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

Abstract

Introduction Glomerular Research And Clinical Experiments–IgA Nephropathy in Indians (GRACE-IgANI) is the first prospective South Asian IgAN cohort with protocolized follow-up and extensive biosample collection. Here we report the baseline clinical, biochemical, and histopathologic characteristics of GRACE IgANI and calculate baseline risk of progression for the cohort. Methods 201 incident adults with kidney biopsy–proven primary IgAN were recruited into GRACE-IgANI between March 2015 and September 2017. As of April 30, 2020, the cohort had completed a median follow-up of 30 months (interquartile range [IQR] 16-39). Results The commonest clinical presentation in GRACE IgANI was hypertension, with or without proteinuria, and nephrotic-range proteinuria was present in 34%, despite <10 months of lead time to kidney biopsy. The GRACE-IgANI kidney biopsy data demonstrated a disproportionate absence of active glomerular lesions and overrepresentation of segmental sclerosing lesions and tubulointerstitial fibrosis at presentation, often coexistent with relatively well-preserved estimated glomerular filtration rate (eGFR) and low levels of proteinuria, especially in males. Baseline risk of progression was calculated for each evaluable patient using 2 different risk prediction tools. The median 5-year absolute risk of end-stage kidney disease (ESKD) was 19.8% (IQR 2.7–57.4) and median 5-year risk of progression to the combined endpoint of 50% decline in eGFR or ESKD was 35.5% using the 2 tools. Conclusions The predicted risk of progression in this cohort was considerable. Over the next 5 years, we will dissect the pathogenic pathways that underlie this severe South Asian IgAN phenotype.

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

“…6 While men presented with a significantly more severe clinical phenotype and more extensive chronicity on kidney biopsy, gender did not influence longitudinal outcomes in our cohort. 4 This is again in contrast to the published literature which reports a worse renal outcome for males with IgAN. 22,23 Contrary to our expectations, residing in peripheral rural locations, distance to the center and socioeconomic status did not affect renal outcomes in our cohort.…”

“…We reported previously that while younger (≤35 years) patients presented with milder clinical disease, reflected by less hypertension, higher eGFR and lower proteinuria, there was no difference in the frequency of chronic lesions on renal histology in terms of S1 and T1/T2 scores. 4 Perhaps reflecting the underlying extent of kidney scarring in these younger patients, we did not observe a greater likelihood of proteinuria remission or lower incidence of the CO in younger patients. This contrasts with other studies reporting a better prognosis in the young.…”

“…As reported previously this is a cohort at high risk of progressive CKD. 4 Consistent with KDIGO guidelines all patients were offered optimized supportive care and optimal BP control and up-titration of RASB was achieved in 70-80% of the cohort over the 3 years of follow-up. In accordance with the prespecified protocol all patients regarded as at high risk of progression were offered immunosuppression and 146/194 (75.3%) patients received systemic corticosteroids.…”

“…2 The baseline characteristics and calculated progression risk for this incident cohort has previously been reported. 4 The median baseline total risk score (TRS) by Tanaka et al, 5 was 19 (IQR [13][14][15][16][17][18][19][20][21][22][23][24], which equated to a predicted 5-year absolute risk of ESKD of 19.8% (IQR 2.7-57.4). The predicted 5-year risk of a 50% decline in eGFR or ESKD using the International IgA Nephropathy Network (IIGANN) risk prediction tool (Barbour et al) 6 was 35.5% (IQR 13.7-56.2).…”

“…The predicted 5-year risk of a 50% decline in eGFR or ESKD using the International IgA Nephropathy Network (IIGANN) risk prediction tool (Barbour et al) 6 was 35.5% (IQR 13.7-56.2). 4 Both scores predicted a high-risk cohort based on baseline variables. Here we report the actual three-year longitudinal clinical outcomes of the GRACE-IgANI cohort.…”