Division of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern; Swiss National Centre of Competence in Research NCCR TransCure, University of Bern, Bern, Switzerland; and the Departments of Internal Medicine and Physiology, and the Charles and Jane Pak Center of Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX.
Division of Nephrology and Hypertension, Inselspital, Bern University Hospital, University of Bern; Swiss National Centre of Competence in Research NCCR TransCure, University of Bern, Bern, Switzerland; and the Departments of Internal Medicine and Physiology, and the Charles and Jane Pak Center of Mineral Metabolism and Clinical Research, University of Texas Southwestern Medical Center, Dallas, TX.
Adv Chronic Kidney Dis. 2018 Jul;25(4):366-374. doi: 10.1053/j.ackd.2018.05.007.
Renal tubular acidosis (RTA) is comprised of a diverse group of congenital or acquired diseases with the common denominator of defective renal acid excretion with protean manifestation, but in adults, recurrent kidney stones and nephrocalcinosis are mainly found in presentation. Calcium phosphate (CaP) stones and nephrocalcinosis are frequently encountered in distal hypokalemic RTA type I. Alkaline urinary pH, hypocitraturia, and, less frequently, hypercalciuria are the tripartite lithogenic factors in distal RTA (dRTA) predisposing to CaP stone formation; the latter 2 are also commonly encountered in other causes of urolithiasis. Although the full blown syndrome is easily diagnosed by conventional clinical criteria, an attenuated forme fruste called incomplete dRTA typically evades clinical testing and is only uncovered by provocative acid-loading challenges. Stone formers (SFs) that cannot acidify urine of pH < 5.3 during acid loading are considered to have incomplete dRTA. However, urinary acidification capacity is not a dichotomous but rather a continuous trait, so incomplete dRTA is not a distinct entity but may be one end of a spectrum. Recent findings suggest that incomplete dRTA can be attributed to heterozygous carriers of hypofunctional V-ATPase. The value of incomplete dRTA diagnosis by provocative testing and genotyping candidate genes is a valuable research tool, but it remains unclear at the moment whether they alter clinical practice and needs further clarification. No randomized controlled trials have been performed in SFs with dRTA or CaP stones, and until such data are available, treatment of CaP stones are centered on reversing the biochemical abnormalities encountered in the metabolic workup. SFs with type I dRTA should receive alkali therapy, preferentially in the form of K-citrate delivered judiciously to treat the chronic acid retention that drives both stone formation and bone disease.
肾小管性酸中毒 (RTA) 是一组由先天性或获得性疾病组成的疾病,其共同特征是肾脏排酸功能缺陷,表现多样,但在成人中,复发性肾结石和肾钙质沉着症主要表现为。Ⅰ型远端低钾性 RTA 中常发现磷酸钙 (CaP) 结石和肾钙质沉着症。碱性尿 pH 值、低柠檬酸尿症和较少见的高钙尿症是导致远端 RTA (dRTA) 形成 CaP 结石的三部分成石因素;后两者也常见于其他尿路结石的病因。虽然完整的综合征很容易通过常规临床标准诊断,但一种称为不完全性 dRTA 的轻度形式通常会逃避临床检测,只有通过激发性酸负荷挑战才能发现。在酸负荷下尿液 pH 值 < 5.3 时不能酸化尿液的结石形成者 (SFs) 被认为患有不完全性 dRTA。然而,尿酸化能力不是二分的,而是连续的特征,因此不完全性 dRTA 不是一个独立的实体,而可能是一个连续谱的一端。最近的研究结果表明,不完全性 dRTA 可能归因于功能低下的 V-ATPase 的杂合子携带者。通过激发性试验和候选基因基因分型诊断不完全性 dRTA 的价值是一种有价值的研究工具,但目前尚不清楚它们是否会改变临床实践,需要进一步澄清。在 dRTA 或 CaP 结石的 SFs 中尚未进行随机对照试验,在获得这些数据之前,CaP 结石的治疗主要集中在纠正代谢研究中遇到的生化异常。Ⅰ型 dRTA 的 SFs 应接受碱治疗,最好以枸橼酸钾的形式给予,以治疗导致结石形成和骨骼疾病的慢性酸潴留。