Proteinuria and Renal Perfusion in Renal Transplant Recipients

End Stage Renal Disease Clinical Trial

Official title:

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

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06051812
• Other study ID #: TxASL2020
• Status: Recruiting
• Start date: September 2, 2021
• Est. completion date: December 31, 2024

Study information

• Verified date: July 2023
• Source: University of Erlangen-Nürnberg Medical School
• Contact: Dennis Kannenkeril, MD
• Phone: +49 9131 85
• Email: dennis.kannenkeril[@]uk-erlangen.de
• Is FDA regulated: No
• Study type: Observational

Clinical Trial Summary

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.

Description:

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 25
• Est. completion date: December 31, 2024
• Est. primary completion date: September 30, 2024
• Gender: All
• Age group: 18 Years to 75 Years

Eligibility

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

Related Conditions & MeSH terms

• End Stage Renal Disease
• Kidney Failure, Chronic
• Living Donor Kidney Transplantation
• Proteinuria
• Renal Perfusion

Locations

Country	Name	City	State
Germany	Clinical Research Center, Department of Nephrology and Hypertension, University of Erlangen-Nuremberg	Erlangen

Sponsors (1)

Lead Sponsor	Collaborator
University of Erlangen-Nürnberg Medical School

Country where clinical trial is conducted

Germany, 

References & Publications (12)

Barnas U, Schmidt A, Haas M, Kaider A, Tillawi S, Wamser P, Mayer G. Parameters associated with chronic renal transplant failure. Nephrol Dial Transplant. 1997;12 Suppl 2:82-5. — View Citation

Chronic Kidney Disease Prognosis Consortium; Matsushita K, van der Velde M, Astor BC, Woodward M, Levey AS, de Jong PE, Coresh J, Gansevoort RT. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet. 2010 Jun 12;375(9731):2073-81. doi: 10.1016/S0140-6736(10)60674-5. Epub 2010 May 17. — View Citation

D'Cunha PT, Parasuraman R, Venkat KK. Rapid resolution of proteinuria of native kidney origin following live donor renal transplantation. Am J Transplant. 2005 Feb;5(2):351-5. doi: 10.1111/j.1600-6143.2004.00665.x. — View Citation

Fernandez-Fresnedo G, Escallada R, Rodrigo E, De Francisco AL, Cotorruelo JG, Sanz De Castro S, Zubimendi JA, Ruiz JC, Arias M. The risk of cardiovascular disease associated with proteinuria in renal transplant patients. Transplantation. 2002 Apr 27;73(8):1345-8. doi: 10.1097/00007890-200204270-00028. — View Citation

Guliyev O, Sayin B, Uyar ME, Genctoy G, Sezer S, Bal Z, Demirci BG, Haberal M. High-grade proteinuria as a cardiovascular risk factor in renal transplant recipients. Transplant Proc. 2015 May;47(4):1170-3. doi: 10.1016/j.transproceed.2014.10.062. — View Citation

Laplante L, Beaudry C, Houde M. [Early disappearance of proteinuria attributed to the original kidneys after kidney transplantation]. Union Med Can. 1975 Feb;104(2):246-8. No abstract available. French. — View Citation

Liefeldt L, Budde K. Risk factors for cardiovascular disease in renal transplant recipients and strategies to minimize risk. Transpl Int. 2010 Dec;23(12):1191-204. doi: 10.1111/j.1432-2277.2010.01159.x. Epub 2010 Sep 7. — View Citation

Ojo AO, Hanson JA, Wolfe RA, Leichtman AB, Agodoa LY, Port FK. Long-term survival in renal transplant recipients with graft function. Kidney Int. 2000 Jan;57(1):307-13. doi: 10.1046/j.1523-1755.2000.00816.x. — View Citation

Peterson JC, Adler S, Burkart JM, Greene T, Hebert LA, Hunsicker LG, King AJ, Klahr S, Massry SG, Seifter JL. Blood pressure control, proteinuria, and the progression of renal disease. The Modification of Diet in Renal Disease Study. Ann Intern Med. 1995 Nov 15;123(10):754-62. doi: 10.7326/0003-4819-123-10-199511150-00003. — View Citation

Roodnat JI, Mulder PG, Rischen-Vos J, van Riemsdijk IC, van Gelder T, Zietse R, IJzermans JN, Weimar W. Proteinuria after renal transplantation affects not only graft survival but also patient survival. Transplantation. 2001 Aug 15;72(3):438-44. doi: 10.1097/00007890-200108150-00014. — View Citation

Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, Held PJ, Port FK. Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med. 1999 Dec 2;341(23):1725-30. doi: 10.1056/NEJM199912023412303. — View Citation

Yildiz A, Erkoc R, Sever MS, Turkmen A, Ecder ST, Turk S, Kilicarslan I, Ark E. The prognostic importance of severity and type of post-transplant proteinuria. Clin Transplant. 1999 Jun;13(3):241-4. doi: 10.1034/j.1399-0012.1999.130304.x. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	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	Perfusion of transplant kidney measured by ASL-MRI	analyze perfusion of renal transplant	2 months after renal transplantation
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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
Secondary	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

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