Urinary dickkopf 3 in a kidney transplant and living donor cohort – independent risk factor or merely GFR-related?

Abstract

Abstract Urinary Dickkopf 3 (uDKK3) is a marker released by kidney tubular epithelial cells that is associated with the progression of chronic kidney disease (CKD) and may cause interstitial fibrosis and tubular atrophy. Recent evidence suggests that uDKK3 can also predict the loss of kidney function in CKD patients and kidney transplant recipients, regardless of their current renal function. We conducted a prospective study on 181 kidney transplant (KTx) recipients who underwent allograft biopsy for cause, analyzing the relationship between uDKK3 levels in urine, histological findings, and future allograft function progression. Additionally, we studied 82 living kidney donors before unilateral nephrectomy (Nx), 1–3 days after surgery, and one year post-surgery to observe the effects of rapid kidney function loss. In living donors, the uDKK3/creatinine ratio significantly increased 5.3-fold 1–3 days after Nx. However, it decreased significantly to a median level of 620 pg/ml after one year, despite the absence of underlying primary kidney pathology. The estimated glomerular filtration rate (eGFR) decreased by an average of 29.3% to approximately 66.5 (± 13.5) ml/min/1.73m² after one year, with no further decline in the subsequent years. uDKK3 levels increased in line with eGFR loss after Nx, followed by a decrease as eGFR partially recovered within the following year. However, uDKK3 did not correlate with eGFR at the single time points in living donors. In KTx recipients, the uDKK3/creatinine ratio was significantly elevated with a median of 1,550 compared to healthy individuals or donors after Nx. The mean eGFR in the recipient group was 35.5 ml/min/1.73m², corresponding to KDIGO stage CKD G3b. The uDKK3/creatinine ratio was statistically associated with eGFR at biopsy, but not independently associated with eGFR one year after biopsy or allograft loss. In conclusion, uDKK3 is associated with recent and future kidney function and kidney allograft survival in the renal transplant cohort. Nevertheless, our findings indicate that uDKK3/creatinine has no prognostic influence on future renal outcome in living donors and kidney recipients beyond eGFR, regardless of the presence of acute renal graft pathology.