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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).
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| HF | 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 | Diagnosed diabetes mellitus, with/without treatment |
| |
| Hypertension | Diagnosed hypertension, with/without treatment |
| |
| Cystic kidney diseases | Diagnosed cystic kidney diseases, with/without treatment |
| |
| Tubulointerstitial diseases |
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| No intervention | Diagnostic Test | No intervention |
|
| Measure | Description | Time Frame |
|---|---|---|
| Association between DKK3 and eGFR decline | DKK3 and eGFR (CKD-Epidemiology Collaboration equation) | 24 months |
| 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) |
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Inclusion Criteria:
Exclusion Criteria:
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Outpatients ≥18 years of age with diagnosed HF or diabetes or hypertension or other etiologies of CKD
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| Name | Affiliation | Role |
|---|---|---|
| Werner Seeger, MD | University Hospital Giessen | Study Chair |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Clinic Giessen and Marburg - Campus Giessen | Giessen | Hesse | 35392 | Germany |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 30279273 | Background | 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. | |
| 27699213 |
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| ID | Term |
|---|---|
| D006333 | Heart Failure |
| D051436 | Renal Insufficiency, Chronic |
| ID | Term |
|---|---|
| D006331 | Heart Diseases |
| D002318 | Cardiovascular Diseases |
| D051437 | Renal Insufficiency |
| D007674 | Kidney Diseases |
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Diagnosed tubulointerstitial diseases, with/without treatment
|
| Glomerular diseases | Diagnosed glomerular diseases, with/without treatment |
|
| 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 |
| 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. |
| D014570 |
| Urologic Diseases |
| D052776 | Female Urogenital Diseases |
| D005261 | Female Urogenital Diseases and Pregnancy Complications |
| D000091642 | Urogenital Diseases |
| D052801 | Male Urogenital Diseases |
| D002908 | Chronic Disease |
| D020969 | Disease Attributes |
| D010335 | Pathologic Processes |
| D013568 | Pathological Conditions, Signs and Symptoms |