Heterogeneous histologic and clinical evolution in 3 cases of dense deposit disease with long-term follow-up

Abstract

Dense deposit disease is characterized by dense deposits in the glomerular and tubular basement membranes. We report 3 cases with long-term follow-up differing in histologic pattern and clinical evolution. Clinical and histologic data were collected between 1976 and 2012. Age at the first manifestations was 6, 11, and 23 years, respectively. They included proteinuria (patient 1) and nephrotic syndrome (patients 2 and 3); renal function was normal in all cases. Two patients (1 and 3) had low complement component 3 (C3) levels. All patients had C3 nephritic factor. Genetic analysis revealed a rare variant of the factor I gene (patient 1) and a heterozygous mutation in complement factor H-related 5 gene (patient 2). Patient 1 underwent 3 biopsies during her 38 years of follow-up. Thickening of the capillary walls of the glomerular and tubular basement membranes was observed, with mild mesangial proliferation and progressive C3 and complement membrane attack complex mesangial deposits. However, renal function remained normal. Patient 2 also underwent 3 biopsies (22 years of follow-up), revealing a gradual decrease in C3 deposition and mesangial cell proliferation. He presented mild renal insufficiency. Patient 3 underwent 2 biopsies, which displayed unusual bulky membranous deposits, confirmed by electron microscopy, with no mesangial cell proliferation and little C3 and complement membrane attack complex deposits. Kidney function remained normal. These 3 cases of dense deposit disease differed in histologic pattern evolution: accumulation of C3 deposits, decrease in C3 deposits and proliferation, and isolated dense deposits. The histologic factors involved in clinical progression remain to be identified.

Keywords: C3 deposits; C3 glomerulopathy; CFHR5; Complement; Dense deposit disease; Factor I.