Clinical, Prognostic Factors Affecting Concurrent IgAN and Membranous Nephropathy Outcomes

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Findings from a recent study are detailing the clinical and prognostic characteristics of concurrent immunoglobulin A nephropathy (IgAN) and membranous nephropathy with those of IgAN and membranous nephropathy alone, calling attention to important distinctions in clinical manifestations and renal prognoses between the diseases.

Patients with concurrent IgAN and membranous nephropathy had pathological types and clinical manifestations more similar to patients with membranous nephropathy than those with IgAN, with further analysis suggesting blood pressure, serum IgA, potassium, and segmental glomerulosclerosis may be predictive of the rapid progression of renal endpoints in this patient population.¹

“Previous studies on [concurrent IgAN and membranous nephropathy] have mainly focused on the description of renal pathology and case reports, and they have shown that the combination of these two pathological processes does not seem to result in a more severe clinical presentation for patients,” wrote investigators.¹ “However, there is still a lack of systematic exploration of the prognosis and risk factors of the disease as well as long-term clinical studies on the prognosis of patients with [concurrent IgAN and membranous nephropathy].”

IgAN and membranous nephropathy are predominant types of glomerulonephritis that are both immune complex-mediated but each has a distinct pathogenesis. Although differentiation between the conditions is necessary for providing appropriate treatment and management strategies, understanding how to best approach concurrent cases is of equal importance but is currently underinformed, leading to low incidence and infrequent reporting.²

To compare the clinical and prognostic characteristics of concurrent IgAN and membranous nephropathy with each individual disease, Shiren Sun, PhD, professor in the department of nephrology at Fourth Military Medical University in China, and a team of investigators retrospectively reviewed pathological and clinical data for patients at Xijing Hospital from December 2012 to December 2020. Propensity score matching was employed to select an equal number of patients with IgAN and membranous nephropathy according to age, sex, and follow-up time.¹

Investigators defined the primary endpoint as a composite of estimated glomerular filtration rate (eGFR) decline ≥30 %, end-stage renal disease (ESRD), or death. Patients with a follow-up duration exceeding 6 months were considered successful cases. During this period, information about general clinical symptoms, medication history, renal function, and urine analysis was collected. Follow-up also included assessment of survival status, progression to ESRD or dialysis, and laboratory examination data.¹

Among 3682 renal biopsy patients, 52 individuals with concurrent IgAN and membranous nephropathy were identified for inclusion and 45 were subsequently enrolled in the study. Additionally, 45 matched controls were identified from 993 patients with primary IgAN and 809 patients with primary membranous nephropathy. Finally, 135 patients from the 3 groups were included in the analysis.¹

Investigators pointed out compared to IgAN patients, those with concurrent IgAN and membranous nephropathy exhibited significantly greater levels of 24h urine total protein (UTP) and lower albumin (ALB), serum creatinine, and blood urea nitrogen (BUN) levels. However, there were no significant differences in other baseline parameters across the concurrent and primary membranous nephropathy groups.¹

Among the cohort, 35 (25.9%) patients reached the primary endpoint. The median follow-up period was 45.9 months in the concurrent IgAN and membranous nephropathy group and 11 (24.4 %) patients experienced renal composite endpoints. Upon analysis, the estimated mean times of renal survival in the concurrent, primary IgAN, and primary membranous nephropathy groups were 76.7 (95% Confidence interval [CI], 66.8-86.6), 63.1 (95% CI, 53.1-73.1), and 85.0 (95% CI, 77.0-93.1) months, respectively.¹

Compared to those with IgAN alone, concurrent IgAN and membranous nephropathy patients had a lower cumulative incidence rate of composite renal endpoints (P = .044), although there was no significant difference between concurrent IgAN and membranous nephropathy compared to primary membranous nephropathy patients (P = .211).¹

Further analysis revealed mean arterial pressure (P = .033), BUN (P = .047), potassium (P = .002), serum IgA (P = .036), segmental glomerulosclerosis (P = .024), and stage III membranous nephropathy (P = .001) were associated with renal composite endpoints.¹

Investigators noted after accounting for clinical variables and histological lesion scoring, potassium (Hazard ratio [HR], 14.350; 95% CI, 2.637-78.090; P = .002), serum IgA (HR, 1.870; 95% CI, 1.109-3.153; P = .019), and segmental glomerulosclerosis (HR, 11.965; 95% CI, 2.166-66.105; P = .004) were independent risk factors influencing renal outcomes in concurrent IgAN and membranous nephropathy patients.¹

“During the long-term clinical follow-up of the cIgAN/MN cohort, we observed that blood pressure, serum IgA, potassium, and segmental glomerulosclerosis may be predictive of the rapid progression of renal endpoints. These findings have the potential to improve clinical decision-making in medical practice, while well-designed studies are warranted for further verification,” investigators concluded.¹

References:

1. Qin Y, Yu Z, Wu H, et al. Prognostic factors affecting long-term outcomes in patients with concurrent IgA nephropathy and membranous nephropathy. Heliyon. 2023;10(1):e23436. doi:10.1016/j.heliyon.2023.e23436
2. He JW, Cui DF, Zhou XJ, et al. Concurrent IgA Nephropathy and Membranous Nephropathy, Is It an Overlap Syndrome? Front. Immunol. https://doi.org/10.3389/fimmu.2022.846323