EPIDEMIOLOGIC OUTCOMES AND PREDICTORS OF OUTCOMES IN KIDNEY TRANSPLANT RECIPIENTS.

Student thesis: Phd

Abstract

This thesis comprehensively examines kidney transplantation outcomes across multiple dimensions, shedding light on the intricate factors influencing renal allograft survival and recipient well-being. Despite remarkable advancements in tissue human leucocyte antigen (HLA) matching, surgical and medical care, immunosuppressive treatment, and complication management, long-term outcomes for kidney allografts have seen limited improvement over the past decades. Several factors influence renal allograft survival, including donor and recipient characteristics, peri- and post-transplant factors, and complications such as cardiovascular disease, immunosuppression-related morbidity, and recurrence of primary renal disease. Understanding the impact of these factors on graft and recipient outcomes is crucial to managing kidney allograft recipients. This research delves into various aspects of kidney transplantation, including the impact of primary renal disease on post-transplant outcomes, the effects of induction agents on long-term results, and the rates and predictors of recurrent glomerulonephritis. Furthermore, it explores the influence of infections, immunologic response to SARS-CoV-2 vaccination, de novo post-transplant cardiovascular disease and malignancy on graft and recipient outcomes. Additionally, predictors and implications of post-transplant tertiary hyperparathyroidism are investigated. Each chapter of the thesis contributes to a nuanced understanding of kidney transplantation complexities, offering insights to enhance patient outcomes in the long term. By compiling several retrospective cohort studies of pre- and post-transplant factors, the research employs epidemiological methodology tailored to meet the requirements of each hypothesis and dataset. Specifically, findings from the study examining the impact of primary renal disease on outcomes revealed significant differences in all-cause graft survival and rate of eGFR decline among recipients with different underlying renal pathologies. Graft survival was shortest in recipients with diabetic kidney disease (11 years) and most prolonged in those with autosomal dominant polycystic kidney disease (18.2 years). The rate of eGFR loss was also the fastest with diabetic kidney disease (-2.1ml/min/year) and least with autosomal dominant polycystic kidney disease (-0.05ml/min/year). Similarly, investigations into the effects of induction type on outcomes highlighted notable differences in graft function, viral infection rates, and long-term survival between recipients receiving different induction agents with matched immunological risk profiles. Alemtuzumab exhibited a significantly lower graft function at 12 months, a higher incidence of CMV and BK viremia, and lower graft survival compared to basiliximab recipients. Additionally, studies on recurrent glomerulonephritis, antibody response to SARS-COV-2, kidney-associated viral infections, post-transplant cardiovascular disease, de novo post-transplant malignancy, and tertiary hyperparathyroidism provide valuable insights into the predictors and implications of these factors on graft and recipient outcomes. The time to glomerulonephritis recurrence was shortest in FSGS (0.6 years) and most prolonged in MN (6.8 years). Recipients with recurrent glomerulonephritis are nine times more likely to lose their graft than those without recurrent glomerulonephritis. Self-administered smartphone-assisted dipstick urinalysis tests were associated with a 75% reduction in hospitalisation for urinary tract infections. Transplant recipients showed a 57% positive antibody response. Glomerular filtration rate, older age, and mycophenolate treatment were predictors of response to the vaccine. The slope of eGFR decline was steeper in recipients with a history of DNA virus infection, irrespective of the type. The predictors of time to cardiovascular disease onset include age at transplantation, dialysis duration, baseline eGFR and slope of eGFR. In
Date of Award31 Dec 2024
Original languageEnglish
Awarding Institution
  • The University of Manchester
SupervisorPhilip Kalra (Supervisor) & Rachel Middleton (Supervisor)

Keywords

  • Tertiary hyperparathyroidism
  • Allograft failure
  • Kidney transplant associated viral infection
  • SARS-CoV-2 vaccination response
  • CMV infection
  • Post-transplant Malignancy
  • Predictors of graft loss
  • Immunosuppression induction
  • Post-transplant cardiovascular disease
  • Recurrent glomerulonephritis
  • Recurrent urinary tract infection
  • kidney transplantation
  • Renal allograft survival
  • Immunosuppression

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