Z. Sainz

Significance of cytomegalovirus infection in renal transplantation

The aim of this study was to establish the relationship between vascular lesion chronic allograft nephropathy (CAN) and the presence of cytomegalovirus (CMV) in kidney transplanted patients. We studied 259 consecutive kidney transplant recipients with a minimum follow-up of 6 months; the induction immunosuppressive therapy included a calcineurin inhibitor, mycophenolate mofetil, steroids, and the use of an antilymphocyte serum if the patients developed delayed graft function. CMV early antigen detection (pp65) was performed on a weekly basis between days 30 and 90 post transplantation. Prophylactic treatment was administered in the donor +/recipient-risk group, and preemptive therapy delivered for positive antigenemia namely 3 days of intravenous [IV] gancyclovir [GCV] plus 11 days of oral therapy [in the case of infection], or 14 days of IV GCV [in the case of disease]). An acute kidney allograft rejection episode preceded CMV in 64.3% of the patients, and CMV preceded acute rejection in 35.7% of the cases. We conclude that CMV disease is an independent risk factor for CAN. CMV infection is probably associated with CAN, suggesting that the greater the viral load, the higher the risk of CAN. It may be advisable to perform universal prophylaxis to lower the viral load and CAN.

Risk factors for cardiovascular disease after renal transplantation.

Cardiovascular diseases (CVD) have become the leading cause of mortality in renal transplant recipients. Well-known cardiovascular (CV) risk factors and graft dysfunction both play an important role in the development of the posttransplantation CV events. We studied 233 stable kidney transplant patients to establish the prevalence of CVD and to assess CV risk factors that can be evaluated (and modified) in daily clinical practice. While 6.2% of the patients had coronary heart disease (CHD) before the transplantation, 16% displayed at least 1 CV event posttransplantation. The most significant factors associated with CV events were as follows: gender, length of smoking, diabetes mellitus, hepatitis C virus antibodies (HCV), dyslipidemia, proteinuria, and serum creatinine levels.

Prevalence Evolution and Impact of Cardiovascular Risk Factors on Allograft and Renal Transplant Patient Survival

OBJECTIVE The prevalence of traditional cardiovascular risk factors in renal transplantation is high. Studying the evolution of cardiovascular risk factors over time may help us to design better strategies to control them. The relative impact of traditional cardiovascular risk factors on allograft survival and mortality in transplant recipients is not clear. This study was performed to determine the incidence and risk factors for allograft survival and mortality among renal transplant patients. PATIENTS AND METHODS We enrolled 250 patients who had undergone transplantation between 1980 and 2004. They were followed for various periods, and we analyzed the impact of traditional and nontraditional risk factors on renal allograft survival. RESULTS The prevalence of hypertension was >80% during all the follow-up periods. Blood pressure diminished, antihypertensive drug prescription increased, and 15% of patients had adequate blood pressure control during follow-up. The prevalence of pretransplant diabetes mellitus was 6.8%; the incidence of posttransplant diabetes mellitus (PTDM) was 14.2%. The prevalence of PTDM increased over the course of patient evolution. The prevalence of dyslipidemia was in all cases >70%; total cholesterol and low-density lipoprotein (LDL)-cholesterol decreased; prescription of statins increased; and the percentage of patients with good lipid control also increased. The 25% prevalence of active smoking at the time of transplantation decreased to 13.6% at 10 years posttransplantation. The mean patient follow-up was 8 +/- 4.6 years. Sixty-five patients (26%) lost their grafts and 40 (16%) died during follow-up. Donor age, exercise, diastolic blood pressure, renal function, and albumin levels were independent risk factors for graft loss. Charlson comorbidity index at transplantation, recipient and donor ages, exercise, diastolic blood pressure, and LDL-cholesterol posttransplantation were independent risk factors for mortality among renal transplant recipients. CONCLUSION Blood pressure and lipid control improved during follow-up, however, insufficiently among renal transplant patients. The prevalence of diabetes gradually increased, and the incidence of smoking cessation was low. Diastolic blood pressure, exercise, and albuminemia were the most significant modifiable cardiovascular risk factors for renal allograft survival. Diastolic blood pressure, LDL-cholesterol level, and exercise were the most relevant modifiable cardiovascular risk factors for the survival of renal transplant patients.

Tacrolimus in induction immunosuppressive treatment in renal transplantation: comparison with cyclosporine.

The aim of the study was to compare the efficacy and safety of induction immunosuppression therapies based on tacrolimus or cyclosporine (CsA) in kidney transplantation. The 240 kidney allograft recipients were divided into two groups: group 1 (n=94) received tacrolimus (.01 mg/kg per day), mycophenolate mofetil (MMF, 2 g/d), and steroids (30 mg/d); and group 2 (n=146) CsA (6 mg/kg per day), MMF (2 g/d), and steroids (30 mg/d). Antilymphocyte serum was administered in cases of acute tubular necrosis. The acute rejection rate was higher among group 2 (30.6%) compared with group 1 patients (12.2%) (P=.001). There were no significant differences between the groups in terms of age, gender, body surface area, serologic virus markers (in donor and recipient), baseline creatinine levels, cause of death, HLA incompatibilities, response to acute tubular necrosis, and number of dialysis sessions. We conclude that both immunosuppressive regimens are effective and safe in kidney transplantation. The survival rates of patients and grafts were similar, but the incidence and degree of acute rejection events were reduced in group 1; this finding may forecast a decreased incidence of chronic renal allograft nephropathy.

Use of recombinant human erythropoietin in kidney transplant patients with stable graft function.

The purpose of this work was to determine the necessity for rhuEPO for 50 kidney transplant patients with stable graft function. We analyzed the red cell series, blood pressure, renal function, anthropometric data of the donor and recipient, proteinuria, and relationship with other factors, including immunosuppressants, angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARB). The patients were divided into three groups depending on renal function: group A (with plasma creatinine <150 micromol/L), group B (151-250 micromol/L), and group C (>250 micromol/L). All patients were studied for 1 year. Erythropoietin use did not affect renal function, proteinuria or number of antihypertensive drugs group. The degree of renal dysfunction determined the time necessary to reach an adequate hemoglobin level (>12 g/L) and and the mean dose of weekly rhuEPO needed. The use of ACE inhibitors or ARBs increased the rhuEPO requirements in each group.

Assessment of cyclosporine therapeutic monitoring with C2 concentrations in stable renal allograft recipients

The optimal long-term C2 target to minimize the risk of chronic allograft nephropathy (CAN) has not yet been established in a prospective study. Furthermore, it is not known whether the target is the same in patients who also receive mycophenolate mofetil (MMF). We determined the 2-hour postdose concentration (C2) in a cohort of 65 maintenance renal transplant patients. The mean C0 level was 0.12 microg/mL and the C2 was 0.62 microg/mL. The overexposed patients are 14%. There was a good correlation between C0 and C2, and between C2 and the cyclosporine (CsA) dose. Patients receiving MMF display lower levels of C0 and C2, lower dosages of CsA, and higher levels of plasma creatinines. We did not observe significant differences on relating the level of absorption to patient age and sex, creatinine level, CsA dose, or coadministration of MMF. In conclusion, there is a low incidence of overexposed patients. C2 levels of approximately 0.6 microg/mL (and possibly may be sufficient in renal transplant patients. somewhat lower [0.5 microg/mL] in patients receiving MMF) Patients who display slow or fast absorption of CsA do not have any apparent characteristic.