Ho Lim Lee1, Meryl A Waldman2, Sungyoung Auh3, James E Balow2, Elaine K Cochran1, Phillip Gorden1, Rebecca J Brown1. 1. Diabetes, Endocrinology, and Obesity Branch; National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK); National Institutes of Health (NIH); Bethesda, MD. 2. Kidney Diseases Branch, NIDDK, NIH, Bethesda, MD. 3. Office of the Clinical Director, NIDDK, NIH, Bethesda, MD.
Abstract
CONTEXT: Patients with lipodystrophy have high prevalence of proteinuria. OBJECTIVE: To assess kidney disease in patients with generalized (GLD) versus partial lipodystrophy (PLD), and effects metreleptin on proteinuria in patients with lipodystrophy. DESIGN/SETTING/PATIENTS/INTERVENTION: Prospective, open-label studies of metreleptin treatment in patients with GLD and PLD at the National Institutes of Health, Bethesda, MD. OUTCOME MEASURES: 24-hour urinary albumin and protein excretion rates, estimated glomerular filtration rate (eGFR), and creatinine clearance (CrCl) were measured at baseline and during up to 24 months of metreleptin treatment. Patients with increases in medications affecting outcome measures were excluded. RESULTS: At baseline, patients with GLD had significantly greater albuminuria, proteinuria, eGFR, and CrCl compared to patients with PLD. CrCl was above the normal range in 69% of patients with GLD, and 39% with PLD (P=0.02). With up to 24 months of metreleptin treatment, there were significant reductions in albuminuria and proteinuria in patients with GLD, but not in those with PLD. No changes in eGFR or CrCl were observed in patients with GLD or PLD during metreleptin treatment. CONCLUSIONS: Patients with GLD had significantly greater proteinuria than those with PLD, which improved with metreleptin treatment. The mechanisms leading to proteinuria in lipodystrophy and improvements in proteinuria with metreleptin are not clear. Hyperfiltration was also more common in GLD versus PLD but did not change with metreleptin.
CONTEXT: Patients with lipodystrophy have high prevalence of proteinuria. OBJECTIVE: To assess kidney disease in patients with generalized (GLD) versus partial lipodystrophy (PLD), and effects metreleptin on proteinuria in patients with lipodystrophy. DESIGN/SETTING/PATIENTS/INTERVENTION: Prospective, open-label studies of metreleptin treatment in patients with GLD and PLD at the National Institutes of Health, Bethesda, MD. OUTCOME MEASURES: 24-hour urinary albumin and protein excretion rates, estimated glomerular filtration rate (eGFR), and creatinine clearance (CrCl) were measured at baseline and during up to 24 months of metreleptin treatment. Patients with increases in medications affecting outcome measures were excluded. RESULTS: At baseline, patients with GLD had significantly greater albuminuria, proteinuria, eGFR, and CrCl compared to patients with PLD. CrCl was above the normal range in 69% of patients with GLD, and 39% with PLD (P=0.02). With up to 24 months of metreleptin treatment, there were significant reductions in albuminuria and proteinuria in patients with GLD, but not in those with PLD. No changes in eGFR or CrCl were observed in patients with GLD or PLD during metreleptin treatment. CONCLUSIONS:Patients with GLD had significantly greater proteinuria than those with PLD, which improved with metreleptin treatment. The mechanisms leading to proteinuria in lipodystrophy and improvements in proteinuria with metreleptin are not clear. Hyperfiltration was also more common in GLD versus PLD but did not change with metreleptin.
Authors: David B Savage; Peter R Murgatroyd; V Krishna Chatterjee; Stephen O'Rahilly Journal: J Clin Endocrinol Metab Date: 2004-12-21 Impact factor: 5.958
Authors: Kitt Falk Petersen; Elif Arioglu Oral; Sylvie Dufour; Douglas Befroy; Charlotte Ariyan; Chunli Yu; Gary W Cline; Alex M DePaoli; Simeon I Taylor; Phillip Gorden; Gerald I Shulman Journal: J Clin Invest Date: 2002-05 Impact factor: 14.808
Authors: Edward D Javor; Stephanie Ann Moran; Janice Ryan Young; Elaine K Cochran; Alex M DePaoli; Elif Arioglu Oral; Martin A Turman; Piers R Blackett; David B Savage; Stephen O'Rahilly; James E Balow; Phillip Gorden Journal: J Clin Endocrinol Metab Date: 2004-07 Impact factor: 5.958