DKK3 for Prognosis and Monitoring of GFR Decline in Heart Failure

Heart Failure Clinical Trial

Official title:

Urinary Dickkopf-3 for Prognosis and Monitoring of Glomerular Filtration Rate Decline in Patients With Heart Failure

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT04111094
• Other study ID #: AZ 122/19
• Status: Completed
• Start date: October 14, 2019
• Est. completion date: May 6, 2024

Study information

• Verified date: May 2024
• Source: University of Giessen
• Contact: n/a
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

The individual course of chronic kidney disease (CKD) may vary, and improved methods for identifying which patients will experience estimated glomerular filtration rate (eGFR) decline are needed. Recently, urinary dickkopf-3 (DKK3) has been proposed to predict eGFR decline in patients with CKD, independent of presence of albuminuria. The investigators sought to examine the association between changes in DKK3 levels and eGFR decline in patients with heart failure (HF).

Description:

The individual course of chronic kidney disease (CKD) may vary, and improved methods for identifying which patients will experience estimated glomerular filtration rate (eGFR) decline are needed. Recently, urinary dickkopf-3 (DKK3) has been identified as an stress-induced, renal tubular epithelia-derived, secreted glycoprotein that induces tubulointerstitial fibrosis. Urinary DKK3 has been found to predict eGFR decline in patients with CKD, independent of presence of albuminuria, but its association with eGFR decline in patients with heart failure (HF) is unknown. The investigators sought to examine the association between changes in DKK3 and eGFR decline in patients with HF.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 290
• Est. completion date: May 6, 2024
• Est. primary completion date: January 21, 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

Inclusion Criteria:

• Outpatients =18 years of age with diagnosed HF or diabetes or hypertension

Exclusion Criteria:

• CKD with estimated GFR <20 ml/min/1.73 m2 (2012 CKD-EPI equation)
• CKD with extracorporeal or peritoneal ultrafiltration due to diuretic-resistant fluid overload
• active tumor disease
• inflammatory or autoimmune disease requiring systemic immunosuppressive treatment
• clinically apparent infections
• recipients of solid-organ transplants
• anticipated life expectancy of <12 months
• likelihood of receiving advanced therapy (mechanical circulatory assist device/cardiac transplant)
• pregnancy or possibility of pregnancy in the next 12 months

Related Conditions & MeSH terms

• Chronic Kidney Diseases
• Heart Failure
• Kidney Diseases
• Renal Insufficiency, Chronic

Intervention

Diagnostic Test:
• No intervention
No intervention

Locations

Country	Name	City	State
Germany	University Clinic Giessen and Marburg - Campus Giessen	Giessen	Hessen

Sponsors (1)

Lead Sponsor	Collaborator
University of Giessen

Country where clinical trial is conducted

Germany, 

References & Publications (2)

Federico G, Meister M, Mathow D, Heine GH, Moldenhauer G, Popovic ZV, Nordstrom V, Kopp-Schneider A, Hielscher T, Nelson PJ, Schaefer F, Porubsky S, Fliser D, Arnold B, Grone HJ. Tubular Dickkopf-3 promotes the development of renal atrophy and fibrosis. JCI Insight. 2016 Jan 21;1(1):e84916. doi: 10.1172/jci.insight.84916. — View Citation

Zewinger S, Rauen T, Rudnicki M, Federico G, Wagner M, Triem S, Schunk SJ, Petrakis I, Schmit D, Wagenpfeil S, Heine GH, Mayer G, Floege J, Fliser D, Grone HJ, Speer T. Dickkopf-3 (DKK3) in Urine Identifies Patients with Short-Term Risk of eGFR Loss. J Am Soc Nephrol. 2018 Nov;29(11):2722-2733. doi: 10.1681/ASN.2018040405. Epub 2018 Oct 2. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Association between DKK3 and eGFR decline	DKK3 and eGFR (CKD-Epidemiology Collaboration equation)	24 months
Secondary	Association between proteinuria and DKK3	DKK3 and proteinuria, albuminuria, and alpha 1 microglobulin excretion	24 months
Secondary	Persistent or worsening of HF	Cardiovascular death, hospital admission for decompensated HF, or clinical HF decompensation without hospital admission (but requiring parenteral HF therapy or changes in oral HF medications including diuretics)	24 months
Secondary	Need for renal replacement therapy	Requirement of incident renal replacement therapy	24 months
Secondary	Association of venous congestion/volume overload with DKK3	B-type natriuretic peptide, clinical examination, bioimpedance analysis, echocardiography	24 months
Secondary	Association of right and left ventricular function with DKK3	Echocardiography	24 months