Pleiotropic effects of heparin and heparinoids in peritoneal dialysis.

Unfractionated heparin, low-molecular-weight heparins, and sulodexide belong to the family of glycosaminoglycans. Recent studies report on properties other than anticoagulant activities of these medications. They include modulation of cell growth and proliferation via actions on numerous growth factors affecting the immune system and matrix molecules production and degradation. Long-term peritoneal dialysis remarkably influences peritoneal cavity homeostasis by mechanisms mediated by growth factors. They initiate progression of pathological processes and further account for morphological and functional alterations of the peritoneal membrane. The best-recognized pathologies in peritoneal cavity under these conditions encompass inflammation, fibrosis, and vasculopathy, often leading to fatal encapsulating peritoneal sclerosis. Intraperitoneal heparin and its derivatives, by their pleiotropic actions, may influence these crucial processes and improve the peritoneal dialysis technique survival in a complex and so far understudied way. These issues, novel medical approaches, and their likely mechanisms have been reviewed.

Endothelial injury markers with high-dose intravenous iron therapy in renal failure.

Endothelial injury is prevalent in patients with chronic renal failure (CRF) and may be exacerbated by commonly used intravenous (IV) iron therapy. The effects of high-dose IV iron sucrose treatment (200 mg daily in 250 mL of 0.9% saline, administered over 1 hour, median treatment duration 5 days) on circulating endothelium and/or tissue injury markers such as hepatocyte growth factor, thrombomodulin, von Willebrand factor, and C-reactive protein levels were studied. The markers were determined in 24 anemic (mean hemoglobin 9.48 g/dL) pre-dialysis (median creatinine clearance 21.5 mL/min) patients with CRF and defined absolute and/or functional iron deficiency. The measurements were performed before iron administration and 24 hours after the last infusion. All the markers remained unchanged following the IV iron therapy (all p < 0.172); no thrombotic or other adverse effects were observed. In conclusion, the above high-dose IV iron sucrose supplementation does not cause evident endothelial or other tissue injury in patients with CRF, and is clinically safe.

Effects of enoxaparin on myeloperoxidase release during hemodialysis.

Myeloperoxidase (MPO) is a proteolytic and prooxidant enzyme largely assembled with the vascular wall, and a heparin-binding protein. We studied if low-molecular-weight heparin enoxaparin administered for hemodialysis (HD) anticoagulation causes systemic MPO activation. Plasma MPO levels were measured in patients undergoing maintenance HD with an intravenous bolus of enoxaparin. Patients were retested during HD employing dialyzers with heparin-grafted polyacrylonitrile membrane and no systemic enoxaparin administration. During enoxaparin-anticoagulated HD plasma MPO levels strikingly increased in all patients (8.6-fold at 10 minutes and 3.3-fold at 120 minutes, both P < 0.0001). The increments were directly associated with the enoxaparin dosage and strongly inversely with the predialysis levels of the enzyme. The increase in plasma MPO during systemic heparin-free HD was significantly less pronounced. Enoxaparin administered for HD anticoagulation induces a marked and dose-dependent increase in plasma MPO as a plausibly favorable result of the liberation of the enzyme from the vascular wall.

Cholecalciferol supplementation reduces soluble Klotho concentration in hemodialysis patients.

INTRODUCTION: Low levels of vitamin D are linked to numerous adverse clinical conditions in hemodialysis (HD) patients, including disturbances of mineral and bone metabolism and increased mortality. Klotho, a molecule involved in such processes as phosphate homeostasis and aging, exists in 2 forms: a transmembrane protein acting as a coreceptor for fibroblast growth factor 23 (FGF-23) and soluble form, which is formed by cleavage of the extracellular domain of this molecule. OBJECTIVES: The aim of the study was to evaluate the effect of cholecalciferol supplementation on soluble Klotho levels in HD patients. PATIENTS AND METHODS: This was a prospective, open-label trial examining the effects of cholecalciferol supplementation on selected laboratory markers in 22 patients on HD. Vitamin D deficiency was assessed by the measurement of 25-hydroxyvitamin D [25(OH)D] levels. Soluble Klotho, intact FGF-23, intact parathormone (iPTH), and markers of bone formation and resorption were measured at baseline and after 12 weeks of cholecalciferol supplementation. RESULTS: The levels of 25(OH)D increased, while those of iPTH and cross-linked C-telopeptide of type 1 collagen decreased significantly. Cholecalciferol treatment reduced the median concentration of soluble Klotho (from 438.73 pg/ml; interquartile range, 257.99-865.51 pg/ml; to 370.94 pg/ml; 181.72-710.91 pg/ml; P <0.05). FGF­23 levels were not affected by the treatment. CONCLUSIONS: Supplementation with cholecalciferol in HD patients decreases soluble Klotho levels without affecting the FGF-23 concentration. Replenishment of vitamin D stores results in a decrease in iPTH levels and reduced bone resorption.