Short summary

The study's specific objective is to analyze the role of aberrant urine protease activity (urokinase, plasmin (ogen), u-prostasin) for activation of ENaC and as a derivative thereof: blood pressure regulation; salt sensitivity of blood pressure and renal outcome in renal transplant patients.

The aim of this register-based retrospective study is to test by which extent high salt intake can predict hypertension and renal and cardiovascular end-points in kidney transplant patients with established microalbuminuria/proteinuria.

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Rationale

Proteinuria is a strong independent risk factor for graft loss in patients with kidney transplant. Sodium intake is associated independently with blood pressure in kidney transplant patients. The present proposal explores a new finding that pathologic loss of plasma proteases, i.e. plasmin, confers to pre-urine the ability to evoke adverse down-stream effects along the renal tubule: Augmented sodium retention with hypertension and edema through ENaC activation.

This project is a register-based retrospective study that encompasses kidney transplant patients at Odense University Hospital. From these patients there exist quarterly records of 24h urine excretion of sodium, potassium, protein and albumin, and ambulatory blood pressure for every year. On the basis of these data, the hypothesis is tested in a longitudinal observational design. Based on the urine samples all patients with significant proteinuria above 300 mg albumin or 500 mg protein/24h are identified. Based on the surrogate marker for sodium intake, which is 24h- urine sodium excretion, patients are divided into quartiles with respect to sodium excretion. During a follow-up time of 5 years, the cardiovascular event-free period, recorded serum creatinine, blood pressure and number of antihypertensives and cardiovascular endpoints (death, stroke or myocardial infarction) are recorded.

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Description of the cohort

This study is a register-based retrospective study that encompasses kidney transplant patients from Odense University Hospital 1995-2011.

Data and biological material

The data will be collected from the patient-journal; medical history, urine and plasma samples and ambulatory blood-pressure.

Collaborating researchers and departments

Department of Cardiovascular and Renal Research, Institute of Molecular Medicine, University of Southern

• PhD-student Gitte Rye Hinrichs
• Professor Boye L. Jensen, MD, PhD

Department of Nephrology, Odense University Hospital

• Senior Hospital Physician Claus Bistrup, PhD