ISSN 1470-3947 (print) | ISSN 1479-6848 (online)

Endocrine Abstracts (2019) 63 P214 | DOI: 10.1530/endoabs.63.P214

Peroxisome proliferator activated receptor gamma mutation responsible for partial lipodystrophy with end stage renal disease: pharmacokinetics of metreleptine during hemodialysis: Clinical case report

Françoise Archambeaud1, Pauline Vital1, Sophie Galinat1, Anne Drutel1, Camille Plas1, Marie Christine Vantyghem2 & Corinne Vigouroux3

1de Medecine B Endocrinologie CHU Dupuytren 87042, Limoges, France; 2Service Endocrinologie Metabolisme Hopital C Huriez CHU Lille 59037, Lille, France; 3Hopital Saint Antoine 75571, Paris, France.

Lipodystrophy is a rare disorder characterised by loss of adipose tissue, severe insulin resistance, diabetes, hypertriglyceridemia, hepatic steatosis with hypoleptinemia. Renal complications are also present but end stage renal disease is less frequent in partial lipodystrophy. We report efficacy and pharmacokinetics of metreleptine during hemodialysis in one case of partial lipodystrophy. A caucasian female presented with acute pancreatitis, major hypertriglyceridemia (25 g/l), and diabetes at the age of 21 years. She was non- obese (body mass index BMI:26) but has hirsutism, acanthosis nigricans, muscle hypertrophy and absence of subcutaneous fat on the limbs with facial sparing. She has severe hypertension, hepatosplenomegaly and renal failure (creatinin clearance 25 ml/min). 15 years later, patient developped proteinuria (10 g/l) with end stage renal disease requiring hemodialysis. She was treated by insulin delivered by external pump (300 ui/day). Diagnosis of partial lipodystrophy was made: plasma leptine level (immunoassay ELISA) was 6.89 μg/l. (for BMI 27, Normal: 37.5) A mutation of peroxisome proliferator activated receptor was identified (G 211E). Metreleptine was started at the dose of 0.04 mg/kg three time per week, after every hemodialysis achievement. Leptin plasma level were mesured at time 0 before injection of metreleptine and +1h, +2h, +3h, +4h, +5h, +6h, +8h, +10h, +12h, +24h+36 hafter. Result showed a rise with normalisation of leptine and return to baseline values by 36 h after the injection. Although, the regimen of metreleptine was increased at 0.08 mg/kg three times per week then plasma leptine level stayed in the normal range during 48 h. In addition patient developped for the first time hypoglycemias and the regimen of insulin was dramatically reduced to 90 ui/day, triglycerides were 3.6 g/l and proteinuria g/l (urinary sample).

This case report confirm the efficacy of metreleptine in partial lipodystrophy. We agree that in case of renal failure, plasma leptine level are modified.We analysed for the first time phamacokinetic profils of metreleptine in case of end renal stage disease and after hemodialysis: our results show a prolonged half life of metreleptine. We suggest in this condition, the delivrance of metreleptine at normal regimen but only three time/week after hemodialysis achievement.