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Two hundred twenty-three recipients of first cadaveric kidney allografts were randomized to receive tacrolimus (TAC) mycophenolate mofetil (MMF), TAC azathioprine (AZA), or cyclosporine (Neoral; CsA) MMF. All regimens contained corticosteroids, and antibody induction was used only in patients who experienced delayed graft function (DGF). Patients were followed-up for 3 years.

Between March 1988 and December 1989, 180 orthotopic liver transplants were performed in 150 adult patients. We have retrospectively reviewed all charts to determine incidence, timing and etiology of major postoperative infections. Major postoperative infection occurred during the 90‐day period following transplantation in 47% of liver transplant patients. Bacterial infections dominated early, while viral and protozoal infections presented later. The most common organisms were Staphylococcus, Enterococcus, and cytomegalovirus. Significant variables associated with infection included pretransplant status, preoperative renal dysfunction, rejection, OKT3 therapy, postoperative renal and liver graft dysfunction, and amount of blood products transfused. By using a stepwise logistic regression analysis, we determined that the best predictors of postoperative infection were rejection and postoperative transfusion requirements. This study emphasizes the need to develop newer immunosuppressive strategics to prevent rejection, but more importantly reemphasizes the critical importance of surgical technique.

One‐hundred‐fifteen patients with no preexisting renal disease underwent orthotopic liver transplantation between December 1984 and February 1988. Immunosuppression was based on cyclosporine and steroids with azathioprine added after treatment for rejection. One‐ and 2‐year patient survival was 88 and 82%, respectively. Glomerular filtration rate averaged 98.4±5.1 cc/min preoperatively and dropped to 54.8±4.2 cc/min 1 month postoperatively. Renal function was stable at 1 and 2 yr postoperatively. A drop in average whole blood cyclosporine levels resulted in better preservation of renal function with no increase in rejection rate or decrease in patient survival. An investigation of factors responsible for the decrease in renal function found no difference in cyclosporine levels, nephrotoxic drugs or events in patients with large or small drops in glomerular filtration rate post‐op. Patients who developed early renal dysfunction (serum creatinine > 2 mg/dl in the first 3 weeks posttransplant) had a significantly lower GFR 1 month and 1 yr post‐op compared with those who did not. There is a predictable decrease in renal function post‐liver transplant and the level of renal function post‐operatively can be predicted by the level of renal function preoperatively. The renal dysfunction appears to be stable at 1 and 2 yr postoperatively.

Cyclosporine (CY) therapy has been reported to produce nephrotoxicity along with various metabolic abnormalities. We have retrospectively analyzed both cadaveric and living related renal transplant patients before, immediately after, and an average of 1 year following CY‐to‐azathioprine (AZA) conversion for serum creatinine, glomerular filtration rate (GFR), serum uric acid, serum triglycerides and serum cholesterol. For comparison, we have also evaluated the above parameters in stable cadaveric and living related renal transplant recipients who were never treated with CY. Our results demonstrate significantly higher creatinine and uric acid levels with a concomitant lowering of GFR in CY‐treated patients compared to non‐CY‐treated patients. These values improved following conversion. By contrast, CY‐to‐AZA conversion had no significant effect on serum lipid levels. The drop in uric acid levels was not correlated with the improvement in GFR, suggesting that CY therapy raises serum uric acid levels through a mechanism other than simply lowering GFR.

A controlled trial was carried out in 209 primary cadaveric renal transplants to compare the effects of cyclosporine and steroids (double therapy) with those of cyclosporine in lower initial dose, azathioprine, and steroids (triple therapy). Patients have been followed 1–36 months since transplantation. Actuarial two-year graft survival (double 74, triple 76) and two-year patient survival (double 90, triple 93) were similar for both groups. Further analysis of particular risk factors including age, diabetes, HLA matching, acute renal failure, and use of sequential Minnesota antilymphocyte globulin in patients with delayed graft function also showed similar outcomes with both immunosuppressive regimens. Initial hospitalization time, rate of rejection, incidence of serious infection, and rate of rehospitalization were not different. Mean CsA doses and mean trough whole-blood levels were higher in double-therapy patients at hospital discharge but not by three months posttransplant. There were no differences between the two groups in iothalamate clearance at any time. Hypertension was more frequent six months post-transplant in the triple-therapy group (p<0,05). Thus, similar results were obtained with both regimens, and except for hypertension no regimen appeared to have increased side effects up to three years posttransplant.

• A retrospective study was undertaken to determine the extent to which analgesic-associated nephropathy (AAN) causes chronic renal failure (CRF) and end-stage renal disease (ESRD). Of 363 cases of CRF diagnosed between 1974 and 1976, 48 were caused by AAN; 14 of 140 cases of ESRD were caused by AAN. Of the 14 patients with ESRD from AAN, 12 initially had ESRD and two progressed to ESRD while continuing consumption of analgesics. The remaining 34 patients who had AAN with CRF discontinued using analgesics and have not progressed to ESRD. Thus, 34 of 36 patients with AAN-CRF who initially did not have ESRD discontinued use of analgesics and have not progressed to ESRD. We conclude that AAN causes a large percentage of CRF and ESRD in our patient population. Early recognition of this entity can prevent progression to ESRD if analgesic consumption is discontinued.(Arch Intern Med 1981;141:462-465)

Liver retransplantation remains the only alternative therapy for irreversible graft failure. Previous studies have demonstrated lower survival rates for liver retransplantation than for primary grafts. After reviewing our clinical experience with 55 retransplantations out of 365 liver transplants, we found that the risk and results depend on the surrounding circumstances. Elective retransplantation was shown to be as safe as the first liver transplantation, while emergency retransplantation yielded significantly higher morbidity and mortality rates.

The results of OKT3 use for steroid-resistant rejection rescue in adult liver transplantation were analyzed retrospectively from a single transplant center. Comparison was made with concurrent patients who had no rejection (NR) or steroid-responsive rejections (SR). The records of 290 patients who underwent 323 liver transplants from April 1985 to December 1989 were examined. The first technically successful grafts were used for this analysis (265 grafts). Follow-up was a minimum of 1 year, or until death or loss of graft. All patients received triple-drug induction immunosuppression (CsA, Aza, steroids). Initial rejection was treated with 1 g methylprednisolone bolus i.v., followed by a 5-day taper of steroids from 200 mg to 20 mg. No rejection occurred in 108 (40.8) and SR in 86 (32.4), and OKT3 was given for persistent rejection in 71 (26.8). The age, sex distribution, mean follow-up, and preoperative status were similar in all three groups. The preoperative diagnoses were similar, except for fulminant liver failure, in which 19 of 20 patients experienced rejection (P< 0.0001). The median hospitalization stay was 37 days for OKT3, 27 days for SR, and 21 days for NR (P< 0.0001). The median ICU stay was similar in the three groups (OKT3, 4; SR, 4; NR, 3). Infections in the first 6 weeks, and in the period of 6 weeks to 1 year posttransplant, were of similar frequency for all three groups. By the Kaplan-Meier estimation, the graft and patient actuarial survival rates were comparable. At 1 year, the graft survival rate was 79.6 for NR, 79.8 for SR, and 67.6 for OKT3. The 1-year patient survival rate was 85.2 for NR, 83.7 for SR, and 84.5 for OKT3. Following treatment by OKT3, rejection was permanently reversed in 42 patients. A temporary response occurred in 12 patients, 16 patients failed to respond to OKT3, 2 patients died during therapy, and 6 of the nonresponders died within 12 months. Additional OKT3 treatment was attempted in 6 patients for persistent rejection within a 1-month interval from the previous OKT3 course. Of these 6, 4 developed