Proteinuric nephropathy in acquired and congenital generalized lipodystrophy: Baseline characteristics and course during recombinant leptin therapy
Proteinuric nephropathy in acquired and congenital generalized lipodystrophy: Baseline characteristics and course during recombinant leptin therapy
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DOI：
10.1210/jc.2003-032140
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发表时间：
2004-07-01
影响因子：
5.8
通讯作者：
Gorden, P
中科院分区：
文献类型：
--
作者：
Javor, ED;Moran, SA;Gorden, P
泛发性脂肪营养不良的特征是脂肪组织缺失、低蛋白血症、高甘油三酯血症、胰岛素抵抗、糖尿病、肝肿大和非酒精性脂肪性肝炎。在招募接受重组瘦素治疗的患者的过程中，我们对蛋白尿的频率和严重程度感到震惊。我们评估了25例全身性脂肪营养不良患者。18例接受重组瘦素治疗，我们对15例瘦素进行了4-36个月的随访。我们跟踪了基线和随访期间的肾脏参数。肾活检按临床指征进行。基线时，25例患者中有22例(88%)有尿白蛋白排泄升高(>；30 mg/24 h)，15例(60%)有大量蛋白尿(>；300 mg/24 h)，5例(20%)有肾病症性蛋白尿(>；3500 mg/24 h)。23例(92%)肌酐清除量升高(>；125ml/分钟1.73m(2))。在接受重组瘦素治疗的15名患者中，有11名(73%)的蛋白尿减少，并伴随着高滤过的减少。四名没有改善的患者被单独讨论。肾活检发现局灶性节段性肾小球硬化4例，膜增生性肾小球肾炎2例，糖尿病肾病1例。总而言之，泛发性脂肪营养不良与蛋白尿和独特的肾脏病理有关，包括局灶节段性肾小球硬化和膜增生性肾小球肾炎。大多数接受重组瘦素治疗的患者显示出蛋白尿和高滤过的减少。
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 macro-albuminuria (>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.1.73m(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.