JCI Insight
Detailed experimental results as well as human data on Dkk3 and kidneys were published 2016 in the Journal of Clinical Investigation Insight. Dkk3 was identified as a stress-induced glycoprotein secreted by renal tubular epithelia. The results demonstrate that Dkk3 is an immunosuppressive molecule that also has a profibrotic effect via the canonical WnT signaling pathway. Because it is secreted into the urine by tubular cells, Dkk3 is a very reliable diagnostic biomarker and possibly also a potential therapeutic target in acute and chronic kidney injury - regardless of the cause of the kidney damage.
Federico G, et al. Tubular dickkopf-3 promotes the development of renal atrophy and fibrosis.
J Clin Invest Insight 2016; 1: e84916
JASN
Important results on urinary Dkk3 from prospective clinical studies were published in the Journal of the American Society of Nephrology. The analysis of a long-term study of 575 patients with CKD stage 2-4 showed that the determination of urinary Dkk3 (ReFiNE) indicates active kidney damage regardless of the cause and predicts a significant short-term loss of GFR. In a randomized treatment trial in patients with IgA nephropathy (STOP IgAN), Dkk3 in urine indicated the changes in kidney function under therapy. The determination of Dkk3 in urine is therefore suitable - also under therapy - for the individual monitoring of CKD progression.
Zewinger S, et al. Dickkopf-3 (Dkk3) in urine identifies patients with short-term risk of eGFR loss.
J Am Soc Nephrol 2018; 29: 2722-2733
Lancet
The Lancet is a renowned international journal in which study results are published that have a significant impact on everyday medical practice. Data on the preoperative diagnosis of acute kidney injury using uDkk3 (ReFiNE) after elective cardiac surgery was published here. Dkk3 in urine was an independent predictor of postoperative acute kidney injury and subsequent progressive loss of kidney function (AKI-CKD transition). Thus, the measurement of uDkk3 enables the identification of patients at high risk of kidney injury to be able to take preventive treatment strategies.
Schunk S, et al. Association between urinary dickkopf-3, acute kidney injury, and subsequent loss of kidney function in patients undergoing cardiac surgery: an observational cohort study.
Lancet 2019; 394: 488-496
NDT
A comprehensive review on the role of Dkk3 in urine in the early detection and monitoring of kidney disease was published in Nephrology, Dialysis and Transplantation, a journal of the European Renal Association.
Schunk SJ, et al. Dickkopf 3 - a novel biomarker of the 'kidney injury continuum'.
Nephrol Dial Transplant 2021; 36: 761-767
Data on the prediction of CKD progression by determination of Dkk3 in urine in patients with diabetes and high risk of progression were also published in NDT.
Sanchez-Alamo B, et al. Urinary dickkopf-3: a new biomarker for CKD progression and mortality.
Nephrol Dial Transplant 2021; 36: 2199-2207
In addition, findings on the influence of a mild Covid-19 infection on Dkk3 in urine (ReFiNE) and kidney function were published in the NDT.
Schmidt-Lauber C, et al. Kidney outcome after mild to moderate COVID-19.
Nephrol Dial Transplant 2023; 38: 2031-2040
Kidney Int
In Kidney International results from a large multi-center study in patients with chronic obstructive pulmonary disease (COPD) were published. The analysis of prospective data from 2,314 patients showed that the determination of Dkk3 in urine (ReFiNE) predicts loss of kidney function even in patients without clinical signs of kidney damage. Baseline uDkk3 but not proteinuria or eGFR identified patients with a significantly higher risk for more than 20% decline of eGFR during follow-up (odds ratio 2.59; p<0.008). In particular, high uDkk3 was associated with a significantly higher risk for declining eGFR in patients with eGFR >90 ml/min/1.73m² and proteinuria <30 mg/g. These results underline the importance of uDkk3 for the individual monitoring of CKD progression regardless of the cause of kidney disease and baseline kidney function.
Schunk S, et al. Measurement of urinary dickkopf-3 uncovered silent progressive kidney injury in patients with chronic obstructive pulmonary disease.
Kidney Int 2021: 100: 1081-1091
JACC & AMJMS
The Journal of the American College of Cardiology published results from a large prospective study in patients with an advanced stage of kidney failure (eGFR <30 ml/min/1.73 m²) who received contrast media for cardiac diagnostics. Dkk3 in urine was an independent predictor of post-interventional acute kidney injury and for the subsequent loss of kidney function, i.e. AKI-CKD transition. These findings confirm that the measurement of Dkk3 in urine allows the identification of patients at high risk of kidney injury.
Roscigno G, et al. Urinary dickkopf-3 and contrast-associated kidney damage.
J Am Coll Cardiol 2021; 77: 2667-2676
In the AMerican Journal of the Medical Sciences a prospective study was published that confirmed the value of Dkk3 in urine in identifying patients at high risk of post-operative acute kidney injury.
Sun Y, et al. Urinary dickkopf-3 as a predictor for post-operative acute kidney injury in the intensive care unit.
Am J Med Sci 2025; 369: 434-442
Front Med & J Clin Med
The authors explored the utility of uDkk3 (ReFiNE) to identify patients at risk for deteriorating graft function after successful kidney transplantation. Three and 12-month uDkk3 levels were significant predictors of subsequent graft function up to 36 months after transplantation: an increase of ≥25% was associated with a reduction in eGFR of 9-10 ml/min. They concluded that the measurement of uDkk3 can predict future graft function.
Schuster A, et al. Dickkopf 3 - a new indicator for the deterioration of allograft function after kidney transplantation.
Front Med 2022; 9: 885018
In a long-term study Dkk3 was measured in urine (ReFiNE) of 117 living kidney donors before organ transplantation. uDkk3 values <200 pg/mg (n=89) were associated with better graft function than uDkk3 values ≥200 pg/mg (n=28), i.e 69 vs. 40 ml/min/1.73m² (p=0.01), after 15 years of follow-up. Remarkably, kidney function before transplantation was almost identical in both groups (93 vs. 94 ml/min/1.73m²; p=0.84).
Schuster A, et al. Dickkopf 3 as a new monitoring tool for kidney function after living kidney donation.
J Clin Med 2024; 13: 7454
Lancet Child Adolesc Health
The Lancet Child & Adolescent Health publishes important study results on the health of children and adolescents. In 2023, data on Dkk3 in urine in children and adolescents with CKD from two large prospective international clinical studies were published here. The analysis of a long-term study of 428 children with CKD stage 2-5 (4C study) showed that the measurement of uDkk3 (ReFiNE) indicates active kidney damage regardless of the cause and also predicts a significant loss of kidney function. In a randomized therapy study in 231 children with CKD stage 2-4 (ESCAPE trial), Dkk3 in urine predicted the changes in kidney function under therapy (intensified blood pressure control). The determination of Dkk3 in urine is therefore suitable for individual monitoring of therapeutic measures to slow CKD progression in children and adolescents regardless of the cause of kidney disease.
Speer T, et al. Urinary Dkk3 as a biomarker for short-term kidney function decline in children with chronic kidney disease: an observational cohort study.
Lancet Child Adolesc Health 2023; 7: 405-414
CKJ & JASN
The Clinical Kidney Journal published results on urinary Dkk3 (ReFiNE) in patients with autosomal dominant polycystic kidney disease (ADPKD). Dkk3 values in urine correlated significantly with both Mayo classification and kidney function in ADPKD patients. The authors concluded that urinary Dkk3 indicates the disproportionate GFR loss in these patients and can therefore improve prediction of progression in ADPKD patients.
Arjune S, et al. Dkk3 as a potential novel biomarker in patients with autosomal polycystic kidney disease.
Clin Kidney J 2024; 17: 1-10
Results of extensive genetic studies in families with ADPKD were published in the Journal of the American Society of Nephrology already in 2010. DKK3 was found to be a significant modulator of cyst growth and is thus involved in CKD progression in patients with ADPKD.
Liu M, et al. Genetic variation of DKK3 may modify renal disease severity in ADPKD.
J Am Soc Nephrol 2010; 21: 1510-1520
AJT
The American Journal of Transplantation published a prospective multicenter study examining whether the measurement of Dkk3 in urine (ReFiNE) can be used to predict future kidney transplant function in post-mortem organ donors. uDkk3 levels before nephrectomy were 100 higher in deceased than in living donors (9,888 vs. 113 pg/mg; p<0.001). uDkk3 levels below median in deceased donors resulted in a significantly higher eGFR within the first three months after transplantation in comparison with uDkk3 above median (56.3 vs. 44.2 ml/min/1.73 m²; p<0.0139). By mixed linear regression modeling, uDkk3 was an independent predictor of kidney function after transplantation, with an eGFR-slope of −4.282 m/min/1.73 m² per logarithmic increase in donor uDkk3 concentration. The authors thus concluded that uDkk3 may serve as a non-invasive, donor-dependent biomarker to assess organ quality and future graft function.
De Fallois J, et al. Deceased donor urinary dickkopf-3 associates with future allograft function following kidney transplantation.
Am J Transplant 2025; 25: 516-530
Ped Res & Ped Nephrol
In Pediatric Research, Chinese authors published data on the measurement of urinary Dkk3 in 420 critically ill children. High urinary Dkk3 levels were predictive of a significantly increased risk of acute kidney injury, sepsis-associated acute kidney injury, and intensive care unit mortality.
Hu J, et al. Prediction of urinary dickkopf-3 for AKI, sepsis-associated AKI, and PICU mortality in children.
Ped Res 2023; 93: 1651-1658
Initial results from the EARLY PRO-TECT Alport trial on uDKK3 in children with Alport syndrome were published in Pediatric Nephrology. uDKK3 levels were significantly elevated even in the early stages of the disease and were associated with the later onset of albuminuria and loss of kidney function.
Boeckhaus J, et al. Urinary dickkopf‑related protein 3 as a novel biomarker for kidney function decline in children with Alport syndrome.
Ped Nephrol 2025; 40: 2205-2213
Kidney Int Rep
In children with renal ciliopathy, uDkk3 levels (ReFiNE) were significantly higher than in children without kidney disease and correlated with CKD stage. Furthermore, elevated uDKK3 levels were associated with a significantly greater annual loss of kidney function (p<0.0029).
Dahmer-Heath M, et al. Urinary dickkopf-3 reflects disease severity and predicts short-term kidney function decline in renal ciliopathies.
Kidney Int Rep 2024; 10: 197-208
In children with progressive CKD, high uDkk3 (ReFiNE) was associated with significantly greater loss of eGFR, also over a longer period of time. These findings support the importance of uDkk3 for monitoring progression in children with CKD, regardless of the cause of kidney injury.
Dittrich K, et al. Urinary dickkopf-related protein 3 - a potential long-term biomarker for progressive CKD in children.
Kidney Int Rep 2025; 10: 1582-1586
JAHA
In the Journal of the American Heart Association, results on uDkk3 (ReFiNE) in heart failure patients were published for the first time. 488 patients with early NYHA I stage were studied: uDkk3 values ≥354 pg/mg were associated with a significantly greater loss of kidney function after 1 year of follow-up, i.e. 4.5 ml/min/1.73m², compared to low uDkk3 values (p=0.004). Even in patients without clinical signs of kidney damage (n=334) uDKK3 levels were higher than in healthy controls (233 [109-437] vs. 108 [61-181] pg/mg; p<0.001). These results confirm that in people with onset heart failure and normal kidney function, uDKK3 is a prognostic marker for future kidney function loss.