#3671 Longitudinal analysis of the urinary Dickkopf-related protein 3 and its association with kidney function following kidney transplantation

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Abstract Background and Aims Previously, urinary Dickkopf-related protein 3 (uDKK3), a stress-induced tubular cell-derived profibrotic glycoprotein, was shown to be associated with tubulointerstitial fibrosis and loss of kidney function in patients with chronic kidney disease. However, its value in kidney transplant recipients (KTR) is debated, potentially because of a disturbing influence of uDKK3 that is also excreted by native kidneys. We aimed to investigate changes of uDKK3 over time and to evaluate its association with changes of kidney function in KTR without urine production prior to transplantation. Method Data of KTR enrolled in the TransplantLines Biobank and Cohort Study were used. To eliminate the influence of uDKK3 from the recipients’ kidneys, we only selected KTR that underwent dialysis and were anuric prior to transplantation. uDKK3 was measured using a commercially available ELISA kit in the 24-hour urine samples that were taken at 3, 6, 12, and 24 months after transplantation. The estimated glomerular filtration rate (eGFR) was calculated using the 2009 CKD-EPI creatinine-based equation. Changes in uDKK3 over time and its association with eGFR were analyzed using a linear mixed model. The fitted model was checked for homogeneity of variance and normality of residuals to ensure that the model assumption was not violated. uDKK3 were log2-transformed when assessing the changes in uDKK3 over time and scaled when assessing the association with eGFR, as it gives the best model fit based on the Akaike Information Criterion values. Missing observations in covariates were multiply imputed using Multiple Imputation by Chained Equations. Results We included 78 KTR (67% male, 63% received a kidney from a deceased donor, 29% with delayed graft function) in the analyses. At baseline (3 months after transplantation), mean (SD) age was 56 (15) years, mean (SD) eGFR was 46 (17) ml/min/1.73 m², median [Q1–Q3] 24 h urinary protein excretion was 0.19 [0.12–0.24] g/24 h, and median [Q1–Q3] 24 h uDKK3 excretion was 1827 [485–5496] ng/24 h. The median [Q1–Q3] intra-individual variation of 24 h uDKK3 excretion over the observed period was 6.8 [5.6–12.4] %. The effect of time on 24 h uDKK3 excretion was not significant (P = 0.3), indicating that the level of 24 h uDKK3 excretion did not significantly change over the observation period (Fig. 1). For the association of 24 h uDKK3 excretion and eGFR, our analysis showed that eGFR decreases by approximately 2.05 mL/min/1.73 m2 per 1 SD increase in 24 h uDKK3 excretion (Table 1). There was no interaction between 24 h uDKK3 excretion and time (pinteraction = 0.2), indicating that the association between 24 h uDKK3 excretion and eGFR did not change over time. Furthermore, there was also no interaction between 24 h uDKK3 excretion and 24 h urinary protein excretion (pinteraction = 0.4). Conclusion Our findings showed that uDKK3 is a stable biomarker. Furthermore, it is independently associated with loss of eGFR, regardless of the time measurement. This showed that uDKK3 is a potential non-invasive biomarker for monitoring the outcome of KTR.

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