Effect of Moderate Caloric Restriction on Glomerular Growth After Kidney Transplantation

Study Overview
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Brief Summary
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One possible reason that weight gain after transplant may interfere with new kidney function is due to the enlargement of a kidney structure called the glomerulus. The researchers believe that modest caloric intake reduction (CIR) early after kidney transplantation can reduce the enlargement (hypertrophy) of the glomerulus associated with kidney transplantation and may improve long term allograft survival, by reducing glomerular hypertrophy mediated progressive glomerulosclerosis.

Official Title
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Effect of Moderate Caloric Restriction on Glomerular Growth After Kidney Transplantation

Conditions
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Kidney Transplant; Complications, Glomerular Disease, Weight Gain, Kidney Transplant

Intervention / Treatment
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* Behavioral: caloric intake reduction


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Recipients of kidney transplants where a post perfusion biopsy is obtained Body Mass Index between 25-30 kg/m2 at the time of randomization Non-diabetic Have a smart phone or active internet connection at home Exclusion Criteria: Patients on dual anti platelet agents or are on oral anti coagulation medication Patients who have had Bariatric Surgery

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 70 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
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Caloric Intake Reduction<br>The intervention group will be seen by the kidney disease dietician at all clinical visits for the first 3 months (weekly for month 1, every other week for months 2 and 3). During months 2 and 3, in the weeks that the patients are not in clinic, they will receive telephone calls from the dietician. Thus the intervention involves weekly assessment for the first 3 months (in person or over the telephone). After 3 months, the patient will not receive any further active dietary intervention from the dieticians unless the patient wishes to continue using the dieticians advice per clinic protocol. | Behavioral: caloric intake reduction<br>* The caloric intake reduction arm will been seen by the kidney disease dietitian at all clinical visits for the first 3 months (weekly for month 1, every other week for months 2 and 3).<br>|
| No Intervention: Standard of care<br>The standard of care arm will receive dietary guidance per current University of Michigan Transplant Center policy, where a one time face-to-face visit is provided in the first month after kidney transplant and then as requested by the patient or referred by physician. | |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in the Change in Baseline and 3 Month Glomerular Volume Between the Intervention and the Control Arm |  | Post-Perfusion (Time 0 or Study Enrollment) and 3 months | 
| Difference in the Number of Glomerular Ki67 Positive Cells Between the Intervention and the Control Arm | 3 month protocol biopsies will be stained with monoclonal antibodies against Ki67 to identify actively dividing cells and counted manually. | 3 months | 
| Difference in the Number of Glomerular DAPI Positive (Nuclei) Between the Intervention and the Control Arm | 3 month protocol biopsies will be stained with monoclonal antibodies against DAPI to identify nucleated cells in the glomerulus and counted manually. | 3 months | 
| Difference in the Number of TLE4 Positive (Podocyte Nuclei) Between the Intervention and the Control Arm | 3 month protocol biopsies will be stained with monoclonal antibodies against TLE4 to identify podocytes and counted manually. | 3 months | 
| Differences in Podocyte Detachment Rate Between the Intervention and the Control Arm | Urine samples obtained at the time of 3-month protocol biopsies will be utilized to compare the urinary podocin mRNA to urinary creatinine ratio | 3 months | 
| Difference in the Podocyte Hypertrophic Stress Between the Intervention and the Control Arm | Urine samples obtained at the time of 3-month protocol biopsies will be utilized to compare the urinary podocin mRNA to nephrin mRNA ratio | 3 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Difference in Glomerular Filtration Rate (GFR) at 3 and 12 Months Between the Intervention and the Control Arm | Differences in glomerular filtration rate (GFR) using both creatinine (modified diet in renal disease) as well as serum cystatin C based equations | 3 months, 12 months | 
| Difference in Proteinuria Between the Intervention and the Control Arm | Proteinuria measured by laboratory samples | Measured through study completion, about 3 months | 
| Difference in Glycosylated Hemoglobin (HbA1c) Percent in the Intervention and the Control Arms | Measure the difference in HbA1c between the two arms during 3 month protocol biopsies | 3 months | 
| Difference in Weight of Participants in the Intervention and Control Arms | Weight as measured by pounds | 3 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Caloric Intake Reduction, Dietician