The Effects of Dietary Nitrate in Patients With Hypertensive Kidney Injury (DINO-CKD)

The study aims to study the effects of diatery nitrate in patients with hypertension and hypertensive kidney injury.

The study is a randomized, placebo-controlled, double-blinded crossover trial. 14-20 patients with hypertension and CKD I-III will be randomized to receive either nitrate or placebo delivered in the form of beetroot juice.

Effect variables will be measured before and after a 2 week treatment. After a washout period of 14 days, the subjects are crossed over to the opposite treatment.

The study is terminated by measuring effect variables after the second treatment period.

Study Overview

• Status: Recruiting
• Conditions: Hypertension; CKD - Chronic Kidney Disease
• Intervention / Treatment: Dietary supplement: Beetroot Juice - Active; Dietary supplement: Beetroot juice placebo

Detailed Description

AIM: We aim to investigate the mechanisms behind the cardiovascular and renal effect of nitrates in patients with hypertension and hypertensive kidney injury.

HYPOTHESIS: Dietary nitrate decreases BP and increases renal blood flow. This is independent of renal function or enhanced during low eGFR due to reduced renal clearance of nitrate.

METHODS: The study is a randomized, placebo-controlled, double-blinded crossover trial. 14-20 patients with hypertension and CKD I-III will be randomized to receive either nitrate or placebo delivered in the form of beetroot juice.

Effect variables will be measured before and after a 2 week treatment. After each treatment period effect variables will be measured, including include 24 hour bloodpressure measurment. Technetium(Tc)99m - Diethylenetriamine pentaacetate (DTPA) clearance and water based positron emission tomography computed tomography (PET/CT) is performed only after the intervention periods.

After a washout period of 14 days, the subjects are crossed over to the opposite treatment. The study is terminated by measuring effect variables after the second treatment period.

PERSPECTIVE: The knowledge gained from these studies can lead to improved dietary counselling, which is a promising approach in the treatment of hypertension.

• Study Type: Interventional
• Enrollment (Estimated): 20
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Kezia T McWhan, MD; Phone Number: 004578436580; Email: kezmcw@rm.dk

Study Locations

• Denmark
  • Herning, Denmark, 7400
    • Recruiting
    • University Clinic in Nephrology and Hypertension, Gødstrup Regional Hospital and Aarhus University
    • Contact: Kezia T McWhan, MD; Phone Number: 004578432390; Email: kezmcw@rm.dk

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

• Hypertension, treated with a maximum of 2 antihypertensive drugs and unattended office BP < 150/95 mmHg at the screening visit, or newly diagnosed without antihypertensive treatment by 24-hour BP or home BP measurement (above 130/80 or 135/85 respectively), and unattended office BP < 160/100 mmHg.

  • CKD I-III based on hypertensive kidney injury. Patients, who previously met the criteria for CKD I within the last 5 years, but no longer has proteinuria after relevant treatment, can also be included. Diagnosis of CKD I can be based on eGFR and either urine albumin/creatine ration or urine-dipstick test with presence of protein.
  • Albumin/creatinine ratio < 500 mg/g
  • eGFR > 30 ml/min/1,73m2
  • Body Mass Index (BMI) ≤ 35 kg/m2
  • Able to adhere to dietary regimen
  • Fertile women must use safe contraception (oral contraceptive pill, hormonal or copper intrauterine device, vaginal ring, contraceptive implant, transdermal contraceptive patch or contraceptive injections) or abstinence. Excluded from this are postmenopausal woman without menstrual bleeding for at least 12 months before inclusion, surgically sterilized women and women with surgically sterilized partner.

Exclusion Criteria:

• • Diagnosis of heart failure, NYHA II-IV

  • Diagnosis of liver failure
  • Diabetes mellitus (all types)
  • Current malignant disease (other than non-melanoma skin cancer)
  • Indicators of other aetiologies of CKD than hypertensive kidney injury, e.g. through kidney biopsy or biochemistry.
  • Previous kidney transplant recipient
  • History of stroke or transient cerebral ischemic attack
  • Current indication of untreated cardiovascular disease, e.g. planned work-up for ischemia.
  • History of myocardial infarction, apart from non-STEMI more than 1 year prior to the study, if the subject is currently revascularized and relevantly medicated.

Organic nitrate treatment Diagnosed secondary hypertension other than renal parenchymal hypertension (i.e. renal artery stenosis, primary hyperaldosteronism, low renin hypertension etc.)

• Pregnancy or lactation
• Alcohol abuse (intake above the recommended guidelines from Danish Health Authorities)
• Conditions treated with medication that investigator finds may interfere with the effect parameters, and cannot be discontinued during the trial (e.g. atrial fibrillation treated with betablockers)
• If, according to the investigator's assessment, the participant is considered unsuitable to participate.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Beetroot juice (active); nitrate content: 400 mg	Dietary supplement: Beetroot Juice - Active; Intervention is beetroot juice ("Beet It concentrated beetroot juice shots", James White Drinks Ltd, Ipswich, England) The nitrate content of the juice is standardized. The dose of nitrate will be 70 ml/day corresponding to intake of 6.5 mmol/400 mg of nitrate.
Placebo Comparator: Beetroot juice (placebo); nitrate free	Dietary supplement: Beetroot juice placebo; The placebo beetroot juice is a corresponding nitrate free beetroot juice, obtained from the manufacturer ("Beet It nitrate depleted shots", James White Drinks Ltd, Ipswich, England.). The placebo juice appears identical to the nitrate containing juice regarding color and taste.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Changes in 24 h systolic blood pressure	Measured by Mobiograph	Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Diastolic blood pressure	Mobil graph with 24 h measurments	Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)
Heart rate	Mobil graph with 24 h measurment	Measured on 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)
Pulsewave velocity	Mobil graph with 24 h measurment	Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)
Augmentation index	Mobilograph with 24 h measurment	Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)
Vascular resistance	Mobilograph 24 hour measurments	Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)
Reflection index	Mobilograph 24 hour measuments	Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)
Dipping status	Mobilograph 24 hour measurments	Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)
Blood pressure variability	Mobil graph with 24 h measurment	Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)
Unattended office blood pressure	Measured on the examination days after 5 minutes rest 3 times by an autoumated ossilometric device in an undisturbed room. The mean of the tre measurments is used.	Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)
Renal Blood Flow (RBF)	Change in RBF determined by water based PET/CT scans	Measured on Day 15 of each intervention period
GFR	Change in GFR measured by Tc99m-DTPA clearance	Measured on Day 15 of each intervention period
Urine concentration of renal tubular transport proteins	Urine excretions of aquaporin 2 (AQP2), thiazide-sensitive sodium-chloride cotransporter (NCC) and distal epithelial sodium channel (ENaC)	Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)
Vasoactive hormones	Change in plasma levels of aldosterone, renin, brain natriuretic peptide (BNP), atrial natriuretic peptide (ANP), copeptin	Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)
Measurements of the NO-system	Blood and urine levels of: Nitrite, nitrate, cyclic guanosine monophosphate (cGMP)	Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)
Plasma and urine levels of sodium, potassium, creatinine, urea, uric acid, albumin and osmolality	Measured in blood and urine (24 h collection). Abbsolute and fractional excretions of sodium and potassium and free water clearence will be calculated.	Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)
Body composition measurments from bioimpedance spectroscopy	Fresenius Body composition monitor is used, which estimates the compartments in the bodycomposition: Extracellular Body Water (L), Total Body Water (L), Intracellular Body Water (L), Overhydration (L)	Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)
Body weight	Patient weight (kg)	Measured on day 1 and day 15 of the intervention period (This represents baseline and after conclusion of the intervention period)
Central Blood pressure	Sphygmocor measurments	Measured on 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)
Microvascular function	Laser speckle contrast imaging	Measured on 1 and day 15 of the intervention period (This represents baseline and after conclusion of each intervention period)

Collaborators and Investigators

• Sponsor: Gødstrup Hospital

Study record dates

Study Major Dates

• Study Start (Actual): December 8, 2025
• Primary Completion (Estimated): January 1, 2028
• Study Completion (Estimated): January 1, 2030

Study Registration Dates

• First Submitted: November 18, 2025
• First Submitted That Met QC Criteria: December 17, 2025
• First Posted (Actual): December 18, 2025

Study Record Updates

• Last Update Posted (Actual): December 18, 2025
• Last Update Submitted That Met QC Criteria: December 17, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: hypertension; nitrate; beetroot
• Additional Relevant MeSH Terms: Urogenital Diseases; Vascular Diseases; Cardiovascular Diseases; Pathologic Processes; Male Urogenital Diseases; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Chronic Disease; Disease Attributes; Renal Insufficiency; Pathological Conditions, Signs and Symptoms; Hypertension; Renal Insufficiency, Chronic
• Other Study ID Numbers: KTM-1-2025

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