title: Glomerular lesions in patients with sickle cell disease.
abstract: Sickle cell disease (SCD) is an increasing cause of chronic kidney disease, but the spectrum of glomerular lesions and their underlying mechanisms remain poorly described. We reviewed 18 renal biopsies from patients with SCD and glomerular involvement and studied the expression of hypoxic markers in the biopsy specimens. Four histopathologic variants were distinguished: focal segmental glomerulosclerosis (FSGS) (39%), membranoproliferative glomerulonephritis (28%), thrombotic microangiopathy glomerulopathy (17%), and specific sickle cell disease glomerulopathy (17%). Chronic organ damage and history of acute chest syndrome were associated with the occurrence of SCD glomerulopathy. All patients exhibited macroalbuminuria but only 6 patients displayed impaired renal function. SCD was not associated with a specific FSGS histologic variant. Long-term follow-up analysis revealed that 50% of patients exhibited chronic kidney disease. Regardless of the histologic variants, immunohistochemistry did not reveal a specific induction of hypoxic markers (inducible nitric oxide synthase [iNOS], nitrotyrosine, hypoxia-inducible factor [HIF]-1 alpha) at the time of renal biopsy. This large study shows that a wide spectrum of glomerular lesions is associated with SCD. Whatever lesions are observed, the renal prognosis is poor, and early renoprotective treatment is necessary. Hypoxic state does not seem to play a key role in the progression of glomerular lesions, but its potential role at an early stage of glomerular injury requires further investigation.
authors.affiliation: From Internal Medicine Unit (GW, SS, OL), Pathology Department (SF), and Nephrology and Renal Transplantation Department (AD), APHP, Hôpital Kremlin Bicêtre, Université Paris 11, Le Kremlin Bicêtre; Sickle Cell Disease Center (FG) and Internal Medicine Unit (BG), APHP, Hôpital Henri Mondor, Université Paris 12, Créteil; Nephrology and Renal Transplantation Department (PL, VA), APHP, Hôpital Henri Mondor, and Institut Francilien de recherche en Néphrologie et Transplantation (IFRNT), INSERM U 955, Université Paris 12, Créteil; Nephrology Department (XB), Hôpital de Montreuil, Montreuil; Nephrology Department (TU), APHP, Hôpital Trousseau, UPMC Université Paris 06, Paris; Pediatric Nephrology Department (PN), APHP, Hôpital Necker-Enfants Malades, Université Paris Descartes, Paris; Nephrology Department (PR), APHP, Hôpital Tenon, UPMC Université Paris 06, Paris; France.
authors.forename: Gwenola
authors.initials: G
authors.lastname: Maigne
authors.forename: Sophie
authors.initials: S
authors.lastname: Ferlicot
authors.forename: Frederic
authors.initials: F
authors.lastname: Galacteros
authors.forename: Xavier
authors.initials: X
authors.lastname: Belenfant
authors.forename: Tim
authors.initials: T
authors.lastname: Ulinski
authors.forename: Patrick
authors.initials: P
authors.lastname: Niaudet
authors.forename: Pierre
authors.initials: P
authors.lastname: Ronco
authors.forename: Bertrand
authors.initials: B
authors.lastname: Godeau
authors.forename: Antoine
authors.initials: A
authors.lastname: Durrbach
authors.forename: Sabrinel
authors.initials: S
authors.lastname: Sahali
authors.forename: Philippe
authors.initials: P
authors.lastname: Lang
authors.forename: Olivier
authors.initials: O
authors.lastname: Lambotte
authors.forename: Vincent
authors.initials: V
authors.lastname: Audard
mesh_terms: D000293:Adolescent; D000328:Adult; D000755:Anemia, Sickle Cell / Q000150:complications*; D002648:Child; D005260:Female; D015432:Glomerulonephritis, Membranoproliferative / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology; D006801:Humans; D008297:Male; D057049:Thrombotic Microangiopathies / Q000453:epidemiology / Q000209:etiology* / Q000473:pathology