Thomas Bogaard

Outcome of en bloc and single kidney transplantation from very young cadaveric donors

BACKGROUND The optimal use of very young cadaveric kidneys (from donors less than 4 years old) remains controversial. High rates of technical complications and poor functional results compared with adult donor kidneys have been reported. The use of en bloc transplantation to overcome these problems has been advocated, although en bloc transplantation halves the number of potential transplants from very young donors. METHODS We studied the technical and functional results of 91 transplants from very young donors performed at our institution between 1984 and 1995. This included 59 single and 22 en bloc procedures involving first transplants and 7 single and 3 en bloc procedures involving retransplantation. Individual surgeon preference dictated the use of either the single or en bloc technique. Kidneys smaller than 6 cm tended to be transplanted en bloc, and lighter patients were generally given preference for receiving pediatric kidneys. Patients received sequential cyclosporine-based quadruple immunosuppression. RESULTS En bloc kidneys had a 1-year and 5-year graft survival of 82% and 70%, respectively. Single kidneys had a 1-year and 5-year graft survival of 64% and 40%. Kidneys that avoided acute rejection episodes and that were transplanted into heavier or male recipients had better long-term survival. Kidneys from donors less than 2 years old did poorly whether transplanted en bloc or singly. Better HLA matching improved short-term, but not long-term, graft survival, whereas cold ischemic time did not have statistically significant association with differences in graft survival. Eleven percent of the transplants had ureteral leaks, but only one kidney was lost. Ten transplants had vascular complications leading to graft loss, whereas two episodes of arterial stenosis were successfully treated with percutaneous angioplasty. CONCLUSIONS En bloc transplantation optimizes the outcome of transplantation with very young kidneys. We recommend induction therapy and cyclosporine immunosuppression with cyclosporine levels similar to adult target levels to minimize rejection episodes and, thus, improve outcome. These kidneys should be distributed nationally, because better HLA matching is associated with improved short-term graft survival. Our high ureteral leak rate indicates that alternatives to unstented ureteroneocystostomy should be considered.

Hyperacute and acute kidney graft rejection due to antibodies against B cells

Because of the perception of its uncertain clinical significance, the B cell crossmatch is not universally performed before renal transplantation. Even though sporadic cases of hyperacute rejection associated with B cell antibodies have been reported, doubts remain in light of other studies suggesting no effect on graft survival. This report describes 4 cases of graft rejection (3 hyperacute and 1 acute) that occurred in patients with anti-B-cell antibodies specific against donor HLA-DR or DQ antigens. Absence of anti-donor class I antibodies was confirmed in all cases by 2-color flow cytometry. Strong evidence for an antibody-mediated mechanism was found in one patient with anti-class I and anti-class II antibodies in serum transplanted with a class II mismatched kidney. In this case, only anti-class II antibodies were recovered in the eluate of the nephrectomy specimen. These four cases were compiled from three different institutions over a four-year period, which confirms the infrequent occurrence of these events. While anti-class II antibodies may not always be detrimental for graft survival, these results also confirm that they have the potential to cause hyperacute or acute graft loss. We conclude that the information provided by the B cell crossmatch should be available at the time that a decision to proceed with a renal transplant is made.

Incidence of new-onset hypercholesterolemia in renal transplant patients treated with FK506 or cyclosporine.

In this study, we compare cholesterol levels during the first year after renal transplantation in FK506 (Prograf)- and cyclosporine-treated patients matched for cumulative first-year steroid dose and hypercholesterolemia risk factors. All patients had pretransplant cholesterol levels < 200 mg/dl. At 3 months posttransplant, 68% of the cyclosporine-treated patients had at least one cholesterol level greater than 200 mg/dl compared with 30% of the FK506-treated patients (P < 0.05). At the end of the year, 26% of FK506- and 67% of cyclosporine-treated patients remained hypercholesterolemic (P < 0.05). We conclude that cyclosporine has inherently more effect on cholesterol levels than FK506 during the first year after kidney transplantation.

Risks of transplanting kidneys from hepatitis B surface antigen-negative, hepatitis B core antibody-positive donors

BACKGROUND As the number of patients on the United States kidney transplant list increases, investigation into the utility of transplanting organs formerly considered marginal or undesirable has intensified. Using kidneys from hepatitis B surface antigen (HBsAg)-positive donors is thought to place recipients at excessive risk of graft failure, morbidity, and mortality. However, the risks of using kidneys from HBsAg-negative but hepatitis B core antibody (HBcAb)-positive donors have not been defined. METHODS Between 1990 and 1994, our group transplanted 1067 cadaveric kidneys, including 38 from HBsAg(-)/HBcAb(+) donors. Of these 38 kidneys, 27 were transplanted into HBcAb(-) recipients (group 1) and 11 were transplanted into HBcAb(+) recipients (group 2). Group 1 and 2 patients received no hepatitis immunoglobulin therapy after transplantation and received the same immunosuppression and rejection therapies as recipients of kidneys from HBcAb(-) donors. RESULTS After transplantation, none of the group 1 patients became HBsAg(+), three became hepatitis B surface antibody (HBsAb)-positive, and two became HBcAb(+). Of the group 2 patients, none became newly HBsAg(+) or HBsAb(+). No patient receiving a kidney from an HBsAg(-)/HBcAb(+) donor developed signs or symptoms of clinical hepatitis B. Graft and patient survival rates were similar in both groups and similar to the rates of the 1029 recipients of kidneys from HBcAb(-) donors. CONCLUSIONS Recipients of kidneys from HBsAg(-)/HBcAb(+) donors are at a small risk of hepatitis B seroconversion but are at no excess risk of graft failure or short-term morbidity or mortality.

Seventeen consecutive successful one haplotype-matched living related first renal transplants using donor-specific blood transfusions

A donor-specific transfusion (DST) protocol was carried out in 25 recipients obtaining kidneys from live-related one-haplotype-disparate high stimulating mixed lymphocyte culture (MLC) donors. The protocol consisted of the recipient receiving a transfusion of 200 ml of donor whole blood every 2 weeks for a total of three transfusions. Before and after each transfusion and just before transplantation, recipient blood samples were tested for cytotoxic antibody studies against a random panel of 30 normal persons, in addition to donor-recipient crossmatches. Patients were followed for a minimum of 8 months and a maximum of 24 months, with a mean followup of 14 months. Seventeen of 17 primary transplants performed were successful. Three second transplants were performed. Two second graft recipients rejected their transplants, while one was successful. Three patients of 25 developed either T-warm- or B-warm-positive crossmatches, while 2 patients who completed the study with negative crossmatches were not transplanted because of donor withdrawal following transfusions. Rejection episodes occurred infrequently, but when present, occurred early in the postoperative period (2nd or 3rd day). Only 6 of 25 subjects developed greater than 10% B-warm or T-warm circulating cytotoxic antibodies. Six of eight subjects who entered the study with greater than 10% cytotoxic antibodies had diminishment in the strength of their antibody response after the DSTs. No patient was rendered untransplantable by the development of large numbers of cytotoxic antibodies. DST appears to be a highly successful technique for primary living related donor transplants in subjects who are one haploid identical but with nonidentical stimulating MLC indices.

Bladder rehabilitation in patients with old spinal cord injuries with bladder neck incision and external sphincterotomy.

Seventy-five patients with neurogenic bladders underwent bladder neck incision and/or external sphincterotomy to establish effective vesical emptying and reverse progressive hydronephrosis. A second operation to achieve these goals was necessary in 11 cases. The over-all success rate of these procedures in improving urinary tract stability was 94 per cent. Complications were infrequent, with hemorrhage and impaired penile erection being the principal problems. Eradication of established urinary tract infections was poor. However, infection-related morbidity was improved.

Improved Allograft Survival in Nonidentical Living Related Donor Transplants using Donor-Specific Blood Transfusions

A total of 78 consecutive HLA nonidentical living related donor transplant recipients with moderate to high stimulating mixed lymphocyte culture indexes underwent a deliberate donor-specific blood transfusion protocol. Of the patients 67 were first and 11 were second allograft recipients. Patients were monitored for immunological responses by cytotoxic B-cold, B-warm and T-warm antibody responses to a random panel of 30 donors, and by serial crossmatches to their donor subset B and T lymphocytes at 5C and 37C before beginning the protocol and after each donor-specific blood transfusion. Patients were followed from 3 months to 2 1/2 years, with allograft survival rates reported by the actuarial method. Survival rates of first allograft recipients were 96.0 plus or minus 2.77, 93.97 plus or minus 3.37, 93.97 plus or minus 3.37 and 90.68 plus or minus 4.50 per cent at 3 and 6 months, and 1 and 2 years, respectively. Of the patients entering the protocol for a primary transplant 20.18 per cent had persistently positive crossmatches. With increasing numbers of previous random blood transfusions a statistically significant sensitization rate was noted. Patient sensitization showed a general pattern of initial development of B-warm lymphocytotoxins resulting in positive B-warm crossmatches, which progressed to T-warm lymphocytotoxins and positive T-warm crossmatches if donor-specific blood transfusions continued. However, on development of B-warm positive crossmatches reversion to a negative crossmatch with successful transplantation was possible upon cessation of transfusions. No patient in the study was rendered nontransplantable due to donor-specific blood transfusions. All 5 patients who were completely disparate suffered amnestic type rejection episodes but following control of the rejection the course mimicked that of mixed lymphocyte culture identical living related donor transplants. Donor-specific blood transfusion is highly successful among first allograft recipients and success in extending the procedure to more disparate relatives is noted.

Bilateral Transitional Cell Carcinoma of the Renal Pelvis with unilateral Non-Functioning Kidney

A case is presented of bilateral transitional cell carcinoma of the renal pelvis with extension of the tumor to involve the renal parenchyma bilaterally. Unilateral complete absence of function was demonstrated and pathological study correlated the absence of function with complete replacement and destruction of the renal parenchyma by transitional cell tumor. Segmental absence of function of the contralateral kidney is also correlated pathologically with complete replacement of the involved renal segment with tumor. Total replacement of renal parenchyma by transitional cell carcinoma of the renal pelvis should be considered in the evaluation of renal non-function.

Effect of Deliberate Blood Transfusions in Cadaveric Kidney Allografts at a Single Center

The effectiveness of deliberate pre-transplant blood transfusions was compared in randomly transfused and nontransfused patients who acted as controls at a single transplant center. The patients in the pre-transplant transfusion group who had never been transfused had better graft survival than all other groups. Next, were those patients who had previous random transfusions and were then placed in the deliberately transfused group. Those who had received random blood transfusions but were not in the protocol and those patients who never had transfusions did the poorest. Those patients never transfused previously who received the scheduled transfusions had far lower levels of antibodies than those who had had previous transfusions and those with previous transfusions who were then entered into the prospective transfusion protocol. The patients who had B cold cytotoxic antibodies had the highest graft survival rates. Timing was important, with the group receiving the last transfusions 3 to 6 weeks before transplantation doing significantly better than any other group. Histocompatibility locus-A and B antigen distribution among the groups did not bias the data.

Prospective HLA-DR Matching in Cadaveric Renal Transplants: A Single Center Study

We reviewed 77 potential cadaveric allograft recipients who had undergone prospective HLA-A and B locus and HLA-DR antigen identification. Matching was accomplished, giving first priority to HLA-DR compatibility and relying on HLA-A and B antigen matching only in situations of total HLA-DR incompatibility. Complete HLA-DR identification occurred in 56 per cent of all patients. There were 15 patients (19.5 per cent) who received a 2/2 HLA-DR perfect match, with 86.7 plus or minus 8.8 per cent 1-year actuarial graft survival, and 41 (53 per cent) who received a 1/2 HLA-DR match, with 58.2 plus or minus 7.8 per cent 1-year actual allograft survival. Finally, 21 patients (27 per cent) received a 0/2 HLA-DR match, with 64.9 plus or minus 10.7 per cent actual survival. These results and their mirrored mismatching results showed statistically significant allograft success in only the HLA-DR 2/2 matches. Matching for HLA 2 DR donors proved a statistically significant success over the other HLA-DR allograft matches and the older controversial matching system based on HLA-A and B locus antigens. The restricted gene polymorphism of the HLA-DR systems allows for a relatively high percentage of perfect HLA-DR matches.