Validation of a Histologic Scoring Index for C3 Glomerulopathy.

RATIONALE & OBJECTIVE: A previous study that evaluated associations of kidney biopsy findings with disease progression in patients with C3 glomerulopathy (C3G) proposed a prognostic histologic index (C3G-HI) that has not yet been validated. Our objective was to validate the performance of the C3G-HI in a new patient population. STUDY DESIGN: Multicenter, retrospective cohort study. SETTING & PARTICIPANTS: 111 patients fulfilling diagnostic criteria of C3G between January 1995 and December 2019, from 33 nephrology departments belonging to the Spanish Group for the Study of Glomerular Diseases (GLOSEN). PREDICTORS: Demographic, clinical parameters, C3G-HI total activity score, and the C3G-HI total chronicity score. OUTCOME: Time to kidney failure. ANALYTICAL APPROACH: Intraclass correlation coefficients and κ statistic were used to summarize inter-rater reproducibility for assessment of histopathology in kidney biopsies. The nonlinear relationships of risk of kidney failure with the total activity score and total chronicity score were modeled using Cox proportional hazards analysis that incorporated cubic splines. RESULTS: The study group included 93 patients with C3 glomerulonephritis and 18 with dense-deposit disease. Participants had an overall meanage of 35±22 (SD) years. Forty-eight patients (43%) developed kidney failure after a mean follow-up of 65±27 months. The overall inter-rater reproducibility was very good for the total activity score (intraclass correlation coefficient [ICC]=0.63) and excellent for total chronicity score (ICC=0.89). Baseline estimated glomerular filtration rate (eGFR), 24-hour proteinuria, and treatment with immunosuppression were the main determinants of kidney failure in a model with only clinical variables. Only tubular atrophy and interstitial fibrosis were identified as predictors in a model with histological variables. When the total activity score and total chronicity score were added to the model, only the latter was identified as an independent predictor of kidney failure. LIMITATIONS: Only a subset of the kidney biopsies was centrally reviewed. Residual confounding. CONCLUSIONS: We validated the performance of C3G-HI as a predictor of kidney failure in patients with C3G. The total chronicity score was the principal histologic correlate of kidney failure.

Gemcitabine-induced hemolytic-uremic syndrome treated with eculizumab or plasmapheresis: two case reports
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BACKGROUND: Drug-induced hemolytic-uremic syndrome (HUS) has shown good response to eculizumab (ECU). We present 2 cases of patients with gemcitabine-induced HUS (GEM-HUS), one of whom was treated with ECU and the other with conventional treatment. Patient 1: A 74-year-old male with resected adenocarcinoma of the pancreas started adjuvant treatment with GEM, but after 5 months GEM was discontinued due to acute kidney injury and severe hypertension. Laboratory analyses identified microangiopathic hemolytic anemia (MHA) and thrombocytopenia. Plasmapheresis (Pph) was initiated but was stopped due to a severe adverse reaction. Treatment with ECU was initiated at the time of clinical progression requiring hemodialysis. After 7 doses of ECU, hemolysis and kidney function improved and the patient was able to stop hemodialysis. 1 month after the last dose of ECU serum creatinine (sCr) was 1.8 mg/dL. Patient 2: A 68-year-old male with resected urothelial carcinoma stopped GEM after 2 months due to hematologic toxicity. 1 month later the patient visited the emergency room due to minimal effort dyspnea, hypertension, and peripheral edema. Laboratory analyses showed decreased kidney function, MHA, and thrombocytopenia. Symptomatic treatment was started. After an initial recovery, kidney dysfunction, hemolysis, and thrombocytopenia progressed. Corticoid boluses were ineffective and hemodialysis was initiated. Eleven Pph treatments were necessary to recover hematologic data. The patient remained on hemodialysis for 2 months and evolved to stage IV chronic kidney disease. 8 months after hospital release, sCr was 3.5 mg/dL. CONCLUSION: ECU successfully improved kidney function in a patient with GEM-HUS, while conventional treatment did not.
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Effect of isolation measures on the incidence and prevalence of hepatitis C virus infection in hemodialysis.

BACKGROUND: Nosocomial transmission of hepatitis C virus (HCV) in hemodialysis (HD) units is well established. In units with a high prevalence of HCV infection, the implementation of universal precautionary measures may not suffice in order to decrease the incidence and prevalence of HCV. In this setting strict isolation practices can be useful in order to achieve this goal. METHODS: The incidence and prevalence of HCV infection amongst all HD and peritoneal dialysis (PD) patients from the province of Albacete, Spain, have been studied from 1992 to 2003.Through the 1993-1995 period chronic HD patients were treated either in a room exclusively for HCV- patients or in a room shared by HCV+ and HCV- patients. Complete separation of HCV+ and HCV- patients was implemented in 1995. Acute patients have been separated since 1992. The implementation of universal precautions was applied throughout the period. RESULTS: There has not been a single seroconversion in the rooms where only HCV- patients were dialyzed during the 11 years of follow-up. There were two seroconversions in the rooms shared for 3 years by both HCV+ and HCV- patients. In 1995 the prevalence of HCV+ cases in HD and PD was 21.6 and 23.2%, respectively. Since then it has decreased steadily and in parallel for both therapies, and the current prevalence is 6.8% in HD and 5.7% in PD. CONCLUSIONS: In HD units with a high prevalence of HCV+ patients, strict isolation in combination with implementation of universal prevention measures can eliminate nosocomial transmission and obtain a long-term reduction in prevalence.