不同尿钙水平的Gitelman综合征患者临床特点比较

目的观察不同尿钙水平Gitelman综合征(GS)患者的临床特点,探讨尿钙在GS疾病临床分型中的价值。方法收集2016—2018年来自中国国家罕见病注册系统(NRSC)、在北京协和医院行SLC12A3基因检测诊断为GS患者的临床资料,分析其尿钙特点,比较不同尿钙水平患者的临床和实验室检查指标。氢氯噻嗪试验按照标准操作流程进行,测定患者基线和用药后3 h内氯离子排泄分数改变量的最大值(ΔFECl)。结果共有83例GS患者被纳入研究,其中低尿钙患者53例(63.86%)。低尿钙组尿钙/肌酐比明显低于非低尿钙组[(0.085±0.058)mmol/mmol比(0.471±0.284)mmol/mmol,t=7.349,P<0.001]。两组患者在年龄、性别、估算肾小球滤过率、血压、血尿电解质水平、代谢性碱中毒方面差异均无统计学意义。低尿钙组患者乏力(χ2=4.595,P=0.032)及多尿(χ2=5.778,P=0.016)发生比例低于非低尿钙组,两组患者在其他临床症状方面差异无统计学意义。低尿钙和非低尿钙组各有16例患者行氢氯噻嗪试验,中位ΔFECl结果分别为0.539%(0.430%,1.283%)和0.829%(0.119%,1.298%),均提示对氢氯噻嗪无反应,组间差异无统计学意义(U=130.000,P=0.956)。结论GS患者中低尿钙比例为63.86%,尿钙水平与疾病临床表型、NCC功能损伤严重程度之间均无明确相关性。

Comparison of clinical features in Gitelman syndrome patients with different urinary calcium excretion

Objective To observe the clinical features in Gitelman syndrome (GS) patients with different urinary calcium excretion, and investigate the value of urinary calcium excretion in the clinical classification for GS. Methods GS cases from the National Rare Diseases Registry System of China (NRSC) (2016 - 2018) with SLC12A3 gene screened in Peking Union Medical College Hospital were collected. The features of urinary calcium excretion were analyzed, and the phenotypes of patients with hypocalciuria were compared to those without. Hydrochlorothiazide (HCT) test was performed according to the standard process, and the maximal increment of chloride excretion fraction (ΔFECl) was calculated. Results A total of 83 GS patients were included, among whom 53 (63.86%) patients had hypocalciuria. The ratio of urinary calcium/creatine was significantly lower in patients with hypocalciuria compared to those without [(0.085±0.058) mmol/mmol vs (0.471±0.284) mmol/mmol, t=7.349, P＜0.001]. Age, gender, estimated glomerular filtration rate, blood pressure, serum and urinary electrolytes, and alkalosis were all comparable between groups. Fatigue (χ2=4.595, P=0.032) and polyuria (χ2=5.778, P=0.016) were less frequently reported in hypocalciuria patients, while all the other clinical symptoms were comparable. Sixteen patients in each group underwent HCT test, and the median value of ΔFECl was comparable between patients with and without hypocalciuria [0.539%(0.430%, 1.283%) vs 0.829% (0.119%,1.298%), U=130.000, P=0.956], both of which indicated no response to HCT. Conclusions The proportion of low urinary calcium in GS patients is 63.86% . There is no definite relationship between urinary calcium excretion, phenotype and the extent of NCC dysfunction.