Department of Biomedicine, Aarhus University, Aarhus, Denmark.
Department of Infectious Diseases, Cystic Fibrosis Center Aarhus, Aarhus University Hospital, Aarhus, Denmark.
Acta Physiol (Oxf). 2024 Nov;240(11):e14233. doi: 10.1111/apha.14233. Epub 2024 Sep 23.
Renal excretion of excess HCO depends on renal cystic fibrosis transmembrane conductance regulator (CFTR) and is impaired in people with cystic fibrosis (pwCF). Urine HCO excretion following oral NaHCO-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-loading to comprehensively assess the physiological response to the test and evaluate HCO as the primary test result.
Urine acid/base parameters (titratable acid (TA), NH , 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 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, NH , and NAE associated with a higher percentage of predicted FEV (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 NaHCO-loading, increased base excretion is mirrored by decreased acid excretion. Urine HCO 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 secretion and the use of the challenged urine HCO test as a possible CFTR-biomarker.
多余 HCO 的肾排泄依赖于肾囊性纤维化跨膜电导调节因子（CFTR），在囊性纤维化（CF）患者中受损。口服 NaHCO 负荷后尿 HCO 的排泄可能是 CFTR 功能的简单体内生物标志物。在这项研究中，我们研究了口服 NaHCO 负荷后尿酸碱参数的变化，以全面评估对该测试的生理反应，并评估 HCO 作为主要测试结果。
从完成挑战尿 HCO 测试的对照组（n=10）和 CF 患者（n=50）的生物样本库尿液样本中测量尿酸碱参数（可滴定酸（TA）、NH 、净酸排泄（NAE）和 pH）。评估尿酸碱排泄参数与临床 CF 疾病特征和 CFTR 调节剂治疗诱导变化之间的关系。
在治疗前，挑战尿酸碱排泄与重要的 CF 疾病特征相关。具有残留功能突变的 CF 患者 TA 排泄和 NAE 较低，分别为 7.9 和 16.6mmol/3h，较低的 TA 排泄和 NAE 与胰腺充足相关。TA、NH 和 NAE 排泄越低，预测 FEV 的百分比越高（分别为每 mmol/3h 高 1.3%、2.5%和 0.8%）。调节剂治疗降低了 TA 排泄和 NAE（分别为-2.9 和-5.3mmol/3h）。
急性 NaHCO 负荷后，基础排泄增加与酸排泄减少相对应。尿 HCO 的排泄足以代表测试结果的其他尿酸碱参数。观察到的酸排泄变化支持 CFTR 调节剂诱导的 CFTR 依赖性 B 型闰细胞 HCO 分泌增加，以及使用挑战尿 HCO 测试作为可能的 CFTR 生物标志物。
