Influence of CYP3A5 genetic differences in tacrolimus on quantitative interstitial fibrosis and long-term graft function in kidney transplant recipients

SummaryWe analysed whether the factor V Leiden mutation – the most common hereditary predisposing factor for venous thrombosis – is associated with early and long-term graft dysfunction after kidney transplantation in 394 Caucasian kidney transplant recipients. The presence of factor V Leiden mutation was identified by allele specific PCR. The prevalence of the factor V Leiden mutation was compared to 32216 unselected neonates. The prevalence of the factor V Leiden mutation (GA genotype) was similar in 394 kidney transplant recipients and 32216 neonates. The frequency of known factors predicting long-term graft function were similar in patients with the GA genotype and with the normal factor V gene (GG genotype). The GA genotype was associated with the occurrence of no primary graft function (risk: 2.87; 95% confidence interval: 1.01-8.26; p < 0.05), the number of dialysis after transplantation in patients with no primary graft function until graft function (7.5 ± 2.06 dialysis in GA patients; 4.2 ± 0.36 dialyses in GG patients; p < 0.05), and the risk for at least one acute rejection episode (risk: 3.83; 95% confidence interval: 1.38-10.59; p < 0.02). The slope of 1/creatinine per year was significantly lower in patients with the GA genotype (GA patients: – 0.0204 ± 0.008 dl/mg per year; GG patients: 0.0104 ± 0.004 dl/mg per year; p < 0.02). The annual enhancement of the daily protein excretion rate was elevated in patients with the GA genotype (GA patients: 38.5 ± 16.6 mg/24 h per year; GG patients: 4.9 ± 4.4 mg/24 h per year; p < 0.02). Our study showed that the factor V Leiden mutation is associated with the occurrence of delayed graft function, acute rejection episodes and chronic graft dysfunction after kidney transplantation.

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Long-Term Care of the Pediatric Kidney Transplant Recipient

Clinical Journal of the American Society of Nephrology ◽

10.2215/cjn.16891020 ◽

2021 ◽

pp. CJN.16891020

Author(s):

Hilda E. Fernandez ◽

Bethany J. Foster

Keyword(s):

Transplant Recipient ◽

Kidney Transplant ◽

Graft Failure ◽

Graft Function ◽

Failure Rates ◽

Care Providers ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Term Care

Pediatric kidney transplant recipients are distinguished from adult recipients by the need for many decades of graft function, the potential effect of CKD on neurodevelopment, and the changing immune environment of a developing human. The entire life of an individual who receives a transplant as a child is colored by their status as a transplant recipient. Not only must these young recipients negotiate all of the usual challenges of emerging adulthood (transition from school to work, romantic relationships, achieving independence from parents), but they must learn to manage a life-threatening medical condition independently. Regardless of the age at transplantation, graft failure rates are higher during adolescence and young adulthood than at any other age. All pediatric transplant recipients must pass through this high-risk period. Factors contributing to the high graft failure rates in this period include poor adherence to treatment, potentially exacerbated by the transfer of care from pediatric- to adult-oriented care providers, and perhaps an increased potency of the immune response. We describe the characteristics of pediatric kidney transplant recipients, particularly those factors that may influence their care throughout their lives. We also discuss the risks associated with the transition from pediatric- to adult-oriented care and provide some suggestions to optimize transition to adult-oriented transplant care and long-term outcomes.

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Long-term protein intake control in kidney transplant recipients: Effect in kidney graft function and in nutritional status

American Journal of Kidney Diseases ◽

10.1053/ajkd.2003.50105 ◽

2003 ◽

Vol 41 (3) ◽

pp. S146-S152 ◽

Cited By ~ 23

Author(s):

Annamaria Bernardi ◽

Franco Biasia ◽

Tecla Pati ◽

Michele Piva ◽

Angela D'Angelo ◽

...

Keyword(s):

Nutritional Status ◽

Kidney Transplant ◽

Protein Intake ◽

Graft Function ◽

Kidney Graft ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Intake Control

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Long-term graft function changes in kidney transplant recipients

Clinical Kidney Journal ◽

10.1093/ndtplus/sfq063 ◽

2010 ◽

Vol 3 (suppl 2) ◽

pp. ii2-ii8 ◽

Cited By ~ 6

Author(s):

R. Marcen ◽

J. M. Morales ◽

A. Fernandez-Rodriguez ◽

L. Capdevila ◽

L. Pallardo ◽

...

Keyword(s):

Kidney Transplant ◽

Graft Function ◽

Transplant Recipients ◽

Kidney Transplant Recipients

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173: Delayed Graft Function (DGF) in HIV+ Kidney Transplant Recipients Predicts Worse Long-Term Renal Function

American Journal of Kidney Diseases ◽

10.1053/j.ajkd.2010.02.180 ◽

2010 ◽

Vol 55 (4) ◽

pp. B75

Author(s):

Lissa Levin ◽

Gregory Malat ◽

Mohit Gupta ◽

Muhammad Saeed ◽

Snehankita Kulkarni ◽

...

Keyword(s):

Renal Function ◽

Kidney Transplant ◽

Graft Function ◽

Delayed Graft Function ◽

Transplant Recipients ◽

Kidney Transplant Recipients

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Association of Slow Graft Function with Long-Term Outcomes in Kidney Transplant Recipients

Annals of Transplantation ◽

10.12659/aot.907397 ◽

2018 ◽

Vol 23 ◽

pp. 224-231 ◽

Cited By ~ 3

Author(s):

Connie J. Wang ◽

Ahmad Tuffaha ◽

Milind A. Phadnis ◽

Jonathan D. Mahnken ◽

James B. Wetmore

Keyword(s):

Kidney Transplant ◽

Graft Function ◽

Transplant Recipients ◽

Kidney Transplant Recipients ◽

Long Term Outcomes

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Long-Term Outcomes in 831 Kidney Transplant Recipients with 20 Years of Graft Function

Integrative Journal of Medical Sciences ◽

10.15342/ijms.2021.451 ◽

2021 ◽

Vol 8 ◽

Author(s):

Varvara Kirchner ◽

Kristen Gillingham ◽

Oscar Serrano ◽

Srinath Chinnakotla ◽

Ty Dunn ◽

...

Keyword(s):

Kidney Transplant ◽

Graft Survival ◽

Interstitial Fibrosis ◽

Graft Loss ◽

Graft Function ◽

Solid Organ ◽

Kidney Transplant Recipients ◽

Long Term Outcomes ◽

Tubular Atrophy

An understanding of long-term outcomes for kidney transplant(KTx) recipients who survive with graft function beyond a specific time posttransplant is the first step in creating protocols to optimize care for current and improve outcomes for future recipients. We studied 831KTx recipients-580 living donor(LD); 251 deceased donor(DD)—with graft survival(GS) >20 years. For primary LD recipients, 25-year patient survival(PS) was 83%; 35-year, 59%. Their 25-year death-censored graft survival(DCGS) was 89%; 35-year, 72%. DD recipients had lower PS(P<0.01), DCGS(P<0.01). After 20 years, two major causes of graft loss(GL) were death with function(DwF)(58%, LD; 58%, DD) and interstitial fibrosis and tubular atrophy(IFTA)(22%, LD; 23%, DD). Two major causes of DwF were cancer(31%, LD; 31%, DD) and cardiovascular disease(CVD)(19%, LD;17%, DD). Per multivariate analysis(MVA), risk factors for GL after 20 years in pre–calcineurin inhibitor(CNI) era were human leukocyte antigen(HLA) mismatches >3 antigens, pretransplant type 1 diabetes mellitus(DM1); in CNI era, a history of rejection, female gender. New comorbidities after 20 years were common: CVD(13%, non-DM1;18%, DM1), infections(27%, non-DM1;37%, DM1), 20-29 years posttransplant. Cancer after 20 years included: nonmelanotic skin cancer,22%; solid organ,7%; post-transplant lymphoproliferative disease(PTLD),2%. To improve long-term outcomes, clinical trials on prevention, recognition, and treatment of new comorbidities are needed.

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