DKK3 as a Biomarker of Peritoneal Fibrosis in Peritoneal Dialysis Patients

Condition(s) studied

Investigational drug(s) / intervention(s)

Modified Peritoneal Equilibration Test and DKK3 Biomarker Measurement: 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 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.

Eligibility

Primary outcome measure(s)

• Change in DKK3/Creatinine Ratio in Urine, Dialysate and Serum — 12 months
  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).

Trial sites (1)

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