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Kidney transplant recipients (KTRs) display higher cardiovascular morbidity and mortality than the general population. Increased short-term blood pressure variability (BPV) is associated with a higher risk of adverse cardiovascular outcomes in chronic kidney disease (CKD). The aim of this study is to investigate sex differences in short-term BPV in KTRs.In total, 136 male and 69 female KTRs with valid 24 h ambulatory blood pressure monitoring were included in this analysis. Systolic and diastolic BPV indices [SD, weighted SD (wSD), coefficient of variation (CV), average real variability (ARV) and variability independent of the mean (VIM)] were calculated with validated formulas for the 24 h, daytime and nighttime periods.Age, time from transplantation surgery and history of major comorbidities did not differ between men and women. During the 24-h period, systolic BPV indices did not differ between men and women (SBP-ARV: 9.4 ± 2.2 vs. 9.9 ± 2.5; P = 0.212). During the daytime period, SBP-CV and SBP-VIM were significantly higher in females compared with male participants (SBP-CV: 9.9 ± 2.4 vs. 11 ± 3.1%; P = 0.022 and SBP-VIM: 12.6 ± 3.0 vs 14.2 ± 3.9; P = 0.008); daytime SBP-SD and SBP-ARV, and all studied indexes during nighttime did not differ between groups. No significant between-group differences in 24 h and daytime diastolic BPV indices were detected. Nighttime DBP-CV was marginally higher in men (12.0 ± 3.6 vs. 11.4 ± 4.0; P = 0.053); the rest nighttime diastolic BPV indices measured were also nonsignificantly higher in men.In conclusion, 24-h systolic and diastolic BPV parameters did not differ between male and female KTRs, but short-term BPV over the respective day- and nighttime periods showed different trends in men and women. Further studies are needed to examine possible differences in long-term BPV in KTRs.

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. 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 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. Short-term BPV did not change significantly 3 and 12 months after kidney transplantation/donation neither in KTRs nor in living kidney donors. Longitudinal studies examining associations of BPV with adverse outcomes in these individuals are needed. What is the context?Previous studies have shown that both office and ambulatory BP levels are significantly reduced after kidney transplantation in KTRs.On the other hand, existing evidence suggests that kidney donors’ BP levels do not change significantly after kidney donation.Existing studies on BPV in KTRs are limited. The available data for living kidney donors are even fewer. Previous studies have shown that both office and ambulatory BP levels are significantly reduced after kidney transplantation in KTRs. On the other hand, existing evidence suggests that kidney donors’ BP levels do not change significantly after kidney donation. Existing studies on BPV in KTRs are limited. The available data for living kidney donors are even fewer. What is new? This is the first study assessing short-term BPV levels in ΚTRs undergoing living donor kidney transplantation, and their respective donors in short-term and mid-term follow-up. The main findings were:All 24-h, daytime and night-time BPV indexes did not change significantly from baseline to 3- and 12-month evaluation after kidney transplantation in the KTRs.No significant changes for the 24-h, daytime and night-time BPV were observed in their respective kidney donors at the same follow-up periods. This is the first study assessing short-term BPV levels in ΚTRs undergoing living donor kidney transplantation, and their respective donors in short-term and mid-term follow-up. The main findings were: All 24-h, daytime and night-time BPV indexes did not change significantly from baseline to 3- and 12-month evaluation after kidney transplantation in the KTRs. No significant changes for the 24-h, daytime and night-time BPV were observed in their respective kidney donors at the same follow-up periods. What is the impact?High BPV, which seems to remain unaltered after kidney transplantation, may be one of the many factors involved in the high cardiovascular risk observed in KTRs.Unchanged BPV levels further supports the evidence suggesting no higher risks of arrhythmias, cardiovascular events or death after living kidney donation. High BPV, which seems to remain unaltered after kidney transplantation, may be one of the many factors involved in the high cardiovascular risk observed in KTRs. Unchanged BPV levels further supports the evidence suggesting no higher risks of arrhythmias, cardiovascular events or death after living kidney donation.

Background Hypertension is the most prevalent cardiovascular risk factor in kidney transplant recipients (KTRs). Preliminary data suggest similar ambulatory blood pressure (BP) levels in KTRs and haemodialysis (HD) patients. This is the first study comparing the full ambulatory BP profile and short-term BP variability (BPV) in KTRs versus HD patients. Methods A total of 204 KTRs were matched (2:1 ratio) with 102 HD patients for age and gender. BP levels, BP trajectories and BPV indices over a 24-h ambulatory BP monitoring (ABPM) in KTRs were compared against both the first and second 24-h periods of a standard 48-h ABPM in HD patients. To evaluate the effect of renal replacement treatment and time on ambulatory BP levels, a two-way ANOVA for repeated measurements was performed. Results KTRs had significantly lower systolic blood pressure (SBP) and pulse-pressure (PP) levels compared with HD patients during all periods studied (24-h SBP: KTR: 126.5 ± 12.1 mmHg; HD first 24 h: 132.0 ± 18.1 mmHg; P = 0.006; second 24 h: 134.3 ± 17.7 mmHg; P Conclusions SBP and PP levels and trajectories, and BPV were significantly lower in KTRs compared with age- and gender-matched HD patients during all periods studied. These findings suggest a more favourable ambulatory BP profile in KTRs, in contrast to previous observations.

Objectives Ambulatory blood pressure (BP) control is worse in men compared with women with chronic kidney disease (CKD) and this may partially explain the faster CKD progression in men. This is the first study investigating possible sex differences in prevalence, control and phenotypes of hypertension in kidney transplant recipients (KTRs) with office-BP and 24-h ambulatory BP monitoring (ABPM). Methods This cross-sectional study included 136 male and 69 female stable KTRs who underwent office-BP measurements and 24-h ABPM. Hypertension thresholds for office and ambulatory BP were defined according to the 2017 ACC/AHA and 2021 KDIGO guidelines for KTRs. Results Age, time from transplantation, eGFR and history of major comorbidities did not differ between groups. Office SBP/DBP levels were insignificantly higher in men than women (130.3 ± 16.3/77.3 ± 9.4 vs. 126.4 ± 17.8/74.9 ± 11.5 mmHg; P = 0.118/0.104) but daytime SBP/DBP was significantly higher in men (128.5 ± 12.1/83.0 ± 8.2 vs. 124.6 ± 11.9/80.3 ± 9.3 mmHg; P = 0.032/P = 0.044). No significant between-group differences were detected for night-time BP. The prevalence of hypertension was similar by office-BP criteria (93.4 vs. 91.3%; P = 0.589), but higher in men than women with ABPM (100 vs. 95.7%; P = 0.014). The use of ACEIs/ARBs and CCBs was more common in men. Office-BP control was similar (43.3 vs. 44.4%, P = 0.882), but 24-h control was significantly lower in men than women (16.9 vs. 30.3%; P = 0.029). White-coat hypertension was similar (5.1 vs. 7.6%; P = 0.493), whereas masked hypertension was insignificantly more prevalent in men than women (35.3 vs. 24.2%; P = 0.113). Conclusion BP levels, hypertension prevalence and control are similar by office criteria but significantly different by ABPM criteria between male and female KTRs. Worse ambulatory BP control in male compared with female KTRs may interfere with renal and cardiovascular outcomes.

Background Hyperkalaemia is a frequent and potentially life-threatening condition in patients with chronic kidney disease (CKD). Even after successful kidney transplantation (KTx), KTx recipients have mild to severe CKD. Moreover, they share comorbid conditions and frequently use medications that predispose to hyperkalaemia. This study aimed to examine the prevalence and factors associated with hyperkalaemia in this population. Methods Over a pre-specified period of 6 months (1 September 2019 to 31 March 2020), we recorded in cross-sectional fashion information on serum potassium (K+) and relevant demographics, comorbidities, medications, laboratory and transplant-associated variables in clinically stable KTx recipients attending the Transplant Outpatient Clinic of our Department. Ηyperkalaemia was classified as follows: serum K+ level >5.0 mEq/L; and further as >5.0 mEq/L with concomitant use of sodium (Na+) polystyrene sulphonate; serum K+ ≥5.2 mEq/L; serum K+ ≥5.5 mEq/L. Univariate and multiple logistic regression analyses were used to identify factors associated with serum K+ >5.0 mEq/L. Results The study population consisted of 582 stable KTx recipients, 369 (63.4%) males, aged 52.4 ± 13.5 years, with estimated glomerular filtration rate (eGFR) of 55.8 ± 20.1 mL/min/1.73 m2 transplanted for >1 year. The prevalence of hyperkalaemia defined as K+ >5.0 mEq/L; >5.0 mEq/L and use of Na+ polystyrene sulphonate; K+ ≥5.2; or K+ ≥5.5 mEq/L, was: 22.7, 22.7, 14.4 and 4.1% (132, 132, 84 and 24 patients), respectively. In multivariate analysis, male gender [odds ratio (OR) = 2.020, 95% confidence interval (CI) 1.264–3.227] and use of renin–angiotensin–aldosterone system (RAAS) 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 use of non-K+-sparing diuretics (OR = 0.140, 95% CI 0.046–0.430) were associated with lower odds of the disorder. Conclusions The prevalence of mild hyperkalaemia in stable KTx recipients is relatively high but that of moderate or severe hyperkalaemia is low. Among a wide range of factors studied, only male gender and RAAS blockade were associated with increased odds of hyperkalaemia, while higher eGFR and diuretics were associated with decreased odds of hyperkalaemia., GRAPHICAL ABSTRACT Graphical Abstract

Background Pneumocystis jiroveci pneumonia (PCP) is a life-threatening pulmonary infection after kidney transplantation (KTx). Its onset in the current era of modern immunosuppression and of routine use of universal PCP prophylaxis seems to differ from its onset in previous decades in terms of late onset with subtle clinical presentation, indicating a need for increased vigilance. Methods We retrospectively studied all KTx recipients from our center who underwent bronchoscopy and bronchoalveolar lavage (BAL) between 2009 and 2018. Of these, all cases with confirmed PCP any time after the first post-KTx year were included in the analysis. Results Among 60 patients with KTx who had undergone bronchoscopy and BAL, 12 cases with late-onset PCP were identified. PCP appeared late at a median of 10.8 (interquartile range, 2.4-15.8) years after transplantation. Patients’ mean age was 59 years, and all were receiving stable low-dose immunosuppression. Most of the patients (67%) had received PCP prophylaxis after KTx. Five out of 12 patients (42%) had concomitant cytomegalovirus (CMV) reactivation at the time of PCP. In almost all cases, clinical presentation was mild. Treatment consisted of trimethoprim-sulfamethoxazole (TMP-SMX) and intravenous corticosteroid administration, and concomitant immunosuppression was temporarily reduced or withdrawn. Outcome was generally good. None of the patients developed respiratory insufficiency or required mechanical ventilation. One patient died as a result of sepsis, and 3 more with preexisting advanced chronic kidney disease subsequently lost their grafts. Conclusion Renal transplant recipients are at risk of late-onset PCP, even at a steady state of low-dose maintenance immunosuppression. Because of its subtle clinical presentation, high suspicion of the disease is warranted. Its early recognition and proper management are essential for a successful outcome.

Introduction Recent evidence suggests that complement activation is important in the pathogenesis of pauci-immune (PI) vasculitis. This is a retrospective investigation of the frequency of hypocomplementemia at pauci-immune glomerulonephritis (PIGN) diagnosis, in relation to vasculitic manifestations, renal histopathology, and treatment outcomes. Methods A total of 115 patients with biopsy-proven PIGN were categorized based on their serum complement C3 (sC3). Histopathology evaluation included activity and chronicity indexes. The primary outcome of interest was treatment resistance, defined as a progressive decline in kidney function, with persistently active urine sediment, leading to dialysis dependency or vasculitis-related death. Results In all, 20.9% of patients had low sC3 levels associated with more advanced renal impairment (P < 0.01), requiring acute dialysis (P < 0.01) more frequently compared to patients with normal sC3. Within 1 year, 85.7% of patients with normal sC3 responded to therapy, versus 58.3% of those with low sC3 (P = 0.001). The probability of treatment resistance was strongly associated with low sC3 (P = 0.004), high serum creatinine (P < 0.001), acute dialysis requirement (P < 0.001), and high histopathological score of chronicity (P < 0.01). Advanced histopathological activity was related to more intense interstitial leukocyte infiltration (P = 0.005) and higher likelihood of fibrinoid necrosis documentation in a vessel wall (P = 0.02). The probability of treatment resistance was higher in patients with low sC3 (odds ratio [OR] = 6.47, 95% confidence interval [CI] 1.47−28.35, P = 0.013), oliguria (OR = 29.57, 95% CI = 4.74−184, P < 0.0001), and high chronicity score (OR = 1.77, 95% CI = 1.23−2.54, P = 0.002). Conclusion Low sC3 is emerging as an independent predictor of treatment resistance in patients with PIGN associated with higher index of histopathological activity at diagnosis compared to normal sC3., Graphical abstract

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

Treatment of the plasma cell clone in monoclonal gammopathy of renal significance (MGRS) is necessary in order to reduce toxic immunoglobulin load to the kidneys and salvage renal function. There are limited data on the use of daratumumab in patients with MGRS. We summarize our experience with the use of daratumumab-based therapy in 25 MGRS patients, 12 of whom were previously untreated. The median follow-up of the cohort is 14 months. The best overall haematologic response in evaluable patients was complete response (CR) in five (22%), very good partial response (VGPR) in five (22%) and partial response (PR) in seven (30%) patients for an overall response rate of 74%. Two of five patients in CR and two patients with initially detectable clones, but non-measurable immunoglobulins, had undetectable minimal residual disease (MRD) with next-generation flow cytometry (NGF) after therapy. Haematologic response rate for previously untreated patients was 83% vs. 69% for previously treated and for daratumumab combinations it was 91% vs. 64%, and with CR/VGPR 82% vs. 29%, compared to daratumumab monotherapy. At six months, 12/22 (55%) patients not on dialysis achieved a reduction of proteinuria >30%, of at least 0·5 g/24 h, without an estimated glomerular filtration rate (eGFR) reduction. The toxicity was mild and predictable. In conclusion, daratumumab-based therapy is a new option for patients with MGRS.

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.

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.

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 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.

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.

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.

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.

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.

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.

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. 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.

The treatment of lupus nephritis still represents a therapeutic challenge for the clinician. Besides early recognition, appropriate guiding by the histologic classification at presentation as well as at relapsing disease, is essential. The most severe proliferative and mixed forms require aggressive induction therapy. Nevertheless, recent but established by RCTs advances, as low dose iv cyclophosphamide, lower doses of cor-ticosteroids and mychophenolate acid (MPA) allow us to achieve remission induction with lower toxicity without any cost in terms of efficacy. For maintenance, azathioprine and mycophenolate acid with concomitant low dose steroids have shown both good results with a slight superiority of mycophenolate acid. Emerging therapies as B cell targeting-either by depleting agents as the anti-CD 20 mAb Rituximab, or by modulating agents as the anti-Bliss Belimumab, further contribute to the effort to minimize toxicity. This review mainly focuses on the recent efforts to treat the most aggressive form of lupus nephritis effectively with the minimal possible toxicity.

Data regarding the prognosis of resistant hypertension (RHTN) with respect to its severity is limited. We investigated the cardiovascular risk of severe RHTN in a prospective observational study. A cohort of 1700 hypertensive patient with treated uncontrolled HTN was followed for a mean period of 3.6 ± 1.8 years. At baseline, standard clinical and laboratory workup was performed, including testing for secondary causes of RHT where applicable. Three groups were identified depending on presence of RHTN (office-based uncontrolled HTN under at least three drugs including a diuretic) and levels of office systolic blood pressure (BP): 1187 patients (70%) without RHTN, 313 (18%) with not-severe RHTN (systolic BP

Hepatitis B virus (HBV) poses a significant challenge for both dialysis patients and kidney transplant recipients despite its decreasing rates, especially in developed countries. The best preventive method is vaccination. Patients with chronic renal disease should ideally be vaccinated prior to dialysis, otherwise, reinforced vaccination practices and close antibody titer monitoring should be applied while on dialysis. HBV infected dialysis patients who are renal transplant candidates must be thoroughly examined by HBV-DNA, and liver enzyme testing and by liver biopsy. When needed, one must consider treating patients with tenofovir or entecavir rather than lamivudine. Depending on the cirrhosis stage, dialysis patients are eligible transplant recipients for either a combined kidney-liver procedure in the case of decompensated cirrhosis or a lone kidney transplantation since even compensated cirrhosis after sustained viral responders is no longer considered an absolute contraindication. Nucleoside analogues have led to improved transplantation outcomes with both long-term patient and graft survival rates nearing those of HBsAg(-) recipients. Moreover, in the cases of immunized HBsAg(-) potential recipients with concurrent prophylaxis, we are enabled today to safely use renal grafts from both HBsAg(+) and HBsAg(-)/anti-HBc(+) donors. In so doing, we avoid unnecessary organ discarding. Universal prophylaxis with entecavir is recommended in HBV kidney recipients and should start perioperatively. One of the most important issues in HBV(+) kidney transplantation is the duration of antiviral prophylaxis. In the absence of robust data, it seems that prophylactic treatment may be discontinued in selected stable, low-risk recipients during maintenance immunosuppression and should be reintroduced when the immune status is altered. All immunosuppressive agents in kidney transplantation can be used in HBV(+) recipients. Immunosuppression is intimately associated with increased viral replication; thus it is important to minimize the total immunosuppression burden long term.

Renal disease in monoclonal gammopathies (MGs) is associated with several different pathologies with prognostic and treatment implications. In symptomatic MM, cast nephropathy is a leading cause of renal dysfunction and acute renal failure (ARF) but in patients with other MGs the diagnoses may be diverse and monoclonal gammopathy of renal significance (MGRS) is well described. Renal biopsy is required in such cases in order to establish the diagnosis, especially if selective Bence Jones proteinuria is absent. MGs are more frequent in the elderly, in which renal diseases are also common, associated with underlying co-morbidities (diabetes, hypertension etc). However, although common, there is limited data on the frequency of monoclonal immunoglobulin (MIg)-unrelated pathologies in patients with a known MG presenting with renal dysfunction. Thus, we evaluated the frequency of non-MIg related renal pathologies in patients with known MGs, in a series of consecutive patients from a single referral center (Department of Clinical Therapeutics, Athens , Greece). We reviewed our database and identified 79 patients with known MGs that had a renal biopsy for evaluation of renal dysfunction, and which was performed after the diagnosis of MG. We excluded patients in which renal biopsy was performed before the diagnosis of the MG. At the time of renal biopsy, median age was 69 years (range 39-84), 63% were males, 28% had diabetes, 72% hypertension, 22.5% CAD, 7% an autoimmune disease ; 45% had known symptomatic MM (N=36) and 55% a prior diagnosis of MGUS or SMM. Median eGFR was 33 ml/min/1.73 m2 (range 4-110), 15% required dialysis, median proteinuria was 3.1 gr/d and was >0.5 gr/d in 93%. Abnormal FLC ratio was present in 69.5%, median dFLC level was 85 mg/L and 62% had dFLC>50 mg/L. In urine protein electrophoresis (PEP), median albumin proportion was 40% (range 3-100%) and median urine monoclonal protein was 2% (range 0-97%) of the total urine protein. Reasons leading to renal biopsy included proteinuria (with Renal pathology revealed a MIg-related diagnosis in 68%, which included cast nephropathy in 13%, MIDD in 25%, AL amyloidosis in 25% and other MGRS in 5%. A non MIg-related diagnosis was established in 32%, and included diabetic nephropathy in 5%, hypertension-associated in 14%, single cases of IgA nephropathy, chinese herb nephropathy, obesity-related GN and in 8% was drug related. Among MM patients, 26/36 were on therapy when renal biopsy was performed, 19/36 (53%) were in hematologic remission. Notably, in 11/19 (58%) of MM patients in remission, renal pathology was not related to MIg vs 6/17 (35%) of those not in remission or at the time of MM diagnosis. Factors that were associated with MIg-related pathology included serum albumin 1.7 gr/d (82% vs 48%, p=0.004), a positive UIFE (75% vs 33%, p=0.039), urine monoclonal protein >100 mg/d (68% vs 25%, p=0.003), dFLC > 50 mg/L (76% vs 37%, p=0.003) and abnormal FLC ratio (78% vs 53%, p=0.044). The presence of other co-morbidities (diabetes, hypertension, history of CAD, history of autoimmune disease) or the presence of hematuria or the reason leading to renal biopsy (proteinuria or ARF) were not associated with a diagnosis of non MIg-related renal pathology. In multivariate analysis, only urine monoclonal protein >100 mg/d (HR:7.95, 95% CI 1.3-47, p=0.024) was independently associated with a diagnosis of MIg-related pathology. If parameters of urine PEP (urine monoclonal protein, urine IFE) were not included in the analysis, then total proteinuria >1.7 gr/d (HR: 4.5, 95% CI 1.1-18, p=0.036) and dFLC>50 mg/L (HR:5.8, 95% CI 1.15-29, p=0.033) were the only independent predictors. By using these two parameters 7% of those without any vs 30% with any of the two vs 63% with both factors had a MIg related renal pathology. In conclusion, among patients with known monoclonal gammopathies and renal dysfunction, 32% had a non MIg-related diagnosis, which had implications in their management. Urine protein electrophoresis can help identify those at higher probability of MIg-related renal disease and should be evaluated in all patients with MGs; otherwise, dFLC > 50 mg/L and proteinuria >1.7 gr/d can be used. Renal dysfunction should not attributed to the underlying MIg without careful consideration of the other parameters and of a renal biopsy. Disclosures Kastritis: Amgen: Honoraria, Research Funding; Janssen: Honoraria, Research Funding; Takeda: Honoraria; Pfizer: Honoraria; Prothena: Honoraria; Genesis: Honoraria. Gavriatopoulou:Genesis: Honoraria, Other: Travel expenses; Amgen: Honoraria; Janssen: Honoraria, Other: Travel expenses; Takeda: Honoraria, Other: Travel expenses. Terpos:Medison: Honoraria; Genesis: Honoraria, Other: Travel expenses, Research Funding; Takeda: Honoraria, Other: Travel expenses, Research Funding; Janssen: Honoraria, Other: Travel expenses, Research Funding; Celgene: Honoraria; Amgen: Honoraria, Research Funding. Dimopoulos:Sanofi Oncology: Research Funding.

Monoclonal Gammopathy of Renal significance encompasses a spectrum of different renal pathologies that have a causal relationship with an underlying monoclonal protein produced by a, relatively indolent, plasma or other B-cell clone. These patients require anti-clonal treatment in order to salvage kidney function, however, there are few prognostic biomarkers that can help identify patients at higher risk for progression of renal disease. Increased plasma levels of soluble urokinase-type plasminogen activator receptor (suPAR) have been associated with focal segmental glomerulosclerosis and an elevated level of suPAR was independently associated with incident chronic kidney disease and an accelerated decline in the eGFR, in a large study (Hayek S et al, N Engl J Med 2015; 373:1916-1925). Increased Growth Differentiation Factor-15 (GDF-15) has been associated with the deterioration of renal function and progression to ESRD in diabetic patients but also in patients with AL amyloidosis. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is one of the earliest and most robust markers of acute kidney injury while serum Cystatin C (CysC) reflects renal function more accurately than creatinine and correlates with both tumor burden and renal function in MM. We measured serum levels of suPAR, NGAL, GDF-15 and CysC in the same frozen serum sample that was collected before any therapy was given. Measurements of the analytes were performed by means of immunoenzymatic techniques: suPAR (ViroGates A/S, Birkerod, Denmark), NGAL and GDF-15 (R&D Systems, Minneapolis, MN, USA), while CysC was measured with an immunoturbidimetric assay using the Roche Cobas 6000 Clinical Chemistry System. The study included 23 patients with MGRS (MIDD: 18, C3GN: 3, PGNMID: 2), 57% were men, median age was 66 years (range 47-85). Median baseline eGFR (by CKD-EPI) was 30.5 ml/min/1.73 m2 (range 3-102) and at the time of initiation of therapy one (4%) required dialysis. Median baseline proteinuria was 1.7 gr/d (range 0.6-10.2). Median dFLC was 57 mg/L (range 2-2,239) and median BM infiltration was 10% (range 0-50%). At initial presentation 92% had hypertension, requiring a median of 2 different drug classes (range 1-5). Median baseline levels of suPAR were 8.02 ng/ml (range 2.2-21), of CysC were 2.33 mg/L (0.94-7.03), of NGAL were 150.6 ng/ml (range 51.7-573) and of GDF-15 were 2,144 pg/ml (range 548-6,956). A correlation of suPAR levels was found with proteinuria (r=0.691, p=0.001), serum albumin levels (r=-0.706, p0.2 for all). All these biomarkers showed significant correlations with each other (p All patients received bortezomib-based therapy (with cyclophosphamide and dexamethasone); median follow up is 9 months and at 3 month landmark, 55% of evaluable patients had achieved a hematologic response while at 6 months 60% had a hematologic response. At the same time points a renal response (>50% reduction of proteinuria and 50% reduction of proteinuria (p=0.096), which after adjustment for baseline proteinuria and eGFR became clearer (p=0.054). We conclude that suPAR, NGAL, GDF-15 and CysC are markers with significant associations with renal function in patients with MGRS, but, from a clinical standpoint suPAR is probably the most promising marker with potential prognostic significance for renal outcomes. Additional follow up of the cohort and inclusion of additional patients will allow us to further evaluate this biomarker in MGRS. Disclosures Kastritis: Janssen: Honoraria, Research Funding; Takeda: Honoraria; Pfizer: Honoraria; Prothena: Honoraria; Amgen: Honoraria, Research Funding; Genesis: Honoraria. Gavriatopoulou:Amgen: Honoraria; Janssen: Honoraria, Other: Travel expenses; Takeda: Honoraria, Other: Travel expenses; Genesis: Honoraria, Other: Travel expenses. Papassotiriou:Roche: Employment. Terpos:Janssen: Honoraria, Other: Travel expenses, Research Funding; Medison: Honoraria; Takeda: Honoraria, Other: Travel expenses, Research Funding; Amgen: Honoraria, Research Funding; Celgene: Honoraria; Genesis: Honoraria, Other: Travel expenses, Research Funding. Dimopoulos:Sanofi Oncology: Research Funding.

Aims: To assess the long-term therapeutic benefit of temporary depletion of B lymphocytes in patients with idiopathic membranous glomerulopathy (MGN) and search for potential predictors of response. Patients and Methods: The patients included had been diagnosed with biopsy-proven MGN in the absence of secondary causes. Estimated glomerular filtration rate should be above 30 ml/min/1.73 m2 and 24-hour proteinuria 3 g/day or more. Patients who had been treated with cyclosporine or cytotoxic agents the year prior to study entry were excluded. Depletion of B cells was achieved with rituximab, which was administered intravenously for 4 consecutive weeks. Partial remission was defined as a >50% decrease in proteinuria with absolute proteinuria 50% decrease in proteinuria and an absolute protein excretion Results: Twelve patients were studied (4 females/8 males) with a mean age of 51.3 years. No major adverse effects were observed. During a median follow-up time of 48 months, 11/12 (91.6%) patients achieved remission [7/12 (58.3%) complete remission and 4/12 (33.3%) partial remission], while 1 patient did not respond to therapy. Twelve months after therapy, 68.8% (p = 0.003) of cases had achieved partial and 28.4% complete remission. Measurements of lymphocyte subpopulations did not reveal any changes except for the B cell depletion. B cell infiltrates captured per mm3 of renal tissue in the diagnostic biopsy did not correlate with subsequent response. Conclusion: Depletion of B cells in idiopathic MGN was well tolerated and resulted in significant and long-lasting response rates in a series of 12 patients.

SummaryIn patients with ANCA-associated vasculitis (AAV), CD25 expression is increased on circulating T cells. Although in animal experiments the role of CD4+ CD25+ T-regulatory-cells (Treg) in protection against autoimmunity is well established, the role of these cells in AAV is unknown. To investigate the hypothesis that an increased expression of CD25 on T cells is related to persistent T cell activation and not to disturbances in Treg cells in AAV (34 patients, six of them after renal transplantation), we investigated CD25 expression in different subpopulations of CD4+ cells and FOXP3 mRNA expression by reverse transcription-polymerase chain reaction (RT-PCR). In addition, T cell proliferation and cytokine secretion after stimulation with anti-CD3 and anti-CD28 and intracellular cytokine production after stimulation with phorbol myristate acetate (PMA)-ionomycin was determined. Controls were non-vasculitic renal transplant patients (n = 9) and healthy controls (HC) (n = 13). In AAV the total number of lymphocytes, CD4+ lymphocytes and the percentage of naive T cells are lower than in HC and RTX. An increased percentage of CD25+ cells was found in AAV and AAV/RTX, irrespective of disease activity, but not in HC or RTX. This was confined to the naive (CD4+ CD45RBhigh) population only. FOXP3 mRNA expression in CD4+ T cells did not differ between AAV patients and healthy controls. In vitro T cell proliferation was enhanced in AAV patients compared to HC (P

SummaryWhile most of our understanding of immune dysfunction in dialysis patients involves alterations in CD28–CD80/86 signalling, nothing is known of CD46-mediated co-stimulation of T cells in these patients. Because C3b/C4b bind to CD46 and complement activation occurs during haemodialysis (HD), we addressed whether CD46-mediated T cell activation is altered in HD (n = 9), peritoneal dialysis (PD) (n = 10) and predialysis patients (n = 8) compared to healthy controls (HC) (n = 8). T cell surface markers, T cell proliferation and interleukin (IL)-10 production were studied in CD4+T cells. In addition, CD46 splice-variants and IL-10 promoter gene polymorphisms were studied by reverse transcription (RT) or amplification refractory mutation system-polymerase chain reaction (ARMS-PCR), respectively. In all uraemic patients, irrespective of the stage of renal insufficiency or dialysis modality, a significant increase in the percentage of CD25 positivity in naive CD4+T cells was found (64% ± 21%versus 23% ± 18%, P < 0·001). Lymphocytes of HD patients proliferated in greater numbers and produced more IL-10 after co-stimulation with anti-CD46 than after co-stimulation with anti-CD28. This was also found in CD4+T cells of PD patients, albeit to a lesser extent. In contrast, with T cells of predialysis patients and of HC, co-stimulation via CD28 was more efficient. The observed alterations in T cell proliferation and IL-10 production were associated neither with CD46 splice variants nor with IL-10 promoter gene polymorphisms. Lymphocytes of HD patients show an increased response on CD46 co-stimulation. These data suggest that ongoing complement activation in HD patients may lead to alterations in acquired immunity.

About 50% of newly diagnosed mutilple myeloma (MM) patients (NDMM) have some degree of renal impairment (RI) at presentation, up to 20% have severe acute kidney injury (AKI) and ~1–5% may require extrarenal dialysis, whereas severe RI is associated with high risk of early death and other complications.1, 2 Immediate effective anti-myeloma therapy and vigorous supportive care are the cornerstones of management.2, 3 However, there are limited data focusing specifically on the management and outcomes of MM patients requiring dialysis as a consequence of MM, mostly including small numbers of patients on dialysis.4, 5, 6, 7, 8 Moreover, the use of high cut-off hemodialysis to rapidly reduce the load of nephrotoxic light chains may provide some additional benefit in patients requiring dialysis when treated with bortezomib-based therapies, but the reported results of two randomized studies are controversial.9, 10 Thus, we analyzed the outcomes of 52 consecutive NDMM with RI requiring dialysis, which were managed and treated in a single center, to provide data on response to therapy, dialysis discontinuation and survival in unselected patients, outside the context of clinical trials.

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.

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.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.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 P0.01) 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, P0.01). 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 (P0.01).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.