Prognostic factors affecting long-term outcomes in patients with concurrent IgA nephropathy and membranous nephropathy

Abstract

Background: The incidence of concurrent immunoglobulin A nephropathy and membranous nephropathy (cIgAN/MN) is low and rarely reported, and the prognosis of patients with cIgAN/MN remains unclear. This study was designed to compare the clinical and prognostic characteristics of cIgAN/MN with IgAN and MN and to identify crucial factors influencing the outcomes of patients with cIgAN/MN.

Methods: We included biopsy-proven cIgAN/MN patients between December 2012 and December 2020 at Xijing Hospital. In the same period, propensity score matching was employed to select an equal number of IgAN and MN patients according to the following criteria: age, sex, and follow-up time. The primary endpoint was defined as a composite of eGFR decline ≥30 %, end-stage renal disease, or death. The patient survival rate was examined using Kaplan-Meier survival curves. Univariate and multivariate Cox regression analysis models were utilized to identify the risk factors affecting renal prognosis.

Results: A total of 135 patients were finally included in this study and 35 (25.9 %) reached the primary endpoint. The median follow-up time of cIgAN/MN was 45.9 (24.0, 72.0) months. Compared to the IgAN group, the cIgAN/MN group exhibited a lower cumulative incidence rate of composite renal endpoints (P = 0.044), while no significant difference was found between MN and cIgAN/MN patients (P = 0.211). Univariate Cox analysis revealed that mean arterial pressure, serum potassium, blood urea nitrogen, serum IgA, segmental glomerulosclerosis (S1), and MN staging were associated with an increased risk of renal composite endpoints. The multivariate Cox regression analysis of clinical variables plus histological lesion scoring demonstrated that potassium (HR = 14.350, 95 % CI 2.637-78.090, P = 0.002), serum IgA (HR = 1.870, 95 % CI 1.109-3.153, P = 0.019), and S1 (HR = 11.965, 95 % CI 2.166-66.105, P = 0.004) were independent risk factors influencing renal outcomes in cIgAN/MN patients.

Conclusion: The prognosis of cIgAN/MN patients may exhibit an intermediate pattern between IgAN and MN, leaning towards being more similar to MN in certain aspects. Within the cIgAN/MN cohort, potassium, and serum IgA may be more predictive of rapid progression of renal endpoints, and S1 may indicate a more aggressive disease course.

Keywords: Chronic kidney disease; Concurrent IgAN and MN; Prognostic model; Risk factor.

Fig. 1

Inclusion flowchart. IgAN, immunoglobulin A nephropathy. MN, membranous nephropathy. cIgAN/MN, concurrent IgAN and MN. PSM, propensity score matching.

Fig. 2

Kidney biopsy pathological results of cIgAN/MN. (A, B) Light microscopy image showing thickened glomerular basement membranes, segmental glomerulosclerosis, spike-like projection, and fuchsin deposition in mesangial and subepithelial regions (arrows; periodic acid-silver methenamine, 400 × and 1000 × ). (C) Immunofluorescence staining for IgA (400 × ). (D) Immunofluorescence staining for IgG (400 × ). (E) Immunofluorescence staining for C3 (400 × ). (F) Electron microscopy showed thickening of glomerular basement membrane (600–700 nm), deposition of electron-dense material in subepithelial, intra-basement membrane and mesangial areas, and extensive fusion of foot processes (4000 × ).

Fig. 3

Kaplan-Meier survival curves for free of combined events of different groups. (A) Cumulative poor event-free renal survival rate. (B) Cumulative incidence of urinary protein PR or CR. IgAN, immunoglobulin A nephropathy. MN, membranous nephropathy. cIgAN/MN, concurrent IgAN and MN.

Fig. 4

Survival curve of cIgAN/MN patients under different factors. (A) MAP, mean arterial pressure. (B) K, potassium. (C) serum IgA. (D) S1, segmental glomerulosclerosis.

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