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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.
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“A notable observation during this protocol was the prevalence of proteinuria and unique nephropathies of these patients (13).”
From Long-Term Efficacy of Leptin Replacement in Patients With Generalized Lipodystrophy (2005) · cites this paper as [13]
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Self-citationA very rare cause of acute pancreatitis: Berardinelli-Seip congenital lipodystrophy
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Metadata
- Authors
- Javor, E. D., Moran, S. A., Young, J. R., Cochran, E. K., DePaoli, A. M., Oral, E. A., Turman, M. A., Blackett, P. R., Savage, D. B., O’Rahilly, S., Balow, J. E., & Gorden, P.
- Affiliations
- National Institutes of Health (US)
- Amgen (United States) (US)
- University of Oklahoma Health Sciences Center (US)
- University of Cambridge (GB)
- Corresponding author
- Javor, Edward D.
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2004-07
- Volume
- 89
- Issue
- 7
- Pages
- 3199-3207
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2113142131
- Cited by
- 114
- References
- 38
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 5 · 2020: 6 · 2019: 8 · 2018: 8 · 2017: 4 · 2016: 5 · 2015: 10 · 2014: 8 · 2013: 3 · 2012: 5
- FWCI
- 2.90
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Nephrology › Renal Diseases and Glomerulopathies
- Health Sciences › Medicine › Nephrology › Chronic Kidney Disease and Diabetes
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
- Keywords
- generalized lipodystrophy, proteinuria, nephrotic-range proteinuria, macroalbuminuria, leptin deficiency, hyperleptinemia, focal segmental glomerulosclerosis, membranoproliferative glomerulonephritis, diabetic nephropathy, glomerular hyperfiltration, renal biopsy findings, congenital lipodystrophy, acquired lipodystrophy
- MeSH terms
- Adolescent, Adult, Aged, Biopsy, Child, Creatinine, Diabetic Nephropathies, Female, Glomerulosclerosis, Focal Segmental, Humans, Kidney, Kidney Diseases, Lipodystrophy, Male, Middle Aged, Proteinuria, Recombinant Proteins, Syndrome, Glomerulonephritis, Membranoproliferative, Leptin
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