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

Suceena Alexander; Santosh Varughese; Rajanbabu Franklin; Grace Rebekah; Sanjeet Roy; Sabina Yusuf; Athul Thomas; Jeethu Joseph Eapen; Elenjickal Elias John; Anna T Valson; Vinoi George David; Mohamed R Daha; John Feehally; Jonathan Barratt; George T John

doi:10.1016/j.ekir.2021.11.012

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

Kidney Int Rep. 2021 Nov 24;7(2):305-318. doi: 10.1016/j.ekir.2021.11.012. eCollection 2022 Feb.

Authors

Affiliations

¹ Department of Nephrology, Christian Medical College, Vellore, India.
² Department of Biostatistics, Christian Medical College, Vellore, India.
³ Department of General Pathology, Christian Medical College, Vellore, India.
⁴ University Medical Center Groningen, Groningen, The Netherlands.
⁵ College of Medicine Biological Sciences and Psychology, University of Leicester, Leicester, UK.
⁶ Present Affiliation: Department of Renal Medicine, Royal Brisbane and Women's Hospital, Queensland, Australia.

Abstract

Introduction: Glomerular Research And Clinical Experiments-IgA Nephropathy in Indians (GRACE-IgANI) is the first prospective South Asian IgA nephropathy (IgAN) cohort with prespecified objectives, protocolized longitudinal follow-up, and extensive biosample collection. The baseline risk scores predicted high risk of kidney disease progression.

Methods: A total of 195 of 201 patients (97%) completed 3-year follow-up in September 2020. All patients received optimized supportive care, and those at high risk of progression were offered systemic corticosteroids.

Results: A total of 76 patients (76 of 193, 39.4%) had rapid progression in 3 years (≥5 ml/min per 1.73 m² decline in estimated glomerular filtration rate [eGFR] per year). A total of 72 patients (72 of 195, 36.9%) experienced the composite outcome (CO), defined as ≥50% fall in eGFR, eGFR < 15 ml/min per 1.73 m², commenced kidney replacement therapy or death, in 3 years. At each scheduled follow-up, achievement of proteinuria level < 1 g/d significantly delayed the time to the CO. The receiver operating characteristic curve of average annual decline in eGFR ≥ 5 ml/min per 1.73 m² had 86% sensitivity and 89% specificity for CO in 3 years and had good discrimination from 1 year onwards (area under the curve 0.8, SE 0.04, 95% CI 0.7-0.9, P < 0.0001). The significant predictors of CO by Cox proportional-hazards model were as follows: baseline MEST-T2 score (hazard ratio [HR] 3.3, 95% CI 1.7-6.5, P < 0.001), along with 24-hour urine protein level ≥ 1 g/d (HR 2.1, 95% CI 1.1-3.9, P = 0.02), eGFR < 60 ml/min per 1.73 m² (HR 2.9, 95% CI 1.1-7.6, P = 0.03), and rate of eGFR decline ≥ 5 ml/min per 1.73 m²/yr (HR 2.7, 95% CI 1.6-4.8, P < 0.001) all measured at 6 months. Mortality was 11 of 195 (5.6%).

Conclusion: We identified longitudinal clinical variables measured at 6 months and ≥5 ml/min per 1.73 m² annual fall in eGFR after kidney biopsy as important predictors for composite outcome in addition to baseline histology.

Keywords: ACE inhibitors; IgA nephropathy; glomerulonephritis; nephrotic syndrome; proteinuria; renal pathology.

Abstract

Grants and funding