DKK3 as a Biomarker of Peritoneal Fibrosis in Peritoneal Dialysis Patients

NCT07806708 | Not Yet Recruiting

• 1 other identifier: PERIMARK-2026-01
• Study Type: observational
• Target: 30
• Locations: 1 country
• Sites: 1

Brief Summary

Peritoneal dialysis (PD) uses the peritoneal membrane as a natural filter to remove waste products from the blood in patients with kidney failure. Over time, the peritoneal membrane can become scarred and less functional - a process called peritoneal fibrosis - which eventually leads to ultrafiltration failure and loss of the PD technique. Currently, there is no reliable early biomarker to detect this process before it causes clinical problems. PERIMARK is a prospective, single-center, observational study investigating whether DKK3 (Dickkopf-3), a protein involved in fibrosis signaling, can serve as an early biomarker of peritoneal membrane deterioration. DKK3 will be measured in urine, peritoneal dialysate and serum at four time points over 12 months (T0: catheter insertion; T1: 12 weeks; T2: 6 months; T3: 12 months). At each follow-up visit, peritoneal membrane function will be assessed by the Modified Peritoneal Equilibration Test (Modified PET) with 3.86% glucose, measuring the sodium dip (ΔDNa) as a marker of aquaporin-1-mediated water transport and D/P creatinine as a marker of small solute transport. The primary endpoint is the intraindividual change in DKK3/creatinine ratio in urine, dialysate and serum from baseline to 12 months. Secondary endpoints include the correlation of DKK3 with the sodium dip, longitudinal changes in peritoneal transport parameters, and the exploratory question of whether an early DKK3 rise predicts a later decline in aquaporin-1 function. The study also includes a biobank of serum, urine, dialysate supernatant and cell pellets for possible future analyses. Target enrollment is 25-30 patients.

Conditions

Peritoneal Dialysis (PD); Peritoneal Fibrosis; Ultrafiltration Failure; End Stage Renal Disease (ESRD)

Keywords

DKK3; Dickkopf-3; peritoneal membrane; biomarker; Modified PET; sodium dip; aquaporin-1; mesothelial-to-mesenchymal transition; longitudinal study; Biobanking

Outcome Measures

Primary Outcomes (1)

• Change in DKK3/Creatinine Ratio in Urine, Dialysate and Serum

  Intraindividual change in DKK3/creatinine ratio in urine, peritoneal dialysate and serum from baseline (T0) to 12 months (T3). Measured by DKK3 ReFine ELISA (DiaRen).

  12 months

Secondary Outcomes (6)

• Change in D/P Creatinine

  12 weeks to 12 months

• Correlation of DKK3 with Sodium Dip (ΔDNa)

  12 weeks, 6 months, 12 months

• Net Ultrafiltration and Ultrafiltration Failure

  12 weeks, 6 months, 12 months

• Change in Residual Renal Function

  12 months

• Peritoneal Transporter Classification

  12 weeks, 6 months, 12 months

Study Arms (1)

PD Patients

Consecutive adult patients with end-stage renal disease starting peritoneal dialysis after PD catheter insertion at the Department of Internal Medicine IV, Saarland University Medical Center. No comparator group.

Diagnostic Test: Modified Peritoneal Equilibration Test and DKK3 Biomarker Measurement

Interventions

Modified Peritoneal Equilibration Test and DKK3 Biomarker Measurement DIAGNOSTIC_TEST

Modified Peritoneal Equilibration Test (Modified PET) performed with 2L of 3.86% glucose solution according to La Milia et al. (Kidney Int 2006; DOI: 10.1038/sj.ki.5000183). Parameters assessed: sodium dip (ΔDNa at 60 min) as aquaporin-1 marker, D/P creatinine at 240 min for transporter classification, and net ultrafiltration by weighing. Concurrent blood, urine and peritoneal dialysate sampling for DKK3 measurement (Human DKK3 DuoSet ELISA, R\&D Systems) and biobanking. No drug or therapeutic agent is administered.

Also known as: Modified PET, mPET

PD Patients

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Consecutive adult patients with end-stage renal disease undergoing PD catheter insertion at the Department of Internal Medicine IV, Saarland University Medical Center, Homburg, Germany.

You may qualify if:

• Age ≥18 years
• End-stage renal disease with decision for peritoneal dialysis
• PD catheter insertion at Department of Internal Medicine IV, Saarland University Medical Center
• Written informed consent obtained at least 24 hours before the first study procedure

You may not qualify if:

• Age \<18 years
• Lack of capacity to give informed consent
• Pregnancy or breastfeeding
• Active malignancy (except basal cell carcinoma of the skin)
• Life expectancy \<12 months as assessed by the treating physician
• Severe peritoneal adhesions precluding PD catheter insertion (intraoperative assessment)

Sponsors & Collaborators

• Universität des Saarlandes: lead

Study Sites (1)

Saarland University Medical Center

Homburg, Saarland, 66421, Germany

Location

Related Publications (5)

• Ehleiter H, Miranda J, Boes D, Scheidt U, von Vietinghoff S, Schwab S. Peritoneal and renal DKK3 clearance in peritoneal dialysis. BMC Nephrol. 2024 Aug 23;25(1):268. doi: 10.1186/s12882-024-03715-7.

  PMID: 39179976 BACKGROUND

• Schunk SJ, Floege J, Fliser D, Speer T. WNT-beta-catenin signalling - a versatile player in kidney injury and repair. Nat Rev Nephrol. 2021 Mar;17(3):172-184. doi: 10.1038/s41581-020-00343-w. Epub 2020 Sep 28.

  PMID: 32989282 BACKGROUND

• Yanez-Mo M, Lara-Pezzi E, Selgas R, Ramirez-Huesca M, Dominguez-Jimenez C, Jimenez-Heffernan JA, Aguilera A, Sanchez-Tomero JA, Bajo MA, Alvarez V, Castro MA, del Peso G, Cirujeda A, Gamallo C, Sanchez-Madrid F, Lopez-Cabrera M. Peritoneal dialysis and epithelial-to-mesenchymal transition of mesothelial cells. N Engl J Med. 2003 Jan 30;348(5):403-13. doi: 10.1056/NEJMoa020809.

  PMID: 12556543 BACKGROUND

• La Milia V, Cabiddu G, Virga G, Vizzardi V, Giuliani A, Finato V, Feriani M, Filippini A, Neri L, Lisi L; Ultrafiltration Failure Assessment (UFFA) Study* of the Italian Society of Nephrology Peritoneal Dialysis Study Group. Peritoneal Equilibration Test Reference Values Using a 3.86% Glucose Solution During the First Year of Peritoneal Dialysis: Results of a Multicenter Study of a Large Patient Population. Perit Dial Int. 2017 Nov-Dec;37(6):633-638. doi: 10.3747/pdi.2017.00004. Epub 2017 Jul 11.

  PMID: 28698252 BACKGROUND

• La Milia V, Pozzoni P, Virga G, Crepaldi M, Del Vecchio L, Andrulli S, Locatelli F. Peritoneal transport assessment by peritoneal equilibration test with 3.86% glucose: a long-term prospective evaluation. Kidney Int. 2006 Mar;69(5):927-33. doi: 10.1038/sj.ki.5000183.

  PMID: 16518353 BACKGROUND

Biospecimen

Retention: SAMPLES WITH DNA

Serum (stored at -80°C), urine (stored at -80°C, only in patients with residual renal function \>0 ml/24h), peritoneal dialysate supernatant (centrifuged at 400×g, 10 min, 4°C, stored at -80°C for DKK3 ELISA and future biomarker analyses), peritoneal dialysate cell pellets (resuspended in CryoStor CS10, cryopreserved at -196°C in liquid nitrogen for possible future single-nucleus RNA sequencing or proteomics). Samples collected at T0 (catheter insertion), T1 (12 weeks), T2 (6 months) and T3 (12 months).

MeSH Terms

Conditions

Kidney Failure, Chronic; Peritoneal Fibrosis

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Peritoneal Diseases; Digestive System Diseases; Fibrosis

Central Study Contacts

Stefan Neuhaus, MD

CONTACT

+49 6841 16 15041; stefan.neuhaus@uks.eu

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: RETROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Consultant Nephrologist, Department of Internal Medicine IV - Nephrology and Hypertensiology

Study Record Dates

• First Submitted: September 1, 2026
• First Posted: September 8, 2026
• Study Start: September 1, 2026
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): June 1, 2029
• Last Updated: September 8, 2026

Record last verified: 2026-09

Data Sharing

• IPD Sharing: Will not share

Locations

DE (1)