CLINICOPATHOLOGIC PHENOTYPE OF IgA NEPHROPATHY (IgAN) WITH NEPHROTIC SYNDROME AND ITS OUTCOME

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Abstract Title *

CLINICOPATHOLOGIC PHENOTYPE OF IgA NEPHROPATHY (IgAN) WITH NEPHROTIC SYNDROME AND ITS OUTCOME

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Co-author 1

Shamira Shahar shamira@upm.edu.my Hospital Sultan Abdul Aziz Shah, Universiti Putra Malaysia Medical Serdang Malaysia *

Co-author 2

Christopher Lim christopher@upm.edu.my Universiti Putra Malaysia Medicine Serdang Malaysia -

Co-author 3

Nor Fadhlina Zakaria n_fadhlina@upm.edu.my Universiti Putra Malaysia Medicine Serdang Malaysia -

Co-author 4

Anim Shah animshah@upm.edu.my Universiti Putra Malaysia Medicine Serdang Malaysia -

Co-author 5

Fairol Huda Ibrahim drfairolhuda@moh.gov.my Hospital Sultan Idris Shah Nephrology Serdang Malaysia -

Co-author 6

Wan Zul Haikal Wan Zukiman wzhaikal@upm.edu.my Universiti Putra Malaysia Medicine Serdang Malaysia -

Co-author 7

Co-author 8

Co-author 9

Co-author 10

Co-author 11

Co-author 12

Co-author 13

Co-author 14

Co-author 15

Introduction

IgA nephropathy (IgAN) is the most prevalent primary glomerular disease, with highly variable clinical presentations. Nephrotic syndrome (NS) is an uncommon form, affecting only 5–15% of patients, and has been linked to more aggressive disease in some reports. However, its clinical characteristics and renal outcomes remain inconsistently described. This study aimed to analyze the clinicopathologic profile and renal prognosis of IgAN with nephrotic presentation compared to non-nephrotic IgAN.

Methods

This retrospective cohort study included 103 patients with biopsy-proven IgAN over a 10-year period. Clinical, biochemical, and histopathological parameters using Oxford MEST-C were compared between the non-nephrotic and nephrotic group. The primary outcome was 50% reduction in eGFR or end stage kidney disease (ESKD).

Results

Of the 103 patients, 32 (31%) presented with nephrotic syndrome. Nephrotic patients were younger [28 vs 32 years, p = 0.12] and had higher baseline eGFR [95 vs 77 mL/min/1.73 m², p = 0.08] but markedly higher proteinuria [5.5 vs 2.3 g/day, p < 0.001]. Histologically, nephrotic IgAN showed fewer chronic changes, including lower frequencies of M1 (62.5% vs 80.3%), S1 (75% vs 88.7%), and T1/T2 (37.5% vs 52.1%) lesions. During follow-up, the composite renal outcome occurred in 28.1% of NS versus 36.6% of non-NS cases (p = 0.40). Rates of ≥50 % eGFR decline and ESKD were numerically lower in the NS group (18.8 % vs 35.7 %; 15.6 % vs 27.1 %) but not significant (p = 0.142, p=0.252). The poor renal outcome was primarily driven by lower eGFR (OR 0.93, p < 0.001) and presence of mesangial hypercellularity (M1) was also associated with increased risk (OR 7.26, p = 0.03).

Conclusion

Nephrotic syndrome in IgA nephropathy was not independently associated with poor renal outcome. Despite heavier proteinuria, nephrotic patients had better baseline renal function and less chronic histologic injury, which likely explained their comparable outcomes. Baseline eGFR and mesangial hypercellularity (M1) were the main predictors of disease progression.

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