Supplementary Material for: First Reported Case of a Pyrophosphate Kidney Stone in a Human

Urolithiasis composed of pyrophosphate salts have only been reported in animals, in the form of potassium magnesium pyrophosphate. However, there have been no reports of pyrophosphate stones in humans. Hypophosphatasia is an inherited disease characterized by low alkaline phosphatase activity and elevated levels of pyrophosphate in blood and urine. Urolithiasis is a part of the hypophosphatasia phenotype. The role of elevated urine pyrophosphate levels in the formation of stones in hypophosphatasia is unknown. Here we report a case of a 60 year old man with recurrent urolithiasis. The patient’s most recent presentation was gross hematuria and his CT scan showed bilateral kidney stones. Stones were removed via retrograde intra-renal surgery. Stone analysis revealed a composition of potassium magnesium pyrophosphate. The patient also has a long history of fracturing bone disease which led to the consideration of hypophosphatasia as the cause of both his bone disease and pyrophosphate stones. Hypophosphatasia was confirmed by genetic analysis. Pyrophosphate has been of interest in the fields of mineral metabolism because of its action as a crystallization inhibitor. However, pyrophosphate at elevated concentrations in the presence of divalent cations can exceed its solubility. Nephrocalcinosis and stone disease have been described in hypophosphatasia, stones have been assumed to be calcium phosphate but no compositional analysis has been reported. This is the first report of human stones composed of pyrophosphate salts, which led to the subsequent diagnosis of hypophosphatasia in this patient.

尿酸盐结石主要由磷酸盐组成，仅见于动物，其形式为磷酸镁钾。然而，关于人类中磷酸盐结石的报道尚无。低碱性磷酸酶活性和血液及尿液中磷酸盐水平升高是磷酸化酶缺乏症的典型特征。尿路结石是磷酸化酶缺乏症表型的一部分。在磷酸化酶缺乏症中，尿液磷酸盐水平升高在结石形成中的作用尚不明确。在此，我们报道了一例60岁男性反复出现尿路结石的病例。患者的最近一次表现为肉眼血尿，其CT扫描显示双侧肾结石。结石通过逆行肾内手术被移除。结石分析表明其成分为磷酸镁钾。患者还患有长期骨折病史，这导致将磷酸化酶缺乏症视为其骨病和磷酸盐结石的潜在原因。通过遗传分析确认了磷酸化酶缺乏症的诊断。磷酸盐因其作为结晶抑制剂的作用而在矿物质代谢领域引起了关注。然而，在存在二价阳离子的条件下，高浓度的磷酸盐可能会超过其溶解度。在磷酸化酶缺乏症中已描述了肾钙质沉着症和结石病，结石被假设为磷酸钙，但尚未报道成分分析。这是首次报道由磷酸盐组成的结石，随后在患者中诊断为磷酸化酶缺乏症。