Transplanting kidneys without points for HLA-B matching: consequences of the policy change.

In 2003, the US kidney allocation system was changed to eliminate priority for HLA-B similarity. We report outcomes from before and after this change using data from the Scientific Registry of Transplant Recipients (SRTR). Analyses were based on 108 701 solitary deceased donor kidney recipients during the 6 years before and after the policy change. Racial/ethnic distributions of recipients in the two periods were compared (chi-square); graft failures were analyzed using Cox models. In the 6 years before and after the policy change, the overall number of deceased donor transplants rose 23%, with a larger increase for minorities (40%) and a smaller increase for non-Hispanic whites (whites) (8%). The increase in the proportion of transplants for non-whites versus whites was highly significant (p < 0.0001). Two-year graft survival improved for all racial/ethnic groups after implementation of this new policy. Findings confirmed prior SRTR predictions. Following elimination of allocation priority for HLA-B similarity, the deficit in transplantation rates among minorities compared with that for whites was reduced but not eliminated; furthermore, there was no adverse effect on graft survival.

Determinants of discard of expanded criteria donor kidneys: impact of biopsy and machine perfusion.

We examined factors associated with expanded criteria donor (ECD) kidney discard. Scientific Registry of Transplant Recipients (SRTR)/Organ Procurement and Transplantation Network (OPTN) data were examined for donor factors using logistic regression to determine the adjusted odds ratio (AOR) of discard of kidneys recovered between October 1999 and June 2005. Logistic and Cox regression models were used to determine associations with delayed graft function (DGF) and graft failure. Of the 12,536 recovered ECD kidneys, 5139 (41%) were discarded. Both the performance of a biopsy (AOR = 1.21, p = 0.02) and the degree of glomerulosclerosis (GS) on biopsy were significantly associated with increased odds of discard. GS was not consistently associated with DGF or graft failure. The discard rate of pumped ECD kidneys was 29.7% versus 43.6% for unpumped (AOR = 0.52, p < 0.0001). Among pumped kidneys, those with resistances of 0.26-0.38 and >0.38 mmHg/mL/min were discarded more than those with resistances of 0.18-0.25 mmHg/mL/min (AOR = 2.5 and 7.9, respectively). Among ECD kidneys, pumped kidneys were less likely to have DGF (AOR = 0.59, p < 0.0001) but not graft failure (RR = 0.9, p = 0.27). Biopsy findings and machine perfusion are important correlates of ECD kidney discard; corresponding associations with graft failure require further study.

Renal transplant patient compliance with free immunosuppressive medications.

BACKGROUND: Noncompliance with immunosuppressive medications after renal transplantation is believed to be a major cause of allograft rejection and graft loss, with the impressive costs of these agents considered a significant reason for noncompliance. Our purpose was to determine the compliance rates of renal transplant patients who received their immunosuppressant therapy free of charge and evaluate their patterns of compliance. METHODS: All patients who received a renal transplant and received their immunosuppressant medications at our institution for their first year posttransplant were included in the study. Compliance rate was calculated and serum immunosuppressant concentrations were obtained to validate compliance assessments. RESULTS: Eighteen patients were included in the study. Approximately 48% of noncompliant patients were found to have subtarget drug concentrations, although only 14% of compliant patients had subtarget levels (chi2=12.9, P<0.001). At 5 months posttransplant, 95% of the patients remained compliant; however, by 12 months posttransplant, only 48% of the patients remained compliant. The mean time to the first noncompliant month was 9.8 months (95% confidence intervals=8.60-11.0). CONCLUSIONS: Patients who received their immunosuppressants free of charge were generally compliant within their first year of transplantation, however, compliance tended to decrease over time. This suggests that drug cost alone does not explain noncompliant behavior. Intensive efforts to increase medication compliance before month 8 posttransplantation should be implemented.

Late results of renal transplantation.

A total of 315 (64%) of 491 primary cadaver and living-related donor transplants performed from 1975 through 1984 were still functioning at 24 months. These selected patients were examined further to assess the impact of several risk factors on late graft and patient survival. Black recipients, patients with underlying diabetes mellitus or hypertension, patients with poor renal function at 24 months, and recipients of cadaver grafts had significantly poorer long-term graft survival. Age greater than or equal to 40, diabetes or hypertension, poor 24-month function, and cadaver donor transplantation were associated with poorer long-term patient survival. Considerable improvement in graft survival at 24 months was seen in 1980-1984 compared with the earlier period, coincident with our adoption of routine pretransplant random donor blood transfusion. In contrast, long-term graft survival in patients with functioning graft at two years did not improve significantly over the same period. Although living-related donor transplants showed greater graft and patient survival than cadaver donor grafts by univariate analysis, no such advantage was demonstrated by multivariate analysis.

Elevated basilic vein arteriovenous fistula.

BACKGROUND: Many surgeons continue to use prosthetic arteriovenous grafts for dialysis access despite the clear superiority of native arteriovenous fistulas. This study was undertaken to review our experience with elevated brachial-basilic fistulas as an alternative to prosthetic grafts in patients lacking veins suitable for more conventional arteriovenous fistulas. METHODS: We retrospectively reviewed the outcomes of 67 patients receiving elevated brachial-basilic arteriovenous fistulas over a 10-year period. Operative complications and causes of failure were identified and actuarial fistula patency determined. RESULTS: No patients suffered wound infections, and only 1 developed a steal syndrome in the late postoperative period. Actuarial fistula patency was 84% at 1 year, 73% at 3 and 5 years, and 52% at 10 years. CONCLUSIONS: The elevated brachial-basilic arteriovenous fistula is a superb alternative to prosthetic arteriovenous grafts in patients lacking suitable cephalic veins for native arteriovenous fistulas. Operative complications are uncommon, vascular steal is rare, and long-term patency is excellent.

Current role of cryoamputation.

Cryoamputation or physiologic amputation has been used at our institution for more than 30 years. From 1971 through 1989, 891 major lower extremity amputations were performed in 750 patients. With the use of dry ice or mechanical refrigeration, 320 (36%) physiologic amputations were performed in 292 patients. After physiologic amputation, the initially elevated white blood cell count and temperature decreased. Complications of physiologic amputation were unusual; 3% of patients developed minor freezing above the tourniquet, which did not alter the amputation level, while 1% had purulence at the level of surgical amputation that required delayed stump closure. The overall operative mortality rate in patients who underwent physiologic amputation was 11%, which was equivalent to the rate in patients undergoing primary amputation. Revision was required in 9% of amputations after preliminary physiologic amputation compared with 17% of primary amputations. Physiologic amputation is a simple technique, controls local infection, avoids emergency surgery, and allows for medical stabilization prior to surgery. Amputation revision after physiologic amputation is required less often than after primary amputation, while the mortality rate is comparable to that of patients undergoing primary amputation.

Nonoperative management of liver and/or splenic injuries: effect on resident surgical experience.

Changes in the management of trauma over the past few years are significantly affecting postgraduate surgical education, with the lack of operative trauma experience being a major concern in some programs. This problem is accentuated in residency programs that obtain their trauma caseload primarily from blunt injury. Our experience over the past 6 years confirms that the growing trend toward nonoperative management of blunt liver and spleen injuries in adults is likely to exacerbate this problem. Blunt trauma admissions to our Level I trauma center increased from 2888 from 1991 through 1993 (group A) to 3587 from 1994 through 1996 (group B). Liver and/or splenic injuries occurred with equal frequency in both groups. Whereas diagnostic peritoneal lavage was used in 26 per cent of group A, its use dropped to 2 per cent in group B as abdominal computerized tomography was used more frequently to evaluate these patients. Nonoperative management increased from 10 per cent of group A to 54 per cent of group B. As a result, therapeutic laparotomies dropped from 85 in group A (58% of patients with liver/splenic injuries) to 74 (35%) in group B and nontherapeutic laparotomies from 48 (33%) to 23 (11%). While the evolution in the management of blunt liver and splenic injuries has resulted in the avoidance of nontherapeutic laparotomies, the operative caseload available to surgical housestaff has been adversely affected. Although the Residency Review Committee has stressed the importance of the critical care management of these patients, the criteria used to evaluate the number of trauma cases in postgraduate surgical education may need to be revised.

In situ dissection of cadaver kidneys.

Major anatomic injuries occurred in 18 of 151 (12%) en bloc kidneys. No injuries occurred among the in situ kidneys. The rates of delayed graft function were equal. All the kidneys removed by the in situ method were removed by one surgeon (ALH). The results are good enough to recommend the technique even without a randomized study.

Living-related kidney donation.

Living renal donation is an effective means to expand the organ donor pool and allow more transplants to be performed at greater convenience for the recipient and with greater long-term success. Risks to the recipient appear to be minimal as long as careful donor screening is employed. Living donation has been implemented in extra-renal transplantation more recently. While the experience is limited so far, living donation is likely to remain an important option for liver and lung recipients.

Aminoglycoside combinations versus beta-lactams alone for penetrating abdominal trauma: a meta-analysis.

Despite several small comparative clinical trials, controversy persists over the best choice of antimicrobial therapy for penetrating abdominal trauma. Some still question whether single drug regimens are as effective as the traditional combinations containing an aminoglycoside. A meta-analysis was performed to address this issue. Meta-analysis is a relatively new statistical tool whereby data from a number of clinical trials is analyzed and pooled to produce useful and more reliable data. In this study, a meta-analysis of 17 published randomized trials was performed to assess the effectiveness of single beta-lactam antimicrobials versus combinations containing aminoglycoside when used for penetrating abdominal trauma. The overall summary odds ratio of the pooled results of these trials was 0.96 (p = 0.833) with a 95% confidence interval of 0.30-3.05. Since not significantly different from unity (1.0), we conclude that single beta-lactam antimicrobials are as effective as traditional combinations containing aminoglycoside in this setting.

Perigraft pseudocyst complicating repair of ruptured aortic aneurysm: successful treatment by percutaneous aspiration.

Occurring rarely after aortic surgery, post-operative pancreatitis is often complicated and carries a high mortality rate. We have reported a case of pancreatic pseudocyst involving a polytef aortic prosthesis used to repair a ruptured abdominal aortic aneurysm. The pseudocyst was treated successfully by repeated percutaneous aspiration, and removal of the aortic prosthesis was not required. Although less successful than operative drainage, percutaneous approaches to pancreatic pseudocysts are an important option for patients who are poor surgical candidates.

Polymicrobial bacteremia during long-term hemodialysis.

A review of hospital epidemiologic data disclosed five cases of polymicrobial bacteremia on a nephrology inpatient service over a period of 30 months. All five cases occurred in patients receiving long-term hemodialysis; four of them had indwelling silicone rubber vascular access devices. Although all patients had risk factors other than uremia and dialysis predisposing to an increased likelihood of infection, no patient had either obvious skin infection at the site of the vascular access or documented visceral infection. One patient died, and the other four recovered after removal of the vascular access device and appropriate antibiotic therapy. The increased risk of polymicrobial bacteremia associated with long-term hemodialysis should be taken into account when empiric antibiotic therapy is undertaken.

A competitive inhibition assay for gelatin binding fibronectin.

A competitive inhibition assay for functional fibronectin (Fn), based on ELISA technology, is described. The assay measures Fn's physiologic ability to bind to denatured collagen (gelatin). Affinity-purified Fn inhibits the binding of alkaline phosphatase coupled Fn to gelatin-coated wells of a microtiter plate in a concentration-dependent manner. The assay range is 50-500 micrograms Fn/ml, which is suitable for the measurement of plasma Fn in both normal and opsonin deficient individuals. It is reproducible over an eightfold dilution of plasma and is resistant to interference by normal plasma proteins. The assay described is quick, quantitative, and reproducible, and satisfies the need for a measure of functional Fn activity in the clinical laboratory.

Effect of experimental hemorrhagic shock on hepatic drug elimination.

OBJECTIVE: Exogenous substrates were used to measure hepatic function for the purposes of determining organ dysfunction and to evaluate the effect of experimental hemorrhagic shock with resuscitation on hepatic drug elimination. DESIGN: Prospective, controlled, non-randomized crossover trial. INTERVENTIONS: Eleven chronically instrumented immature swine were studied using a fixed-volume hemorrhage model (45 mL/kg blood removal over 15 mins) followed by resuscitation with lactated Ringer's solution at three times the volume of shed blood. One week before and immediately after hemorrhage and resuscitation, hepatic function markers (indocyanine green and antipyrine) were simultaneously administered intravenously. MEASUREMENTS: Physiologic data and blood samples were collected over 12 hrs after drug administration. Drug clearances, volumes of distribution, and half-lives were determined. MAIN RESULTS: For indocyanine green, there was no substantial change in pharmacokinetics from preshock to postshock, suggesting minimal change in hepatic blood flow. For antipyrine, clearance was decreased by 30% after shock and resuscitation (p = .05), suggesting that oxidative metabolism was acutely impaired. CONCLUSIONS: The information indicates that hepatic oxidative drug metabolism may be impaired early after hemorrhagic shock and that dosages of drugs in this class should be carefully examined when administered to patients who have sustained injury with hemorrhagic shock.

The impact of pre-transplant obesity on renal transplant outcomes.

The impact of obesity on graft survival after renal transplantation continues to be controversial. We have reviewed our experiences with living donor and cadaver transplantation in the current decade, focusing specifically on the impact of obesity on transplant outcome. Preoperative body mass index (BMI, kg/m2) was calculated for all adult renal transplant recipients between January 1990 and December 1995 and was used to classify patients as non-obese, moderately obese or morbidly obese. The effect of the degree of obesity on early and late outcomes after renal transplantation was examined. Three hundred and thirty-three recipients had pre-transplant BMI < 30 (normal or mild obesity), 68 BMI 30-40 (moderate obesity), and 7 BMI over 40 (morbid obesity). There was no correlation between obesity and other demographic factors. Wound infections and delayed graft function occurred more commonly in moderately and morbidly obese than in other cadaver donor recipients. Obese patients gained more weight after surgery and were given lower doses per kilogram of cyclosporine. There was, however, no significant correlation between obesity and graft survival for either cadaver or living donor transplants. Although obese patients have an increased risk of delayed graft function with cadaver donor transplantation, obesity has no discernible impact on either immunologic or overall graft survival with cadaver or living donor transplantation. The impact of moderate obesity on transplant outcome is modest and should not prevent these patients from receiving a transplant.

Cost-benefit analysis of a clinical pharmacist-managed medication assistance program in a renal transplant clinic.

UNLABELLED: Medicare pays for 80% of the cost of immunosuppressant agents needed within the first 3 years of solid organ transplantation; however, many patients cannot afford the remaining 20%. Furthermore, many patients who are beyond 3 years post-transplantation and have prescription coverage cannot afford the co-payment for these medications. Other patients may not be able to afford their medications due to limited or no insurance coverage. The Medical College of Georgia (MCG) has been giving immunosuppressant medications to renal transplant patients if they cannot afford to pay for them. To assist MCG with drug cost for medications and maintain quality care for renal transplant patients, a clinical pharmacist-managed medication assistance program was implemented to procure immunosuppressants from pharmaceutical manufacturers. METHODS: All patients enrolled in medication assistance programs from 1 January 1998 through 31 December 1998 were included in this analysis. Medication acquisition costs with and without Medicare reimbursement and the cost of implementing the clinical pharmacist-managed medication assistance program were used to determine the value of implementing this service. RESULTS: Sixty-one patients were enrolled in manufacturers' assistance programs and a net cost avoidance of $124,793 was realized for the year of the program (benefit-to-cost ratio of 7.5:1). Assuming that the hospital collected the maximum amount allowed for patients receiving Medicare benefits, a cost avoidance of $69,233 was calculated (benefit-to-cost ratio of 4.16:1). CONCLUSIONS: A clinical pharmacist-managed medication assistance program in a renal transplant clinic produced substantial cost savings over this 1-year study period. For each dollar spent in pharmacist's time, a minimum of $4 was returned to the institution.

Renal transplantation: a 20-year experience at the University of Florida.

Substantial gains have been made in both patient and graft survival during 20 years of transplanting kidneys at the University of Florida. The number of transplant recipients yearly has increased from six in 1966 to more than 100 in 1986. The use of immunosuppression reflects our evolving understanding of transplant immunology, with current morbidity and mortality rates considerably improved over those of the early years. This paper summarizes our transplantation experience over the past two decades.