Peritoneal Dialysis (PD)PERIMARKNCT07806708
DKK3 as a Biomarker of Peritoneal Fibrosis in Peritoneal Dialysis Patients
An observational study of Peritoneal Dialysis (PD) and End Stage Renal Disease (ESRD), run by Universität des Saarlandes at 1 site in Germany.
Trial 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… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Peritoneal Dialysis (PD), End Stage Renal Disease (ESRD), Peritoneal Fibrosis
- What is being tested?
- Modified Peritoneal Equilibration Test and DKK3 Biomarker Measurement
- Type of treatment
- Injection or infusion
- How many people
- 30 participants
- Where
- 1 siteGermany
- Study dates
- 1 Sep 2026to 1 Jun 2029
- Phase
- Observational
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
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.
Who may be able to join
- 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
Who cannot join
- Age <18 years
- Lack of capacity to give informed consent
- Pregnancy or breastfeeding
- Active malignancy (except basal cell carcinoma of the skin)
- Active peritonitis at time of inclusion
- Life expectancy <12 months as assessed by the treating physician
- Severe peritoneal adhesions precluding PD catheter insertion (intraoperative assessment)
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Germany1 site
Saarland University Medical Center
Homburg, Saarland, 66421
Stefan Neuhaus, MD, +49 6841 16 15042, stefan.neuhaus@uks.eu
About this study
Official title: PERIMARK - DKK3 as a Biomarker of Peritoneal Fibrosis in Peritoneal Dialysis Patients: A Prospective, Monocentric, Exploratory Longitudinal Study With Biobanking
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.
Read more
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.
Read the detailed description
Background: Peritoneal fibrosis is the main limiting factor for long-term peritoneal dialysis. The underlying mechanism is mesothelial-to-mesenchymal transition (MMT), driven by TGF-β1 and the Wnt/β-catenin pathway. DKK3 is a profibrotically active glycoprotein acting as an amplifier in this network. The only published study of DKK3 in PD dialysate (Ehleiter et al., BMC Nephrology 2024, n=29) demonstrated measurable DKK3 levels and called for longitudinal follow-up studies. No prospective 12-month longitudinal study exists.
Study Design: Prospective, monocentric, non-interventional, exploratory cohort study with biobanking. No randomization, no blinding, no intervention. All treatment decisions remain with the treating physician.
Time Points:
T0 (Day 0): PD catheter insertion. Baseline blood and urine sampling. Initial peritoneal lavage sample for dialysate DKK3 baseline.
T1 (12 weeks / ~90 days): First Modified PET. Blood, urine and dialysate sampling. Combined with catheter quality control assessment.
T2 (6 months): Second Modified PET. Blood, urine and dialysate sampling. T3 (12 months): Third Modified PET. Blood, urine and dialysate sampling. Primary endpoint time point.
T30 (30 days): Telephone interview for catheter complication assessment only.
Modified PET Method: Performed according to La Milia et al. (Kidney Int 2006; DOI: 10.1038/sj.ki.5000183) using 2L of 3.86% glucose solution. Key parameters: sodium dip (ΔDNa at 60 min, reference value 8.4 ± 3.8 mmol/L) as aquaporin-1 marker, D/P creatinine at 240 min for transporter classification, and net ultrafiltration by weighing.
Biobanking: Dialysate samples are centrifuged at 400×g, 4°C, 10 minutes. Supernatant is stored at -80°C for DKK3 ELISA and future biomarker analyses. Cell pellets are cryopreserved in CryoStor CS10 at -196°C for possible future single-nucleus RNA sequencing or proteomics. Serum and urine aliquots are stored at -80°C.
DKK3 Measurement: Human DKK3 ELISA ReFine (by DiaRen). Dialysate samples diluted 1:50 in kit sample buffer prior to measurement (validated by spike-recovery: ~102% at 1:50 dilution). Creatinine in dialysate measured by enzymatic method (Jaffé method excluded due to glucose interference validated internally). Sodium measured by indirect ISE (COBAS); no correction formula required as validated internally.
Statistical Analysis: Exploratory study, no confirmatory hypothesis testing. Wilcoxon signed-rank test for paired comparisons, Spearman correlation for association analyses. No correction for multiple testing. Separate analysis of intention-to-treat and per-protocol populations. Urinary DKK3 evaluated only in patients with residual renal function >0 ml/24h.
- Conditions
- Peritoneal Dialysis (PD), End Stage Renal Disease (ESRD), Peritoneal Fibrosis, Ultrafiltration Failure
- Being tested
- Modified Peritoneal Equilibration Test and DKK3 Biomarker Measurement
- Keywords
- DKK3, Dickkopf-3, peritoneal membrane, biomarker, Modified PET, sodium dip, aquaporin-1, mesothelial-to-mesenchymal transition, longitudinal study, Biobanking
- Medical subject headings
- Kidney Failure, Chronic, Peritoneal Fibrosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Modified Peritoneal Equilibration Test and DKK3 Biomarker MeasurementDiagnostic test
Also called Modified PET, mPET
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.
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: Diagnostic Test: Modified Peritoneal Equilibration Test and DKK3 Biomarker Measurement |
What is being measured
The primary outcome is the main question the study is designed to answer.
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).
Measured: 12 months
Secondary outcomes (6)
Change in D/P Creatinine
Longitudinal change in dialysate-to-plasma creatinine ratio (D/P creatinine) at 240 minutes in Modified PET from T1 to T3.
Measured: 12 weeks to 12 months
Correlation of DKK3 with Sodium Dip (ΔDNa)
Spearman correlation between DKK3/creatinine ratio in dialysate and sodium dip (ΔDNa) in Modified PET at T1, T2 and T3.
Measured: 12 weeks, 6 months, 12 months
Net Ultrafiltration and Ultrafiltration Failure
Net ultrafiltration (ml) after 4-hour dwell with 3.86% glucose solution. Incidence of ultrafiltration failure defined as net UF <400 ml.
Measured: 12 weeks, 6 months, 12 months
Change in Residual Renal Function
Change in 24-hour urine volume and eGFR (CKD-EPI) from baseline to 12 months.
Measured: 12 months
Peritoneal Transporter Classification
Classification of peritoneal transport type (Low, Low-Average, High-Average, High) based on D/P creatinine at 240 minutes according to La Milia 2006.
Measured: 12 weeks, 6 months, 12 months
Early DKK3 Rise as Predictor of Later Aquaporin-1 Decline
Exploratory linear regression analysis: association between early DKK3 change (T0 to T1) and subsequent decline in sodium dip ΔDNa (T1 to T2).
Measured: 12 weeks to 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 Sep 2026
- Study start1 Sep 2026 (estimated)
- Primary completion1 Dec 2028 (estimated)
- Study completion1 Jun 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Peritoneal Dialysis (PD)Studies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Universität des Saarlandes
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Stefan Neuhaus, Universität des Saarlandes
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07806708
- Sponsor's protocol ID
- PERIMARK-2026-01
- Acronym
- PERIMARK
- Status last verified
- Sep 2026
- First submitted
- 1 Sep 2026
- Last updated
- 8 Sep 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No: No plan to share individual participant data. Aggregated, anonymized study results will be published in a peer-reviewed journal upon study completion.
Publications
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.
PubMed 39179976Schunk 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.
PubMed 32989282Yanez-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.
PubMed 12556543La 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.
PubMed 28698252La 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.
PubMed 16518353