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 [version 1; referees: 2 approved]

• Main Authors: Suceena Alexander, George T. John, Anila Korula, T. S. Vijayakumar, Vinoi George David, Anjali Mohapatra, Anna T. Valson, Shibu Jacob, Pradeep Mathew Koshy, Gautam Rajan, Elenjickal Elias John, Smita Mary Matthai, L. Jeyaseelan, Babu Ponnusamy, Terence Cook, Charles Pusey, Mohamed R. Daha, John Feehally, Jonathan Barratt, Santosh Varughese
• Format: Article
• Language: English
• Published: Wellcome 2018-07-01
• Series: Wellcome Open Research
• Online Access: https://wellcomeopenresearch.org/articles/3-91/v1

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- IgA 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.