Renal transplant recipients (RTRs) are at increased risk of cardiovascular complications. An altered hemorheological profile may determine both cardiovascular complications and progression of renal failure in RTRs. We performed this study to evaluate the rheologic status in 239 RTRs at least 12 months after transplantation with stable and normal renal function compared with 90 control subjects. In RTRs, a significantly higher hematocritadjusted, but not native, whole blood viscosity was found (P Ͻ .0001). Moreover, plasma viscosity and red blood cell deformability were significantly higher in patients than in control subjects (P Ͻ .0001), whereas no difference in erythrocyte aggregation between patients and control subjects was observed (P ϭ .5). Fibrinogen, but not hematocrit, significantly increased in RTRs (P ϭ .001). This preliminary study provides evidence of an altered hemorheologic profile in RTRs. C ardiovascular disease is the main cause of mortality and morbidity in transplant recipients. Traditional risk factors, such as smoking habit, hypertension, dyslipidemia, and diabetes, do not completely account for the high incidence of cardiovascular risk in these patients. Novel markers of cardiovascular risk, such as an altered hemorheologic profile may influence cardiovascular mortality in these patients. Clinical studies 1 provided evidence that abnormalities in blood flow properties may contribute to cardiovascular events, and an altered hemorheologic profile, which worses microcirculatory blood flow and influences vascular disease, might determine both cardiovascular complications and progression of renal failure in renal transplant recipients (RTRs). Few data are available concerning the impact of blood rheology in affecting cardiovascular risk in RTRs. 2,3 We performed the present study to investigate the rheologic status in RTR patients at least 12 months after transplantation with stable and normal renal function. METHODSWe investigated 239 RTR patients at least 12 months after transplantation with stable and normal renal function [156 men, median age 53 (range 17-75) y; 83 women, median age 50 (range 17-74) y] compared with 90 control subjects [38 men, median age 38 (range 22-63) y; 52 women, median age 41 (range 26 -61) y] with no history of renal or cardiovascular disease. Patients and control subjects gave their informed consents and the study was approved by the local Ethics Committee. Hemorheologic profile was performed by assessing both whole-blood viscosity (at shear rates of 0.512 and 94.5/s), plasma viscosity, erythrocyte deformability and aggregability, and coagulation parameters (hemoglobin, hematocrit, and fibrinogen concentrations) as previously described. 4 Statistical AnalysisData are reported as mean Ϯ SD and median (range) for nonparametric parameters, and the comparison between patients and controls was performed with the Mann-Whitney U test. All probability values were two tailed, with values of Ͻ.05 considered to be statistically significant. RESULTS
Peripheral arterial disease (PAD), is a common manifestation of systemic atherosclerosis. Advances on the development of such vascular disease have described with a number of novel risk factors. Hyperviscosity, due to alterations of blood cells and plasma components, may play a role on the pathogenesis of the disease. Aim of this study was to evaluate the possible association between hemorheological variables and PAD. The hemorheological variables [whole blood viscosity (WBV), erythrocyte deformability index (DI), plasma viscosity (PLV)] were analyzed in 90 patients and in 180 healthy subjects. WBV and PLV were measured by a Rotational Viscosimeter and DI by a filtrometer. DI and PLV were significantly different in patients as compared to controls. To investigate the possible association between these parameters and the disease we divided the study population into tertiles. At the univariate analysis, we found a significant association between the highest tertiles of PLV, of DI and the disease. A model adjusted for traditional risk factors showed an association between highest tertiles of PLV and PAD. After adjustment for confounding parameters highest tertiles of PLV remained to be significantly associated with the disease. Our data indicate that an alteration of plasma viscosity may modulate the predisposition to PAD.
Introduction: Cytomegalovirus (CMV) is still a major morbidity of organ transplantation. One of the strategies to deal with it is routine prophylaxis. This can be prohibitively expensive in a self financed health care system like in India. We planned to evaluate the efficacy and cost effectiveness of pre-emptive therapy (over routine prophylaxis) in donor and recipient seropositive (D+/R+) renal transplant patients at our centre. Methods: After appropriate consent, D+/R+ patients undergoing renal transplant at our centre were not given routine CMV prophylaxis. They were closely monitored with CMV quantitative DNA PCR every 15 days for six months post transplant. If PCR reported DNA copies of > 600, patients were started on pre-emptive therapy with 14 day therapy of intravenous (IV) gancyclovir (5 mg/kg) followed by oral vangancyclovir (900 mg per day adjusted according to GFR) given for 3 months (or till titres were below 600 copies). Incidence of CMV infection, DNA copies >600 and cost of therapy were analyzed. Results: Over a two year period (2007-09) we included 21 D+/R+ patients in this study. One patient was lost to follow up one month after transplant after detection of onset of humoral rejection. Another patient was excluded from the study since he received ATG for induction (delayed graft function) and therefore was shifted on routine prophylaxis. Of the 19 patients included for analysis, mean age was 36 years (range 22-55 years). Of these 14 were males and five were females. Twelve (63.15%) patients received induction therapy with IL2 receptor blocker (Simulect) while the remaining seven (36.85%) did not receive any induction therapy. All patients received triple immunosuppressive therapy with a combination of tacrolimus (serum level monitoring and dose adjustments), mycophenolate (fixed dose therapy) and prednisolone. We had one case of biopsy proven acute cellular rejection which was treated successfully with three bolus doses of 250 mg prednisolone. We noted a raised CMV DNA titre >600 copies in only one patient (5.26%). This patient had no clinical evidence of disease and was successfully treated with the pre-emptive protocol for the study. At our centre routine prophylaxis with oral vangancyclovir (450 mg twice daily) for 3 months costs INR 84,000 (US $ 1,807) while the cost of CMV DNA PCR monitoring for six months was INR 48,000 (US $ 904). The cost of pre-emptive therapy in the single patient needing this was INR 124,000 (US $ 2668). Conclusions: In this pilot study of D+/R+ renal transplant patients we noted a low incidence of significant CMV viremia (5.26%). The cost of CMV DNA PCR monitoring is more rational compared to routine prophylaxis (half the cost spread over twice the time period) for self financing patients. Thus, in living related renal transplant programme it is both safe and economical to use close monitoring with pre-emptive therapy instead of routine prophylaxis for D+/R+ patients. We need larger studies to confirm these preliminary results.
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