Effects of Exogenous Ketosis on Proteinuria and Renal Function

Not Applicable

Recruiting

• Conditions: Renal Insufficiency, Chronic; Polycystic Kidney Diseases; Proteinuria; Ketosis

• Registration Number: NCT06867471
• Lead Sponsor: Gødstrup Hospital

Brief Summary

A randomized, placebo-controlled, double-blinded crossover study will be conducted. Fourteen patients with polycystic kidney disease (PKD) and 29 patients with proteinuric kidney disease will receive ketone bodies (Ketone-IQ) and placebo in a randomized order. Each treatment period is four weeks. There will be a wash-out period of two weeks in between treatment periods. Effect variables will be measured in the last day of each treatment period.

Detailed Description

Background: Until recently, the only treatment shown to slow progression of chronic kidney disease (CKD) has been angiotensin converting enzyme (ACE) inhibitors and angiotensin receptor blockers (ARBs).

The use of sodium glucose transporter 2 (SGLT2)-inhibitors, which work by blocking the activity of sodium-glucose-cotransporter 2 channels in the proximal kidney tubule, has completely transformed the treatment of proteinuric kidney disease, with a 28% decrease in the risk for cardiorenal outcomes. Despite these new treatment options, a significant proportion of patients still succumb to kidney failure, require hospitalization for heart failure and die prematurely. Thus, additional preventive measures are essential.

Renewed interest in the physiological role of ketone bodies (KB) has emerged. It has become increasingly clear that ketosis has several beneficial effects including anti-epileptic effects, improved exercise capacity, lipid profile, cardiac function and cognition.

However, only few clinical studies have studied renal effects of exogenous ketosis, and to our knowledge there are no clinical studies examining the effects long term effects of renal ketosis in patients with CKD.

Hypothesis: Ketosis decreases urine albumin to creatinine ratio (ACR) and glomerular filtration rate (GFR) in patients with CKD/PKD.

Methods: A randomized, placebo-controlled, double-blinded crossover study will be conducted. Twenty-nine patients with proteinuric kidney disease (study a) and 14 patients with PKD (study b) will receive ketone bodies (Ketone-IQ) and placebo in a randomized order. Each treatment period is four weeks. There will be a wash-out period of two weeks in between treatment periods. Effect variables will be measured in the last day of each treatment period.

Perspectives: The study has the potential to provide information regarding the therapeutic potential of ketone bodies in patients with CKD/PKD.

Study Timeline

• Study Start: 2024-09-11
• Study First Submitted: 2024-11-20
• Status Verified: 2025-03
• Study First Submitted QC: 2025-03-06
• Last Update Submitted: 2025-03-06
• Study First Posted: 2025-03-10
• Last Update Posted: 2025-03-10
• Primary Completion: 2025-12
• Study Completion: 2025-12

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 43

Inclusion Criteria

Not provided

Exclusion Criteria

Not provided

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Proteinuria	Measured on 24 hour urine collection on the last day in each treatment period (each treatment period is 4 weeks)	Mean difference between Log UACR after 4 weeks treatment with ketone bodies and placebo (primary outcome study a)
GFR	Measured on the last day in each treatment period (each treatment period is 4 weeks)	Mean difference between GFR measured by Technetium99 (Tc99m) - Diethylene Triamine Pentaacetic Acid (DTPA) clearance after 4 weeks treatment with ketone bodies and placebo (primary outcome study b, secondary outcome in study a)

Secondary Outcome Measures

Name	Time	Method
Aldosterone	Measured on the last day in each treatment period (each treatment period is 4 weeks)	Mean difference in plasma levels of aldosterone (pmol/L) after 4 weeks treatment with ketone bodies and placebo
P-Beta-hydroxybutyrate	Measured on the last day in each treatment period (each treatment period is 4 weeks)	Change ind p-beta-hydroxybutyrate concentration
Excretion rate of renal tubular transport proteins	Measured on the last day in each treatment period (each treatment period is 4 weeks)	Mean difference between urine excretion rate of aquaporin 2 (AQP2) (pq/min), thiazide-sensitive sodium-chloride cotransporter (NCC)(pg/min), and distal epithelial sodium channel (ENaC)(pg/min) after 4 weeks treatment with ketone bodies and placebo
24-hour Ambulatory Blood Pressure	Measured using a Mobil-o-graph on the last day in each treatment period (each treatment period is 4 weeks)	Mean difference between systolic and diastolic 24-hour ambulatory blood pressure (mmHg) after treatment with ketone bodies and placebo.
Sodium and potassium excretion	Measured on 24 hour urine collection on the last day in each treatment period (each treatment period is 4 weeks)	Diffeence between mean fractional and absolute excretion af sodium and postassium after 4 weeks treatment with ketone bodies and placebo
Peripherial Vascular Resistance	Measured using a Mobil-o-graph on the last day in each treatment period (each treatment period is 4 weeks)	Mean difference between peripherial vascular resistance (dyn\*s/cm5) during treatment with ketone bodies compared to placebo
Heart rate	Measured using a Mobil-o-graph on the last day in each treatment period (each treatment period is 4 weeks)	Mean difference between heart rate after 4 weeks treatment with ketone bodies and placebo
Pulse Wave Velocity	Measured using a Mobil-o-graph on the last day in each treatment period (each treatment period is 4 weeks)	Mean difference between pulse wave velocity (m/s) after 4 weeks treatment with ketone bodies and placebo
Renin	Measured on the last day in each treatment period (each treatment period is 4 weeks)	Mean difference in plasma concentration of renin(pmol/L) after 4 weeks treatment with ketone bodies and placebo

Trial Locations

Locations (1)

University Clinic in Nephrology and Hypertension, Gødstrup Region Hospital; 🇩🇰 Herning, Jutland, Denmark