Fatores de risco associados à perda do enxerto e óbito após o transplante renal / Risk factors associated with graft loss and death after kidney transplantation

Objetivo: Avaliar os fatores de risco relacionados à mortalidade e à perda do enxerto nos primeiros dois anos após o transplante renal. Métodos: Análise retrospectiva de transplantes renais realizados entre 2003-2006, utilizando banco de dados informatizado. os desfechos analisados foram: sobrevidas do paciente, do enxerto e fatores de risco através de análise multivariada de Cox. Resultados: Dos 2.364 transplantes, 67% foram com doador vivo (DV), 6% com doadores falecidos (DF) com critério expandido (DCE). As sobrevidas do paciente e do enxero foram superiores entre receptores de DV do que entre os de DF (97% vs 91%; 96% vs 83%, p<0,001). Ao final de 24 meses, os receptores de etnia negra apresentaram sobrevida do enxerto (84% vs 89%, p<0,05) inferior devido à maior mortalidade (sobrevida do paciente: 87% vs 93%, p<0,01). Na data do transplante, os fatores de risco relacionados à mortalidade do receptor foram o tipo de doador (DF, RR=2,4, IC 1,6-3,6) e a etnia negra (RR=1,8, IC 1,2-2,9). Os fatores de risco relacionados à perda do enxerto foram o tipo de doador (DF,RR=2,1, IC 1-3,2), DCE (RR=2,0 IC:1,2-3,3), presença de função retardada do enxerto (RR=1,8, IC 1,2-2,7) e ocorrência de rejeição aguda (RA, RR=3,5, IC2,5-4,8) no primeiro ano após o transplante. Aos seis meses de transplante, os fatores de risco relacionados à mortalidade do receptor foram o tipo de doador (DF, RR=2,5, IC 1,5-4,3) e a ocorrência de RA (RA, RR=2,4, IC 1,6-3,8). Os fatores de risco para a perda do enxerto foram o tipo de doador (DF, RR=2,0, IC 1,1-3,7), rins de DCE (DCE, RR=2,6, IC 1,1-6,2), a ocorrência de RA (RA, RR=9,5, IC 5,4-16,4) e a função renal no 6º mês (creatinina> 1,5 md/dL) (RR=2,1, IC 1,3-3,4). Conclusão: Os fatores de risco tradicionais continuam a exercer influência negativa nos desfechos do transplante.

Objective: To evaluate the risk factors related to mortality and graft loss in the first two years after renal transplantation. Methods: Retrospective analysis of renal transplants performed between 2003-2006, using computerized database. outcomes analyzed were patient survival, graft and risk factors by multivariate Cox Results: Of the 2364 transplants, 67% were living donor (DV), 6% with deceased donors (DF) with expanded criteria ( DCE). The survival of patients and grafts were higher among recipients than among DV DF (97% vs 91%, 96% vs 83%, p <0.001). At the end of 24 months, recipients of black ethnicity had graft survival (84% vs 89%, p <0.05) lower due to higher mortality (patient survival: 87% vs 93%, p <0.01) . At the time of transplant, the risk factors related to mortality of the recipient were donor type (FD, RR = 2.4, CI 1.6 to 3.6) and black race (RR = 1.8, CI 1, 2 to 2.9). Risk factors related to graft loss were donor type (FD, RR = 2.1, CI 1 to 3.2), DCE (RR = 2.0 CI :1,2-3, 3), presence delayed graft function (RR = 1.8, CI 1.2 to 2.7) and the occurrence of acute rejection (AR, RR = 3.5, IC2 0.5 to 4, 8) in the first year after transplantation. At six months after the transplant, the risk factors related to mortality of the recipient were donor type (FD, RR = 2.5, CI 1.5 to 4.3) and the occurrence of RA (RA, RR = 2.4 CI 1.6 to 3.8). Risk factors for graft loss were donor type (FD, RR = 2.0, CI 1.1 to 3.7), kidney DCE (DCE, RR = 2.6, CI 1.1 - 6.2), the occurrence of RA (RA, RR = 9.5, CI 5.4 to 16.4) and renal function at 6 months (creatinine> 1.5 md / dL) (RR = 2.1, CI 1.3 to 3.4). Conclusion: The traditional risk factors continue to exert negative influence on the outcomes of transplantation.

Mycophenolate mofetil vs. sirolimus in kidney transplant recipients receiving tacrolimus-based immunosuppressive regimen.

UNLABELLED: Mycophenolate mofetil (MMF) and sirolimus (SRL) are effective immunosuppressive drugs with distinct safety profile. METHODS: Kidney transplant recipients receiving tacrolimus (TAC)-based immunosuppressive regimen were randomized to receive fixed daily doses of MMF (2 g/d, n = 50) or SRL (one loading dose of 15 mg, 5 mg/d till day 7 and 2 mg/d thereafter, n = 50) without induction therapy. RESULTS: No differences were observed in the incidence of the composite (biopsy-confirmed acute rejection, graft loss or death) end-point (18% vs. 16%, p = 1.000), biopsy confirmed acute rejection (12% vs. 14%, p = 1.000), one-yr patient (94% vs. 98%, p = 0.308), graft (92% vs. 98%, p = 0.168), and death-censored graft survival (98% vs. 100%, p = 0.317) comparing patients receiving MMF or SRL respectively. Patients receiving SRL showed worse safety outcomes, higher mean creatinine (1.6 +/- 0.5 mg/dL vs. 1.4 +/- 0.3 mg/dL, p = 0.007), higher proportion of patients with proteinuria (52.0% vs. 10.7%, p = 0.041), higher mean urinary protein concentrations (0.3 +/- 0.5 g/L vs. 0.1 +/- 0.2 g/L, p = 0.012), higher mean cholesterol concentration (217 mg/dL vs. 190 mg/dL, p = 0.030), and higher proportion of patients prematurely discontinued from randomized therapy (26% vs. 8%, p = 0.031). CONCLUSION: In patients receiving TAC, MMF produced similar efficacy but superior safety profile compared with SRL.

Concentration-controlled use of sirolimus associated with reduced exposure of cyclosporine in black recipients of primarily living renal allograft donors: 12-month results.

AIM: This study was designed to identify optimal therapeutic sirolimus (SRL) concentrations in black kidney transplant recipients on reduced cyclosporine (CsA) exposure and prednisone. METHODS: Seventy patients (64 living/six deceased) received CsA (8-10 mg/kg/d), prednisone, and 15 mg loading dose followed by 5-mg fixed doses of SRL till day 7 when they were randomized to maintain SRL trough concentrations (high-performance liquid chromatography) of 8-12 (GI = 34) or 15-20 (GII = 36) ng/mL. RESULTS: Mean CsA concentrations were 109 +/- 53 vs. 89 +/- 41 ng/mL and 75 +/- 54 vs. 60 +/- 35 ng/mL (ns) at 2 and 6 months. Accordingly, mean SRL trough concentrations were 12.4 +/- 6.1 vs. 20.0 +/- 9.5 ng/mL (p < 0.001) and 10.8 +/- 5.8 vs. 18.0 +/- 6.1 ng/mL (p < 0.001). The incidence of biopsy-proven acute rejection [13% (GI: 18% vs. GII: 8%, ns)], graft loss or death was 16% (GI: 21% vs. GII: 11%, ns]. There were no deaths and three graft losses (GI = 1; GII = 2). Creatinine clearance was higher in GI (64.5 +/- 17 vs. 54.4 +/- 14.7 mL/min, p = 0.011). The incidence of post-transplant diabetes mellitus was 13% and no CMV disease was observed. CONCLUSION: In black recipients of primarily living renal allograft donors reduced CsA exposure and SRL concentration-controlled regimens produced low incidences of acute rejection, post-transplant diabetes mellitus and CMV disease, with no significant impairment in graft function.

An open-label randomized trial of the safety and efficacy of sirolimus vs. azathioprine in living related renal allograft recipients receiving cyclosporine and prednisone combination.

BACKGROUND: The ability of sirolimus (SRL), in combination with reduced exposure of cyclosporine, was investigated to prevent acute rejection and associated side effects. METHODS: Between June 1999 and February 2000, 70 recipients of primary one-haplotype living-related donor renal allografts were randomized to receive SRL (2 mg/d) or azathioprine (AZA) (2 mg/kg/d) combined with cyclosporine and prednisone. The primary end-point was a composite of first occurrence of biopsy-confirmed acute rejection, graft loss, or death during the first 3 months after transplantation. RESULTS: From week 4 to month 12, SRL patients received lower cyclosporine (week 4: 364 mg/d vs. 455 mg/d, p = 0.004; month 12: 195 mg/d vs. 255 mg/d, p = 0.038) doses and showed lower cyclosporine concentrations (week 4: 247 ng/mL vs. 309 ng/mL, p = 0.04; month 12: 143 ng/mL vs. 188 ng/mL, p = 0.045). Compared with AZA, SRL patients showed reduced 3-month primary end point (0% vs. 17.1%, p = 0.025), and reduced incidence of biopsy-confirmed acute rejection at 3 months (0% vs. 14.3%, p = 0.01) but not at 12 months (11.4% vs. 14.3%, NS). Mean creatinine at 12 months were not different (1.8 +/- 0.6 vs. 1.6 +/- 0.6, p = 0.23). Hyperlipidemia was the only adverse event more frequent among SRL patients (49% vs. 17%, p = 0.01). There were no differences in infections and no malignancies in both groups. CONCLUSIONS: The combination of 2 mg fixed doses of SRL, reduced cyclosporine exposure and prednisone was associated with a low incidence of acute rejection and did not result in significantly impaired graft function compared with patients receiving AZA, standard doses of cyclosporine and prednisone.

Time-dependent changes in cyclosporine exposure: implications for achieving target concentrations.

This study analyzed early changes in trough blood cyclosporine concentrations and cyclosporine exposures after kidney transplantation. Seventy-two patients who received cyclosporine-based immunosuppressive therapy were intensively monitored (C0) during the first 6 months after transplantation. Full pharmacokinetic studies were performed at day 4, and months 2, 3, and 6 after transplantation. Mean steady-state, dose-adjusted trough cyclosporine blood concentrations increased from 1.1+/-0.60 (day 7) to 2.0+/-1.20 ng/ml per mg (day 30, P<0.01). Steady-state, dose-adjusted cyclosporine exposure parameters (C0, Cmax, AUC, Cavg, and C12) were significantly lower at day 4 than at months 2, 3, and 6 after transplantation ( P<0.01). Initial cyclosporine doses produced target concentrations in only 30% of the patients at day 3. C2 was the single concentration that showed high and consistent correlation with serial AUC measurements ( r(2)>/=0.76). The incidence of biopsy-proven acute rejection was 20.5% and was not associated with ethnicity, HLA mismatch, adjunctive therapy, or blood trough cyclosporine concentrations below 200 ng/ml at day 3. Significant time-dependent increases in steady-state cyclosporine exposure occur during the first month after kidney transplantation. Due to the low relative bioavailability early after surgery, higher doses and more frequent cyclosporine dose adjustments are necessary to produce target exposures early after transplantation.