Clinical trial NCT04111094: DKK3 for Prognosis and Monitoring of GFR Decline in Heart Failure
Official title: Urinary Dickkopf-3 for Prognosis and Monitoring of Glomerular Filtration Rate Decline in Patients With Heart Failure
Study type: OBSERVATIONAL
Overall status: COMPLETED
Conditions: Heart Failure
Chronic Kidney Diseases
Lead sponsor: University of Giessen
Sponsor class: OTHER
First posted: 2019-10-01
Enrollment: 290
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: COHORT
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Outpatients ≥18 years of age with diagnosed HF or diabetes or hypertension or other etiologies of CKD

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.

Eligibility criteria: 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

Primary outcomes:
measure: Association between DKK3 and eGFR decline
timeFrame: 24 months
Secondary outcomes:
measure: Association between proteinuria and DKK3
timeFrame: 24 months
measure: Persistent or worsening of HF
timeFrame: 24 months
measure: Need for renal replacement therapy
timeFrame: 24 months
measure: Association of venous congestion/volume overload with DKK3
timeFrame: 24 months
measure: Association of right and left ventricular function with DKK3
timeFrame: 24 months
Other outcomes:
Locations:
city: Giessen
country: Germany
facility: University Clinic Giessen and Marburg - Campus Giessen
state: Hessen
Study officials:
affiliation: University Hospital Giessen
name: Werner Seeger, MD
role: STUDY_CHAIR
References:
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.
citation: 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.