The challenged urine bicarbonate excretion test in cystic fibrosis: A comprehensive analysis of urine acid/base parameters

Aim Renal excretion of excess HCO 3 − depends on renal cystic fibrosis transmembrane conductance regulator (CFTR) and is impaired in people with cystic fibrosis (pwCF). Urine HCO 3 − excretion following oral NaHCO 3 ‐loading may be a simple in vivo biomarker of CFTR function. In this study, we investigated changes in urine acid/base parameters following oral NaHCO 3 ‐loading to comprehensively assess the physiological response to the test and evaluate HCO 3 − as the primary test result. Methods Urine acid/base parameters (titratable acid (TA), NH 4 + , net acid excretion (NAE) and pH) were measured in bio‐banked urine samples from controls ( n = 10) and pwCF ( n = 50) who completed the challenged urine HCO 3 − test. The association between urine acid/base excretion parameters and clinical CF disease characteristics and CFTR modulator therapy‐induced changes were assessed. Results Before treatment, challenged urine acid/base excretion associated with important CF disease characteristics. TA excretion and NAE were lower in pwCF with residual function mutations, 7.9 and 16.6 mmol/3 h, respectively, and lower TA excretion and NAE associated with pancreatic sufficiency. A lower excretion of TA, NH 4 + , and NAE associated with a higher percentage of predicted FEV 1 (1.3%, 2.5% and 0.8% per mmol/3 h higher, respectively). Modulator treatment decreased TA excretion and NAE (−2.9 and −5.3 mmol/3 h, respectively). Conclusion Following acute NaHCO 3 ‐loading, increased base excretion is mirrored by decreased acid excretion. Urine HCO 3 − excretion sufficiently represents the additional urine acid/base parameters as test result. The observed changes in acid excretion support CFTR modulator‐induced increase of CFTR‐dependent type B intercalated cell HCO 3 − secretion and the use of the challenged urine HCO 3 − test as a possible CFTR‐biomarker.