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Membranoproliferative GN (MPGN) was recently reclassified as alternative pathway complement–mediated C3 glomerulopathy (C3G) and immune complex–mediated membranoproliferative GN (IC-MPGN). However, genetic and acquired alternative pathway abnormalities are also observed in IC-MPGN. Here, we explored the presence of distinct disease entities characterized by specific pathophysiologic mechanisms. We performed unsupervised hierarchical clustering, a data-driven statistical approach, on histologic, genetic, and clinical data and data regarding serum/plasma complement parameters from 173 patients with C3G/IC-MPGN. This approach divided patients into four clusters, indicating the existence of four different pathogenetic patterns. Specifically, this analysis separated patients with fluid-phase complement activation (clusters 1–3) who had low serum C3 levels and a high prevalence of genetic and acquired alternative pathway abnormalities from patients with solid-phase complement activation (cluster 4) who had normal or mildly altered serum C3, late disease onset, and poor renal survival. In patients with fluid-phase complement activation, those in clusters 1 and 2 had massive activation of the alternative pathway, including activation of the terminal pathway, and the highest prevalence of subendothelial deposits, but those in cluster 2 had additional activation of the classic pathway and the highest prevalence of nephrotic syndrome at disease onset. Patients in cluster 3 had prevalent activation of C3 convertase and highly electron-dense intramembranous deposits. In addition, we provide a simple algorithm to assign patients with C3G/IC-MPGN to specific clusters. These distinct clusters may facilitate clarification of disease etiology, improve risk assessment for ESRD, and pave the way for personalized treatment.

Background: Geographical differences in disease prevalence and mortality have been described in the general population and in chronic kidney disease patients in Europe. In this secondary analysis of the Membrane Permeability Outcome (MPO) study, we addressed differences in patient and treatment patterns, and whether these affect patient outcomes. Methods: Participating countries were grouped according to geographical location; thus study centers in France, Greece, Italy, Portugal and Spain were allocated to southern Europe (n=499), and those in all other countries (Belgium, Germany, Poland and Sweden) to northern Europe (n=148). Descriptive analysis of patient and treatment patterns at study start, as well as survival analysis, was performed. Results: In patients from the northern European countries, a higher prevalence of diabetes mellitus and of cardiovascular disease was observed than in those from southern Europe (diabetes 35.1% vs. 21.0%, p=0.0007; cardiovascular disease 40.5% vs. 22.8%, p

Introduction: Kidney biopsy is performed to assess if an extended criteria graft can be used for transplantation. It may be performed before or after cross-clamping during organ procurement. This study aims to evaluate whether the timing of biopsy may modify cold ischemia times (CIT) and/or graft outcomes. Methods: Kidney transplants performed in our center from January 2007 to December 2017 were analyzed. Grafts with preimplantation kidney biopsy were included. Biopsies were performed during surgical back table (ex situ kidney biopsy [ESKB]) until 2012 and since then before the aortic cross-clamping (in situ kidney biopsy [ISKB]). To overcome biases owing to different distributions, a propensity score model was developed. The study population consists in 322 patients, 115 ESKB, and 207 ISKB. Results: CIT was significantly lower for ISKB (730 min ISKB vs. 840 min ESKB, p value = 0.001). In both crude (OR 0.27; 95% confidence interval, 95% CI 0.12–0.60; p value = 0.002) and adjusted analyses (OR 0.37; 95% CI 0.14–0.94; p value = 0.039), ISKB was associated with a reduced odd of graft loss when compared to ESKB. Discussion/Conclusion: Performing preimplantation kidney biopsy during the recovery, prior to the aortic cross-clamping, may be a strategy to reduce CIT and improve transplant outcomes.

Introduction: Renal allograft biopsy is the gold standard for the detection of histological lesions of chronic allograft dysfunction. The identification of a noninvasive routine test would be desirable. Elastosonography is used to assess tissue stiffness according to viscosity, and no data are available on the use of point quantification shear-wave elastography (ElastPQ) for the evaluation of renal chronic lesions. Research Question: To evaluate the feasibility of ElastPQ to assess cortical allograft stiffness and to determine the correlation of clinical, biological, and pathological factors with the diagnostic accuracy of kidney stiffness values in patients with histological lesions. Design: Forty-two patients underwent kidney transplant biopsy and 10 valid measurements of ElastPQ, blindly performed by 2 operators. The interobserver reproducibility was assessed according to intraclass correlation coefficient. The ElastPQ measurements and the clinical data were compared using the Spearman correlation analysis. Results: 97.6% reliable measurements were obtained using ElastPQ, with an excellent interobserver agreement. The kidney stiffness was significantly higher in the patients with a time since transplantation >12 months and was correlated with chronic lesions (interstitial fibrosis, tubular atrophy transplant glomerulopathy, and mesangial matrix), with the interstitial fibrosis/tubular atrophy, score and with the sum of the scores of the chronic lesions. Mesangial matrix increase is the only independent determinant of kidney stiffness. Discussion: ElastPQ is a noninvasive, reproducible, and sensitive diagnostic tool able to detect moderate/severe chronic lesions. Its routine use during follow-up can identify patients eligible for biopsy, which remains the gold standard exam for detecting chronic allograft dysfunction.

A patient with advanced gastrointestinal stromal tumor (GIST) receiving second-line treatment with sunitinib developed edema, increase of the serum creatinine, weight gain, nephrotic syndrome with proteinuria of 12 g/24 h, dyslipidemia, hypoalbuminemia and also presented with hypertension. A kidney biopsy showed an immunocomplex glomerulonephritis. Steroid treatment was started, but the clinical conditions and laboratory values did not improve. So in the hypothesis that the nephrotic syndrome was induced by sunitinib, sunitinib was temporarily discontinued with a subsequent reduction of proteinuria and improvement in blood pressure control. In the last years, the introduction of sunitinib has modified the natural history of advanced GIST. However, due to chronic and prolonged intake of this drug, there is increasingly frequent detection of late and unknown toxicities in clinical practice. In particular, the late renal toxicity from sunitinib may be the primary clinical problem with this drug in the case of prolonged treatment. Monitoring of kidney function and blood pressure should be performed for early detection of side effects such as hypertension and kidney dysfunction in advanced GIST patients receiving long-term treatment with sunitinib. A clinical collaboration between oncologists and nephrologists could be useful with the objective to optimize the management of sunitinib.

Background Restless legs syndrome (RLS) is a sensorimotor neurological disorder characterized by paraesthesia, dysaesthesia and the irresistible urge to move the legs especially at night. Its prevalence is much higher among dialysis patients at 12 to 62% compared to 3 to 9% in the general population. Here, we investigated the association between RLS and cardiovascular events risk and laboratory parameters in end-stage kidney disease (ESKD) patients on dialysis. Methods One hundred ESKD patients undergoing haemodialysis were enrolled in an 18-month prospective observational study. The main outcomes were the associations of RLS with new cardiovascular events and cardiovascular mortality. Results RLS affected 31% of the study population. It was associated with female gender, gradual reduction in residual diuresis, lower albumin (P = 0.039) and inflammation, but not the dialysis parameters Kt/V and URR. During observation, 47% of patients experienced new cardiovascular events (64.5% with and 39.1% without RLS; P = 0.019). New cardiovascular events increased with severity of RLS [intermittent (I-RLS) vs continuous (C-RLS)]. Mortality was 20.0% in all patients, 32.3% in those with and 14.5% in patients without RLS (P = 0.04). In patients with I-RLS, mortality was 23.8% compared to 55.6% in patients with C-RLS (P = 0.014). Multivariate analysis confirmed the relationship between RLS and mortality. Conclusions This study confirmed the high prevalence of RLS among dialysis patients and the associations between the severity of RLS and the risk of new cardiovascular events and higher short-term mortality.

Immunological evaluation by panel-reactive antibody (PRA) and determination of anti-HLA specificity are important phases in the evaluation of patients awaiting kidney transplantation. The main causes of immunization are previous solid organ transplantation, hemotransfusion, and pregnancy. It is also possible that immunogenicity can be triggered by vascularized tissue grafts. Immune induction by cryopreserved bone prostheses is not yet understood. A 19-year-old patient with osteosarcoma had undergone resection of the left proximal tibia with reconstruction using human bone in 1997. The donor HLA typing was as follows: A3, A29 (19); B44 (12), Bw4; DR13 (6), DR7, DR52, DR53. The patient was subsequently enrolled onto the waiting list for cadaveric donor kidney transplantation due to chronic kidney failure caused by cisplatin toxicity. Pretransplantation immunological screening using the complement-dependent cytotoxicity (CDC) technique revealed a PRA of 63%. IgG antibody specificities were detected against class I and class II donor antigens, specifically anti-A3, B44, DR7 antibodies, using flow cytometry (Tepnel Luminex). Further immunological studies using single HLA specificity analysis (LSA Class I degrees -II degrees , Tepnel-Luminex) showed direct antibodies against all donor antigen specificities. This case showed immune induction after the implantation of bone prosthesis in a kidney transplant candidate, underlining the importance of the availability of HLA typing data of donors of a human prosthesis.