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Abstract Background Dyslipidemia represents an important risk factor for cardiovascular diseases, although its optimal management after kidney transplantation remains unclear. The present meta-analysis aimed to shed light on the efficacy and safety of statins among kidney transplant recipients, evaluating their potential effects on the risk of cardiovascular events, mortality and graft survival. Methods Medline, Scopus, Web of Science, CENTRAL, Clinicaltrials.gov and Google Scholar were systematically searched from their inception through April 20, 2024. Both randomized controlled trials and observational studies evaluating the effects of statin administration after kidney transplantation were held eligible. Random-effects models were fitted using the maximum likelihood method, while the certainty of evidence was appraised following the GRADE (Grading of Recommendations, Assessment, Development, and Evaluations) approach. Results Overall, 27 studies (10 randomized controlled trials and 17 observational studies) were included. Statin use compared to no use was associated with a lower risk of major adverse cardiovascular events [Relative risk (RR): 0.87, 95% confidence interval (CI): 0.67–0.96, moderate certainty] and overall mortality (RR: 0.84, 95% CI: 0.74–0.94, low certainty). The risk of graft loss did not differ between the compared groups (RR: 0.72, 95% CI: 0.48–1.08, very low certainty). Regarding safety endpoints, statin use was associated with a lower risk of hepatotoxicity (RR: 0.81, 95% CI: 0.70–0.93, moderate certainty), but with a greater risk of rhabdomyolysis (RR: 1.37, 95% CI: 1.10–1.70, low certainty) and cataract (RR: 1.22, 95% CI: 1.14–1.31, moderate certainty). No statistically significant differences between the compared groups with and without statin use were observed concerning the risk of creatine kinase elevation, post-transplant diabetes mellitus, hip fracture, venous thromboembolism, or cancer. Conclusions Among kidney transplant recipients, statin use is associated with a lower risk of cardiovascular events and better patient survival, presenting an acceptable safety profile. Further large-scale studies are needed to determine the optimal statin dosing strategy and lipid-lowering goals, depending on comorbidities and immunosuppression regimens. Registration https://doi.org/10.17504/protocols.io.5qpvok3yzl4o/v1 .

IntroductionThis study aimed to describe the clinical course of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection in patients with glomerular diseases (GDs) and its impact on the probability of relapse.MethodsPatients with biopsy-proven GD and positive PCR test for SARS-CoV-2 from glomerular clinics across Greece were studied retrospectively. Those who received the GD diagnosis after the SARS-CoV-2 vaccination or coronavirus disease 2019 (COVID-19) or ended in ESKD prior to infection were excluded. Demographics, histopathological diagnoses, past medical history, immunosuppression, and GD activity status were recorded.ResultsA total of 219 patients with GDs and documented SARS-CoV-2 infection were included. The mean time from the diagnostic kidney biopsy to SARS-CoV-2 infection was 67.6 ( ± 59.3) months. Among the participants, 82.5% had been vaccinated against SARS-CoV-2 with three doses (range: 2.5–3) without subsequent GD reactivation in 96.2% of them. Twenty-two patients (10%) were hospitalized for COVID-19 and one (0.5%) required mechanical ventilation. Four (1.8%) died due to COVID-19 and one (0.5%) had long COVID-19 symptoms. Among patients in remission prior to SARS-CoV-2 infection, 22 (11.2%) experienced a GD relapse within 2.2 (range: 1.5–3.7) months from the diagnostic test. The relapse-free survival after COVID-19 was significantly shorter for patients with minimal change disease, pauci-immune glomerulonephritis, and focal segmental glomerulosclerosis. No difference was observed in the relapse-free survival post-COVID-19 based on the history of SARS-CoV-2 vaccination.ConclusionsSARS-CoV-2 infection appears to have a symptomatic but uncomplicated sequence in vaccinated patients with GDs, with a significant impact on the clinical course of GD, associated with an increased probability of relapse in certain histopathological types.

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.

Introduction: The recurrence of idiopathic membranous nephropathy (iMN) after kidney transplantation is common, although its exact clinical significance remains unclear. This systematic review aims to elucidate the effects of iMN recurrence on graft survival. Materials and methods: A literature search was performed by systematically searching Medline, Scopus, Web of Science, and Google Scholar from inception. Cohort studies examining iMN recurrence after kidney transplantation were deemed eligible. Meta-analysis was performed by fitting random-effects models. Results: Twelve (12) articles published from 1995 to 2016 reporting on 139 transplant patients with recurrent iMN were included. The median time of the diagnosis of recurrent iMN was 18 months during follow-up from 35 to 120 months. Risk factors for iMN recurrence in the renal allograft are a positive serum test for anti-PLA2R antibodies pretransplant, female sex, younger age, high proteinuria pretransplant, the longest interval from initial disease to end-stage chronic kidney disease, and the combination of alleles HLA DQA1 05:01 and HLA DQB1 02:01. In the pretransplant period, 37 (26.61%) patients had a positive serum test and 18 (12.94%) patients had a positive biopsy stain for anti-PLA2R antibodies. The sensitivity of the pretransplant positive serum test for these antibodies ranges from 57% to 85.30% and the specificity is 85.10–100%. A total of 81.80% of patients who received rituximab as treatment for iMN recurrence achieved complete and partial remission, while 18.20% had no response to treatment. iMN recurrence was not associated with significantly different rates of graft loss (odds ratio = 1.03, 95% CI: 0.52–2.04, p = 0.524, I2 = 0.00%). Recurrence of iMN was not associated with increased risk of graft loss independently of whether patients were treated with rituximab (OR: 0.98, 95% CI: 0.39–2.50, I2: 0%) or not (OR: 1.22, 95% CI: 0.58–2.59, I2: 3.8%). Patients with iMN recurrence who achieved remission had significantly reduced risk of graft loss (OR: 0.14, 95% CI: 0.03 to 0.73). Conclusion: The main outcome from this systematic review is that there is no statistically significant difference in graft survival in patients with iMN recurrence compared to those without recurrence in long-term follow-up. The achievement of remission is associated with significantly reduced risk of graft loss.

In our prospective, unicenter cohort study, we collected blood samples from 30 newly kidney transplanted patients, at month 1, 2, 3, and 5 for dd-cfDNA analysis, along with creatinine/eGFR and DSA monitoring, and from 32 patients who underwent an indication biopsy and whose dd-cfDNA levels were measured at the time of biopsy and 1 month afterwards. Fourteen of 32 (43.8%) patients in the biopsy group were diagnosed with TCMR and 5 of 32 (15.6%) with ABMR. Dd-cfDNA proved to be better than creatinine in diagnosing rejection from non-rejection in patients who were biopsied. When a dd-cfDNA threshold of 0.5% was chosen, sensitivity was 73.7% and specificity was 92.3% (AUC: 0.804, 0.646–0.961). In rejection patients, levels of dd-cfDNA prior to biopsy (0.94%, 0.3–2.0) decreased substantially after initiation of treatment with median returning to baseline already at 1 month (0.33%, 0.21–0.51, p = 0.0036). In the surveillance group, high levels of dd-cfDNA (>0.5%) from second month post-transplantation were correlated with non-increasing eGFR 1 year post-transplantation. The study used AlloSeq kit for kidney transplant surveillance for first time and confirmed dd-cfDNA’s ability to detect rejection and monitor treatment, as well as to predict worse long-term outcomes regarding eGFR.

Chronic kidney disease patients, especially those on hemodialysis, are at the highest risk of a severe course and death from COVID-19. Moreover, they appear to have suboptimal response in both cellular and humoral immunity after vaccination. The present study investigated humoral and cellular response and safety after two doses of either of the two authorized mRNA vaccines in a cohort of 310 patients on maintenance dialysis. The antibody response rate was 94.5%, with a median (25th, 75th) antibody titer of 3478 (1236, 8141) AU/mL. Only mild adverse effects were observed. Only vaccine type was independently associated with immunogenicity. Α statistically significant difference in favor of mRNA1273 versus BNT162b2 vaccine was observed. Antibody positivity (100% vs. 94.3%, p < 0.001), median (25th, 75th) antibody levels: 9499 (6118, 20,780) AU/mL vs. 3269 (1220, 7807) AU/mL (p < 0.001). Among the 65 patients tested for T-cell response, 27 (41.5%) had a positive one with a median (25th, 75th) antibody titer of 6007 (3405, 12,068) AU/mL, while 38 with no T-cell response presented a lower median (25th, 75th) antibody titer of 1744 (850, 4176) AU/mL (p < 0.001). Both mRNA vaccines are safe for dialysis patients and can trigger humoral and cellular responses, although with lower titers than those that have been reported to healthy individuals.

Autosomal Dominant Polycystic Kidney Disease (ADPKD) stands as the most prevalent hereditary renal disorder in humans, ultimately culminating in end-stage kidney disease. Animal models carrying mutations associated with polycystic kidney disease have played an important role in the advancement of ADPKD research. The Han:SPRD rat model, carrying an R823W mutation in the Anks6 gene, is characterized by cyst formation and kidney enlargement. The mutated protein, named Samcystin, is localized in cilia of tubular epithelial cells and seems to be involved in cystogenesis. The homozygous Anks6 mutation leads to end-stage renal disease and death, making it a critical factor in kidney development and function. This review explores the utility of the Han:SPRD rat model, highlighting its phenotypic similarity to human ADPKD. Specifically, we discuss its role in preclinical trials and its importance for investigating the pathogenesis of the disease and developing new therapeutic approaches.

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.

Background Hypertension is a major cardiovascular risk factor in both kidney transplant recipients (KTRs) and patients with chronic kidney disease (CKD). Ambulatory blood pressure monitoring (ABPM) is considered the gold-standard method for hypertension management in these subjects. This is the first study evaluating the full ambulatory blood pressure (BP) profile and short-term BP variability (BPV) in KTRs versus CKD patients without kidney replacement therapy. Methods Ninety-three KTRs were matched with 93 CKD patients for age, sex, and estimated glomerular filtration rate. All participants underwent 24-hour ABPM. Mean ambulatory BP levels, BP trajectories, and BPV indices (standard deviation [SD], weighted SD, and average real variability) were compared between the two groups. Results There were no significant between-group differences in 24-hour systolic BP (SBP)/diastolic BP (DBP) (KTRs: 126.9 ± 13.1/79.1 ± 7.9 mmHg vs. CKD: 128.1 ± 11.2/77.9 ± 8.1 mmHg, p = 0.52/0.29), daytime SBP/DBP and nighttime SBP; nighttime DBP was slightly higher in KTRs (KTRs: 76.5 ± 8.8 mmHg vs. CKD: 73.8 ± 8.8 mmHg, p = 0.04). Repeated measurements analysis of variance showed a significant effect of time on both ambulatory SBP and DBP (SBP: F = [19, 3002] = 11.735, p < 0.001, partial η2 = 0.069) but not of KTR/CKD status (SBP: F = [1, 158] = 0.668, p = 0.42, partial η2 = 0.004). Ambulatory systolic/diastolic BPV indices were not different between KTRs and CKD patients, except for 24-hour DBP SD that was slightly higher in the latter group (KTRs: 10.2 ± 2.2 mmHg vs. CKD: 10.9 ± 2.6 mmHg, p = 0.04). No differences were noted in dipping pattern between the two groups. Conclusion Mean ambulatory BP levels, BP trajectories, and short-term BPV indices are not significantly different between KTRs and CKD patients, suggesting that KTRs have a similar ambulatory BP profile compared to CKD patients without kidney replacement therapy.

Objective A preliminary definition of disease modification (DM) in lupus nephritis (LN) was recently developed focusing on long-term remission and damage prevention, with minimal treatment-associated toxicity. We aimed to further specify aspects of DM criteria in LN, assess DM achievement in a real-world setting and examine potential DM predictors and long-term outcomes.Methods We collected clinical/laboratory and histological inception cohort data from biopsy-proven LN patients (82% females) with ≥72 months follow-up at two joint academic centres. Specific criteria for 24-hour proteinuria, estimated glomerular filtration rate (eGFR), renal flares and glucocorticoids dose were set at three time frames (months 0–12, 13–60 and 72) to assess DM. In the first model, DM was achieved if patients fulfilled all four criteria at all three time frames (achievers). In the second model, the continued glucocorticoids reduction criterion was excluded. Logistic regression analyses were performed. Possible different trends in DM achievement between past and recent decades were also investigated.Results DM was achieved by 60% of patients, increased to 70% when glucocorticoids excluded from DM criteria. 24-hour proteinuria at 9 months predicted DM achievement (OR 0.72, 95% CI 0.53 to 0.97, p=0.03), but none of baseline characteristics. Among patients with >72 month follow-up, non-achievers had worse renal outcomes (flares, >30% proteinuria increase, eGFR decline) than achievers at the end of follow-up (median 138 months). Patients diagnosed between 1992 and 2005 were found to have significantly lower percentages of DM achievement and met less often the glucocorticoids dose reduction criterion in all three time frames, compared with those diagnosed between 2006 and 2016 (p=0.006 and p

Background: Nirmatrelvir/ritonavir (NMV/r) and three-day course remdesivir (3RDV) have been approved as early treatments for COVID-19 outpatients not requiring supplemental oxygen. Real-life data on the efficacy of antivirals among immunocompromised patients or directly comparing their effectiveness in preventing hospitalization and/or death are scarce. Methods: Prospective, observational study conducted in a tertiary care hospital, from 1 January 2022 until 15 March 2023, during the prevalence of the Omicron variant. Inverse probability of treatment weighting (IPTW) was used to account for differences between treatment groups. Results: We included 521, mainly immunocompromised (56%), patients in our analysis; 356 (68.3%) received 3RDV and 165 (31.7%) NMV/r. Overall, 15/521 (2.9%) patients met the primary end-point of hospitalization at 30 days (3RDV arm: 10/356, 2.8% vs. NMV/r arm: 5/165, 3%, p = 1). On IPTW-adjusted univariable analysis, the choice of treatment did not affect outcomes. In multivariable logistic regression analysis, we found that one (OR 0.26, 95%CI 0.07–0.99, p = 0.049) or two (OR 0.06, 95%CI 0.01–0.55, p = 0.014) vaccine booster shots reduced the risk for adverse outcomes. Conclusion: In our patient population of high-risk, mainly immunocompromised, vaccinated patients during the prevalence of the Omicron variant, NMV/r and 3RDV were equally effective early treatments for the prevention of hospitalization and/or death.

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.

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.

IntroductionPure membranous lupus nephritis (MLN) accounts for 10–20% of total cases of lupus nephritis and is generally associated with a better patient and renal survival compared to proliferative classes. Studies of MLN are limited by small sample size and heterogeneity of included populations since patients with pure MLN and those with mixed classes are usually examined together.Aim of the StudyTo describe clinical and laboratory characteristics of patients with pure MLN, therapeutic regimens, response to treatment, renal relapses, and their long-term renal survival and to define prognostic factors of remission and relapse.MethodsWe retrospectively studied an inception cohort of 27 patients with histologically proven pure MLN. Clinical, laboratory and therapeutical parameters were recorded at diagnosis, at different time points (3–6–9–12–18–24–36–72 months) during the course of the disease, at time of renal flare, and at last follow up visit.Results48.1% (13/27) of patients were treated with mycophenolic acid (MPA), 29.6% (8/27) with cyclophosphamide (CYC), and 3.7% (1/27) with cyclosporine (all in combination with corticosteroids). Five patients (18.5%) did not receive any immunosuppressive treatment. Mean duration of treatment was 4.7 ± 2.3 years. Median time to complete remission was 9 months (IQR = 7) and median time to partial remission was 4 months (IQR = 4). No clinical or laboratory parameter was found to be significantly associated with time to remission. Time to remission was not significantly affected by either of the two treatment regimens (CYC and MPA) (p = 0.43). Renal flare was observed in 6 (22%) of the 27 patients in a median time of 51 months (IQR = 63). Proteinuria >1 g/24 h at 1 year significantly correlated with risk of flare (OR 20, p = 0.02). After a median follow up period of 77 months, all patients had an eGFR > 60 ml/min/1.73 m2 (mean eGFR 100 ± 32 ml/min/1.73 m2).ConclusionsIn a small cohort of patients with pure MLN, long-term renal survival was very good. With the limitation of the small sample size, we could not find any baseline clinical, biochemical or therapeutic factor that could predict time to remission. Proteinuria > 1 g/24 h at 1 year should be further examined in larger cohorts as a possible predictor of flare.

Abstract Background Hypocomplementemic urticarial vasculitis syndrome is an infrequent condition characterized by ocular, renal, gastrointestinal and pulmonary involvement with low serum complement levels and autoantibodies. Renal manifestations vary from microscopic hematuria to nephrotic syndrome and acute kidney injury. Accordingly differing histologic patterns have been reported. Case presentation We present the case of a 65 years old woman with a history of chronic uveitis who presented with arthralgias, urticarial rush, nephrotic syndrome, glomerular hematuria and low serum complement. Kidney biopsy revealed an immune-complex membranoproliferative glomerulonephritis. The patient received induction therapy with steroids, cyclophosphamide and hydroxychloroquine followed by rapid clinical improvement and remission of proteinuria. Maintenance treatment consisted of rituximab pulses. Conclusions The majority of hypocomplementemic urticarial vasculitis syndrome cases is idiopathic, although an association to drugs, infections or other autoimmune disorders has been recorded. Given the rarity and heterogeneity of the disease, no standard treatment is established.

AimWomen with glomerular diseases are often of childbearing age. Besides lupus nephritis, data regarding pregnancy in patients with glomerular diseases are limited, posing a challenging task to attending nephrologists. This study aimed to investigate the pregnancy outcomes and the impact on the underlying glomerular disease among women followed in our institution.MethodsA single-center retrospective cohort study of women with biopsy-proven glomerular diseases who experienced pregnancy between 2010 and 2020. We analyzed data before, during, and after gestation.ResultsA total of 22 women, 13 women with primary and 9 women with secondary glomerular diseases, were included in this study. Most patients (82%) had received immunosuppressive treatment at various times before pregnancy. All the women were in remission, either complete (62%) or partial (38%), with well-preserved renal function (82%) before conception. A total of 30 live births and 1 stillbirth were recorded; the rate of preterm delivery was 23%. Renal function and proteinuria remained stable during pregnancy. Preeclampsia was observed in 6.7% of patients and disease relapse in 6.9% of the pregnancies.ConclusionPregnancy was associated with a low frequency of adverse events in women with underlying glomerular diseases, provided they have quiescent disease and preserved renal function.

BackgroundImmunoglobulin A nephropathy (IgAN) is among the commonest glomerulonephritides in Greece and an important cause of end-stage kidney disease (ESKD) with an insidious chronic course. Thus, the recently published International IgAN prediction tool could potentially provide valuable risk stratification and guide the appropriate treatment module. This study aimed to externally validate this prediction tool using a patient cohort from the IgAN registry of the Greek Society of Nephrology.MethodsWe validated the predictive performance of the two full models (with or without race) derived from the International IgAN Prediction Tool study in the Greek Society of Nephrology registry of patients with IgAN using external validation of survival prediction models (Royston and Altman). The discrimination and calibration of the models were tested using the C-statistics and stratified analysis, coefficient of determination (RD2) for model fit, and the regression coefficient of the linear predictor (βPI), respectively.ResultsThe study included 264 patients with a median age of 39 (30–51) years where 65.2% are men. All patients were of Caucasian origin. The 5-year risk of the primary outcome (50% reduction in estimated glomerular filtration rate or ESKD) was 8%. The RD2 for the full models with and without race when applied to our cohort was 39 and 35%, respectively, and both were higher than the reported RD2 for the models applied to the original validation cohorts (26.3, 25.3, and 35.3%, respectively). Harrel's C statistic for the full model with race was 0.71, and for the model without race was 0.70. Renal survival curves in the subgroups (84th percentiles of linear predictor) showed adequate separation. However, the calibration proved not to be acceptable for both the models, and the risk probability was overestimated by the model.ConclusionsThe two full models with or without race were shown to accurately distinguish the highest and higher risk patients from patients with low and intermediate risk for disease progression in the Greek registry of IgAN.

Renal complications of HIV infection are common and histologically diverse. Besides HIV-associated nephropathy, which is the most well-defined glomerular disorder, immune-complex-mediated glomerulonephritis (HIVICK) is also encountered in the setting of HIV infection and may occasionally present with “lupus-like” features by light microscopy and immunofluorescence. Management of HIVICK remains controversial and mainly focuses on HIV viremia suppression with combined antiretroviral therapy. Immunosuppressive therapy may be used in order to mitigate the renal inflammation induced by the immune complex deposition. Data regarding the use of immunosuppressants in HIVICK are very limited, mostly including corticosteroids and mycophenolate acid analogues. Herein, we present the case of a 40-year-old HIV-infected Caucasian man with nephrotic syndrome, renal impairment, and a “lupus-like” membranous pattern in the kidney biopsy, who achieved a partial response of his proteinuria with a tacrolimus-based regimen in combination with antiretroviral therapy.

ObjectivesKidney transplant (KTx) recipients with IgAN as primary disease, were compared with recipients with other causes of renal failure, in terms of long-term outcomes.MethodsNinety-nine KTx recipients with end-stage kidney disease (ESKD) due to IgAN, were retrospectively compared to; i/ a matched case-control group of patients with non-glomerular causes of ESKD, and ii/ four control groups with ESKD due to glomerular diseases; 44 patients with primary focal segmental glomerulosclerosis (FSGS), 19 with idiopathic membranous nephropathy (IMN), 22 with lupus nephritis (LN) and 21 with pauci-immune glomerulonephritis (PIGN).ResultsAt end of the observation period, graft function and survival, were similar between KTx recipients with IgAN and all other groups, but the rate of disease recurrence in the graft differed significantly across groups. The rate of IgAN recurrence in the graft was 23.2%, compared to 59.1% (pConclusionRecipients with IgAN as primary disease, experienced outcomes comparable to those of recipients with other causes of ESKD. The rate of IgAN recurrence in the graft was significantly lower than the rate of FSGS recurrence, but higher than the one recorded in recipients with LN or PIGN. Tacrolimus, as part of the KTx maintenance therapy, was associated with lower rates of IgAN recurrence in the graft, compared to the rate cyclosporine.

Due to their higher risk of developing life-threatening COVID-19 disease, solid organ transplant (SOT) recipients have been prioritized in the vaccination programs of many countries. However, there is increasing evidence of reduced immunogenicity to SARS-CοV-2 vaccination. The present study investigated humoral response, safety, and effectiveness after the two mRNA vaccines in 455 SOT recipients. Overall, the antibody response rate was low, at 39.6%. Higher immunogenicity was detected among individuals vaccinated with the mRNA1273 compared to those with the BNT162b2 vaccine (47% vs. 36%, respectively, p = 0.025) as well as higher median antibody levels of 31 (7, 372) (AU/mL) vs. 11 (7, 215) AU/mL, respectively. Among the covariates assessed, vaccination with the BNT162b2 vaccine, antimetabolite- and steroid-containing immunosuppression, female gender, the type of transplanted organ and older age were factors that negatively influenced immune response. Only mild adverse effects were observed. Our findings confirm poor immunogenicity after vaccination, implicating a reevaluation of vaccination policy in SOT recipients.

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.

Patients with chronic kidney disease (CKD), particularly those with end-stage renal disease (ESRD), are at increased risk of cardiovascular events and mortality. The spectrum of arterial remodeling in CKD and ESRD includes atheromatosis of middle-sized conduit arteries and, most importantly, the process of arteriosclerosis, characterized by increased arterial stiffness of aorta and the large arteries. Longitudinal studies showed that arterial stiffness and abnormal wave reflections are independent cardiovascular risk factors in several populations, including patients with CKD and ESRD. Kidney transplantation is the treatment of choice for patients with ESRD, associated with improved survival and better quality of life in relation to hemodialysis or peritoneal dialysis. However, cardiovascular mortality in transplanted patients remains much higher than that in general population, a finding that is at least partly attributed to adverse lesions in the vascular tree of these patients, generated during the progression of CKD, which do not fully reverse after renal transplantation. This article attempts to provide an overview of the field of arterial stiffness in renal transplantation, discussing in detail available studies on the degree and the associations of arterial stiffness with other co-morbidities in renal transplant recipients, the prognostic significance of arterial stiffness for cardiovascular events, renal events and mortality in these individuals, as well as studies examining the changes in arterial stiffness following renal transplantation.

IntroductionManagement of the Primary Membranous Nephropathy (PMN) usually involves administration of immunosuppressives. Cyclophosphamide (Cyclo) and Calcineurin Inhibitors (CNIs) are both widely used but only limited data exist to compare their efficacy in long term follow-up.AimThe aim of the present study was to estimate and compare long term effects of Cyclo and CNIs in patients with PMN.Patients-methodsClinical data, histologic findings and long term outcome were retrospectively studied. The response to treatment and rate of relapse was compared between patients treated with CNIs or Cyclo based immunosuppressive regimens.ResultsTwenty three centers participated in the study, with 752 PMN patients (Mean age 53.4(14-87) yrs, M/F 467/285), followed for 10.1±5.7 years. All patients were initially treated with Renin Angiotensin Aldosterone System inhibitors (RAASi) for at least 6 months. Based on their response and tolerance to initial treatment, patients were divided into 3 groups, group I with spontaneous remission, who had no further treatment, group II, continued on RAASi only, and group III on RAASi+immunosuppression. Immunosuppressive regimes were mainly based on CNIs or Cyclo. Frequent relapses and failure to treatment were more common between patients who had started on CNIs (n = 381) compared to those initially treated with Cyclo (n = 110), relapse rate: 25.2% vs. 6.4%, pConclusionsLong term follow up showed that administration of Cyclo in PMN is followed by better preservation of renal function, increased response rate and less frequent relapses, compared to CNIs.

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.

Aim: Glomerular diseases (GD) associated with malignancies (AM, GDAM) have unique features, which are important to recognize, in the light of the progress made in cancer therapy. We aimed to describe the clinical and histopathological characteristics of patients with GDAM in relation to the presence of circulating autoantibodies, pointing to potential immune pathogenic pathways connecting cancer to GD. Materials and Methods: The included patients were studied retrospectively on the basis of a kidney biopsy proving GD and a related biopsy to establish the diagnosis of AM. We recorded patients’ demographics, serological and laboratory parameters, histopathological findings, and the type of malignancy, GD, and therapy. Results: In total, 41 patients with GDAM, with a mean age of 63.1 (±10.7) years, were studied. In 28 (68.3%) cases, GD was associated with a solid tumor, and in 13 (31.7%) patients with a lymphoid malignancy. The most frequent histopathological pattern was membranous nephropathy (43.9%). Overall, at the time of GD diagnosis, 17% of the patients were positive for antinuclear antibodies (ANA), and 12.2% for antineutrophil cytoplasmic autoantibodies (ANCA), all against myeloperoxidase (MPO). In addition, 93.3% of the patients who had membranous nephropathy were negative for transmembrane glycoprotein M-type phospholipase A2 receptor (PLA2R) antibody. Sixteen patients (39.0%) presented with acute nephritic syndrome, of whom five (31.25%) developed rapidly progressive glomerulonephritis. In a mean follow-up time of 36.1 (±28.3) months, nine (21.95%) patients ended up with end-stage kidney disease, and eight (19.5%) died. Conclusion: We found that 3.2% of patients who underwent a native kidney biopsy in our institution during the past decade, for any reason, were identified as having some type of GD associated with a malignancy. Serology indicated a significant presence of ANA or MPO-ANCA antibodies in patients with nephritic syndrome and the absence of PLA2R antibodies in patients with membranous nephropathy.

Background. Although colonic injury is a well-known complication of mycophenolic acid (MPA), the involvement of the upper gastrointestinal tract is less extensively documented. We present the occurrence of celiac-like duodenopathy manifested as a severe diarrhea syndrome in 2 renal transplant recipients on enteric-coated mycophenolate sodium. Methods. The patients belong to a setting of 16 renal transplant recipients under MPA suffering from chronic diarrhea in the absence of MPA-related colitis. Results. Both patients had a history of persistent diarrhea with significant weight loss. Colonic mucosa was unremarkable, whereas duodenal biopsies revealed celiac-like changes with increased epithelial cell apoptosis. Clinical symptoms completely resolved, and follow-up biopsies demonstrated normalization of histology after enteric-coated mycophenolate sodium withdrawal and switching to azathioprine. Conclusions. Celiac-like enteropathy seems to represent a rare side effect of MPA-associated immunosuppressive therapy and should be taken into account in the differential diagnosis of diarrhea in transplant recipients treated with MPA particularly in the absence of MPA-related colitis. As macroscopic lesions are usually missing, blind duodenal biopsies are necessary to establish the diagnosis.

Background. Although in antineutrophil cytoplasmic autoantibodies (ANCA)-associated systemic vasculitis (AASV) patients, activation of T-cells has been described, persistence of these alterations has not been well characterized. This study was conducted to define persistent T-cell activation (PTA) in AASV patients and to assess whether this correlates with disease activity, disease severity, age or therapy.Methods. The expression of CD4, CD45RO, CD25, CD26, CD28, CCR7 and HLA-DR was examined longitudinally in 38 consecutive AASV patients. Clinical parameters were compared by univariate and multiple analysis and Kaplan–Meier curves for relapse-free survival were calculated.Results. PTA could be defined as either of two activation phenotypes, i.e. a low percentage of CD4+ CD45RO− T-cells or a high percentage of CD25 in the naïve CD4+ population (n = 26), since only these phenotypes were stable over time and were not associated with active disease. In patients with PTA, major organ involvement was significantly more often found than in patients without PTA. Moreover, the cumulative cyclophosphamide dose (26.86 vs 8.53 P<0.01) was significantly increased in these patients, suggesting that PTA was associated with disease severity. In general, patients with PTA were older than those without (62.92±9.4 years vs 48.42±16.9 years respectively, P<0.01). PTA was independent of disease duration. Interestingly, patients with a low percentage of CD4+CD45RO− T-cells were significantly more often diagnosed as microscopic polyangiitis (P<0.01).Conclusion. We identified two independent phenotypes of T-cell activation in AASV patients. These phenotypes are persistent and do not reflect disease activity. PTA predominantly occurs in patients with severe disease. This might explain the higher cumulative cyclophosphamide dose found in these patients. [ABSTRACT FROM AUTHOR]

Aim: To investigate the long-term results of ABO-incompatible (ABOi) kidney transplantation in a single center in Greece., Methods: Thirty consecutive ABOi kidney transplantations were performed from June 2005 to December 2013. All patients received rituximab one month prior to transplantation. Immunoadsorption therapy was performed for the removal of anti-A/B IgG antibodies until the titer was ≤ 1:16. Additional apheresis sessions were performed post-operatively. Intravenous immunoglobulin and oral immunosuppression consisting of tacrolimus (TAC) in combination with either everolimus or mycophenolate acid was administered. We compared the long term results of our ABOi group to those of a matched group of 30 ABO compatible (ABOc) living kidney recipients with similar baseline characteristics. The ABOc recipients received an immunosuppressive regimen consisting of TAC and mycophenolate acid. All patients in both groups received induction therapy with Basiliximab or Daclizumab, whereas corticosteroids were instituted on the day of surgery. During the follow-up period, indication biopsies were performed and interpreted by an experienced nephropathologist. The parameters we analyzed included the following: Donor/recipient age, gender, blood type, human leukocyte antigen mismatches, panel reactive antibodies, primary cause of renal failure, mean time on dialysis, immunosuppressive regimen, patient survival, graft outcome, incidence of rejections, surgical and infectious complications., Results: The mean follow-up period was 6 years (range 1 to 9 years). A mean of 5.0 ± 3.0 (range 0-14) pre-transplant immunoadsorptions were required in order to reach the target titer. Patient survival in ABOi group in comparison to ABOc group at 1, 3, 5 and 8 years did not differ significantly (100% vs 100%, 96% vs 100%, 92% vs 100% and 92% vs 100%, P = ns). Additionally, graft survival was similar in the two groups at the same time points (100% vs 100%, 96% vs 96%, 92% vs 96% and 81% vs 92%, P = ns). The mean serum creatinine and the estimated glomerular filtration rate by the modification of diet in renal disease formula at 1, 3, 5 and 8 years did not differ significantly between ABOi and ABOc group. None of the patients in the ABOi group developed acute or chronic antibody-mediated rejection evidenced by histological signs. Four patients (13.3%) in the ABOi group and 3 (10%) in the ABOc group experienced acute cellular rejection, which was treated successfully in all cases. Bacterial and viral infections were also similar between the two groups., Conclusion: ABOi kidney transplantation is a safe and effective alternative that enables kidney transplantation in countries with unacceptably long deceased-donor waiting lists.

Despite reduction of hepatitis C prevalence after recognition of the virus and testing of blood products, hemodialysis (HD) patients still comprise a high risk group. The natural history of hepatitis C virus (HCV) infection in dialysis is not fully understood while the clinical outcome differs from that of the general population. HD patients show a milder liver disease with lower aminotransferase and viral levels depicted by milder histological features on liver biopsy. Furthermore, the "silent" clinical course is consistent with a slower disease progression and a lower frequency of cirrhosis and hepatocellular carcinoma. Potential explanations for the "beneficial" impact of uremia and hemodialysis on chronic HCV infection are impaired immunosurveillance leading to a less aggressive host response to the virus and intradialytic release of "hepatoprotective" cytokines such as interferon (IFN)-α and hepatocyte growth factor. However, chronic hepatitis C is associated with a higher liver disease related cardiovascular and all-cause mortality of HD patients. Therapy is indicated in selected patients groups including younger patients with low comorbidity burden and especially renal transplant candidates, preferably after performance of a liver biopsy. According to current recommendations, choice of treatment is IFN or pegylated interferon with a reported sustained viral response at 30%-40% and a withdrawal rate ranging from 17% to 30%. New data regarding combination therapy with low doses of ribavirin which provide higher standard variable rates and good safety results, offer another therapeutic option. The new protease inhibitors may be the future for HCV infected HD patients, though data are still lacking.