Integration of Genetics Into the Design and Conduct of Clinical Trials in Nephrology.

Advances in genomic diagnostics have enabled earlier and more precise identification of genetic kidney disease, but the translation of these insights into trial methodology and therapeutic development has lagged. This review examines the current challenges in nephrology trials-including disease heterogeneity, slow progression, and limited industry engagement-and explores how genomic information can address these barriers. Examples from trials in autosomal dominant polycystic kidney disease and other genetic kidney diseases demonstrate the feasibility and value of genomics-informed approaches, including genotype-based recruitment, post hoc genetic stratification, and drug repurposing.

Patients' Perspectives on Living With Primary Membranous Nephropathy: A Semi-Structured Interview Study.

Rationale & Objective: Membranous nephropathy (MN) is characterized by a relapsing remitting course with a third of patients developing kidney failure if untreated. Little is known about the experiences patients have when living with MN. This study described those experiences to inform choices of clinical care and guide future research.

Genotype-Phenotype Correlations and Clinical Outcomes of Genetic TRPC6 Podocytopathies.

Background And Hypothesis: Podocytopathy associated with likely pathogenic/pathogenic variants of TRPC6 (TRPC6-AP) has been recognised for about 20 years. As a result of its rarity however, the spectrum of clinical phenotypes and genotype-phenotype correlation of TRPC6-AP remains poorly understood. Here, we characterised clinical, histological, and genetic correlates of familial and sporadic patients with TRPC6-AP.

CD8 Regulatory T Cells Induced by Peptide Vaccination Ameliorates Experimental Model of Membranous Nephropathy.

Aim: CD8 regulatory T cells (Tregs) are cross-protective across multiple animal models of autoimmunity. Recently, specific peptides from a yeast-peptide-major histocompatibility complex library that expanded CD8 Tregs in murine experimental multiple sclerosis were reported. Whether these peptides also expand CD8 Tregs and protect against Heymann nephritis (HN), an experimental model of membranous nephropathy is unknown.

T cell costimulatory blockade ameliorates induction of experimental membranous nephropathy potentially through T-helper 17 cell suppression in the kidney.

Background And Hypothesis: Recent advances in membranous nephropathy treatment have focused on B cell depletion, which is incompletely effective, potentially due to persistent autoantibody-producing plasma cells or alternative pathways of injury. T cell costimulatory blockade (cytotoxic-T-lymphocyte-associated antigen 4 (CTLA4)-Ig) to prevent T cell-dependent B cell activation and short-course proteasome inhibition (bortezomib) to deplete plasma cells may represent a complementary form of treatment.

Methods: Lewis rats were immunized with Fx1A and complete Freund's adjuvant (CFA) to induce experimental membranous nephropathy (Heymann nephritis or HN) and treated with CTLA4-Ig alone or CTLA4-Ig plus a short-course of bortezomib.

Enhancing diagnostic outcomes in kidney genetic disorders: the KidGen national kidney genomics study protocol.

Background: Genetic kidney disease (GKD) significantly affects the community and is responsible for a notable portion of adult kidney disease cases and about half of cases in paediatric patients. It substantially impacts the quality of life and life expectancy for affected children and adults across all stages of kidney disease. Precise genetic diagnosis in GKD promises to improve patient outcomes, provide access to targeted treatments, and reduce the disease burden for individuals, families, and healthcare systems.

Perspectives of Caregivers on Access to Health Care for Children with CKD.

Introduction: Inequitable access to health care based on demographic factors such as ethnicity, socioeconomic status and geographical location has been consistently found in children with chronic kidney disease (CKD). However, little is known about the perspectives of caregivers on accessing health care. We described caregivers' perspectives on accessing health care for children with CKD from socioeconomically disadvantaged backgrounds and/or rural or remote areas.

Shaping the future of kidney genetics in Australia: proceedings from the KidGen policy implementation workshop 2023.

The KidGen Collaborative's Policy Implementation Workshop 2023 celebrated the 10th anniversary of Australia's first kidney genetics clinic in Brisbane. This event marked the establishment of a national network now comprising 19 kidney genetics clinics across Australia, all dedicated to providing equitable access to genomic testing for families affected by genetic kidney diseases. The workshop reflected on past progress and outlined future objectives for kidney genetics in Australia, recognising the collaborative efforts of clinical teams, researchers, and patients.

Genomic testing for suspected monogenic kidney disease in children and adults: A health economic evaluation.

Purpose: To assess the relative cost-effectiveness of genomic testing compared with standard non-genomic diagnostic investigations in patients with suspected monogenic kidney disease from an Australian health care system perspective.

Methods: Diagnostic and clinical information was used from a national cohort of 349 participants. Simulation modelling captured diagnostic, health, and economic outcomes during a time horizon from clinical presentation until 3 months post-test results based on the outcome of cost per additional diagnosis and lifetime horizon based on cost per quality-adjusted life-year (QALY) gained.

Timing of Kidney Replacement Therapy among Children and Young Adults.

Background: No randomized trials exist to guide the timing of the initiation of KRT in children. We sought to define trends and predictors of the eGFR at initiation of KRT, center-related clinical practice variation, and any association with patient survival.

Methods: Children and young adults (1-25 years) commencing KRT (dialysis or kidney transplantation) between 1995 and 2018 were included using data from the Australia and New Zealand Dialysis and Transplant Registry.

A multicenter retrospective study of calcineurin inhibitors in nephrotic syndrome secondary to podocyte gene variants.

While 44-83% of children with steroid-resistant nephrotic syndrome (SRNS) without a proven genetic cause respond to treatment with a calcineurin inhibitor (CNI), current guidelines recommend against the use of immunosuppression in monogenic SRNS. This is despite existing evidence suggesting that remission with CNI treatment is possible and can improve prognosis in some cases of monogenic SRNS. Herein, our retrospective study assessed response frequency, predictors of response and kidney function outcomes among children with monogenic SRNS treated with a CNI for at least three months.

Variant Location Is a Novel Risk Factor for Individuals With Arrhythmogenic Cardiomyopathy Due to a Desmoplakin () Truncating Variant.

Background: Truncating variants in desmoplakin (tv) are an important cause of arrhythmogenic cardiomyopathy; however the genetic architecture and genotype-specific risk factors are incompletely understood. We evaluated phenotype, risk factors for ventricular arrhythmias, and underlying genetics of tv cardiomyopathy.

Methods: Individuals with tv and any cardiac phenotype, and their gene-positive family members were included from multiple international centers.

Understanding the ongoing learning needs of Australian paediatricians: Evaluation of a pilot paediatric video teaching programme.

Aim: The purpose of this study was to evaluate whether pre-recorded video-based lectures (VBLs) covering a range of paediatric topics are an acceptable means of providing ongoing education for consultant and trainee paediatricians in Australia.

Methods: Previous participants (paediatric consultants and junior medical officers) of a neurology outreach teleconference programme offered by a paediatric neurologist between 2017 and 2020 were invited to participate in a multi-specialty pre-recorded video-based education programme. Acceptability was explored by assessing relevance, likelihood of utilising VBL's in the future, uptake and learning activity preferences.

Membranous nephropathy: Clearer pathology and mechanisms identify potential strategies for treatment.

Primary membranous nephropathy (PMN) is one of the common causes of adult-onset nephrotic syndrome and is characterized by autoantibodies against podocyte antigens causing immune complex deposition. Much of our understanding of the disease mechanisms underpinning this kidney-limited autoimmune disease originally came from studies of Heymann nephritis, a rat model of PMN, where autoantibodies against megalin produced a similar disease phenotype though megalin is not implicated in human disease. In PMN, the major target antigen was identified to be M-type phospholipase A2 receptor 1 (PLA2R) in 2009.

Participant Choice towards Receiving Potential Additional Findings in an Australian Nephrology Research Genomics Study.

The choices of participants in nephrology research genomics studies about receiving additional findings (AFs) are unclear as are participant factors that might influence those choices. : Participant choices and factors potentially impacting decisions about AFs were examined in an Australian study applying research genomic testing following uninformative diagnostic genetic testing for suspected monogenic kidney disease. : 93% of participants (195/210) chose to receive potential AFs.

Baseline characteristics of participants in the NAVKIDS trial: a patient navigator program in children with chronic kidney disease.

Background: Children with chronic kidney disease (CKD) require multidisciplinary care to meet their complex healthcare needs. Patient navigators are trained non-medical personnel who assist patients and caregivers to overcome barriers to accessing health services through care coordination. This trial aims to determine the effectiveness of a patient navigator program in children with CKD.

NAVKIDS trial: a multi-centre, waitlisted randomised controlled trial of a patient navigator intervention in children with chronic kidney disease - statistical analysis plan and update to the protocol.

Background: This update summarises key changes made to the protocol since the publication of the original protocol for the NAVKIDS trial of patient navigators for children with chronic kidney disease (CKD) experiencing social disadvantage and provides the statistical analysis plan (SAP) which has not previously been published.

Methods/design: The original protocol was published in BMC Nephrology ( https://doi.org/10.