Exercise tolerance changes following renal transplantation.

Maximal exercise capacity was measured in 20 nondiabetic patients with end-stage renal disease before and soon after successful renal transplantation. Maximal oxygen consumption increased significantly in all patients posttransplant. Increases in maximal heart rate and heart rates at 70% of maximal levels were also observed. The changes in maximal oxygen consumption were not significantly correlated with changes in hematocrit. The removal of uremia may result in improved functioning of one or more of the systems involved in oxygen transport and utilization that determine exercise capacity.

Exercise capacity in hemodialysis, CAPD, and renal transplant patients.

Eighteen hemodialysis, 12 chronic ambulatory peritoneal dialysis (CAPD), and 20 renal transplant patients performed maximal treadmill exercise tests. Heart rates and blood pressures were determined every minute and maximal oxygen consumption was measured directly. Exercise capacity as measured by VO2 max is low in dialysis patients and similar to sedentary normal individuals in renal transplant patients. Maximal heart rates were significantly lower in hemodialysis patients than transplant recipients. The lower exercise tolerance in end-stage renal disease indicates that most patients regardless of the treatment mode could benefit from attempts through exercise training to increase physical working capacity.

A four-year experience with donor blood transfusion protocols for living-donor renal transplantation.

Our experience over the last 4 years with HLA-identical, donor-specific transfusion (DST), and Imuran (IM) + DST living-donor transplants in 206 patients is presented. Transplants from 8 completely incompatible sibling donors, 4 distantly related donors, and 7 unrelated donors are included. Except for a slightly higher average serum creatinine, and a markedly reduced rate of donor-specific sensitization in the IM + DST group when compared with the DST group (14% vs. 31%, P less than .005), the results of transplantation using these 3 protocols have been equivalent. Actuarial one-year survival was 97% for patients and 93% for grafts for the combined group of 206 patients. Of the 44 patients who entered the DST or IM + DST protocols but were not transplanted, 31 patients (70%) have subsequently been transplanted, and all 5 recipients of living-donor kidneys and 20 of 26 recipients of cadaveric kidneys (77%) have functioning grafts. Because it optimizes the availability of transplantable living-donor kidneys, gives results equivalent to those obtained with HLA-identical donors and the DST protocol, and is not associated with clinically apparent adverse effects, we now use the IM + DST protocol for all living-donor transplants except those between HLA-identical donor-recipient pairs.

Renal transplantation using ileal conduits in 5 cases.

We report our experience with 5 cases of renal transplantation into ileal conduits and review the literature. In 2 cases a modified surgical procedure was used, which combines a groin extraperitoneal approach for the vascular portion of the operation and a peritoneal window for the anastomosis between the urinary collecting system and the ileal loop. Of our 5 patients 3 are alive with functioning grafts, 1 has undergone retransplantation and 1 with a functioning kidney died of sepsis originating in a decubitus ulcer. Two patients had conduit-related complications. In our literature review of 16 reports 52 per cent of 68 patients were alive with functioning grafts and 32 per cent had conduit-related complications, usually involving urosepsis, calculous disease or stenosis. With a high index of suspicion, and an aggressive diagnostic and therapeutic approach to these problems, a good prognosis can be expected when transplantation is performed in these patients.

Neutropenic enterocolitis in adults. Review of the literature and assessment of surgical intervention.

We have reported two cases of neutropenic enterocolitis (one of them being the first reported case occurring in a patient with multiple myeloma), which is a necrotizing lesion in the gastrointestinal tract that is seen in patients usually on aggressive chemotherapeutic regimens and associated with leukemias, lymphomas, malignant neoplasms, and other disorders in which neutropenia is present. Although once considered to have a dismal prognosis, favorable outcomes have occurred when this clinical entity is recognized early and surgical intervention is undertaken to resect the necrotic portion of the gastrointestinal tract. A review of the literature is included that encompasses adult patients with this syndrome.

Improved renal allograft survival following donor-specific transfusions. I. Induction of antibodies that inhibit primary antidonor MLC response.

Our purpose was to identify humoral factors induced by donor-specific transfusion (DST) plus azathioprine (AZA) that correlate with improved renal allograft survival (92% at 3-34 months posttransplantation) in a group of 24 DST patients. Plasma was obtained from patients prior to AZA and DST (to), 2-6 weeks after the final transfusion but immediately prior to transplant (tt), and 6-12 weeks after renal transplantation and initiation of standard posttransplant immunosuppressive therapy (tx). Plasma was screened for inhibitory or stimulatory activity in a 6-day primary MLC, with either patient to PBL or unrelated control PBL used as responders. Patient tx plasma was uniformly inhibitory of MLC responses to donor and to pooled third-party stimulators, regardless of the source of responding cells. The tx plasma inhibition was mediated by a nondialysable factor, ruling out a direct drug effect. In contrast, the effect of tt plasma was less pronounced but more specific. In some patients, we observed a strong reproducible inhibition of antidonor MLC by tt plasma. However, other patients did not show this inhibitory effect; thus the inhibition was not statistically significant (1 greater than P greater than .05 by the Wilcoxon t test) when all patients were analyzed. Overall, patient tt plasma affected neither control antidonor MLC nor patient MLC responses to pooled allogenic stimulating cells. In two patients showing strong tt plasma inhibition of antidonor MLC, the inhibition appeared to be Ig-mediated. The results are discussed in relation to current theories of DST mechanisms.

Donor-specific transfusions in unrelated and related HLA-mismatched donor-recipient combinations.

The donor-specific transfusion protocol (DST) with (DST+I) or without Imuran has resulted in improved graft survival in one-haplotype-mismatched high-MLC-reactive donor-recipient combinations. In this study we have extended the use of donor-specific transfusions to unrelated individuals (group 1), distant relatives (group 2), and two-haplotype-mismatched siblings (group 3). All grafts in group 1 and group 2 are functioning. In group 3, one patient was lost from a myocardial infarct and one kidney was lost due to rejection. In vitro testing was performed using cryopreserved cells obtained prior to transfusion (t0), after the third transfusion (tt), and after transplantation (tx). We observed patient-specific suppression in tt plasma and nonspecific suppression by tx plasma. We also found ADCC-like activity in tx, but not in t0 or tt plasma in 2 out of 3 patients. The suppressor effect of tt plasma is mediated by IgG antibody and possibly reflects an antiidiotypic antibody.

Comparative analysis of the DST and Imuran-plus-DST protocols for live donor renal transplantation.

We have done a comparative analysis of two consecutive clinical trials at our center: the first in 56 patients who received blood transfusions from their prospective donors (DST group), and the second in 36 patients who received such transfusions while they were taking Imuran in an attempt to reduce the incidence of sensitization against the donor (IM + DST group). The major findings of our study are: (1) Imuran significantly (P less than .05) reduced the rate of sensitization from 27% to 11%; (2) Patients who had prolonged dialysis before entering one of these protocols were significantly more likely to become sensitized against their living donors, and had significantly higher sensitization against the leukocyte panel, although panel-reactive antibodies were not significantly changed by transfusions from the live donor; (3) MLC reactivity against the living donor was not significantly altered by donor transfusions, and was also not different for sensitized and transplanted patients; (4) Results of transplantation were excellent in both patient groups, with only two grafts and two patients lost in 68 transplants (actuarial one-year survival of 97% and 93% of patients alive and with functional grafts at one year in the DST and IM + DST groups, respectively); (5) Rejection episodes occurred in about 50% of each group, but were of a special type (DST-type rejection) in about 30% of the DST patients and 10% of the IM + DST patients (P = .07); (6) The probability of transplantation, and the results of transplantation after unsuccessful entry into one of these protocols was not adversely affected. We think that primarily because of the low rate of sensitization the IM + DST protocol is superior to the DST protocol. Both, however, are established clinical tools that have increased our clinical transplant volume by a large number of highly successful transplants.

Current status of organ transplantation.

Recent advances in the understanding of mechanisms of graft rejection and in the prevention and treatment of rejection are discussed. The clinical success of kidney, liver, heart, and pancreas transplants is analyzed.

Beneficial effects of adenosine and phosphate in kidney preservation.

A new perfusate developed in the animal laboratory has been used in our clinical transplantation program in the last year. This perfusate provides excellent clinical results even with less-than-ideal kidneys, as manifested by an 83% immediate function rate and a 96.5% one-month graft survival. Optimum utilization of all donors referred to a transplant center may lessen the problem of insufficient donor organs. Continued basic research in the laboratory to optimize perfusion preservation may produce even better perfusates that can be adapted to the clinical situation and further improve graft survival.

Renal transplantation in patients with systemic lupus erythematosus.

The activity of systemic lupus erythematosus (SLE) was investigated in 18 recipients of 20 renal transplants by retrospective analysis of their medical records and by screening the ten patients with more than one year follow-up. Eight grafts were lost, all because of rejection occurring within the first year. From the 12 patients with functioning transplants, one was lost to follow-up at seven years and another had not completed one year. The remaining ten patients were studied, and no evidence of lupus nephritis was found despite serologically active SLE in four cases. Their follow-up was 4.5 +/- 1.3 years. Our study provides the relatively scarce literature on renal transplantation in patients with SLE with a series of 18 recipients of 20 allografts, confirms that the recurrence of lupus nephritis in the allografts is very rare, as previously suggested, and discloses that graft and patient survivals are comparable with those of the general nondiabetic transplant population.

Can the results of live donor kidney transplantation be improved?

According to an analysis of 100 consecutive kidney transplants from live donors performed at our center over a 25-month period beginning in June 1980, only two patients have died, and five other patients had graft loss from acute or chronic rejection; this resulted in an overall actuarial 2-year patient survival rate of 98% and a graft survival rate of 90%. Eighty-five of the 93 patients with functioning grafts have excellent renal function, with serum creatinine levels less than or equal to 2 mg/dl. Complications occurred in 24 patients but rarely jeopardized the patients' lives or grafts or resulted in permanent disability. The functional capacity of most of the patients was improved by transplantation or was excellent both before and after transplantation. Forty-three transplants were possible through the use of the original or Imuran-modified donor-specific transfusion protocol, so that the lack of compatible donors rarely limited the availability of this therapy. New therapies that might improve graft or patient survival rate cannot reasonably be evaluated in recipients of live donor kidney transplants, because these results are already good. We have estimated that as much as $3.6 million in health care funds could be saved every 2 years at our center if we offered kidney transplants from healthy willing donors to all recipients before instituting dialysis. From our study we conclude that live donor kidney transplantation is an available, highly effective, and cost-efficient form of therapy for patients with end-stage renal disease.