[Daclizumab in combination with mycophenolate mofetil and a late introduction of Tacrolimus at low doses, as a therapeutic approach in the elderly renal transplant donor-recipients pairs in kidney transplant]. / Daclizumab en combinación con Micofenolato Mofetil e introducción tardía de Tacrolimus a dosis bajas, como opción terapéutica en la pareja donante-receptor añoso en trasplante renal.

BACKGROUND: Nowadays, it is more frequent the use of kidneys from older donors in the renal transplantation. Moreover, it is also increasing the age of the recipients due to the ageing of the population treated with hemodialysis. This makes that recipients become older more commonly. This situation raises specific problems in the renal graft and in the recipient as well. In this manuscript we present the results of a multicenter study that analyzed an immunosuppressive strategy specifically designed to elderly renal transplant donor-recipients. METHODS: Patients > or =50 years were transplanted from donors > or =55 years. Immunosuppressive strategy consisted of daclizumab (2 doses of 1mg/Kg) in combination with steroids, mycophenolate mofetil (2g/daily during the first 45 days and then adjusted according to local practice) and Tacrolimus. Tacrolimus was introduced between 5 and 7 day post-transplantation, adjusting the predose levels between 4-8 ng/mL. Mean follow-up was 12 months. RESULTS: A total of 133 patients were included in the study. Mean age of recipients and donors was 61.3+/-6.2 years and 64.4+/-5.3, respectively. 42.9% of patients needed dialysis during the first week (median 4 days). Between first month and first year, serum creatinine improved from 2.0+/-1.0 mg/dl to 1.5+/-0.4 mg/dl. Similar improvements were observed when creatinine clearance (Cockroft-Gault) was calculated. The survival of patient and renal graft at 12 months was 97.7% and 96.1%, respectively. The acute rejection rate was 13.5%. Security profile was good, as expected. CONCLUSIONS: The Daclizumab and mycophenolate mofetil regimen with a late introduction of Tacrolimus at low doses is a good alternative in the elderly renal transplant recipients with a low immunologic risk.

De novo hemolytic-uremic syndrome/thrombotic microangiopathy in renal transplant patients receiving calcineurin inhibitors: role of sirolimus.

The aim of this study was to evaluate the outcome of ten renal transplant recipients who developed de novo hemolytic uremic syndrome/thrombotic microangiopathy (DnHUS) after treatment with calcineurin inhibitors among 3,862 patients transplanted during the period 2000-2001 in Spain, and the results of switching to sirolimus for resolution of this pathologic condition. No patient had end-stage disease due to primary HUS. The criteria of diagnosis were decreased renal function, biopsy-proven thrombotic microangiopathy, and no signs of acute rejection. Calcineurin inhibitors were completely removed and immediate treatment with sirolimus started after diagnosis. The follow-up period was 19.0+/-4.3 months, at least 12 months after diagnosis. One patient died of sepsis shortly after starting sirolimus therapy. The serum creatinine level in the series decreased from 5.2+/-2.6 mg/dL at the time of biopsy to 2.15+/-1.9 mg/dL 1 month later (P=.011). All but one of the nine recipients, who lost his graft 3 months later (80% success) maintained function, with a serum creatinine of 2.1+/-1.4 mg/dL and Cockroft index of 61.3+/-34 mL/min at the end of follow up. During this time, none of the patients experienced an acute rejection episode and sirolimus was maintained without any remarkable secondary effect. Sirolimus seems to be a promising alternative for the treatment of renal transplant patients who develop calcineurin inhibitor-induced DnHUS.

Efficacy and safety of losartan in the treatment of hypertension in renal transplant recipients.

Arterial hypertension, which represents a common problem in patients with renal transplant, contributes to the cardiovascular morbidity and mortality of these patients. The most usual immunosuppressive drugs (cyclosporine and FK-506) collaborate on the development of hypertension. Calcium channel blockers are the most habitually used antihypertensive drugs in this population, although its long-term hemodimamycs effects could be deleterious especially in transplanted patients with chronic graft nephropathy. Losartan, a specific blocker of angiotensin II (AT1) receptors, has demonstrated a potent antihypertensive effect with a good safety and tolerance profile. The glomerular effects of losartan could be useful in transplanted patients. The present open, prospective and multicenter study evaluated the efficacy and safety of losartan in the treatment of hypertension in a group of patients with a renal transplant. Seventy-six patients with systolic blood pressure > or = 140 and/or diastolic blood pressure > or = 90 mm Hg, and/or patients on therapy with one antihypertensive drug and related side effects were included. After inclusion, therapy with losartan 50 mg/24 hr was started, discontinuing the previous antihypertensive therapy and/or therapy which caused the side effects. At four weeks, if blood pressure (BP) was not controlled, hydrochlorothiazide 25 mg or furosemide 40 mg/24 hr was added. At baseline and at weeks 2, 4, 8 and 12, the following parameters were monitored: BP, creatinine, hematocrit, hemoglobin, glucose, ions, uric acid, cholesterol, triglycerides, bilirubin, SGOT, SGPT, GGT, LDH, calcium, phosphate, alkaline phosphatase, proteinuria, and both cyclosporine and FK-506 levels in whole blood. Sixty-seven patients completed the 12-week study period. Mean blood pressure decreased from 113 +/- 10 to 102 +/- 9 mm Hg at the end of the study (P < 0.0001); 38 of the 67 patients (56.7%) who completed the study had a SBP lower than 140 mm Hg and a DBP lower than 90. These blood pressures were obtained in 30 patients on monotherapy with losartan (78.9%). Proteinuria decreased significantly at week 4 and was confirmed at week 12, especially in patients with proteinuria > or = 300 mg/24 hr. Nine patients were withdrawn during the study period for different reasons. Serum creatinine showed a slight, non-clinically significant increase at week 4, remaining stable until the end of the study. Two patients developed a mild normocytic anemia, and three others presented a mild impairment of pre-existent anemia. No interactions with cyclosporine or FK-506 were described. These results indicate that losartan is effective in reducing BP in hypertensive patients with a renal transplant. It has a good tolerance profile and does not interfere with immunosuppressive therapy.