*Purpose: Although the current gold standard of monitoring kidney transplant function relies on glomerular filtration rate (GFR) assessment, little is known about GFR trajectories after transplantation, their determinants, and their association with end stage renal disease (ESRD). Such information would be key for improving prediction and risk stratification in kidney transplantation.

*Methods: International population-based cohort involving 15 kidney transplant referral centers (10 in Europe and 5 in the US) including patients from 2000 to 2016. Patients underwent assessment of clinical, histological, immunological parameters including repeated eGFR measurements (MDRD estimation) after transplantation. Additional validation took place in seven randomized controlled trials (RCT). Latent class mixed models were used to identify distinct profiles of eGFR trajectories. Multinomial regression analysis was used to assess transplant parameters associated with the eGFR trajectories.

*Results: A total of 14,132 patients were included (4,140 patients in the derivation cohort, 5,155 in the European validation cohort, 2,328 in the US validation cohort and 2,509 in the seven RCTs). 403,497 repeated eGFR measures were assessed, corresponding on average to 35 ± 10 eGFR assessments per patient. After a median follow-up of 6.5 years (IQR 4.0-8.6), 1,688 patients developed ESRD and 1,240 died. Eight eGFR trajectories were identified and demonstrated good discrimination (i.e., the capacity to classify patient within the trajectories). Seven independent predictors of eGFR trajectories were identified, including donor age (p<0.001), and the following assessed at 1-year post-transplantation: eGFR (p<0.001), proteinuria level (p<0.001), allograft scarring (p<0.001), allograft interstitial inflammation and tubulitis (p=0.033), microcirculation injury (p<0.001), and circulating anti-HLA DSA (p=0.026). The eGFR trajectories were highly associated with progression to ESRD and mortality. The eGFR trajectories, their determinants and respective associations with ESRD were independently validated in the European and US validation cohorts, as well as in diverse clinical scenarios, therapeutic eras and in the 7 randomized controlled trials.

*Conclusions: We identified universal eGFR trajectories and their determinants, that are associated with progression to ESRD and all-cause mortality. Given the long-term course of chronic kidney diseases and their varied determinants, our results provide the basis for a trajectory-based assessment of kidney transplant patients for risk stratification and monitoring.

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