Podocyturia, a Non-Invasive Predictor of Renal Dysfunction in Fabry Nephropathy

进行性肾功能衰竭是法布里病(FD)的主要并发症。FD的异质性 表型阻碍了关于需要和剂量调整的共识指南的建立 酶替代疗法(ERT)。而ERT开始的年龄和ERT的剂量都会影响其 功效[1，2]。因此，当患者有1g/d蛋白尿时，晚期启动ERT不能阻止进展 肾小球滤过率(GFR)下降和较低的ERT剂量对清除足细胞(PC)的效果较差， FN进展中的一个重要细胞，来自GL3[2]。因此，有强烈的需求 早期发现FD肾病(FN)并根据FN风险对患者进行分层以指导治疗的生物标志物 启动和剂量调整。目前，蛋白尿和微量白蛋白尿用于此目的[3，4]，但是， 这些指标对发现早期FN损害不敏感[3，5，6]，而且对肾脏疾病的预测精度要低得多 患有FD的女性[7]。活检研究表明，PC损伤发生在早期，并随着年龄的增长而进展 年轻的FD患者[5]。因此，PC损伤标志物有望成为早期发现FN的候选指标。个人电脑数量有限 再生能力[8]。PC损伤和丢失导致节段性和全局性肾小球硬化[9，10]， FN晚期常见且不可逆的病变。受伤的PC落入尿液中。尿PC的定量检测 (足细胞尿[PCU])是PC损伤的有力证据，对其他肾脏具有诊断和预后价值 疾病[11-13]。在FD患者中，PCU可能先于并导致蛋白尿、肾小球硬化和减少 GFR。如果是真的，PCU可能有助于预测FN风险和指导FD治疗。初步数据显示，尿液 每肌酐的凋亡性PC(以下为简单起见与PCU互换使用)与年龄相关， 成人FD患者的尿白蛋白(UACR)和蛋白肌酐比值(UPCr)。然而，我们没有 年轻FD患者的PCU信息，其中FN的非侵入性和敏感的生物标志物是最多的 需要指导治疗。

Progressive renal failure is a major complication of Fabry disease (FD). Heterogeneity of FD phenotype has hampered establishment of a consensus guideline for the need and dose adjustment for enzyme replacement therapy (ERT). This is while both age of ERT initiation and ERT dosage can affect its efficacy [1, 2]. Thus, late ERT initiation when patients have >1 g/d proteinuria cannot prevent progressive glomerular filtration rate (GFR) decline and lower ERT doses are less efficacious in clearing podocytes (PC), an essential cell in FN progression, from globotriaocylceramide (GL3) [2]. Therefore, there is a strong need for a biomarker to detect early FD nephropathy (FN) and stratify patient based on FN risk to guide treatment initiation and dose adjustment. Currently, proteinuria and microalbuminuria are used for this purpose [3, 4], but, these are not sensitive to detect early FN lesions [3, 5, 6] and are much less precise renal disease predictors in females with FD [7]. Biopsy studies suggest PC injury occurs early and is progressive with increasing age in young FD patients [5]. Thus, markers of PC injury are promising candidates to detect early FN. PC have limited capacity to regenerate [8]. PC injury and loss leads to segmental and global glomerulosclerosis [9, 10], common and irreversible lesions in late stages of FN. Injured PC fall into the urine. Quantification of urine PC (podocyturia [PCU]) is robust evidence of PC injury with diagnostic and prognostic values in other kidney diseases [11-13]. It is likely that PCU in FD precedes and leads to proteinuria, glomerulosclerosis and reduced GFR. If true, PCU may be useful to predict FN risk and guide FD treatment. Preliminary data show that urine apoptotic PC per creatinine (hereafter used interchangeably with PCU for simplicity) correlates with age, urinary albumin (UACR) and protein creatinine ratios (UPCR) in adult FD patients. However, we have no information about PCU in young FD patients, where a non-invasive and sensitive biomarker of FN is most needed to guide treatments.