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

Abstract

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 invivo 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. 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. 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). 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.