Focal segmental glomerulosclerosis, excluding atypical lesion, is a predictor of renal outcome in patients with membranous nephropathy: a retrospective analysis of 716 cases

BACKGROUND: Focal segmental lesions (FSLs) are not uncommon in idiopathic membranous nephropathy (IMN). The reported percentage of IMN patients with focal segmental glomerulosclerosis (FSGS) lesions varies widely between studies. The objective of this study was to differentiate atypical FSL (aFSL) from typical FSGS in IMN and to analyse the clinicopathological predictors of primary outcome of IMN patients. METHODS: A total of 716 patients with biopsy-proven IMN between January 1, 2007 and December 31, 2017 were enrolled in the study. An atypical focal segmental lesion was defined as pure synechia, segmental hyperplasia of podocytes or thickening of the GBM accompanied by proliferation of the mesangial matrix, and absence of typical FSGS. The patients were divided into three groups: patients without FSL (FSL(−)), patients with typical FSGS (FSGS(+)), and patients with aFSL (aFSL(+)).The primary outcome was a 50% decline in the initial estimated glomerular filtration rate or end-stage renal disease (ESRD) incidence. Secondary outcomes included all-cause death and ESRD. RESULTS: FSGS was present in 174 patients, while aFSL was noted in 161 patients. Systolic blood pressure was higher in both aFSL(+) group and FSGS(+) groups compared with the FSL(−) group. IMN patients without FSL and with aFSL had lower serum creatinine levels than IMN patients with FSGS. Both the FSGS(+) and aFSL(+) groups had higher levels of proteinuria and lower albumin levels than the FSL(−) group. Renal tissue lesions, including tubulointerstitial fibrosis, glomerular obsolescence, and vascular sclerosis were significantly more severe in the FSGS(+) group. Cox multivariate analysis showed that older age ≥ 60 years, eGFR< 60 ml/(min·1.73m(2)), tubulointerstitial fibrosis area ≥ 15% and FSGS at biopsy were independent risk factors for the primary outcome. CONCLUSIONS: No significant difference in outcome was found between the FSL(−) and aFSL(+) groups, although the patients with aFSL had lower levels of serum albumin and eGFR, higher level of urinary protein, more severe renal lesions with proliferation of the mesangial area,tubulointerstitial fibrosis and vascular sclerosis. FSGS, excluding atypical lesions, was an independent predictor of the primary outcome.