Department of Pediatric Subspecialties, Division of Nephrology, Bambino Gesù Children's Hospital-IRCCS, Rome, Italy.
Renal Unit, Great Ormond Street Hospital for Children, NHS Foundation Trust, London, UK.
Kidney Int. 2021 Nov;100(5):1112-1123. doi: 10.1016/j.kint.2021.06.019. Epub 2021 Jul 6.
Nephropathic cystinosis is a rare disease secondary to recessive mutations of the CTNS gene encoding the lysosomal cystine transporter cystinosin, causing accumulation of cystine in multiple organs. Over the years, the disease has evolved from being a fatal condition during early childhood into a treatable condition, with patients surviving into adulthood. Data on cystinosis are limited by the rarity of the disease. Here, we have investigated factors associated with kidney and growth outcome in a very large cohort of 453 patients born between 1964 and 2016 and followed in Belgium, Germany, Austria, France, Italy, Spain, The Netherlands, Turkey and United Kingdom. From the 1970s to the 1990s, the median increase in kidney survival was 9.1 years. During these years, cysteamine, a cystine-depleting agent, was introduced for the treatment of cystinosis. Significant risk factors associated with early progression to end-stage kidney disease assessed by Cox proportional multivariable analysis included delayed initiation of cysteamine therapy and higher mean leucocyte cystine levels. No significant effect on kidney function was observed for gender, pathogenic variant of the CTNS gene, and the prescription of indomethacin or renin angiotensin system blockers. Significantly improved linear growth was associated with early use of cysteamine and lower leukocyte cystine levels. Thus, our study provides strong evidence in favor of early diagnosis and optimization of cystine depletion therapy in nephropathic cystinosis.
遗传性胱氨酸贮积症是一种罕见疾病，继发于编码溶酶体胱氨酸转运蛋白胱氨酸的 CTNS 基因的隐性突变，导致胱氨酸在多个器官中蓄积。多年来，该病已从儿童早期的致命疾病发展为可治疗的疾病，患者可存活至成年。由于该疾病罕见，因此关于胱氨酸贮积症的数据有限。在这里，我们研究了在 1964 年至 2016 年间出生并在比利时、德国、奥地利、法国、意大利、西班牙、荷兰、土耳其和英国接受随访的 453 例非常大的队列中与肾脏和生长结局相关的因素。从 20 世纪 70 年代到 90 年代，肾脏存活率中位数增加了 9.1 年。在此期间，引入了半胱氨酸耗竭剂半胱氨酸治疗胱氨酸贮积症。Cox 比例多变量分析显示，与早期进展为终末期肾病相关的显著危险因素包括半胱氨酸治疗开始延迟和白细胞胱氨酸水平升高。性别、CTNS 基因突变、吲哚美辛或肾素-血管紧张素系统阻滞剂的使用对肾功能无显著影响。早期使用半胱氨酸和较低的白细胞胱氨酸水平与线性生长显著改善相关。因此，我们的研究为遗传性胱氨酸贮积症的早期诊断和优化胱氨酸耗竭治疗提供了有力证据。
