Case Report: Patient with Hepatitis C, p-ANCA, and Cryoglobulin Antibodies Presenting with Necrotizing Crescentic p-ANCA Glomerulonephritis

Hepatitis C (HCV) infection has a prevalence of 3 million infected individuals in the United States, according to recent Center for Disease Control reports, and can have various renal manifestations. Cryoglobulins, antibodies that precipitate at colder temperatures in vitro, are a relatively common cause of renal disease in HCV infection. The cryoglobulin proteins can form occlusive aggregates in small glomerular capillary lumina or deposit in other areas of the glomerulus, resulting in hypocomplementemia, proteinuria, hematuria, and renal injury. The typical biopsy pattern is that of membranoproliferative glomerulonephritis (MPGN). There are, however, other HCV-related patterns of glomerular injury. Anti-neutrophil cytoplasmic antibodies (ANCA) are known to exist in HCV-infected patients. In many reported cases, ANCA serologic testing may appear positive due to cross-reactivity of the immune assays; however, the biopsy findings do not support ANCA-associated crescentic glomerulonephritis (GN)/vasculitis as the primary cause of glomerular injury. There are rare reports of microscopic polyangiitis (MPA) p-ANCA vasculitis, in patients with HCV infection. In comparison with the MPGN pattern of cryoglobulinemic glomerular injury, biopsies from these HCV-infected patients with concomitant MPA revealed a crescentic GN, associated with normal serum complement levels. We present a case of HCV-associated glomerular disease with the surprising biopsy finding of necrotizing and crescentic p-ANCA GN, with a background, low-grade mesangial immune complex GN. Thus, p-ANCA disease should also be considered in HCV-infected patients, in addition to the more typical lesions of MPGN or cryoglobulinemic GN

Effect of Intensive Versus Standard Blood Pressure Control on Stroke Subtypes

In the SPRINT (Systolic Blood Pressure Intervention Trial), the number of strokes did not differ significantly by treatment group. However, stroke subtypes have heterogeneous causes that could respond differently to intensive blood pressure control. SPRINT participants (N=9361) were randomized to target systolic blood pressures of \u3c120 mm Hg (intensive treatment) compared with \u3c140 mm Hg (standard treatment). We compared incident hemorrhage, cardiac embolism, large- and small-vessel infarctions across treatment arms. Participants randomized to the intensive arm had mean systolic blood pressures of 121.4 mm Hg in the intensive arm (N=4678) and 136.2 mm Hg in the standard arm (N=4683) at one year. Sixty-nine strokes occurred in the intensive arm and 78 in the standard arm when SPRINT was stopped. The breakdown of stroke subtypes across treatment arms included hemorrhagic (intensive treatment, n=6, standard treatment, n=7) and ischemic stroke subtypes (large artery atherosclerosis: intensive treatment n=11, standard treatment, n=13; cardiac embolism: intensive treatment n=11, standard treatment n=15; small artery occlusion: intensive treatment n=8, standard treatment n=8; other ischemic stroke: intensive treatment n=3, standard treatment n=1). Fewer strokes occurred among participants without prior cardiovascular disease in the intensive (n=43) than the standard arm (n=61), but the difference did not reach predefined statistical significance level of 0.05 (P=0.09). The interaction between baseline cardiovascular risk factor status and treatment arm on stroke risk did not reach significance (P=0.05). Similar numbers of stroke subtypes occurred in the intensive BP control and standard control arms of SPRINT

Atrasentan and renal events in patients with type 2 diabetes and chronic kidney disease (SONAR): a double-blind, randomised, placebo-controlled trial

Background: Short-term treatment for people with type 2 diabetes using a low dose of the selective endothelin A receptor antagonist atrasentan reduces albuminuria without causing significant sodium retention. We report the long-term effects of treatment with atrasentan on major renal outcomes. Methods: We did this double-blind, randomised, placebo-controlled trial at 689 sites in 41 countries. We enrolled adults aged 18–85 years with type 2 diabetes, estimated glomerular filtration rate (eGFR)25–75 mL/min per 1·73 m 2 of body surface area, and a urine albumin-to-creatinine ratio (UACR)of 300–5000 mg/g who had received maximum labelled or tolerated renin–angiotensin system inhibition for at least 4 weeks. Participants were given atrasentan 0·75 mg orally daily during an enrichment period before random group assignment. Those with a UACR decrease of at least 30% with no substantial fluid retention during the enrichment period (responders)were included in the double-blind treatment period. Responders were randomly assigned to receive either atrasentan 0·75 mg orally daily or placebo. All patients and investigators were masked to treatment assignment. The primary endpoint was a composite of doubling of serum creatinine (sustained for ≥30 days)or end-stage kidney disease (eGFR <15 mL/min per 1·73 m 2 sustained for ≥90 days, chronic dialysis for ≥90 days, kidney transplantation, or death from kidney failure)in the intention-to-treat population of all responders. Safety was assessed in all patients who received at least one dose of their assigned study treatment. The study is registered with ClinicalTrials.gov, number NCT01858532. Findings: Between May 17, 2013, and July 13, 2017, 11 087 patients were screened; 5117 entered the enrichment period, and 4711 completed the enrichment period. Of these, 2648 patients were responders and were randomly assigned to the atrasentan group (n=1325)or placebo group (n=1323). Median follow-up was 2·2 years (IQR 1·4–2·9). 79 (6·0%)of 1325 patients in the atrasentan group and 105 (7·9%)of 1323 in the placebo group had a primary composite renal endpoint event (hazard ratio [HR]0·65 [95% CI 0·49–0·88]; p=0·0047). Fluid retention and anaemia adverse events, which have been previously attributed to endothelin receptor antagonists, were more frequent in the atrasentan group than in the placebo group. Hospital admission for heart failure occurred in 47 (3·5%)of 1325 patients in the atrasentan group and 34 (2·6%)of 1323 patients in the placebo group (HR 1·33 [95% CI 0·85–2·07]; p=0·208). 58 (4·4%)patients in the atrasentan group and 52 (3·9%)in the placebo group died (HR 1·09 [95% CI 0·75–1·59]; p=0·65). Interpretation: Atrasentan reduced the risk of renal events in patients with diabetes and chronic kidney disease who were selected to optimise efficacy and safety. These data support a potential role for selective endothelin receptor antagonists in protecting renal function in patients with type 2 diabetes at high risk of developing end-stage kidney disease. Funding: AbbVie

Design and baseline characteristics of the finerenone in reducing cardiovascular mortality and morbidity in diabetic kidney disease trial

Background: Among people with diabetes, those with kidney disease have exceptionally high rates of cardiovascular (CV) morbidity and mortality and progression of their underlying kidney disease. Finerenone is a novel, nonsteroidal, selective mineralocorticoid receptor antagonist that has shown to reduce albuminuria in type 2 diabetes (T2D) patients with chronic kidney disease (CKD) while revealing only a low risk of hyperkalemia. However, the effect of finerenone on CV and renal outcomes has not yet been investigated in long-term trials. Patients and Methods: The Finerenone in Reducing CV Mortality and Morbidity in Diabetic Kidney Disease (FIGARO-DKD) trial aims to assess the efficacy and safety of finerenone compared to placebo at reducing clinically important CV and renal outcomes in T2D patients with CKD. FIGARO-DKD is a randomized, double-blind, placebo-controlled, parallel-group, event-driven trial running in 47 countries with an expected duration of approximately 6 years. FIGARO-DKD randomized 7,437 patients with an estimated glomerular filtration rate >= 25 mL/min/1.73 m(2) and albuminuria (urinary albumin-to-creatinine ratio >= 30 to <= 5,000 mg/g). The study has at least 90% power to detect a 20% reduction in the risk of the primary outcome (overall two-sided significance level alpha = 0.05), the composite of time to first occurrence of CV death, nonfatal myocardial infarction, nonfatal stroke, or hospitalization for heart failure. Conclusions: FIGARO-DKD will determine whether an optimally treated cohort of T2D patients with CKD at high risk of CV and renal events will experience cardiorenal benefits with the addition of finerenone to their treatment regimen. Trial Registration: EudraCT number: 2015-000950-39; ClinicalTrials.gov identifier: NCT02545049

Anemia management for home dialysis including the new US public policy initiative

Patients with end-stage kidney disease (ESKD) requiring kidney replacement therapy are often treated in conventional dialysis centers at substantial cost and patient inconvenience. The recent United States Executive Order on Advancing American Kidney Health, in addition to focusing on ESKD prevention and reforming the kidney transplantation system, focuses on providing financial incentives to promote a shift toward home dialysis. In accordance with this order, a goal was set to have 80% of incident dialysis patients receiving home dialysis or a kidney transplant by 2025. Compared with conventional in-center therapy, home dialysis modalities, including both home hemodialysis and peritoneal dialysis, appear to offer equivalent or improved mortality, clinical outcomes, hospitalization rates, and quality of life in patients with ESKD in addition to greater convenience, flexibility, and cost-effectiveness. Treatment of anemia, a common complication of chronic kidney disease, may be easier to manage at home with a new class of agents, hypoxia-inducible factor-prolyl hydroxylase inhibitors, which are orally administered in contrast to the current standard of care of i.v. iron and/or erythropoiesis-stimulating agents. This review evaluates the clinical, quality-of-life, economic, and social aspects of dialysis modalities in patients with ESKD, including during the coronavirus disease 2019 pandemic; explores new therapeutics for the management of anemia in chronic kidney disease; and highlights how the proposed changes in Advancing American Kidney Health provide an opportunity to improve kidney health in the United States

Hyperphosphatemia in patients with ESRD: assessing the current evidence linking outcomes with treatment adherence

Abstract In recent years, the imbalance in phosphate homeostasis in patients with end-stage renal disease (ESRD) has been the subject of much research. It appears that, while hyperphosphatemia may be a tangible indicator of deteriorating kidney function, lack of phosphate homeostasis may also be associated with the increased risk of cardiovascular events and mortality that has become a hallmark of ESRD. The need to maintain phosphorus concentrations within a recommended range is reflected in evidence-based guidelines. However, these do not reflect serum phosphorus concentrations achieved by most patients in clinical practice. Given this discrepancy, it is important to consider ways in which dietary restriction of phosphorus intake and, in particular, use of phosphate binders in patients with ESRD can be made more effective. Poor adherence is common in patients with ESRD and has been associated with inadequate control of serum phosphorus concentrations. Studies indicate that, among other factors, major reasons for poor adherence to phosphate binder therapy include high pill burden and patients’ lack of understanding of their condition and its treatment. This review examines available evidence, seeking to understand fully the reasons underlying poor adherence in patients with ESRD and consider possible strategies for improving adherence in clinical practice