Proteinuria and Renal Perfusion in Renal Transplant Recipients

Study Overview
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Brief Summary
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Cardiovascular disease remains one of the major cause of mortality in renal transplant recipients, with the rate of cardiac death 10-times higher than that of the general population. An independent association between post-transplant proteinuria and cardiovascular risk has been previously reported. Diseased native kidneys with residual urine output or the transplanted kidney could be the source of proteinuria following renal transplantation. A clear differentiation of the source of proteinuria (native kidneys versus allograft) could be important for appropriate management. Proteinuria from native kidneys falls rapidly after renal transplantation, and persistent or worsening proteinuria is usually indicative of allograft pathology. The mechanisms behind the resolution of proteinuria of native kidney origin in the early post-transplant period are not well described. An association between vascular parameters of the macrocirculation and post-transplant proteinuria has been described. To the best of our knowledge no data is available describing a link between post-transplant proteinuria and vascular parameters of the microcirculation. In this study our goal is to analyze in a clinical trial in patients with end stage renal disease and residual urine output the relationship between proteinuria and renal perfusion of native kidneys before and after renal transplantation. In addition the investigators analyse if pre or post-transplant proteinuria is associated vascular and circulatory changes in the retinal circulation. Our hypothesis is that renal perfusion of native kidneys correlates with early post-transplant proteinuria. Moreover the investigators hypothesize that post-transplant proteinuria is associated with vascular remodeling processes of the microcirculation 2 and 4 to 12 months after transplantation. To prove this hypothesis the investigators aim to include 25 pre kidney transplant patients of our living donor kidney transplantation program. Total duration of this study for each patient is 5-12 months with total 4 visits, of which all are performed at the Clinical Research Center of the Department of Nephrology and Hypertension, University of Erlangen-Nuremberg. This study is important to better understand the mechanisms behind the fall of proteinuria after renal transplantation and the association between post-transplant proteinuria and cardiovascular risk.

Detailed Description
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Renal transplantation is the treatment of choice for patients with end-stage kidney disease. Although renal transplantation is associated with reduced morbidity and mortality compared to chronic dialysis, cardiovascular disease remains one of the major cause of mortality in this population, with the rate of cardiac death 10-times higher than that of the general population. Proteinuria is not only considered as a diagnostic marker of renal disease in both native as well as the transplanted kidney, but also is widely described as an independent risk factor for cardiovascular morbidity and mortality in general population. Analogous to its impact in the general population, an independent association between post-transplant proteinuria and cardiovascular risk has been previously reported. The prevalence of proteinuria in renal transplant recipients is reported between 10% and 45%. Fernandez-Fresnedo et al. demonstrated that persistent proteinuria doubles the risk of cardiovascular disease and all-cause mortality in renal transplant recipients. Diseased native kidneys with residual urine output or the transplanted kidney could be the source of proteinuria following renal transplantation. A clear differentiation of the source of proteinuria (native kidneys versus allograft) is important for appropriate management. Proteinuria from native kidneys falls rapidly after renal transplantation, and persistent or worsening proteinuria is usually indicative of allograft pathology. The mechanisms behind the resolution of proteinuria of native kidney origin in the early post-transplant period are not well described. CNI-induced renal vasoconstriction causing reduction in urine output from the native kidneys may be an explanation for the early resolution of native kidney proteinuria. However, the resolution of proteinuria of native kidney origin post-transplant have been reported in the pre-cyclosporine era. An association between vascular parameters of the macrocirculation and post-transplant proteinuria has been described. High-grade post-transplant proteinuria has been found to be associated with higher pulse wave velocity, which is a marker of arterial stiffness of large arteries. Up to our knowledge no data is available describing a link between post-transplant proteinuria and vascular parameters of the microcirculation. In this study our goal is to analyze in a clinical trial in patients with end stage renal disease and residual urine output the relationship between proteinuria and renal perfusion of native kidneys before and after renal transplantation. In addition the investigators analyse if pre- or post-transplant proteinuria is associated with vascular and circulatory changes in the retinal circulation. This study is a single-centre clinical study with 25 pre-kidney transplant patients of our living donor kidney transplantation program. This is an exploratory and non-confirmatory study, in which the investigators analyse renal perfusion of native kidneys in patients with end stage renal disease before and after kidney transplantation. Our hypothesis is that renal perfusion of native kidneys correlates with early post-transplant proteinuria. Moreover the investigators hypothesize that post-transplant proteinuria is associated with vascular remodeling processes of the microcirculation 2 and 4-12 months after transplantation.

Official Title
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A Prospective, Observational, Non-interventional, Single-center Study to Analyze the Relationship Between Proteinuria and Renal Perfusion in Renal Transplant Recipients

Conditions
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Pre-kidney Transplant, Living Donor Kidney Transplantation, Renal Perfusion, End Stage Renal Disease

Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Age of 18 - 75 years Male and Female patients Patients evaluated and accepted for living donor kidney transplantation with residual urine output of at least 500 ml/24 hours Informed consent has to be given in written form Exclusion Criteria: Patients in unstable conditions due to any kind of serious disease, that infers with the conduction of the trial active Drug or alcohol abuse Pregnant and breast-feeding patients Body mass index > 35 kg/m² Subjects who do not give written consent, that pseudonymous data will be transferred in line with the duty of documentation and the duty of notification according to § 12 and § 13 GCP-V Implanted pacemakers or defibrillators Other implanted metallic devices, which are not MRI compatible Claustrophobia Any other relevant clinical contraindication of MRI examination

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Study Plan
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How is the study designed?
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What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perfusion of native kidneys measured by ASL-MRI | The primary objective of the study is to analyze is to measure renal perfusion of native kidneys before and after renal transplantation | change from baseline perfusion of native kidneys at 2 months after renal transplantation | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Perfusion of transplant kidney measured by ASL-MRI | analyze perfusion of renal transplant | 2 months after renal transplantation | 
| Wall to lumen ratio of retinal arterioles by SLDF measurement | analyze wall to lumen ratio of retinal arterioles before and after renal transplant | change from baseline Wall to lumen ratio of retinal arterioles at 2 months and 12 months after renal transplantation | 
| Retinal capillary flow determined by SLDF measurement | analyze retinal capillary flow before and after renal transplant | change from baseline retinal capillary flow at 2 months and 12 months after renal transplantation | 
| Central systolic pressure assessed by Sphygmocor XCEL | analyze central systolic pressure before and after renal transplant | change from baseline central systolic pressure at 2 months and 12 months after renal transplantation | 
| Pulse pressure assessed by Sphygmocor XCEL | analyze pulse pressure before and after renal transplant | change from baseline pulse pressure at 2 months and 12 months after renal transplantation | 
| Pulse wave velocity assessed by Sphygmocor XCEL | analyze pulse wave velocity before and after renal transplant | change from baseline pulse wave velocity at 2 months and 12 months after renal transplantation | 
| estimated glomerular filtration rate assessed in our central lab | analyze estimated glomerular filtration rate before and after renal transplant | change from baseline estimated glomerular filtration rate at 2 months and 12 months after renal transplantation | 
| Cystatin C assessed in our central lab | analyze Cystatin C before and after renal transplant | change from baseline Cystatin C at 2 months and 12 months after renal transplantation | 
| Urinary albumin creatinine ratio assessed in our central lab | analyze Urinary albumin creatinine ratio before and after renal transplant in both spot and 24-h urine | change from baseline urinary albumine creatinine ratio at 2 months and 12 months after renal transplantation | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Kidney transplantation