Study Describes Clinical Features, Prognosis of Patients with IgAN, Nephrotic Syndrome

New research is shedding light on notable differences in the clinicopathological characteristics and long-term prognosis of patients with IgA nephropathy (IgAN) and nephrotic syndrome (NS) across different pathological phenotypes.1

Study findings suggest differences in the clinical features and renal prognosis of patients with IgAN-NS and minimal change disease (MCD), membranous nephropathy (MN), membranoproliferative glomerulonephritis (IgAN-MPGN), and mesangial proliferative glomerulonephritis (IgAN-MsPGN).1

A leading cause of glomerulonephritis and renal failure, IgAN is a gradually progressing disease that results in hematuria, proteinuria, and renal insufficiency, with between 20% and 50% of affected patients developing end-stage renal disease (ESRD) within 20 years of diagnosis.2 NS occurs in 5%-15% of patients with IgAN, but the clinical features and renal prognosis for patients with both NS and IgAN across different kidney pathologies are not well understood.1

“Following the publication of the 2021 KDIGO guideline on glomerulonephritis, the significance of further dividing pathological subtypes in patients with NS-IgAN becomes clear,” Qiong Wen, MD, PhD, associate chief physician in the department of nephrology at Sun Yat-sen University in China, and colleagues wrote.1 “Our cohort is the first to analyze differences in clinical presentations, pathological features, therapeutic response, and renal outcomes between patients with NS-IgAN and various renal biopsy findings.”

In the study, investigators retrospectively screened patients with biopsy-proven primary IgAN at the First Affiliated Hospital of Sun Yat-sen University between January 2001 and December 2021. Those with a history of systemic disease; secondary IgAN; > 8 glomeruli under light microscopy; and missing or poor-quality electron microscopy results were excluded.1

Of 4963 patients with primary IgAN, 276 (5.6%) also had NS, defined as the presence of massive proteinuria (24-hour urinary protein > 3.5 g) and hypoalbuminemia (ALB < 30 g/L) with or without edema and hyperlipidemia. In total, 207 of these patients met the study’s inclusion and exclusion criteria and were included in the analysis.1

Investigators divided these patients into 4 categories based on their light microscopy, immunofluorescence, and electron microscopy findings:

• IgAN-MCD (n = 49)
• IgAN-MN (n = 7)
• IgAN-MPGN (n = 1)
• IgAN-MsPGN (n = 150)

The renal endpoint was a 50% decrease in estimated glomerular filtration rate (eGFR) or progression to ESRD, defined as eGFR < 15 ml/min per 1.73 m2.1

Among the entire study cohort, the mean age was 31.13 ± 12.84 years and 53.1% of patients were male. Compared to the IgAN-MsPGN group, investigators noted the IgAN-MCD group consisted of more males, had a younger average age, lower blood pressure, a lower prevalence of hematuria, and lower serum albumin and creatinine levels, whereas the IgAN-MN group was characterized by an older average age and lower serum creatinine levels.1

Additionally, they pointed out patients with IgAN-MCD exhibited the least severe pathological features compared to those with IgAN-MsPGN, noting the incidence of S1 was significantly greater in patients with IgAN-MsPGN than in those with IgAN-MN.1

Investigators did not observe any significant differences in the proportion of patients receiving ACEis, ARBs, or immunosuppressants between the IgAN-MsPGN, IgAN-MN, and IgAN-MCD groups. Patients with IgAN-MCD all received oral corticosteroid therapy, while 31.4% of patients with IgAN-MsPGN and 28.6% with IgAN-MN received corticosteroid pulse therapy for managing crescentic lesions. Additionally, 2 patients with IgAN-MsPGN received the modified POZZI regimen.1

Among the cohort, 133 patients were followed for an average duration of 52.07 ± 44.04 months, during which time 37 (27.8%) patients reached the renal endpoint. Investigators noted the IgAN-MCD group showed a greater rate of proteinuria remission and a better renal prognosis than the IgAN-MsPGN group.1

Multivariate COX regression analysis revealed crescentic lesions (hazard ratio [HR], 5.71; P = .025) were a significant independent risk factor for a poorer renal prognosis in NS-IgAN patients, whereas eGFR (HR, 0.98; P = 0.010) and ACEi/ARB treatments (HR, 0.31; P = .005) were protective factors. Kaplan–Meier curves indicated patients with NS-IgAN who did not receive ACEi/ARB had a worse renal prognosis than those who did.1

“The findings strongly support the presence of significant differences in clinical-pathological characteristics, efficacy of steroid treatment, and long-term prognosis among patients with NS-IgAN across different pathological types,” investigators concluded.1 “Consequently, further delineation of the pathological features within the NS-IgAN patient population holds substantial value for guiding therapeutic decisions and enhancing prognostic outcomes.”

References

1. Tan L, Jin LH, Wang YQ, et al. Clinical features, pathological characteristics, and prognosis of patients with IgA nephropathy complicated with nephrotic syndrome. Sci Rep. https://doi.org/10.1038/s41598-025-86081-0
2. Rout P, Limaiem F, Hashmi MF. IgA Nephropathy (Berger Disease). StatPearls. April 22, 2024. Accessed January 17, 2025. https://www.ncbi.nlm.nih.gov/books/NBK538214/