T. Quinn

Transplantation of pediatric donor kidneys to adult recipients. Is there a critical donor age

Cadaver kidneys remain a scarce resource, yet single pediatrie donor kidneys are underutilized at some centers. Between 1967 and 1984, 133 single pediatrie and 318 adult donor cadaver transplants were performed. Patient and graft survival, renal function, and complications in adult recipients grouped by donor age were compared. Recipient age for all groups was similar (34–36 years). Life table analysis revealed no difference in graft survival in recipients of kidneys from donors aged 2, 3, 4, 5–10, and 11–15 when compared with adult donors. Graft survival in these groups improved over time with current 1-year survival over 75%. Recipients from donors less than 24 months of age demonstrated significantly poorer results, with no kidney surviving >2 months. Serum creatininc of grafts functioning >6 months was similar in all groups. It is concluded that single pediatrie kidneys from donors greater than 2 years of age can be successfully transplanted to adults with good long-term results.

ALG treatment of steroid-resistant rejection in patients receiving cyclosporine.

Thirty-one episodes of biopsy-proved acute rejection (R) in 28 patients maintained on cyclosporine did not respond to high-dose steroids and were treated with antilymphocyte globulin (ALG). Cyclosporine was discontinued in all but three during ALG administration. (A) Twenty-four patients received 26 courses of ALG within 90 days of transplant (11 1st R, 15 2nd or 3rd). Seven treatment courses were cut short due to infection (4), ongoing R (2) and a combination of infection and rejection (1). Only 1 of 7 has a functioning graft. Of the remaining 19 full ALG courses (17 patients) (8 1st R, 11 2nd or 3rd), 13 (11 patients) responded (7 1st R, 6 greater than 1st). The remaining 6 patients lost their grafts to ongoing acute rejection. (B) Five patients were treated after 6 months posttransplant; two responded but no grafts currently function

Individualization of immediate posttransplant immunosuppression: the value of antilymphocyte globulin in patients with delayed graft function

In patients with delayed graft function (DGF), the use of cyclosporine (CsA) has been reported to prolong DGF, increase the number of required dialyses, increase the duration of hospitalization, and be associated with decreased graft survival. Routine postoperative antilymphocyte globulin (ALG) use has been advocated, but ALG is associated with increased viral infection. We studied outcome of individualization of immunosuppression. Between 11/84 and 8/86, first-cadaver transplant recipients whose serum creatinine (Cr) fell >30% in the first 24 hr (immediate function) were started on CsA and prednisone (P) (group 1, n=26). The remainder were randomized to P and azathioprine (group 2, n=32) or P and ALG (group 3, n=26), and switched to CsA when serum Cr fell >30% (minimum 5 days ALG for the ALG group). P taper was the same in all groups. Patients with DGF (groups 2 and 3) had longer preservation time and higher peak PRA (P<.05) than group 1. Groups were otherwise equivalent. One and 2-year patient survival was 96% (3 cardiovascular deaths; all with functioning grafts). One-year graft survival was 87% for group 1, 87% for group 2, and 82% for group 3(NS). In patients requiring dialysis, mean day off dialysis was 12±3 in both groups 2 and 3. Mean hospital stay was 12.5±1.3 days for group 1, 21.6±2.1 days for group 2 (P<.05 vs. 1 & 3), and 14.5 ± 1.2 days for group 3 (NS vs. 1). The increased hospital stay for group 2 patients was mainly due to increased in-hospital rejections: 75% for group 2, (P<.05 vs. group 1 [35%], and group 3 [11.5%]). In addition, more group 2 in-hospital 1st rejections were steroid resistant as compared to group 1; 46% group 1 patients have remained rejection free as compared to 0% group 2 (P<.05 vs. 1 and 3) and 35% of group 3 (P<.05 vs. 1 and 2). Mean serum creatinine at 6–12 months remained higher in patients with DGF (group 1 P<.05 vs. 2 and 3). Rejection was the major cause of graft loss in all groups. There was no difference between groups in the incidence of infection. We conclude that: (1) with individualization of immunosuppression, graft survival is equivalent with and without DGF; (2) Cr remains higher in patients with DGF; (3) in patients with DGF, ALG or azathioprine in the immediate postoperative period gives equivalent graft survival; prophylactic ALG is associated with significantly decreased early rejection and hospital stay, and with more patients remaining rejection free.

Timing of cyclosporine administration in patients with delayed graft function

Cyclosporine in renal transplant recipients with delayed graft function (DGF) has been reported to decrease graft survival and prolong both DGF and hospitalization. In some centers, antilymphocyte globulin (ALG) has been used perioperatively to obviate these problems, but ALG is associated with increased viral infections. In this study, first cadaver transplant recipients with a fall in serum creatinine level of greater than or equal to 30% in the first 24 hr were started on prednisone (P) and cyclosporine (Group 1, n = 18). Those whose creatinine level did not fall were started on P and azathioprine (Group 2, n = 23) and switched to P and cyclosporine when serum creatinine fell 30%. One-year patient survival was 98%. One-year graft survival was 83% for both Groups 1 and 2 (NS). Results were compared to historical controls with DGF who received P and cyclosporine (Group 3, n = 19). Patients with DGF and requiring dialysis had fewer dialyses (P less than 0.05) and a shorter hospital stay (P less than 0.05) if started on azathioprine, as compared to those started on cyclosporine. Patients with DGF had a higher serum creatinine at 12 months than those with immediate function (P less than 0.05). We conclude that withholding cyclosporine until DGF is resolving decreases the duration of dialysis, decreases hospital stay, and without the use of prophylactic ALG, is associated with graft survival equivalent to that in patients with immediate function.

Treatment of renal transplant rejection episodes in patients receiving prednisone and azathioprine. A cost-effective approach.

Antilymphocyte globulin (ALG) has been advocated for the treatment of renal transplant rejection episodes in patients maintained on prednisone and azathioprine. Treatment with steroids (outpatient) is considerably less expensive than with ALG (inpatient), so we studied whether routine ALG was necessary. Between 3/82 and 11/83, 54 cadaver transplant recipients maintained on prednisone and azathioprine who developed a first rejection episode were randomized to receive–for treatment of their first, and if necessary second, rejection– methylprednisolone (MP) plus ALG (n = 24), or MP alone, with ALG added if treatment failed (n = 30). Treatment failure was defined as continuing deterioration on T131 iodohippuran scan, rising serum creatinine level, or lack of improvement within 7 days. There was no significant difference in patient survival, graft survival, mean number of rejections, and infection rate between the two groups: 60% (18/30) of first and 50% (10/10) of second rejection episodes responded to MP alone. We conclude that patients are not penalized by initial rejection treatment with MP. Many rejection episodes respond to steroids alone; elimination of routine ALG use will save hospitalization time and expense.

The effect of the referring dialysis center on renal transplant results

Between 1/1/76 and 12/31/86, 448 patients underwent transplantation (360 first transplants). Of these, 286 (230 first) were referred by 5 dialysis centers, each referring more than 40 recipients. The remainder were referred by a large number of centers. Using our 5 largest referral centers, we studied the effect of dialysis center on graft and patient survival. There was no difference between dialysis centers in patient survival. Actuarial graft survival differed significantly for all cadaver transplants and for first cadaver transplants (P < 105). Significant differences persisted when groups were subdivided by type of immunosuppression (azathioprine vs cyclosporine). Demographic (age, race, cause of renal disease) and immunologic (transfusions, PRA, matching) differences between groups did not explain the difference in graft survival.