Early Posttransplant urine ammonium-pH index levels and graft outcomes in kidney transplant recipients

INTRODUCTION: Functional assessment is essential to quantify kidney graft quality early after kidney transplantation. Kidney transplantation is inherently associated with ischemia-reperfusion-injury, a noxious insult for proximal tubule cells that may not be captured by glomerular function markers. The urine ammonium-pH index (uAPI) is a functional measure of the tubulointerstitial capacity for ammonium excretion. Here, we aimed to investigate the association between the uAPI and graft function in kidney transplant recipients. METHODS: In this post-hoc observational analysis of the CONTEXT trial (NCT01395719), kidney transplant recipients with available urine samples were divided into an exploration cohort (n = 112) and a validation cohort (n = 88). The uAPI was assessed at baseline, 90 min after reperfusion, day 1, 2 and 3 posttransplant. Day 6 kidney graft biopsies were stained for VCAM1 as a marker of tubular injury. Outcomes were delayed graft function, estimated time to 50% reduction in plasma creatinine, and measured GFR on day 5 and 12 months posttransplant. Results were adjusted for age, sex, plasma creatinine and albuminuria. RESULTS: In the exploration cohort, a higher uAPI on day 2 and day 3 was associated with lower VCAM1 expression (p < 0.001 and p = 0.002, respectively), lower risk of delayed graft function, and shorter estimated time to 50% reduction in plasma creatinine (p < 0.001). A higher uAPI on day 3 was associated with higher measured GFR on day 5 (p < 0.001) and at 12 months (p < 0.001) posttransplant. These findings were confirmed in the validation cohort and robust to adjustments. Associations between day 3 uAPI and long-term graft function were consistent in subgroup analyses, including in patients with vs. without delayed graft function. Inclusion of day 3 uAPI improved prediction of measured GFR > 60 at 12 months posttransplant. CONCLUSIONS: A higher uAPI likely informs about better tubulointerstitial function posttransplant and is associated with better early and 12-month kidney graft function.