Role of pulsatile perfusion with tissue plasminogen activator in deceased donor kidneys with extensive glomerular thrombosis.

BACKGROUND: Pulsatile perfusion (PP) improves delayed graft function, whereas tissue plasminogen activator (tPA) lyses thrombi. We studied the role of PP with tPA containing perfusate in deceased donor kidneys (DDK) with 50% thrombosed glomeruli. METHODS: Fourteen DDK with extensive glomerular thrombi on biopsies were preserved using PP with histidine-tryptophan-ketoglutarate solution containing tPA. Wedge biopsies were repeated after PP. RESULTS: Causes of donor death included closed head trauma in 8, anoxia in 2, and stroke in 4. Donors who averaged 33.3 years old displayed a final 24-hour urine volume of 1933 mL, a terminal serum creatinine level of 1.8 mg/dL, a blood urea nitrogen of 20 mg/dL, and a platelet count of 128,000/microL. The initial flow of 47 mL improved to 111 mL/min after 16.17 hours of perfusion. Resistive indices (RI) decreased from 0.69 to 0.26 at 4.2 degrees C. Biopsy specimens after PP showed a reduction in glomerular thrombi from 50% to 23%. Recipients averaged 54.9 years old. Cold ischemia time averaged 35.5 hours. One patient displayed primary allograft nonfunction, 3 required transient dialysis, and 10 showed prompt allograft function. Recipient follow-up averaged 12 months, with serum creatinine levels of 4.3 mg/dL at 1 week, 2.0 mg/dL at 1 month, and 1.6 mg/dL at last follow-up. CONCLUSIONS: Renal allografts with extensive glomerular thrombosis improved their biopsy appearance following PP with tPA. Improvement in PP parameters allowed successful transplantation of such kidneys that otherwise would have been discarded. PP with tPA appears to be beneficial for kidneys with extensive glomerular thrombosis.

Ipsilateral portal enteric drained pancreas-kidney transplantation: a novel technique.

In conventionally described simultaneous pancreas-kidney transplantation with portoenteric drainage, renal revascularization is derived from the left iliac vessels and pancreatic revascularization, from the right iliac artery. A newer technique utilizing the right iliac artery as a single inflow to both organs is described in six patients herein. The technique is less time-consuming and tedious than the standard method, which involves dissection of both iliac vessels. Advantages include shortened dissection time and preservation of the contralateral side for future use.

Orthotopic kidney retransplantation in simultaneous pancreas kidney transplant patients with renal failure.

Traditionally transplant nephrectomy was required as a separate procedure prior to retransplantation in simultaneous pancreas kidney transplant patients. An alternative approach combining both procedures is described, during which the rejected kidney is removed and replaced orthotopically by the new allograft.

The cost of steroid-free protocols in primary cadaver kidney transplantation.

Steroid-free immunosuppression regimens have been enjoying recent success in clinical transplantation. The use of antibodies required for such protocols can be an economic burden. We proposed to study their cost in our center. This retrospective study involved 147 consecutive patients subjected to 4 protocols of immunosuppression. The first received triple therapy. The second group received induction with basiliximab, whereas the third received Basiliximab plus cyclosporine (CSA) plus mycophenolate mofetil (MMF), and the fourth received Thymoglobulin plus CSA plus MMF in conjuction with only 4 days of steroid. Rejection episodes were treated with Solumedrol. Six-month charges were obtained from computerized records of the finance department, the in-house laboratories, and the transplantation service registry. All charges were expressed in 2004 dollars. Statistical analyses were obtained using chi-square, analysis of variance (ANOVA) and Kaplan-Meier tests. The 4 groups were similar with regard to donor and/or recipient gender, race, panel reactive antibodies, cold ischemia, dialysis requirements length of stay and readmission, graft survival, and function. Charges were significantly higher in the last 2 groups as compared with triple therapy.

Effect of transfusion of donor on allograft survival.

It has been reported by two European transplant centers that blood transfusion of cadaver donors with third-party blood prior to nephrectomy increases renal allograft survival rates by approximately 30% at 1 year. A retrospective analysis in our center was performed on 293 kidney recipients, 110 of whom received kidneys from untransfused donors. Actuarial analyses revealed no significant differences in graft survival rates between all nontransfused donor kidneys and all transfused donor kidneys. Considering only first transplant recipients, there was no difference in graft survival rates between nontransfused donor kidneys and transfused donor kidneys. In addition, when only preoperatively transfused recipients receiving first transplants were examined, there was no difference in graft survival rates between nontransfused donor kidneys and transfused donor kidneys. Animal studies were performed with (Lewis x Brown Norway)F1 (LBNF1) hybrid rat hearts transplanted heterotopically to the abdomens of Lewis rat recipients. Six LBNF1 heart grafts had a mean survival time of 8.0 +/- 1.1 days. Five LBNF1 rats received 2 ml of heparinized whole blood from Charles River (CD) rats 24 hr before heart transplantation to Lewis recipients. The transfused LBNF1 grafts had a mean survival time of 6.6 +/- 0.9 days. Therefore, donor blood transfusion does not appear to prolong graft survival in this retrospective human study or in the animal model.

Metabolic effects of urinary diversion of exocrine secretions in pancreatic transplantation.

We have compared the metabolic consequences of two forms of exocrine drainage for pancreaticoduodenal transplant, duodenojejunostomy (DJ) and duodenocystostomy (DC). DC offered the advantage of avoiding opening of the recipient small intestine with its potential for wound sepsis, as well as a reliable method for early detection of pancreatic rejection as measured by an abrupt fall in urinary amylase and bicarbonate concentration. However, DC led to a large urinary loss of bicarbonate with a concomitant mild metabolic acidosis. During periods of renal dysfunction, the patients with DC developed severe hyperchloremic acidosis. Use of DC for pancreatic exocrine diversion may require patients to take supplemental bicarbonate even with a well-functioning renal transplant.

Failure of cyclosporine to prevent in vivo T cell priming in man. Studies in allogeneic spleen transplantation.

Cyclosporine is a potent new immunosuppressive agent utilized in clinical organ transplantation. Available evidence suggest that it interferes with the secretion of interleukin-2. However, the long term efficacy of cyclosporine in preventing allograft rejection may depend on a relative sparing of suppressor cells early in the allogeneic response, allowing them to mature and effect a state of operational tolerance. If this is the case, cyclosporine must not affect antigen priming or recognition. Two patients in our center underwent allogeneic spleen transplant in conjunction with renal and pancreatic transplant. Both patients were treated with therapeutic levels of cyclosporine during the course of transplant. Neither developed any clinical signs of renal or pancreatic transplant rejection. Both patients developed graft-versus-host disease and eventually required allogeneic (donor) splenectomy. Studies performed on the splenocytes recovered from these specimens demonstrate alloantigen-specific cytotoxic T cell precursors. These studies demonstrate that although cyclosporine can prevent allograft rejection it does not necessarily prevent or ameliorate graft-versus-host disease. Furthermore, cyclosporine does not prevent in vivo T cell priming of alloantigen recognition. The primed cytotoxic precursors can be expanded in the presence of exogenous interleukin-2 to become fully active cytoxic cells.

Results of conversion from cyclosporine to azathioprine in cadaveric renal transplantation.

Between December 1983 and August 1985, 110 cadaver transplants were performed at our institution. All were started on cyclosporine (CsA) and prednisone (P) for immunosuppressive therapy. Of the 110 patients, 46 were converted from CsA to azathioprine (AZA) for a variety of reasons (cost, toxicity, patient preference, prolonged dysfunction posttransplant, or nonresponsive rejection). The course and outcome of these patients are described. The only group of patients who had consistent benefit and stable course following the CsA-to-AZA switch were primary cadaver transplants with stable renal function (serum creatinine less than 2 mg/dl) who were converted an average of 7.97 months posttransplant. All other groups of patients had severe problems or graft loss postconversion.

Elevated soluble interleukin 2 receptor levels found among kidney transplant recipients.

Although previous studies have not demonstrated a clear correlation between interleukin (IL) 2 receptor levels and immunological events after transplantation, many still suggest that these levels have clinical utility. A total of 759 serial measurements of both IL-2R and creatinine were compared over time and correlated with rejection episodes, clinical course, and immunosuppression. The profiles for the 40 patients showed several patterns, including correlation with changes in creatinine levels or with renal dysfunction, peaks in the absence of clinical findings, and discordant IL-2R and creatinine levels. Wide baseline variations in IL-2R levels confounded comparison of mean values and definition of a statistically significant rise. While tending to correlate with immunological events, elevations in IL-2R also occurred in clinically normal patients. IL-2R appears to lack specificity for immunological events. Thus, we conclude that IL-2R measurement does not have clinical diagnostic utility for monitoring renal transplant recipients.

Successful DR-incompatible cadaver kidney transplantation. Combined effect of HLA A and B matching and blood transfusion.

The purpose of this retrospective analysis of DR-incompatible cadaver renal transplantation was to evaluate the effect of HLA A and B matching and blood transfusion status on actual one-year graft survival. There were 31 2-DR, 111 1-DR, and 27 0-DR grafts at risk during the study period. First, a comparison was made between preoperative (PRE) and peroperative (PER) transfusions alone. Graft survivals were 70% vs. 92% (2 DR), 67% vs. 52% (1 DR) and 71% vs. 39% (0 DR) for the PRE and PER groups, respectively. Statistical significance was not found between the two values in each DR subgroup, although the difference approached significance in the O DR group (0.1 greater than P greater than 0.05). Matching for greater than or equal to 2 A and B antigens significantly improved graft survival in the 1 DR-matched group when compared with those matched for less than 2 antigens (76% vs. 44%, P less than 0.005). While marked differences between the greater than or equal to 2 and less than 2 A and B matched groups were observed for both the 2 DR (92% vs. 68%, P greater than 0.1) and O DR groups (59% vs. 40%, P greater than 0.3) these differences were not significant. Stratifying the data for transfusion status revealed that the positive influence of HLA A and B matching in the 1 DR group was dependent upon the presence of preoperative blood administration. Graft survival of 87% for the PRE transfused recipients of grafts matched for greater than or equal to 2 A and B antigens was significantly better (P less than 0.001) than the 42% survival observed in similarly transfused recipients of poorer matched organs. Conversely, A and B matching was not significantly beneficial in the 1 DR recipients transfused only at the time of transplant with graft survivals of 57% vs. 43% for those matched for greater than or equal to 2 or less than 2 A and B antigens, respectively (P greater than 0.3). This analysis suggests that a combined effect of both HLA A and B matching and preoperative blood transfusions may allow for highly successful first cadaver renal transplantation in the face of DR incompatibility.

Molecular compatibility and renal graft survival--the HLA DQB1 genotyping.

Renal donor-recipient HLA DQB1 typing at the DNA level provides a new avenue to study graft survival (GS) and compatibility. HLA DQB1 genotypes of 63 renal donor-recipient pairs were typed simultaneously by assessing patterns from electrophoresed restriction fragments (PCR-RFLP) of amplified DNA (ADNA) and hybridization patterns of sequence specific oligonucleotides (PCR-SSO) of ADNA. Thus the clinical applicability of these two protocols for HLA DQB1 typing was assessed in addition to the compatibility study. Typing results of these two protocols gave overall agreeable results. Sixty-seven per cent of 150 alleles from 75 heterozygotes typed by both protocols had identical allelic type assignments. Serotyping shared more concordant results to PCR-RFLP determined types than to PCR-SSO determined types. The PCR-RFLP protocol can be easily implemented for clinical DNA typing because of its clarity in assigning allelic types and the possible handling of a small number of typing samples, even a single sample, in a single run. The degree of compatibility of these donor-recipient pairs was measured by matching (M) or mismatching (MM) the PCR-RFLP determined DQB1 allelic types. The Kaplan-Meier method was used to estimate GS. Significantly higher GS rates (P < 0.03) were found in donor-recipient pairs with 2 M (GS:74%) as compared with those with 1 M (GS:68%) or 0 M (GS:40%). Higher graft survival was also associated with 0 MM (GS:86%) compared with those with 1 MM (GS:60%) or 2 MM (GS:40%), although the significance level is P = 0.08 for both Mantel-Cox and Breslow tests. These findings indicate the importance of determining HLA DQB1 molecular alleles for assessing GS.

Molecular compatibility and renal graft survival--the HLA DRB1 genotyping.

HLA DRB1 allelic types were determined by using sequence-specific oligonucleotides for the analysis of 91 renal donor-recipient pairs that were followed for 30 months. The Kaplan-Meier method was used to evaluate graft survivals (GS) of the matched and mismatched groups. The degree of compatibility was measured by allelic type matches and mismatches of the pairs. Furthermore, HLA DR genotypes were categorized into five groups, namely DR1, DR2, DR4, the group that also has the DRw52 allele, and the group of DR7, DR9, and DR10. All types within a group were considered a match. Serotypes of the same study group were also included for comparison. Associations of superior GS with compatible DRB1 allelic types, serotypes, and grouped DRB1 types were observed. A significantly higher GS rate was found in donor-recipient pairs when HLA DRB1 types were analyzed by group mismatching (P = 0.03) rather than type mismatching (P > 0.34). Because of the numerous allelic types that can be assigned on the basis of nucleotide sequence variations, a larger number of donor-recipient pairs is required to derive statistically significant results.

Duodenopancreatectomy for transplantation.

Forty duodenopancreatectomies for transplantation were performed. The technique focused on the maintenance of the cardiovascular hemodynamics of the donor during the procedure, the meticulous dissection and preservation of all vascular supplies to the duodenum and the pancreas, and the suppression of warm ischemia by in situ cooling. Recipient euglycemia was established within two hours of the revascularization in 37 of 38 pancreata transplanted. Only six of the 78 renal transplant recipients receiving more than one organ from the same donor required postoperative dialysis, for a 7.7% incidence of delayed graft function. Immediate function was observed in all six cardiac allograft recipients.

Evaluation of techniques of controlling exocrine drainage after segmental pancreatectomy in dogs. Implications for pancreatic transplantation.

Pancreatic transplantation is hampered by difficulties in controlling exocrine drainage. Methods of controlling exocrine drainage were assessed in 30 dogs receiving right lobe pancreatectomy. In the sham group, laparotomy and dissection of the pancreas were performed. In the others, the duct was either left open, ligated, anastomosed to jejunal mucosa, or injected with 1.5 mL of either silicone rubber, Neoprene, or Prolamine. Serial serum glucose and amylase levels were obtained at regular intervals and pancreatic biopsies were performed at two and eight weeks for examination. Glucose homeostasis was maintained throughout the study period. All animals developed severe pancreatitis as shown by hyperamylasemia by the second postoperative day, which resolved in most animals by the tenth to 14th day. Animals were free of ascites, pancreatic abscesses, and pseudocysts. All methods of ductal obstruction as well as the open duct drainage led to islet and acinar fragmentation and fibrosis. Endocrine function was preserved in all groups. In three animals with patent ductal-jejunal anastomoses, the pancreas appeared normal. Duct-to-jejunum anastomosis was the preferred method to preserve pancreatic function and morphology.

Ambulatory peritoneal dialysis. Exploratory laparotomy for peritonitis.

We present our experience with performing an exploratory laparotomy for peritonitis in patients undergoing continuous ambulatory peritoneal dialysis (CAPD). Six of 134 patients undergoing CAPD during the study period underwent surgical intervention because of abdominal sepsis. Two patients had bacterial peritonitis without abscess formation or evidence of visceral perforation and they recovered readily and, in retrospect, may not have required an operation. Of the three patients with fungal abscesses, two died of subsequent bacterial sepsis, while one patient survived, albeit after drainage of a recurrent pelvic abscess. One patient died because of extensive intestinal gangrene that was misdiagnosed as CAPD-related peritonitis initially. Our experience with these cases suggests that fungal peritonitis is a life-threatening complication that may result in both formation of an abscess and death. Therefore, it warrants aggressive antifungal chemotherapy and surgical intervention should an abscess be discovered. In contrast, bacterial peritonitis should be treated with appropriate antibiotic regimens until adequate evidence indicating the presence of a surgical condition is obtained.

Factors influencing male sexual impotence after renal transplantation.

Sexual impotence has been reported sixfold after sequential renal transplantation. The effects of race, age, diabetes mellitus, hypertension, uremia, arteriosclerosis (by ABI = ankle BP/brachial BP), penile blood flow (by PBI = penile BP/brachial BP), length of dialysis and transplantation, and patency of hypogastric arteries (by angiogram and operative description) on impotence were examined in a retrospective study of 61 male transplant patients followed from six to 108 months and a prospective study of 15 patients evaluated before and after transplantation with a six-month follow-up. Age (greater than forty years) was the only factor deleterious to male potency (potent patients 40.1 +/- 10.40 years vs impotent patients 48.6 +/- 10.06 years significant at p less than 0.006). Impotence did not correlate with ABI and PBI. Interruption of both hypogastric arteries is not necessarily related to impotence. Vascular impotence is more uncommon in renal transplant recipients than we had anticipated. Post-transplantation male impotence is perhaps best treated by penile prosthesis insertion.

En bloc transplantation of infant kidneys: ten-year experience.

BACKGROUND: Recent data have shown that en bloc infant kidneys transplanted to adult recipients functioned well. Longterm graft survival and function are not available, however. This study analyzes the 10-year experience with transplantation of en bloc infant kidneys from 1987-1997. STUDY DESIGN: This is a chart review of adult recipients of en bloc infant kidneys with respect to donors' and recipients' age, weight, creatinine, HLA antigen matching, panel reactive antibodies, cold ischemia time, surgical complications, original disease, and longterm graft function and survival. RESULTS: Five en bloc kidneys thrombosed (6.4%). Two ureteral fistulas were repaired successfully. Five patients underwent dialysis (6.4%). Two patients died of infection, six of heart attack and stroke, and one of cancer. All had excellent graft function at patients' death. Renal artery stenosis was dilated in seven patients. Six grafts were lost to rejection (one from noncompliance at 20 months). The original disease recurred in three patients with massive proteinuria despite excellent function. Graft survival at 43 months (range, 6-123 months) was 79%, with serum creatinine levels at 1, 3, 9 and 10 years of 1.2, 1.0, 0.8 and 0.8 mg/dl, respectively. Creatinine clearance averaged 88 mL/min (range, 34-188 mL) and 24-hour proteinuria was 146 mg (normal range, 10-150). CONCLUSIONS: In conclusion, en bloc infant kidneys can be transplanted successfully with excellent longterm function, hyperfiltration injury was not observed, and infant kidneys should be used more frequently.

Angioaccess by reverse brachiocephalic fistula.

Reverse vascularization of the cephalic vein using the medial cubital vein was performed in 16 patients. No complications were found in a follow-up period that ranged from 2 to 47 months. In selected anatomic cases, this reverse fistula is preferable to the direct brachiocephalic fistula.

Technique of simultaneous renal pancreatoduodenal transplantation with urinary drainage of pancreatic secretion.

There are many advantages to transplanting the pancreas in the right iliac fossa and draining the pancreatic exocrine secretions into the bladder. This technique has been performed successfully in nine patients and the details have been discussed herein.

The third kidney transplant.

To determine the feasibility of third kidney transplantation, the experience at the University of Iowa was evaluated. The success of 14 such transplantations was dependent on the outcome of both of the previous graft operations. Three successful third transplantations with graft survival of 6 years, 3 years, and 1 year have occurred in recipients with more than 1 year survival of a previous kidney. Conversely, graft loss due to rejection developed in all patients who experienced graft survival of less than 1 year for both antecedent grafts. Moreover, HLA-A and -B matching and level of presensitization were not predictive of success in this series. These data suggest that third kidney transplantation using conventional immunosuppression may not be appropriate in the subgroup of patients who have clearly lost their first two grafts to early rejection.