Mayo Clinic Consensus Report on Membranous Nephropathy: Proposal for a Novel Classification.

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms.

Mayo Clinic consensus report on membranous nephropathy: proposal for a novel classification.

Membranous nephropathy (MN) is a pattern of injury caused by autoantibodies binding to specific target antigens, with accumulation of immune complexes along the subepithelial region of glomerular basement membranes. The past 20 years have brought revolutionary advances in the understanding of MN, particularly via the discovery of novel target antigens and their respective autoantibodies. These discoveries have challenged the traditional classification of MN into primary and secondary forms.

An Analysis of Vascular Access Thrombosis Events From the Proactive IV irOn Therapy in hemodiALysis Patients Trial.

Introduction: Treatment of anemia in dialysis patients has been associated with increased risk of vascular access thrombosis (VAT). Proactive IV irOn Therapy in hemodiALysis Patients (PIVOTAL) was a clinical trial of proactive compared with reactive i.v.

Stroke in Hemodialysis Patients Randomized to Different Intravenous Iron Strategies: A Prespecified Analysis from the PIVOTAL Trial.

Background: People with kidney failure treated with hemodialysis (HD) are at increased risk of stroke compared with similarly aged people with normal kidney function. One concern is that treatment of renal anemia might increase stroke risk. We studied risk factors for stroke in a prespecified secondary analysis of a randomized, controlled trial of intravenous iron treatment strategies in HD.

Intravenous Iron Dosing and Infection Risk in Patients on Hemodialysis: A Prespecified Secondary Analysis of the PIVOTAL Trial.

Background: Experimental and observational studies have raised concerns that giving intravenous (IV) iron to patients, such as individuals receiving maintenance hemodialysis, might increase the risk of infections. The Proactive IV Iron Therapy in Haemodialysis Patients (PIVOTAL) trial randomized 2141 patients undergoing maintenance hemodialysis for ESKD to a high-dose or a low-dose IV iron regimen, with a primary composite outcome of all-cause death, heart attack, stroke, or hospitalization for heart failure. Comparison of infection rates between the two groups was a prespecified secondary analysis.

Long term outcomes in monoclonal gammopathy of renal significance.

Unlike AL amyloid and cast nephropathy, the long-term outcomes of monoclonal gammopathy of renal significance (MGRS) patients with other renal histopathologies remain unclear. It is uncertain if early intervention improves renal outcomes, because of a lack of evidence from prospective studies. In this retrospective study, we examined outcomes of 41 MGRS patients treated between 2004 and 2017 across five centres: four in the UK and one in the Republic of Ireland.

High cutoff versus high-flux haemodialysis for myeloma cast nephropathy in patients receiving bortezomib-based chemotherapy (EuLITE): a phase 2 randomised controlled trial.

Background: In multiple myeloma, severe acute kidney injury due to myeloma cast nephropathy is caused by pathogenic free light chain immunoglobulin in serum. High cutoff haemodialysis (HCO-HD) can remove large quantities of free light chain immunoglobulin from serum, but its effect on clinical outcomes is uncertain. We therefore aimed to assess whether HCO-HD could increase the frequency of renal recovery in patients with de novo multiple myeloma, severe acute kidney injury, and myeloma cast nephropathy relative to treatment with standard high-flux haemodialysis (HF-HD).

Intravenous Iron in Patients Undergoing Maintenance Hemodialysis.

Background: Intravenous iron is a standard treatment for patients undergoing hemodialysis, but comparative data regarding clinically effective regimens are limited.

Methods: In a multicenter, open-label trial with blinded end-point evaluation, we randomly assigned adults undergoing maintenance hemodialysis to receive either high-dose iron sucrose, administered intravenously in a proactive fashion (400 mg monthly, unless the ferritin concentration was >700 μg per liter or the transferrin saturation was ≥40%), or low-dose iron sucrose, administered intravenously in a reactive fashion (0 to 400 mg monthly, with a ferritin concentration of <200 μg per liter or a transferrin saturation of <20% being a trigger for iron administration). The primary end point was the composite of nonfatal myocardial infarction, nonfatal stroke, hospitalization for heart failure, or death, assessed in a time-to-first-event analysis.

Randomized Trial Comparing Proactive, High-Dose versus Reactive, Low-Dose Intravenous Iron Supplementation in Hemodialysis (PIVOTAL): Study Design and Baseline Data.

Background: Intravenous (IV) iron supplementation is a standard maintenance treatment for hemodialysis (HD) patients, but the optimum dosing regimen is unknown.

Methods: PIVOTAL (Proactive IV irOn Therapy in hemodiALysis patients) is a multicenter, open-label, blinded endpoint, randomized controlled (PROBE) trial. Incident HD adults with a serum ferritin < 400 µg/L and transferrin saturation (TSAT) levels < 30% receiving erythropoiesis-stimulating agents (ESA) were eligible.

Declining comorbidity-adjusted mortality rates in English patients receiving maintenance renal replacement therapy.

We aimed to compare long-term mortality trends in end-stage renal disease versus general population controls after accounting for differences in age, sex and comorbidity. Cohorts of 45,000 patients starting maintenance renal replacement therapy (RRT) and 5.3 million hospital controls were identified from two large electronic hospital inpatient data sets: the Oxford Record Linkage Study (1965-1999) and all-England Hospital Episode Statistics (2000-2011).

Biliary Tract and Liver Complications in Polycystic Kidney Disease.

Polycystic liver disease is a well described manifestation of autosomal dominant polycystic kidney disease (ADPKD). Biliary tract complications are less well recognized. We report a 50-year single-center experience of 1007 patients, which raised a hypothesis that ADPKD is associated with biliary tract disease.

A proposal for standardized grading of chronic changes in native kidney biopsy specimens.

Chronic changes represent an important component of native kidney biopsy evaluation and have a major bearing on predicting prognosis and guiding treatment. We propose here a uniform, semiquantitative approach to assessing such changes, which include glomerulosclerosis, tubular atrophy, interstitial fibrosis, and arteriosclerosis, and we report these findings as an overall chronicity grade.

Outcomes in patients with chronic kidney disease not on dialysis receiving extended dosing regimens of darbepoetin alfa: long-term results of the EXTEND observational cohort study.

Background: Extended dosing of the erythropoiesis-stimulating agent (ESA) darbepoetin alfa (DA) once biweekly or monthly reduces anaemia treatment burden. This observational study assessed outcomes and dosing patterns in patients with chronic kidney disease not on dialysis (CKD-NoD) commencing extended dosing of DA.

Methods: Adult CKD-NoD patients starting extended dosing of DA in Europe or Australia in June 2006 or later were followed up until December 2012.

Mayo Clinic/Renal Pathology Society Consensus Report on Pathologic Classification, Diagnosis, and Reporting of GN.

Renal pathologists and nephrologists met on February 20, 2015 to establish an etiology/pathogenesis-based system for classification and diagnosis of GN, with a major aim of standardizing the kidney biopsy report of GN. On the basis of etiology/pathogenesis, GN is classified into the following five pathogenic types, each with specific disease entities: immune-complex GN, pauci-immune GN, antiglomerular basement membrane GN, monoclonal Ig GN, and C3 glomerulopathy. The pathogenesis-based classification forms the basis of the kidney biopsy report.

Circuit life versus bleeding risk: the impact of achieved activated partial thromboplastin time versus achieved filtration fraction.

Whilst prolonging hemofilter (circuit) life, heparin increases bleeding risk. The impact of achieved activated partial thromboplastin time (APTT) on circuit life and bleeding risk has not been assessed in a modern critically ill cohort. Lowering filtration fraction may be an alternative means of prolonging circuit life, but is often overlooked in critical care.

Does prophylactic anticoagulation reduce the risk of femoral tunneled dialysis catheter-related complications.

Purpose: To determine the incidence and predictors of femoral tunneled dialysis catheter (TDC)-related complications and whether prophylactic anticoagulation is associated with reduced catheter-related deep vein thrombosis (CRT) or prolonged patency.

Methods: A retrospective review of femoral TDCs inserted for maintenance hemodialysis in patients from two dialysis units that have used two different strategies to reduce thrombotic complications. One center routinely considered all femoral TDCs for prophylactic anticoagulation, whilst the other restricted anticoagulation to TDCs that had required repeated treatment with urokinase locks to maintain patency.

Myeloma kidney: improving clinical outcomes?

Renal impairment is a common complication of multiple myeloma, affecting 20% to 40% of new cases (depending on the definition). Most cases are mild and easily reversible, but it may manifest as severe acute renal injury requiring dialysis. Renal impairment is associated with a large tumor mass and consequently confers a poor prognosis.

Identification of gene mutations in autosomal dominant polycystic kidney disease through targeted resequencing.

Mutations in two large multi-exon genes, PKD1 and PKD2, cause autosomal dominant polycystic kidney disease (ADPKD). The duplication of PKD1 exons 1-32 as six pseudogenes on chromosome 16, the high level of allelic heterogeneity, and the cost of Sanger sequencing complicate mutation analysis, which can aid diagnostics of ADPKD. We developed and validated a strategy to analyze both the PKD1 and PKD2 genes using next-generation sequencing by pooling long-range PCR amplicons and multiplexing bar-coded libraries.

Novel approaches for reducing free light chains in patients with myeloma kidney.

Myeloma kidney is a tubulointerstitial pathology that accounts for approximately 80-90% of severe acute kidney injury in patients with multiple myeloma. Unless there is rapid intervention, progressive irreversible damage from interstitial fibrosis and tubular atrophy occurs. Work over the past decade has demonstrated that an early sustained reduction in serum concentrations of pathogenic monoclonal free light chains (FLCs) leads to improved renal recovery rates.

Survival after starting renal replacement treatment in patients with autosomal dominant polycystic kidney disease: a single-centre 40-year study.

Background/aims: Adult polycystic kidney disease (ADPKD) has a predictable natural history and the relative lack of co-morbidity allows a relatively unconfounded assessment of survival. We examined whether survival on renal replacement treatment (RRT) has improved over the last four decades compared to that in the general population.

Methods: We conducted a retrospective cohort study of all patients with ADPKD who received RRT between 1971 and 2000 at the Oxford Kidney Unit.

An observational cohort study of extended dosing (once every 2 weeks or once monthly) regimens with darbepoetin alfa in patients with chronic kidney disease not on dialysis: the EXTEND study.

Background: Darbepoetin alfa (DA) has been shown to be an effective treatment of anaemia in patients with chronic kidney disease (CKD) not on dialysis (NoD). EXTEND is an observational study assessing the effectiveness of DA administered once biweekly (Q2W) or monthly (QM) in a general CKD-NoD population.

Methods: Adult CKD-NoD patients starting DA Q2W/QM treatment in June 2006 or later were eligible.

Classification of chronic kidney disease in the elderly: pitfalls and errors.

The average glomerular filtration rate (GFR) is lower in the elderly than in the young and is usually a consequence of biological ageing, the rate of which varies between individuals. In some subjects, the decline is aggravated by concomitant vascular disease. The prevalence of significant kidney disease in the elderly has been overestimated - largely by rendering a diagnosis of chronic kidney disease by reference to estimates of GFR which are found in the young.