Faculté de Médecine, Sorbonne Université, Paris, France.
Service de Médecine Génomique des Maladies Rares, Groupe Hospitalier Universitaire Centre, Site Hôpital Européen Georges Pompidou, Assistance Publique Hôpitaux de Paris, 75015, Paris, France.
J Nephrol. 2024 Sep;37(7):1973-1983. doi: 10.1007/s40620-024-02054-y. Epub 2024 Sep 11.
Inherited tubulopathies are rare kidney diseases with few data available in the literature regarding their long-term renal prognosis. This study aimed to evaluate the prevalence of kidney failure in adults with confirmed genetic tubulopathy and to describe the corresponding clinical and genetic findings.
In this observational cohort study, we focused on genetic tubulopathies assumed to impact kidney function. In all adult patients genetically diagnosed in our laboratory between 2001 and 2019, we estimated Glomerular Filtration Rate (eGFR) at diagnosis using the Modification of diet in renal disease (MDRD) formula. Kidney failure was defined as an eGFR < 60 ml/min/1.73 m.
A total of 2145 patients underwent genetic testing, confirming a genetic tubulopathy in 1031 cases (48%). We identified 116 patients out of 885 with available data with kidney failure, mostly diagnosed with Dent disease and distal renal tubular acidosis (respectively, 31% and 20%), followed by familial hypomagnesemia with hypercalciuria and nephrocalcinosis and renal hypophosphatemia/infantile hypercalcemia. Renal prognosis appeared particularly impacted in familial hypomagnesemia with hypercalciuria and nephrocalcinosis and Dent disease, while preserved in Gitelman syndrome.
In this cohort, 13% of adults with genetic tubulopathy had kidney failure at diagnosis, with this rate varying greatly according to tubulopathies and suggesting a significant impact on renal prognosis. Even in adults, genetic analyses yield a good diagnostic rate in selected patients, and should be performed as soon as possible, in order to improve the renal management of patients and their relatives.
遗传性肾小管疾病较为罕见，相关文献中关于其长期肾脏预后的数据较少。本研究旨在评估已确诊遗传性肾小管疾病患者发生肾衰竭的概率，并描述相应的临床和遗传学发现。
本观察性队列研究重点关注可能影响肾功能的遗传性肾小管疾病。在我们实验室于 2001 年至 2019 年期间诊断的所有成年患者中，我们使用肾脏病饮食改良公式（MDRD）估计诊断时的肾小球滤过率（eGFR）。肾衰竭定义为 eGFR＜60 ml/min/1.73 m。
共有 2145 名患者接受了基因检测，其中 1031 例（48%）被确诊为遗传性肾小管疾病。在 885 例有可用数据的患者中，我们共发现 116 例发生肾衰竭，其中大部分诊断为 Dent 病和远端肾小管酸中毒（分别为 31%和 20%），其次为家族性低镁血症伴高钙尿和肾钙质沉着症及肾性磷酸尿/婴儿高钙血症。Dent 病和家族性低镁血症伴高钙尿和肾钙质沉着症患者的肾脏预后似乎受到严重影响，而 Gitelman 综合征患者的肾脏预后则得到保留。
在本队列中，13%的遗传性肾小管疾病成年患者在诊断时即发生肾衰竭，不同肾小管疾病的发生率差异较大，提示对肾脏预后有重大影响。即使在成年人中，针对特定患者的基因分析也能获得良好的诊断率，应尽快进行，以便改善患者及其亲属的肾脏管理。
