan in dual treated mice was extended compared to untreated mice. However, lifespan was not superior to ACEi monotherapy–despite improved urea-nitrogen levels in the dual therapy group. In conclusion, adding the aldosterone-antagonist spironolactone to ACEi therapy further improved kidney function and reduced proteinuria and fibrosis. However, survival was not improved further, possibly due to premature death from side effects of dual therapy such as hyperkalemia. Thus, dual therapy could offer an effective therapy option for Alport syndrome patients with progressive proteinuria. However, the risks of adverse events require close monitoring. Full article

(This article belongs to the Special Issue Optimizing Drug Therapy and Developing Novel Therapeutic Interventions in Nephrology)

► Show Figures

Figure 1

14 pages, 1237 KiB

Open AccessArticle

Gene Expression as a Guide to the Development of Novel Therapies in Primary Glomerular Diseases

by Panagiotis Garantziotis, Stavros A. P. Doumas, Ioannis Boletis and Eleni Frangou

J. Clin. Med. 2021, 10(11), 2262; https://doi.org/10.3390/jcm10112262 - 24 May 2021

Viewed by 1990

Abstract

Despite improvements in understanding the pathogenic mechanisms of primary glomerular diseases, therapy still remains nonspecific. We sought to identify novel therapies targeting kidney-intrinsic injury of distinct primary glomerulonephritides through computational systems biology approaches. We defined the unique transcriptional landscape within kidneys from patients with focal segmental glomerulosclerosis (FSGS), minimal change disease (MCD), immunoglobulin A nephropathy (IgAN), membranous nephropathy (MN) and thin basement membrane nephropathy (TBMN). Differentially expressed genes were functionally annotated with enrichment analysis, and distinct biological processes and pathways implicated in each primary glomerular disease were uncovered. Finally, we identified novel drugs and small-molecule compounds that may reverse each glomerulonephritis phenotype, suggesting they should be further tested as precise therapy in primary glomerular diseases. Full article

(This article belongs to the Special Issue Optimizing Drug Therapy and Developing Novel Therapeutic Interventions in Nephrology)

► Show Figures

Figure 1

10 pages, 1097 KiB

Open AccessArticle

The Relation of Clinic and Ambulatory BP with the Risk of Cardiovascular Events and All-Cause Mortality among Patients on Peritoneal Dialysis

by Panagiotis I. Georgianos, Vasilios Vaios, Pantelis E. Zebekakis and Vassilios Liakopoulos

J. Clin. Med. 2021, 10(11), 2232; https://doi.org/10.3390/jcm10112232 - 21 May 2021

Cited by 2 | Viewed by 1604

Abstract

Large observational studies showed a U-shaped association of clinic blood pressure (BP) with mortality among patients undergoing peritoneal dialysis (PD). Whether ambulatory BP provides a more direct risk signal in this population remains unknown. In a prospective cohort of 108 PD patients, standardized clinic BP was recorded at baseline with the validated device HEM-705 (Omron, Healthcare, Bannockburn, IL, USA) and 24-h ambulatory BP monitoring was performed using the Mobil-O-Graph monitor (IEM, Stolberg, Germany). Over a median follow-up of 16 months (interquartile range: 19 months), 47.2% of the overall population reached the composite outcome of non-fatal myocardial infarction, non-fatal stroke, or all-cause death. In Cox-regression analysis, systolic but not diastolic BP was prognostically informative. Compared with the reference quartile 1 of 24-h systolic BP (SBP), the multivariate-adjusted hazard ratio for the composite outcome was 1.098 (95% confidence interval (CI): 0.434–2.777) in quartile 2, 1.004 (95% CI: 0.382–2.235) in quartile 3 and 2.449 (95% CI: 1.156–5.190) in quartile 4. In contrast, no such association was observed between increasing quartiles of clinic SBP and composite outcome. The present study shows that among PD patients, increasing ambulatory SBP is independently associated with higher risk of adverse cardiovascular events and mortality, providing superior prognostic information than standardized clinic SBP. Full article

(This article belongs to the Special Issue Optimizing Drug Therapy and Developing Novel Therapeutic Interventions in Nephrology)

► Show Figures

Figure 1

13 pages, 9017 KiB

Open AccessArticle

Serum Levels of miR-148b and Let-7b at Diagnosis May Have Important Impact in the Response to Treatment and Long-Term Outcome in IgA Nephropathy

by Nikoleta M. Kouri, Maria Stangou, George Lioulios, Zoi Mitsoglou, Grazia Serino, Samantha Chiurlia, Sharon Natasha Cox, Persia Stropou, Francesco P. Schena and Aikaterini Papagianni

J. Clin. Med. 2021, 10(9), 1987; https://doi.org/10.3390/jcm10091987 - 05 May 2021

Cited by 9 | Viewed by 1770

Abstract

Background/aims: Previous studies showed that two microRNAs, let-7b and miR-148, which regulate the O-glycosylation process of IgA1, may predict diagnosis of primary IgA nephropathy (IgAN). The combined analysis of their serum levels in calculated statistical models may act as serum biomarkers for the diagnosis of primary IgAN. In the present study, we aimed to assess their impact not only on clinical and histological findings at onset but also on renal function after a long-term follow-up. Patients and methods: We enrolled 61 Caucasian patients with biopsy-proven IgAN. Serum levels of miR-148b, let-7b, and galactose-deficient IgA1 (Gd-IgA1) at the time of diagnosis were measured using real-time quantitative PCR and enzyme-linked immunosorbent assay using the monoclonal antibody KM55, respectively. Their values along with calculated Models 1 and 2 were correlated with histologic scoring system (Oxford classification system) and with renal function at diagnosis and after 11.9 ± 6.6 years. Fifty-five healthy volunteers were enrolled as controls. Results: No significant correlation was found between miRNA and Gd-IgA1 levels and eGFR and proteinuria at diagnosis. A significant negative association was detected between the presence of crescents and serum levels of let-7b (p = 0.002), miR-148b (p = 0.01), and Models 1 and 2 (p = 0.02 and p = 0.007, respectively). At the end of follow-up, eGFR correlated with let-7b levels (p = 0.01), Model 1 (p = 0.002), and Model 2 (p = 0.004). Patients with fast progression of the renal damage had significantly increased levels of let-7b (p = 0.01), Model 1 (p = 0.003), and Model 2 (p = 0.005) compared to slow progressors, as did those who reached ESKD (p = 0.002, p = 0.001, and p = 0.001, respectively). Results were most prominent in those treated with corticosteroids. Finally, cut off levels in Models 1 and 2 could also predict the renal function outcome after long-term follow-up. Conclusions: Serum levels of let-7b and miR-148b and their combination, may serve as predictors for long-term renal function outcomes, particularly in patients treated with corticosteroids. Full article

(This article belongs to the Special Issue Optimizing Drug Therapy and Developing Novel Therapeutic Interventions in Nephrology)

► Show Figures

Figure 1

10 pages, 1023 KiB

Open AccessArticle

Impaired Kidney Function Associated with Increased Risk of Side Effects in Patients with Small Vessel Vasculitis Treated with Rituximab as an Induction Therapy

by Aleksandra Rymarz, Anna Matyjek, Magdalena Sułek-Jakóbczyk, Magdalena Mosakowska and Stanisław Niemczyk

J. Clin. Med. 2021, 10(4), 786; https://doi.org/10.3390/jcm10040786 - 16 Feb 2021

Cited by 5 | Viewed by 1691

Abstract

Rituximab (RTX), a monoclonal antibody against the CD20 molecule, is used as an induction therapy in the treatment of small vessel vasculitis (SVV). The aim of the study was to evaluate the efficacy and safety of RTX induction therapy for refractory SVV. A retrospective analysis of 20 patients treated with RTX for active SVV (BVAS/WG ≥ 3) was performed to assess the remission rate and the drug-related severe adverse events 6 months after therapy. The mean age of the studied population was 49 ± 13 years (50% female), 90% of which were PR3-ANCA positive. Complete remission was achieved in 85% of patients, and partial remission was achieved in a further 10% within 6 months after RTX infusions. The remission rate was not influenced by kidney function. Adverse events such as infections (25%), a late onset of neutropenia (10%) and severe hypogammaglobulinemia (5%) were noted. The patients who developed adverse events were older (42 ± 11 vs. 57 ± 12 years; p = 0.014) and had a higher serum creatinine level (1.3 mg/dL vs. 3.35 mg/dL; p = 0.044). Patients with a glomerular filtration rate (eGFR) lower than 30 mL/min/1.73 m² had a nine-fold higher risk of side effects (OR 9.0, 95%CI: 1.14–71.0). In conclusion, RTX was highly effective as an induction therapy in patients with SVV. Advanced kidney failure with an eGFR lower than 30 mL/min/1.73 m² was one of the risk factors for the occurrence of side effects. Full article

(This article belongs to the Special Issue Optimizing Drug Therapy and Developing Novel Therapeutic Interventions in Nephrology)

► Show Figures

Figure 1

11 pages, 392 KiB

Open AccessArticle

Impact of Angiotensin-Converting Enzyme Inhibitors or Angiotensin Receptor Blockers on Acute Kidney Injury in Emergency Medical Admissions

by Athanasios Feidakis, Maria-Rosa Panagiotou, Emmanouil Tsoukakis, Dimitra Bacharaki, Paraskevi Gounari, Petros Nikolopoulos, Katerina P. Marathias, Sophia Lionaki and Demetrios Vlahakos

J. Clin. Med. 2021, 10(3), 412; https://doi.org/10.3390/jcm10030412 - 22 Jan 2021

Cited by 7 | Viewed by 2160

Abstract

Background: Acute kidney injury (AKI) has been observed in up to 20% of adult hospital admissions. Sepsis, diarrhea and heart failure, all causing reduced effective volume, are considered risk factors for AKI, especially among patients treated with medications that block the Renin-Angiotensin System (RAS), such as angiotensin-converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB). We aimed to determine the incidence of acute kidney injury (AKI) in emergency medical admissions in relation to the use and dosage of ACEi/ARB. Methods: A single-center observational study conducted in 577 consecutive medical admissions via the Emergency Room (ER) at a University General Hospital in Athens, Greece, between June and July 2018. Patients with incomplete medical records, discharged within 24 h, maintained on chronic renal replacement therapy, admitted to the Cardiology Department or the ICU were excluded. Thus, a total of 309 patients were finally included in this analysis. Results: We compared 86 (28%) patients who presented in the ER with AKI (AKIGroup) with 223 (72%) patients without AKI (non-AKI Group) at the time of admission. Patients in the AKI Group were more frequently male (58% vs. 46%, p = 0.06), with a higher frequency of diarrhea (16% vs. 6%, p = 0.006), edema (15% vs. 6%, p = 0.014) and lower systolic blood pressure (120 (107–135) vs. 126 (113–140), p = 0.007) at presentation, despite higher prevalence of hypertension (64% vs. 47%, p = 0.006). Overall, ACEi/ARB were more likely to have been prescribed in the AKI Group than in the non-AKI Group (49% vs. 28%, p = 0.001). Interestingly, AKI was more frequently observed in patients treated with the target or above target dosage of ACEi/ARB, but not in those receiving lower than the recommended dosage. Conclusion: The risk of AKI in emergency medical admissions is higher among users of ACEIs/ARB at target or above target dosages. Physicians should adjust RAS blockade according to estimated Glomerular Filtration Rate (eGFR) and advise their patients to withhold ACEi/ARB in cases of acute illness. Full article

(This article belongs to the Special Issue Optimizing Drug Therapy and Developing Novel Therapeutic Interventions in Nephrology)

► Show Figures

Figure 1

11 pages, 718 KiB

Open AccessArticle

Therapeutic Options for Recurrence of Primary Focal Segmental Glomerulonephritis (FSGS) in the Renal Allograft: Single-Center Experience

by Kalliopi Vallianou, Smaragdi Marinaki, Chrysanthi Skalioti, Sophia Lionaki, Maria Darema, Christina Melexopoulou and Ioannis Boletis

J. Clin. Med. 2021, 10(3), 373; https://doi.org/10.3390/jcm10030373 - 20 Jan 2021

Cited by 11 | Viewed by 2275

Abstract

Focal Segmental Glomerulosclerosis (FSGS) recurrence after kidney transplantation (KTx) is relatively frequent and is associated with poor graft survival. The aim of this study was to investigate which management strategies were associated with better outcomes in our cohort of KTx recipients with primary FSGS. We retrospectively collected data on patients with primary FSGS who received a KTx between 1993 and 2019. A history of biopsy proven FSGS in native kidneys and new onset of significant proteinuria early post-KTx led to the diagnosis of recurrence, which was confirmed by graft biopsy. From 1993 to 2019 we performed 46 KTxs in patients with primary FSGS. We identified 26 episodes of recurrence in 25 patients, 67% of them occurring in males. They were younger at the time of KTx (33.8 vs. 41.1 years old, p = 0.067) and had progressed to end stage renal disease (ESRD) faster after FSGS diagnosis (61.4 vs. 111.2 months, p = 0.038), while they were less likely to have received prophylactic plasmapheresis (61.5% vs. 90%, p = 0.029). 76.7% of recurrences were found early, after a median of 0.5 months (IQR 0.1–1) with a median proteinuria was 8.5 (IQR 4.9–11.9) g/day. All patients with recurrence were treated with plasmapheresis, while 8 (30.7%) additionally received rituximab, 1 (3.8%) abatacept, and 4 (15.4%) ACTH. 7 (27%) patients experienced complete and 11 (42.3%) partial remission after a mean time of 3 (±1.79) and 4.4 (±2.25) months, respectively. Prognosis was worse for patients who experienced a recurrence. Eleven (42.3%) patients lost their graft from FSGS in a median time of 33 (IQR 17.5–43.3) months. In this series of patients, primary FSGS recurred frequently after KTx. Prophylacic plasmapheresis was shown efficacious in avoiding FSGS recurrence, while timely diagnosis and plasmapheresis-based regimens induced remission in more than half of the patients. Full article

(This article belongs to the Special Issue Optimizing Drug Therapy and Developing Novel Therapeutic Interventions in Nephrology)

► Show Figures

Figure 1

Review

Jump to: Research

9 pages, 244 KiB

Open AccessReview

Plasma Exchange in ANCA-Associated Vasculitis: A Narrative Review

by Stathis Tsiakas, Smaragdi Marinaki, Sophia Lionaki and John Boletis

J. Clin. Med. 2021, 10(21), 5154; https://doi.org/10.3390/jcm10215154 - 03 Nov 2021

Viewed by 2016

Abstract

Therapeutic plasma exchange (TPE) is an adjunctive intervention to immunosuppression for the treatment of severe renal involvement or lung hemorrhage in patients with ANCA-associated vasculitis (AAV). Patients with AAV have an increased risk for progression to end-stage kidney disease (ESKD) or death despite advances in immunosuppressive therapy. The potential pathogenicity of ANCA makes TPE a reasonable treatment approach for the life-threatening complications of AAV. The efficacy of intensive TPE in rapidly progressive glomerulonephritis was originally described in small studies almost four decades ago. Further randomized trials examined the addition of TPE to standard of care, exhibiting mixed results in both patient and renal survival. The largest clinical trial to date, PEXIVAS, failed to demonstrate a clear benefit for TPE in severe AAV. In light of new evidence, the role of TPE remains controversial across the vasculitis medical community. The purpose of this review is to summarize the clinical indications and the current available data for the use of TPE in patients with severe AAV. Full article

(This article belongs to the Special Issue Optimizing Drug Therapy and Developing Novel Therapeutic Interventions in Nephrology)

18 pages, 358 KiB

Open AccessReview

Optimal Immunosuppression Strategy in the Sensitized Kidney Transplant Recipient

by Danae Olaso, Miriam Manook, Dimitrios Moris, Stuart Knechtle and Jean Kwun

J. Clin. Med. 2021, 10(16), 3656; https://doi.org/10.3390/jcm10163656 - 18 Aug 2021

Cited by 4 | Viewed by 3169

Abstract

Patients with previous sensitization events against anti-human leukocyte antigens (HLA) often have circulating anti-HLA antibodies. Following organ transplantation, sensitized patients have higher rates of antibody-mediated rejection (AMR) compared to those who are non-sensitized. More stringent donor matching is required for these patients, which results in a reduced donor pool and increased time on the waitlist. Current approaches for sensitized patients focus on reducing preformed antibodies that preclude transplantation; however, this type of desensitization does not modulate the primed immune response in sensitized patients. Thus, an optimized maintenance immunosuppressive regimen is necessary for highly sensitized patients, which may be distinct from non-sensitized patients. In this review, we will discuss the currently available therapeutic options for induction, maintenance, and adjuvant immunosuppression for sensitized patients. Full article

(This article belongs to the Special Issue Optimizing Drug Therapy and Developing Novel Therapeutic Interventions in Nephrology)

Journal Menu

Journal Browser

Optimizing Drug Therapy and Developing Novel Therapeutic Interventions in Nephrology

Share This Special Issue

Special Issue Editors

Special Issue Information

Keywords

Published Papers (13 papers)

Research

Review

Further Information

Guidelines

MDPI Initiatives

Follow MDPI