Clinical trial NCT04769778: Renin Angiotensin System Blockade in Renal Transplant Patients With Presence of PECs in Urine
Official title: Renin Angiotensin System Blockade in Renal Transplant Patients With Presence of PECs in Urine
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE4
Conditions: Chronic Kidney Allograft Nephropathy
Keywords: renin angiotensin
kidney transplant
PEC's
Lead sponsor: Hospital Universitari de Bellvitge
Sponsor class: OTHER
First posted: 2021-02-25
Enrollment: 180
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: Treatment with valsartan versus no treatment
Primary purpose: PREVENTION

Brief 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.

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.

Eligibility criteria: 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.

Primary outcomes:
measure: prevention of fall of glomerular filtration rate
timeFrame: 12 months
Secondary outcomes:
measure: SN-GFR
timeFrame: 12 months
measure: Single cell RNA sequencing
timeFrame: 12 months
measure: podocyturia
timeFrame: 12 months
measure: graft survival
timeFrame: 12 months
measure: patient survival
timeFrame: 12 months
measure: Chronic Glomerular Lessions
timeFrame: 12 months
measure: Suspected Unexpected Serious Adverse Reaction (SUSAR) reporting unexpected serious adverse reactions)
timeFrame: 12 months
measure: Proteinuria
timeFrame: 12 months
Other outcomes:
Locations:
city: L'Hospitalet de Llobregat
country: Spain
facility: Nephrology Department. Hospital Universitari de Bellvitge
state: Barcelona
Study officials:
References: