DKK3 for Prognosis and Monitoring of GFR Decline in Heart Failure

Study Overview
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Brief Summary
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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
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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.

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

Conditions
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Heart Failure, Chronic Kidney Diseases

Intervention / Treatment
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* Diagnostic Test: No intervention


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Outpatients ≥18 years of age with diagnosed HF or diabetes or hypertension Exclusion Criteria: CKD with estimated GFR <30 ml/min/1.73 m2 CKD with extracorporeal or peritoneal ultrafiltration due to diuretic-resistant fluid overload autosomal dominant polycystic kidney disease active tumor disease inflammatory or autoimmune disease requiring systemic immunosuppressive treatment clinically apparent infections recipients of solid-organ transplants patients who received non-steroidal anti-inflammatory drugs or intravenous contrast media within 72 hours prior to recruitment

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| HF<br>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. | Diagnostic Test: No intervention<br>* No intervention<br>|
| Diabetes mellitus/hypertension<br>Diagnosed diabetes mellitus, with/without treatment | Diagnostic Test: No intervention<br>* No intervention<br>|
| Hypertension<br>Diagnosed hypertension, with/without treatment | Diagnostic Test: No intervention<br>* No intervention<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association between DKK3 and eGFR decline | DKK3 and eGFR (CKD-Epidemiology Collaboration equation) | 24 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Association between proteinuria and DKK3 | DKK3 and proteinuria, albuminuria, and alpha 1 microglobulin excretion | 24 months | 
| 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 | 
| Need for renal replacement therapy | Requirement of incident renal replacement therapy | 24 months | 
| Association of venous congestion/volume overload with DKK3 | B-type natriuretic peptide, clinical examination, bioimpedance analysis, echocardiography | 24 months | 
| Association of right and left ventricular function with DKK3 | Echocardiography | 24 months |