Patients With Combined Membranous Nephropathy and Focal Segmental Glomerulosclerosis Have Comparable Clinical and Autoantibody Profiles With Primary Membranous Nephropathy: A Retrospective Observational Study

Abstract

Patients with combined membranous nephropathy (MN) and focal segmental glomerulosclerosis (FSGS) have been reported with different clinical significance. Investigations on the possible mechanisms of the combined glomerular lesions are necessary but scarce. Twenty patients with both MN and FSGS lesions were enrolled in the study. Sixty-five patients with primary MN and 56 patients with primary FSGS were used as disease controls. Clinical data on renal biopsy and during follow-up were collected. Circulating anti-phospholipase A2 receptor (PLA2R) antibody, glomerular PLA2R expression, IgG4 deposition, and soluble urokinase receptor (suPAR) levels were detected. We found that patients with combined lesions presented with older age, less proteinuria, higher albumin, and better renal function on biopsy. These were comparable to the patients with primary MN, but differed from the patients with primary FSGS. Patients with combined lesions showed higher stages of MN, no cellular variant on FSGS classification, and more common (100.0%) tubulointerstitial injury than both primary MN and primary FSGS patients. In the patients with combined lesions, 80.0% had circulating anti-PLA2R antibody and 68.4% had IgG4 predominant deposition in glomeruli, which were comparable to primary MN. The patients with combined lesions had significantly lower urinary suPAR concentrations, than the primary FSGS patients (315.6 ± 151.0 vs 752.1 ± 633.9 pg/μmol; P = 0.002), but similar to the primary MN patients (267.9 ± 147.5 pg/μmol). We conclude that patients with combined MN and FSGS may share the same underlying pathogenesis with primary MN. The FSGS lesion might be secondary to primary MN.

FIGURE 1

Schematic illustration of the study design.

FIGURE 2

Kidney histopathological parameters of patients with combined MN and FSGS, primary MN, and primary FSGS. A, Comparison of histopathology stages of MN between MN patients with and without FSGS lesions. B, Comparison of the proportion of glomerular sclerosis between patients with combined MN and FSGS and patients with primary FSGS. C, Comparison of tubular atrophy lesions among patients with combined MN and FSGS, primary MN, and primary FSGS. D, Comparison of the interstitial infiltration lesions among the patients with combined MN and FSGS, primary MN, and primary FSGS. E, Comparison of interstitial fibrosis lesions among the patients with combined MN and FSGS, primary MN, and primary FSGS.

FIGURE 3

The detection of circulating anti-PLA2R antibody. A, Detection of positive circulating anti-PLA2R antibody in a patient with combined MN and FSGS. B, Detection of positive circulating anti-PLA2R antibody in a patient with primary MN. C, Negative result in a patient with primary FSGS.

FIGURE 4

The correlations between plasma anti-PLA2R antibody level and clinical parameters. A, The correlation between plasma anti-PLA2R antibody level and urinary protein in patients with combined MN and FSGS. B, The correlation between plasma anti-PLA2R antibody level and serum albumin in patients with combined MN and FSGS. C, The correlation between plasma anti-PLA2R antibody level and urinary protein in patients with primary MN. D, The correlation between plasma anti-PLA2R antibody level and serum albumin in patients with primary MN.

FIGURE 5

The detection of glomerular PLA2R expression (x400). A, Enhanced glomerular staining of PLA2R in a patient with combined MN and FSGS. B, Enhanced glomerular staining of PLA2R in a patient with primary MN. C, Faint glomerular staining of PLA2R in a patient with primary FSGS. D, Faint glomerular staining of PLA2R in a healthy control. E, Negative control (PBS).

FIGURE 6

The deposition of the IgG subclasses on the glomeruli of a patient with combined MN and FSGS (x400). A, Weak IgG1 staining. B, Weak IgG2 staining. C, Weak IgG3 staining. D, Strong IgG4 staining. E, Negative control (PBS).

FIGURE 7

The suPAR levels of patients with combined MN and FSGS, primary MN, and primary FSGS. A, Comparison of plasma suPAR levels. Although not statistically significant, the mean plasma suPAR levels of patients with combined lesions were lower than those with primary FSGS. Significant differences were shown between patients with primary MN and primary FSGS. B, Comparison of urinary suPAR levels. The mean urinary suPAR level in patients with combined lesions was significantly lower than those with primary FSGS, but comparable to those with primary MN.