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

TY - JOUR

T1 - The challenged urine bicarbonate excretion test in cystic fibrosis

T2 - A comprehensive analysis of urine acid/base parameters

AU - Rousing, Amalie Q.

AU - Jeppesen, Majbritt

AU - Jensen-Fangel, Søren

AU - Leipziger, Jens

AU - Sorensen, Mads V.

AU - Berg, Peder

N1 - e14233 APH-2024-03-0154.R2

PY - 2024/11

Y1 - 2024/11

N2 - 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.

AB - 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.

KW - CFTR

KW - acid/base

KW - bicarbonate

KW - cystic fibrosis

KW - kidney

UR - http://www.scopus.com/inward/record.url?scp=85204611622&partnerID=8YFLogxK

U2 - 10.1111/apha.14233

DO - 10.1111/apha.14233

M3 - Journal article

C2 - 39308271

SN - 1748-1708

VL - 240

JO - Acta Physiologica

JF - Acta Physiologica

IS - 11

M1 - e14233

ER -