The effect of calcineurin inhibitors on endothelial and platelet function in renal transplant patients.

BACKGROUND/AIM: Posttransplant cardiovascular mortality is still an important problem in renal transplant patients. In addition to conventional coronary risk factors, coagulation abnormalities play a key role in the hypercoagulable state observed in transplanted patients. Though renal transplantation eliminates cardiovascular disease risk factors by restoring renal function, it introduces new cardiovascular risks derived, in part from immunosupressive medications. We aimed to assess the effect of calcineurin inhibitors on endothelial function, platelet activation and aggregation in renal transplant patients. METHODS: 62 renal transplant were studied. Staging was performed according to immunosuppression regimen. Group 1 (n = 37) were treated with cyclosporine/mycophenolate mofetil/methylprednisolone and Group 2 (n = 25) were treated with tacrolimus/mycophenolate mofetil/methylprednisolone. The control group consisted of 16 healthy subjects (Group 3). Hematological and biochemical tests, asymmetric dimethyl arginine (ADMA), sP-selectin levels and platelet aggregation tests were studied. RESULTS: ADMA levels were higher in Group1 and statistically significant differences were observed compared with those of Group 2 and Group 3 (p < 0.05). Platelet aggregation values induced by all agonists (Adenosine diphosphate (ADP), epinephrine, ristocetin, collagen) were lower in Group 1 than Group 2 and Group 3, but the difference did not reach statistical significance (p > 0.05). There was a negative correlation between cyclosporine level and platelet aggregation values induced by ADP (r = -0.43, p < 0.01), ristocetin (r = -0.40, p < 0.05), epinephrine (r = -0.41, p < 0.05), and collagen (r = -0.43, p < 0.01). sP-selectin levels were appreciably higher in Group 1 and statistically significant differences were observed compared with those of Group 2 (p < 0.05) and Group 3 (p < 0.01). CONCLUSION: The results of our study suggest that CsA induces platelet activation without inducing platelet aggregation. Endothelial dysfunction due to vascular endothelial damage reflected by increases in ADMA values may increase the tendency for thrombotic events in patients who had undergone renal transplantation.

Late effects of renal transplantation on endothelial functions and cardiac morphology.

BACKGROUND: Endothelial dysfunction is common in patients undergoing hemodialysis (HD), and cardiovascular morbidity and mortality are higher in these patients. In this study, we evaluated the late posttransplantation effects of cyclosporine and tacrolimus on endothelial function, inflammation, and cardiac architecture. METHODS: The study included 12 patients undergoing hemodialysis (group 1); 22 renal transplant recipients, of which 13 were receiving cyclosporine therapy (group 2) and 9 were receiving tacrolimus therapy (group 3); and 12 healthy control individuals (group 4). Kidney recipients were included if the transplantation procedure had been performed at least 1 year before the study. Asymmetric dimethylarginine, C-reactive protein, carotid intima-media thickness, left ventricular posterior wall thickness, interventricular septal thickness, left ventricular muscle mass index, flow-mediated dilation, and nitroglycerine-induced dilation of the brachial artery were evaluated. RESULTS: Serum asymmetric dimethylarginine, C-reactive protein, carotid intima-media thickness, left ventricular posterior wall thickness, interventricular septal thickness, and left ventricular muscle mass index values were significantly higher in patients undergoing HD than in the other 3 groups (P < .05), whereas percent change in flow-mediated dilation and nitroglycerine-induced dilation of the brachial artery was significantly lower (P < .05). CONCLUSION: Patients undergoing HD demonstrate endothelial dysfunction. In the late posttransplantation period, kidney recipients seem to have similar endothelial function and cardiac architecture as in the healthy population. This result may explain the reduction in cardiovascular morbidity and mortality after transplantation in patients undergoing HD. Tacrolimus and cyclosporine have similar effects on endothelial function.

Successful treatment of nephrotic syndrome due to systemic AL amyloidosis after autologous stem cell transplantation: renal response is an important therapeutic end point.

Primary systemic (AL) amyloidosis involves vital organs from the early phase of illness, resulting in poor prognosis. Today, high-dose melphalan followed by autologous peripheral blood stem cell transplantation is an effective treatment for systemic AL amyloidosis. We report a patient with nephrotic syndrome due to systemic AL amyloidosis, who was successfully treated with autologous peripheral blood stem cell transplantation. At follow-up 36 months from ASCT, the patient showed a significant improvement in the signs of peripheral neuropathy and reduction in proteinuria without further organ involvement. Due to poor prognosis with conventional therapy, autologous stem cell transplantation should be considered for treatment in patients with systemic AL amyloidosis, and favorable outcome is ensured with achievement of renal response after ASCT.

Erythropoietin resistance as a result of oxalosis in bone marrow.

Anemia is an important cause of morbidity in patients suffering from chronic renal failure, and erythropoietin is a milestone of anemia treatment. Various factors may cause erythropoietin resistance. Herein, we describe the case of 32-year-old man who presented with anemia and weakness. He developed progressive renal failure secondary to recurrent kidney stones. One year before admission, he developed anemia for which he had been treated with erythropoietin. However, the anemia persisted. Examination of bone marrow biopsy specimen showed that the marrow was extensively replaced with oxalate crystals and fibrous connective tissue with severe decrease of hematopoietic cells. To the best of our knowledge, our patient represents the first case in the literature describing the association between the oxalate deposition and EPO resistance.

Renal involvement in primary antiphospholipid syndrome and its response to immunosuppressive therapy.

Antiphospholipid syndrome (APS) is the association between antiphospholipid antibodies, venous and arterial thrombosis and pregnancy morbidity. Although the kidney may be affected in APS, the treatment of renal involvement is yet to be elucidated. This report describes the clinical and laboratory features of four patients with primary APS nephropathy, and the beneficial effect of immunosuppressive therapy accompanied by warfarin and angiotensin-converting enzyme inhibitor. We also briefly discuss the possible mechanisms of the beneficial effects of immunosuppressives on primary APS nephropathy.

Coagulation, fibrinolysis and fibrinolysis inhibitors in haemodialysis patients: contribution of arteriovenous fistula.

BACKGROUND: End-stage renal disease (ESRD) patients, not uncommonly, might exhibit thrombotic complications, as well as they may present with a bleeding diathesis. Changes in vessel wall and/or blood flow in native arteriovenous fistula (AVF) might also augment these disarrangements, as vascular endothelium is predominantly involved in the regulation of haemostatic pathways. OBJECTIVE: This study was designed to evaluate the state of coagulation and fibrinolysis and the role of AVF on haemostatic defects, in ESRD patients on maintenance haemodialysis. METHODS: Plasma samples for prothrombin fragment 1+2, thrombin-antithrombin III complex, plasmin-alpha2 antiplasmin complex, tissue type plasminogen activator antigen, urokinase type plasminogen activator antigen, u-PA activity, plasminogen activity, alpha2-antiplasmin and alpha2-macroglobulin assays were obtained from AVF and contralateral large veins of ESRD patients and from peripheral veins of the control group. RESULTS: Our results indicate a predominant thrombotic state as evidenced by activated coagulation markers and enhanced fibrinolysis in systemic circulation of ESRD patients. However the most novel finding is the probable contribution of AVF on haemostatic activation, as proven by the statistically different and positively correlated concentrations of both coagulation, fibrinolysis, and fibrinolysis inhibitors in AVF when compared to the levels in peripheral venous circulation. CONCLUSION: In addition to systemic derangements of haemostasis in ESRD patients, AVF individually might have a substantial role in the modulation of coagulation and fibrinolytic cascade.

Effect of extracorporeal shock wave lithotripsy on glomerular and tubular functions.

To evaluate the early and late effects of extracorporeal shock wave lithotripsy on renal function, we prospectively designed a controlled study using a Direx lithotriptor. Twenty-five patients with renal stones and 16 healthy volunteers as the control group were included in the study. Blood and urine samples were collected before and after 24 hours, seven days and 8 months in the patient group. White blood cell count, serum levels of haemoglobin, urea, creatinine, SGOT, SGPT, AP, and LDH were determined. 24-hour urine specimens were collected to be tested for volume, excretion of creatinine, albumin, N-acetyl-beta-glucosaminidase, gamma-glutamyltransferase and beta-2-microglobulin. There were statistically significant increments in the secretion of urinary enzymes and albumin in the early period after ESWL, no longer lasting 8 months after the procedure. At 8 months one patient was hypertensive as judged by the diastolic pressure above 95 mm Hg. The results of this study showed that, although there was a transient glomerular and tubular damage after extracorporeal shock wave lithotripsy, the procedure seems safe and causes no permanent deterioration in renal function.