Early Renal Insufficiency and Hospitalized Heart Disease after Renal Transplantation in the Era of Modern Immunosuppression

Abbott, Kevin C.; Yuan, Christina M.; Taylor, Allen J.; Cruess, David F.; Agodoa, Lawrence Y.

doi:10.1097/01.asn.0000083008.25305.67

Cited by 68 publications

(41 citation statements)

References 42 publications

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“…Serious infections occurred in 16% of belatacept recipients, comparable to recent reports of 10 to 13% with CNIs at 3 years 14 ; five (5%) belatacept recipients developed malignancies versus 13% reported with CNIs at 5 years; 13 and the 2% rate of serious cardiac events with belatacept was within the estimated range of 1 to 5% for major adverse cardiac events after transplantation. 15,16 Overall, infection rates with belatacept were typical for long-term renal transplant recipients, with the possible exception of herpes, which occurred at a higher rate than in previous reports in renal transplant recipients: 21 versus 7%. 17 UTI was the most common late serious infection, as was reported previously, 18 and CMV and BK polyomavirus infection rates with belatacept were similar to published results in CNItreated patients.…”

Section: Discussionmentioning

confidence: 75%

Five-Year Safety and Efficacy of Belatacept in Renal Transplantation

Vincenti

Blancho

Dürrbach

et al. 2010

Journal of the American Society of Nephrology

175

139

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Belatacept is a first-in-class co-stimulation blocker in development for primary maintenance immunosuppression. A Phase II study comparing belatacept with cyclosporine (CsA) for prevention of acute rejection and protection of renal function in kidney transplant recipients demonstrated similar efficacy and significantly higher measured GFR at 1 year for belatacept, but the incidence of posttransplantation lymphoproliferative disorder was higher. Here, we present the results for the extension of this trial, which aimed to assess long-term safety and efficacy of belatacept. Seventy-eight of 102 patients who were receiving belatacept and the 16 of 26 who were receiving CsA completed the long-term extension period. GFR remained stable in patients who were receiving belatacept for 5 years, and the incidences of death/graft loss or acute rejection were low. The frequencies of serious infections were 16% for belatacept and 27% for CsA, and neoplasms occurred in 12% of each group. No patients who were treated with belatacept and one patient who was treated with CsA developed posttransplantation lymphoproliferative disorder during the follow-up period. Serious gastrointestinal disorders occurred more frequently with belatacept (12% belatacept versus 8% CsA), and serious cardiac disorders occurred more frequently with CsA (2% belatacept versus 12% CsA). Pharmacokinetic analyses showed consistent exposure to belatacept over time. CD86 receptor saturation was higher in patients who were receiving belatacept every 4 weeks (74%) compared with every 8 weeks (56%). In conclusion, this study demonstrated high patient persistence with intravenous belatacept, stable renal function, predictable pharmacokinetics, and good safety with belatacept over 5 years.

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Section: Discussionmentioning

confidence: 75%

Five-Year Safety and Efficacy of Belatacept in Renal Transplantation

Vincenti

Blancho

Dürrbach

et al. 2010

Journal of the American Society of Nephrology

175

139

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“…Even mild renal insufficiency is independently associated with risk of CCF and IHD. An eGFR of < 44.8 mL/min per 1.73 m 2 compared to an eGFR > 69.7 mL/min per 1.73 m 2 at the end of the first year after transplantation was independently associated with increased risks of both acute coronary syndrome (ACS) (HR = 2.16; 95%CI: 1.39-3.35) and CCF (HR = 2.95; 95%CI: 2.24-3.90) [83] . In the event of graft failure, ACS incidence was around double that of RTRs who had a functioning graft (12.1 vs 6.5 per 1000 patientyears).…”

Section: Renal Impairmentmentioning

confidence: 99%

Cardiovascular risk factors following renal transplant

Neale

Smith

2015

WJT

118

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Kidney transplantation is the gold-standard treatment for many patients with end-stage renal disease. Renal transplant recipients (RTRs) remain at an increased risk of fatal and non-fatal cardiovascular (CV) events compared to the general population, although rates are lower than those patients on maintenance haemodialysis. Death with a functioning graft is most commonly due to cardiovascular disease (CVD) and therefore this remains an important therapeutic target to prevent graft failure. Conventional CV risk factors such as diabetes, hypertension and renal dysfunction remain a major influence on CVD in RTRs. However it is now recognised that the morbidity and mortality from CVD are not entirely accounted for by these traditional risk-factors. Immunosuppression medications exert a deleterious effect on many of these well-recognised contributors to CVD and are known to exacerbate the probability of developing diabetes, graft dysfunction and hypertension which can all lead on to CVD. Nontraditional CV risk factors such as inflammation and anaemia have been strongly linked to increased CV events in RTRs and should be considered alongside those which are classified as conventional. This review summarises what is known about risk-factors for CVD in RTRs and how, through identification of those which are modifiable, outcomes can be improved. The overall CV risk in RTRs is likely to be multifactorial and a complex interaction between the multiple traditional and non-traditional factors; further studies are required to determine how these may be modified to enhance survival and quality of life in this unique population. Core tip: Cardiovascular disease (CVD) is the leading cause of death and disability in patients following a renal transplant. Identification of risk factors for CVD and strategies for their improvement are required in order to prevent graft failure in this complex patient

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“…Details of the source USRDS data files, as well as limitations of Medicare claims data, have been described previously (7,15).…”

Section: Data Sourcesmentioning

confidence: 99%

“…Several investigations have approached estimation of the incidence and predictors of MI after kidney transplantation by modeling primary hospital discharge diagnoses (5,7). These studies are limited by the quantity of available information for many clinical variables and, in not ascertaining other presentations including secondary diagnoses and fatal MI, underestimate risk.…”

mentioning

confidence: 99%

Incidence and Predictors of Myocardial Infarction after Kidney Transplantation

Lentine¹,

Brennan²,

Schnitzler³

2005

Journal of the American Society of Nephrology

319

235

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The risk and predictors of post-kidney transplantation myocardial infarction (PTMI) are not well described. Registry data collected by the United States Renal Data System were used to investigate retrospectively PTMI among adult first renal allograft recipients who received a transplant in 1995 to 2000 and had Medicare as the primary payer. PTMI events were ascertained from billing and death records, and participants were followed for up to 3 yr after transplant or until the end of observation (December 31, 2000 R ecent studies demonstrate that myocardial infarction (MI) and renal dysfunction form a "high-risk combination" (1,2). Patients with mild chronic renal insufficiency faced more than twofold higher death rates after MI than those with normal renal function in one center's experience (2), and post-MI mortality increases explosively among ESRD patients on dialysis (1,2). Although kidney transplantation may reduce the risk for MI and improve post-MI survival (1,3), mortality rates after hospitalization for acute coronary syndromes among renal allograft recipients remain sobering, ranging from approximately 24% at 1 yr (1,4), to 30 to 38% at 2 yr (1,4,5), to Ͼ45% at 5 yr (1,4). Furthermore, as a leading cause of death (and thus graft loss) in patients with functioning renal transplants (6), posttransplantation MI (PTMI) has important implications for allograft longevity in this population.Several investigations have approached estimation of the incidence and predictors of MI after kidney transplantation by modeling primary hospital discharge diagnoses (5,7). These studies are limited by the quantity of available information for many clinical variables and, in not ascertaining other presentations including secondary diagnoses and fatal MI, underestimate risk. Candidate risk factors for PTMI include characteristics of the recipient, the kidney donor, transplantation management, and transplant course. Renal allograft recipients have a higher prevalence of "traditional" Framingham atherosclerotic vascular disease risk factors, including advanced age, diabetes, hypertension, and dyslipidemia (8). Time on dialysis before transplantation (9), donor history of hypertension (10), immunosuppressive regimen (11), quality of allograft function (12), and posttransplantation diabetes (13,14) also are implicated as mediators of cardiovascular risk in this population. Along with current uncertainty for the magnitude of PTMI incidence rates, the independent predictive values of putative posttransplantation cardiovascular risk factors for PTMI specifically, potential for risk modification, and the spectrum of clinical consequences after this complication are not yet known.Prompted by the limited available evidence on the risk and outcomes of PTMI, we undertook a retrospective study of a large cohort of recent kidney transplant recipients recorded in the United States Renal Data System (USRDS). We aimed to quantify the risk for PTMI in all presentations, identify clinically relevant risk factors, and estimate the impact of thi...

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Early Renal Insufficiency and Hospitalized Heart Disease after Renal Transplantation in the Era of Modern Immunosuppression

Cited by 68 publications

References 42 publications

Five-Year Safety and Efficacy of Belatacept in Renal Transplantation

Five-Year Safety and Efficacy of Belatacept in Renal Transplantation

Cardiovascular risk factors following renal transplant

Incidence and Predictors of Myocardial Infarction after Kidney Transplantation

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