Aim: Renal excretion of excess HCO3 - depends on renal cystic fibrosis transmembrane conductance regulator (CFTR) and is impaired in people with cystic fibrosis (pwCF). Urine HCO3 - excretion following oral NaHCO3-loading may be a simple in vivo biomarker of CFTR function. In this study, we investigated changes in urine acid/base parameters following oral NaHCO3-loading to comprehensively assess the physiological response to the test and evaluate HCO3 - as the primary test result.
Methods: Urine acid/base parameters (titratable acid (TA), NH4 +, 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 HCO3 - 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, NH4 +, and NAE associated with a higher percentage of predicted FEV1 (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 NaHCO3-loading, increased base excretion is mirrored by decreased acid excretion. Urine HCO3 - 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 HCO3 - secretion and the use of the challenged urine HCO3 - test as a possible CFTR-biomarker.
Keywords: CFTR; acid/base; bicarbonate; cystic fibrosis; kidney.
© 2024 The Author(s). Acta Physiologica published by John Wiley & Sons Ltd on behalf of Scandinavian Physiological Society.