protocolSection identificationModule nctId: NCT06363097, orgStudyIdInfo id: ΔΔ5032, briefTitle: Urinary Uromodulin, Dietary Sodium Intake and Ambulatory Blood Pressure in Patients With Chronic Kidney Disease, statusModule overallStatus: RECRUITING, startDateStruct date: 2023-09-04, primaryCompletionDateStruct date: 2024-12, completionDateStruct date: 2025-06, studyFirstPostDateStruct date: 2024-04-12, lastUpdatePostDateStruct date: 2024-04-12, sponsorCollaboratorsModule leadSponsor name: Aristotle University Of Thessaloniki, class: OTHER, descriptionModule briefSummary: In chronic kidney disease (CKD), hypertension is characterized by the phenomenon of sodium-sensitivity, i.e., the disproportionate increase in blood pressure (BP) due to an increase in dietary sodium consumption to maintain homeostasis through urinary sodium excretion. Impaired renal circulation, blunt suppression of renin-angiotensin-aldosterone system, sympathetic nervous system overactivity, paradoxically reduced levels of atrial natriuretic peptide and hyperinsulinemia represent the main pathophysiologic mechanisms. Accumulated evidence has suggested that uromodulin plays a central role in the development of sodium-sensitive hypertension. Uromodulin is a kidney-specific glycoprotein which is exclusively produced by the epithelial cells lining the thick ascending limb and early distal convoluted tubule. It is currently recognized as a multifaceted player in kidney physiology and disease, with discrete roles for intracellular, urinary, interstitial and serum uromodulin. Among these, urinary uromodulin modulates renal sodium handling through regulating tubular transporters that reabsorb sodium and are targeted by diuretics, i.e., the loop diuretic-sensitive Na+-K+-2Cl- cotransporter type 2 (NKCC2) and the thiazide-sensitive Na+/Cl- cotransporter (NCC). Given these roles, the contribution of uromodulin to sodium-sensitive hypertension has been proposed. In preclinical models, uromodulin deficiency causes decreased BP that is resistant to dietary salt, while uromodulin overexpression causes hypertension due to increased tubular sodium reabsorption that is responsive to furosemide. Genetic human studies have identified robust associations of specific UMOD gene variants with sodium sensitivity and incident hypertension risk, while comprehensive Mendelian randomization studies have affirmed these associations by highlighting the causal relationship between UMOD variants, urinary uromodulin levels and hypertension. Furthermore, clinical studies in both healthy individuals and hypertensive patients have indicated a link between sodium sensitivity and uromodulin, directly affecting mean BP levels and BP response to salt intake. With regards to CKD population, solid data on the link of uromodulin with sodium sensitivity are currently missing from the literature. There is only a pediatric study in the setting of CKD (stages 2-3), which failed to show an association between urinary uromodulin levels indexed to urinary creatinine (UMOD/uCr) and either 24-hour or office BP; however, this study has several limitations, and its results should be interpreted with caution. To best of our knowledge, there is no study up to date investigating the effect of dietary sodium intake on 24-hour ambulatory blood pressure depending on urinary uromodulin levels in adult CKD patients., conditionsModule conditions: Chronic Kidney Disease, conditions: Hypertension, designModule studyType: OBSERVATIONAL, designInfo observationalModel: OTHER, timePerspective: CROSS_SECTIONAL, enrollmentInfo count: 130, type: ESTIMATED, armsInterventionsModule, outcomesModule primaryOutcomes measure: Effect of urinary uromodulin levels on the relationship between 24-hour urinary sodium excretion and 24-hour ambulatory systolic blood pressure., primaryOutcomes measure: Effect of urinary uromodulin levels on the relationship between 24-hour urinary sodium excretion and 24-hour ambulatory diastolic blood pressure., secondaryOutcomes measure: Effect of urinary uromodulin levels on the relationship between nighttime/daytime ratio of urinary sodium excretion and 24-hour ambulatory systolic blood pressure., secondaryOutcomes measure: Effect of urinary uromodulin levels on the relationship between nighttime/daytime ratio of urinary sodium excretion and 24-hour ambulatory diastolic blood pressure., secondaryOutcomes measure: Effect of urinary uromodulin levels on the relationship between urinary sodium-to-potassium (Na+/K+) ratio and 24-hour ambulatory systolic blood pressure., secondaryOutcomes measure: Effect of urinary uromodulin levels on the relationship between urinary sodium-to-potassium (Na+/K+) ratio and 24-hour ambulatory diastolic blood pressure., secondaryOutcomes measure: The difference in 24-hour ambulatory brachial SBP/DBP between patients with high and low urinary uromodulin excretion., secondaryOutcomes measure: The difference in 24-hour ambulatory brachial SBP/DBP standard deviation (SD) between patients with high and low urinary uromodulin excretion., secondaryOutcomes measure: The difference in 24-hour ambulatory brachial SBP/DBP weighted SD (wSD) between patients with high and low urinary uromodulin excretion., secondaryOutcomes measure: The difference in 24-hour ambulatory brachial SBP/DBP coefficient of variation (CV) between patients with high and low urinary uromodulin excretion., secondaryOutcomes measure: The difference in 24-hour ambulatory brachial SBP/DBP average real variability (ARV) between patients with high and low urinary uromodulin excretion., secondaryOutcomes measure: Effect of 24-hour urinary sodium excretion on 24-hour ambulatory brachial SBP/DBP standard deviation (SD)., secondaryOutcomes measure: Effect of 24-hour urinary sodium excretion on 24-hour ambulatory brachial SBP/DBP weighted SD (wSD)., secondaryOutcomes measure: Effect of 24-hour urinary sodium excretion on 24-hour ambulatory brachial SBP/DBP coefficient of variation (CV)., secondaryOutcomes measure: Effect of 24-hour urinary sodium excretion on 24-hour ambulatory brachial SBP/DBP average real variability (ARV)., secondaryOutcomes measure: Effect of nighttime/daytime ratio of urinary sodium excretion on 24-hour ambulatory brachial SBP/DBP standard deviation (SD)., secondaryOutcomes measure: Effect of nighttime/daytime ratio of urinary sodium excretion on 24-hour ambulatory brachial SBP/DBP weighted SD (wSD)., secondaryOutcomes measure: Effect of nighttime/daytime ratio of urinary sodium excretion on 24-hour ambulatory brachial SBP/DBP coefficient of variation (CV)., secondaryOutcomes measure: Effect of nighttime/daytime ratio of urinary sodium excretion on 24-hour ambulatory brachial SBP/DBP average real variability (ARV)., secondaryOutcomes measure: Effect of urinary sodium-to-potassium (Na+/K+) ratio on 24-hour ambulatory brachial SBP/DBP standard deviation (SD)., secondaryOutcomes measure: Effect of urinary sodium-to-potassium (Na+/K+) ratio on 24-hour ambulatory brachial SBP/DBP weighted SD (wSD)., secondaryOutcomes measure: Effect of urinary sodium-to-potassium (Na+/K+) ratio on 24-hour ambulatory brachial SBP/DBP coefficient of variation (CV)., secondaryOutcomes measure: Effect of urinary sodium-to-potassium (Na+/K+) ratio on 24-hour ambulatory brachial SBP/DBP average real variability (ARV)., secondaryOutcomes measure: Effect of 24-hour urinary sodium excretion on hydration status (US-B lines)., secondaryOutcomes measure: Effect of nighttime/daytime ratio of urinary sodium excretion on hydration status (US-B lines)., secondaryOutcomes measure: Effect of urinary sodium-to-potassium (Na+/K+) ratio on hydration status (US-B lines)., secondaryOutcomes measure: Effect of 24-hour urinary sodium excretion on MMSE score., secondaryOutcomes measure: Effect of nighttime/daytime ratio of urinary sodium excretion on MMSE score., secondaryOutcomes measure: Effect of urinary sodium-to-potassium (Na+/K+) ratio on MMSE score., secondaryOutcomes measure: Effect of 24-hour urinary sodium excretion on PSQI score., secondaryOutcomes measure: Effect of nighttime/daytime ratio of urinary sodium excretion on PSQI score., secondaryOutcomes measure: Effect of urinary sodium-to-potassium (Na+/K+) ratio on PSQI score., secondaryOutcomes measure: Effect of 24-hour urinary sodium excretion on ESS score., secondaryOutcomes measure: Effect of nighttime/daytime ratio of urinary sodium excretion on ESS score., secondaryOutcomes measure: Effect of urinary sodium-to-potassium (Na+/K+) ratio on ESS score., secondaryOutcomes measure: Effect of 24-hour urinary sodium excretion on nocturnal urinations., secondaryOutcomes measure: Effect of nighttime/daytime ratio of urinary sodium excretion on nocturnal urinations., secondaryOutcomes measure: Effect of urinary sodium-to-potassium (Na+/K+) ratio on nocturnal urinations., eligibilityModule sex: ALL, minimumAge: 18 Years, stdAges: ADULT, stdAges: OLDER_ADULT, contactsLocationsModule locations facility: 1st Department of Nephrology, status: RECRUITING, city: Thessaloníki, state: Central Macedonia, zip: 54642, country: Greece, contacts name: Artemios G Karagiannidis, MD, MSc, role: CONTACT, phone: +30 6970362392, email: artemiskaragiannidis@gmail.com, geoPoint lat: 40.64361, lon: 22.93086, hasResults: False