Effects of Metreleptin on Proteinuria in Patients With Lipodystrophy

Patients with lipodystrophy have high prevalence of proteinuria.

To assess kidney disease in patients with generalized (GLD) vs partial lipodystrophy (PLD), and the effects of metreleptin on proteinuria in patients with lipodystrophy.

Prospective, open-label studies of metreleptin treatment in patients with GLD and PLD at the National Institutes of Health.

The 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.

At baseline, patients with GLD had significantly greater albuminuria, proteinuria, eGFR, and CrCl compared with 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.

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 vs PLD but did not change with metreleptin.