ABSTRACT
BACKGROUND: This study compared the long-term effects of switching from cyclosporine to tacrolimus on the incidence, progression, and severity of chronic renal allograft failure in patients with elevated serum creatinine levels. METHODS: Patients were assigned randomly (2:1) to switch to tacrolimus or remain on cyclosporine. Tacrolimus was initiated at 1/50th of the cyclosporine dose or 0.15 mg/kg/day, whichever dose was lower, to maintain trough concentrations between 5 and 15 ng/mL. Cyclosporine doses were adjusted to achieve trough concentrations between 100 and 300 ng/mL. RESULTS: At 60 months, the median change from baseline in serum creatinine was -0.2 mg/dL in the tacrolimus group and 0.3 mg/dL in the cyclosporine group (P=0.003). Median change in estimated creatinine clearance was 1.2 mL/min in the tacrolimus group and -4.1 mL/min in the cyclosporine group (P=0.019). The incidence of new-onset diabetes, hyperglycemia, hypertension, lymphoma, and malignancies was generally low and comparable between groups. Fewer patients in the tacrolimus group than in the cyclosporine group developed new cardiac conditions (11% vs. 28%, P=0.004), had low-density lipoprotein (LDL) cholesterol values more than 130 mg/dL (29% vs. 57%, P=0.002), or developed hyperlipidemia (24% vs. 67%, P=0.046) during the 60-month follow-up period. Despite these changes, patient and graft survival were similar for both groups. CONCLUSION: Switching from cyclosporine to tacrolimus resulted in improved renal function and a reduction in the occurrence of new-onset cardiac conditions and hyperlipidemia, with no increase in the incidence of new-onset diabetes or new-onset hyperglycemia. However, after 5 years there was no impact on patient or graft survival.
Subject(s)
Cyclosporine/therapeutic use , Kidney Transplantation/immunology , Tacrolimus/therapeutic use , Adult , Cyclosporine/adverse effects , Female , Follow-Up Studies , Humans , Immunosuppressive Agents/therapeutic use , Kidney Function Tests , Kidney Transplantation/mortality , Kidney Transplantation/pathology , Kidney Transplantation/statistics & numerical data , Male , Middle Aged , Patient Selection , Survival Analysis , Treatment Failure , Treatment OutcomeABSTRACT
A patient with a history of type II diabetes mellitus (DM), end stage renal disease (ESRD), and congestive heart failure (CHF) developed necrotizing fasciitis caused by Serratia marcescens after scraping his leg on rocks in a river while fishing. Aggressive management with surgical debridement, antibiotics, and pressure support was unsuccessful.
Subject(s)
Fasciitis, Necrotizing/diagnosis , Serratia Infections/diagnosis , Serratia marcescens/isolation & purification , Anti-Bacterial Agents , Combined Modality Therapy , Debridement/methods , Diabetes Mellitus, Type 2/complications , Diabetes Mellitus, Type 2/diagnosis , Diabetes Mellitus, Type 2/drug therapy , Disease Progression , Drug Therapy, Combination/therapeutic use , Fasciitis, Necrotizing/therapy , Fatal Outcome , Heart Failure/complications , Heart Failure/diagnosis , Heart Failure/therapy , Humans , Kidney Failure, Chronic/complications , Kidney Failure, Chronic/diagnosis , Kidney Failure, Chronic/therapy , Lower Extremity , Male , Middle Aged , Serratia Infections/therapy , Severity of Illness IndexABSTRACT
This study prospectively compared immunoprophylaxis with a single intraoperative dose (2 mg/kg) of monoclonal interleukin-2 receptor (IL-2R) antibody vs. noninduction in kidney transplant recipients treated with tacrolimus (FK 506), mycophenolate mofetil (MMF) and a prednisone-based immunosuppression regimen. One hundred recipients of first-kidney transplant were enrolled into the study to receive either anti-IL-2R monoclonal antibody, daclizumab (2 mg/kg intraoperatively, limited anti-IL-2R) or no induction (control). Each patient also received oral tacrolimus (dosed to target trough level 10-15 ng/mL), MMF (500 mg bid) and prednisone. The primary efficacy end-point was the incidence of biopsy proven acute rejection during the first 6 months post-transplant. The patients were also followed for 12-month graft function, and graft and patient survival rates. Other than the donor's age being significantly lower in the control group, both groups were comparable with respect to age, weight, gender, race, human leukocyte antigen (HLA)-DR mismatch, panel reactive antibody (%PRA), cold ischemic time, cytomegalovirus (CMV) status, causes of renal failure, and duration and modes of renal replacement therapy (RRT). During the first 6 months, episodes of first biopsy confirmed acute rejection was 3/50 (6%) in the limited anti-IL-2R group and 8/50 (16%) in the controls (p < 0.05). Twelve-month patient 100/98 (%) and graft survival 100/96 (%) were not statistically different. The group receiving limited anti-IL-2R did not have any adverse reactions. Our study demonstrates that a limited (single) 2 mg/kg immunoprophylaxis dose with monoclonal IL-2R antibody (daclizumab) when combined with tacrolimus/MMF/steroid allows significant reduction in early renal allograft rejection to the single digit level. The therapy with anti-IL-2R antibody is simple and is well tolerated.
