title: Proteinuric nephropathy in acquired and congenital generalized lipodystrophy: baseline characteristics and course during recombinant leptin therapy.
abstract: Generalized lipodystrophy is characterized by adipose tissue absence, hypoleptinemia, hypertriglyceridemia, insulin resistance, diabetes, hepatomegaly, and nonalcoholic steatohepatitis. In the course of recruiting patients for treatment with recombinant leptin, we were struck by the frequency and severity of proteinuria. We evaluated 25 patients with generalized lipodystrophy. Eighteen were treated with recombinant leptin, and we have followed 15 on leptin for 4-36 months. We followed renal parameters at baseline and during follow-up visits. Renal biopsies were performed as clinically indicated. At baseline, 22 of 25 patients (88%) had elevated urine albumin excretion (>30 mg/24 h), 15 (60%) had macroalbuminuria (>300 mg/24 h), and five (20%) had nephrotic-range proteinuria (>3500 mg/24 h). Twenty-three (92%) had elevated creatinine clearance (>125 ml/min.1.73 m(2)). Eleven of 15 patients (73%) treated with recombinant leptin exhibited reduction in proteinuria, associated with reduction of hyperfiltration. Four patients who did not improve are discussed individually. Renal biopsy findings were remarkable for focal segmental glomerulosclerosis in four patients, membranoproliferative glomerulonephritis in two patients, and diabetic nephropathy in one patient. In conclusion, generalized lipodystrophy is associated with proteinuria and unique renal pathologies, including focal segmental glomerulosclerosis and membranoproliferative glomerulonephritis. The majority treated with recombinant leptin demonstrated reduction in proteinuria and hyperfiltration.
authors.affiliation: National Institute of Diabetes and Digestive and Kidney Diseases/NIH, 10 Center Drive, Room 8D20, Bethesda, MD 20892-1770, USA. edwardj@intra.niddk.nih.gov
authors.forename: Edward D
authors.initials: ED
authors.lastname: Javor
authors.forename: Stephanie Ann
authors.initials: SA
authors.lastname: Moran
authors.forename: Janice Ryan
authors.initials: JR
authors.lastname: Young
authors.forename: Elaine K
authors.initials: EK
authors.lastname: Cochran
authors.forename: Alex M
authors.initials: AM
authors.lastname: DePaoli
authors.forename: Elif Arioglu
authors.initials: EA
authors.lastname: Oral
authors.forename: Martin A
authors.initials: MA
authors.lastname: Turman
authors.forename: Piers R
authors.initials: PR
authors.lastname: Blackett
authors.forename: David B
authors.initials: DB
authors.lastname: Savage
authors.forename: Stephen
authors.initials: S
authors.lastname: O'Rahilly
authors.forename: James E
authors.initials: JE
authors.lastname: Balow
authors.forename: Phillip
authors.initials: P
authors.lastname: Gorden
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D001706:Biopsy; D002648:Child; D003404:Creatinine / Q000097:blood / Q000652:urine; D003928:Diabetic Nephropathies / Q000150:complications / Q000473:pathology; D005260:Female; D015432:Glomerulonephritis, Membranoproliferative / Q000150:complications / Q000473:pathology; D005923:Glomerulosclerosis, Focal Segmental / Q000150:complications / Q000473:pathology; D006801:Humans; D007668:Kidney / Q000187:drug effects / Q000473:pathology; D007674:Kidney Diseases / Q000150:complications* / Q000473:pathology / Q000503:physiopathology*; D020738:Leptin / Q000627:therapeutic use*; D008060:Lipodystrophy / Q000150:complications* / Q000151:congenital* / Q000188:drug therapy / Q000473:pathology; D008297:Male; D008875:Middle Aged; D011507:Proteinuria / Q000209:etiology* / Q000378:metabolism; D011994:Recombinant Proteins / Q000627:therapeutic use; D013577:Syndrome
chemical_list: D020738:Leptin; D011994:Recombinant Proteins; D003404:Creatinine