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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

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

Conditions
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Chronic Kidney Allograft Nephropathy

Intervention / Treatment
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* Drug: Valsartan 80Mg Oral Tablet


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Prevention
Allocation: Randomized
Intervention Model: Parallel Assignment
Interventional Model Description: Treatment with valsartan versus no treatment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Valsartan<br>Treatment with valsartan | Drug: Valsartan 80Mg Oral Tablet<br>* treatment with 80mg /day of valsartan<br>|
| No Intervention: no treatment<br>no treatment received | |

What is the study measuring?
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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 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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renin angiotensin, kidney transplant, PEC's