Risk Factors Associated With Graft Loss and Patient Survival After Kidney Transplantation

Harada, Kelly Miyuki; Mandia-Sampaio, E.L.; Sandes‐Freitas, Tainá Veras de; Felipe, Cláudia Rosso; Park, S.I.; Pinheiro-Machado, Paula G.; Garcia, Ricardo M; Tedesco‐Silva, Hélio; Medina-Pestana, J.O.

doi:10.1016/j.transproceed.2009.04.013

Cited by 59 publications

(41 citation statements)

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“…(5, 17–27) A rejection event then increases an individual’s risk of chronic graft dysfunction or graft loss. (28–31) Thus a reliable predictive marker of toxicity risk prior to CNI initiation is needed. Preemptive strategies that protect the kidney, or CNI free or minimization protocols could then be used to individualize immunosuppression in at risk patients.…”

Section: Introductionmentioning

confidence: 99%

Genetic and Clinical Determinants of Early, Acute Calcineurin Inhibitor-Related Nephrotoxicity

et al. 2012

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Background Calcineurin inhibitor (CNI)-related acute nephrotoxicity is a common complication of transplantation. Clinical factors and elevated CNI levels are associated with nephrotoxicity; however, they do not completely explain the risk. Genetics factors may also predispose individuals to nephrotoxicity. Methods We enrolled 945 kidney recipients into a multicenter, prospective study. DNA was genotyped for 2,724 single nucleotide polymorphism (SNP) using a customized chip. Cox models, unadjusted and adjusted for clinical factors, examined the association between SNPs and time to early CNI-related acute nephrotoxicity in the first six months posttransplant. Results Cyclosporine was associated with a 1.49 hazard (95% CI, 1.04–2.14) of acute nephrotoxicity relative to tacrolimus. Acute nephrotoxicity occurred in 22.6% of cyclosporine and 19.8% of tacrolimus recipients. The median (inter-quartile range) daily dose and trough concentration at time of nephrotoxicity were 400mg (400–500mg) and 228ng/ml (190–272ng/ml) in the cyclosporine group, and 6 mg (4–8mg) and 12.6ng/ml (10.2–15.9ng/ml) in the tacrolimus group, respectively. In single-SNP adjusted analysis, nine SNPs in the XPC, CYP2C9, PAX4, MTRR and GAN genes were associated with cyclosporine nephrotoxicity. In a multi-SNP analysis, SNPs from the same genes remained significant after adjusting for the clinical factors, showing that the SNPs are jointly and independently predictive of cyclosporine nephrotoxicity. No SNPs were associated with tacrolimus nephrotoxicity. Conclusion We identified SNPs potentially associated with early, acute cyclosporine-related nephrotoxicity. Identifying risk SNPs prior to transplantation provides an opportunity for personalization of immunosuppression by identifying those who may benefit from CNI-avoidance or minimization, or assist in selecting CNI type. These SNPs require independent validation.

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Section: Introductionmentioning

confidence: 99%

Genetic and Clinical Determinants of Early, Acute Calcineurin Inhibitor-Related Nephrotoxicity

et al. 2012

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“…Conversely, numerous studies have established acute rejection as an independent risk factor for graft loss. [48][49][50][51][52][53][54] In addition, patients who develop early rejection were at a higher risk of developing chronic allograft rejection. 55,56 In 1 study, the cause for graft failure was attributed to antibody-mediated rejection in one-half of patients requiring an indication biopsy.…”

Section: Discussionmentioning

confidence: 99%

Untitled

Buttigieg

Julie

Sharma³

et al. 2016

Exp Clin Transplant

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Kidney transplant remains the best type of renal replacement therapy in most patients with end-stage kidney disease, even in those with high immunologic risk. Immunosuppression in these patients is regarded as more complex, owing to the higher risk of both acute and chronic rejection. The advent of induction immunosuppression has resulted in a lower incidence of acute rejection and consequently improved shortterm patient and allograft outcomes. Indeed, the use of these agents, especially in high-risk recipients, has become standard of care at most transplant centers. Transplant physicians are constantly faced with the challenge of estimating the recipients' immunologic risk and tailoring their immunosuppression ac cordingly. This review article aims to provide an up-to-date evaluation of the various studies available, which investigated the use of induction agents in kidney transplant, specifically in high-risk recipients. It evaluates the use of the most frequently used polyclonal antibody (rabbit antithymocyte globulin) versus the less commonly used monoclonal antibody alemtuzumab, superseded agents such as muromonab-CD3, and potentially emerging agents such as rituximab, bortezomib, and eculizumab. With this systematic review, we hope to inform the scientific community and facilitate this controversial decision through the implementation of robust scientific evidence.

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“…In addition, we showed in our univariate analysis that metastasis increased the cumulative incidence of chronic graft loss. Tiong et al and Harada et al showed in their studies that acute rejection episodes and any treated rejection episode (27), delayed graft function, black race, and recurrence of glomerular disease were independent risk factors of graft loss (28). Moreover, donor risk factors affecting long-term post-transplantation graft survival included age, small donor size with large recipient size, race, sex, cause of death, cold ischemia time, female donor gender, HLA mismatch, organs from expanded-criteria donors, and cytomegalovirus (CMV) status (25, 27).…”

Section: Discussionmentioning

confidence: 99%

“…Recipient factors include age, gender, BMI (kg/m 2 ), race, cause of renal failure, induction therapy, and use of mycophenolate mofetil, sirolimus and/or calcineurin inhibitors, acute rejection episodes and any treated rejection episode (27), delayed graft function, black race, and recurrence of glomerular disease (28). Donor factors include BMI (kg/m 2 ), creatinine (mg/dL), HLA mismatch, age, gender, race, donor-recipient relationship, and type of operation procedure (open vs. laparoscopic) (27).…”

Section: Introductionmentioning

confidence: 99%

Chronic Graft Loss and Death in Patients With Post-Transplant Malignancy in Living Kidney Transplantation: A Competing Risk Analysis

et al. 2014

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Background:Malignancy is a common complication after renal transplantation. Death with functioning graft and chronic graft loss are two competing outcomes in patients with post-transplant malignancies.Objectives:The purpose of our study was to evaluate the risk factors associated with cumulative incidence of these two outcomes.Patients and Methods:Fine-Gray model was used for 266 cases with post-transplant malignancy in Iran. These patients were followed-up from the diagnosis until the date of last visit, chronic graft loss, or death, subsequently.Results:At the end of the study, as competing events, chronic graft loss and death with functioning graft were seen in 27 (10.2%) and 53 cases (19.9%), respectively, while 186 cases (69.9%) were accounted as censored. The incidence rate of death was approximately two-time of the incidence rate of chronic graft loss (8.6 vs. 4.4 per 100 person-years). In multivariate analysis, significant risk factors associated with cumulative incidence of death included age (P < 0.007, subhazard ratio (SHR) = 1.03), type of cancer (P < 0.0001), and response to treatment (P < 0.0001, SHR = 0.027). The significant risk factors associated with cumulative incidence of chronic graft loss were gender (P = 0.05, SHR = 0.37), treatment modality (P < 0.0001), and response to treatment (P = 0.048, SHR = 0.47).Conclusions:Using these factors, nephrologists may predict the occurrence of graft loss or death. If the probability of graft loss was higher, physicians can decrease the immunosuppressive medications dosage to decrease the incidence of graft loss.

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Risk Factors Associated With Graft Loss and Patient Survival After Kidney Transplantation

Cited by 59 publications

References 5 publications

Genetic and Clinical Determinants of Early, Acute Calcineurin Inhibitor-Related Nephrotoxicity

Genetic and Clinical Determinants of Early, Acute Calcineurin Inhibitor-Related Nephrotoxicity

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Chronic Graft Loss and Death in Patients With Post-Transplant Malignancy in Living Kidney Transplantation: A Competing Risk Analysis

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