Fuad Afzal

Does bioequivalence between modified cyclosporine formulations translate into equal outcomes

Neoral was replaced with a generic cyclosporine formulation on our hospital formulary. We compared outcomes for de novo kidney transplant recipients who either received Gengraf (n=88) or Neoral (n=100) in a single-center, retrospective review. As compared to patients who received Neoral, patients who received Gengraf were significantly more likely to have an acute rejection episode (39% vs. 25%, P=0.04), more likely to have a second rejection episode (13% vs. 4%; P=0.03), or to have received an antibody preparation to treat acute rejection (19% vs. 8%; P=0.02). Patients treated with Gengraf had a higher degree of intrapatient variability for cyclosporine trough concentrations as determined by %CV (P<0.05). The incidence of acute rejection at 6 months posttransplant was significantly higher in patients who received Gengraf compared to Neoral. A larger, prospective analysis is warranted to compare these formulations of cyclosporine in de novo kidney transplant recipients.

Valganciclovir prophylaxis in patients at high risk for the development of cytomegalovirus disease

Abstract: Background. Despite advances in antiviral therapies, cytomegalovirus (CMV) remains the leading opportunistic infection in the transplant population. Valganciclovir (VGC), the l‐valyl ester prodrug of ganciclovir (GCV), provides an excellent oral alternative to GCV for the prevention of CMV in transplant recipients. We investigated the use of VGC for CMV prevention in high‐risk renal and pancreas transplant recipients.

Influence of mild obesity on outcome of simultaneous pancreas and kidney transplantation.

The influence of body mass index (BMI) on outcome of simultaneous pancreas-kidney transplantation (SPK) has not been well described. We retrospectively reviewed 88 consecutive primary SPKs performed at our institution between March 15, 1995 and August 28, 2001. All patients received antibody induction and maintenance immunosuppression with tacrolimus, mycophenolate mofetil, and steroids. Systemicenteric implantation was performed in all patients. Primary end points were patient, pancreas, and kidney survival. Secondary end points were rates of anastomotic leakage, pancreas thrombosis, major infection, rejection, repeat laparotomy, and length of hospital stay. Values are shown as mean ± standard deviation, range, or percentage. Fifty-two patients (59.1%) were nonobese with a BMI ≦24.9 (mean 21.7 ± 2.2, range 15.4 to 24.9). Thirty-six patients were mild to moderately obese with a BMI ≧25 (mean 27.7 ± 2.2, range 25 to 35.1). Distribution of recipient age, sex, and ethnicity was similar between groups. Kidney and pancreas preservation times were similar between nonobese and obese patients. One-, three-, and five-year actuarial patient (nonobese: 95%, 95%, 95% vs. obese: 95%, 95%, 89%), kidney graft (nonobese: 91%, 91%, 87% vs. obese: 97%, 91%, 85%), and pancreas graft (nonobese: 78%, 78%, 73% vs. obese: 70%, 62%, 62%) survival were comparable between nonobese and obese (P = NS). The mean rates of pancreas thrombosis, major infection, pancreas rejection, kidney rejection, relaparotomy, and length of hospital stay were similar in the two groups. The overall duodenojejunal anastomotic leakage rate was 8%. Obese patients had a 17% incidence of leakage (6 of 36) compared to a 2% incidence of leakage in nonobese patients (P = 0.012). Six of seven leaks occurred in obese patients. Mean BMI in the seven patients with a leak (27 ± 1.9) was significantly higher than in patients who did not develop a leak (24 ± 3.7; P = 0.05). Although obesity had no effect on patient or graft survival, it was associated with a significantly higher leakage rate. There should therefore be a higher degree of suspicion for the presence of duodenojejunal anastomotic leaks in obese SPK recipients.

Effect of Ethnicity on Outcome of Simultaneous Pancreas and Kidney Transplantation

The influence of ethnicity on outcome of simultaneous pancreas‐kidney transplantation (SPK) is poorly defined. After excluding technical failures, we retrospectively reviewed 96 consecutive SPKs (63 Caucasians [C], 33 African‐Americans [AA]). All patients received antibody induction, tacrolimus, mycophenolate mofetil, and steroids. One‐, 3‐, and 5‐year actuarial patient survival was similar between C (98%, 95%, 87%) and AA (90%, 90%, 81%), p=NS. One‐, 3‐, and 5‐year kidney graft survival was similar between C (98%, 86%, 81%) and AA (85%, 85%, 78%), p =NS. One‐, 3‐, and 5‐year pancreas graft survival was significantly worse in AA (71%, 68%, 46%) than in C (90%, 85%, 81%), p = 0.008. The cumulative incidence of kidney and pancreas acute rejection (AR) was higher in AA compared with C. Distribution of kidney and pancreas rejection grade was similar between C and AA. AA experienced more pancreas graft losses from early death with functioning graft, AR, and late chronic rejection. The higher incidence of AR and resistance to currently employed induction, maintenance, and antirejection immunosuppression therapies in AA may account for their inferior pancreas graft survival. More aggressive immunosuppression strategies may improve pancreas graft survival in AA but may be associated with increased morbidity and mortality. Further study is warranted.

Long-term outcome of sirolimus rescue in kidney-pancreas transplantation

Sirolimus (SRL) rescue in kidney-pancreas transplantation has not been well described. We reviewed 112 KPTxs performed at our institution between December 3, 1995 and June 27, 2002. All patients received antibody induction, tacrolimus (TAC), mycophenolate mofetil (MMF), and steroids. In 35 patients, SRL was substituted for MMF for the following reasons: acute rejection (AR) of kidney or pancreas despite adequate TAC levels, MMF intolerance, increasing creatinine levels, and TAC-induced hyperglycemia. Three-year kidney and pancreas graft survivals were 97% and 90%, respectively. Of 10 patients who were switched to SRL because of AR, one kidney failed because of antibody-resistant AR, and one kidney developed borderline AR; the other eight patients remain AR-free. AR developed in seven other patients despite therapeutic SRL levels; six had TAC levels less than 4.5 ng/mL. The mean creatinine levels overall and for the group with increasing creatinine remained stable. All patients who were switched to SRL for TAC-induced hyperglycemia or MMF intolerance improved. Kidney-pancreas transplant recipients can be safely switched to SRL with excellent graft and patient survival.

Living donor transplantation of a pelvic kidney

Abstract:  Pelvic kidneys are uncommon anomalies rarely utilized in kidney transplantation. We describe a successful case of living‐donor transplantation using a pelvic kidney in a 17‐month‐old infant with congenital renal dysplasia. The recipient had exhausted all options for renal replacement therapy, and urgent transplantation was considered a life saving treatment.