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Hyperhomocysteinemia is now recognized as an independent risk factor for atherosclerotic cardiovascular disease in patients with normal renal function. Hyperhomocysteinemia is common in patients with chronic renal failure. Kidney transplant recipients have a high risk of cardiovascular death. Recently, attention has been paid to the association between homocysteine and cardiovascular disease. Dyslipidemia is also common in kidney transplant recipients. The purpose of this study was to assess whether fluvastatin in a dose of 20 mg affects homocysteine concentration in 10 stable renal transplant recipients. We evaluated Hcy, lipoprotein (a) by the use of commercially available kits as well as plasma fibrinogen and cholesterol, triglycerides and albumin levels. All the parameters were studied before and after 1, 2 and 3 months of fluvastatin treatment. Cholesterol and LDL decreased significantly as early as after 1 month and remained lowered during the therapy. No significant changes in Hcy, lipoprotein (a) and fibrinogen were found during therapy with fluvastatin. Fluvastatin is an effective hypolipemic agent and has no effect on Hcy and fibrinogen concentration in kidney transplant recipients.

Hyperleptinemia is also common in chronic renal failure, particularly in CAPD. On the other hand, cardiovascular events related to thrombosis are a predominant cause of death and account also for an important morbidity in uremic patients. Treatment with recombinant human erythropoietin (rHuEPO) may shift the precarious hemostatic balance towards thrombosis. Therefore, the aim of the study was to assess the relationships between leptin and platelet aggregation and some hemostatic parameters in CAPD patients treated with rHuEPO. The study was performed on 15 patients maintained on CAPD given rHuEPO and 13 subjects without rHuEPO therapy served as a control group. Platelet aggregation was studied in both platelet-rich plasma (PRP) and in the whole blood. Tissue factor (TF) and tissue factor pathway inhibitor (TFPI) (antigens and activities), von Willebrand factor, trombomodulin, protein C, thrombin activatable fibrinolysis inhibitor (TAFI) and leptin (serum and dialysate) were assayed by using commercially available kits. Patients in both groups studied did not differ significantly with respect to age, BMI, duration of renal replacement therapy, and other hematological and hemostatic parameters studied as well as leptin serum and dialysate leptin. In CAPD patients treated with rHuEPO serum and dialysate leptin significantly correlated with tissue factor pathway inhibitor, protein C, thrombomodulin, ristocetin-induced platelet aggregation in the whole blood and PRP. In CAPD patients not treated with rHuEPO the significant correlations were observed between serum and dialysate leptin and protein C. Positive correlations between platelet aggregation and leptinemia in CAPD patients might indicate that hyperleptinemia could be associated with the cardiovascular disease in dialyzed patients. Leptin might contribute at least in part to the thrombotic complications observed in CAPD patients., (Copyright 2002 S. Karger AG, Basel)

Kidney transplantation restores renal function (glomerular filtration and production of vitamin D), thereby improving renal bone disease observed during the dialysis period. But the degree of improvement is often incomplete. Some of bone disorders related to pre-transplant renal osteodystrophy can persist after transplantation. Furthermore, immunosuppressive drug regimens effect bone remodeling in kidney transplant recipients. Post-transplant bone and mineral disorders can be classified, according to their pathogenesis and appearance time, into two groups of entities: (i) bone disorders related to pre-transplant renal osteodystrophy that persist after renal transplantation and (ii) disorders arising de novo. The first group includes: secondary hyperparathyroidism, aluminium bone disease, and dialysis-related amyloid bone disease. Post-transplant bone disorders comprise a painful legs syndrome, avascular bone necrosis, and osteopenia. Glucocorticosteroids still play a significant role in the pathogenesis of bone disease in renal transplant recipients. Due to disturbances in bone remodeling that commonly occur after renal transplantation, it is important to monitor bone metabolism in these patients.

Complex disturbances in hemostasis characterise chronic renal insufficiency. Defect of primary hemostasis is a common cause of bleeding complications. The hemodialysis procedure (HD), by itself, influences platelet function (the key part of primary hemostasis) which is compromised after the procedure. Many functional defects of thrombocytes have been described in end stage renal failure (ESRF) patients; one of them is adhesion defect where the pivotal role plays the complex of glycoprotein Ib (GP Ib) and IX. The aim of the study was to determine the extent of activation, reactivity of platelets and expression of GP Ib in ESRF patients. The flow cytometry method was used, and thrombin was used for stimulation of thrombocytes. Membrane expression of GP Ib and selectin P was assessed in 14 hemodialysed patients before and after stimulation with thrombin, before and after HD and in 10 healthy persons. The patient group had lower expression of GP Ib on resting platelets and significantly lower expression of selectin P after stimulation with thrombin when compared to the control group. After HD, thrombocytes had much lower expression of GP Ib; however there was no difference in expression of selectin P when compared to the state before HD. A lower reduction of GP Ib expression after stimulation with thrombin was observed after and before HD. On the basis of the results the following conclusions may be drawn: hemo-dialysed ESRF patients have lower expression of platelet GP Ib and reactivity of thrombocytes; the HD results in further depression in expression of GP Ib and reactivity of thrombocytes. It is plausible that nitric oxide (NO) released during HD modulates the expression of selectin P, but it remains to be confirmed.

Disturbances in platelet functions are found in kidney diseases and may contribute to the progression of atherosclerosis with its thrombotic complications. Kidney allograft recipients are particularly prone to dyslipidemia and have a high risk of cardiovascular death. The purpose of this work was to assess effects of various immunosuppressive drugs on aggregation of platelets obtained from healthy volunteers and chronically hemodialyzed patients. Platelet aggregation in the whole blood and in PRP was induced by collagen (2-microgram/ml whole blood and PRP) arachidonic acid (0.75 mM whole blood and PRP), ADP (10 microM--whole blood and 5 microM--PRP), ristocetin (0.75 mg/ml--whole blood and 1.5 mg/ml--PRP) and was studied after preincubation with clinically relevant concentrations of cyclosporine A, FK 506, 15-deoxyspergualin, azathioprine, mizoribine, mycophenolic acid and mycophenolate mofetil. Preincubation with cyclosporine A resulted in a significant increase in platelet aggregation, whereas preincubation with FK 506, azathioprine, mizoribine, mycophenolic acid and mycophenolate mofetil caused a decrease in platelet aggregation. 15-deoxyspergualin did not affect platelet aggregation. Enhanced platelet aggregation in CSA-treated kidney allograft recipients may have clinical implications in regard to the reported tendency to thrombosis in those patients, and to CSA-induced nephrotoxicity. Thus, inhibition of platelet activity in these patients might be of clinical benefit.