Renin Angiotensin System Blockade in Renal Transplant Patients With Presence of PECs in Urine
试验速览
- 阶段
- 4 期
- 发起方
- 入组人数
- 180
- 试验地点
- 1
- 主要终点
- prevention of fall of glomerular filtration rate
研究概览
简要总结
By means of a personalized medicine strategy, investigators are going to evaluate if the treatment with an angiotensin II receptor antagonist (ARAII) in renal transplant patients with the presence of renal progenitor cells (PECs) in the urine is able to prevent the expected loss of glomerular filtration (GFR) observed in this subgroup of patients. In addition, investigators intend to deepen the mechanisms of glomerular damage and glomerular repair involved in the process of chronic allograft damage.
详细描述
A randomized, double-blind clinical trial will be performed in renal transplant patients in month 6 post-transplant, at the time of protocol renal biopsy. After verifying the inclusion and exclusion criteria, informed consent will be obtained. Patients with urinary PECs will be randomized to 80 mg of valsartan vs. placebo (sample size calculated for a superiority study, 45 patients per group). Patients without PECs in urine will be followed according to usual clinical practice. The follow-up will be up to 2 years post-transplant. At baseline (6 m post-transplant) and at 2 years the GFR will be measured by means of iohexol clearance (main variable) and, in addition, we will analyze safety variables such as patient and graft survival and RAGIs. By means of morphometry techniques on renal biopsy and by measuring the renal cortical volume by high resolution CT, the number of glomeruli will be determined, which in turn, will allow to calculate the SN-GFR. Finally, in 5 patients per study group and in 5 controls, PECs of renal tissue will be isolated by means of laser microdissection techniques to perform single-cell RNA sequencing techniques to assess the molecular pathways involved in the glomerular damage and repair process and how the RAAS blockade modifies such molecular pathways.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Prevention
- 盲法
- None
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
- •Written informed consent
- •Stable renal function understood as a variation of eGFR of less than 15% in the last 3 months
- •Immunosuppression maintenance based on tacrolimus and MMF / MPA
排除标准
- •Chronic active infection by HCV, HBV, HIV.
- •Treatment with inhibitors of the renin angiotensin system.
- •Double kidney transplant or combined with another organ.
- •Immunosuppression of maintenance other than tacrolimus and MMF / MPA.
- •eGFR <20 ml / min / 1.73m
- •History of allergy or intolerance to inhibitors of the renin angiotensin system.
- •Physically fertile women who plan to become pregnant, are pregnant and
- •/ or breast-feeding, or who do not want to use effective contraception during their participation in the study.
- •Any other medical condition that, in the opinion of the investigator, based on the counting or review of clinical records, could affect the completion of the study, including, but not limited to, visual problems or cognitive impairment.
研究组 & 干预措施
Valsartan
Treatment with valsartan
干预措施: Valsartan 80Mg Oral Tablet (Drug)
结局指标
主要结局
prevention of fall of glomerular filtration rate
时间窗: 12 months
To assess whether treatment with an angiotensin II receptor antagonist (AIIRA) prevents the fall of glomerular filtration in the subgroup of kidney transplant patients with presence of PECs in urine.
次要结局
- podocyturia(12 months)
- Suspected Unexpected Serious Adverse Reaction (SUSAR) reporting unexpected serious adverse reactions)(12 months)
- Proteinuria(12 months)
- SN-GFR(12 months)
- Single cell RNA sequencing(12 months)
- graft survival(12 months)
- patient survival(12 months)
- Chronic Glomerular Lessions(12 months)
研究者
Josep M Cruzado
Head of Nephrology
Hospital Universitari de Bellvitge