title: 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.
authors.affiliation: Department of Pathology, Hôpital Necker, AP-HP, Paris, France 75015.
authors.forename: Marie-Lucile
authors.initials: ML
authors.lastname: Figuères
authors.affiliation: Department of Immunology, Hôpital Européen Georges Pompidou, AP-HP, Paris, France 75015; Cordeliers Research Center, INSERM UMRS 872, Paris, France 75006.
authors.forename: Véronique
authors.initials: V
authors.lastname: Frémeaux-Bacchi
authors.affiliation: Department of Pathology, Hôpital Necker, AP-HP, Paris, France 75015; Paris Descartes University, Paris, France 75006.
authors.forename: Marion
authors.initials: M
authors.lastname: Rabant
authors.affiliation: Department of Pathology, Hôpital Necker, AP-HP, Paris, France 75015; Paris Descartes University, Paris, France 75006.
authors.forename: Louise
authors.initials: L
authors.lastname: Galmiche
authors.affiliation: Cordeliers Research Center, INSERM UMRS 872, Paris, France 75006.
authors.forename: Maria Chiara
authors.initials: MC
authors.lastname: Marinozzi
authors.affiliation: Paris Descartes University, Paris, France 75006; Department of Nephrology, Hôpital Necker, AP-HP, Paris, France 75015.
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Grünfeld
authors.affiliation: Department of Pathology, Hôpital Necker, AP-HP, Paris, France 75015; Unité INSERM U1016, Hôpital Necker, Paris, France 75015.
authors.forename: Laure-Hélène
authors.initials: LH
authors.lastname: Noël
authors.affiliation: Paris Descartes University, Paris, France 75006; Department of Nephrology, Hôpital Necker, AP-HP, Paris, France 75015. Electronic address: aude.servais@nck.aphp.fr.
authors.forename: Aude
authors.initials: A
authors.lastname: Servais
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D005921:Glomerulonephritis / Q000473:pathology*; D015432:Glomerulonephritis, Membranoproliferative / Q000473:pathology*; D006801:Humans; D007678:Kidney Glomerulus / Q000473:pathology*; D008297:Male; D009404:Nephrotic Syndrome / Q000473:pathology*; D051437:Renal Insufficiency / Q000473:pathology*; D055815:Young Adult
keywords: C3 deposits; C3 glomerulopathy; CFHR5; Complement; Dense deposit disease; Factor I