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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.

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.

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.

The main purpose of this study is to explore characteristics of patients with chronic kidney disease in tuberous sclerosis (TSC) and to underline differences in clinical characteristics between end-stage renal disease (ESRD) patients and patients in earlier stages of chronic kidney disease.This multicentric, retrospective study included data for 48 patients from seven South-Eastern European countries (Albania, Bosnia and Herzegovina, Croatia, Greece, Montenegro, Serbia, Slovenia) in the period from February to August 2020. Researchers collected data from local and national nephrological and neurological registries and offered clinical and laboratory results from medical histories in follow-up periods.This study enrolled 48 patients with a median age of 32.3 years (range, 18-46 years), and predominant female gender (60.45%). The percentage of patients with chronic kidney disease (CKD) diagnosis of the total number of patients was 66.90%, with end-stage renal disease development in 39.6%. The most prevalent renal lesions leading to chronic kidney disease were angiomyolipomas (AMLs) in 76.6%, while multiple renal cysts were present in 42.6% of patients. Nephrectomy was performed in 43% of patients, while the mTOR inhibitors were used in 18 patients (37.5%). The majority of patients had cutaneous manifestations of tuberous sclerosis-83.30% had hypomelanotic cutaneous lesions, and 68.80% had angiofibromas. Multiple retinal nodular hamartomas and "confetti" skin lesions were more frequent in end-stage renal disease (ESRD) than in patients with earlier stages of chronic kidney disease (p-0.033 and 0.03, respectively).Our study has also shown that retinal hamartomas and "confetti" skin lesions are more frequent in end-stage renal diseases (ESRD) patients than in other chronic kidney disease (CKD) patients. Usage of mTOR inhibitors can also reduce the number of complications and associated with tuberous sclerosis, such as dermatological manifestations and retinal hamartoma, which are more common in the terminal stage of chronic kidney disease.

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 &amp, 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.

Aims Diagnosis of primary membranous nephropathy (PMN) is mainly based on immunofluorescence/immunohistochemistry findings. However, assessment of specific features on optical microscopy can help to estimate the severity of the disease, guide treatment and predict the response. The aim of this study was to identify, classify and grade the precise histological findings in PMN to predict renal function outcome and guide treatment. Methods and results Histological parameters, including focal segmental sclerosis (FSGS), tubular atrophy (TA), interstitial fibrosis (IF) and vascular hyalinosis (VH), were re‐evaluated in 752 patients with PMN. Their predictive value was estimated separately, and also in a combination score (FSTIV) graded from 0 to 4. Finally, the impact of histology was assessed in the response to immunosuppressive treatment. Mean age of patients was 53.3 (15–85) years and most presented with nephrotic syndrome. FSGS was present in 32% and VH in 51% of the patients, while TA and IF were graded as stage ≥1 in 52% and 51.4%, respectively. The follow‐up period was 122.3 (112–376) months. FSGS, TA and IF and VH were associated with impaired renal function at diagnosis (P = 0.02, P 50% eGFR reduction, FSGS (P = 0.001) and TA (P = 0.02). Also, patients presented with FSGS, IF, VH and/or with FSTIV > 1 could benefit from immunosuppression, regardless of clinical presentation. Conclusions The presence and degree of four histological indices, FSGS, VH, TA and IF, assessed separately or in combination, and FSTIV score not only predict renal function outcome after long‐term follow‐up, but can also help in the choice of appropriate treatment. Decisions concerning immunosuppressive treatment can be guided by pathology regardless of clinical findings.

Background: Patients with diabetic kidney disease (DKD) are at increased risk for cardiovascular events but traditional risk factors do not fully explain this association. Evaluation of subclinical vascular disease might improve risk stratification and management of these patients. The aim of the study was to compare the prevalence of markers of arterial stiffness, carotid atherosclerosis and peripheral arterial disease between patients with DKD and patients with type 2 diabetes mellitus (T2DM) and preserved kidney function. Methods: We prospectively enrolled patients with DKD and age- and gender-matched patients with T2DM but without DKD (estimated glomerular filtration rate < and ≥60 mL/min/1.73 m2, respectively). The presence of arterial stiffness was evaluated by measuring pulse wave velocity (PWV), augmentation index (AIx), AIx adjusted to a heart rate of 75 beats/min (AIx@75) and central systolic, diastolic, pulse and mean blood pressure. The presence of carotid atherosclerosis was evaluated by measuring carotid stenosis, carotid intima-media thickness and maximal plaque thickness. The presence of PAD was evaluated with the measurement of ankle-brachial index (ABI). Results: Forty patients with T2DM were included in the study (mean age 71.6 ± 8.9 years). The prevalence of cardiovascular risk factors was similar in patients with and without DKD. PWV was higher in the former (9.8 ± 5.5 and 6.6 ± 4.4 m/s, respectively; p < 0.05) and carotid stenosis of the left carotid artery was also greater in patients with DKD (36.5 ± 12.6 and 22.1 ± 17.2%, respectively; p < 0.05). Other markers of arterial stiffness and carotid atherosclerosis and ABI did not differ between patients with DKD and those without DKD. Conclusions: Patients with DKD appear to have more pronounced arterial stiffness and carotid atherosclerosis than patients with T2DM and preserved kidney function despite the similar prevalence of traditional cardiovascular risk factors in the two groups. Therefore, evaluating the presence of subclinical vascular disease in these patients could be a useful tool for the personalization of their management.

Background and Aims 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. Method 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. Results 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. 11 (42.3%) patients lost their graft from FSGS in a median time of 33 (IQR 17.5-43.3) months. Conclusion 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.

Background and Aims Cardiovascular disease is highly prevalent in the chronic kidney disease population and associates with higher morbidity and mortality even in young ages. The aim of the present study was to assess data from 24h ambulatory blood pressure monitoring (ABPM) and 24h pulse wave analysis (PWA) in dialyzed children and investigate their association with left ventricular mass as a marker of increased cardiovascular risk. Method Children and adolescents aged 6 to 18 years, on dialysis for more than 12 months, [16 on peritoneal dialysis (PD) and 12 on hemodialysis (HD)], underwent 24h ABPM, 24h PWA, and echocardiography. Results Peripheral and central blood pressures (BPs), mean pulse wave velocity (PWV) and left ventricular mass index (LVMI) were similar between PD and HD patients (figure 1a,b). Among PWA hemodynamic parameters, augmentation index (AIx75), cardiac index (CI), and heart rate were higher in the HD group (p Conclusion HD pediatric patients demonstrate higher AIx75 and CI compared to PD patients even in the absence of LVH. These results suggest distinct patterns of vascular and cardiac functional changes in HD patients that may increase cardiovascular risk beyond LVH.

Background and Aims Hyperkalaemia is a frequent and potentially life-threatening condition in patients with CKD. Even after successful kidney transplantation, kidney transplant recipients have mild to severe CKD. Moreover, they share co-morbid conditions and frequently use medications that predispose to hyperkalaemia. This study aimed to examine the prevalence and factors associated with hyperkalaemia in this population. Method Over a pre-specified period of 6 months (September 1st 2019 to March 31st 2020), we recorded in a cross-sectional fashion information on serum potassium and relevant demographics, co-morbidities, medications, laboratory and transplant-associated variables in clinically stable kidney transplant recipients attending the Transplant Outpatient Clinic of our Department. Ηyperkalaemia was classified as follows: serum potassium level >5 mEq/L or >5 with concomitant use of sodium polystyrene sulfonate; ≥5.2; and ≥5.5 mEq/L. Univariate and multiple logistic regression analyses were used to identify factors associated with increased serum potassium >5.0 mEq/L. Results The study population consisted of 582 stable kidney transplant recipients, 369 (63.4%) males, aged 52.4±13.5 years, with eGFR of 55.8±20.1 ml/min/1.73m2 transplanted for more than one year. The prevalence of hyperkalaemia defined as potassium >5, >5 and use of sodium polystyrene sulfonate, ≥ 5.2 or ≥5.5, was 22.7%, 22.7%, 14.4% and 4.1% (132, 132, 84 and 24 patients), respectively. In multivariate analysis, male gender (OR 2.020, 95% CI 1.264-3.227) and use of renin-angiotensin-aldosterone-system blockers (OR 1.628, 95% CI 1.045-2.536), were independently associated with hyperkalaemia, while higher eGFR (OR 0.967, 95% CI 0.955-0.979) and diuretic use (OR 0.140, 95% CI 0.046-0.430) were associated with lower odds of the disorder. Conclusion The prevalence of mild hyperkalaemia in stable kidney transplant recipients is common but that of moderate or severe hyperkalemia is relatively uncommon. Male gender and low eGFR are the most potent factors associated with hyperkalaemia. Among a wide range of factors only male gender, RAAS blockade and low eGFR increased the odds of hyperkalemia.

Since its introduction in 1995, laparoscopic nephrectomy has emerged as the preferred surgical approach for living donor nephrectomy. Given the ubiquity of the surgical procedure and the need for favorable outcomes, as it is an elective operation on otherwise healthy individuals, it is imperative to ensure appropriate preoperative risk stratification and anticipate intraoperative challenges. The aim of the present study was to compare peri-and postoperative outcomes of living kidney donors (LD), who had undergone laparoscopic nephrectomy (LDN), with a control group of those who had undergone open nephrectomy (ODN). Health-related quality of life (QoL) was also assessed using the validated SF-36 questionnaire. Data from 252 LD from a single transplant center from March 2015 to December 2020 were analyzed retrospectively. In total, 117 donors in the LDN and 135 in the ODN groups were assessed. Demographics, type of transplantation, BMI, duration of surgery, length of hospital stay, peri- and postoperative complications, renal function at discharge and QoL were recorded and compared between the two groups using Stata 13.0 software. There was no difference in baseline characteristics, nor in the prevalence of peri-and postoperative complications, with a total complication rate of 16% (mostly minor, Clavien–Dindo grade II) in both groups, while a different pattern of surgical complications was noticed between them. Duration of surgery was significantly longer in the ODN group (median 240 min vs. 160 min in LDN, p &lt, 0.01), warm ischemia time was longer in the LDN group (median 6 min vs.2 min in ODN, p &lt, 0.01) and length of hospital stay shorter in the LDN group (median 3 days vs. 7 days in ODN). Conversion rate from laparoscopic to open surgery was 2.5%. There was a drop in estimated glomerular filtration rate (eGFR) at discharge of 36 mL/min in the LDN and 32 mL/min in the ODN groups, respectively (p = 0.03). No death, readmission or reoperation were recorded. There was a significant difference in favor of LDN group for each one of the eight items of the questionnaire (SF1–SF8). As for the two summary scores, while the total physical component summary (PCS) score was comparable between the two groups (57.87 in the LDN group and 57.07 in the ODN group), the mental component summary (MCS) score was significantly higher (62.14 vs. 45.22, p &lt, 0.001) in the LDN group. This study provides evidence that minimally invasive surgery can be performed safely, with very good short-term outcomes, providing several benefits for the living kidney donor, thereby contributing to expanding the living donor pool, which is essential, especially in countries with deceased-donor organ shortage.

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&ndash, 1) with a median proteinuria was 8.5 (IQR 4.9&ndash, 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 (&plusmn, 1.79) and 4.4 (&plusmn, 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&ndash, 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.

The first steps in the development of nephrology in Greece can be traced in the early 1950s, driven by the vision of a small number of pioneering physicians. Nephrology was recognized as a distinctive medical specialty in 1976, and since the 1980s, a vast expansion of nephrology and dialysis services has occurred. Incidence and prevalence of end-stage renal disease are high, and the population affected by this condition is still growing. Although all renal replacement therapy modalities are developed, transplant rates are low, as well as the use of peritoneal dialysis. Renal replacement therapy is fully reimbursed by the insurance system, but due to Greece’s financial constraints and given the increasing end-stage renal disease population, careful planning is needed in order to achieve sustainable quantity and quality of services in the future. The main areas for future development include an increase in transplant rates, which is the top priority, further development of clinical research, a possible increase in peritoneal dialysis use, and finally, exploiting the potential for dialysis-related medical tourism.

Cardiovascular events are one of the leading causes of mortality in kidney transplant recipients. Hypertension is the most common comorbidity accompanying chronic kidney disease, with prevalence remaining as high as 90% even after kidney transplantation. It is often poorly controlled. Abnormal blood pressure profiles, such as masked or white-coat hypertension, are also extremely common in these patients. The pathophysiology of blood pressure elevation in kidney transplant recipients is complex and includes transplantation-specific risk factors, which are added to the traditional or chronic kidney disease-related factors. Despite these observations, hypertension management has been an under-researched area in kidney transplantation. Thus, relevant evidence derives either from studies in the general population or from small trials in kidney transplant recipients. Based on the relevant guidelines in the general population, lifestyle modifications should probably be applied as the first step of hypertension management in kidney transplant recipients. The optimal pharmacological management of hypertension in kidney transplant recipients is also not clear. Dihydropyridine calcium channel blockers are commonly used as first line agents because of their lack of adverse effects on the kidney, while other antihypertensive drug classes are under-utilised due to fear of the possible haemodynamic consequences on renal function. This review summarizes the existing data on the pathophysiology, diagnosis, prognostic significance and management of hypertension in kidney transplantation.

Monoclonal gammopathies have been associated with a wide spectrum of renal pathologies [1,2]. In symptomatic MM, cast nephropathy is a leading cause of renal dysfunction and acute renal failure [3]...

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.

Background and Aims Severe kidney involvement represents a frequent clinical scenario for patients with pauci-immune (PI) vasculitis. We aimed to explore the factors, which are associated with prognosis, in short and long term, following administration of appropriate immunosuppressive therapy. Method Patients were included if they had biopsy proven PI glomerulonephritis (GN) with estimated GFR20 ml/min/1.73 m2 with no signs of vasculitis. Histopathological evaluation included arteriosclerosis, % of normal glomeruli, activity index, chronicity index. Results A total of 83 patients, with a mean age of 59.6 (15.05) years were included. There were, 45 males (54.2%). After 3 months, 59 patients (71.1%) had responded to immunosuppressive therapy, 16 (19.3%) were dialysis depended, 5(6.02%) died and 2 were lost in follow up. By the end of the 1st year, 59 patients (71.1%) achieved remission, 16(19.3%) ended up in ESKD and 6(7.4%) died. Factors which were associated with treatment response included MPO-ANCA positivity [odds ratio OR:3.9, 95%CI (1.13-13.37) p=0.03], eGFR>10ml/min/1.73m2 at presentation [OR:2.5, 95% CI(0.86-7.30), p=0.009], normal glomeruli >10% [OR:3.8, 95%CI (1.24-12.1), p=0.02], and chronicity index more than 6 [OR:6.2, 95% CI(1.77-22.4), p=0.004]. Risk factors associated with ESKD included non-response to immunosuppressive therapy [Relative Risk RR:0.05, 95%CI (0.01-0.2) p75 years [RR:3.2, 95% CI (0.9-10.6) p=0.055]. Two of the 6 deaths were disease related. Conclusion A significant proportion of patients with PI-GN, who presented with severe renal dysfunction, responded to immunosuppressive therapy and recovered renal function approximately 3 months after initiation of therapy. The most important risk factors for ESKD were age>75 years

Background and Aims Advances in immunosuppressants, used for kidney transplantation (KTx) have significantly improved outcomes in this field. We aimed to compare the long-term results of KTx in recipients with IgAN, as cause of end stage kidney disease (ESKD), with those of patients, with non-glomerular causes of renal failure, during the modern era of immunosuppression for KTx. Method This is a retrospective, case control study, in which were included patients who received a KTx after 2000. Patients were eligible to be included, if they had IgAN in a native kidney biopsy specimen and follow up longer than 1 year after KTx. IgAN patients were compared to a control-group of patients with non-glomerular primary causes of ESKD matched for age, gender, date of KTx and donor source. Graft biopsies were performed by clinical indication. Patients with ABO incompatible KTx, preemptive KTx, re-KTx, PRA>50%, major surgical complications during the 1st post-KTx month or non-compliance were excluded from the analysis of outcome. Primary outcomes of interest included graft function, patient and graft survival at end of follow up. The rate of IgAN recurrence in the graft and its impact in renal function and survival were also recorded. Computed GFR was calculated using the Modification of Diet in Renal Disease formula. Results A total of 102 KTx recipients with biopsy-proven IgAN, were compared to 204 controls with non-glomerular causes of ESKD. The mean age of patients with IgAN was 43.2(±10.15) years and 68(66.7%) were men. The mean time in dialysis was 50.2(±48.7) months and 59(57.8%) of them received a graft from a living donor. The mean cold ischemia time was 17.5(±6.7) hours, while 22(21.6%) of patients experienced delayed graft function. 97.05% of patients received induction therapy with an anti-CD25 inhibitor and 99.3% were maintained with a triple immunosuppressive regimen consisted of a mycophenolate mofetil formulation, a calcineurin inhibitor and glucocorticoids. The mean serum creatinine and eGFR at end of follow up were significantly lower for the IgAN group (p=0.001 and p=0.02 respectfully) with no difference in the frequency of acute rejection. However, graft and patient survival were not different even after controlling for follow up longer than one decade. During a mean follow up time of 120.8(±49.1) months, IgAN recurrence in the graft was documented in 23(22.5%) patients. The mean time to recurrence was 47.8(41.8) months, with a mean serum creatinine 1.83(±0.52) mg/dl and eGFR of 43.45(±18.4) ml/min/1.73m2 at the end of follow up. Within the IgAN group, although graft function was significantly lower in patients with disease recurrence, compared with that of patients without recurrence (p=0.003), graft loss remained not different between these two subgroups (p=0.49). Conclusion In the newer era of immunosuppression, long-term outcomes of KTx in patients with IgAN, as primary disease, appear significantly improved, and although graft function was significantly lower in patients with IgAN at the end of follow up, graft and patient survival was not different, compared to patients with non-glomerular causes of ESKD. Recurrence of IgAN in the graft was documented in 22.5% of patients and was associated with significantly lower eGFR at end of follow up compared to patients without recurrence but it did not impact graft survival in this time period.

Glomerular crescents in kidney transplantation are indicative of severe glomerular injury and constitute a hallmark of RPGN. Their concurrence with ABMR has been rarely described only in adult patients. We report a case of 10-year-old boy with compound heterozygous Fin-major Finnish-type congenital nephrotic syndrome, who had received a deceased-donor kidney transplant 5 years before onset of acute kidney injury and nephrotic range proteinuria without hematuria. Kidney allograft biopsy illustrated 6 glomeruli with global sclerosis and 6 with remarkable circumferential or segmental cellular crescents. Negative glomerular immunofluorescence for immune-complex deposits and the absence of serum ANCA eliminated the presence of immune-mediated and ANCA-positive pauci-immune crescentic glomerulonephritis. Diagnosis of ABMR was based on the high levels of HLA class II DSA and the histological evidence of glomerulitis, peritubular capillaritis, and acute tubular injury with positive linear peritubular capillary C4d staining. The patient despite plasmapheresis and enhanced immunosuppressive treatment progressed to end-stage renal disease. We conclude that glomerular crescents may represent a finding of AMBR and possibly a marker of poor allograft prognosis in pediatric patients.

B-cell clonal expansion has been sporadically described in the blood and/or renal tissue of patients with glomerulonephritides, albeit with unclear pathogenetic role. Herein, using spectratyping analysis, we observed oligoclonal intrarenal B-cell populations in 59% of glomerulonephritis patients with podocyte injury (6/7 with focal segmental glomerulosclerosis, 1/3 minimal change disease, 1/3 idiopathic membranous nephropathy, 3/4 IgA nephropathy, 2/5 membranous lupus nephritis), 20% of glomerulonephritis patients without podocyte involvement (4/13 with mesangial or proliferative lupus nephritis, 0/3 idiopathic membranoproliferative glomerulonephritis, 0/4 pauci-immune vasculitis) and 17% of control patients with renal cancer. In multivariate analysis, oligoclonal B-cells were associated with podocyte injury and the grade of glomerulosclerosis (both p = .009). B-cell oligoclonal expansions were not found in the paired peripheral blood samples. We postulate that B-cell expansion in the kidney results from local stimuli, including antigens expressed on podocytes. Further studies to unravel the role of oligoclonal B-cells in (auto)immune-mediated kidney disease are warranted.

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&rsquo, 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 (&plusmn, 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 (&plusmn, 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.

We retrospectively evaluated 55 consecutive patients who received at least one dose of lenalidomide for relapsed/refractory AL amyloidosis. Their median age was 63 years; 72% had heart and 75% kidney involvement and 13% were on dialysis; while 20%, 46% and 34% had Mayo stage -1, -2 and -3 disease, respectively. Median time from start of primary therapy to lenalidomide was 15 months (range 2–100) and median number of prior therapies was 1 (range 1–4); 73% of the patients had prior bortezomib and 42% were bortezomib-refractory. On intent to treat, haematologic response rate was 51% (5.5% CRs, 20% VGPRs) and was 56% versus 40% for patients with and without prior bortezomib and 47% versus 62.5% for bortezomib refractory versus non-refractory patients (p = .351). Organ response was achieved by 16% of evaluable patients (22% renal, 7% liver and 3% cardiac); however, 10 (21%) patients progressed to dialysis. Median survival post lenalidomide was 25 months. Bortezomib-refractory patients had worse outcome (median survival of 10.5 versus 25 months for bortezomib-sensitive patients versus not reached for bortezomib-naive patients, p = .011). Median lenalidomide dose was 10 mg and no patient received the 25 mg dose; however, in 60% a dose reduction was required. Median duration of lenalidomide therapy was 7.2 months and 46% discontinued lenalidomide before completion of planned therapy, mainly due to toxicity (26%) or disease progression/no response (13%). We conclude that although lenalidomide is a major salvage option for patients with relapsed/refractory AL amyloidosis, its toxicity in patients with AL amyloidosis is significant and doses should be adjusted for optimal tolerability.

Background Infection by Nocardia species is an uncommon cause of severe clinical syndromes, particularly in immunocompromised patients, and solid-organ transplantation is the most common underlying condition. The syndrome of inappropriate antidiuretic hormone secretion (SIADH) has been described thus far in lung and stem cell transplants with systemic nocardiosis. Case Report We report the first case of SIADH in a female elderly renal transplant recipient diagnosed with systemic nocardiosis 2 years after transplantation. The SIADH was managed appropriately, and her immunosuppressive regimen remained unchanged but was adjusted at a lower level. The systemic Nocardia infection was successfully treated with intravenous administration of trimethoprim-sulfamethoxazole and imipenem for 2 weeks followed by oral trimethoprim-sulfamethoxazole for a total of 12 months. Conclusions The SIADH syndrome is a recognizable complication of Nocardia infection in renal transplant recipients. Prompt identification along with proper management and prolonged antimicrobial treatment are essential to improve patients' outcome.

Patients with diabetic kidney disease (DKD) are at very high risk for cardiovascular events. Only part of this increased risk can be attributed to the presence of diabetes mellitus (DM) and to other DM-related comorbidities, including hypertension and obesity. The identification of novel risk factors that underpin the association between DKD and cardiovascular disease (CVD) is essential for risk stratification, for individualization of treatment and for identification of novel treatment targets.In the present review, we summarize the current knowledge regarding the role of emerging cardiovascular risk markers in patients with DKD. Among these biomarkers, fibroblast growth factor-23 and copeptin were studied more extensively and consistently predicted cardiovascular events in this population. Therefore, it might be useful to incorporate them in risk stratification strategies in patients with DKD to identify those who would possibly benefit from more aggressive management of cardiovascular risk factors.

Objectives Kidney transplant (KTx) recipients with IgAN as primary disease, were compared with recipients with other causes of renal failure, in terms of long-term outcomes. Methods Ninety-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). Results At 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% (p Conclusion Recipients 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.

Background Natural history, predisposing factors to an unfavourable outcome and the effect of various therapeutic regimens were evaluated in a cohort of 457 patients with immunoglobulin A nephropathy (IgAN) and follow-up of at least 12 months. Methods Patients with normal renal function and proteinuria 2.5 mg/dL and/or severe glomerulosclerosis received no treatment. Patients with normal or impaired renal function and proteinuria >1 g/24 h for >6 months received daily oral prednisolone or a 3-day course of intravenous (IV) methylprednisolone followed by oral prednisolone per os every other day or a combination of prednisolone and azathioprine. The clinical outcome was estimated using the primary endpoints of end-stage renal disease and/or doubling of baseline SCr. Results The overall 10-year renal survival was 90.8%, while end-stage renal disease and doubling of baseline SCr developed in 9.2% and 14.7% of patients, respectively. Risk factors related to the primary endpoints were elevated baseline SCr, arterial hypertension, persistent proteinuria >0.5 g/24 h and severity of tubulointerstial fibrosis. There was no difference in the clinical outcome of patients treated by the two regimens of corticosteroids; nevertheless, remission of proteinuria was more frequent in patients who received IV methylprednisolone (P = 0.000). The combination of prednisolone with azathioprine was not superior to IV methylprednisolone followed by oral prednisolone. Side effects related to immunossuppressive drugs were observed in 12.8% of patients. Conclusion The clinical outcome of patients with IgAN was related to the severity of clinical and histological involvement. The addition of azathioprine to a corticosteroid-based regimen for IgAN does not improve renal outcome.

A staging system for patients with renal AL amyloidosis, based on eGFR ( 100) at 3 months had a 2-year progression to dialysis of 0% vs 24% for patients who either did not reduce to or still had a ratio >100 (P = .001); similar results were obtained by applying the same criteria at 6 months; thus, the evaluation of treatment effect on renal function may be identified early. Furthermore, primary bortezomib-based therapy was more effective than lenalidomide-based therapy, in terms of renal outcomes, especially in patients at intermediate renal risk, but without affecting overall survival.

Glomerular diseases and renal transplantation are the main fields of nephrology in which the immune system plays a prevalent role. Glomerular diseases have traditionally been attributed to auto-immune conditions, whereas allograft rejection has been considered an allo-immune response. However, common immunopathologic mechanisms that include Toll-like receptors, complement and B-cell activation, as well as genetic and infectious factors appear to be involved in the pathogenesis of both entities. Novel therapeutic regimens directed against specific targets of the immune system show promising results in glomerulopathies as well as in renal transplantation.

Objective The clinical impact of repeat renal biopsies in patients with lupus nephritis (LN) is still debatable. The aim of this retrospective analysis was to assess whether repeat renal biopsy is a reliable tool in guiding therapeutic decisions. Methods Laboratory and histological parameters and therapeutic changes in 35 patients with LN and repeat renal biopsies were retrospectively analyzed. Biopsies were performed in the presence of clinical evidence of an active glomerular disease. Biopsy specimens were retrospectively re-assessed by two renal pathologists and were compared according to the last International Society of Nephrology/ Renal Pathology Society classification. Results Thirty-five patients had two, 13 had three, 5 had four, 4 had five, and 1 had six renal biopsies. Fifty-eight comparisons of renal biopsies were made. Median times between the first and second, second and third, third and fourth, and fourth and fifth biopsies were 31, 27, 34, and 28 months, respectively. The mean activity indices from the first to the fifth biopsy were 8.7, 6.6, 7.8, 9.4, and 4.7, whereas the mean chronicity indices were 1.7, 2.3, 4.3, 5.2, and 7.7, respectively. Conversion was observed in 65.5% of cases with the most frequent (21%) being between classes III and IV. Conversion to a more severe type of nephritis occurred in 19% of cases. There was no correlation of laboratory parameters to the type of nephritis upon conversion. In 79% of cases, immunosuppressive therapy was modified after repeat biopsy. Conclusion Repeat biopsy is a reliable tool for monitoring the activity and chronicity status of LN and for tailoring immunosuppressive therapy to the needs of the patient, especially late in the course of the disease.

Background The recent interferon-free direct-acting antiviral (DAA) regimens have very good safety and efficacy profiles and are highly recommended for kidney transplant (KT) recipients with chronic hepatitis C (CHC). Methods All KT recipients with CHC followed at our hospital and who received therapy with the current DAAs were included. At the baseline visit, demographic, clinical and laboratory variables before and after KT, as well as at the commencement of DAAs, at the end of antiviral therapy and the end of follow up, were recorded, including assessment of glomerular filtration rate (eGFR). The changes in eGFR (DGFR) between baseline and end of therapy (1st period), and between end of therapy and end of follow up (2nd period), were evaluated. Results Twelve KT recipients were retrospectively evaluated: 2 had received antiviral therapy in the past; 4 (33.3%) patients had genotype 1 and 3 (25%) genotype 4 CHC. The median stiffness was 11.9 kPa (range 5-16.8), while 5 patients, none with decompensated cirrhosis, had stiffness >12.5 kPa. Eight patients received a sofosbuvir-containing antiviral regimen (Group 1) and 4 patients received an antiviral regimen without sofosbuvir (Group 2). Eleven (91.7%) patients achieved a sustained virological response (SVR). One patient discontinued DAAs early after treatment and did not achieve SVR. Otherwise, DAAs were well tolerated and no rejection episode was recorded. The DGFRs in the 1st period and 2nd period did not differ significantly between Group 1 and Group 2 patients. Conclusion In this real-world study of KT recipients with CHC, the high efficacy and clinically acceptable tolerability of DAAs were confirmed.

Management 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.Aimof 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.

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.

Fibrillary glomerulonephritis (FGN) is a diverse glomerular disease with poor renal prognosis. The optimal therapeutic approach remains undetermined, as treatment outcomes vary across different studies.We retrospectively reviewed the medical data of 10 patients diagnosed with biopsy-proven FGN at our center between 2004 and 2019. Clinical and histological features, as well as therapeutic regimens and treatment response, are reported.The patients were predominantly men (2.5/1 men-female ratio) with a mean age at diagnosis of 46.5 years (IQR: 41.5-59.5). The median proteinuria and creatinine levels at presentation were 2.55 g/day (IQR: 0.4-8.9) and 1.35 mg/dl (IQR: 0.94-1.88), respectively. Four out of 10 patients presented with nephrotic syndrome, 5 patients with nephritic syndrome and 1 with isolated microscopic hematuria. Light microscopy showed mesangial proliferative (n = 7), membranoproliferative-like (n = 2), and diffuse sclerosing patterns (n = 1). Rituximab was used in 7/10 patients, either as monotherapy (n = 3) or combined with cyclophosphamide and corticosteroids (n = 4). Patients who were treated with immunosuppression had higher median levels of creatinine (1.40 mg/dl) and proteinuria (3.5 g/d) compared to those who received supportive treatment alone (0.94 mg/dl and 0.6 g/d, respectively). After a median follow-up of 30 months (IQR:18-66.5), 4 out of 7 patients (57%) treated with immunosuppression achieved a clinical response, 1 had persistent renal dysfunction and 2 patients progressed to end-stage renal disease.The present case series extends the existing literature on the clinical features and outcomes of FGN, as well as the use of rituximab-based regimens for the treatment of the disease. Further research is needed to establish the proper management of the disease.

Glomerular diseases and renal transplantation are the main fields in nephrology in which the immune system plays a prevalent role. They have for long been considered as independent conditions due to the prominent role of autoimmunity in glomerular diseases and of alloimmunity in renal transplantation. Moreover, histologic features differ between glomerular diseases and transplantation: in glomerular diseases, histologic damage involves primarily the glomeruli and secondarily the tubulointerstitium and small vessels, whereas in transplantation, allograft injury comprises primarily the tubulointerstitium and vessels and to a lesser degree the glomeruli. However, recent research has shown that the pathogenetic mechanisms in both conditions share common pathways and that there is cross-reaction between innate and adaptive immunity as well as between auto- and alloimmunity [1].

Background Previous studies have shown, using polymerase chain reaction (PCR), cloning, sequencing and analysis of rearranged immunoglobulin heavy-chain (Ig-VH/DH/JH) genes, that clusters of clonally-related sequences are commonly found in the peripheral blood of patients with active lupus nephritis. Objectives Using an easy-to-perform method such as spectratyping analysis, to test the hypothesis that clonal B-cell populations are present in the renal tissue of lupus nephritis patients, induced perhaps as a result of local (auto)antigenic stimulation. Methods Genomic DNA extracted from renal biopsy samples from 18 patients with active lupus nephritis and 24 control patients with other (auto)immune-mediated glomerular diseases, as well as DNA from 25 paired peripheral blood samples, was subjected to multiplex PCR for the detection of Ig-VH clonal rearrangement. PCR products were analysed by capillary electrophoresis according to the Biomed-2 standard guidelines for the definition of clonal B cell populations. Immunohistochemistry using the B-cell-specific L-26 antibody was also performed in available renal samples. Results Electrophoregrams of PCR products derived from patients with biopsy proven active lupus nephritis revealed the presence of oligoclonal B-cell populations among polyclonal B-cells in renal tissue of 6/18 patients. No associations with clinical or histology class were evident. Oligoclonal B-cell populations were also found in renal samples derived from patients with untreated focal segmental glomerulosclerosis (6 of 7), minimal change disease (1 of 3), membranous nephropathy (1 of 3) and IgA nephropahy (3 of 4), and not in patients with pauci-immune vasculitis (n=4) or membranoproliferative glomerulonephritis (n=3). Oligoclonal B-cell populations were not found in any of the paired peripheral blood samples derived from 13 patients having renal B-cell oligoclonality, suggesting the existence of local (auto)antigens leading to clonal expansion rather than B-cell transfer through peripheral circulation. Finally, spectratyping analysis identified polyclonal or oligoclonal B-cells in all renal tissues in the absence of detectable B-cells by immunohistochemistry in the same samples. Conclusions These novel findings show that spectratyping analysis can detect oligoclonal B-cell expansions in renal tissue from patients with active lupus nephritis and other (auto)immune-mediated glomerular diseases. Whether this standardised method can identify individual patients who could benefit from therapeutic B cell depletion deserves further study. Reference [1] Sfikakis PP, et al. Clonal expansion of B-cells in human systemic lupus erythematosus: evidence from studies before and after therapeutic B-cell depletion. Clin Immunol. 2009Jul;132(1):19–31. Disclosure of Interest None declared

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.

Colchicine is a lipophilic alkaloid drug, which exhibits ant-inflammatory and anti-fibrotic properties. Cardinal mechanisms of action of colchicine are the disruption of the microtubule system and the inhibition of neutrophil adhesion and recruitment. Colchicine is indicated in the prevention and treatment of gouty arthritis and familial Mediterranean fever. In this review, we summarize current and potentially future pharmacologic activities of colchicine in various renal disease entities along with pharmacokinetic and pharmacodynamic properties. Additionally, we will refer to main interactions of colchicine with medications used in renal medicine, as well as dosing recommendations in patients with reduced glomerular filtration rate.

Patients returning to dialysis after kidney transplant failure represent approximately 5%-15% of the population starting hemodialysis. These patients exhibit a high risk of morbidity and mortality attributed mainly to the exposure to immunosuppressive medications and to a uremic environment. The purpose of this paper was to review data regarding survival after renal allograft failure and the optimal management of patients before returning to dialysis. Moreover, issues surrounding nephrectomy after renal allograft failure, the tapering of immunosuppression and the possibility of retransplantation are examined, because they seem to be crucial for patient survival and the quality of life.

Background Long-term allograft survival is a major challenge in kidney transplantation. This study sought to estimate the evolution of renal function in patients receiving different immunosuppressive regimens based on everolimus (EVR). Methods Ninety-nine renal allograft recipients were included in a 12-month open-label, noninterventional, prospective, single-center study. Patients were divided into 2 groups, de novo and late conversion to EVR. Results Group A included 40 patients under calcineurin inhibitor (CNI) plus EVR. Median time posttransplantation was 33.06 months (interquartile range 18.25 to 42.85). Mean estimated glomerular filtration rate (eGFR) the first month posttransplantation (using Modification of Diet in Renal Disease formula) was 54.89 ± 19.08 mL/min, and mean proteinuria was 0.54 ± 0.38 g/24 h. At the end of follow up, mean eGFR and mean proteinuria significantly improved (65.49 ± 20.79 mL/min; P = .011 and 0.157 ± 0.089 g/24 h; P = .002, respectively). Group B consisted of 59 patients; 49 of them initially received mycophenolic acid (MPA) plus CNI, and 10 had been on azathioprine plus CNI. Initial immunosuppression was switched to MPA plus EVR in 49 patients, CNI plus EVR in 4 patients, and EVR in 6 patients, in a median time of 37 months (interquartile range 14.75 to 112.5) posttransplantation. Main indications for conversion were malignancies and biopsy-proven chronic allograft injury. Mean eGFR 1 month posttransplantation and at the time of conversion were 50.79 ± 17.83 mL/min and 57.39 ± 19.17 mL/min, respectively (P = .014). After conversion, mean eGFR increased (66 ± 24.89 mL/min; P = .006). Mean proteinuria was 0.509 ± 0.530 g/24 h the first posttransplantation month, and it remained stable at 0.415 ± 0.431 g/24 h until study completion. Two acute rejection episodes occurred. At the end of follow-up, patient and death-censored graft survival were 97% and 100%, respectively. Conclusions In kidney transplant recipients, EVR either de novo or after conversion with or without CNI is a safe and effective treatment that preserves renal function.