Michael H. Gallichio

A Multicenter Pilot Study of Early (4-Day) Steroid Cessation in Renal Transplant Recipients Under Simulect, Tacrolimus and Sirolimus

This study presents the first prospective multicenter study assessing sirolimus‐based immunosuppression with early (4‐day) corticosteroid withdrawal (CSWD) in renal transplantation. Immunosuppression included: anti‐IL‐2 receptor antibody and tacrolimus/sirolimus. Inclusion criteria included adult primary recipients. Exclusion criteria included: (i) African Americans, (ii) current PRA >50%, (iii) multiple organ transplants, (iv) WBC < 3000 cells/μL and (v) fasting hypercholesterolemia/hypertriglyceridemia. The primary endpoints were acute rejection and the proportion of patients off corticosteroids. Seventy‐seven patients were enrolled: mean age of 49.7 ± 12 years. Transplants included: cadaveric (26%) and living donor (74%). Patient and graft survival were 100%. Biopsy proven acute rejection occurred in 13%; presumptive rejection in 10.5%. Banff grades included: IA (seven patients), IB (one patient), IIA (one patient) and IIB (one patient). Renal function at 1 year: serum creatinine (1.18 ± 0.06 mg/dL). Mean weight gain was minimal at 1 year: 3 ± 2 kg/patient. Mild increases in total, LDL and HDL cholesterol were observed and new antilipid agent use occurred in 26 patients. In conclusion, early CSWD under tacrolimus/sirolimus‐based immunosuppression in selected, low‐risk renal transplant recipients provides: (i) excellent patient and graft survival, (ii) good renal function, (iii) reduced hyperlipidemia and antilipid agent use and (iv) low acute rejection rates.

Improved outcomes in cadaveric renal allografts with pulsatile preservation

Background: Early immunologic and non‐immunologic injury of renal allografts adversely affects long‐term graft survival. Some degree of preservation injury is inevitable in cadaveric renal transplantation, and, with the reduction in early acute rejection, this non‐immunologic injury has assumed a greater relative importance. Optimal graft preservation will maximize the chances of early graft function and long‐term graft survival, but the best method of preservation – pulsatile perfusion (PP) versus cold storage (CS) – is debated. 
Methods: Primary cadaveric kidney recipients from January 1990 through December 1995 were evaluated. The effects of implantation warm ischemic time (WIT) (≤20 min, 21–40 min, or >40 min) and total ischemic time (TIT) (< or ≥20 h) on death‐censored graft survival were compared between kidneys preserved by PP versus those preserved by CS. The effect of preservation method on delayed graft function (DGF) was also examined. 
Results: There were 568 PP kidneys and 268 CS kidneys. Overall death‐censored graft survival was not significantly different between groups, despite worse donor and recipient characteristics in the PP group. CS kidneys with an implantation WIT >40 min had worse graft survival than those with <40 min (p=0.0004). Survival of PP kidneys and those transplanted into 2 DR‐matched recipients was not affected by longer implantation WIT. Longer TIT did not impact survival. DGF was more likely after CS preservation (20.2% versus 8.8%, p=0.001). 
Conclusions: Preservation with PP improves early graft function and lessens the adverse effect of increased warm ischemia in cadaveric renal transplantation. This method is likely associated with less preservation injury and/or increases the threshold for injury from other sources and is superior to CS.

IMPROVED OUTCOMES IN CADAVERIC RENAL ALLOGRAFTS WITH PULSATILE PRESERVATION.

BACKGROUND Early immunologic and non-immunologic injury of renal allografts adversely affects long-term graft survival. Some degree of preservation injury is inevitable in cadaveric renal transplantation, and, with the reduction in early acute rejection, this non-immunologic injury has assumed a greater relative importance. Optimal graft preservation will maximize the chances of early graft function and long-term graft survival, but the best method of preservation pulsatile perfusion (PP) versus cold storage (CS) is debated. METHODS Primary cadaveric kidney recipients from January 1990 through December 1995 were evaluated. The effects of implantation warm ischemic time (WIT) ( < or = 20 min, 21-40 min, or > 40 min) and total ischemic time (TIT) ( < or > or = 20 h) on death-censored graft survival were compared between kidneys preserved by PP versus those preserved by CS. The effect of preservation method on delayed graft function (DGF) was also examined. RESULTS There were 568 PP kidneys and 268 CS kidneys. Overall death-censored graft survival was not significantly different between groups, despite worse donor and recipient characteristics in the PP group. CS kidneys with an implantation WIT > 40 min had worse graft survival than those with < 40 min (p = 0.0004). Survival of PP kidneys and those transplanted into 2 DR-matched recipients was not affected by longer implantation WIT. Longer TIT did not impact survival. DGF was more likely after CS preservation (20.2% versus 8.8%, p = 0.001). CONCLUSIONS Preservation with PP improves early graft function and lessens the adverse effect of increased warm ischemia in cadaveric renal transplantation. This method is likely associated with less preservation injury and/or increases the threshold for injury from other sources and is superior to CS.

Improving renal allograft survival in black transplant recipients1

Abstract Purpose: Historically, black patients have had 1-year renal allograft survival rates which is 8% to 10% worse than those for whites. With the use of quadruple immunosuppression, we have sought to find a reversal in this trend. Methods: The outcomes of 572 renal allografts—cadaveric (CAD, 477), living related [68; 0-HM (haplomatch), and 1-HM], and living unrelated (UNR, 37) between August 1995 and August 1998 were analyzed. There were 276 black recipients and 295 white recipients. Immunosuppression consisted of induction with either OKT3 10 mg/day for 7 to 10 days (485), Zenapax 1 mg/kg in two doses (86), or ATGAM 15 mg/kg for 10 days (1). Maintenance immunosuppression consisted of cellcept 2 to 3 g/day, prednisone 10 mg/day, and cyclosporine 2 to 4 mg/kg b.i.d. Cyclosporine levels were calculated by using standard fluorescence polarization immunoassay. Patients were followed for occurrence of rejection, infection, death, loss of graft, and other complications. Actuarial analysis of survival was performed by the Kaplan-Meier method, with p values generated by the Wilcoxon test. Confidence limits for survival analysis were expressed as 70%. A p value ≤ .05 was considered significant. All patients with a functioning graft have a minimum of 3 months of follow-up; graft loss was considered to be at the time of nephrectomy, return to dialysis, or death if the graft was functioning. The mean values of descriptive variables between groups were compared with the t -test, and the chi-square test or Fisher’s exact test was used to evaluate independence of groups. Results: Graft Survival BLACK WHITE COMBINED 1-yr (n) 2-yr (n) 1-yr (n) 2-yr (n) 1-yr (n) 2-yr (n) CAD 89% (179) 81% (81) 91% (147) 89% (80) 90% (326) 84% (161) 0-HM 84% (8) 84% (4) 83% (7) 83% (5) 84% (15) 84% (9) 1-HM 90% (5) 45% (1) 95% (5) n/a 94% (10) 78% (5) UNR n/a n/a 97% (30) 92% (17) 97% (30) 92% (17) Conclusions: With use of quadruple immunosuppression, there was no difference in 1-year CAD patient and graft survival between blacks and whites (p = n.s.); however, 2-year graft survival was worse in blacks (p ≤ .05). Despite the aggressive use of anti-T cell antibodies, there was no increase in infectious complications, graft loss due to death, or other complications among the groups (p = n.s.). Living related graft survival showed the same trend, with no difference at 1-year (p = n.s.). Increased graft loss between 1 and 2 years for black versus white CAD patients is attributed to a higher rate of acute/chronic rejection (p = .03). Therefore, improved renal allograft survival is possible in black patients with the use of quadruple immunosuppression; however, black patients remain at increased risk of graft loss due to rejection beyond 1 year.