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

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

Suceena Alexander  1 , Santosh Varughese  1 , Rajanbabu Franklin  1 , Grace Rebekah  2 , Sanjeet Roy  3 , Sabina Yusuf  1 , Athul Thomas  1 , Jeethu Joseph Eapen  1 , Elenjickal Elias John  1 , Anna T Valson  1 , Vinoi George David  1 , Mohamed R Daha  4 , John Feehally  5 , Jonathan Barratt  5 , George T John  1   6
Affiliations

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

Suceena Alexander et al. Kidney Int Rep. .

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.

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Figures

None
Graphical abstract
Figure 1
Figure 1
Treatment subgroups. All patients with ≥1 g/d of proteinuria and/or renal impairment were treated with short course of oral steroids (subgroup 2) except for patients with chronic sclerosing IgAN or with compelling contraindications. eGFR, estimated glomerular filtration rate; GRACE-IgANI, Glomerular Research And Clinical Experiments—IgA Nephropathy in Indians; IgAN, IgA nephropathy.
Figure 2
Figure 2
(a) KM curves of kidney survival (defined here as having N/SP) for the entire cohort and the treatment subgroups. (b) Trends in RASB use in patients with RP and N/SP. (c) KM curves of kidney survival (defined as composite outcome-free survival) for the entire cohort and treatment subgroups. (d) Trends in RASB use in the patients who did and did not experience the composite outcome. (e) ROC curve of average annual rate of eGFR change and the composite outcome at 3 years. (f) ROC curve for annualized fall in eGFR at each time period and the composite outcome at 3 years. #, number; CO, composite outcome; eGFR, estimated glomerular filtration rate; GRACE-IgANI, Glomerular Research And Clinical Experiments—IgA Nephropathy in Indians; IgAN, IgA nephropathy; KM, Kaplan–Meier; N/SP, no/slow progression; RASB, renin-angiotensin system blocker; ROC, receiver operating characteristic; RP, rapid progression.
Figure 3
Figure 3
(a) KM curves of CR of proteinuria for the entire cohort and the treatment subgroups. (b) KM curves of PR of proteinuria for the entire cohort and the treatment subgroups. (c) KM curves of proteinuria remission stratified by rate of progression. (d) KM curves of proteinuria remission stratified by composite outcome status. (e) Proteinuria status at each time period in the outcome groups. #, number; CO, composite outcome; CR, complete remission; GRACE-IgANI, Glomerular Research And Clinical Experiments—IgA Nephropathy in Indians; IgAN, IgA nephropathy; KM, Kaplan–Meier; N/SP, no/slow progression; PR, partial remission; RP, rapid progression.
Figure 4
Figure 4
(a) Kaplan–Meier curves of kidney survival (defined as composite outcome-free survival) stratified by the achieved proteinuria at 6 months follow-up for the entire cohort. (b) Kaplan–Meier curves of kidney survival (defined as composite outcome-free survival) stratified by the achieved proteinuria at 6 months follow-up for treatment subgroup 1. (c) Kaplan–Meier curves of kidney survival (defined as composite outcome-free survival) stratified by the achieved proteinuria at 6 months follow-up for treatment subgroup 2. Linear trends in (d) mean arterial pressure, (e) proteinuria, and (f) eGFR over time and in relation to the development of the composite outcome. #, number; CO, composite outcome; eGFR, estimated glomerular filtration rate; IQR, interquartile range.
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References

    1. GBD 2015 Mortality and Causes of Death Collaborators Global, regional, and national life expectancy, all-cause mortality, and cause-specific mortality for 249 causes of death, 1980–2015: a systematic analysis for the Global Burden of Disease Study 2015 [published correction appears in Lancet. 2017;389:e1] Lancet. 2016;388:1459–1544. doi: 10.1016/S0140-6736(16)31012-1. - DOI - PMC - PubMed
    1. Alexander S., John G.T., Korula A., et al. 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. Wellcome Open Res. 2018;3:91. doi: 10.12688/wellcomeopenres.14644.1. - DOI - PMC - PubMed
    1. Alexander S. IgA Nephropathy Study in Indians. ISRCTN registry. https://www.isrctn.com/ISRCTN36834159 Updated November 10, 2017.
    1. Alexander S., Varughese S., Franklin R., et al. Epidemiology, baseline characteristics and risk of progression in the first South-Asian prospective longitudinal observational IgA nephropathy cohort. Kidney Int Rep. 2020;6:414–428. doi: 10.1016/j.ekir.2020.11.026. - DOI - PMC - PubMed
    1. Tanaka S., Ninomiya T., Katafuchi R., et al. Development and validation of a prediction rule using the Oxford classification in IgA nephropathy. Clin J Am Soc Nephrol. 2013;8:2082–2090. doi: 10.2215/CJN.03480413. - DOI - PMC - PubMed