EPS3.02 The cystic fibrosis urine test: A comprehensive analysis of all renal acid-base parameters following acute oral bicarbonate loading

Objective: Urine HCO-3 excretion depends on renal CFTR and is markedly impaired in people with CF (pwCF). Urine HCO-3 excretion following an oral HCO-3 load may be a simple in vivo biomarker of CFTR function. Urine acid and base excretion is a function of the sum of all acids and bases. The objective of this study was to investigate the value of all urine acid-base parameters as test read-outs following oral HCO-3 loading. Methods: Follow-up measurements of all urine acid-base paramenters of urine samples from a previous observational study are presented. PwCF completed an oral NaHCO3 challenge test at baseline (n = 50) and 6 months after initiating Elexacaftor/tezacaftor/Ivacaftor (ETI) therapy (n = 38). Urine excretion of acids (titratable acids (TA) and NH+4) and bases (net base (NB) and titratable bases (TB)) were assessed for association with clinical CF disease characteristics. Also, ETI-induced changes of challenged urine acid-base excretion were measured. Results: At baseline, challenged urine acid-base excretion was associated with several CF disease characteristics. NB and TB excretion were higher and TA excretion was lower in patients with residual function mutations and in pancreatic-sufficient patients. A higher excretion of NB and TB and a lower excretion of TA and NH+4 were associated with higher ppFEV1. ETI treatment increased excretion of NB and TB and decreased excretion of TA. Conclusion: Urine excretion of acid-base after an oral NaHCO3 load correlates with typical CF disease characteristics. Further, the test reports treatment effect of ETI shown as increased NB and TB excretion and as decreased TA excretion. No additional value regarding the ability to excrete base was found when combining the different acid-base parameters. This indicates complete interdependency of acid-base parameters in the urine following acute base challenge. Eventually, urine excretion of HCO-3 sufficiently represents all urine acid-base parameters as test read-out.