Abstract
BackgroundAlthough young adulthood is associated with transplant loss, many studies do not examine eGFR decline. We aimed to establish clinical risk factors to identify where early intervention might prevent subsequent adverse transplant outcomes.MethodsRetrospective cohort study using UK Renal Registry and UK Transplant Registry data, including patients aged < 30 years transplanted 1998–2014. Associations with death-censored graft failure were investigated with multivariable Cox proportional hazards. Multivariable linear regression was used to establish associations with eGFR slope gradients calculated over the last 5 years of observation per individual.ResultsThe cohort (n = 5121, of whom n = 371 received another transplant) was 61% male, 80% White and 36% had structural disease. Live donation occurred in 48%. There were 1371 graft failures and 145 deaths with a functioning graft over a 39,541-year risk period. Median follow-up was 7 years. Fifteen-year graft survival was 60.2% (95% CI 58.1, 62.3).Risk associations observed in both graft loss and eGFR decline analyses included female sex, glomerular diseases, Black ethnicity and young adulthood (15–19-year and 20–24-year age groups, compared to 25–29 years). A higher initial eGFR was associated with less risk of graft loss but faster eGFR decline. For each additional 10 mL/min/1.73m2 initial eGFR, the hazard ratio for graft loss was 0.82 (95% CI 0.79, 0.86), p < 0.0001. However, compared to < 60 mL/min/1.73m2, higher initial eGFR was associated with faster eGFR decline (> 90 mL/min/1.73m2; − 3.55 mL/min/1.73m2/year (95% CI -4.37, − 2.72), p < 0.0001).ConclusionsIn conclusion, young adulthood is a key risk factor for transplant loss and eGFR decline for UK children and young adults. This study has an extended follow-up period and confirms common risk associations for graft loss and eGFR decline, including female sex, Black ethnicity and glomerular diseases. A higher initial eGFR was associated with less risk of graft loss but faster rate of eGFR decline. Identification of children at risk of faster rate of eGFR decline may enable early intervention to prolong graft survival.
Highlights
Young adulthood is associated with transplant loss, many studies do not examine estimated glomerular filtration rate (eGFR) decline
By using a multivariable Cox proportional hazards model, we explored the association of evidence-based variables as well as initial eGFR post-transplant on the risk of deathcensored graft failure [hazard ratio (HR) (95% confidence interval (CI)), p-value]
White Asian Black Mixed/other Primary kidney disease groupa Glomerular disease Systemic diseases affecting the kidney Familial/hereditary nephropathies Tubulointerstitial disease Miscellaneous kidney disorders Late presentationb Age when first seen Age at kidney replacement therapy (KRT) start Years to KRT start from first nephrology review Tertiles of year started KRT 1983–2003 2004–2008 2009–2014 Start modality Haemodialysis Peritoneal dialysis Transplant Age at transfer Died Age at death Transplanted during study period Graft 1 Graft 2 Graft 3 Re-transplanted during study period Graft 2 Graft 3 Time from listing to transplant Year of transplant 1998–2003 2004–2009 2010–2014 Donor type Live donation Donation after brainstem death Donation after circulatory death Donor age
Summary
Young adulthood is associated with transplant loss, many studies do not examine eGFR decline. A large registry study analysing the effect of age identified graft failure rates were highest at 19 years and that those aged 17–24 years were at the highest risk of graft failure [3], with similar findings from other studies not including patients from the UK [4,5,6,7]. This may be because both adolescence and young adulthood are associated with increased risk-taking behaviour, poor medication compliance and changes to care as patients transfer to adult services [3, 5]. Following periods of stable graft function, typically, this may be followed by period of worsening graft function and potential sudden graft failure
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