Cochran Benjamin, Kovačíková Tereza, Hodaňová Kateřina, Živná Martina, Hnízda Aleš, Niehaus Angela G, Bonnecaze Alex, Balasubraminiam Gowrie, Ceballos-Picot Irene, Hawfield Amret, Kidd Kendrah, Kmoch Stanislav, Bleyer Anthony J
Clin Nephrol. 2018 Oct;90(4):296-301. doi: 10.5414/CN109460.
Adenine phosphoribosyltransferase (APRT) deficiency (OMIM #614723) is a rare autosomal recessive defect in the purine salvage pathway that causes excessive production of 2,8-dihydroxyadenine, leading to nephrolithiasis and chronic kidney disease (CKD). This case report describes the natural history of CKD in untreated APRT deficiency. We describe a novel APRT mutation (chr16:88877985 G / C; c.195 C>/G; p.His54Asp) presenting with CKD without nephrolithiasis. The patient initially required dialysis, but kidney function improved with allopurinol. We reviewed APRT deficiency reported in the literature to determine the loss of kidney function in individuals with untreated APRT deficiency and its relationship to nephrolithiasis. We identified 95 individuals in whom kidney function was assessed prior to treatment. There was a bimodal distribution of kidney failure. AKI occurred frequently in childhood due to obstructing nephrolithiasis or crystalline nephropathy and was usually reversible. CKD developed after age 20 in all patients irrespective of nephrolithiasis history, with 36/42 patients > 40 years of age having at least stage 3 CKD, and 24/42 having an eGFR > 10 mL/min/1.73m2 or being on dialysis. There were 13 adults without nephrolithiasis and 50 adults with nephrolithiasis. The mean age of end-stage renal diesease (ESRD) was 50.52 ± 13.9 for those without nephrolithiasis and 43.4 ± 15.8 years for those with nephrolithiasis (p = 0.24). APRT deficiency is associated with slowly progressive CKD that occurs independently of nephrolithiasis. Diagnosis should be considered in all individuals with chronic tubulointerstitial kidney disease, with or without the presence of nephrolithiasis. In our patient, allopurinol 300 mg/day resulted in improvement of kidney function. .
腺嘌呤磷酸核糖转移酶（APRT）缺乏症（OMIM #614723）是嘌呤补救途径中一种罕见的常染色体隐性缺陷，可导致2,8 - 二羟基腺嘌呤过度产生，进而引发肾结石和慢性肾脏病（CKD）。本病例报告描述了未经治疗的APRT缺乏症患者CKD的自然病程。我们描述了一种新的APRT突变（chr16:88877985 G / C；c.195 C>/G；p.His54Asp），该突变患者表现为CKD但无肾结石。患者最初需要透析，但使用别嘌醇后肾功能有所改善。我们回顾了文献中报道的APRT缺乏症病例，以确定未经治疗的APRT缺乏症患者的肾功能丧失情况及其与肾结石的关系。我们确定了95例在治疗前评估过肾功能的个体。肾衰竭呈双峰分布。儿童期因梗阻性肾结石或结晶性肾病常发生急性肾损伤（AKI），且通常可逆。所有患者在20岁后均出现CKD，无论有无肾结石病史，42例患者中有36例年龄>40岁，至少处于3期CKD，24例患者的估算肾小球滤过率（eGFR）>10 mL/min/1.73m²或正在接受透析。其中13例成年患者无肾结石，50例成年患者有肾结石。无肾结石患者终末期肾病（ESRD）的平均年龄为50.52±13.9岁，有肾结石患者为43.4±15.8岁（p = 0.24）。APRT缺乏症与缓慢进展的CKD相关，且该疾病的发生与肾结石无关。对于所有患有慢性肾小管间质性肾病的个体，无论有无肾结石，均应考虑进行诊断。在我们的患者中，每天服用300毫克别嘌醇可使肾功能得到改善。
