What is it about?

Overhydration is a common feature of patients with chronic kidney disease (CKD) and is associated with hypertension. It leads to cardiovascular diseases, progression of the CKD and eventually increased risk of death. In our study, we analyzed the body fluid status of 171 patients with CKD using bioimpedance spectroscopy (Body Composition Monitor [BCM], Fresenius Medical Care, Germany). We found that overhydration was present in more than a quarter of the investigated CKD patients and that it was associated with the following investigated parameters: edema, higher blood pressure, higher stages of the CKD, and proteinuria. The association of overhydration with proteinuria was very dominant in the statistical analyses. We further investigated the link between proteinuria and salt and water retention. It has been shown that the serine protease plasmin can activate the Epithelial Sodium Channel (ENaC) in the tubulus system of the kidney by cutting off a certain part of the γ-unit. Sodium (Na+) can pass through the activated channel from the urine side of the tubulus back to the blood. Sodium is followed by water, the consequence is overhydration. We found that the excretion of plasmin correlates with overhydration in CKD patients with proteiunuria in the non-nephrotic range. Plasmin concentrations in the urine of CKD patients were in a range sufficient to activate epithelial sodium channel currents in an oocyte expression model of the ENaC.

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Why is it important?

Our findings support the hypothesis that plasmin ending up in the urine of CKD patients might be a link between proteinuria and overhydration that needs to be investigated as a possible target for pharmacological treatment of overhydration in CKD patients.

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This page is a summary of: Association of Plasminuria with Overhydration in Patients with CKD, Clinical Journal of the American Society of Nephrology, March 2016, American Society of Nephrology,
DOI: 10.2215/cjn.12261115.
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