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

Chronic Kidney Allograft Nephropathy Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT04769778
• Other study ID #: PRONE
• Status: Recruiting
• Phase: Phase 4
• Start date: February 19, 2020
• Est. completion date: June 2023

Study information

• Verified date: May 2021
• Source: Hospital Universitari de Bellvitge
• Contact: JOSEP M CRUZADO, MD, PhD
• Phone: 932607385
• Email: jmcruzado[@]bellvitgehospital.cat
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 180
• Est. completion date: June 2023
• Est. primary completion date: June 2023
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years and older

Eligibility

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.

Related Conditions & MeSH terms

• Chronic Kidney Allograft Nephropathy
• Kidney Diseases

Intervention

Drug:
• Valsartan 80Mg Oral Tablet
treatment with 80mg /day of valsartan

Locations

Country	Name	City	State
Spain	Nephrology Department. Hospital Universitari de Bellvitge	L'Hospitalet de Llobregat	Barcelona

Sponsors (1)

Lead Sponsor	Collaborator
Josep M Cruzado

Country where clinical trial is conducted

Spain, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	SN-GFR	Compare the SN-GFR (nephron glomerular filtration rate)	12 months
Secondary	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
Secondary	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
Secondary	graft survival	Evaluate the influence of treatment on graft survival	12 months
Secondary	patient survival	Evaluate the influence of treatment on patient survival and proteinuria.	12 months
Secondary	Chronic Glomerular Lessions	Evaluate the influence of treatment on number of participants with chronic glomerular lesions.	12 months
Secondary	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
Secondary	Proteinuria	Evaluate the influence of treatment on measure of proteinuria	12 months