DKK3 for Prognosis and Monitoring of GFR Decline in Heart Failure

Completed

• Conditions: Heart Failure; Chronic Kidney Diseases
• Interventions: Diagnostic Test: No intervention

• Registration Number: NCT04111094
• Lead Sponsor: University of Giessen

Brief 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).

Detailed 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.

Study Timeline

• Study First Submitted: 2019-09-27
• Study First Submitted QC: 2019-09-27
• Study First Posted: 2019-10-01
• Study Start: 2019-10-14
• Primary Completion: 2023-01-21
• Status Verified: 2024-05
• Study Completion: 2024-05-06
• Last Update Submitted: 2024-05-07
• Last Update Posted: 2024-05-09

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 290

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

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
HF	No intervention	Diagnosed heart failure as described by recent guidelines. Inclusion criteria will be applied: i) minimum one symptom typical of HF: positive physical examination (e.g., bilateral oedema, increased jugular pressure) or positive clinical history (e.g., orthopnoea, history of coronary vascular disease, history of arterial hypertension, exposition to cardiotoxic drug/radiation, diuretic use); b-type natriuretic peptide (BNP) or N-terminal pro-BNP levels ≥35 or ≥125 pg/ml, respectively; and iii) classification as New York Heart Association (NYHA) functional class 2 or 3. There is no prespecified inclusion criterion with respect to left ventricular ejection fraction as congestive symptoms and prevalence of kidney dysfunction are comparable in patients with HF across the left ventricular ejection fraction spectrum.
Diabetes mellitus/hypertension	No intervention	Diagnosed diabetes mellitus, with/without treatment
Tubulointerstitial diseases	No intervention	Diagnosed tubulointerstitial diseases, with/without treatment
Glomerular diseases	No intervention	Diagnosed glomerular diseases, with/without treatment
Cystic kidney diseases	No intervention	Diagnosed cystic kidney diseases, with/without treatment
Hypertension	No intervention	Diagnosed hypertension, with/without treatment

Primary Outcome Measures

Name	Time	Method
Association between DKK3 and eGFR decline	24 months	DKK3 and eGFR (CKD-Epidemiology Collaboration equation)

Secondary Outcome Measures

Name	Time	Method
Association between proteinuria and DKK3	24 months	DKK3 and proteinuria, albuminuria, and alpha 1 microglobulin excretion
Persistent or worsening of HF	24 months	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)
Association of venous congestion/volume overload with DKK3	24 months	B-type natriuretic peptide, clinical examination, bioimpedance analysis, echocardiography
Need for renal replacement therapy	24 months	Requirement of incident renal replacement therapy
Association of right and left ventricular function with DKK3	24 months	Echocardiography

Trial Locations

Locations (1)

University Clinic Giessen and Marburg - Campus Giessen; 🇩🇪 Giessen, Hessen, Germany