Subclinical inflammation and chronic renal allograft injury in a randomized trial on steroid avoidance in pediatric kidney transplantation.

Steroid avoidance is safe and effective in children receiving kidney transplants in terms of graft function and survival, but the effects on allograft histology are unknown. In this multicenter trial, 130 pediatric renal transplant recipients were randomized to steroid-free (SF; n = 60) or steroid-based (SB; n = 70) immunosuppression, and underwent renal allograft biopsies at the time of graft dysfunction and per protocol at implantation and 6, 12 and 24 months after transplantation. Clinical follow-up was 3 years posttransplant. Subclinical acute rejection was present in 10.6% SF versus 11.3% SB biopsies at 6 months (p = 0.91), 0% SF versus 4.3% SB biopsies at 1 year (p = 0.21) and 0% versus 4.8% at 2 years (p = 0.20). Clinical acute rejection was present in 13.3% SF and 11.4% SB patients by 1 year (p = 0.74) and in 16.7% SF and 17.1% SB patients by 3 years (p = 0.94) after transplantation. The cumulative incidence of antibody-mediated rejection was 6.7% in SF and 2.9% in SB by 3 years after transplantation (p = 0.30). There was a significant increase in chronic histological damage over time (p < 0.001), without difference between SF and SB patients. Smaller recipient size and higher donor age were the main risk factors for chronic histological injury in posttransplant biopsies.

Complete steroid avoidance is effective and safe in children with renal transplants: a multicenter randomized trial with three-year follow-up.

To determine whether steroid avoidance in pediatric kidney transplantation is safe and efficacious, a randomized, multicenter trial was performed in 12 pediatric kidney transplant centers. One hundred thirty children receiving primary kidney transplants were randomized to steroid-free (SF) or steroid-based (SB) immunosuppression, with concomitant tacrolimus, mycophenolate and standard dose daclizumab (SB group) or extended dose daclizumab (SF group). Follow-up was 3 years posttransplant. Standardized height Z-score change after 3 years follow-up was -0.99 ± 2.20 in SF versus -0.93 ± 1.11 in SB; p = 0.825. In subgroup analysis, recipients under 5 years of age showed improved linear growth with SF compared to SB treatment (change in standardized height Z-score at 3 years -0.43 ± 1.15 vs. -1.07 ± 1.14; p = 0.019). There were no differences in the rates of biopsy-proven acute rejection at 3 years after transplantation (16.7% in SF vs. 17.1% in SB; p = 0.94). Patient survival was 100% in both arms; graft survival was 95% in the SF and 90% in the SB arms (p = 0.30) at 3 years follow-up. Over the 3 year follow-up period, the SF group showed lower systolic BP (p = 0.017) and lower cholesterol levels (p = 0.034). In conclusion, complete steroid avoidance is safe and effective in unsensitized children receiving primary kidney transplants.

A peripheral blood diagnostic test for acute rejection in renal transplantation.

Monitoring of renal graft status through peripheral blood (PB) rather than invasive biopsy is important as it will lessen the risk of infection and other stresses, while reducing the costs of rejection diagnosis. Blood gene biomarker panels were discovered by microarrays at a single center and subsequently validated and cross-validated by QPCR in the NIH SNSO1 randomized study from 12 US pediatric transplant programs. A total of 367 unique human PB samples, each paired with a graft biopsy for centralized, blinded phenotype classification, were analyzed (115 acute rejection (AR), 180 stable and 72 other causes of graft injury). Of the differentially expressed genes by microarray, Q-PCR analysis of a five gene-set (DUSP1, PBEF1, PSEN1, MAPK9 and NKTR) classified AR with high accuracy. A logistic regression model was built on independent training-set (n = 47) and validated on independent test-set (n = 198)samples, discriminating AR from STA with 91% sensitivity and 94% specificity and AR from all other non-AR phenotypes with 91% sensitivity and 90% specificity. The 5-gene set can diagnose AR potentially avoiding the need for invasive renal biopsy. These data support the conduct of a prospective study to validate the clinical predictive utility of this diagnostic tool.

Steroid-free immunosuppression since 1999: 129 pediatric renal transplants with sustained graft and patient benefits.

Despite early promising patient and graft outcomes with steroid-free (SF) immunosuppression in pediatric kidney transplant recipients, data on long-term safety and efficacy results are lacking. We present our single-center experience with 129 consecutive pediatric kidney transplant recipients on SF immunosuppression, with a mean follow-up of 5 years. Outcomes are compared against a matched cohort of 57 concurrent recipients treated with steroid-based (SB) immunosuppression. In the SF group, 87% of kidney recipients with functioning grafts remain corticosteroid-free. Actual intent-to-treat SF (ITT-SF) and still-on-protocol SF patient survivals are 96% and 96%, respectively, actual graft survivals for both groups are 93% and 96%, respectively and actual death-censored graft survivals for both groups are 97% and 99%, respectively. Unprecedented catch-up growth is observed in SF recipients below 12 years of age. Continued low rates of acute rejection, posttransplant diabetes mellitus (PTDM), hypertension and hyperlipidemia are seen in SF patients, with sustained benefits for graft function. In conclusion, extended enrollment and longer experience with SF immunosuppression for renal transplantation in low-risk children confirms protocol safety, continued benefits for growth and graft function, low acute rejection rates and reduced cardiovascular morbidity.

A randomized, prospective trial of rituximab for acute rejection in pediatric renal transplantation.

We report 1-year outcomes of a randomized study of Rituximab versus standard-of-care immunosuppression (Thymoglobulin and/or pulse steroids) for treatment of biopsy confirmed, acute transplant rejection with B-cell infiltrates, in 20 consecutive recipients (2-23 years). Graft biopsies, with Banff and CADI scores, CD20 and C4d stains, were performed at rejection and 1 and 6 months later. Peripheral blood CMV, EBV and BK viral loads, graft function, DSA, immunoglobulins, serum humanized antichimeric antibody (HACA) and Rituximab, and lymphocyte counts were monitored until 1 year posttreatment. Rituximab infusions were given with a high index of safety without HACA development and increased infections complications. Rituximab therapy resulted in complete tissue B-cell depletion and rapid peripheral B-cell depletion. Peripheral CD19 cells recovered at a mean time of approximately 12 months. There were some benefits for the recovery of graft function (p = 0.026) and improvement of biopsy rejection scores at both the 1- (p = 0.0003) and 6-month (p < 0.0001) follow-up biopsies. Reappearance of C4d deposition was not seen on follow-up biopsies after Rituximab therapy, but was seen in 30% of control patients. There was no change in DSA in either group, independent of rejection resolution. This study reports safety and suggests further investigation of Rituximab as an adjunctive treatment for B-cell-mediated graft rejection.

Potential influence of tacrolimus and steroid avoidance on early graft function in pediatric renal transplantation.

With the increasing adoption of steroid-sparing immunosuppression protocols in renal transplantation, it is important to evaluate any adverse effects of steroid avoidance on graft function. Early graft function, measured by CrCl was retrospectively studied in 158 consecutive pediatric renal transplant recipients from 1996 to 2005, receiving either steroid-free or steroid-based immunosuppression. Patients receiving steroid-free immunosuppression vs. steroid-based immunosuppression had no difference change in CrCl (DeltaCrCl) in the first week post-transplantation (p = 0.12). When stratified by corticosteroid usage, patients with higher tacrolimus trough levels (> or =14 ng/mL) had slower graft function recovery in the first week post-transplantation than those with lower tacrolimus trough levels (p = 0.008) in the steroid-free group only. Despite initial slower graft function recovery in this subgroup, there was no negative impact on graft function in the steroid-free group; in fact steroid-free patients trended towards better CrCl at six months (p = 0.047) and 12 months (p < 0.001) post-transplant than the steroid-based group. With the improved immunological outcomes with steroid avoidance, close surveillance should be performed of tacrolimus levels to avoid levels >14 ng/mL. In patients with slow recovery of early graft function, short-term perioperative steroids may be considered.

Access to kidney transplantation. Has the United States eliminated income and racial differences?

We analyzed the effect of patient and dialysis unit characteristics on access to kidney transplantation using several different approaches, including an analysis of individual patient data from a systematic random sample of 2900 new dialysis patients from each year 1981 to 1985 (14721 patients total). Additional analyses focused on the composition of transplant waiting lists and aggregate data from a 1984 census of 1133 dialysis and transplant units. White, male, young, nondiabetic, high-income patients treated in smaller units are more likely to receive a cadaver transplant under Medicare than are other kidney patients. Profit status of the dialysis unit was not found to be correlated to access to transplantation, although size of the unit may be correlated to access. Future analysis should focus on whether patient access has been inappropriately compromised. Possible factors unexplored in this analysis include differential patient preferences and medical suitability, as well as differential medical access.

Prednisolone disposition in cushingoid and noncushingoid kidney transplant patients.

Little information is available on the disposition of prednisolone in kidney transplant patients and whether correlations exist between the pharmacokinetics and therapeutic or toxic effects of this drug. The present study was designed to determine the pharmacokinetics of prednisolone in six noncushingoid and six cushingoid transplant recipients. The elimination half-lives were not significantly different in the noncushingoid and cushingoid patients (2.3 vs. 3.3 h). However, other pharmacokinetic parameters were significantly lower in the cushingoid group: plasma clearance (147 vs. 82 ml/min) and volume of distribution (32 vs. 20 liters). In addition, the availability of prednisolone after oral prednisone administration was considerably variable (overall range, 27-108%) and was not significantly different between the two groups. Thus, in kidney transplant patients it appears that the plasma clearance and volume of distribution of prednisolone may distinguish between noncushingoid and cushingoid patients.

Improved outcome following renal transplantation with reduction in the immunosuppression therapy for rejection episodes.

Renal transplantation is superior to hemodialysis in terms of rehabilitation and cost, but it is offered to only a minority of patients with end-stage renal failure because of complications related to immunosuppression therapy. To reduce morbidity, we modified out therapy of patients with transplant rejection from high dose intravenous methylprednisolone (group A: January 1968--September 1972) to lower dose oral prednisone (group B: September 1972--December 1977). Patient survival in group B was significantly improved over that in group A, both in recipients of cadaver transplants (91 per cent versus 81 per cent, respectively, at one year, p less than 0.0009) and in recipients of transplants from living related donors (99 per cent versus 86 per cent, respectively, at one year p less than 0.001). The improvement in patient survival was the result of a significant decrease in the incidence of infections. Patients with multiple rejection episodes, a very high risk group, experienced an 18 per cent increase in patient survival in group B. With reduction and rapid tapering of corticosteroids for the treatment of patients with acute rejection and curtailment of the therapy of patients with multiple rejection episodes, survival after renal transplantation becomes comparable to that following hemodialysis; in addition, graft function is not compromised.

The role of hypertension in hemodialysis-associated atherosclerosis.

Atherosclerosis in 50 nondiabetic patients undergoing hemodialysis was assessed at the time of renal transplantation by intraoperative examination and histologic evaluation of the iliac vasculature. Patients were grouped accordingly: minimal (group 1), moderate (group 2) or severe (group 3) atherosclerosis. Sixty-two per cent of the patients had atherosclerosis, half of them with severe involvement. No sex differences were noted. There was a significant correlation between the patient's age and the degree of atherosclerosis (p less than 0.02). Thirty-five per cent of the patients under 30 years of age had atherosclerosis whereas similarly studied nonuremic control subjects had no atherosclerosis. Metabolic and lipid abnormalities, and duration of hemodialysis did not correlate with degree of atherosclerosis. Hypertension was present in 90 per cent of the patients in groups 2 and 3. When patients between the ages of 25 and 40 years were selected, atherosclerosis was present only in previously hypertensive patients (p less than 0.02). Atherosclerosis may not be accelerated by hemodialysis and may be prevented by more stringent control of hypertension in uremia.

Prediction of donor-specific transfusion sensitization. I. A linear logistic model.

Using linear logistic regression, six factors were identified as important predictors of risk of DST sensitization in a group of 195 patients. Factors increasing the risk were: percent panel reactive antibody (PRA), previous transplants, and pregnancy; those decreasing the risk were HLA antigens matched, third-party blood transfusions, and Imuran administration. From this analysis, the magnitude of the effect of each factor on the risk of sensitization was obtained. An equation was then obtained that can be used to compute an estimated probability of sensitization (PS) for each patient. As a test of predictive ability of the model, the PS was calculated for 66 patients in an independent patient group. These observations were arranged according to the estimated probability and then divided into intervals of risk. Overall, for each interval, a very high level of agreement was found between the predicted and actual number of sensitized patients. A total of 16.13 patients were predicted to become sensitized and 17 actually did.

Two patterns of sensitization demonstrated by recipients of donor-specific transfusion. Limitations to control by Imuran.

Characteristics of the sensitization response to donor-specific transfusion (DST) have been studied in the context of the pretransfusion panel reactive antibody (PRA) status of the recipient. Two distinct patterns of response to DST and Imuran treatment have been found. In patients with one-haplotype-matched donors, the panel nonreactive patient (PRA less than 10%) has a 19% incidence of DST sensitization that is further reduced by Imuran treatment to 6%; antibodies are both anti-T cell and anti-B cells, are transient, and are specific to the mismatched HLA antigens of the blood donor. Panel-reactive patients (PRA greater than 10%) have a 56% incidence of DST sensitization; the antibodies appear within 2 weeks of the first transfusion, are anti-T cell, and are generally of broad specificity and persistent duration consistent with amplification of a previous antigenic exposure; Imuran seems to have little or no effect in reducing the incidence of sensitization in these panel-reactive patients. However, panel reactive patients whose PRA levels spontaneously fall to panel-nonreactive levels immediately prior to DST therapy have an exceedingly low (0-8%) incidence of sensitization with or without Imuran coverage.

Adult-size kidneys without acute tubular necrosis provide exceedingly superior long-term graft outcomes for infants and small children: a single center and UNOS analysis. United Network for Organ Sharing.

BACKGROUND: Infants with end-stage renal disease are at highest risk for early graft loss and mortality of any subgroup undergoing renal transplantation. This study evaluates the influence of donor tissue mass and acute tubular necrosis (ATN) on graft survival and incidence of acute rejection episodes in infant and small child recipients of living donor (LD) and cadaver (CAD) adult-size kidneys (ASKs), pediatric CAD kidneys and combined kidney-liver transplants. Methods. Kidney transplants in infants and small children at a single center and those reported to the UNOS Scientific Renal Transplant Registry were analyzed. At Stanford, multi-variate analysis was conducted on 45 consecutive renal allograft recipients weighing < or = 15 kg, mean weight 11.2 +/- 2.6 kg. The UNOS Registry results in age groups 0-2.5 (n=548) and 2.5-5 years (n=743) were compared with age groups 6-12, 13-18, and the lowest risk adult group of 19-45 years. STANFORD RESULTS. Graft survival was 97.8 +/- 0.0 at 2 years and 84.6 +/- 0.1% at 8 years. The incidence of biopsy proven rejection was 8.8% in the first 3 months and 15.5% over the 8-year follow-up. None of the pediatric CAD kidneys had ATN. Rejection episodes were restricted to the pediatric CAD kidneys alone (3/3), with no kidney rejections in the combined pediatric CAD kidney-liver transplants (0/6; P=0.003). Four ASK transplants had ATN (1 postoperative and 3 late), and all predisposed to subsequent acute rejection episodes (4/4), whereas there were no rejection episodes in ASK transplants without ATN (0/32; P<0.001). At 3 years posttransplantation, mean serum creatinines were worse in ASKs with ATN (1.5 vs. 0.9 mg/dL; P<0.001) and in all grafts with rejection episodes (1.2 vs. 0.9 mg/dL; P<0.05). UNOS RESULTS: Among the 5 age groups studied, significantly better (P<0.001) long-term graft survival rates were observed in allograft recipients in the 2 youngest age groups with ASKs without ATN: 82 +/- 3% and 81 +/- 3% for LD and 70 +/- 7% and 78 +/- 4% for CAD recipients in the 0-2.5 and 2.5- to 5-year age groups, respectively, at 6 years after transplantation. Moreover, the projected graft half-lives after the 1st year in the LD groups without ATN were at least equivalent to those of HLA-identical sibling recipients ages 19-45 years: 26.3 +/- 5 and 29.3 +/- 6 years for the 0- to 2.5- and 2.5- to 5-year age groups, respectively, and 23.3 +/- 1 years for HLA-identical transplants. The graft half-lives for CAD recipients without ATN ages 0-2.5 and 2.5-5 yearswere equivalent or better than those for LD transplants without ATN in recipients aged 19-45 years: 15.4+/- 7 and 23.7 +/- 8 years versus 15.0 +/- 0.3 years. Mean serum creatinines were superior in the 2 younger recipient age groups compared with older age groups. CONCLUSIONS: Increased donor tissue mass of the ASK or kidney-liver transplants, in the absence of ATN, seems to confer a protective effect to infant and small child recipients of these allografts. This is manifested by a prolonged rejection-free state in the single center experience and enhanced graft survival and function in the UNOS analysis, comparable to HLA identical sibling transplants for LD infant and small child recipients and to LD adult results for CAD infant and small child recipients. To optimize this protective effect by whatever mechanism, absolute avoidance of ATN is essential in infant recipients of ASK or combined kidney-liver transplants.

Prevention of rejection and graft loss with an aggressive quadruple immunosuppressive therapy regimen in children and adolescents.

During the two-year period May 1991 to April 1993, 36 kidney transplants were performed in children less than 18 years of age at California Pacific Medical Center using an aggressive quadruple-therapy regimen of immunosuppression. The regimen consisted of induction with an antilymphocyte preparation (MALG in 21, OKT3 in 2, ATGAM in 12, none in 1), initial moderate-dose steroid therapy, early intravenous cyclosporine therapy, and azathioprine. Twenty living-related graft recipients were pretreated with donor-specific transfusions. Long-term cyclosporine was dosed by levels to keep through whole-blood levels (RIA) at 200-300 ng/ml. Twenty-five grafts were from living-related donors, two from living unrelated donors, and nine from cadaveric donors. Eleven (30%) recipients were five years old or under at the time of transplantation. Of these recipients 44% had complex congenital urologic disease and required urologic surgery prior to or at the time of transplantation. Patients have been followed for a mean of one year, with actual patient and graft survivals of 100% and 97%, respectively. Only one graft has been lost, to severe, early recurrent focal segmental glomerulosclerosis. Four of the 36 patients have had one rejection episode each, all reversed completely. Graft function is stable, with serum creatinine proportionate to age--mean serum creatinine in the children under two years old being 0.4 mg/dl, and in the adolescents 1.3 mg/dl, with two adolescent boys having the highest creatinine levels at 1.8 mg/dl. We conclude that an aggressive approach to immunosuppressive therapy in the early posttransplant period with MALG/OKT3/ATGAM induction and rapid achievement of therapeutic cyclosporine levels prevents rejection and results in excellent patient and graft survival with subsequent stable good graft function.

Long-term renal function in kidney donors. Sustained compensatory hyperfiltration with no adverse effects.

Twenty patients who underwent uninephrectomy for kidney donation between 1964 and 1968 participated in a long-term study of the function of the solitary kidney. Mean follow up after uninephrectomy was 15.8 +/- .3 years. One patient with a strong family history of essential hypertension developed de novo mild hypertension. The current creatinine clearance of the donors was 80 +/- 4 ml/min. The 1-week, 3-6 months and 14-18 years postuninephrectomy percentages of predonation creatinine clearance were 72 +/- 3%, 76 +/- 3% and 78 +/- 2%, respectively. The 24-hr urine protein excretion in kidney donors was significantly higher than in controls (141 +/- 20 mg vs. 74 +/- 3 mg, respectively, P less than .0005). Except for one donor who may have developed glomerulonephritis, the donors had normal urinary albumin excretion. The cause of the slightly elevated nonalbumin proteinuria is not known. However, this long-term study of kidney donors shows no adverse effects on the blood pressure and renal function after many years of compensatory hyperfiltration.

De novo and recurrent membranous glomerulopathy following kidney transplantation.

Membranous glomerulopathy, de novo or recurrent, in the allograft kidney is a recognized, albeit uncommon, clinical entity. We examined the records of 936 renal allograft recipients in a seven and one-half year period. De novo membranous glomerulopathy developed in six patients. The mean onset of nephrotic-range proteinuria after transplantation was at 18.1 months (with a range of from 4 to 30 months). De novo membranous glomerulopathy did not adversely affect graft survival. Twenty-five patients were transplanted for end-stage renal disease caused by membranous glomerulopathy. The rate of recurrence of membranous glomerulopathy in patients who did not lose their allograft to rejection in the immediate posttransplant period was 7%. Additional prednisone therapy to the standard immunosuppressive protocol did not appear to be beneficial. One patient, who developed a recurrence of the original lesion, received an HLA-identical kidney. Onset of nephrotic-range proteinuria occurred four weeks post-transplant. Recurrent membranous glomerulopathy has been reported in five other patients. In the two recipients of living related allografts nephrotic-range proteinuria developed within two weeks of the transplant. Patients with end-stage renal disease caused by membranous glomerulopathy who receive a living related allograft, especially one that is HLA-identical, may be at a higher risk for morbidity and for early recurrence. We recommend caution in the use of a living related transplant for patients with end-stage renal disease caused by membranous glomerulopathy.

Do blood transfusions enhance the possibility of a compatible transplant?

Blood transfusions prior to first cadaver kidney transplants have a significant beneficial effect on graft survival and, in this sense, appear to enhance the possibility of a compatible transplant. This desirable effect, however, occurs concomitantly with an increased degree of sensitization, which in turn reduces the likelihood of identifying a compatible kidney by direct crossmatch testing. This report illustrates that the beneficial effect is achieved with one to five transfusions prior to transplantation, but that more transfusions afford no additional benefits. In addition, the presence of cytotoxic antibodies per se does not have an adverse influence on graft survival. Liberal transfusion policies are therefore indicated in cadaver transplant candidates, but more than five transfusions prior to transplantation should probably be avoided unless clinically necessary.

The clinical course of IgA-nephropathy and Henoch-Schönlein purpura following renal transplantation.

Recurrence of IgA-nephropathy and Henoch-Schönlein purpura is a common finding after renal transplantation. From 1970 to 1984, 1788 transplants were performed at our center. 13 patients had IgA-nephropathy and 3 patients had Henoch-Schönlein purpura. No patient with Henoch-Schönlein purpura had a proved recurrence. Six patients with IgA-nephropathy had a recurrence of IgA disease in the allograft within 3 to 8 months of transplantation. Three patients with a recurrence have retained their kidneys with stable renal function (follow-up of 1.7-2.7 years). Two of these patients lost their graft from severe rejection. One patient, who received an HLA-identical transplant, lost the graft from recurrent IgA disease associated with crescenteric glomerulonephritis. We found no difference in the prevalence of HLA-B 35 among the IgA patients compared with our total transplant population. IgA patients who received living related transplants had a higher recurrence rate of IgA in their allograft when compared with recipients of cadaveric kidneys (83% vs. 14%). Some caution is recommended in using related donors, especially HLA-identical siblings in patients with renal failure secondary to IgA-nephropathy.

Inability of cyclosporine to completely prevent the recurrence of focal glomerulosclerosis after kidney transplantation.

From January 1984 through July 1986, 15 patients with biopsy-proven focal glomerulosclerosis (FGS) underwent kidney transplantation. Following transplantation, all patients were immunosuppressed with cyclosporine and prednisone. There were 8 men and 7 women with a mean age of 33 years (range, 16-47 years). Five patients (33%) had recurrence of FGS. Two patients had received kidneys from HLA identical siblings, and 3 patients were transplanted with cadaveric kidneys. In 4 out of 5 patients, the recurrence of FGS occurred within 3 months of transplantation. Of the 2 graft losses in this group, one was from recurrence of FGS. Ten patients followed for a mean of 25 months did not develop recurrence of FGS. No graft loss occurred in this group. Three patients with end-stage renal disease of unknown etiology were found to have FGS in the renal allograft and were presumed to have recurrence of FGS. All 3 patients developed the nephrotic syndrome following transplantation, and 1 patient has had progressive renal failure. Cyclosporine did not prevent the recurrence or the clinical manifestations of FGS following kidney transplantation. Additional studies are needed to determine if cyclosporine is effective in certain subgroups of patients with FGS.

The beneficial effect of pretransplant blood transfusions in cyclosporine-treated cadaver renal allograft recipients.

212 cyclosporine-treated recipients of mismatched first cadaveric renal allografts are evaluated with respect to the effect of pretransplant random blood transfusions. It is determined that transfusions do not effect patient survival or morbidity. Pretransplant random blood transfusions correlate with significantly improved allograft success. There is also a trend, although not statistically significant, for further improvement of allograft survival with increasing numbers of transfusions. The transfusion effect is not related to the time at which the transfusions are given up to 2 years prior to transplantation. Transfused patients have a higher percent reactive antibody (PRA) than untransfused patients, but this does not cause them to wait for a cadaveric allograft significantly longer than the untransfused patients. Rejections are less severe in transfused patients. It is concluded that cyclosporine-treated recipients of first cadaveric renal allografts benefit from pretransplant blood transfusions.