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Biomedical subjects

Robert M Merion

Publications and source records attributed to Robert M Merion.

At least 37 records · Page 2Linked to original sources

Immunosuppression and the risk of post-transplant malignancy among cadaveric first kidney transplant recipients.

The success of renal transplantation may be counterbalanced by serious adverse medical events. The effect of immunosuppression on the incidence of de novo neoplasms among kidney recipients should be monitored continuously. Using data from the Scientific Registry of Transplant Recipients, we studied the association of induction therapy by immunosuppression with antilymphocyte antibodies, with the development of de novo neoplasms. The study population included more than 41 000 recipients who received a cadaveric first kidney transplant after December 31, 1995, and were followed through February 28, 2002. Using Cox regression models, we estimated time to development of two types of malignancy: de novo solid tumors and post-transplant lymphoproliferative disorder (PTLD). We made adjustments for several patient demographic factors and comorbidities. Induction therapy was significantly associated with a higher relative risk (RR) of PTLD (RR = 1.78, p < 0.001), but not with a greater likelihood of de novo tumors (RR = 1.07, p = 0.42). Treatment with maintenance tacrolimus vs. cyclosporine showed a significantly different RR of developing de novo tumors for recipients with induction than for those not receiving induction (p = 0.024). These new estimates of the magnitude of malignancy risk associated with induction therapy may be useful for clinical practice.

Cadaver↗

Prevalence and outcomes of multiple-listing for cadaveric kidney and liver transplantation.

Transplant candidates are permitted to register on multiple waiting lists. We examined multiple-listing practices and outcomes, using data on 81 481 kidney and 26 260 liver candidates registered between 7/1/95 and 6/30/00. Regression models identified factors associated with multiple-listing and its effect on relative rates of transplantation, waiting list mortality, kidney graft failure, and liver transplant mortality. Overall, 5.8% (kidney) and 3.3% (liver) of candidates multiple-listed. Non-white race, older age, non-private insurance, and lower educational level were associated with significantly lower odds of multiple-listing. While multiple-listed, transplantation rates were significantly higher for nearly all kidney and liver candidate subgroups (relative rate [RR]= 1.42-2.29 and 1.82-7.41, respectively). Waiting list mortality rates were significantly lower while multiple-listed for 11 kidney subgroups (RR = 0.22-0.72) but significantly higher for 7 liver subgroups (RR = 1.44-5.93), suggesting multiple-listing by healthier kidney candidates and sicker liver candidates. Graft failure was 10% less likely among multiple-listed kidney recipients. Multiple- and single-listed liver recipients had similar post-transplant mortality rates. Although specific factors characterize those transplant candidates likely to multiple-list, transplant access is significantly enhanced for almost all multiple-listed kidney and liver candidates.

Adolescent↗

Improving liver allocation: MELD and PELD.

On February 27, 2002, the liver allocation system changed from a status-based algorithm to one using a continuous MELD/PELD severity score to prioritize patients on the waiting list. Using data from the Scientific Registry of Transplant Recipients, we examine and discuss several aspects of the new allocation, including the development and evolution of MELD and PELD, the relationship between the two scoring systems, and the resulting effect on access to transplantation and waiting list mortality. Additional considerations, such as regional differences in MELD/PELD at transplantation and the predictive effects of rapidly changing MELD/PELD, are also addressed. Death or removal from the waiting list for being too sick for a transplant has decreased in the MELD/PELD era for both children and adults. Children younger than 2 years, however, still have a considerably higher rate of death on the waiting list than adults. A limited definition of ECD livers suggests that they are used more frequently for patients with lower MELD scores.

Adult↗

Influence of graft type on outcomes after pediatric liver transplantation.

We sought to determine which type of donor graft provides children and young adults with the best outcomes following liver transplantation. Using the US Scientific Registry of Transplant Recipients database, we identified 6467 recipients of first liver transplants during 1989-2000 aged < 30 years. We used Cox models to examine adjusted patient and graft outcomes by age (< 2, 2-10, 11-16, 17-29) and donor graft type (deceased donor full size (DD-F), split (DD-S), living donor (LD)]. For patients aged < 2, LD grafts had a significantly lower risk of graft failure than DD-S (RR = 0.49, p < 0.0001) and DD-F (RR = 0.70, p = 0.02) and lower mortality risk than DD-S (RR = 0.71, p = 0.08) during the first year post-transplant. In contrast, older children exhibited a higher risk of graft loss and a trend toward higher mortality associated with LD transplants. In young adults, DD-S transplants were associated with poor outcomes. Three-year follow up yielded similar graft survival results but no significant differences in mortality risk by graft type within age group. For recipients aged < 2, LD transplants provide superior graft survival than DD-F or DD-S and trend toward better patient survival than DD-S. Living donor is the preferred donor source in the most common pediatric age group (< 2 years) undergoing liver transplantation.

Adolescent↗

Association of center volume with outcome after liver and kidney transplantation.

Outcomes for certain surgical procedures have been linked with volume: hospitals performing a high number of procedures demonstrate better outcomes than do low-volume centers. This study examines the effect of volume on hepatic and renal transplant outcomes. Data from the Scientific Registry of Transplant Recipients were analyzed for transplants performed from 1996-2000. Transplant centers were assigned to volume quartiles (kidney) or terciles (liver). Logistic regression models, adjusted for clinical characteristics and transplant center clustering, demonstrate the effect of transplant center volume quantile on 1-year post-transplant patient mortality (liver) and graft loss (kidney). The unadjusted rate of renal graft loss within 1 year was significantly lower at high volume centers (8.6%) compared with very low (9.6%), low (9.9%) and medium (9.7%) volume centers (p = 0.0014). After adjustment, kidney transplant at very low [adjusted odds ratio (AOR) 1.22; p = 0.043) and low volume (AOR 1.22 p = 0.041) centers was associated with a higher incidence of graft loss when compared with high volume centers. Unadjusted 1-year mortality rates for liver transplant were significantly different at high (15.9%) vs. low (16.9%) or medium (14.7%) volume centers. After adjustment, low volume centers were associated with a significantly higher risk of death (AOR 1.30; p = 0.0036). There is considerable variability in the range of failure between quantiles after kidney and liver transplant. Transplant outcomes are better at high volume centers; however, there is no clear minimal threshold volume.

Adolescent↗

Predicted lifetimes for adult and pediatric split liver versus adult whole liver transplant recipients.

Split liver transplantation allows 2 recipients to receive transplants from one organ. Comparisons of predicted lifetimes for two alternatives (split liver for an adult and pediatric recipient vs. whole liver for an adult recipient) can help guide the use of donor livers. We analyzed mortality risk for 48,888 waitlisted candidates, 907 split and 21,913 whole deceased donor liver transplant recipients between January 1, 1995 and February 26, 2002. Cox regression models for pediatric and adult patients assessed average relative wait list and post-transplant death risks, for split liver recipients. Life years gained compared with remaining on the waiting list over a 2-year period were calculated. Seventy-six splits (152 recipients) and 24 re-transplants resulted from every 100 livers (13.1% [adult] and 18.0% [pediatric] 2-year re-transplant rates, respectively). Whole livers used for 93 adults also utilized 100 livers (re-transplant rate 7.0%). Eleven extra life years and 59 incremental recipients accrued from each 100 livers used for split compared with whole organ transplants. Split liver transplantation could provide enough organs to satisfy the entire current demand for pediatric donor livers in the United States, provide more aggregate years of life than whole organ transplants and result in larger numbers of recipients.

Adult↗

Review of transplantation in HIV patients during the HAART era.

Human immunodeficiency virus (HIV) infection was once thought to be a relative or even absolute contraindication to transplantation. With the recent advent of highly active antiretroviral therapy (HAART), those infected with HIV are now living longer and dying from illnesses other than acquired immunodeficiency syndrome (AIDS). Although studies prior to the HAART era suggested poor outcomes might occur with transplantation in those infected with HIV, more recent studies have demonstrated results comparable to those of recipients without HIV infection. A number of issues persist regarding ethics, patient selection, post-operative management, and drug interactions between antiretroviral and immunosuppression agents. In this review, kidney, liver, and heart transplantation in the HIV-positive population were analyzed using data from the Organ Procurement and Transplantation Network/ Scientific Registry of Transplant Recipients.

Antiretroviral Therapy, Highly Active↗

Chronic renal failure after transplantation of a nonrenal organ.

BACKGROUND: Transplantation of nonrenal organs is often complicated by chronic renal disease with multifactorial causes. We conducted a population-based cohort analysis to evaluate the incidence of chronic renal failure, risk factors for it, and the associated hazard of death in recipients of nonrenal transplants. METHODS: Pretransplantation and post-transplantation clinical variables and data from a registry of patients with end-stage renal disease (ESRD) were linked in order to estimate the cumulative incidence of chronic renal failure (defined as a glomerular filtration rate of 29 ml per minute per 1.73 m2 of body-surface area or less or the development of ESRD) and the associated risk of death among 69,321 persons who received nonrenal transplants in the United States between 1990 and 2000. RESULTS: During a median follow-up of 36 months, chronic renal failure developed in 11,426 patients (16.5 percent). Of these patients, 3297 (28.9 percent) required maintenance dialysis or renal transplantation. The five-year risk of chronic renal failure varied according to the type of organ transplanted - from 6.9 percent among recipients of heart-lung transplants to 21.3 percent among recipients of intestine transplants. Multivariate analysis indicated that an increased risk of chronic renal failure was associated with increasing age (relative risk per 10-year increment, 1.36; P<0.001), female sex (relative risk among male patients as compared with female patients, 0.74; P<0.001), pretransplantation hepatitis C infection (relative risk, 1.15; P<0.001), hypertension (relative risk, 1.18; P<0.001), diabetes mellitus (relative risk, 1.42; P<0.001), and postoperative acute renal failure (relative risk, 2.13; P<0.001). The occurrence of chronic renal failure significantly increased the risk of death (relative risk, 4.55; P<0.001). Treatment of ESRD with kidney transplantation was associated with a five-year risk of death that was significantly lower than that associated with dialysis (relative risk, 0.56; P=0.02). CONCLUSIONS: The five-year risk of chronic renal failure after transplantation of a nonrenal organ ranges from 7 to 21 percent, depending on the type of organ transplanted. The occurrence of chronic renal failure among patients with a nonrenal transplant is associated with an increase by a factor of more than four in the risk of death.

Cohort Studies↗

Internet-based intervention to promote organ donor registry participation and family notification.

BACKGROUND: Little is known regarding the potential of Internet-based educational interventions to increase organ donor registry participation and family notification of donation wishes. We studied the effects of an Internet-based multimedia intervention (www.journey.transweb.org) on donor registry participation and family notification. METHODS: Visitors to a specially designed web site were studied between December 14, 2000, and March 31, 2002. Demographic characteristics were requested, and a pretest was administered to one half of the participants (selected randomly) before web site content exposure. All visitors were offered a posttest. Eight knowledge questions (true/false), three attitude questions (7-point scale), and three behaviors (yes/no) were assessed. RESULTS: A total of 10,884 visitors provided demographic data. Correct answers to knowledge questions increased from 85.1% to 87.0% overall (pretest vs. posttest; P<0.001) and from 80.6% to 82.0% for teenagers (P<0.001). Willingness to donate increased (scores of 6.34 vs. 6.39; P<0.001), as did willingness to join a donor registry (scores of 5.53 vs. 5.67; P<0.001). Willingness measures were less positive among teenagers but increased significantly after exposure to the intervention. Almost 10% of visitors directly linked to an online registry and 2,489 (23%) used the web site facilities to communicate donation wishes. Increases in knowledge were not associated with changes in attitudes, but an increase in pro-donation attitude was a significant predictor of donor registry participation (P<0.001). CONCLUSIONS: Increases in donation attitudes among visitors to an organ donation web site resulted in positive behaviors, such as enrollment in a donor registry and family notification. Future efforts should focus on using Internet-based interventions to improve attitudes toward donation and to facilitate pro-donation behaviors.

Adolescent↗

Vascular access outcomes using the transposed basilic vein arteriovenous fistula.

BACKGROUND: Although the transposed basilic vein arteriovenous fistula (TBAVF) is increasingly performed for hemodialysis vascular access in patients lacking adequate superficial veins, little is known about the long-term patency or risk factors for failure. METHODS: A retrospective analysis was conducted for 99 patients who had a TBAVF created between April 1997 and October 2001. Primary outcomes were unassisted and assisted patency rates and primary failure rates. RESULTS: This was the first access procedure in 46% of patients, mean age was 55 years, and 46% were men. Unassisted and assisted patency rates were 47% and 64% at 1 year and 41% and 58% at 2 years, respectively. Primary access failure occurred in 23% of cases. Unassisted access patency was significantly worse in patients with a previous access (relative risk [RR], 2.04; confidence interval [CI], 1.09 to 3.85; P = 0.03) or an ipsilateral central venous catheter (RR, 2.92; CI, 1.34 to 6.38; P < 0.01). Primary access failure was affected by older age (RR, 2.0; CI, 1.20 to 3.38; P < 0.01), obesity (RR, 7.1; CI, 1.65 to 30.1; P < 0.05), and a previous vascular access (RR, 6.4; CI, 1.49 to 27.6; P = 0.01). Steal syndrome requiring intervention occurred in 5% of cases. CONCLUSION: In summary, the TBAVF provides a viable option for vascular access; however, certain patient characteristics seem to affect long-term patency and should be considered when exploring access options.

Adult↗

Liver transplantation in children with metabolic disorders in the United States.

We studied pediatric liver transplantation for metabolic disease in a large national cohort to determine whether smaller studies suggesting a survival advantage for these recipients could be corroborated. We also hoped to determine whether higher survival rates in recipients with metabolic disease are associated with lack of structural liver disease, and to evaluate these recipients' risk factors for mortality. Data from the Scientific Registry of Transplant Recipients were used to analyze nationwide results (1990-99) of pediatric liver transplantation for patients with biliary atresia and metabolic disease. Adjusted patient survival rates for children with metabolic disease at 1 and 5 years were 94% and 92%, respectively, - significantly higher than for recipients with biliary atresia (90% and 86%) (p = 0.008). Cox regression models identified recipient black race [relative risk (RR) = 5.1] and simultaneous transplantation of other organs (RR = 3.2) as significant risk factors for mortality in the metabolic group. Adjusted survival rates for metabolic patients with structural and nonstructural liver diseases were similar to each other at both 1 and 5 years. Children with metabolic disease had significantly higher adjusted short- and long-term post-transplant survival rates than those with biliary atresia. Structural disease was not a risk factor for worse outcomes.

Adolescent↗

Gender imbalance and outcomes in living donor renal transplantation in the United States.

In living donor kidney transplantation there are disproportionately more female-to-male donations and fewer male-to-female donations. Given the rapid increase in living donor transplantation, we studied gender demographics and outcomes of these transplants. We analyzed living donor kidney transplants in the Scientific Registry of Transplant Recipients (SRTR) database between 1990 and 1999. There were 30 258 living donor transplants [26 510 (87%) biologically related; 2367 (8%) spousal; 1381 (5%) nonspousal unrelated]. Females comprised 68% of spousal and 56% of related and unrelated nonspousal donors (p < 0.0001). The distributions of gender pairings in nonspousal groups (related and unrelated) were significantly imbalanced (p < 0.0001). Opposite-sex pairs demonstrated more female-to-male donations among living related (64%, p < 0.0001), unrelated nonspousal (65%, p < 0.0001), and spousal pairs (68%). The higher incidence of end-stage renal disease among males and the slight predominance of females in the general population did not explain these gender disparities. Male recipients of male donor kidneys demonstrated significantly higher graft survival than other combinations (p < 0.006). Gender disparities in living donor transplantation result from a higher proportion of wife-to-husband donations and disproportionate female-to-male donations among biological relatives and unrelated pairs. There appears to be a graft survival advantage for male recipients of male donor kidneys.

Adult↗

The report of a national conference on the wait list for kidney transplantation.

In March, 2002, over 100 members of the transplant community assembled in Philadelphia for a meeting designed to address problems associated with the growing number of patients seeking kidney transplantation and added to the waiting list each year. The meeting included representatives of nine US organizations with interests in these issues. Participants divided into work groups addressing access to the waiting list, assigning priority on the list, list management, and identifying appropriate candidates for expanded criteria donor kidneys. Each work group outlined problems and potential remedies within each area. This report summarized the issues and recommendations regarding the waiting list for kidney transplantation addressed in the Philadelphia meeting.

Congresses as Topic↗

Prospective, randomized, multi-center trial of antibody induction therapy in simultaneous pancreas-kidney transplantation.

A randomized, multicenter, prospective study was conducted at 18 pancreas transplant centers in the United States to determine the role of induction therapy in simultaneous pancreas-kidney (SPK) transplantation. One hundred and 74 recipients were enrolled: 87 recipients each in the induction and noninduction treatment arms. Maintenance immunosuppression consisted of tacrolimus, mycophenolate mofetil, and corticosteroids. There were no statistically significant differences between treatment groups for patient, kidney, and pancreas graft survival at 1-year. The 1-year cumulative incidence of any treated biopsy-confirmed or presumptive rejection episodes (kidney or pancreas) in the induction and noninduction treatment arms was 24.6% and 31.2% (p = 0.28), respectively. The 1-year cumulative incidence of biopsy-confirmed, treated, acute kidney allograft rejection in the induction and noninduction treatment arms was 13.1% and 23.0% (p = 0.08), respectively. Biopsy-confirmed kidney allograft rejection occurred later post-transplant and appeared to be less severe among recipients that received induction therapy. The highest rate of Cytomegalovirus (CMV) viremia/syndrome was observed in the subgroup of recipients who received T-cell depleting antibody induction and received organs from CMV serologically positive donors. Decisions regarding the routine use of induction therapy in SPK transplantation must take into consideration its differential effects on risk of rejection and infection.

Antibodies↗

Model for end-stage liver disease (MELD) and allocation of donor livers.

BACKGROUND & AIMS: A consensus has been reached that liver donor allocation should be based primarily on liver disease severity and that waiting time should not be a major determining factor. Our aim was to assess the capability of the Model for End-Stage Liver Disease (MELD) score to correctly rank potential liver recipients according to their severity of liver disease and mortality risk on the OPTN liver waiting list. METHODS: The MELD model predicts liver disease severity based on serum creatinine, serum total bilirubin, and INR and has been shown to be useful in predicting mortality in patients with compensated and decompensated cirrhosis. In this study, we prospectively applied the MELD score to estimate 3-month mortality to 3437 adult liver transplant candidates with chronic liver disease who were added to the OPTN waiting list at 2A or 2B status between November, 1999, and December, 2001. RESULTS: In this study cohort with chronic liver disease, 412 (12%) died during the 3-month follow-up period. Waiting list mortality increased directly in proportion to the listing MELD score. Patients having a MELD score <9 experienced a 1.9% mortality, whereas patients having a MELD score > or =40 had a mortality rate of 71.3%. Using the c-statistic with 3-month mortality as the end point, the area under the receiver operating characteristic (ROC) curve for the MELD score was 0.83 compared with 0.76 for the Child-Turcotte-Pugh (CTP) score (P < 0.001). CONCLUSIONS: These data suggest that the MELD score is able to accurately predict 3-month mortality among patients with chronic liver disease on the liver waiting list and can be applied for allocation of donor livers.

Adult↗