Renin Angiotensin System Blockade in Renal Transplant Patients With Presence of PECs in Urine

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.

Study Overview

• Status: Recruiting
• Conditions: Chronic Kidney Allograft Nephropathy
• Intervention / Treatment: Drug: Valsartan 80Mg Oral Tablet

Detailed Description

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.

• Study Type: Interventional
• Enrollment (Anticipated): 180
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: JOSEP M CRUZADO, MD, PhD; Phone Number: 932607385; Email: jmcruzado@bellvitgehospital.cat
• Study Contact Backup: Name: Carolina Polo, PhD; Phone Number: +34 93 260 73 85; Email: cpolo@idibell.com

Study Locations

• Spain
  • Barcelona
    • L'Hospitalet de Llobregat, Barcelona, Spain, 08907
      • Recruiting
      • Nephrology Department. Hospital Universitari de Bellvitge
      • Contact: Josep M Cruzado, Medical Doctor; Phone Number: 0034932607602; Email: 27541jcg@comb.es
      • Contact: CAROLINA POLO, PhD; Phone Number: 932607385; Email: cpolo@idibell.cat

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• 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

Exclusion Criteria:

• 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 / 1.73m2.
• 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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Prevention
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Valsartan; Treatment with valsartan	Drug: Valsartan 80Mg Oral Tablet; treatment with 80mg /day of valsartan
No Intervention: no treatment; no treatment received

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
prevention of fall of glomerular filtration rate	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.	12 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
SN-GFR	Compare the SN-GFR (nephron glomerular filtration rate)	12 months
Single cell RNA sequencing	Carry out single cell RNA sequencing studies using cell microdissection techniques of PEC cells isolated from renal biopsies performed at 6 and 24 m after transplantation in patients without uPECs and in patients with uPECs included in the therapeutic intervention study. These studies will allow us to know the changes of gene expression in PECS cells that can be associated with the favorable response in treated or untreated patients.	12 months
podocyturia	To determine the influence of the treatment on podocyturia and the preservation of the number of podocytes at 2 years post transplant.	12 months
graft survival	Evaluate the influence of treatment on graft survival	12 months
patient survival	Evaluate the influence of treatment on patient survival and proteinuria.	12 months
Chronic Glomerular Lessions	Evaluate the influence of treatment on number of participants with chronic glomerular lesions.	12 months
Suspected Unexpected Serious Adverse Reaction (SUSAR) reporting unexpected serious adverse reactions)	Evaluate the safety of the treatment on the number of patients with Suspected Unexpected Serious Adverse Reaction (SUSAR) reporting unexpected serious adverse reactions) unexpected adverse reactions) and rate of treatment discontinuations.	12 months
Proteinuria	Evaluate the influence of treatment on measure of proteinuria	12 months

Collaborators and Investigators

• Sponsor: Josep M Cruzado

Study record dates

Study Major Dates

• Study Start (Actual): February 19, 2020
• Primary Completion (Anticipated): June 1, 2023
• Study Completion (Anticipated): June 1, 2023

Study Registration Dates

• First Submitted: January 7, 2021
• First Submitted That Met QC Criteria: February 21, 2021
• First Posted (Actual): February 25, 2021

Study Record Updates

• Last Update Posted (Actual): May 19, 2021
• Last Update Submitted That Met QC Criteria: May 17, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: kidney transplant; renin angiotensin; PEC's
• Additional Relevant MeSH Terms: Urologic Diseases; Kidney Diseases; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Angiotensin II Type 1 Receptor Blockers; Angiotensin Receptor Antagonists; Valsartan
• Other Study ID Numbers: PRONE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No