PERIMARK - DKK3 as a Biomarker of Peritoneal Fibrosis in Peritoneal Dialysis Patients: A Prospective, Monocentric, Exploratory Longitudinal Study With Biobanking
试验速览
- 阶段
- 不适用
- 状态
- 尚未招募
- 入组人数
- 30
- 试验地点
- 1
- 主要终点
- Change in DKK3/Creatinine Ratio in Urine, Dialysate and Serum
研究概览
简要总结
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.
详细描述
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.
研究设计
- 研究类型
- Observational
- 观察模型
- Cohort
- 时间视角
- Retrospective
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •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
排除标准
- •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)
研究组 & 干预措施
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.
干预措施: Modified Peritoneal Equilibration Test and DKK3 Biomarker Measurement (Diagnostic Test)
结局指标
主要结局
Change in DKK3/Creatinine Ratio in Urine, Dialysate and Serum
时间窗: 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).
次要结局
- 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)
- Early DKK3 Rise as Predictor of Later Aquaporin-1 Decline(12 weeks to 6 months)
研究者
Stefan Neuhaus
Consultant Nephrologist, Department of Internal Medicine IV - Nephrology and Hypertensiology
Universität des Saarlandes