Abstract
Response to antihypertensive drugs in patients with chronic kidney disease (CKD) has great interindividual variability. Adrenomedullin (ADM) is produced abundantly in hypertension, but clearance is very rapid. Mid-regional proADM (MR-proADM) produced from an ADM precursor is considered a surrogate biomarker for quantification of ADM. We investigated the association of MR-proADM with antihypertensive resistance in CKD patients with poor blood pressure (BP) control. This cross-sectional study analyzed 33 CKD patients with poor BP control defined as failure to achieve target BP despite at least two classes of antihypertensive drugs. Treatment intensity score was calculated to facilitate comparability of antihypertensive regimens across subjects taking different drugs. Plasma MR-proADM concentration was measured using ultra-performance liquid chromatography coupled with tandem mass spectrometry. Plasma MR-proADM concentration correlated with estimated glomerular filtration rate (eGFR) (r = − 0.777, p < 0.001). Treatment intensity score correlated positively with plasma MR-proADM concentration (r = 0.355, p = 0.043), and the correlation was further enhanced after correction by weight (r = 0.538, p = 0.001). Single and multiple regression analysis identified MR-proADM concentration (p = 0.005) as independently associated with weight-corrected treatment intensity score. MR-proADM may be useful as a biomarker to determine the therapeutic intensity of antihypertensive drugs in CKD patients with poor BP control.
Highlights
Chronic kidney disease (CKD) is defined in the Kidney Disease: Improving Global Outcomes (KDIGO) guideline as abnormalities of kidney structure or function, present for more than 3 months, with implications for health[1]
CKD was defined as glomerular filtration rate (GFR) lower than 60 mL/min/1.73 m 2, according to the Clinical practice guidebook for diagnosis and treatment of chronic kidney disease 2018 published by the Japanese Society of Nephrology[18]
As sustained hypertension is associated with the progression of CKD or the development of cardiovascular disease (CVD), a biomarker that reliably determines the therapeutic intensity of antihypertensive drugs is useful for early achievement of the target blood pressure
Summary
Chronic kidney disease (CKD) is defined in the Kidney Disease: Improving Global Outcomes (KDIGO) guideline as abnormalities of kidney structure or function, present for more than 3 months, with implications for health[1]. Previous reports suggested that the progression of CKD is a risk factor for complication with cardiovascular disease (CVD)[2,3]. Some patients, especially those who have CKD, exhibit poor response to antihypertensive therapy, and determination of the optimal antihypertensive therapy to achieve the target blood pressure takes time[6]. Patients with high risk for CVD are recommended to achieve target blood pressure within a few weeks if possible, because the difference in blood pressure lowering during 1–3 months after antihypertensive initiation affects the onset of CVD7. We hypothesized that MR-proADM level serves as a predictive biomarker for the responsiveness to antihypertensive drugs in CKD patients with poor blood pressure control. We conducted a cross-sectional study in CKD patients with poor blood pressure control and determined the relation between MR-proADM and antihypertensive resistance
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