The late adverse effect of splenectomy on patient survival following cadaveric renal transplantation.

Kidney and patient survival of 351 consecutive patients undergoing first cadaveric renal transplants since 1968 were reviewed to determine the effects of splenectomy on outcome. Special emphasis was given to analysis of 106 splenectomized and 102 nonsplenectomized patients treated since 1975. During the first two years after transplant, kidney survival was better in the splenectomized patients, with no adverse effect on patient survival. However, after the first two years, patient survival became significantly worse in splenectomized patients (35.5% vs. 60.5% at 84 months). Of the deaths, infection was the cause in 26.7% of nonsplenectomized patients compared with 50% of splenectomized patients (P less than 0.07). Of patients alive at one year posttransplant, death rates were not different in patients splenectomized before 1975 or after 1975. Timing of splenectomy (prior vs. concurrent) had no effect on outcome. The adverse effect of splenectomy on mortality appeared to be more pronounced in younger (less than or equal to 45 year-old) than in older (greater than 45 year-old) patients. Splenectomy should not be performed routinely in preparation for a cadaveric transplant because of an unacceptably high late mortality that is primarily from sepsis.

Proteinuria following transplantation. Correlation with histopathology and outcome.

A review of 693 renal transplant recipients revealed 77 (11%) in whom persistent, heavy proteinuria (greater than 2 g/24 hr) developed. Renal histology was available in all 77 patients. Twenty-one patients had received kidneys from living-related donors, the remaining 56 from cadaveric donors. The cause of proteinuria in these 77 patients was as follows: transplant glomerulopathy (30), allograft glomerulonephritis (22), chronic rejection (21), renal vein thrombosis (2), diabetic glomerulosclerosis (1), and hypertensive nephrosclerosis (1). Of the 22 patients who developed glomerulonephritis in the transplanted kidney, 6 had recurrent disease (3--membranous glomerulopathy, 2--focal sclerosis and hyalinosis, 1--membranoproliferative glomerulonephritis); 6 developed de novo glomerulonephritis; and in 10 the type of glomerulonephritis could not be classified as recurrent or as de novo because of lack of characterization of the original kidney disease. Renal vein thrombosis occurred in association with other lesions in an additional 5 cases (3--chronic rejection; 2--membranous glomerulopathy). In follow-up only 23.4% (18 of 77) of the patients maintained prolonged graft function; the majority of grafts being lost within one year of the development of persistent, heavy proteinuria. Of the 18 patients who retained their grafts, 8 had glomerulonephritis, 5 transplant glomerulopathy, and 5 chronic rejection. This study confirms the poor prognosis that has been reported with the development of nephrotic-range proteinuria in renal allograft recipients.

The induction of immunologic hyporesponsiveness by preoperative donor-specific transfusions and cyclosporine in human cadaveric transplants. A preliminary trial.

A prospective randomized preliminary trial was performed in patients undergoing cadaveric renal transplantation to determine the potential benefits, disadvantages, and logistic problems associated with the administration of donor-specific transfusions and cyclosporine initiated 24 hr before transplantation. Ten patients received DST followed by continuous intravenous CsA approximately 24 hr before cadaveric renal transplantation from the same donor. Twelve patients receiving sequential therapy with Minnesota antilymphoblast globulin, azathioprine, and steroids with subsequent conversion to CsA served as controls. Patient demographics and the donor characteristics were evenly matched in the two groups. While the study group had longer cold ischemia time and more evidence of renal dysfunction within the first two weeks, subsequent renal function was identical in the groups and there were fewer episodes of severe rejection requiring treatment with OKT3 within the first six months in the DST group (5 vs. 0, P less than 0.05), which also had less reactivity in mixed lymphocyte cultures against preserved donor-specific lymphocytes than did the control group (stimulation index 9.0 +/- 3.0 vs. 25.3 +/- 6.0, respectively, P less than 0.05). The need for dialysis, incidence of infections and other complications, and subsequent immunosuppressive therapy were not different in the two groups. It is concluded that DSTs and intravenous CsA initiated 24 hr prior to transplantation are capable of inducing reduced immunologic responsiveness against the specific donor. Patients treated with this therapy should receive organs from "ideal" donors without risk factors and cold ischemia time should not exceed 30 hr. Further clinical studies of this approach are warranted.

Successful retreatment of allograft rejection with OKT3.

OKT3 is a murine monoclonal antibody to the CD3 antigen of human T lymphocytes. The production of human antimurine antibodies after treatment with OKT3 has been perceived as a major limitation to its extended use and reuse. Treatment of 142 patients with 168 courses of OKT3 resulted in the development of antimouse antibody in 28% of the patients. Twenty-six patients (16 kidney, 6 liver, 3 heart, 1 pancreas) have been retreated with 27 courses of OKT3. Eighteen patients had no antimurine antibodies present, and the rejection reversal rate was 83% (15/18). Six patients had a low-titer antimurine antibody present, and rejection reversal occurred in 5 (83%). Rejection was not reversed in 2 patients with a high-titer antibody. Development of antimurine antibody was more frequent in renal transplant recipients (33%) than in hepatic (12%) or cardiac transplant recipients (18%). We believe that this reflects the fact that concomitant immunosuppressive therapy is more likely to be reduced during OKT3 therapy in renal transplant recipients than in hepatic or cardiac transplant recipients. Retreatment of patients with no anti-OKT3 antibody resulted in depletion of CD3+ cells from the peripheral blood, but it took longer than in patients being treated with OKT3 for the first time. Similarly, serum OKT3 levels rose more slowly in retreated patients compared to first treatment. In retreating patients with a low-titer antimurine antibody, it often was necessary to increase the dose of OKT3 in order to achieve adequate serum OKT3 levels and to deplete CD3+ cells. De novo antimurine antibody developed in 4 of the 18 (22%) antibody-negative patients who were retreated. In conclusion, retreatment with OKT3 should not be considered unless the antibody status of the patient is known. Development of low-titer antibodies does not preclude successful retreatment with OKT3; however, alternate antirejection therapy should be used in patients with high-titer antimurine responses.

Thromboembolic disease in renal allograft recipients. What is its clinical significance?

Detailed analysis of the clinical data and autopsy material of 100 consecutive renal transplant recipients revealed significant thromboembolic disease in 25 patients and a total of 41 complications. In six of them, thromboembolism was associated with sepsis. Nine patients died (20% of total number of deaths) due to a primary thromboembolic event. The incidence of pulmonary embolism was 14%; myocardial infarction, 3%; cerebrovascular disease, 4%; renal artery thrombosis, 2%; renal vein thrombosis, 3%; thrombophlebitis/deep vein thrombosis, 13%; and miscellaneous, 2%. The incidence of thromboembolism was higher in patients older than 40 years of age (P = .02) and during the earlier months after transplantation. We summarize the general incidence and mortality related to thromboembolism and discuss the factors predisposing the graft recipient to thromboembolic disease. Prevention and therapy of this complication should decrease the morbidity and mortality in graft recipients and enhance the success of renal transplantation.

Transplantation of microbially contaminated cadaver kidneys.

Bacterial cultures of graft perfusion fluid were taken on 514 renal perfusions during a ten-year period. A total of 22 positive cultures were found. Two sets of kidneys were discarded because of the bacteriology report. Only two possible wound infections were found that could be attributable to the preoperative contamination even though 19 of 24 patients with "contaminated" kidneys received no antibiotics. No loss of kidneys or life was found. Of the 22 contaminated perfusates, 18 (80%) originated from other institutions although only 144 (28%) of the total kidneys that were perfused came from other institutions. The majority of cultures indicated that the organisms were skin contaminants or organisms of low virulence. Microbial contamination of perfused cadaver kidneys is uncommon (1.2% in local kidneys and 9.3% in shared kidneys). Contaminated kidneys are not a major source of infection in renal transplant recipients. Kidneys that are contaminated with frequently virulent Gram-negative bacteria, such as Escherichia coli, should be discarded. Contamination of kidneys with Gram-positive organisms should not be a contraindication for transplantation, but the patients should probably be given prophylactic antibiotics.

Laser surgery for blue rubber bleb nevus.

A 21-year-old man has had extensive cutaneous and visceral manifestations of the blue rubber bleb nevus syndrome since birth. Surgical therapy with the carbon dioxide laser was successful in removing 225 skin hemangiomas without recurrences or complications such as hemorrhage and infection. The cosmetic and follow-up results have been excellent.

Further evidence against the routine use of parathyroid ultrasonography prior to initial neck exploration for hyperparathyroidism.

The role of preoperative localization tests in patients undergoing initial neck exploration for hyperparathyroidism (HPT) is controversial. The use of parathyroid ultrasonography (US) in 46 patients (7 men, 39 women; mean age: 60 years) who underwent initial neck exploration for hypercalcemia and who had the diagnosis of HPT confirmed at surgery is reported. At surgery, a single adenoma was found in 40 patients and multiple hyperplastic glands in 6 patients. Of the 40 adenomas, only 22 (58%) were localized to the correct side by the preoperative US, and only 5 of 18 hyperplastic glands (28%) were correctly localized. The rates of false-positive and false-negative results were 10% and 46%, respectively. The sensitivity of parathyroid US was 54%, the specificity 90%, and the accuracy 70%. The low sensitivity and accuracy and the high rate of false-negative test results that were observed suggest that there is no role for the routine use of parathyroid US in patients undergoing initial neck exploration for HPT.

Renal allograft artery stenosis.

Thirteen renal artery stenoses occurred in 127 renal allograft transplantations performed at the University of Cincinnati Medical Center over a four year period. The most common symptoms were hypertension and decreasing renal function occurring from three days to three years post transplantation. Eight lesions occurred in patients with a single artery and five when double arteries had been joined together prior to anastomosis rather than implanted separately. The most common causes of renal artery stenosis was intimal hyperplasia of the donor vessel distal to the anastomosis (8 patients), atheromatous plaques (2), technical failure (2), and external compression (1). Surgical correction was facilitated by a midline incision. Resection of the stenotic segment and reanastomosis was the preferred procedure. Surgical failure and recurrence of hypertension were associated with involvement of small arteries or distal arteriolar level. When kidneys with multiple arteries are available, Carrel patches should be used when possible; if not, they should be implanted separately rather than joined together prior to anastomosis, thus decreasing the possibility of creating turbulent blood flow.

Hypothermic pulsatile perfusion and transplantation of pediatric cadaveric kidneys into adults.

Twenty-seven adults received en block or single renal allografts from pediatric donors less than 12 years of age. Hypothermic pulsatile perfusion of these small kidneys presented no technical difficulties. Flow rates ranged between 0.8-1.2 ml/min/gm. Single pediatric kidneys from donors as young as three years were able to produce a creatinine clearance of 50 ml/min in adults by one month posttransplant. No differences in renal function were noted between en bloc or single kidneys. En bloc transplants were associated with an increased incidence of renal arterial thromboses (3/8 cases). Because of this, pediatric cadaver kidneys were transplanted as single units, and an additional advantage was that they could provide donor kidneys for two recipients. In our series, one year pediatric graft survival is less than a comparable group of adult cadaveric kidney recipients.

Use of dacron vascular graft in arterial stenosis following renal allotransplantation.

Stenosis of the artery supplying the kidney allograft can produce a decrease in kidney function. A case is presented in which surgical reconstruction necessitated the use of a synthetic graft.

Renal transplantation in Alport's syndrome.

Nineteen patients (3 women and 16 men) with Alport's Syndrome and endstage renal failure received 23 allograft kidneys at two medical centers between 1972 and 1983. Ten patients had pretransplant splenectomies, and four patients had pretransplant thoracic duct drainage. After a mean follow-up time of 49 months, analysis revealed total allograft survival was 65 per cent at 1 year, 50 per cent at 2 years, and 57 per cent at 5 years. Pretransplant splenectomy resulted in 60 per cent allograft survival at 24 months mean follow-up. Pretransplant thoracic duct drainage resulted in 100 per cent allograft survival at 15.6 months mean follow-up. The overall allograft survival was greatest for three and four antigen-matched kidneys and for living related donor kidneys. Data indicated that 50 per cent of all allografts in men were functional at 50.8 months mean follow-up. All allografts in women were functional at 48.3 months mean follow-up. Three of four patients who expired had pretransplant splenectomies. From this study, the authors conclude that renal transplantation is the preferred method of treatment for patients with Alport's Syndrome.