Mechanisms and Phenotypes of Hypertension in Patients in Chronic Hemodialysis

The goal of this study is to evaluate interdialytic blood pressure changes of the patients in chronic hemodialysis.

The main question to be answered is: What is the relative importance of weight gain, the renin angiotensin system, the sympathetic nervous system and inflammatory immune reactivity in the interdialytic hypertension of patients in chronic hemodialysis, The participants will have hemodynamic evaluation (cardiac output and peripheral vascular resistance) at the end of dialysis, ambulatory monitoring of blood pressure in the interdialytic period. Serum samples will be collected at the end of dialysis and before the start of the next dialysis, 2-3 days later.

Study Overview

• Status: Completed
• Conditions: Hemodialysis; Arterial Hypertension
• Intervention / Treatment: Other: There will be no intervention

Detailed Description

This is a prospective observational study that will study stable patients in the chronic hemodialysis program of the Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán" (INCMNSZ) patients. There will be no modifications in the dialysis prescriptions or treatments and the patients with inclusion criteria will be studied after and before their usual hemodialysis sesion.

• Weight changes will be studied after dialysis and before the next dialysis session (2-3 days later)
• Serum samples will be obtained at the end of dialysis and before the next session (2-3 days later).
• ultrasound estimation of cardiac output and peripheral vascular rersistance will be done after dialysis
• Ambulatory blood pressure (ABP) monitoring will be done in the interdialytic period (24-40 hours) between the end of dialysis and the next dialysis session.
• If possible there will be a predialysis study of bioimpedance.
• Associations of interdialytic weight gain, serum angiotensin II, copeptin levels (surrogate of arginine vasopressin) and norepinephrine levels with ABP, systolic and diastolic blood pressure before and after dialysis will be explored.
• Phenotypes of blood pressure (sustained hypertension, nocturnal and diurnal hypertension, dippers, non-dippers, extreme dippers and reverse dippers) determined by ambulatory monitoring will be studied in relation of levels of angiotensin II, inflammatory markers, copeptin and norepinephrine levels.

All serum levels will be determined by commercial ELISA kits

• Study Type: Observational
• Enrollment (Actual): 32

Contacts and Locations

Study Locations

• Mexico
  • Mexico City, Mexico, 14080
    • Instituto Nacional de Ciencias Médicas y Nutrición "Salvador Zubirán"

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Participantes will be patients in the chronic hemodialysis program of the INCMNSZ assigned to the groups depending on the ambulatory blood pressure (ABP) monitoring: Group A (TA < 130/80 mmHg), group B (TA 130-139/80-89 mmHg and group C (TA > 140mmHg)

Description

Inclusion Criteria:

• Patients with more than 3 months in the chronic hemodialysis program in the INCMNSZ and assumed to remained in the program for longer than 3 months
• Stable patients with no change in medication 1 month prior to the study
• Unchanged drug therapy and dialysis prescription for >1 month prior to the studies
• Informed consent to participate in the study

Exclusion Criteria:

• Patients unable to give informed consent or withdrawal of informed consent to the study
• Patients with active infection
• Patients with prosthesis or pacemakers
• Patients with immunosuppressive treatment of more than 10mg Prednisone daily
• Prior nephrectomy
• incomplete collection of data specified in the study protocol

Study Plan

How is the study designed?

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Group A; There will be no intervention. Group A will be patients with ABP (ambulatory blood pressure) <130/80 mmHg (controlled hypertension)	Other: There will be no intervention; There will be no intervention. This is an observational studies and 3 groups will be organized depending on the level of ABP in the interdialytic period
Group B; There will be no intervention. Group B will be patients with ABP 130-139/80-89 mmHg (insufficiently controled hypertension)	Other: There will be no intervention; There will be no intervention. This is an observational studies and 3 groups will be organized depending on the level of ABP in the interdialytic period
Group C; There will be no intervention. Group C will be patients with ABP ≥140/90 mmHg (uncontrolled hypertension)	Other: There will be no intervention; There will be no intervention. This is an observational studies and 3 groups will be organized depending on the level of ABP in the interdialytic period

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cardiac Output	Cardiac output (systolic volume x heart rate) was determined by 2 experienced observers using a Siemens Acuson P500 ultrasound equipment with a phased array transducer . Systolic volume was calculated with the velocity time integral of the flow of the left ventricle outflow tract of the aortic area.	Each participant was studied once 1-3 hours after dialysis ended
Interdialytic Weight Change	The weight was determined in 2 ocassions: first, immediately after dialysis and second, 2-3 days later, before the next dialysis. The weight change in this interval is expressed as percentage change of the second measure in relation to the first measure.	Interdialytic weight change was studied once, by the difference between the weight at the end of dialysis and the weight 2-3 days later, before the next dialysis.
Systemic Vascular Resistance	Systemic vascular resistance was calculated using MediCalcR using the mean arterial pressure (MAP), the central venous pressure (CVP) anf the cardiac output (CO) and the equation: SVR=[(MAP-CVP)x79.92]/CO. Cardiac output (CO= systolic volume x heart rate) and central venous pressure were determined by 2 experienced observers using a Siemens Acuson P500 ultrasound equipment with a phased array transducer. Systolic volume was calculated with the velocity time integral of the flow of the left ventricle outflow tract of the aortic area.	Systemic vascular resistance was determined once in the participants 1-3 hours after dialysis

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Angiotensin II Serum Levels	Angiotensin serum levels (pg/ml) were determined once at the end of the interdialytic period, before dialysis, using ELISA (my BioSource Cat.# MBS703599)	Each participant was studied once. Serum samples taken before dialysis
Monocyte+Neutrophiles/Lymphocyte Ratio (MNLR)	Monocyte+Neutrophile/lymphocyte ratio obtained from peripheral blood counts in samples taken before dialysis (following the end of the interdialytic period).	Each participant was studied once. Blood samples taken before dialysis (following the end of the interdialytic period).
Serum Norepinephrine Levels	Interdialytic serum norepinephrine levels determined in blood samples obtained before dialysis (end of interdialytic period) using ELISA (ABCAM, Cat. # AB287789);	Each participant was studied once. Serum samples taken before dialysis
Serum Copeptin Levels	The copeptin levels (surrogate for arginine vasopressin) were measured before dialyisis (end of the interdialytic period) using ELISA (Bio-techne/NovusBiological, Cat, # NBP2-69822)	Each participant was studied once. Serum samples taken before dialysis
Hypertension Phenotypes	Interdialytic ambulatory blood pressure determined during 24-44 hours using Space Labs Health Care, model 90217A and Contec ABPM50 equipment. Determinations every 30 minutes during daytime and every hour during the night. We are here reporting the phenotypes in the total number of participants (n=32) instead that in each group (groups A n=15, B n=7 and C n=10) because our main interest was to determine the incidence of each phenotyte in stable patients treated with chronic dialysis, rather than in each group that, individually, had few patients	Each participant was studied once. Ambulatory blood pressure was monitored or 24-44 hours during the interdialytic perdiod starting 1-3 hours after dialysis

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in copeptin levels in the interdialytic period (2-3 days)	The copeptin levels (surrogate for arginine vasopressin) will be measured (pg/ml) at the end of dialysis and at the beginning of the next (2-3 days later) and evaluated in relation to weight gain (kg) and blood pessure changes (mmHg)	Determinations before and after dialysis (2-3 days interdialytic period). Reports through study completion, an average of 1 year

Collaborators and Investigators

• Sponsor: Bernardo Rodríguez Iturbe
• Investigators: Principal Investigator: Bernardo RODRIGUEZITURBE, MD, PhD, Department of Nephrology, Instituto Nacional de Ciencias Medicas y Nutrición "Salvador Zubirán"

Publications and helpful links

General Publications

• Rodriguez-Iturbe B. Autoimmunity in the Pathogenesis of Hypertension. Hypertension. 2016 Mar;67(3):477-83. doi: 10.1161/HYPERTENSIONAHA.115.06418. Epub 2015 Dec 7. No abstract available.
• Fay KS, Cohen DL. Resistant Hypertension in People With CKD: A Review. Am J Kidney Dis. 2021 Jan;77(1):110-121. doi: 10.1053/j.ajkd.2020.04.017. Epub 2020 Jul 23.
• Abais-Battad JM, Rudemiller NP, Mattson DL. Hypertension and immunity: mechanisms of T cell activation and pathways of hypertension. Curr Opin Nephrol Hypertens. 2015 Sep;24(5):470-4. doi: 10.1097/MNH.0000000000000146.
• Agarwal R, Weir MR. Dry-weight: a concept revisited in an effort to avoid medication-directed approaches for blood pressure control in hemodialysis patients. Clin J Am Soc Nephrol. 2010 Jul;5(7):1255-60. doi: 10.2215/CJN.01760210. Epub 2010 May 27.
• Rodriguez-Iturbe B, Pons H, Johnson RJ. Role of the Immune System in Hypertension. Physiol Rev. 2017 Jul 1;97(3):1127-1164. doi: 10.1152/physrev.00031.2016.
• Neumann J, Ligtenberg G, Klein II, Koomans HA, Blankestijn PJ. Sympathetic hyperactivity in chronic kidney disease: pathogenesis, clinical relevance, and treatment. Kidney Int. 2004 May;65(5):1568-76. doi: 10.1111/j.1523-1755.2004.00552.x.
• Kim KE, Onesti G, Schwartz AB, Chinitz JL, Swartz C. Hemodynamics of hypertension in chronic end-stage renal disease. Circulation. 1972 Sep;46(3):456-64. doi: 10.1161/01.cir.46.3.456. No abstract available.
• Buckalew VM Jr, Berg RL, Wang SR, Porush JG, Rauch S, Schulman G. Prevalence of hypertension in 1,795 subjects with chronic renal disease: the modification of diet in renal disease study baseline cohort. Modification of Diet in Renal Disease Study Group. Am J Kidney Dis. 1996 Dec;28(6):811-21. doi: 10.1016/s0272-6386(96)90380-7.
• Saad E, Charra B, Raj DS. Hypertension control with daily dialysis. Semin Dial. 2004 Jul-Aug;17(4):295-8. doi: 10.1111/j.0894-0959.2004.17330.x.

Study record dates

Study Major Dates

• Study Start (Actual): August 14, 2023
• Primary Completion (Actual): December 20, 2024
• Study Completion (Actual): June 6, 2025

Study Registration Dates

• First Submitted: December 19, 2024
• First Submitted That Met QC Criteria: January 1, 2025
• First Posted (Actual): January 8, 2025

Study Record Updates

• Last Update Posted (Actual): February 3, 2026
• Last Update Submitted That Met QC Criteria: January 30, 2026
• Last Verified: January 1, 2026

More Information

Terms related to this study

• Keywords: hypertension; inflammation; hemodialysis; sympathetic nervous system; renin angiotensin system; Interdialytic weight gain; interdialysis
• Additional Relevant MeSH Terms: Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hypertension; Inflammation
• Other Study ID Numbers: NMM-4512-23-24-1

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No