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Urinary Dickkopf-3 as a Potential Marker for Estimated Glomerular Filtration Rate Decline in Patients With Heart
Dennis Pieper1, Anja Sandek2,3, Ann-Kathrin Schäfer1
1Department of Nephrology and Rheumatology University Medical Center Göttingen, Georg-August-University Göttingen Göttingen Germany.
Insights
Urinary Dickkopf-3 (uDKK3) elevation predicts kidney function decline in heart failure (HF) patients. This biomarker aids early intervention for cardiorenal syndrome, even in early HF stages.
Area of Science:
- Nephrology
- Cardiology
- Biomarker Discovery
Background:
- Heart failure (HF) patients face increased risk of chronic kidney disease (CKD) and cardiorenal syndrome.
- Urinary Dickkopf-3 (uDKK3), a profibrotic glycoprotein, may rise early in HF, predicting kidney function decline.
Purpose of the Study:
- To investigate the association between urinary Dickkopf-3 (uDKK3) levels and estimated glomerular filtration rate (eGFR) decline in chronic heart failure (HF) patients.
- To assess uDKK3 as a prognostic biomarker for kidney function deterioration in HF.
Main Methods:
- Enzyme-linked immunosorbent assay (ELISA) measured uDKK3 levels in 488 HF patients and 45 controls.
- Estimated glomerular filtration rate (eGFR) was monitored for up to 5 years.
- Regression models analyzed the relationship between baseline uDKK3 and eGFR changes.
Main Results:
- HF patients exhibited significantly higher median uDKK3 levels than controls (259.6 vs. 107.5 pg/mg creatinine).
- Elevated log uDKK3 strongly correlated with eGFR decline over a median of 13 months.
- uDKK3 levels ≥354 pg/mg creatinine indicated a significantly higher risk of eGFR decline within 1 year.
Conclusions:
- Urinary Dickkopf-3 (uDKK3) shows promise as a prognostic biomarker for eGFR decline in HF patients.
- uDKK3 may predict kidney function decline irrespective of CKD presence or HF stage.
- Early identification via uDKK3 could enable timely interventions to preserve kidney function.
Background:
Patients with chronic heart failure (HF) show an increased risk for the occurrence of chronic kidney disease and cardiorenal syndrome. Urinary Dickkopf-3 (uDKK3), a stress-induced, tubular profibrotic glycoprotein, may be elevated in HF as early as in New York Heart Association class I HF and may indicate subsequent decline in estimated glomerular filtration rate (eGFR).
Methods And Results:
uDKK3 levels in patients with HF and controls were measured by enzyme-linked immunosorbent assay. eGFR was determined up to 5 years in HF. Change in eGFR was assessed with respect to baseline uDKK3 using (mixed-effect) linear and logistic regression models. A total of 488 patients with chronic HF and 45 control patients were included. Patients with HF showed higher median uDKK3 levels than controls (259.6 pg/mg creatinine [interquartile range (IQR), 119.2-509.4 pg/mg creatinine] versus 107.5 pg/mg creatinine [IQR, 60.5-181.2 pg/mg creatinine], P<0.001). Regression models demonstrated a significant association between log uDKK3 and the decline in eGFR during a median of 13 months (IQR, 12-59 months) (estimated higher eGFR loss, 0.8039 mL/min per 1.73 m2/year [95% CI, 0.002-1.606 mL/min per 1.73 m2/year], P=0.049; odds ratio, 1.345 [95% CI, 1.049-1.741], P=0.021). uDKK3 levels ≥354 pg/mg creatinine were associated with a significantly higher risk for eGFR decline at 1-year follow-up (estimated higher eGFR loss, 4.538 mL/min per 1.73 m2 [95% CI, 1.482-9.593 mL/min per 1.73 m2]), P=0.004). Even patients with HF without chronic kidney disease (n=334) had higher uDKK3 levels compared with controls (233.4 [IQR, 109.0-436.9 pg/mg creatinine] versus 107.5 [IQR, 60.5-181.2 pg/mg creatinine], P<0.001).
Conclusions:
The present findings indicate that uDKK3 is a promising prognostic biomarker for subsequent eGFR decline in patients with HF, irrespective of the presence of chronic kidney disease and even in the early stages of HF. This potential allows for early intervention to mitigate the deterioration of kidney function. Further investigation is warranted to validate its clinical utility.
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