Protocol and rationale for the first South Asian 5-year prospective longitudinal observational cohort study and biomarker evaluation investigating the clinical course and risk profile of IgA nephropathy: GRACE IgANI cohort

Abstract

Background: IgA nephropathy (IgAN) is the most common primary glomerulonephritis and an important cause of end-stage kidney disease. Unlike the slowly progressive course seen among Caucasian and East Asian subjects (actuarial survival 80-85% over 10 years), in India about 30-40% of patients have nephrotic syndrome and renal dysfunction at presentation and a 10-year renal survival of 35%, as reported from a retrospective registry. These observations cannot be entirely attributed to a lack of uniform screening protocols or late referral and attest to the probability that IgAN may not be the same disease in different parts of the world. Methods: We will prospectively recruit 200 patients with IgAN (the GRACE IgANI— Glomerular Research And Clinical Experiments- Ig A Nephropathy in Indians—cohort) and stratify them into low and high risk of progression based on published absolute renal risk scores. We will test the validity of this risk score in an unselected Indian IgAN population over a 5-year follow-up period. In parallel, we will undertake extensive exploratory serum, urine, renal and microbiome biomarker studies, firstly, to determine if the underlying pathogenic pathways are the same in Indian IgAN compared to those reported in Caucasian and East Asian IgAN. Secondly, we will systematically assess the value of measuring selected biomarkers and adding this data to traditional measures of risk in IgAN to predict kidney failure. We ultimately hope to generate a composite IgAN risk score specific for the Indian population. Ethics and data dissemination: Approval was obtained from the Institutional Review Board (Silver, Research and Ethics Committee) of the Christian Medical College, Vellore, India (Ref. No. IRB Min. No. 8962 [Other] dated 23.07.2014 and IRB Min. No. 9481 [Other] dated 24.06.2015). It is anticipated that results of this study will be presented at national and international meetings, with reports being published from late 2018.

Epidemiology, baseline characteristics and risk of progression in the first South-Asian prospective longitudinal observational IgA nephropathy cohort

“…, 21 and this was used to risk stratify 185 IgAN patients with complete MEST-C scores for longitudinal follow-up. 17 This risk prediction tool uses 5 parameters: proteinuria, eGFR, and the M, S, and T scores of the Oxford classification to give a total risk score (TRS) between 0 and 34, which translates to a 5-year absolute risk of ESKD. In 2019, a new IgAN risk prediction tool was published by Barbour et al.…”

“…The study protocol has previously been published 17 and is registered with WHO trial id: ISRCTN36834159. In brief, all patients with a diagnosis of primary IgAN based on a kidney biopsy performed at Christian Medical College, Vellore, and who satisfied the eligibility criteria ( Supplementary Table S1 ) were consecutively and prospectively recruited into GRACE-IgANI after informed consent.…”

“…The full GRACE-IgANI protocol has been published separately. 17 In brief, this J o u r n a l P r e -p r o o f prospective study was specifically designed to enable collection of a full complement of biosamples (including DNA, serum, plasma, urine, faeces, kidney tissue) for in depth biomarker analysis to elucidate pathogenic pathways operating in the cohort and directly link these to clinical phenotype and kidney disease progression during follow-up.…”

Three-Year Clinical Outcomes of the First South Asian Prospective Longitudinal Observational IgA Nephropathy Cohort

“…The GRACE-IgANI (Glomerular Research And Clinical Experiments-IgA Nephropathy in Indians) prospective longitudinal cohort study was designed specifically to address this gap. The study protocol has been published 2 and is registered with WHO trial id: ISRCTN36834159. 3 Two hundred and one consenting adult IgAN patients who satisfied the prespecified inclusion criteria (Table S1) were consecutively recruited post kidney biopsy from March 2015 to September 2017.…”

Recurrent glomerulonephritis in the kidney allograft

“…In this review, we will focus on the clinicopathological characteristics of certain recurrent glomerular diseases: immunoglobulin A (IgA) nephropathy,[ 4 5 ] membranous nephropathy (MN),[ 5 6 ] focal segmental glomerulosclerosis (FSGS),[ 5 ] lupus nephritis, complement-mediated glomerulonephritis,[ 5 ] and some monoclonal gammopathy-related renal diseases.…”