摘要：

Phenotypic heterogeneity and unpredictability of individual disease progression present enormous challenges in ultrarare renal ciliopathies. The tubular-derived glycoprotein, Dickkopf-related protein 3 (DKK3) is a promising biomarker for kidney fibrosis and prediction of kidney function decline. Here, we measured urinary DKK3 (uDKK3) levels in 195 pediatric patients with renal ciliopathy to assess its potential as a discriminative and prediction marker. uDKK3 concentration was measured in 357 spot urine samples from 247 individuals, including 52 healthy age-matched controls. Disease entities comprised nephronophthisis (NPH) (n = 37), autosomal recessive polycystic kidney disease (ARPKD) (n = 61), Bardet Biedl syndrome (BBS) (n = 57), and hepatocyte nuclear factor 1 beta (HNF1B)-nephropathy (n = 40). The results were correlated with chronic kidney disease (CKD) stage and annual estimated glomerular filtration rate (eGFR) decline. Median uDKK3-to-creatinine ratios (uDKK3/crea) in all disease entities were significantly higher compared with healthy controls (11pg/mg uDKK3/crea, P < 0.001): NPH, 1.219 pg/mg; HNF1B, 731 pg/mg; BBS, 541 pg/mg; and ARPKD, 437 pg/mg. A significant correlation of CKD stage with uDKK3 levels was observed for all disease entities (P < 0.0001) with no other clinical parameter having a relevant impact. In our cohort, uDKK3 values >4.700 pg/mg were associated with a significantly greater annual eGFR loss independently of diagnosis and eGFR (P = 0.0029). Although we observed a trend toward lower uDKK3 levels in glomerulopathies compared to renal ciliopathies, there was no discriminative difference between individual ciliopathy entities (P = 0.2637). In renal ciliopathies, uDKK3 is a marker to assess disease severity and estimate short-term kidney function decline.

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