The National Organ Donation and Transplantation Program in Greece: Gap Analysis and Recommendations for Change.

Greece has fallen far behind many comparable European countries in the field of organ donation and transplantation and has made little progress over the past decade. Despite efforts to improve its organ donation and transplantation program, systemic problems persist. In 2019, the Onassis Foundation commissioned a report to be prepared by the London School of Economics and Political Science that focused on the state of the Greek organ donation and transplantation program and proposed recommendations for its improvement. In this paper, we present our analysis of the Greek organ donation and transplantation program together with an overview of our specific recommendations. The analysis of the Greek program was undertaken in an iterative manner using a conceptual framework of best practices developed specifically for this project. Our findings were further developed via an iterative process with information provided by key Greek stakeholders and comparisons with case studies that featured successful donation and transplantation programs in Croatia, Italy, Portugal, Spain, and the United Kingdom. Because of their overall complexity, we used a systems-level approach to generate comprehensive and far-reaching recommendations to address the difficulties currently experienced by the Greek organ donation and transplantation program.

Kidney transplantation and kidney donation do not affect short-term blood pressure variability.

PURPOSE: Blood pressure variability (BPV) is an independent cardiovascular risk factor in CKD. Kidney transplantation (KTx) is associated with improved BP levels for kidney transplant recipient (KTRs), without evoking significant changes in donors. The aim of this study was to assess the short- and mid-time effects of KTx and donation on short-term BPV in KTRs and their respective living kidney donors. MATERIALS AND METHODS: Forty KTRs and their respective donors were evaluated with 24-h ABPM (Mobil-O-Graph-NG) at baseline (1 month before), 3-months and 12-months after KTx. Standard-deviation (SD), weighted-SD (wSD), coefficient-of-variation (CV), average-real-variability (ARV) and variability independent of mean (VIM) for SBP/DBP were calculated with validated formulas. RESULTS: All 24-h systolic and diastolic BPV indexes studied did not change significantly from baseline to 3-month (SBP-wSD: 12.8 ± 3.0 vs 13.2 ± 3.4 mmHg, p = 0.608; SBP-ARV: 10.3 ± 2.4 vs 10.8 ± 2.6 mmHg, p = 0.463) and 12-month evaluation (SBP-wSD 12.8 ± 3.0 vs 12.1 ± 2.8; p = 0.424 and SBP-ARV: 10.3 ± 2.4 vs 10.2 ± 2.5; p = 0.615) after kidney transplantation in the KTRs.In kidney donors, all 24-h systolic BPV indices displayed a trend towards higher values at 3 months compared to baseline, but without reaching statistical significance (SBP-wSD: 12.2 ± 2.8 vs 13.6 ± 4.2 mmHg, p = 0.107 and SBP-ARV: 10.1 ± 2.1 vs 11.2 ± 3.1 mmHg, p = 0.099), the levels of 24-h systolic SBP indices at 12-months were almost identical to baseline values. 24-h diastolic BPV indices at 3-month and 12-month evaluation were similar to baseline. CONCLUSION: Short-term BPV did not change significantly 3 and 12 months after kidney transplantation/donation neither in KTRs nor in living kidney donors. Longitudinal studies examining associations of BPV with adverse outcomes in these individuals are needed.

What is the context? Previous studies have shown that both office and ambulatory BP levels are significantly reduced after kidney transplantation in KTRs.On the other hand, existing evidence suggests that kidney donors' BP levels do not change significantly after kidney donation.Existing studies on BPV in KTRs are limited. The available data for living kidney donors are even fewer.What is new? This is the first study assessing short-term BPV levels in ΚTRs undergoing living donor kidney transplantation, and their respective donors in short-term and mid-term follow-up. The main findings were:All 24-h, daytime and night-time BPV indexes did not change significantly from baseline to 3- and 12-month evaluation after kidney transplantation in the KTRs.No significant changes for the 24-h, daytime and night-time BPV were observed in their respective kidney donors at the same follow-up periods.What is the impact?High BPV, which seems to remain unaltered after kidney transplantation, may be one of the many factors involved in the high cardiovascular risk observed in KTRs.Unchanged BPV levels further supports the evidence suggesting no higher risks of arrhythmias, cardiovascular events or death after living kidney donation.

Assessment of mRNA Vaccine Immunogenicity in Solid Organ Transplant Recipients.

Background and Objectives: Solid organ transplant (SOT) recipients have a higher risk of suffering from severe Coronavirus (COVID-19) compared to the general population. Studies have shown impaired immunogenicity of mRNA vaccines in this high-risk population; thus, SOT recipients have been prioritized globally for primary and booster doses. Materials and Methods: We analyzed 144 SOT recipients who had previously received two doses of BNT162b2 or mRNA1273 vaccine, and who were subsequently vaccinated with a booster dose of the mRNA1273 vaccine. Humoral and cellular immune responses were measured 1 and 3 months after the second dose, and 1 month after the third dose. Results: One month after the second dose, 33.6% (45/134) of patients displayed a positive antibody response with a median (25th, 75th) antibody titer of 9 (7, 161) AU/mL. Three months after the second dose, 41.8% (56/134) tested positive with a median (25th, 75th) antibody titer of 18 (7, 251) AU/mL. After the booster dose, the seropositivity rate increased to 69.4% (93/134), with a median (25th, 75th) titer of 966 (10, 8027) AU/mL. The specific SARS-CoV-2 T-cell response was assessed in 44 randomly selected recipients 3 months after the second dose, and 11.4% (5/44) of them had a positive response. Following the third dose, 42% (21/50) tested positive. Side effects after the third dose were mild, with pain at the injection site being the most frequent adverse effect, reported by 73.4% of the recipients. Conclusion: Our study shows a mild delayed increase in antibody titer, three months after primary vaccination compared to one month after. It also shows a robust augmentation of humoral and specific T-cell responses after the booster dose, as well as the safety and tolerability of the mRNA vaccines in SOT recipients.

Diagnostic Performance of Office versus Ambulatory Blood Pressure in Kidney Transplant Recipients.

INTRODUCTION: Hypertension is the most prominent risk factor in kidney transplant recipients (KTRs). No study so far assessed in parallel the prevalence, control, and phenotypes of blood pressure (BP) or the accuracy of currently recommended office BP diagnostic thresholds in diagnosing elevated ambulatory BP in KTRs. METHODS: 205 stable KTRs underwent office BP measurements and 24-h ambulatory BP monitoring (ABPM). Hypertension was defined as follows: (1) office BP ≥140/90 mm Hg or use of antihypertensive agents following the current European Society of Cardiology/European Society of Hypertension (ESC/ESH) guidelines, (2) office BP ≥130/80 mm Hg or use of antihypertensive agents following the current American College of Cardiology/American Heart Association (ACC/AHA) guidelines, (3) ABPM ≥130/80 mm Hg or use of antihypertensive agents, and (4) ABPM ≥125/75 mm Hg or use of antihypertensive agents. RESULTS: Hypertension prevalence by office BP was 88.3% with ESC/ESH and 92.7% with ACC/AHA definitions compared to 94.1 and 98.5% at relevant ABPM thresholds. Control rates among hypertensive patients were 69.6 and 43.7% with office BP compared to 38.3 and 21.3% with ABPM, respectively. Both for prevalence (κ-statistics = 0.52, p < 0.001 and 0.32, and p < 0.001) and control rates (κ-statistics = 0.21, p < 0.001 and 0.22, and p < 0.001, respectively), there was moderate or fair agreement of the 2 techniques. White-coat and masked hypertension were diagnosed in 6.7 and 39.5% of patients at the 140/90 threshold and 5.9 and 31.7% of patients at the 130/80 threshold. An office BP ≥140/90 mm Hg had 35.3% sensitivity and 84.9% specificity for the diagnosis of 24-h BP ≥130/80 mm Hg. An office BP ≥130/80 mm Hg had 59.7% sensitivity and 73.9% specificity for the diagnosis of 24-h BP ≥125/75 mm Hg. Receiver operating curve analyses confirmed this poor diagnostic performance. CONCLUSIONS: At both corresponding thresholds studied, ABPM revealed particularly high hypertension prevalence and poor BP control in KTRs. Misclassification of KTRs by office BP is substantial, due to particularly high rates of masked hypertension. The diagnostic accuracy of office BP for identifying elevated ambulatory BP is poor. These findings call for a wider use of ABPM in KTRs.

Blood pressure monitoring in kidney transplantation: a systematic review on hypertension and target organ damage.

BACKGROUND: Sparse studies show that ambulatory blood pressure monitoring (ABPM) is superior to office BP (oBP) measurements to predict target organ damage and cardiovascular (CV) events in kidney transplant recipients (KTRs). We performed a systematic review aimed at determining the potential associations between BP recordings by different methods and renal and CV outcomes in this population. METHODS: Major medical databases were searched for studies enrolling adult KTRs undergoing 24h ABPM compared to office or home BP measurements. Main outcomes were: associations between different BP recordings and renal and CV outcomes. Additionally, any association between the circadian BP pattern (dipping/non-dipping status) and outcomes was assessed. RESULTS: Twenty-two studies (2078 participants) were reviewed. Amongst 12 studies collecting data on renal endpoints, ten studies found that BP assessed by ABPM was a stronger predictor of renal function decline, assessed by serum creatinine (SCr) and/or creatinine clearance (CrCl) or estimated glomerular filtration rate (eGFR), than traditional office measurements. Twelve studies analyzed the relation between different BP recordings and CV target organ damages and reported robust correlations between echocardiographic abnormalities [i.e. left ventricular mass index (LVM/LVMI)] and 24h ABPM, but not with office BPs. Furthermore, 24h ABPM correlated better than oBP with markers of vascular damage, such as carotid intima-media thickness (IMT), diffuse thickening, and endothelial dysfunction. Additionally, abnormal circadian BP pattern (non-dippers and reverse dippers) identified a group of kidney recipients at risk for kidney function loss and CV abnormalities. CONCLUSIONS: In our systematic review, ABPM reflected target organ damage more closely than oBP in KTRs. Furthermore, altered circadian BP profile associated with renal and CV target organ damages.

De Novo Minimal Change Disease following Vaccination with the Pfizer/BioNTech SARS-CoV-2 Vaccine in a Living Kidney Donor.

Coronavirus disease 2019 has developed as a pandemic. Immunization with the introduction of vaccines against COVID-19 seems be the only way to end this pandemic. We report on a case of a kidney donor, who developed minimal change disease (MCD) within 4 days post-vaccination with the SARS-CoV-2 BNT162b2 mRNA vaccine (Pfizer/BioNTech). She donated her kidney to her husband 4 years ago. After receiving the 1st vaccine dose, she presented with nephrotic syndrome, with complete remission 5 days later. She proceeded with the second dose of the BNT162b2 vaccine at the appointed time. Two days later, she presented with a relapse of full-blown nephrotic syndrome with preserved renal function. We performed an ultrasound-guided percutaneous kidney biopsy and the final diagnosis was consistent with minimal change disease. Oral prednisolone was promptly initiated at a dosage of 1 mg/kg daily and complete remission was achieved 10 days later. More data about this rare appearance of de novo glomerular diseases after SARS-CoV-2 vaccination are emerging and should be interpreted rigorously.

A Patient with Cryoglobulinemic Membranoproliferative GN (MPGN) Who Survived COVID-19 Disease: Case Presentation and Current Data of COVID-19 Infection in Dialysis and Transplanted Patients in Greece.

The evolving pandemic of Coronavirus Disease 2019 has posed a substantial health risk worldwide. However, there is a paucity of data regarding the clinical course and the therapeutic management of patients with chronic kidney disease and COVID-19 infection. To date, most evidence has come from renal transplantation, with about 45 patients reported thus far, and the current data from the ERA-EDTA (ERACODA) registry for transplanted patients and patients on Renal Replacement Therapy (RRT); as for those with glomerular diseases, data are lacking. Herein, we report the case of a 62-year-old patient with severe membranoproliferative glomerulonephritis who had been receiving a high burden of immunosuppression until four months before the COVID-19 infection. He developed severe disease with acute respiratory failure requiring mechanical ventilation. After treatment with hydroxychloroquine and azithromycin, despite his low chances, he gradually recovered and survived. To the best of our knowledge, this is one of the few reported patients with glomerulonephritis who had COVID-19 Besides our single case with glomerulonephritis early during the disease outbreak, the very low prevalence of COVID-19 infection in the country's transplant recipients (0.038%) and dialysis patients (0.24%) reflects the impact of the rapid implementation of social distancing rules as well as of preventive measures for disease control in the hospitals and dialysis units in our country.

Incidence and risk factors of herpes zoster among adult renal transplant recipients receiving universal antiviral prophylaxis.

BACKGROUND: Herpes zoster (HZ) is a significant cause of morbidity and complications in adult renal transplant recipients. We determined the incidence, complications and risk factors for the development of HZ after renal transplantation in a setting using universal antiviral prophylaxis. METHODS: The medical files of all adult renal transplants, performed between 2004 and 2008, were retrospectively reviewed to assess the clinical characteristics and risk factors of HZ. Incident cases of HZ were determined and the probability of developing post-transplant HZ for all subjects was calculated using the Kaplan Meier method. A multivariable Cox proportional hazards model was applied to assess the risk factors associated with the development of HZ. RESULTS: A total of 450 patients were eligible with a median follow up of 38 months. Twenty nine subjects (6.4%) developed HZ, the median time to onset was 18 months, only three of them (10.3%) required hospitalization, and none developed disseminated or visceral disease and death directly attributed to zoster. However, high rates of post-herpetic neuralgia (48.7%) were observed. Overall incidence was calculated at 20.6 cases per 1000 patient-years of follow-up. Following multivariate analysis, increased age ≥ 60 years old, positive pre-transplant history of varicella related disease and administration of rejection treatment conferred an increased risk of 4.00-fold (CI: 1.79-8.92), 16.00-fold (CI: 4.62-55.52), and 5.57-fold (CI: 1.56-19.84) respectively, for the development of post-transplant zoster. CONCLUSIONS: HZ remains a common complication after renal transplantation in adults under current immunosuppession protocols and universal antiviral prophylaxis.

A phase 1/2 study of lenalidomide with low-dose oral cyclophosphamide and low-dose dexamethasone (RdC) in AL amyloidosis.

In this phase 1/2 study, we explored the feasibility and activity of an oral regimen of lenalidomide with low-dose dexamethasone and low-dose oral cyclophosphamide (RdC) in patients with primary systemic light chain amyloidosis. RdC was given for up to 12 cycles in prespecified cohorts at escalated doses: 13 patients were treated in phase 1 and 24 in phase 2; 65% were previously untreated, and most had renal and/or cardiac involvement and elevated cardiac biomarkers. Lenalidomide 15 mg/d and cyclophosphamide 100 mg/d were further evaluated in phase 2. On intention to treat, 20 (55%) patients achieved a hematologic response, including 3 (8%) complete remissions. Hematologic responses were seen at all dose levels and in 4 of 5 patients who had received bortezomib previously. An organ response was recorded in 22% of patients on intention-to-treat and in 40% of patients who survived at least 6 months. The median time to progression was 10 months and the 2-year survival was 41%. Fatigue, nonneutropenic infections, and rash were the most common toxicities. The results of the present study show that RdC is an oral regimen with activity in primary systemic light chain amyloidosis and may be an additional treatment option, especially for patients with preserved organ function or for patients who cannot receive or who relapse after bortezomib. This study is registered at www.clinicaltrials.gov as NCT00981708.

Sociodemographic Disparities in Adults with Kidney Failure: A Meta-Analysis.

This meta-analysis aims to assess current evidence regarding sociodemographic disparities among adults with kidney failure. Medline, Scopus, Web of Science, CENTRAL, and Google Scholar were systematically searched from inception to 20 February 2022. Overall, 165 cohort studies were included. Compared to White patients, dialysis survival was significantly better among Black (hazard ratio-HR: 0.68; 95% CI: 0.61-0.75), Asian (HR: 0.67; 95% CI: 0.61-0.72) and Hispanic patients (HR: 0.80; 95% CI: 0.73-0.88). Black individuals were associated with lower rates of successful arteriovenous fistula use, peritoneal dialysis and kidney transplantation, as well as with worse graft survival. Overall survival was significantly better in females after kidney transplantation compared to males (HR: 0.87; 95% CI: 0.84-0.90). Female sex was linked to higher rates of central venous catheter use and a lower probability of kidney transplantation. Indices of low SES were associated with higher mortality risk (HR: 1.22, 95% CI: 1.14-1.31), reduced rates of dialysis with an arteriovenous fistula, peritoneal dialysis and kidney transplantation, as well as higher graft failure risk. In conclusion, Black, Asian and Hispanic patients present better survival in dialysis, while Black, female and socially deprived patients demonstrate lower rates of successful arteriovenous fistula use and limited access to kidney transplantation. PROSPERO registration: CRD42022300839.

Association of kidney function with physical performance: the Maastricht study.

BACKGROUND: Kidney failure has been associated with decreased physical capacity, although evidence regarding the physical performance of individuals with earlier stages of chronic kidney disease (CKD) remains limited. METHODS: Cross-sectional data were derived from the prospective, population-based Maastricht Study. Multivariate linear regression models were fitted to assess the association of estimated glomerular filtration rate (eGFR) and albuminuria categories with physical performance test outcomes. RESULTS: Overall, 7396 participants were included. Compared to eGFR 60-90 ml/min/1.73 m2, values < 60 ml/min/1.73 m2 were associated with significantly shorter 6-min walk distance (ß: - 13.04 m, 95% confidence intervals-CI - 19.95; - 6.13), worse timed chair rise stand test time (ß: 0.91 s, 95% CI 0.36; 1.47), lower maximal grip (ß: - 0.83 kg, 95% CI - 1.50; - 0.15) and elbow flexion (ß: - 3.64 Nm, 95% CI - 7.11; - 0.16) strength. Additionally, eGFR > 90 ml/min/1.73 m2 was linked to significantly shorter 6-min walk distance (ß: - 6.13 m, 95% CI - 9.44; - 2.82). Urinary albumin excretion > 30 mg/24 h was associated with shorter 6-min walk distance (ß: - 12.48 m, 95% CI - 18.28; - 6.68), worse timed chair rise stand test time (ß: 0.51 s, 95% CI 0.11; 1.06), lower maximal grip (ß: - 1.34 kg, 95% CI - 1.91; - 0.76) and elbow flexion strength (ß: - 3.31 Nm, 95% CI - 5.80; - 0.82). CONCLUSIONS: Reduced eGFR and higher albuminuria levels were associated with worse physical performance, especially shorter 6-min walk distance and lower muscle strength. The relationship between eGFR and physical function was non-linear, with also high eGFR values being associated with worse performance, especially in the six-minute walk test.

Impact of donor and recipient age difference on long-term allograft survival after living donor renal transplantation: analysis of 478 cases.

INTRODUCTION: Either deceased or living-related renal transplantation constitutes the best therapeutic option for patients with end-stage renal disease. In this retrospective study, an attempt to identify parameters that affect allograft survival in living donor renal transplantation was made. METHODS: Between January 2000 and July 2012, 478 adult patients received a renal transplant from a living-related donor in our center and their records were retrospectively reviewed in November 2012. Data concerning donor age, recipient age, donor/recipient age difference, donor/recipient gender, and ABO compatibility/incompatibility were recorded and associated with renal allograft survival rate. RESULTS: Renal allograft survival rate was 96%, 89.5%, and 77.7% in the first, fifth, and 10th yr after transplantation, respectively. Only the difference between donor and recipient age was statistically significant in relation to graft survival. In cases with age difference >13 yr, graft survival rate was lower from the third yr onward. CONCLUSIONS: Only the age difference between donor and recipient exerts an adverse impact on graft outcome after living donor renal transplantation, whereas donor age, recipient age, donor/recipient gender, and ABO incompatibility do not significantly influence renal allograft survival.

Analysis of effects of fixation type on renal function after endovascular aneurysm repair.

PURPOSE: To report a prospective nonrandomized study comparing the effects of suprarenal (SR) vs. infrarenal (IR) stent-graft fixation on renal function in patients undergoing endovascular aneurysm repair (EVAR) for abdominal aortic aneurysm (AAA). METHODS: Patients with AAA undergoing elective EVAR between June 2008 and June 2010 were eligible for the comparative study of fixation method on renal function. Patients with impaired renal function [estimated creatinine clearance (eCrCl) <30 mL/min] or a history of renal impairment were not eligible. Renal function was assessed by measuring serum creatinine (SCr) and total proteins and microalbumin in the urine preoperatively, on postoperative day 1, and at 1, 6, and 12 months. The eCrCl was calculated using the Cockcroft-Gault formula. A standard preoperative hydration protocol was followed in all patients, and stent-graft choice was at the operator's discretion. Of 116 patients undergoing elective EVAR in the study period, 16 were ineligible, leaving 100 patients (95 men; median age 74 years) enrolled in the study (49 SR and 51 IR). RESULTS: There was no statistically significant difference between the groups in the prevalence of any risk factor, the baseline SCr and eCrCl values, contrast usage, or procedure duration. At the postoperative measurement, there was no significant deterioration of renal function in either group, although total urinary proteins increased significantly in both groups (IR p=0.01, SR p<0.001). At the 12-month follow-up, patients in the IR group had no significant alteration in any marker vs. baseline, while patients in the SR group had significant alterations in SCr (p=0.001), eCrCl (p<0.001), and microalbumin (p=0.04) in urine. The number of patients with a >20% decrease in eCrCl was not significantly different between the groups. No patient had an adverse renal event. CONCLUSION: Deterioration in renal function was observed 12 months after EVAR in patients receiving a stent-graft with suprarenal fixation, even though this did not seem to increase the likelihood of postoperative renal impairment. Furthermore, suprarenal fixation may be responsible for progressively significant proteinuria. Further studies are needed to determine the long-term impact of suprarenal fixation on renal function and investigate the potential risk of progressive renal disease in relation to type of fixation.

Pulmonary hypertension in dialysis patients.

Pulmonary hypertension in end-stage renal disease patients is associated with significantly increased morbidity and mortality. The prevalence of pulmonary hypertension in dialysis patients is relatively high and varies in different studies from 17% to 49.53% depending on the mode of dialysis and other selection factors, such as the presence of other cardiovascular comorbidities. The etiopathogenic mechanisms that have been studied in relatively small studies mainly include arteriovenous fistula-induced increased cardiac output, which cannot be accomodated by, the spacious under normal conditions pulmonary circulation. Additionally, pulmonary vessels show signs of endothelial dysfunction, dysregulation of vascular tone due to an imbalance in vasoactive substances, and local as well as systemic inflammation. It is also believed that microbubbles escaping from the dialysis circuit can trigger vasoconstriction and vascular sclerosis. The non-specific therapeutic options that proved to be beneficial in pulmonary artery pressure reduction are endothelin inhibitors, phosphodiesterase inhibitor sildenafil, and vasodilatory prostaglandins in various forms. The specific modes of treatment are renal transplantation, size reduction or closure of high-flow arteriovenous fistulas, and transfer from hemodialysis to peritoneal dialysis-a modality that is associated with a lesser prevalence of pulmonary hypertension.

Translational research and innovation in modern transplant practice: Paradigms from Greece and around the world.

The continuous clinical and technological advances, together with the social, health and economic challenges that the global population faces, have created an environment where the evolution of the field of transplantation is essentially necessary. The goal of this special issue is to provide a picture of the current status of transplantation in Greece as well as in many other countries in Europe and around the world. Authors from Greece and several other countries provide us with valuable insight into their respective areas of transplant expertise, with a main focus on the field of translational research and innovation. The papers that are part of this Special Issue "Translational Research and Innovation and the current status of Transplantation in Greece" have presented innovative and meaningful approaches in modern transplant research and practice. They provide us with a clear overview of the current landscape in transplantation, including liver transplantation in the context of a major pandemic, the evolution of living donor kidney transplantation or the evolution of the effect of hepatitis C virus infection in transplantation, while at the same time explore more recent challen ges, such as the issue of frailty in the transplant candidate and the changes brought by newer treatments, such as immunotherapy, in transplant oncology. Additionally, they offer us a glimpse of the effect that technological innovations, such as virtual reality, can have on transplantation, both in terms of clinical and educational aspects. Just as critical is the fact that this Special Issue emphasizes the multidisciplinary, collaborative efforts currently taking place that link transplant research and innovation with other cutting-edge disciplines such as bioengineering, advanced information technology and artificial intelligence. In this Special Issue, in addition to the clinical and research evolution of the field of transplantation, we are witnessing the importance of interdisciplinary collaboration in medicine.

Drug-Induced Podocytopathies: Report of Four Cases and Review of the Literature.

Kidney injury due to medications is a well-known clinical entity. Although drug-induced tubulointerstitial disease is commonly encountered, there are few reports in the literature associated with glomerular injury due to medications. The recognition of this type of kidney injury is crucial, as rapid discontinuation of the offending agent is critical to maximizing the likelihood of quick and effective renal function recovery. In this article, we present four cases that presented with nephrotic syndrome and were diagnosed with biopsy-proven podocytopathies, associated with exposure to a certain medication. All of them experienced complete resolution of nephrotic syndrome within days or weeks after discontinuation of the offending drug. We also present the data, which were found in a Medline search from the year 1963 until the present, regarding cases with podocytopathies associated with penicillamine, tamoxifen and the combination of pembrolizumab-axitinib, including only adult cases from the English literature. The Medline search revealed nineteen cases of penicillamine-induced minimal-change disease (MCD), one case of tamoxifen-induced MCD, and none associated with pembrolizumab-axitinib therapy. We also searched for the largest studies and meta-analyses regarding drug-induced podocytopathies after a Medline search from 1967 to the present of the English literature.

Analysis of glucocorticoid receptor and microRNAs expression in pathological renal tissues.

Glucocorticoid receptor (GR) is expressed in normal renal podocytes; however, its expression differs among renal diseases. The expression of GR as well as its epigenetic regulators microRNA (miR)30a, miR24 and miR370 was studied in the renal tissues of patients with systemic lupus nephritis (LN), minimal changes disease (MCD) and pauci-immune glumeronephritis (PIN). A total of 51 patients undergoing renal biopsy and 22 nephrectomised controls with no history of parenchymal renal disease were recruited from the Clinic of Nephrology and Renal Transplantation of General Laikon hospital between November 2016 and March 2019. All patients were newly-diagnosed and they were naïve of any treatment. The mRNA and protein expression were analyzed through reverse transcription-quantitative PCR and immunohistochemistry respectively. Written consent was obtained from all participants. GR mRNA expression was significantly reduced in all pathological samples compared with the 'normal' renal tissues used as controls (P=0.023 for LN, P=0.05 for MCD and P=0.004 for PIN). Similarly, GR protein expression was lower in all pathological samples (>6 GR positive podocytes/glomerulus in 50% of patients with LN and MCD and 18% with PIN) compared with controls (>6 positive podocytes/glomerulus in all the controls). PIN samples presented significantly lower GR mRNA and protein expression compared with LN and MCD samples. No significant differences were observed in the miR30a expression when comparing pathological with 'normal' renal samples. miR24 and miR370 expression demonstrated statistically significant difference in all pathological compared with 'normal' tissues. Moreover, GR expression was not significantly associated with either LN disease activity score or the response to the treatment. GR and miR24 expression was significantly reduced whereas miR370 significantly increased in all pathological compared with 'normal' renal tissues implying their protentional role in nephritis pathogenesis and treatment. Analysis of larger samples are required for more robust statistical analysis.

Disease Course, Management and Outcomes in Kidney Transplant Recipients with SARS-CoV-2 Infection during the Omicron-Variant Wave: A Single-Center Experience.

BACKGROUND: Since December 2019, kidney transplant recipients (KTRs) have experienced a great impact of the coronavirus disease 2019 (COVID-19) pandemic, with a higher risk of morbidity and mortality compared to the general population. Preliminary data in KTRs suggest that the Omicron variant, which has been dominant since December 2021, is more infectious than the previous ones but is associated with reduced risk of severity and low lethality rates. The purpose of our study was to assess the disease course and outcomes of the SARS-CoV-2 infection in KTRs during the Omicron-surge. METHODS: This retrospective study included 451 KTRs diagnosed with SARS-CoV-2 infection between 1 December 2021 and 30 September 2022. Demographic and clinical characteristics at the time of infection, vaccination data, treatment, clinical course, and outcomes were recorded and analyzed. RESULTS: Mean age was 51.8 ± 13.7 years with a male predominance (61.2%). The majority (76.1%) were vaccinated with at least three doses of the available mRNA vaccines, although serology revealed low anti-SARS-CoV-2 antibody titers before infection (33 [3.3-1205] AU/mL). Only 6% of the patients experienced moderate-severe disease. Accordingly, there was low prevalence of adverse outcomes, such as SARS-CoV-2-related hospitalization (11.3%) and death (0.9%). Multivariate analysis revealed that only age significantly increased the risk of SARS-CoV-2-related hospitalization. CONCLUSIONS: During the Omicron wave, the clinical course of the SARS-CoV-2 infection in KTRs has substantially changed, with lower rates of moderate and severe disease and a low prevalence of adverse outcomes. Prospective clinical trials are warranted to further elucidate the evolving pathogenesis, management, and long-term outcomes of COVID-19 in such high-risk populations.