Urinary Dickkopf-3 (DKK3) Is Associated with Greater eGFR Loss in Patients with Resistant Hypertension

Patients with resistant hypertension (HTN) demonstrate an increased risk of chronic kidney disease and progression to end-stage renal disease; however, the individual course of progression is hard to predict. Assessing the stress-induced, urinary glycoprotein Dickkopf-3 (uDKK3) may indicate ongoing renal damage and consecutive estimated glomerular filtration rate (eGFR) decline. The present study aimed to determine the association between uDKK3 levels and further eGFR changes in patients with resistant HTN. In total, 31 patients with resistant HTN were included. Blood pressure and renal function were measured at baseline and up to 24 months after (at months 12 and 24). uDKK3 levels were determined exclusively from the first available spot urine sample at baseline or up to a period of 6 months after, using a commercial ELISA kit. Distinctions between different patient groups were analyzed using the unpaired t-test or Mann-Whitney test. Correlation analysis was performed using Spearman's correlation. The median uDKK3 level was 303 (interquartile range (IQR) 150-865) pg/mg creatinine. Patients were divided into those with high and low eGFR loss (≥3 vs. <3 mL/min/1.73 m²/year). Patients with high eGFR loss showed a significantly higher median baseline uDKK3 level (646 (IQR 249-2555) (n = 13) vs. 180 (IQR 123-365) pg/mg creatinine (n = 18), p = 0.0412 (Mann-Whitney U)). Alternatively, patients could be classified into those with high and low uDKK3 levels (≥400 vs. <400 pg/mg creatinine). Patients with high uDKK3 levels showed significantly higher eGFR loss (-6.4 ± 4.7 (n = 11) vs. 0.0 ± 7.6 mL/min/1.73 m²/year (n = 20), p = 0.0172 (2-sided, independent t-test)). Within the entire cohort, there was a significant correlation between the uDKK3 levels and change in eGFR at the latest follow-up (Spearman's r = -0.3714, p = 0.0397). In patients with resistant HTN, high levels of uDKK3 are associated with higher eGFR loss up to 24 months later.