Renal comorbidities in collapsing variant focal segmental glomerulosclerosis: more than a coincidence?

Abstract

Background Collapsing focal segmental glomerulosclerosis (FSGS) has various underlying etiologies and often leads to renal failure. The impact of biopsy-proven renal comorbidities in promoting collapsing glomerulopathy (CG) has not been systematically evaluated in large comparative studies. Those data are reported here. Methods Biopsies with the initial diagnosis of CG in native (n = 321) or transplant kidneys (n = 30) were identified in the University of North Carolina nephropathology database (1 January 2011 to 1 January 2016). Two cohorts were defined: ‘sole’ CG without and ‘accompanied’ CG with significant morphologic renal comorbidities. Tip-variant FSGS (T-FSGS) and time-matched biopsies served as control cohorts for comparative analyses. Results CG was significantly more common in native (4.4%) and transplant biopsies (4.1%) compared with T-FSGS (0.7 and <0.1%, respectively, difference versus CG P < 0.01). ‘Associated’ disease was significantly more common in CG (native: 151/321; 47.0%, transplant: 21/30; 70%, P < 0.05) versus T-FSGS (native: 14/51; 27.5%, transplant: exceptional; all differences versus CG P < 0.05). In native biopsies with ‘accompanied’ CG but not in control groups, stenosing vasculopathies including thrombotic microangiopathies were significantly more prevalent (P < 0.01). In transplants, the high incidence of ‘accompanied’ CG was linked to de novo diseases, mainly rejection and vascular injury. In native kidneys, membranous glomerulopathies were prevalent in ‘accompanied’ T-FSGS (36%) and CG (14%) (difference versus time-matched controls P < 0.01 and P < 0.05, respectively); they were uncommon in transplants. Conclusions CG but not T-FSGS shows a high rate of comorbidities, with prominent vasculopathies presumably driving ‘ischemic’ CG-specific glomerular injury and also the disease course. These findings facilitate future studies into therapy, prognosis and reversibility of ‘accompanied’ CG.