Hypertension Clinical Trial
Official title:
The Effect of Dietary Sodium Intake on Ambulatory Blood Pressure Levels According to Urinary Uromodulin Levels in Patients With Chronic Kidney Disease
NCT number | NCT06363097 |
Other study ID # | ??5032 |
Secondary ID | |
Status | Recruiting |
Phase | |
First received | |
Last updated | |
Start date | September 4, 2023 |
Est. completion date | June 2025 |
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.
Status | Recruiting |
Enrollment | 130 |
Est. completion date | June 2025 |
Est. primary completion date | December 2024 |
Accepts healthy volunteers | No |
Gender | All |
Age group | 18 Years and older |
Eligibility | Inclusion Criteria: 1. Age =18 years 2. CKD defined based on the KDIGO criteria 3. Provision of informed written consent Exclusion Criteria: 1. Kidney transplantation or end-stage kidney disease (ESKD) under hemodialysis or peritoneal dialysis 2. Chronic atrial fibrillation or other diagnosed arrhythmia intervening with a proper 24-hour ABPM recording 3. Inability to reliably complete the study questionnaires 4. Pregnancy |
Country | Name | City | State |
---|---|---|---|
Greece | 1st Department of Nephrology | Thessaloníki | Central Macedonia |
Lead Sponsor | Collaborator |
---|---|
Aristotle University Of Thessaloniki |
Greece,
Bakhoum CY, Anderson CAM, Juraschek SP, Rebholz CM, Appel LJ, Miller ER, Parikh CR, Obeid W, Rifkin DE, Ix JH, Garimella PS. The Relationship Between Urine Uromodulin and Blood Pressure Changes: The DASH-Sodium Trial. Am J Hypertens. 2021 Mar 11;34(2):154-156. doi: 10.1093/ajh/hpaa140. — View Citation
Bakhoum CY, Matheson MB, Greenberg JH, Furth SL, Ix JH, Garimella PS. Urine Uromodulin Is Not Associated With Blood Pressure in the Chronic Kidney Disease in Children Cohort. Hypertension. 2022 Oct;79(10):2298-2304. doi: 10.1161/HYPERTENSIONAHA.122.19566. Epub 2022 Aug 3. — View Citation
Karagiannidis AG, Theodorakopoulou MP, Pella E, Sarafidis PA, Ortiz A. Uromodulin biology. Nephrol Dial Transplant. 2024 Jan 11:gfae008. doi: 10.1093/ndt/gfae008. Online ahead of print. — View Citation
McCallum L, Brooksbank K, McConnachie A, Aman A, Lip S, Dawson J, MacIntyre IM, MacDonald TM, Webb DJ, Padmanabhan S. Rationale and Design of the Genotype-Blinded Trial of Torasemide for the Treatment of Hypertension (BHF UMOD). Am J Hypertens. 2021 Feb 18;34(1):92-99. doi: 10.1093/ajh/hpaa166. — View Citation
Padmanabhan S, Melander O, Johnson T, Di Blasio AM, Lee WK, Gentilini D, Hastie CE, Menni C, Monti MC, Delles C, Laing S, Corso B, Navis G, Kwakernaak AJ, van der Harst P, Bochud M, Maillard M, Burnier M, Hedner T, Kjeldsen S, Wahlstrand B, Sjogren M, Fava C, Montagnana M, Danese E, Torffvit O, Hedblad B, Snieder H, Connell JM, Brown M, Samani NJ, Farrall M, Cesana G, Mancia G, Signorini S, Grassi G, Eyheramendy S, Wichmann HE, Laan M, Strachan DP, Sever P, Shields DC, Stanton A, Vollenweider P, Teumer A, Volzke H, Rettig R, Newton-Cheh C, Arora P, Zhang F, Soranzo N, Spector TD, Lucas G, Kathiresan S, Siscovick DS, Luan J, Loos RJ, Wareham NJ, Penninx BW, Nolte IM, McBride M, Miller WH, Nicklin SA, Baker AH, Graham D, McDonald RA, Pell JP, Sattar N, Welsh P; Global BPgen Consortium; Munroe P, Caulfield MJ, Zanchetti A, Dominiczak AF. Genome-wide association study of blood pressure extremes identifies variant near UMOD associated with hypertension. PLoS Genet. 2010 Oct 28;6(10):e1001177. doi: 10.1371/journal.pgen.1001177. — View Citation
Ponte B, Pruijm M, Ackermann D, Olinger E, Youhanna S, Vogt B, Burnier M, Pechere-Bertschi A, Bochud M, Devuyst O. Uromodulin, Salt, and 24-Hour Blood Pressure in the General Population. Clin J Am Soc Nephrol. 2021 May 8;16(5):787-789. doi: 10.2215/CJN.11230720. Epub 2021 Jan 21. No abstract available. — View Citation
Ponte B, Sadler MC, Olinger E, Vollenweider P, Bochud M, Padmanabhan S, Hayward C, Kutalik Z, Devuyst O. Mendelian randomization to assess causality between uromodulin, blood pressure and chronic kidney disease. Kidney Int. 2021 Dec;100(6):1282-1291. doi: 10.1016/j.kint.2021.08.032. Epub 2021 Oct 9. — View Citation
Torffvit O, Melander O, Hulten UL. Urinary excretion rate of Tamm-Horsfall protein is related to salt intake in humans. Nephron Physiol. 2004;97(1):p31-6. doi: 10.1159/000077600. — View Citation
Trudu M, Janas S, Lanzani C, Debaix H, Schaeffer C, Ikehata M, Citterio L, Demaretz S, Trevisani F, Ristagno G, Glaudemans B, Laghmani K, Dell'Antonio G; SKIPOGH team; Loffing J, Rastaldi MP, Manunta P, Devuyst O, Rampoldi L. Common noncoding UMOD gene variants induce salt-sensitive hypertension and kidney damage by increasing uromodulin expression. Nat Med. 2013 Dec;19(12):1655-60. doi: 10.1038/nm.3384. Epub 2013 Nov 3. — View Citation
Type | Measure | Description | Time frame | Safety issue |
---|---|---|---|---|
Primary | Effect of urinary uromodulin levels on the relationship between 24-hour urinary sodium excretion and 24-hour ambulatory systolic blood pressure. | In patients with high and low urinary uromodulin excretion, investigation of the relationship of 24-hour urinary sodium excretion with 24-hour ambulatory systolic blood pressure. | Baseline | |
Primary | Effect of urinary uromodulin levels on the relationship between 24-hour urinary sodium excretion and 24-hour ambulatory diastolic blood pressure. | In patients with high and low urinary uromodulin excretion, investigation of the relationship of 24-hour urinary sodium excretion with 24-hour ambulatory diastolic blood pressure. | Baseline | |
Secondary | Effect of urinary uromodulin levels on the relationship between nighttime/daytime ratio of urinary sodium excretion and 24-hour ambulatory systolic blood pressure. | In patients with high and low urinary uromodulin excretion, investigation of the relationship between nighttime/daytime ratio of urinary sodium excretion and 24-hour ambulatory systolic blood pressure. | Baseline | |
Secondary | Effect of urinary uromodulin levels on the relationship between nighttime/daytime ratio of urinary sodium excretion and 24-hour ambulatory diastolic blood pressure. | In patients with high and low urinary uromodulin excretion, investigation of the relationship between nighttime/daytime ratio of urinary sodium excretion and 24-hour ambulatory diastolic blood pressure. | Baseline | |
Secondary | Effect of urinary uromodulin levels on the relationship between urinary sodium-to-potassium (Na+/K+) ratio and 24-hour ambulatory systolic blood pressure. | In patients with high and low urinary uromodulin excretion, investigation of the relationship between urinary sodium-to-potassium (Na+/K+) ratio and 24-hour ambulatory systolic blood pressure. | Baseline | |
Secondary | Effect of urinary uromodulin levels on the relationship between urinary sodium-to-potassium (Na+/K+) ratio and 24-hour ambulatory diastolic blood pressure. | In patients with high and low urinary uromodulin excretion, investigation of the relationship between urinary sodium-to-potassium (Na+/K+) ratio and 24-hour ambulatory diastolic blood pressure. | Baseline | |
Secondary | The difference in 24-hour ambulatory brachial SBP/DBP between patients with high and low urinary uromodulin excretion. | Baseline | ||
Secondary | The difference in 24-hour ambulatory brachial SBP/DBP standard deviation (SD) between patients with high and low urinary uromodulin excretion. | Baseline | ||
Secondary | The difference in 24-hour ambulatory brachial SBP/DBP weighted SD (wSD) between patients with high and low urinary uromodulin excretion. | Baseline | ||
Secondary | The difference in 24-hour ambulatory brachial SBP/DBP coefficient of variation (CV) between patients with high and low urinary uromodulin excretion. | Baseline | ||
Secondary | The difference in 24-hour ambulatory brachial SBP/DBP average real variability (ARV) between patients with high and low urinary uromodulin excretion. | Baseline | ||
Secondary | Effect of 24-hour urinary sodium excretion on 24-hour ambulatory brachial SBP/DBP standard deviation (SD). | (This blood pressure variability (BPV) parameter of SBP/DBP will be calculated based on the ABPM recordings obtained with the ABPMpro device). | Baseline | |
Secondary | Effect of 24-hour urinary sodium excretion on 24-hour ambulatory brachial SBP/DBP weighted SD (wSD). | (This blood pressure variability (BPV) parameter of SBP/DBP will be calculated based on the ABPM recordings obtained with the ABPMpro device). | Baseline | |
Secondary | Effect of 24-hour urinary sodium excretion on 24-hour ambulatory brachial SBP/DBP coefficient of variation (CV). | (This blood pressure variability (BPV) parameter of SBP/DBP will be calculated based on the ABPM recordings obtained with the ABPMpro device). | Baseline | |
Secondary | Effect of 24-hour urinary sodium excretion on 24-hour ambulatory brachial SBP/DBP average real variability (ARV). | (This blood pressure variability (BPV) parameter of SBP/DBP will be calculated based on the ABPM recordings obtained with the ABPMpro device). | Baseline | |
Secondary | Effect of nighttime/daytime ratio of urinary sodium excretion on 24-hour ambulatory brachial SBP/DBP standard deviation (SD). | (This blood pressure variability (BPV) parameter of SBP/DBP will be calculated based on the ABPM recordings obtained with the ABPMpro device). | Baseline | |
Secondary | Effect of nighttime/daytime ratio of urinary sodium excretion on 24-hour ambulatory brachial SBP/DBP weighted SD (wSD). | (This blood pressure variability (BPV) parameter of SBP/DBP will be calculated based on the ABPM recordings obtained with the ABPMpro device). | Baseline | |
Secondary | Effect of nighttime/daytime ratio of urinary sodium excretion on 24-hour ambulatory brachial SBP/DBP coefficient of variation (CV). | (This blood pressure variability (BPV) parameter of SBP/DBP will be calculated based on the ABPM recordings obtained with the ABPMpro device). | Baseline | |
Secondary | Effect of nighttime/daytime ratio of urinary sodium excretion on 24-hour ambulatory brachial SBP/DBP average real variability (ARV). | (This blood pressure variability (BPV) parameter of SBP/DBP will be calculated based on the ABPM recordings obtained with the ABPMpro device). | Baseline | |
Secondary | Effect of urinary sodium-to-potassium (Na+/K+) ratio on 24-hour ambulatory brachial SBP/DBP standard deviation (SD). | (This blood pressure variability (BPV) parameter of SBP/DBP will be calculated based on the ABPM recordings obtained with the ABPMpro device). | Baseline | |
Secondary | Effect of urinary sodium-to-potassium (Na+/K+) ratio on 24-hour ambulatory brachial SBP/DBP weighted SD (wSD). | (This blood pressure variability (BPV) parameter of SBP/DBP will be calculated based on the ABPM recordings obtained with the ABPMpro device). | Baseline | |
Secondary | Effect of urinary sodium-to-potassium (Na+/K+) ratio on 24-hour ambulatory brachial SBP/DBP coefficient of variation (CV). | (This blood pressure variability (BPV) parameter of SBP/DBP will be calculated based on the ABPM recordings obtained with the ABPMpro device). | Baseline | |
Secondary | Effect of urinary sodium-to-potassium (Na+/K+) ratio on 24-hour ambulatory brachial SBP/DBP average real variability (ARV). | (This blood pressure variability (BPV) parameter of SBP/DBP will be calculated based on the ABPM recordings obtained with the ABPMpro device). | Baseline | |
Secondary | Effect of 24-hour urinary sodium excretion on hydration status (US-B lines). | (The hydration status will be assessed through quantification of US-B lines using GE VScan lung ultrasound device). | Baseline | |
Secondary | Effect of nighttime/daytime ratio of urinary sodium excretion on hydration status (US-B lines). | (The hydration status will be assessed through quantification of US-B lines using GE VScan lung ultrasound device). | Baseline | |
Secondary | Effect of urinary sodium-to-potassium (Na+/K+) ratio on hydration status (US-B lines). | (The hydration status will be assessed through quantification of US-B lines using GE VScan lung ultrasound device). | Baseline | |
Secondary | Effect of 24-hour urinary sodium excretion on MMSE score. | Baseline | ||
Secondary | Effect of nighttime/daytime ratio of urinary sodium excretion on MMSE score. | Baseline | ||
Secondary | Effect of urinary sodium-to-potassium (Na+/K+) ratio on MMSE score. | Baseline | ||
Secondary | Effect of 24-hour urinary sodium excretion on PSQI score. | Baseline | ||
Secondary | Effect of nighttime/daytime ratio of urinary sodium excretion on PSQI score. | Baseline | ||
Secondary | Effect of urinary sodium-to-potassium (Na+/K+) ratio on PSQI score. | Baseline | ||
Secondary | Effect of 24-hour urinary sodium excretion on ESS score. | Baseline | ||
Secondary | Effect of nighttime/daytime ratio of urinary sodium excretion on ESS score. | Baseline | ||
Secondary | Effect of urinary sodium-to-potassium (Na+/K+) ratio on ESS score. | Baseline | ||
Secondary | Effect of 24-hour urinary sodium excretion on nocturnal urinations. | Baseline | ||
Secondary | Effect of nighttime/daytime ratio of urinary sodium excretion on nocturnal urinations. | Baseline | ||
Secondary | Effect of urinary sodium-to-potassium (Na+/K+) ratio on nocturnal urinations. | Baseline |
Status | Clinical Trial | Phase | |
---|---|---|---|
Terminated |
NCT04591808 -
Efficacy and Safety of Atorvastatin + Perindopril Fixed-Dose Combination S05167 in Adult Patients With Arterial Hypertension and Dyslipidemia
|
Phase 3 | |
Recruiting |
NCT04515303 -
Digital Intervention Participation in DASH
|
||
Completed |
NCT05433233 -
Effects of Lifestyle Walking on Blood Pressure in Older Adults With Hypertension
|
N/A | |
Completed |
NCT05491642 -
A Study in Male and Female Participants (After Menopause) With Mild to Moderate High Blood Pressure to Learn How Safe the Study Treatment BAY3283142 is, How it Affects the Body and How it Moves Into, Through and Out of the Body After Taking Single and Multiple Doses
|
Phase 1 | |
Completed |
NCT03093532 -
A Hypertension Emergency Department Intervention Aimed at Decreasing Disparities
|
N/A | |
Completed |
NCT04507867 -
Effect of a NSS to Reduce Complications in Patients With Covid-19 and Comorbidities in Stage III
|
N/A | |
Completed |
NCT05529147 -
The Effects of Medication Induced Blood Pressure Reduction on Cerebral Hemodynamics in Hypertensive Frail Elderly
|
||
Recruiting |
NCT05976230 -
Special Drug Use Surveillance of Entresto Tablets (Hypertension)
|
||
Completed |
NCT06008015 -
A Study to Evaluate the Pharmacokinetics and the Safety After Administration of "BR1015" and Co-administration of "BR1015-1" and "BR1015-2" Under Fed Conditions in Healthy Volunteers
|
Phase 1 | |
Completed |
NCT05387174 -
Nursing Intervention in Two Risk Factors of the Metabolic Syndrome and Quality of Life in the Climacteric Period
|
N/A | |
Completed |
NCT04082585 -
Total Health Improvement Program Research Project
|
||
Recruiting |
NCT05121337 -
Groceries for Black Residents of Boston to Stop Hypertension Among Adults Without Treated Hypertension
|
N/A | |
Withdrawn |
NCT04922424 -
Mechanisms and Interventions to Address Cardiovascular Risk of Gender-affirming Hormone Therapy in Trans Men
|
Phase 1 | |
Active, not recruiting |
NCT05062161 -
Sleep Duration and Blood Pressure During Sleep
|
N/A | |
Not yet recruiting |
NCT05038774 -
Educational Intervention for Hypertension Management
|
N/A | |
Completed |
NCT05087290 -
LOnger-term Effects of COVID-19 INfection on Blood Vessels And Blood pRessure (LOCHINVAR)
|
||
Completed |
NCT05621694 -
Exploring Oxytocin Response to Meditative Movement
|
N/A | |
Completed |
NCT05688917 -
Green Coffee Effect on Metabolic Syndrome
|
N/A | |
Recruiting |
NCT05575453 -
OPTIMA-BP: Empowering PaTients in MAnaging Blood Pressure
|
N/A | |
Completed |
NCT03875768 -
Nourish: A Digital Health Program to Promote the DASH Eating Plan Among Adults With High Blood Pressure
|
N/A |