Long-term follow-up of an IgA nephropathy cohort: outcomes and risk factors

Abstract

Aim: IgA nephropathy (IgAN), the most common glomerulopathy worldwide and in Uruguay, raised treatment controversies. The study aimed to analyze long-term IgAN outcomes and treatment.

Methods: A retrospective analysis of a Uruguayan IgAN cohort, enrolled between 1985 and 2009 and followed up until 2020, was performed. The Ethics Committee approved the study. The inclusion criteria were (a) biopsy-proven IgAN; (b) age ≥12 years; and (c) available clinical, histologic, and treatment data. The patients were divided into two groups, with immunosuppressive (IS) or without (NoIS) treatment. Outcomes (end-stage kidney disease/kidney replacement therapy [ESKD/KRT] or all-cause death) were obtained from mandatory national registries.

Results: The study population included 241 patients (64.7% men), median age 32 (19.5) years, baseline blood pressure <130/80 mmHg in 37%, and microhematuria in 67.5% of patients. Baseline proteinuria, glomerulosclerosis, and a higher crescent percentage were significantly more frequent in the IS group. Proteinuria improved in both groups. Renal survival at 20 years was 74.6% without difference between groups. In the overall population and in the NoIS group, bivariate Cox regression analysis showed that baseline proteinuria, endocapillary hypercellularity, tubule interstitial damage, and crescents were associated with a higher risk of ESKD/KRT or death, but in the IS group, proteinuria and endocapillary hypercellularity were not. In the multivariate Cox analysis, proteinuria in the NoIS group, crescents in the IS group and tubule interstitial damage in both groups were independent risk factors.

Conclusion: The IS group had more severe risk factors than the NoIS group but attained a similar outcome.

Keywords: IgA nephropathy; kidney replacement therapy; outcomes; risk factors.

Figure 1.

Algorithm with the studied population, immunosuppressive (IS), and no immunosuppressive (NoIS) groups.

Figure 2.

Studied population renal survival curves. A. Kaplan–Meier renal survival curve (Event = ESKD/KRT or death). (B) Kaplan–Meier renal survival curve (Event = ESKD/KRT or death) according to immunosuppressive treatment, and the number of exposed patients at each time. (Log-rank p = 0.127). Mean survival time to combined event (CI 95%) was 28.9 (27.1–30.8) years the in global population, 30.2 (27.9–32.6) years in the No IS group, and 23.6 (21.4–25.8) years in the IS group.

Figure 3.

(A) Baseline and Last available proteinuria data (n = 177). Levels: Mild <0.75 g/L o 1 g/d, Moderate between 0.75 g/L or 1 g/d and 3 g/L or 3.5 g/d and Severe > 3 g/L or 3.5 g/d. (B) Baseline and (C). Last proteinuria, in No Immunosuppressive (No IS, n = 88) and Immunosuppressive (IS, n = 89) Groups. Baseline vs Last proteinuria was significantly different in the No IS group (Chi² p = 0.04) and in the IS group (Chi² p = 0.007). The time between baseline and last data (median, IQR): Studied population 65 (82) months, IS group 64 (74) months, no IS group 65 (93) months.

Figure 4.

Survival to KRT or death according to crescent’s percentage in KB. Global Mean survival (CI 95%) was 28.7 (26.7–30.7) years, No-crescents group was 30.8 (28.4–33.2) years and for the ≥30% crescents was 9.4 (5.9–12.9) years. Survival at 20 years was 78.8% (group without crescents), 86.4% (group with 1–10% crescents), 72.6% (group with 11–29% crescents), and 36.4% (group ≥30% crescents). Log-rank p = 0.000.