Igarashi Takashi, Sekine Takashi, Inatomi Jun, Seki George
Department of Pediatrics and Department of Internal Medicine, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
J Am Soc Nephrol. 2002 Aug;13(8):2171-7. doi: 10.1097/01.asn.0000025281.70901.30.
Proximal renal tubular acidosis (pRTA) results from an impairment of bicarbonate (HCO(3)(-)) reabsorption in the renal proximal tubules and is characterized by a decreased renal HCO(3)(-) threshold. Proximal RTA most commonly occurs in association with multiple defects of proximal tubular transport (renal Fanconi syndrome). Although much more rare, pRTA may occur without other functional defects in proximal tubules (isolated pRTA). The presenting clinical symptom of isolated pRTA is usually growth retardation in infancy or early childhood. Three categories of isolated pRTA have been identified: (1) autosomal dominant pRTA; (2) autosomal recessive pRTA with ocular abnormalities; and (3) sporadic isolated pRTA. Autosomal dominant and autosomal recessive pRTA are usually permanent; life-long alkali therapy is needed. In contrast, sporadic isolated pRTA is transient; alkali therapy can be discontinued after several years without reappearance of symptoms. Recent genetic studies have begun to elucidate the molecular pathogenesis of inherited isolated pRTA. Studies in knockout mice have identified a candidate gene for autosomal dominant pRTA, SLC9A3, a gene encoding one of the five plasma membrane Na(+)/H(+) exchangers (NHE3). Patients with autosomal recessive pRTA and ocular abnormalities have recently been found to have mutations in the kidney type Na(+)/HCO(3)(-) cotransporter gene (SLC4A4). Identification of these gene mutations provides new insights into the molecular pathogenesis of pRTA.
近端肾小管酸中毒（pRTA）是由于近端肾小管对碳酸氢盐（HCO₃⁻）重吸收受损所致，其特征为肾HCO₃⁻阈值降低。近端RTA最常与近端肾小管转运的多种缺陷（肾范科尼综合征）相关。尽管更为罕见，但pRTA也可能在近端肾小管无其他功能缺陷的情况下发生（孤立性pRTA）。孤立性pRTA的主要临床症状通常是婴儿期或幼儿期生长发育迟缓。已确定三类孤立性pRTA：（1）常染色体显性pRTA；（2）伴有眼部异常的常染色体隐性pRTA；（3）散发性孤立性pRTA。常染色体显性和常染色体隐性pRTA通常是永久性的；需要终身进行碱治疗。相比之下，散发性孤立性pRTA是短暂性的；几年后可停用碱治疗且症状不会再次出现。最近的基因研究已开始阐明遗传性孤立性pRTA的分子发病机制。对基因敲除小鼠的研究已确定常染色体显性pRTA的一个候选基因SLC9A3，该基因编码五种质膜Na⁺/H⁺交换体（NHE3）之一。最近发现伴有眼部异常的常染色体隐性pRTA患者在肾型Na⁺/HCO₃⁻共转运体基因（SLC4A4）中有突变。这些基因突变的鉴定为pRTA的分子发病机制提供了新的见解。
