Advanced diabetic nephropathy with nephrotic range proteinuria: a pilot study of the long-term efficacy of subcutaneous ACTH gel on proteinuria, progression of CKD, and urinary levels of VEGF and MCP-1.
Advanced diabetic nephropathy with nephrotic range proteinuria: a pilot study of the long-term efficacy of subcutaneous ACTH gel on proteinuria, progression of CKD, and urinary levels of VEGF and MCP-1.
复制标题
伴有肾病范围蛋白尿的晚期糖尿病肾病：皮下 ACTH 凝胶对蛋白尿、CKD 进展以及尿 VEGF 和 MCP-1 水平的长期疗效的初步研究。
DOI：
10.1155/2013/489869
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发表时间：
2013
影响因子：
4.3
通讯作者：
Rovin,BH
中科院分区：
文献类型：
--
作者：
Tumlin,JA;Galphin,CM;Rovin,BH
促肾上腺皮质激素（ACTH）能够通过激活足细胞中表达的黑皮质素受体（MCR）来减少非糖尿病性肾小球疾病的蛋白尿。为了确定ACTH的疗效，我们进行了一项随机，ACTH凝胶在晚期糖尿病肾病患者中的开放性先导试验研究设计23例糖尿病肾病患者随机接受每日皮下注射16或32单位的ACTH凝胶，持续6个月。（<300 mg/24小时）。探索性终点包括部分（50%减少）缓解，铬的变化，和尿细胞因子markers.ResultsAfter 6个月的ACTH凝胶治疗的百分比，8 14例（57%）患者达到了完全（n= 1）或部分（n= 7）缓解。在低剂量ACTH凝胶组（16单位）中，尿蛋白从6709 ± 953 mg/24小时降至2224 ± 489 mg/24小时（P< 0.001）。相比之下，32单位组6例患者中有2例达到部分缓解，但总蛋白尿（5324 + 751至5154 + 853 mg/24小时）没有变化。低剂量组尿VEGF从388增加到1346 pg/mg尿肌酐（P< 0.02），但高剂量组无变化。ClinTrials.gov标识符是NCT 01028287。
Background and ObjectiveAdrenocorticotropic hormone (ACTH) is able to reduce proteinuria in nondiabetic glomerulopathies through activation of melanocortin receptors (MCR) expressed in the podocyte. To determine the efficacy of ACTH, we conducted a randomized, open‐label pilot trial of ACTH gel in patients with advanced diabetic nephropathy.Study DesignTwenty‐three (23) patients with diabetic nephropathy were randomized to daily subcutaneous (SQ) injections of 16 or 32 units of ACTH gel for six months.OutcomeThe primary endpoint was the percentage of patients achieving a complete remission (<300 mg/24 hours) within 6 months. Exploratory endpoints included the percentage of partial (50% reduction) remissions, changes in Cr, and urinary cytokine markers.ResultsAfter 6 months of ACTH gel therapy, 8 of 14 (57%) patients achieved a complete (n= 1) or partial (n= 7) remission. In the low‐dose ACTH gel group (16 units), urinary protein fell from 6709 + 953 to 2224 + 489 mg/24 hrs (P< 0.001). In contrast, 2 of 6 patients in the 32‐unit group achieved partial remission, but aggregate proteinuria (5324 + 751 to 5154 + 853 mg/24 hours) did not change. Urinary VEGF increased from 388 to 1346 pg/mg urinary creatinine (P< 0.02) in the low‐dose group but remained unchanged in the high‐dose group.ConclusionACTH gel stabilizes renal function and reduces urinary protein for up to 6 months after treatment. The ClinTrials.gov identifier is NCT01028287.