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Background Secondary hyperparathyroidism in patients with end stage renal disease on dialysis is associated with bone pain and fractures in addition to cardiovascular morbidity. Cinacalcet is the most commonly used drug to treat such patients, but it has never been compared to surgery. The goal of this study is to compare the long-term outcomes and survival between cinacalcet and parathyroidectomy in the treatment of secondary hyperparathyroidism in hemodialysis patients. Methods Adult patients on hemodialysis who were treated with cinacalcet or parathyroidectomy in the United States Renal Data System were included. Patients treated with surgery (n = 2023) were compared using 1:1 propensity score matching ratio to a cohort of patients treated with cinacalcet. A Cox regression analysis was conducted to compare the overall mortality. Results The propensity score matching successfully created two groups with similar demographics. Patients in the surgery group had a higher mean peak PTH level prior to therapy (2066.8 vs 1425.4, P P = 0.8) or cerebrovascular disease (7% vs 6.7%, P = 0.8). Surgical patients had a higher rate of pathologic fractures (27.8% vs 24.9%, P = 0.04). Survival analysis showed that patients undergoing surgery had a better 5-year survival (65.6% vs 57.8%) and were less likely to die within the study period (HR 0.77, 95% CI 0.7–0.85, P Conclusions Patients on dialysis undergoing parathyroidectomy for the treatment of secondary hyperparathyroidism have a better overall survival than those treated with cinacalcet.

Objective Delayed detection of LN associates with worse outcomes. There are conflicting recommendations regarding a threshold level of proteinuria at which biopsy will likely yield actionable management. This study addressed the association of urine protein:creatinine ratios (UPCR) with clinical characteristics and investigated the incidence of proliferative and membranous histology in patients with a UPCR between 0.5 and 1. Methods A total of 275 SLE patients (113 first biopsy, 162 repeat) were enrolled in the multicentre multi-ethnic/racial Accelerating Medicines Partnership across 15 US sites at the time of a clinically indicated renal biopsy. Patients were followed for 1 year. Results At biopsy, 54 patients had UPCR Conclusion In this prospective study, three-quarters of patients with UPCR

Background: Minimal-change glomerulopathy is defined histologically by the presence of normal glomeruli on light microscopy and diffuse podocyte effacement on electron microscopy. Although effective in children, corticosteroid treatment in adults is more variable and time to response can be prolonged. Data to support rituximab use in adults with corticosteroid-dependent or resistant minimal-change glomerulopathy are limited. Here, we describe the clinical course of adults with corticosteroid-dependent or -resistant minimal-change glomerulopathy who received rituximab. Methods: Demographic and clinical data were collected and analyzed from all adult patients with native kidney, biopsy-proven, minimal-change glomerulopathy who were administered rituximab between 2009 and 2014 and cared for at the UNC Kidney Center. Results: Ten patients with corticosteroid-resistant (n = 5) or corticosteroid-dependent (n = 5) idiopathic minimal-change glomerulopathy were treated with rituximab between 2009 and 2014. Rituximab treatment induced remission in all 10 patients with a median time to remission of 2 months. The median time from rituximab to corticosteroid discontinuation was 3.5 months. The median remission time was 29 months and follow-up time was 39.5 months. No serious adverse events attributable to rituximab were observed. Conclusion: Rituximab induced remission in all patients with corticosteroid-dependent or -resistant minimal-change glomerulopathy, and may hold great therapeutic potential with good efficacy and minimal toxicity. Mounting evidence implies that a well-conducted randomized controlled clinical trial using rituximab in adults with minimal-change glomerulopathy in both corticosteroid-resistant and corticosteroid-dependent patients is warranted.

Lupus nephritis is a potentially fatal autoimmune disease for which the current treatment is ineffective and often toxic. To develop mechanistic hypotheses of disease, we analyzed kidney samples from patients with lupus nephritis and from healthy control subjects using single-cell RNA sequencing. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid cells, T cells, natural killer cells and B cells that demonstrated both pro-inflammatory responses and inflammation-resolving responses. We found evidence of local activation of B cells correlated with an age-associated B-cell signature and evidence of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, implying a potentially central role in cell trafficking. Gene expression of immune cells in urine and kidney was highly correlated, which would suggest that urine might serve as a surrogate for kidney biopsies.

Systemic lupus erythematosus (SLE) is characterized by frequent renal involvement in approximately 50 % of patients. Lupus nephritis (LN) remains the most important predictor of morbidity and mortality for patients with SLE. A recent international inception cohort reported 80 % of patients develop LN within the first 2 years of disease; thus, it is imperative to screen SLE patients frequently early in disease and at routine clinical visits thereafter. Patients with proteinuria, active urinary sediment, or decreased effective glomerular filtration rate (eGFR) without other explanation should undergo a kidney biopsy to determine the histologic class and chronicity of LN to guide therapy. In general, we advocate initial treatment of proliferative lupus nephritis with intravenous (IV) cyclophosphamide according to the Euro-Lupus regimen. After initial treatment with cyclophosphamide, we transition patients to maintenance immunosuppression with mycophenolate mofetil or azathioprine for at least 3 to 5 years. Recent maintenance trials in LN report an increased proportion of patients achieving complete remission and fewer renal flares with this approach. Failure to attain a complete remission and renal flares are highly associated with progression to ESKD. Recently, repeat biopsy studies report substantial discordance between clinical measures of complete remission with up to 30 % of patients showing continued histologic activity despite these features. We advocate that patients undergo repeat renal biopsy to ensure complete histological remission prior to discontinuing immunosuppressive therapy. In recent LN trials, only 50 % of patients achieve complete or partial remission at 6 months. Patients with lupus nephritis should preferentially be enrolled in clinical trials as newer agents are needed to increase the proportion of patients responding to therapy. Patients also benefit greatly from more frequent monitoring and additional clinical support in trials. While recent clinical trials have not been successful including epratuzumab, tabalumab, and abatacept, promising new agents are in early phase trials.

Lupus nephritis is a potentially fatal autoimmune disease, whose current treatment is ineffective and often toxic. To gain insights into disease mechanisms, we analyzed kidney samples from lupus nephritis patients and healthy controls using single-cell RNA-seq. Our analysis revealed 21 subsets of leukocytes active in disease, including multiple populations of myeloid, T, NK and B cells, demonstrating both pro-inflammatory and resolving responses. We found evidence of local activation of B cells correlated with an age-associated B cell signature, and of progressive stages of monocyte differentiation within the kidney. A clear interferon response was observed in most cells. Two chemokine receptors, CXCR4 and CX3CR1, were broadly expressed, pointing to potential therapeutic targets. Gene expression of immune cells in urine and kidney was highly correlated, suggesting urine may be a surrogate for kidney biopsies. Our results provide a first comprehensive view of the complex network of leukocytes active in lupus nephritis kidneys.

Pathogenetic markers of diabetic kidney disease (DKD) progression to ESRD are lacking. We characterized the prognostic value of histologic findings in DKD for time to ESRD in native kidney specimens from biopsies performed from 1995 to 2011 with diabetic glomerulosclerosis as the only glomerular disease diagnosis (n=109). Biopsy specimens were analyzed according to standard methods, including determination of diabetic nephropathy class, as defined by the Renal Pathology Society. Clinical data were extracted from electronic medical records. We used competing risk models, with death as the competing risk, to estimate subdistribution hazard ratios (HRs) for ESRD. All multivariable models included age, sex, black race, baseline eGFR, and baseline proteinuria. Pathologic characteristics achieving P

Background: Fibrillary glomerulonephritis is characterized by randomly arranged fibrils, approximately 20 nm in diameter by electron microscopy. Patients present with proteinuria, hematuria and kidney insufficiency, and about half of the reported patients progress to end-stage kidney disease within 4 years. The dependence of patient characteristics and outcomes on race has not been explored. In this study, we describe a cohort of patients with fibrillary glomerulonephritis and compare their clinical characteristics and outcomes with those of patients previously described. Methods: The University of North Carolina (UNC) Nephropathology Database was used to retrospectively identify patients diagnosed with fibrillary glomerulonephritis between 1985 and 2015. Of these patients, those treated at UNC were selected. Their demographic and clinical characteristics - including signs and symptoms, comorbidities, laboratory values, treatments and outcomes - were compared with those of patients described earlier. Results: Among the 287 patients identified, 42 were treated at the UNC Kidney Center. When compared to earlier cohorts, a higher frequency of black race, hepatitis C virus (HCV) infection and use of hemodialysis were noted in both black and HCV-positive patients. Autoimmune diseases, infections and malignancies were frequently observed, present in over half of all cases. Conclusion: According to this study, fibrillary glomerulonephritis represents a secondary glomerular disease process (associated with autoimmune disease, infection or malignancy) in many cases and hence screening is essential. As the screening for comorbidities increased over time, more underlying causes were identified. We noted a high frequency of HCV among black patients, suggesting a possible causative association. Treatment of underlying disease is essential for patients for the best outcome.

Kidney involvement in patients with systemic lupus erythematosus (SLE) portends a worse prognosis; thus, early and accurate detection of lupus nephritis is key. Unfortunately, current clinical markers, including creatinine clearance, autoantibodies, serum complement levels, urine sediment and proteinuria, do not always reliably identify patients with kidney disease. Moreover, these biomarkers do not help distinguish between various histopathological classes of lupus nephritis, which are often used as benchmarks to guide treatment. An intensely hot area of lupus research currently revolves around biased and unbiased approaches to identify biomarkers that can more reliably predict clinical and histopathological lupus-associated kidney activity and, perhaps even more importantly, durable response to treatment. Novel biomarkers of lupus nephritis currently under investigation include but are not limited to B Lymphocyte Stimulator (BLyS), A Proliferation-Inducing Ligand (APRIL), tumor necrosis factor (TNF)-like WEAK inducer of apoptosis (TWEAK), and Monocyte Chemoattractant Protein-1 (MCP-1). BLyS, also known as B cell Activating Factor belonging to the TNF Family (or BAFF), is a transmembrane protein that is cleaved by a furin protease into a biologically active soluble protein that is important for B cell activation and differentiation. Numerous studies have shown that serum BLyS levels are elevated in patients with SLE compared with controls, making it the target of the recently Food and Drug Administration (FDA)-approved lupus drug, belimumab.1 Currently, the Belimumab International Lupus Nephritis Study clinical trial is underway to determine the efficacy of belimumab in patients with lupus nephritis (http://www.clinicaltrials.gov, NCT01639339). Like BLyS, APRIL is a member of the TNF family, and is thought to have a regulatory role in B cell proliferation. APRIL levels have been shown to be elevated in patients with lupus compared with healthy controls, although one study has found that levels may be lower in patients with lupus nephritis compared with patients who have …