Death after graft loss: a novel endpoint for renal tranplantation

ABSTRACT. The impact of graft loss on acute coronary syndromes (ACS) after renal transplantation has not been studied in a national population. It was hypothesized that ACS might be more frequent after graft loss, as many of the benefits of a functioning allograft on metabolism and volume regulation would be lost. Data from the 2000 United States Renal Data System (USRDS) was used to conduct an historical cohort study of ACS in 14,237 patients who received renal transplants between April 1, 1995, and June 30, 1998, (followed until April 28, 2000) with valid information from CMS Form 2728, excluding patients with hospitalized ACS before renal transplant. Cox nonproportional regression models were used to calculate the time-dependent adjusted hazard ratio (AHR) of graft loss (censored for death) for time-to-first hospitalization for ACS (International Classification of Diseases 9th Modification Diagnosis Codes [ICD9] code 410.x or 411.x) occurring after transplant. The incidence of ACS was 12.1 per 1000 patient-years (PY) in patients after graft loss versus 6.5 per 1000 PY after transplantation (excluding patients with graft loss). As a time-dependent variable, graft loss had an AHR of 2.54 (95% confidence interval, 1.09 to 5.96; P = 0.031 by Cox regression). Other risk factors associated with ACS included diabetes, older recipient, and male recipient. Allograft rejection was NS. Renal transplant recipients share some of the risk factors for ACS with the general population. In addition, graft loss was identified as a unique risk factor for ACS in this population. E-mail: kevin.abbott@na.amedd.army.mil

Section: Discussionmentioning

confidence: 99%

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confidence: 99%

Graft Loss and Acute Coronary Syndromes after Renal Transplantation in the United States

Abbott¹,

Bucci²,

Cruess³

et al. 2002

“…Therefore, models were also performed excluding medication overlap. Graft loss was analyzed as a time-dependent variable using previously described methods (6) because it has recently been recognized as an independent predictor of patient mortality in kidney transplant recipients (7). Stratified Cox models were performed for each of the following subgroups of particular clinical interest: recipients who were HCVϪ, recipients who were HCVϩ, and recipients who were age 65 yr or older.…”

Section: Analytic Variables and Outcome Measuresmentioning

confidence: 99%

Hepatitis C and Renal Transplantation in the Era of Modern Immunosuppression

Abbott¹,

Bucci²,

Matsumoto³

et al. 2003

102

Abstract. Kidneys from donors who are positive for hepatitis C virus (DHCVϩ) have recently been identified as an independent risk factor for mortality after renal transplantation. However, it has not been determined whether risk persists after adjustment for baseline cardiac comorbidity or applies in the era of modern immunosuppression. Therefore, a historical cohort study was conducted of US adult cadaveric renal transplant recipients from January 1, 1996, to May 31, 2001 followed until October 31, 2001. A total of 36,956 patients had valid donor and recipient HCV serology. Cox regression analysis was used to model adjusted hazard ratios for mortality and graft loss, respectively, adjusted for other factors, including comorbid conditions from Center for Medicare and Medicaid Studies Form 2728 and previous dialysis access-related complications. It was found that DHCVϩ was independently associated with an increased risk of mortality (adjusted hazard ratio, 2.12, 95% confidence interval, 1.72 to 2.87; P Ͻ 0.001), primarily as a result of infection. Mycophenolate mofetil was associated with improved survival in DHCVϩ patients, primarily related to fewer infectious deaths. Adjusted analyses limited to recipients who were HCVϩ, HCV negative, or age 65 and over, or by use of mycophenolate mofetil confirmed that DHCVϩ was independently associated with mortality in each subgroup. It is concluded that DHCVϩ is independently associated with an increased risk of mortality after renal transplantation adjusted for baseline comorbid conditions in all subgroups. Recipients of DHCVϩ organs should be considered at high risk for excessive immunosuppression.The expected clinical course of hepatitis C infection as it affects organ transplant recipients, as well as the use and effect of kidneys from donors who are positive for hepatitis C, remain controversial topics in renal transplantation. Recently published data confirmed that kidneys from donors who were hepatitis C positive (HCVϩ) were associated with an independently increased risk of death in renal transplant recipients regardless of recipient HCV status (1). However, donor hepatitis C seropositivity (DHCVϩ) was not independently associated with mortality when limited to patients with valid information (Centers for Medicare and Medicaid Studies [CMS] Form 2728) on comorbid conditions at the time of dialysis initiation. This may have been because of the relatively small numbers of transplant recipients for whom complete data were available during the study period or because cardiovascular comorbidity was actually lower in patients who received DHCVϩ kidneys, yet the mortality risk for recipients of DHCVϩ kidneys was still greater than for patients who received DHCVϪ kidneys. Possibly, recipients of DHCVϩ kidneys were sicker to start with and thus had a higher risk of death unrelated to receiving a DHCVϩ kidney. Since that study, there have been substantial changes in maintenance immunosuppression practices in the United States. In particular, recent reports have confirmed tha...

“…R enal transplant failure is a leading cause of dialysis initiation (1)(2)(3)(4)(5). Despite that 44% of renal transplant failure patients are listed for repeat transplantation, only 15% of transplant failure patients will ever receive another transplant (2).…”

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confidence: 99%

Prevention of Sepsis during the Transition to Dialysis May Improve the Survival of Transplant Failure Patients

Johnston¹,

Zalunardo²,

Rose³

et al. 2007

Dialysis patients are at risk for sepsis, and the risk may be even higher among transplant failure patients because of previous or ongoing immunosuppression. The incidence and the consequences of sepsis as defined by International Classification of Diseases, Ninth Revision, Clinical Modification hospital discharge diagnoses codes were determined among 5117 patients who initiated dialysis after transplant failure between 1995 and 2004 in the United States. The overall sepsis rate was 11.8 per 100 patient years (95% confidence interval [CI] 11.5 to 12.1). Sepsis was highest in the first 6 mo after transplant failure (35.6 per 100 patient years [95% CI 29.4 to 43.0] between 0 to 3 mo after transplant failure; 19.7 per 100 patient years [95% CI 17.2 to 22.5] between 3 to 6 mo after transplant failure). In comparison, the sepsis rate among incident dialysis patients between 3 and 6 mo after dialysis initiation was 7.8 per 100 patient years (95% CI 7.3 to 8.3), whereas the sepsis rate among transplant recipients between 3 and 6 mo after transplantation was 5.4 per 100 patient years (95% CI 4.9 to 5.9). Patients who were >60 yr, obese patients, patients with diabetes, and patients with a history or peripheral vascular disease or congestive heart failure were at risk for sepsis. Transplant nephrectomy was not associated with septicemia. The role of continued immunosuppression and vascular access creation was not assessed and should be addressed in future studies. In a multivariate analysis, patients who were hospitalized for sepsis had an increased risk for death (hazard ratio 2.93; 95% CI 2.64 to 3.24; P < 0.001). Strategies to prevent sepsis during the transition from transplantation to dialysis may improve the survival of patients with allograft failure.