title: Cyclosporin therapy in patients with Alport syndrome.
abstract: Alport syndrome (AS) is a hereditary disorder of type IV collagen characterized by the association of progressive hematuric nephritis and sensorineural hearing loss. An increase in proteinuria is linked with progressive renal failure. Preliminary data have shown that cyclosporin therapy reduces proteinuria, thereby suggesting that it may also slow the progression of AS nephropathy. We treated nine AS patients manifesting proteinuria >1 g/m(2)/day and a glomerular filtration rate (GFR) >50 ml/min/1.73 m(2) with cyclosporin for at least 6 months. At the end of this 6-month period, mean proteinuria had decreased from 2+/-1.06 to 0.65+/-0.73 g/day, and mean albuminemia had increased from 29+/-5.2 to 35+/-6.5 g/l. Mean inulin clearance had decreased from 102+/-29 to 74+/-16.3 ml/min/1.73 m(2). Cyclosporin treatment was stopped in four patients because of inefficacy or adverse effects and continued in the remaining five patients for an additional 14-42 months. At the end of this second treatment period, control renal biopsies revealed significant lesions of cyclosporin nephrotoxicity in three patients. Based on these results we conclude that while cyclosporin therapy can decrease proteinuria in most patients with AS, it may be associated with nephrotoxicity, thereby precluding its long-term use.
authors.affiliation: Service de Néphrologie Pédiatrique, Hôpital Necker-Enfants Malades, 149 rue de sèvres, 75743, Paris Cedex 15, France.
authors.forename: Marina
authors.initials: M
authors.lastname: Charbit
authors.forename: Marie-Claire
authors.initials: MC
authors.lastname: Gubler
authors.forename: Michèle
authors.initials: M
authors.lastname: Dechaux
authors.forename: Marie-France
authors.initials: MF
authors.lastname: Gagnadoux
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Grünfeld
authors.forename: Patrick
authors.initials: P
authors.lastname: Niaudet
mesh_terms: D000293:Adolescent; D000328:Adult; D001706:Biopsy; D002648:Child; D003404:Creatinine / Q000097:blood; D016572:Cyclosporine / Q000009:adverse effects / Q000627:therapeutic use*; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects / Q000502:physiology; D006801:Humans; D007166:Immunosuppressive Agents / Q000009:adverse effects / Q000627:therapeutic use*; D007444:Inulin / Q000097:blood; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007676:Kidney Failure, Chronic / Q000209:etiology; D008297:Male; D009394:Nephritis, Hereditary / Q000188:drug therapy* / Q000503:physiopathology; D011507:Proteinuria / Q000150:complications / Q000517:prevention & control; D016896:Treatment Outcome
chemical_list: D007166:Immunosuppressive Agents; D016572:Cyclosporine; D007444:Inulin; D003404:Creatinine