Long-Term Results from an Open-Label Extension Study of Atacicept for the Treatment of IgA Nephropathy.

Background: B-cell activating factor (BAFF) and A proliferation-inducing ligand (APRIL) play key roles in the pathogenesis of IgA nephropathy. Atacicept is a novel fully humanized fusion protein, self-administered at home by subcutaneous injection, that binds and inhibits BAFF and APRIL. By inhibiting BAFF and APRIL, atacicept targets the underlying B-cell–mediated pathogenesis driving disease progression.

Alternative Complement Pathway Inhibition with Iptacopan in IgA Nephropathy.

Background: The alternative complement pathway plays a key role in the pathogenesis of IgA nephropathy. Iptacopan specifically binds to factor B and inhibits the alternative pathway.

Methods: In this phase 3, double-blind, randomized, placebo-controlled trial, we enrolled adults with biopsy-confirmed IgA nephropathy and proteinuria with a 24-hour urinary protein-to-creatinine ratio of 1 or higher (with protein and creatinine both measured in grams) despite optimized supportive therapy.

A phase 2b, randomized, double-blind, placebo-controlled, clinical trial of atacicept for treatment of IgA nephropathy.

Atacicept is a first-in-class, dual anti-B-cell Activation Factor-A Proliferation-Inducing Ligand fusion protein in clinical evaluation for treatment of IgA nephropathy. To compare efficacy and safety of atacicept versus placebo in patients with IgAN, this randomized, double-blind, placebo-controlled phase 2b clinical trial ORIGIN enrolled 116 individuals with biopsy-proven IgA nephropathy. Participants were randomized to atacicept 150, 75, or 25 mg versus placebo once weekly for up to 36 weeks.

A meta-analysis of GFR slope as a surrogate endpoint for kidney failure.

Glomerular filtration rate (GFR) decline is causally associated with kidney failure and is a candidate surrogate endpoint for clinical trials of chronic kidney disease (CKD) progression. Analyses across a diverse spectrum of interventions and populations is required for acceptance of GFR decline as an endpoint. In an analysis of individual participant data, for each of 66 studies (total of 186,312 participants), we estimated treatment effects on the total GFR slope, computed from baseline to 3 years, and chronic slope, starting at 3 months after randomization, and on the clinical endpoint (doubling of serum creatinine, GFR < 15 ml min per 1.

Change in Albuminuria and GFR Slope as Joint Surrogate End Points for Kidney Failure: Implications for Phase 2 Clinical Trials in CKD.

Significance Statement: Changes in albuminuria and GFR slope are individually used as surrogate end points in clinical trials of CKD progression, and studies have demonstrated that each is associated with treatment effects on clinical end points. In this study, the authors sought to develop a conceptual framework that combines both surrogate end points to better predict treatment effects on clinical end points in Phase 2 trials. The results demonstrate that information from the combined treatment effects on albuminuria and GFR slope improves the prediction of treatment effects on the clinical end point for Phase 2 trials with sample sizes between 100 and 200 patients and duration of follow-up ranging from 1 to 2 years.

Evaluation of Variation in the Performance of GFR Slope as a Surrogate End Point for Kidney Failure in Clinical Trials that Differ by Severity of CKD.

Background: The GFR slope has been evaluated as a surrogate end point for kidney failure in meta-analyses on a broad collection of randomized controlled trials (RCTs) in CKD. These analyses evaluate how accurately a treatment effect on GFR slope predicts a treatment effect on kidney failure. We sought to determine whether severity of CKD in the patient population modifies the performance of GFR slope.

Clinicopathological characteristics and disease chronicity in native kidney biopsies in Flanders.

Background: The Flemish Collaborative Glomerulonephritis Group (FCGG) registry provides complete population data on kidney disease epidemiology in the region of Flanders (Belgium), as it captures all native kidney biopsies performed in its population of 6.5 million inhabitants.

Methods: From 2017 until 2019, 2054 adult kidney biopsies were included from 26 nephrology centers (one biopsy per patient).

RSV induced rhabdomyolysis: a case report.

Objective: Rhabdomyolysis induced by an RSV infection is a clinical entity.

Case Presentation: A few years ago, one case of severe rhabdomyolysis associated with RSV was described. We present the case of an 18-year-old patient without relevant medical history with a nearly asymptomatic presentation of severe rhabdomyolysis induced by an RSV infection.

Epidemiology of native kidney disease in Flanders: results from the FCGG kidney biopsy registry.

Background: The Flemish Collaborative Glomerulonephritis Group (FCGG) registry is the first population-based native kidney biopsy registry in Flanders, Belgium. In this first analysis, we report on patient demographics, frequency distribution and incidence rate of biopsied kidney disease in adults in Flanders.

Methods: From January 2017 to December 2019, a total of 2054 adult first native kidney biopsies were included.

Acute Treatment Effects on GFR in Randomized Clinical Trials of Kidney Disease Progression.

Background: Acute changes in GFR can occur after initiation of interventions targeting progression of CKD. These acute changes complicate the interpretation of long-term treatment effects.

Methods: To assess the magnitude and consistency of acute effects in randomized clinical trials and explore factors that might affect them, we performed a meta-analysis of 53 randomized clinical trials for CKD progression, enrolling 56,413 participants with at least one estimated GFR measurement by 6 months after randomization.

Association of Treatment Effects on Early Change in Urine Protein and Treatment Effects on GFR Slope in IgA Nephropathy: An Individual Participant Meta-analysis.

Rationale & Objective: An early change in proteinuria is considered a reasonably likely surrogate end point in immunoglobulin A nephropathy (IgAN) and can be used as a basis for accelerated approval of therapies, with verification in a postmarketing confirmatory trial. Glomerular filtration rate (GFR) slope is a recently validated surrogate end point for chronic kidney disease progression and may be considered as the end point used for verification. We undertook a meta-analysis of clinical trials in IgAN to compare treatment effects on change in proteinuria versus change in estimated GFR (eGFR) slope.

Performance of GFR Slope as a Surrogate End Point for Kidney Disease Progression in Clinical Trials: A Statistical Simulation.

Background: Randomized trials of CKD treatments traditionally use clinical events late in CKD progression as end points. This requires costly studies with large sample sizes and long follow-up. Surrogate end points like GFR slope may speed up the evaluation of new therapies by enabling smaller studies with shorter follow-up.

Observational study on the incidence of nephrogenic systemic fibrosis in patients with renal impairment following gadoterate meglumine administration: the NSsaFe study.

Background: Nephrogenic systemic fibrosis (NSF) is a rare life-threatening condition strongly associated with the administration of gadolinium-based contrast agents in patients with severe or endstage renal impairment.

Purpose: To prospectively determine the incidence of NSF in patients with renal impairment after administration of gadoterate meglumine.

Study Type: Prospective.

Hereditary polycystic kidney disease is characterized by lymphopenia across all stages of kidney dysfunction: an observational study.

Background: Polycystic kidney disease (PKD) is characterized by urinary tract infections and extrarenal abnormalities such as an increased risk of cancer. As mutations in polycystin-1 and -2 are associated with decreased proliferation of immortalized lymphoblastoid cells in PKD, we investigated whether lymphopenia could be an unrecognized trait of PKD.

Methods: We studied 700 kidney transplant recipients with (n = 126) or without PKD at the time of kidney transplantation between 1 January 2003 and 31 December 2014 at Ghent University Hospital.

Targeted-release budesonide versus placebo in patients with IgA nephropathy (NEFIGAN): a double-blind, randomised, placebo-controlled phase 2b trial.

Background: IgA nephropathy is thought to be associated with mucosal immune system dysfunction, which manifests as renal IgA deposition that leads to impairment and end-stage renal disease in 20-40% of patients within 10-20 years. In this trial (NEFIGAN) we aimed to assess safety and efficacy of a novel targeted-release formulation of budesonide (TRF-budesonide), designed to deliver the drug to the distal ileum in patients with IgA nephropathy.

Methods: We did a randomised, double-blind, placebo-controlled phase 2b trial, comprised of 6-month run-in, 9-month treatment, and 3-month follow-up phases at 62 nephrology clinics across ten European countries.

Early Change in Urine Protein as a Surrogate End Point in Studies of IgA Nephropathy: An Individual-Patient Meta-analysis.

Background: The role of change in proteinuria as a surrogate end point for randomized trials in immunoglobulin A nephropathy (IgAN) has previously not been thoroughly evaluated.

Study Design: Individual patient-level meta-analysis.

Setting & Population: Individual-patient data for 830 patients from 11 randomized trials evaluating 4 intervention types (renin-angiotensin system [RAS] blockade, fish oil, immunosuppression, and steroids) examining associations between changes in urine protein and clinical end points at the individual and trial levels.

Performance assessment of the Illumina massively parallel sequencing platform for deep sequencing analysis of viral minority variants.

Massively parallel sequencing (MPS) technology has opened new avenues to study viral dynamics and treatment-induced resistance mechanisms of infections such as human immunodeficiency virus (HIV) and hepatitis C virus (HCV). Whereas the Roche/454 platform has been used widely for the detection of low-frequent drug resistant variants, more recently developed short-read MPS technologies have the advantage of delivering a higher sequencing depth at a lower cost per sequenced base. This study assesses the performance characteristics of Illumina MPS technology for the characterization of genetic variability in viral populations by deep sequencing.

Safety of meglumine gadoterate (Gd-DOTA)-enhanced MRI compared to unenhanced MRI in patients with chronic kidney disease (RESCUE study).

Objective: To prospectively compare the renal safety of meglumine gadoterate (Gd-DOTA)-enhanced magnetic resonance imaging (MRI) to a control group (unenhanced MRI) in high-risk patients.

Methods: Patients with chronic kidney disease (CKD) scheduled for MRI procedures were screened. The primary endpoint was the percentage of patients with an elevation of serum creatinine levels, measured 72 ± 24 h after the MRI procedure, by at least 25 % or 44.

Light chain deposition disease as a rare cause of restrictive cardiomyopathy.

We report an unusual case of a 47-year-old Caucasian woman who presented with severe dyspnoea as a manifestation of restrictive cardiomyopathy, found to be due to myocardial deposition of kappa light chains. Non-routine specific immunofluorescence stainings of endomyocardial biopsy specimens were key for the diagnosis of myocardial light chain deposition disease. We discuss non-amyloidotic cardiac immunoglobulin deposition disease in contrast to cardiac amyloidosis.

A new electronic monitoring device to measure medication adherence: usability of the Helping Hand™.

The aim of this study was to test the user performance, satisfaction and acceptability of the Helping Hand™ (B&O Medicom) electronic medication adherence monitor. Using a mixed-method design, we studied 11 kidney transplant patients and 10 healthy volunteers during three weeks. Although testing showed positive usability aspects, several areas requiring technical improvement were identified: the most important obstacles to usability and acceptability were the weak sound signal, problems loading the medication, and the fact that only one medication could be used at a time.