Two doses of daclizumab with delayed introduction of low-dose tacrolimus in elderly recipients of cadaveric renal transplants from donors >55 years of age.

BACKGROUND: Renal transplants from elderly donors have a high incidence of delayed graft function, which can be increased by the initial use of calcineurin inhibitors. Our purpose was to assess the safety and efficacy of an immunosuppressive regimen using anti-IL-2R antibodies and MMF that allows delayed introduction of low-dose tacrolimus using elderly donors to elderly recipients. METHODS: This observational study involved 13 transplant centers. In total there were 119 patients (age 60.5 +/- 6.6 years, range 50 to 77) who received a kidney from a donor of mean age 64 +/- 5 years (range 55 to 76), 94% of whom died from a CVA. Immunosuppression consisted of daclizumab (1 mg/kg in two doses; preoperatively and on day 14) combined with steroids, mycophenolate mofetil (initial dose of 2 g/d), and tacrolimus (0.1 mg/kg per day). Tacrolimus was introduced before day 7 (mean 5.5 days) and adjusted to a target level of 5 to 8 ng/mL. The mean follow-up was 8 months. RESULTS: Two grafts were lost due to primary nonfunction and acute rejection and 48 patients (40%) required dialysis due to delayed graft function, although it was generally of short duration (median 4 days; only 2 cases >2 weeks). Acute rejection occurred in 16 patients (13.4%), of whom 13 were biopsy-confirmed (10.9%; Banff 1997 grades I and II). Three patients withdrew from the study, and three died (sepsis, accident, and cardiovascular event). The remaining 111 patients continued follow-up, with a median creatinine value of 1.5 mg/dL at 12-months. Eighty-six percent of patients had at least one episode of infection, half of which were urinary tract infections. There were 16 cases of CMV infection. CONCLUSIONS: Based on the initial results, our immunosuppressive regimen seems to offer good short-term renal function while maintaining an acceptable rejection rate and a low incidence of serious infections.

Influence of the current management of renal transplant recipients on the prevalence of anemia and related costs.

The use of mycophenolate mofetil (MMF) and renin-angiotensin system blockers (RAB) to prevent and treat chronic graft nephropathy may affect the incidence of anemia in renal transplant recipients. We compared 2 sets of cadaver-donor recipients, namely those followed at the end of 1995 (group 1; n = 252) versus 2003 (group 2; n = 530) in terms of general characteristics, incidence of anemia (hemoglobin [Hb] < or =13 g/L males, 12 g/L females) or severe anemia (Hb < or =11 g/L males, 10 g/L females) and use cost of treatment with erythropoietin (EPO). Group 2 was significantly older, heavier and longer since grafting. Fifty-seven percent received MMF, 21% received azathioprine, and 5% received rapamycin. In group 1, 83% were given azathioprine. RAB were administered to 35.1% in group 2 versus 14.7% in group 1 (P < .001). Mean blood pressure was identical in the 2 groups, but graft function was worse in group 2 (Cockroft, 62 vs 74 mL/min; P < .001). Mean Hb levels (13.66 + - 3.1 vs 13.82 + - 1.7 g/L) and prevalence of anemia (36.9% vs 34.5%) for groups 1 and 2, respectively, were similar. The rate of severe anemia, however, was lower in group 2 (2.3% vs 8.7%; P < .001). The use of EPO increased from 2.8% (group 1) to 8.7% (group 2; P < .01). In 2003, the cost of EPO was calculated at 1982 Euros/patient-year and 91,150 Euros per year for the whole patient group. Despite accumulation of predisposing factors, the control of anemia in our patients has improved due to the expanded use of EPO. Along with its high cost, EPO therapy has potential positive repercussions on the quality of life and patient prognosis. Therefore, we need to precisely define the optimal use of EPO in renal transplant recipients.

[Interstitial pneumonitis associated with sirolimus administration in a renal transplantation patient: a clinical case]. / Neumonitis intersticial asociada al uso de sirolimus en un trasplantado renal: un caso clínico.

Sirolimus is an immunosuppressive drug which has proved its effectivity to reduce the incidence of acute rejection in renal transplantation receptors. As this drug lacks nephrotoxic effects, its simultaneous use with other anticalcineurinic drugs allows the use of reduced doses. Thrombocytopenia and hyperlipidemia are the best known side-effects of sirolimus administration. Alterations in hepatic biochemistry results are also common. Some instances of interstitial pneumonitis associated to its use have been recently reported. In this paper we present a clinical case related to this rare but already confirmed adverse side-effect, which apart from the other more common nosologies occurring in immunosuppressed patients, should be taken into account in the differential diagnosis of interstitial pneumonitis in patients who are being administered this drug.

Neumonitis intersticial asociada al uso de sirolimus en un trasplantado renal: un caso clínico / Interstitial pneumonitis associated to sirolimus administrion in a patient with renal transplantation: a clinical case

El sirolimus es un fármaco inmunosupresor que se ha demostrado eficaz en la reducción de la incidencia de rechazo agudo en los receptores de trasplante renal. Al no tener efectos nefrotóxicos, su uso sinérgico con otros anticalcineurínicos permite potencialmente la reducción de la dosis de estos. Entre sus efectos secundarios más conocidos se encuentra la trombocitopenia y la hiperlipidemia. También es frecuente la aparición de alteraciones en la bioquímica hepática. Recientemente se ha comunicado la existencia de algunos casos de neumonitis intersticial asociada al uso de sirolimus. Presentamos un caso clínico relativo a este infrecuente pero ya constatado efecto adverso, que creemos debe ser tenido en cuenta en el diagnóstico diferencial de las neumonías intersticiales que aparezcan en los pacientes que estén en tratamiento con este fármaco, junto con las otras nosologías de más frecuente aparición en el paciente inmunodeprimido (AU)

Sirolimus is an immunosuppressive drug which has proved its effectivity to reduce the incidence of acute rejection in renal transplantation receptors. As this drug lacks nephrotoxic effects, its simultaneous use with other anticalcineurinic drugs allows the use of reduced doses. Thrombocytopenia and hyperlipidemia are the best known side-effects of sirolimus administration. Alterations in hepatic biochemistry results are also common. Some instances of interstitial pneumonitis associated to its use have been recently reported. In this paper we present a clinical case related to this rare but already confirmed adverse side-effect, which apart from the other more common nosologies occurring in immunosuppressed patients, should be taken into account in the differential diagnosis of interstitial pneumonitis in patients who are being administered this drug (AU)

Safety and efficacy of delayed introduction of low-dose tacrolimus in elderly recipients of cadaveric renal transplants from donors over 55 years of age.

BACKGROUND: Renal transplants (RTs) from elderly donors show a high incidence of delayed graft function, which may be increased by the initial use of calcineurin inhibitors. OBJECTIVES: The purpose of this study was to assess the safety and efficacy of an immunosuppressive regimen using anti-IL-2R antibodies and mycophenolate mofetil (MMF) with delayed introduction of low-dose tacrolimus in RT from elderly donors to elderly recipients. METHODS: This observational study in 13 centers included 78 patients, aged 61+/-7 years (range, 50-77), who received a kidney from a donor with a mean age of 64+/-5 years (range, 55-76), 94% of whom had died from a cardiovascular accident (CVA). Immunosuppression consisted of 1 mg/kg daclizumab in two doses (pre-RT and on day 14) combined with steroids, mycophenolate mofetil (initial dose of 2 g/d), and tacrolimus (0.1 mg/kg per day). Tacrolimus was introduced before day 7 (mean, 5.5 days) and adjusted to a target level of 5 to 8 ng/ml. The mean follow up was 27 weeks. RESULTS: One graft was lost due to primary renal failure and 28 patients (36.4%) required dialysis due to delayed graft function, although it was generally of short duration (median, 4 days; only 2 cases >2 weeks). Acute rejection was seen in 11 patients (14%), with 9 of these confirmed by biopsy (11%, Banff 1997 grade I or II). Three patients withdrew from the study and two patients died (sepsis and accident). The remaining 72 patients continued follow up with a median 6-month creatinine value of 1.6 mg/dL. Sixty-seven percent of patients had at least one episode of infection, half of which were of urinary tract infections. There were nine cases of CMV infection. CONCLUSIONS: These initial results suggest that this immunosuppressive regimen offers good efficacy with regard to short-term renal function, while maintaining both an acceptable low rejection rate and incidence of serious infections.

Hepatitis C and the incidence of diabetes mellitus after renal transplant: influence of new immunosuppression protocols.

BACKGROUND: Hepatitis C has been associated with an increased incidence of diabetes mellitus (DM) following renal transplantation (RT). METHODS: Patients who underwent RT between 1985 and 2001 were excluded if they showed DM prior to RT, graft survival of less than 90 days, and unknown anti-HCV status (n=15). Two groups (G1 and G2) were distinguished according to the immunosuppressive regimen: G1 (transplanted 1985-1996) received steroids, azathioprine, and cyclosporine (n=330), whereas G2 (1997-2000) received new drugs in several combinations (MMF in 87% and/or tacrolimus in 35% [n=240]). Patients with HCV antibodies pre- and/or post-RT were considered HCV-positive. Post-RT DM requiring prolonged treatment with oral antidiabetics or insulin (>1 month) was assessed using Kaplan-Meier curves and Cox analysis. RESULTS: G2 patients were significantly older, had a greater body mass index (BMI), and suffered significantly less from acute rejection episodes during the first year than G1 patients. Furthermore, fewer required maintenance steroids. HCV-positivity was more common in G1 than in G2 (n=96, 29.1% vs n=27, 11.3%). Six G2 patients were successfully treated with interferon pre-RT, achieving negative PCR-HCV status (maintained post-RT). DM incidence at 4 years was similar in G1 and G2 (8.8% and 8.2%). G1 HCV-positive patients showed a greater risk of developing DM than HCV-negative patients (28.0% vs 6.2% at 10 years; P=001). In G1, multivariate analysis showed that age, BMI, and HCV-positivity were significant risk factors predicting DM (relative risk, 5.7; 95% confidence interval 2.7-12). In G2 patients, HCV was not associated with an increased risk of DM; in the multivariate analysis only age appeared to be a risk factor. CONCLUSIONS: The reported relationship between hepatitis C and post-RT DM was not observed among patients receiving new immunosuppressive treatments. Confirmation of this finding requires extended follow up. The reduced use of steroids and effective pre-RT use of interferon may also be responsible for the benefit.

Impaired kidney transplant survival in patients with antibodies to hepatitis C virus.

BACKGROUND: With a few exceptions, most published studies do not show an influence of antibodies to the hepatitis C virus (HCV) on the success of a kidney transplant. METHODS: We studied all our renal transplant recipients who had received kidneys from cadaver donors (n = 335) and had been treated with quadruple immunosuppression (steroids, azathioprine, and antilymphocyte antibodies, followed by cyclosporin). We had information on the status of the hepatitis C antibodies before and/or after the transplant in 320 cases (95.5%; in 300, pre-transplant). Patients with HCV antibodies before and/or after the transplant were considered to be HCV positive (HCV+). RESULTS: The HCV+ patients had more time in dialysis and a greater number of transfusions, hyperimmunized cases, and re-transplants. The evolution in the first post-transplant year was similar in both groups, but afterwards, the HCV+ patients had proteinuria more often as well as worse kidney function. The survival rate of the graft was significantly less in the HCV+ cases: 90.6, 68.3 and 51.0% at respectively 1, 5 and 10 years, compared with 91.5, 84.7 and 66.5% in HCV-patients (P<0.01). The patient survival rate was: 96.4, 87.0, and 71.9% in the HCV+ patients at 1, 5, and 10 years, compared with 98.2, 96.0 and 90.0% in the HCV- cases respectively (P<0.01). The differences remained the same in stratified studies according to time spent in dialysis or pre/post-transplant evolution of HCV antibodies, even when immunologically high-risk patients were excluded. In multivariant analysis, the presence of HCV antibodies acted as a independent prognostic factor for the survival of the kidney and the patient: 3.0 (1.8-5.0) and 3.1 (1.2-7.8) odds-ratio (95% of the confidence interval), respectively. The main cause of death among HCV+ patients was cardiovascular; there was no apparent increase in mortality rate due to infections or chronic liver disease. The loss of organs was mainly due to chronic nephropathy or death with a functioning kidney. CONCLUSION: The presence of hepatitis C antibodies, before or after transplantation, is associated with a worse long-term survival rate for both the patient and the transplanted kidney in our patients treated with quadruple therapy.