title: Association of Plasminuria with Overhydration in Patients with CKD.
abstract: 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.
  
  
  
  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.
  
  
  
  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.
  
  
  
  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.
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital of Tuebingen, Tuebingen, Germany.
authors.forename: Anja
authors.initials: A
authors.lastname: Schork
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital of Tuebingen, Tuebingen, Germany.
authors.forename: Matthias
authors.initials: M
authors.lastname: Woern
authors.affiliation: Interfacultary Institute of Biochemistry, University Tuebingen, Tuebingen, Germany; and.
authors.forename: Hubert
authors.initials: H
authors.lastname: Kalbacher
authors.affiliation: Interfacultary Institute of Biochemistry, University Tuebingen, Tuebingen, Germany; and.
authors.forename: Wolfgang
authors.initials: W
authors.lastname: Voelter
authors.affiliation: Institute of Cellular and Molecular Physiology, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Regina
authors.initials: R
authors.lastname: Nacken
authors.affiliation: Institute of Cellular and Molecular Physiology, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Marko
authors.initials: M
authors.lastname: Bertog
authors.affiliation: Institute of Cellular and Molecular Physiology, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Silke
authors.initials: S
authors.lastname: Haerteis
authors.affiliation: Institute of Cellular and Molecular Physiology, Friedrich Alexander University Erlangen-Nürnberg, Erlangen, Germany.
authors.forename: Christoph
authors.initials: C
authors.lastname: Korbmacher
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital of Tuebingen, Tuebingen, Germany.
authors.forename: Nils
authors.initials: N
authors.lastname: Heyne
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital of Tuebingen, Tuebingen, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Peter
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital of Tuebingen, Tuebingen, Germany.
authors.forename: Hans-Ulrich
authors.initials: HU
authors.lastname: Häring
authors.affiliation: Department of Internal Medicine, Division of Endocrinology, Diabetology, Vascular Disease, Nephrology and Clinical Chemistry, University Hospital of Tuebingen, Tuebingen, Germany.
authors.forename: Ferruh
authors.initials: F
authors.lastname: Artunc
mesh_terms: D000328:Adult; D001823:Body Composition; D015992:Body Mass Index; D003430:Cross-Sectional Studies; D004487:Edema / Q000150:complications / Q000503:physiopathology*; D017097:Electric Impedance; D053503:Epithelial Sodium Channels / Q000378:metabolism; D045604:Extracellular Fluid; D005260:Female; D005341:Fibrinolysin / Q000652:urine*; D006801:Humans; D007424:Intracellular Fluid; D008297:Male; D008875:Middle Aged; D000074267:Organism Hydration Status; D010958:Plasminogen / Q000652:urine; D011507:Proteinuria / Q000209:etiology / Q000503:physiopathology; D051436:Renal Insufficiency, Chronic / Q000150:complications / Q000503:physiopathology* / Q000652:urine; D012737:Sex Factors
chemical_list: D053503:Epithelial Sodium Channels; D010958:Plasminogen; D005341:Fibrinolysin
keywords: Edema; Humans; Overhydration; Plasminogen; Plasminuria; body composition monitor; chronic kidney disease; epithelial sodium channel; plasmin; proteinuria