遗传性胱氨酸病：一种特殊形式的 CKD-MBD，为 FGF23 的调控提供新的见解。
Nephropathic Cystinosis: A Distinct Form of CKD-Mineral and Bone Disorder that Provides Novel Insights into the Regulation of FGF23.
机构信息
Skeletal Disorders and Mineral Homeostasis Section, National Institutes of Dental and Craniofacial Research, Bethesda, Maryland
Endocrinology Department, School of Medicine, Pontificia Universidad Católica de Chile, Santiago, Chile.
出版信息
J Am Soc Nephrol. 2020 Sep;31(9):2184-2192. doi: 10.1681/ASN.2019111172. Epub 2020 Jul 6.
BACKGROUND
The rare lysosomal storage disease nephropathic cystinosis presents with renal Fanconi syndrome that evolves in time to CKD. Although biochemical abnormalities in common causes of CKD-mineral and bone disorder have been defined, it is unknown if persistent phosphate wasting in nephropathic cystinosis is associated with a biochemical mineral pattern distinct from that typically observed in CKD-mineral and bone disorder.
METHODS
We assessed and compared determinants of mineral homeostasis in patients with nephropathic cystinosis across the predialysis CKD spectrum to these determinants in age- and CKD stage-matched patients, with causes of CKD other than nephropathic cystinosis.
RESULTS
The study included 50 patients with nephropathic cystinosis-related CDK and 97 with CKD from other causes. All major aspects of mineral homeostasis were differentially effected in patients with CKD stemming from nephropathic cystinosis versus other causes. Patients with nephropathic cystinosis had significantly lower percent tubular reabsorption of phosphate and fibroblast growth factor-23 (FGF23) at all CKD stages, and lower blood phosphate in CKD stages 3-5. Linear regression analyses demonstrated lower FGF23 levels in nephropathic cystinosis participants at all CKD stages when corrected for eGFR and age, but not when adjusted for serum phosphate.
CONCLUSIONS
Nephropathic cystinosis CKD patients have mineral abnormalities that are distinct from those in CKD stemming from other causes. Persistently increased urinary phosphate excretion maintains serum phosphate levels within the normal range, thus protecting patients with nephropathic cystinosis from elevations of FGF23 during early CKD stages. These findings support the notion that phosphate is a significant driver of increased FGF23 levels in CKD and that mineral abnormalities associated with CKD are likely to vary depending on the underlying renal disease.
背景
罕见的溶酶体贮积病胱氨酸贮积症表现为肾范可尼综合征，随着时间的推移发展为 CKD。尽管已经确定了常见 CKD 病因的生化异常——矿物质和骨代谢紊乱，但尚不清楚胱氨酸贮积症中的持续性磷酸盐丢失是否与不同于 CKD 矿物质和骨代谢紊乱的生化矿物质模式相关。
方法
我们评估并比较了不同 CKD 阶段的胱氨酸贮积症患者和年龄及 CKD 分期匹配的非胱氨酸贮积症 CKD 患者的矿物质稳态决定因素。
结果
本研究共纳入 50 例胱氨酸贮积症相关 CKD 患者和 97 例非胱氨酸贮积症 CKD 患者。所有主要方面的矿物质稳态在胱氨酸贮积症和其他病因引起的 CKD 患者中均有差异。在所有 CKD 阶段，胱氨酸贮积症患者的磷酸盐肾小管重吸收百分率和成纤维细胞生长因子 23（FGF23）显著降低，而 CKD 3-5 期的血磷酸盐水平较低。线性回归分析显示，在所有 CKD 阶段，胱氨酸贮积症患者的 FGF23 水平较低，在校正 eGFR 和年龄后，但在调整血清磷酸盐后则不然。
结论
胱氨酸贮积症 CKD 患者的矿物质异常与其他病因引起的 CKD 不同。持续增加的尿磷酸盐排泄使血清磷酸盐水平保持在正常范围内，从而使胱氨酸贮积症患者在早期 CKD 阶段免受 FGF23 升高的影响。这些发现支持磷酸盐是 CKD 中 FGF23 水平升高的重要驱动因素的观点，并且与 CKD 相关的矿物质异常可能因潜在的肾脏疾病而异。
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