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.

Keywords: IgA nephropathy; South Asia; chronic kidney disease; glomerulonephritis; immune-mediated kidney disease; renal risk score.

Graphical abstract

Figure 1

Geographic distribution of patients enrolled in the Glomerular Research And Clinical Experiments–IgA Nephropathy in Indians (GRACE-IgANI) cohort. The country and state of origin of the 201 IgAN patients consecutively recruited into the GRACE-IgANI cohort.

Figure 2

Patterns of clinical presentation of the Glomerular Research And Clinical Experiments–IgA Nephropathy in Indians (GRACE-IgANI) cohort. Each circle represents 1% of the selected population. Percentage shown for each clinical presentation is stratified by CKD-EPI eGFR and proteinuria. eGFR, estimated glomerular filtration rate; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration; UP, urine protein.

Figure 3

Time to renal biopsy from onset of symptoms or detection of abnormal laboratory parameters. (a) Categorized for 24-hour urine protein (UP) at baseline; (b) categorized for CKD-EPI eGFR at baseline.

Figure 4

Relationship of the presence of the S and T lesions of the Oxford Classification with key clinical variables. There were significant associations between the presence of segmental glomerular sclerosis (S1) and 24-hour urine protein excretion and eGFR (CKD-EPI) at the time of diagnosis, but not mean arterial blood pressure. Similarly, there were significant associations between the extent of tubulointerstitial inflammation and fibrosis (T1 and T2) and 24-hour urine protein excretion and eGFR (CKD-EPI) at the time of kidney biopsy, as well as mean arterial blood pressure. eGFR, estimated glomerular filtration rate; CKD-EPI, Chronic Kidney Disease Epidemiology Collaboration.

Figure 5

Baseline risk of progression in the Glomerular Research And Clinical Experiments–IgA Nephropathy in Indians (GRACE-IgANI) cohort using 2 different risk prediction scores. (a) We calculated the 5-year risk of a 50% decline in eGFR or ESKD using the International IgA Nephropathy Network (IIGANN) risk prediction tool (Barbour et al.) and the 5-year risk of ESKD using the renal risk equation developed by Tanaka et al. for the 185 IgAN patients with complete MEST-C scores in the GRACE-IgANI cohort. Each patient is represented in a separate column and ordered according to increasing 5 year risk of ESKD using the renal risk equation developed by Tanaka et al. (b) There was a clear correlation between each patients 5-year risk of a 50% decline in eGFR or ESKD using the International IgA Nephropathy Network (IIGANN) risk prediction tool (Barbour et al.) and the 5-year risk of ESKD using the renal risk equation developed by Tanaka et al. for the 185 IgAN patients with complete MEST-C scores in the GRACE-IgANI cohort. As would be expected a number of patients with no risk of ESKD at 5 years using the Tanaka et al. prediction tool had appreciable risk of progression using the IIGANN tool which likely represents those at risk of a 50% decline in eGFR rather than ESKD within 5 years. (c) We also calculated the corresponding 2 year risk of a 50% decline in eGFR or ESKD using the International IgA Nephropathy Network (IIGANN) risk prediction tool (Barbour et al.) in the 185 IgAN patients with complete MEST-C scores in the GRACE-IgANI cohort. Short term risk of progression in this incident cohort was high.