Improving patient education delivery to increase living donation rates.
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Black or African American↗
Biomedical subjects
D C Brennan
Publications and source records attributed to D C Brennan.
Prophylactic versus preemptive oral valganciclovir for the management of cytomegalovirus infection in adult renal transplant recipients.
Prophylaxis reduces cytomegalovirus (CMV) disease, but is associated with increased costs and risks for side effects, viral resistance and late onset CMV disease. Preemptive therapy avoids drug costs but requires frequent monitoring and may not prevent complications of asymptomatic CMV replication. Kidney transplant recipients at risk for CMV (D+/R-, D+/R+, D-/R+) were randomized to prophylaxis (valganciclovir 900 mg q.d. for 100 days, n=49) or preemptive therapy (900 mg b.i.d. for 21 days, n=49) for CMV DNAemia (CMV DNA level>2000 copies/mL in >or=1 whole blood specimens by quantitative PCR) assessed weekly for 16 weeks and at 5, 6, 9 and 12 months. More patients in the preemptive group, 29 (59%) than in the prophylaxis group, 14 (29%) developed CMV DNAemia, p=0.004. Late onset of CMV DNAemia (>100 days after transplant) occurred in 11 (24%) randomized to prophylaxis, and none randomized to preemptive therapy. Symptomatic infection occurred in five patients, four (3 D+/R- and 1 D+/R+) in the prophylactic group and one (D+/R-) in the preemptive group. Peak CMV levels were highest in the D+/R- patients. Both strategies were effective in preventing symptomatic CMV. Overall costs were similar and insensitive to wide fluctuations in costs of either monitoring or drug.
Administration, Oral↗
BK virus infection in transplant recipients: an overview and update.
BK virus infection after kidney transplantation has been a subject of great interest in the past decade. This article traces the discovery of BK virus and the subsequent development of our knowledge about this emerging pathogen. The pathobiology of the virus is summarized with particular reference to epidemiology, interactions with host cell receptors, cell entry, cytoplasmic trafficking and targeting of the viral genome to the nucleus. This is followed by a discussion of clinical features, laboratory monitoring and therapeutic strategies. Finally, we present potential cellular mechanisms that explain the basis of virus-mediated damage to the human kidney.
BK Virus↗
The incidence and costs of sepsis and pneumonia before and after renal transplantation in the United States.
We compared the graft survival and accumulative costs associated with sepsis and pneumonia pre- and post-transplantation. We analyzed 44 916 first kidney transplants from 1995 to 2001 USRDS where Medicare was the primary payer. We drew five cohorts for each disease from the baseline population: patients who had a disease onset in the first or second years pre-transplantation (cohorts 1 and 2) or post-transplantation (cohorts 3 and 4) and patients who were disease-free (cohort 5). For each cohort, we calculated graft survival and average accumulated Medicare payments (AAMPs) for the two pre- and post-transplantation years. Graft survival: new-onset sepsis and pneumonia both significantly (p <0.01) lowered graft survival during the year of onset. AAMPs: the AAMPs incurred by sepsis- (pneumonia-) free patients during the first and second years post-transplantation were dollar 50,000 and 13,000 (dollar 51,100 and 13,500), respectively. Patients with a sepsis (pneumonia) onset post-transplantation cost on average dollar 48,400 (dollar 38,400) extra (p<0.01). Episodes of sepsis and pneumonia have a strong and independent impact on graft survival and costs.
Adolescent↗
Effect of extended coverage of immunosuppressive medications by medicare on the survival of cadaveric renal transplants.
Between 1993 and 1995, Medicare extended its coverage of maintenance immunosuppression medications following renal transplantation from 1 to 3 years. We hypothesized that Medicare's extension of immunosuppressive coverage would improve graft survival among low-income transplant recipients. We merged patient-level clinical data from the USRDS-distributed UNOS registry of kidney transplants throughout the USA with median family income for each patient's ZIP code from the 1990 Census. We were able to merge median incomes to 10,837 first cadaveric renal transplants performed in 1992-93 and 16,732 performed in 1995-97. Each of these chronological cohorts was divided into two groups, those with family incomes above (high-income group) and those below (low-income group) $36,033. There were no differences in graft survival at 1 year based on income in either chronological era. However, when Medicare covered immunosuppression medications for just 1 year, the low-income group of 1-year graft survivors had a 4.5% lower graft survival at the end of 3 years post-transplant (p < 0.001). During the 1995-97 period, during which Medicare provided 3 years' immunosuppression coverage, the low-income and high-income groups had equivalent graft survival at 3 years post-transplant.
Cadaver↗
The economic impact of preservation time in cadaveric liver transplantation.
There has been considerable recent debate concerning the reconfiguration of the cadaveric liver allocation system with the intent to allocate livers to more severely ill patients over greater distances. We sought to assess the economic implications of longer preservation times in cadaveric liver transplantation that may be seen in a restructured allocation system. A total of 683 patients with nonfulminant liver disease, aged 16 years or older, receiving a cadaveric donor liver as their only transplant, were drawn from a prospective cohort of patients who received transplants between January 1991 and July 1994 at the University of California, San Francisco, the Mayo Clinic, Rochester, Minnesota, or the University of Nebraska, Omaha. The primary outcome measure was standardized hospitalization resource utilization from the day of transplantation through discharge. Secondary outcome measures included 2-year patient survival, and 2-year retransplantation rates. Results indicated that each 1-h increase in preservation time was associated with a 1.4% increase in standardized hospital resource utilization (p = 0.014). The effects on 2-year patient survival and retransplantation rates were not measurably affected by an increase in preservation time. We conclude that policies that increase preservation time may be expected to increase the cost of liver transplantation.
Body Constitution↗
Renal transplantation following previous heart, liver, and lung transplantation: an 8-year single-center experience.
BACKGROUND: Long-term follow-up of heart, liver, and lung transplantation has led to an increased recognition of secondary end-stage renal failure (ESRF) in transplant recipients. This study examines our center's experience with renal transplantation following previous solid organ transplantation. METHODS: From January 1, 1992, to September 30, 1999, our center performed 18 renal transplants in previous solid organ recipients. During the same period, 815 total renal transplants were performed. One- and 3-year graft and patient survival, recipient demographics, donor type, and reason for transplantation were compared between these groups. RESULTS: Of the 18 recipients, 7 had prior heart transplants, 4 had prior liver transplants, and 7 had prior lung transplants. Cyclosporine toxicity contributed to renal failure in 17 (94.4%) of the patients-either as a sole factor (11 patients) or in combination with hypertension, renal artery stenosis, or tacrolimus toxicity (6 patients). Kaplan-Meier 1- and 3-year patient survival was 82.9% and 73.7%, compared with 95.5% and 90.7% in all renal transplant recipients. No surviving patient has suffered renal allograft loss. Mean current creatinine level is 1.4 mg/dL. CONCLUSIONS: Renal transplantation is an excellent therapy for ESRF following prior solid organ transplantation. One and 3-year patient and graft survival demonstrate the utility of renal transplantation in this patient population.
Follow-Up Studies↗
Current review of cytomegalovirus in renal transplantation.
Cytomegalovirus (CMV) continues to be a common cause of morbidity and mortality in transplant recipients. It has shifted from being overtly to insidiously lethal. Even with effective prophylactic and preemptive treatment strategies it is the most concerning viral agent in transplant recipients. CMV disease has been associated with the two most common causes of late graft loss; cardiovascular disease and chronic rejection. The incidence and morbidity of CMV infection and disease is probably a reflection of immunosuppressive strategies, and ability to diagnose and monitor for CMV. New molecular tests have been developed which include the antigenernia assay, the hybrid capture assay, RNA detection by nucleic acid sequence based amplification (NASBA), and DNA PCR. New insights have also been reported in the diagnostic, monitoring and treatment of the emergent problem of resistance. Nevertheless, the Holy Grail of CMV is in the development of an effective vaccination against this serious viral pathogen.
Cytomegalovirus Infections↗
The Barnes-Jewish Hospital/Washington University Renal Transplant Program: comparison of two eras 1991-1994 and 1995-2000.
The first cadaveric transplant at Barnes-Jewish Hospital/Washington University was performed in 1963, the first living related transplant in 1965, and the first living unrelated transplant in 1983. Changes in the renal transplant program initiated in 1993 and 1994 resulted in many improvements over the past decade. Our comparison of 2 modern eras of transplant, 1991-1994 and 1995-2000, showed the following: 1. No significant differences in patient and donor characteristics. 2. Trends toward greater use of living donors (p = 0.07), older cadaveric donors (p = 0.084) and particularly cadaveric donors > 55 years of age (p = 0.09). 3. Decreasing mean CIT: 19.2 hours vs. 14.2 hours (p < 0.001). 4. Decreasing use of donors with CIT > 24 hours: 22% to 3%, (p < 0.001). 5. Decreased rate of DGF: 13% vs. 8% (p = 0.044). 6. Decreased rate of symptomatic CMV: 35% vs. 14% (p < 0.001). 7. Decreased rate of PTLD: 3.5% vs. 0.5% (p = 0.004). 8. Decreased one-year rate of acute rejection: 41% vs. 15% (p < 0.001). 9. Current one-year rate of acute rejection < 8%. 10. Decreased length of initial hospital stay: 12.7 days to 8.0 days (p < 0.001). 11. Decreased length of hospital in the first year after transplant: 10.6 days vs. 6.4 days (p < 0.001). 12. There were no improvements in patient and graft survival at one and 3 years. a. one-year patient survival rates: 95% vs. 96%. b. 3-year patient survival rates: 90% vs. 90%. c. one-year death-censored graft survival rates: 91% vs. 94%. d. 3-year death-censored graft survival rates: 87% vs. 88%.
Academic Medical Centers↗
Economic cost of expanded criteria donors in cadaveric renal transplantation: analysis of Medicare payments.
BACKGROUND: The use of expanded criteria donors (ECDs) in cadaveric renal transplantation is increasing in the US. We assess the economic impact of the use of ECDs to the Medicare end stage renal disease program. METHODS: The United Nations for Organ Sharing renal transplant registry was merged to Medicare claims data for 42,868 cadaveric renal transplants performed between 1991-1996 using USRDS identifiers. Only recipients for whom Medicare was the primary payer were considered, leaving 34,534 transplants. An ECD was defined as (1) age < or =5 or > or =55 years, (2) nonheart-beating donors, donor history of (3) hypertension or (4) diabetes. High-risk recipients (HRR) were age >60 years, or a retransplant. Medicare payments from the pretransplant dialysis period were projected forward to provide a financial "breakeven point" with transplantation. RESULTS: There were 25,600 non-HRR transplants, with 5,718 (22%) using ECDs, and 8,934 HRR transplants, of which 2,200 (25%) used ECDs. The 5-year present value of payments for non-ECD/non-HRR donor/recipient pairings was $121,698 vs. $143,329 for ECD/non-HRR pairings (P<0.0001) and, similarly was $134,185 for non-ECD/HRR pairings vs. $165,716 for ECD/HRR pairings (P<0.0001). The break even point with hemodialysis ranged from 4.4 years for non-ECD/ non-HRR pairings to 13 years for the ECD/HRR combinations but was sensitive to small changes in graft survival. Transplantation was always less expensive than hemodialysis in the long run. CONCLUSIONS: The impact of ECDs on Medicare payments is most pronounced in high-risk recipients. Cadaveric renal transplantation is a cost-saving treatment strategy for the Medicare ESRD program regardless of recipient risk status or the use of ECDs.
Aged↗
The economic benefit of allocation of kidneys based on cross-reactive group matching.
BACKGROUND: Recently the United Network for Organ Sharing (UNOS) began a pilot study to evaluate prospectively the merits of an allocation of cadaveric kidneys based on broader classes of HLA antigens, called cross-reactive groups (CREG). The objectives of the pilot study consider patient outcomes, but not the potential economic impact of a CREG-based allocation. This study predicts the impact of a CREG-based local allocation of cadaveric kidneys on 3-year Medicare payments and graft survival. METHODS: The UNOS renal transplant registry was merged to Medicare claims data for 1991-1997 by the United States Renal Data System. Average accumulated Medicare payments and graft survival up to 3 years posttransplant for first cadaveric renal transplant recipients were stratified by cross-reactive group mismatch categories. The economic impact was defined as the difference in average 3-year costs per transplant between the current and proposed allocation algorithms. Average 3-year costs were computed as a weighted average of costs, where the weights were the actual and predicted distributions of transplants across cross-reactive group categories. RESULTS: Results suggest that an organ allocation based on cross-reactive group matching criteria would result in a 3-year cost savings of $1,231 (2%) per transplant, and an average 3-year graft survival improvement of 0.6%. CONCLUSIONS: Cost savings and graft survival improvements can be expected if CREG criteria were to replace current criteria in the current allocation policy for cadaveric kidneys, although the savings appear to be smaller than may be achievable through expanded HLA matching.
Algorithms↗
The prevalence of human herpesvirus-7 in renal transplant recipients is unaffected by oral or intravenous ganciclovir.
The purpose of this study was to compare the prevalence of human herpesvirus (HHV)-7 and cytomegalovirus (CMV) viremia and the effects of oral and intravenous (iv) ganciclovir in renal transplant recipients at risk for CMV. Stored lysates from peripheral blood leukocytes from 92 patients, who had been previously analyzed for CMV viremia by polymerase chain reaction (PCR) for 12 weeks after transplantation, were analyzed for HHV-7 viremia. Baseline and peak prevalences of HHV-7 viremia were 22% and 54%, respectively (P<. 0001). Eighty-two (89%) of 92 patients had at least 1 positive PCR for HHV-7. Oral ganciclovir and treatment with iv ganciclovir had no effect on the prevalence of HHV-7 viremia. In contrast, CMV was almost completely suppressed in patients who received oral ganciclovir, and when present, CMV responded to iv therapy. These results indicate that HHV-7 is resistant to ganciclovir at levels that were effective for prevention and treatment of CMV.
Administration, Oral↗
The domino transplant: transplant recipients as organ donors.
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Adolescent↗
Cadaveric versus living donor kidney transplantation: a Medicare payment analysis.
BACKGROUND: We found previously that the clinical advantages of living donor (LD) renal transplantation lead to financial cost savings compared to either cadaveric donation (CAD) or dialysis. Here, we analyze the sources of the cost savings of LD versus CAD kidney transplantation. METHODS: We used United States Renal Data System data to merge United Network for Organ Sharing registry information with Medicare claims data for 1991-1996. Information was available for 42,868 CAD and 13,754 LD transplants. More than 5 million Medicare payment records were analyzed. We calculated the difference in average payments made by Medicare for CAD and LD for services provided during the first posttransplant year. RESULTS: Average total payments were $39,534 and $24,652 for CAD and LD, respectively (P<0.0001) during the first posttransplant year. The largest source of the difference in payments was in inpatient hospitals, representing $10,653.67 (P<0.0001). For patients who had Medicare as the primary payer, average transplant charges were significantly higher for CAD donation ($79,730 vs. $69,547, P<0.0001); average transplant payments demonstrated no statistical differences ($28,483 vs. $28,447, P = 0.858). Therefore, inferred profitability was significantly higher for LD. CONCLUSIONS: Medicare payments are remarkably lower for LD compared to CAD in every category. The single largest cost saving comes from inpatient hospital services. A portion of the savings from LD could be invested in programs to expand living kidney donation.
Cadaver↗
Cytomegalovirus immune globulin intravenous (human) administration modulates immune response to alloantigens in sensitized renal transplant candidates.
One of the important parameters for prolonged waiting time for potential renal transplant recipients is the presence of preformed antibodies to human leucocyte antigen (HLA) antigens, which is often caused by previous transplants, pregnancy or transfusions. In vivo administration of specific and unselected polyclonal intravenous immunoglobulin (IVIGs) preparations have been shown to inhibit anti-HLA alloantibodies in highly sensitized patients. We sought to determine whether Cytogam (Medimmune Inc., Gaithersburg, MD, USA), a hyperimmune anticytomegalovirus immunoglobulin would (1) effect either in vitro or in vivo alloreactivity, and (2) whether Cytogam therapy could reduce the titre of preformed anti-HLA antibodies in highly sensitized patients. Alloreactivity was assessed by mixed lymphocyte reaction (MLR) and cytotoxic T lymphocyte (CTL) assay. A complement dependent microlymphocytotoxicity assay was done to assess for panel reactive antibody (PRA) status and the presence of anti-idiotypic antibodies in the Cytogam preparation. The MLR was inhibited by Cytogam in vitro in a dose-dependent fashion ranging from 31-92%. Significant inhibition of the MLR responses was not observed in recipients who received Cytogam in vivo (50 mg/kg). This could be a result of adminstration of a low dose of IVIG. However, CTL activity against the alloantigens in all individuals assessed was significantly inhibited after in vivo administration of Cytogam. Three of five individuals experienced a decrease of 5-32% in the PRA status at 4 weeks post administration of Cytogam. Cytogam also blocked the anti-HLA antibody titres in a microlymphocytotoxicity assay, suggesting the presence of anti-idiotypic antibodies. Our study was based on a single prophylactic dose of Cytogam (50 mg/kg), however, higher dose administration could be feasible by removing more fluid at dialysis, but should be given intradialytically to avoid volume overload. Overall, our results suggest that Cytogam can modulate the in vivo and in vitro T cell responses against the alloantigens.
Adult↗
Infectious complications in renal transplant recipients.
Infectious complications present major challenges to physicians caring for renal transplant recipients. The high rate of infection reflects the net state of immunosuppression associated with end-stage renal disease, transplantation, donor and environmental exposure. An understanding of the factors that affect the patients' overall state of immunosuppression is essential to prevent and treat infectious complications, which may lead to significant morbidity, graft dysfunction, or mortality. Familiarity with the various pathogens, clinical presentation, diagnostic options, treatment, and prophylaxis is important to care for renal transplant patients. The authors present their approach, based on review of current literature, to these issues.
Anti-Bacterial Agents↗
Pheochromocytoma presenting as a giant cystic tumor of the liver.
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Adrenal Gland Neoplasms↗
Economics of the antithymocyte globulins Thymoglobulin and Atgam in the treatment of acute renal transplant rejection.
OBJECTIVE: To evaluate the economic implications for transplant centres, Medicare and society of treatment of corticosteroid-resistant Banff Grades I, II and III acute kidney transplant rejection with the antithymocyte globulins Thymoglobulin or Atgam. DESIGN AND SETTING: This was a cost analysis of a randomised double-blind multicentre clinical trial comparing the safety and efficacy of Thymoglobulin and Atgam that was performed at 25 centres in the US in 1994 to 1996. PATIENTS AND PARTICIPANTS: The study enrolled 163 patients, 82 in the Thymoglobulin arm and 81 in the Atgam arm. METHODS: Estimates of the cost of care from the initiation of rejection therapy to 90 days post-therapy were derived from various publicly available sources and applied to patient-specific clinical events documented in the clinical trial. Patients received either intravenous Thymoglobulin (1.5 mg/kg/day) for an average of 10 days or intravenous Atgam (15 mg/kg/day) for an average of 9.7 days. RESULTS: On average, Thymoglobulin provided significant cost savings compared with Atgam from the perspective of society [$US5977 (1996 values); 95% confidence interval (CI) $US3719 to $US8254], Medicare ($US4967; 95% CI $US3256 to $US6678) and the transplant centre ($US3087; 95% CI $US1512 to $US4667). The overall advantage attributable to Thymoglobulin was primarily due to savings from fewer recurrent rejection treatments and less frequent return to dialysis. CONCLUSIONS: Treatment of acute renal transplant rejection with Thymoglobulin is a cost saving strategy when compared with treatment with Atgam.
Acute Disease↗