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Association of Plasminuria with Overhydration in Patients with CKD
Anja Schork1, Matthias Woern1, Hubert Kalbacher2
1Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital of Tuebingen, Tuebingen, Germany.
Insights
Hypervolemia is common in chronic kidney disease (CKD) and linked to proteinuria. This study suggests urinary plasmin, found in protein-rich urine, may connect proteinuria to fluid overload in CKD patients.
Area of Science:
- Nephrology
- Physiology
- Biochemistry
Background:
- Hypervolemia and hypertension are common in chronic kidney disease (CKD).
- Urinary plasmin has been implicated in sodium retention in nephrotic syndrome.
- The role of plasminuria in stable CKD with non-nephrotic proteinuria is not well understood.
Purpose of the Study:
- To investigate the association between fluid status and urinary plasminogen/plasmin excretion in patients with stable CKD.
- To determine if urinary plasmin can activate the epithelial sodium channel.
Main Methods:
- Cross-sectional study of 171 CKD patients.
- Bioimpedance spectroscopy (BCM) for fluid status assessment.
- ELISA for urinary plasminogen and plasmin quantification; in vitro oocyte experiments for channel activation.
Main Results:
- Overhydration was prevalent (29% >5%, 17% >10%) and associated with edema, hypertension, CKD stage, and proteinuria.
- Proteinuria was the strongest predictor of overhydration.
- Urinary plasmin(ogen) strongly correlated with proteinuria and overhydration; active plasmin found in 44% of patients.
Conclusions:
- Hypervolemia in CKD, even non-nephrotic, is strongly linked to proteinuria.
- Protein-rich urine contains significant plasminogen and active plasmin.
- Plasminuria may serve as a mechanism linking proteinuria to hypervolemia in CKD.
Background And Objectives:
Hypervolemia is a common feature of patients with CKD and associated with hypertension. Recent work has shown stimulation of sodium retention by urinary plasmin during nephrotic syndrome. However, it is unclear whether plasminuria plays a role in patients with stable CKD and non-nephrotic proteinuria.
Design, Setting, Participants, & Measurements:
In this cross-sectional study, we analyzed the fluid status of 171 patients with CKD consecutively presenting to our outpatient clinic from 2012 to 2013 using bioimpedance spectroscopy (Body Composition Monitor [BCM]; Fresenius Medical Care, Germany) and its associations to the urinary excretion of plasminogen and plasmin from a spot urine sample. Two-electrode voltage clamp measurements were performed in Xenopus laevis oocytes expressing human epithelial sodium channel to investigate whether plasmin in concentrations found in urine can activate the channel.
Results:
Overhydration >5% and overhydration >10% of the extracellular volume were found in 29% and 17% of the patients, respectively, and overhydration was associated with edema, hypertension, higher stages of CKD, and proteinuria. Proteinuria was the strongest independent predictor for overhydration (+0.58 L/1.73 m(2) per 10-fold increase; P<0.001). Urinary excretion of plasmin(ogen) quantified by ELISA correlated strongly with proteinuria (r=0.87) and overhydration (r=0.47). Using a chromogenic substrate, active plasmin was found in 44% of patients and correlated with proteinuria and overhydration. Estimated urinary plasmin concentrations were in a range sufficient to activate epithelial sodium channel currents in vitro. In multivariable analysis, urinary excretion of plasmin(ogen) was associated with overhydration similar to proteinuria.
Conclusions:
Hypervolemia in patients with CKD is strongly associated with proteinuria, even in the non-nephrotic range. Protein-rich urine contains high amounts of plasminogen and active plasmin, rendering plasminuria as a possible link between proteinuria and hypervolemia.
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