D'Alessandri-Silva Cynthia, Carpenter Melinda, Ayoob Rose, Barcia John, Chishti Aftab, Constantinescu Alex, Dell Katherine M, Goodwin Julie, Hashmat Shireen, Iragorri Sandra, Kaspar Cristin, Mason Sherene, Misurac Jason M, Muff-Luett Melissa, Sethna Christine, Shah Shweta, Weng Patricia, Greenbaum Larry A, Mahan John D
Division of Nephrology, Connecticut Children's Medical Center, Hartford, CT, United States.
Department of Pediatrics, University of Connecticut Health Center, Farmington, CT, United States.
Front Pediatr. 2020 Jan 21;7:550. doi: 10.3389/fped.2019.00550. eCollection 2019.
Congenital or primary nephrogenic diabetes insipidus (NDI) is a rare genetic disorder that severely impairs renal concentrating ability, resulting in massive polyuria. There is limited information about prognosis or evidence guiding the management of these patients, either in the high-risk period after diagnosis, or long-term. We describe the clinical presentation, genetic etiology, treatment and renal outcomes in a large group of children <21 years with NDI. A multi-center retrospective chart review. We report on 66 subjects from 16 centers. They were mainly male (89%) and white (67%). Median age at diagnosis was 4.2 months interquartile range (IQR 1.1, 9.8). A desmopressin acetate loading test was administered to 46% of children at a median age of 4.8 months (IQR 2.8, 7.6); only 15% had a water restriction test. Genetic testing or a known family history was present in 70% of the patients; out of those genetically tested, 89 and 11% had mutations in and , respectively. No positive family history or genetic testing was available for 30%. The most common treatments were thiazide diuretics (74%), potassium-sparing diuretics (67%) and non-steroidal anti-inflammatory drugs (42%). At the time of first treatment, 70 and 71% of children were below -2 standard deviations (SD) for weight and height, respectively. At last follow-up, median age was 72.3 months (IQR 40.9, 137.2) and the percentage below -2 SD improved to 29% and 38% for weight and height, respectively. Adverse outcomes included inpatient hospitalizations (61%), urologic complications (37%), and chronic kidney disease (CKD) stage 2 or higher in 23%. We found the majority of patients were treated with thiazides with either a potassium sparing diuretic and/or NSAIDs. Hospitalizations, urologic complications, short stature, and CKD were common. Prospective trials to evaluate different treatment strategies are needed to attempt to improve outcomes.
先天性或原发性肾性尿崩症（NDI）是一种罕见的遗传性疾病，会严重损害肾脏的浓缩功能，导致大量多尿。无论是在诊断后的高危期还是长期，关于这些患者的预后信息或指导治疗的证据都很有限。我们描述了一大组21岁以下NDI儿童的临床表现、遗传病因、治疗方法和肾脏转归。这是一项多中心回顾性病历审查。我们报告了来自16个中心的66名受试者。他们主要为男性（89%）和白人（67%）。诊断时的中位年龄为4.2个月，四分位间距（IQR）为1.1至9.8个月。46%的儿童在中位年龄4.8个月（IQR 2.8，7.6）时接受了醋酸去氨加压素负荷试验；只有15%的儿童进行了禁水试验。70%的患者进行了基因检测或有已知家族史；在接受基因检测的患者中，分别有89%和11%在[相关基因名称1]和[相关基因名称2]中存在突变。30%的患者没有阳性家族史或基因检测结果。最常用的治疗方法是噻嗪类利尿剂（74%）、保钾利尿剂（67%）和非甾体抗炎药（42%）。在首次治疗时，70%和71%的儿童体重和身高分别低于-2标准差（SD）。在最后一次随访时，中位年龄为72.3个月（IQR 40.9，137.2），体重和身高低于-2 SD的百分比分别改善至29%和38%。不良转归包括住院治疗（61%）、泌尿系统并发症（37%）以及慢性肾脏病（CKD）2期或更高分期（23%）。我们发现大多数患者接受了噻嗪类药物治疗，并联合使用保钾利尿剂和/或非甾体抗炎药。住院治疗、泌尿系统并发症、身材矮小和CKD很常见。需要进行前瞻性试验来评估不同的治疗策略，以试图改善转归。
