Ketogenic Diet for Kidney Disease

Overseen By Jeff Volek, PhD

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: Ohio State University

Must not be taking: Tolvaptan

Disqualifiers: Diabetes, Pregnancy, Severe kidney disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Compensation: Varies

Number of Visits: 3

Duration: 52 weeks

20 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

This is a prospective study to determine ketogenic diet effect on htTKV, GFR, microalbuminuria. This is a single-center study of 20 patients with ADPKD and deemed high risk for progression to ESRD. This determined by combination of features of ADPKD and htTKV as assessed by prior computed tomography (CT) or MRI. Patients will be recruited from the Polycystic Kidney Disease (PKD) Clinic at Ohio State University Wexner Medical Center. Enrolled patients will have MRI for htTKV, urinary studies, blood tests at baseline, 6 months, and 52 weeks. Blood for GFR will be assessed three times over the course of the study including baseline, 6 months, and 1 year. Participants will follow ketogenic diet for 52 weeks. Investigatory diet team will manage the ketogenic diet.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications, but you must not have changed medications in the last three months to be eligible.

Is the ketogenic diet safe for people with kidney disease?

Research suggests that a very low-calorie ketogenic diet can be safe for weight loss in people with obesity and mild kidney failure when supervised by healthcare professionals, showing no significant harm to kidney function. However, there are reports of potential complications like hypercalcemia (high calcium levels in the blood) in children using the ketogenic diet, indicating the need for careful monitoring. ^{1 2 3 4 5}

How is the ketogenic diet treatment different from other treatments for kidney disease?

The ketogenic diet is unique for kidney disease as it focuses on high fat and low carbohydrate intake, which is different from the typical low-protein diets often recommended for kidney health. This diet is being studied for its potential benefits in weight loss and metabolic changes in patients with mild-to-moderate chronic kidney disease and obesity, which is not a common focus of traditional kidney disease treatments. ^{2 6 7 8 9}

What data supports the effectiveness of the treatment Ketogenic Diet, High Fat, Low Carb Diet for kidney disease?

The study on the ketogenic diet for CKD patients aims to explore its impact on weight loss and metabolic changes, which could indirectly benefit kidney health by reducing obesity-related stress on the kidneys. While direct evidence for kidney disease is limited, the ketogenic diet has shown effectiveness in weight loss and metabolic improvements in other conditions, which may suggest potential benefits for CKD patients. ^{1 2 10 11 12}

Are You a Good Fit for This Trial?

This trial is for adults aged 18-65 with Polycystic Kidney Disease at high risk of kidney failure, specifically those classified as Mayo Class 1C-1E. Participants should be able to follow a ketogenic diet and have stable medication use for the last three months. They must also have a GFR (a measure of kidney function) of at least 25 mg/dl.

Inclusion Criteria

I haven't changed my medications in the last 3 months.

I can follow the required diet plan.

I have been diagnosed with ADPKD through imaging or genetic tests.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants follow a ketogenic diet for 52 weeks with monitoring of htTKV, GFR, and microalbuminuria

52 weeks

3 visits (in-person) at baseline, 6 months, and 1 year

Follow-up

Participants are monitored for safety and effectiveness after treatment

4 weeks

What Are the Treatments Tested in This Trial?

Interventions

• Ketogenic Diet

Trial Overview The study tests how a well-formulated ketogenic diet affects kidney size, function, and protein leakage in urine over one year. It involves regular blood draws, monitoring ketone/glucose levels using CGM/CKM devices, MRI scans to assess changes in kidney volume and filtration rate, and body composition analysis.

How Is the Trial Designed?

Group I: Ketogenic Diet Experimental Treatment 6 Interventions

The KD will follow general principles the investigators have described with the aim to achieve blood ketones \>0.5 mM, which will require most participants to consume \<50 g/day carbohydrate and \~1.5 g/kg reference weight protein. Fat will comprise the remaining calories with an emphasis on monounsaturated and saturated sources from whole foods.

Who Is Running the Clinical Trial?

Ohio State University

Lead Sponsor

Trials

891

Recruited

2,659,000+

Published Research Related to This Trial

This multicentre randomized controlled trial aims to evaluate the effects of a ketogenic diet on weight loss and metabolic changes in adult patients with mild-to-moderate chronic kidney disease (CKD) and obesity, enrolling participants with specific health criteria over a 6-month period.

The study will assess various outcomes, including weight loss, adherence to the diet, and changes in metabolic and renal function, to better understand the potential benefits and risks of the ketogenic diet for CKD patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The effect of a ketogenic diet on weight loss in CKD: a randomized controlled trial in obese stage G1-3a CKD patients. Zoccali, C., Bellizzi, V., Minutolo, R., et al.[2023]

In a study of 223 patients with chronic kidney disease (CKD) over a median of 74.2 months, a very low-protein diet supplemented with ketoanalogues (sVLPD) did not show a significant advantage over a standard low-protein diet (LPD) in terms of renal death or overall survival.

Both diets were safe, but adherence to protein restriction was low, and neither diet led to changes in nutritional status, indicating that while sVLPD is safe, it does not improve kidney outcomes compared to LPD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

No additional benefit of prescribing a very low-protein diet in patients with advanced chronic kidney disease under regular nephrology care: a pragmatic, randomized, controlled trial. Bellizzi, V., Signoriello, S., Minutolo, R., et al.[2023]

A meta-analysis of 17 randomized controlled trials involving 1,459 participants found that a restricted protein diet supplemented with ketoanalogues (KAs) significantly preserved kidney function (eGFR) and reduced proteinuria, blood pressure, and markers of CKD-mineral bone disorder.

The very low protein diet (VLPD) with KAs was more effective than a low protein diet (LPD) with KAs in slowing the decline of eGFR and improving blood pressure and parathyroid hormone levels, while both diets effectively decreased serum phosphate without causing malnutrition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

The Effects of Restricted Protein Diet Supplemented With Ketoanalogue on Renal Function, Blood Pressure, Nutritional Status, and Chronic Kidney Disease-Mineral and Bone Disorder in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis. Chewcharat, A., Takkavatakarn, K., Wongrattanagorn, S., et al.[2022]

Supplemental ketoanalogues (KA) combined with low-protein diets (LPD) or very-low protein diets (VLPD) showed favorable effects on renal and metabolic outcomes in patients with diabetic kidney disease (DKD), based on a systematic review of 11 studies.

The regimens were found to be safe and well tolerated, with no adverse effects on nutritional status, suggesting that KA supplementation could be an effective dietary strategy for managing DKD in non-dialysis dependent patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Ketoanalogue Supplementation in Patients with Non-Dialysis Diabetic Kidney Disease: A Systematic Review and Meta-Analysis. Bellizzi, V., Garofalo, C., Ferrara, C., et al.[2022]

In a study of 330 patients with pre-dialysis stage 5 chronic kidney disease (CKD) on a low-protein diet, ketoanalogues (KA) supplementation did not significantly affect mortality rates, with a hazard ratio of 1.41, indicating no clear benefit or harm in terms of survival.

However, KA supplementation was associated with a significantly increased risk of progressing to long-term dialysis, with an adjusted hazard ratio of 1.41, particularly in patients with diabetes mellitus, suggesting that while KA may not affect mortality, it could lead to worse kidney outcomes.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-Term Effects of Ketoanalogues on Mortality and Renal Outcomes in Advanced Chronic Kidney Disease Patients Receiving a Low-Protein Diet. Wang, YC., Juan, SH., Chou, CL., et al.[2021]

A very low-calorie ketogenic diet (VLCKD) led to an average weight loss of nearly 20% in 92 patients over approximately 3 months, with significant reductions in fat mass and improvements in metabolic parameters.

The study found no clinically relevant changes in liver and kidney function, and notably, 27.7% of patients with mild kidney failure experienced normalization of their kidney function after the diet, suggesting that VLCKD can be safe and effective even for those with mild renal issues.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Very Low-Calorie Ketogenic Diet: A Safe and Effective Tool for Weight Loss in Patients With Obesity and Mild Kidney Failure. Bruci, A., Tuccinardi, D., Tozzi, R., et al.[2020]

In a study of 14 children aged 0.9 to 18 years, acute hypercalcemia was observed as a complication of the ketogenic diet, typically occurring 2.1 years after starting the diet, particularly in those with impaired renal function.

The condition was associated with low parathyroid hormone levels and reduced osteoblast activity, suggesting a need for careful monitoring of bone health in children on the ketogenic diet.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Hypercalcemia in Children Using the Ketogenic Diet: A Multicenter Study. Hawkes, CP., Roy, SM., Dekelbab, B., et al.[2021]

The severe hypoproteic diet supplemented with ketoanalogues (SVLPD) significantly reduced serum urea levels and improved acid-base and calcium-phosphorus balance in patients with chronic kidney disease (CKD) over 48 weeks, indicating its efficacy in managing metabolic disorders associated with CKD.

Patients on the SVLPD had a lower initiation rate of renal replacement therapy (4% vs. 27% in the control group), suggesting that this dietary intervention may help delay the progression of kidney disease without compromising nutritional status.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of a supplemented hypoproteic diet in chronic kidney disease. Mircescu, G., Gârneaţă, L., Stancu, SH., et al.[2022]

In a study of 90 patients with chronic kidney disease (CKD), those on a low-protein diet (LPD) combined with keto/amino acids (ketosteril or ketoaminol) showed no signs of malnutrition, while a control group without these supplements experienced significant weight loss and lean mass reduction.

The use of keto/amino acids not only helped maintain protein balance but also prevented increases in parathyroid hormone levels and hyperphosphatemia, which are common issues in CKD, indicating their importance in managing long-term dietary restrictions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Effects of keto/amino acids and a low-protein diet on the nutritional status of patients with Stages 3B-4 chronic kidney disease]. Milovanova, SY., Milovanov, YS., Taranova, MV., et al.[2022]

In a study of 313 children on the ketogenic diet for epilepsy, those who received potassium citrate (Polycitra K) had a significantly lower incidence of kidney stones (2.0%) compared to those who did not receive the supplement (10.5%).

Starting potassium citrate supplementation at the onset of the ketogenic diet resulted in an even lower kidney stone incidence of 0.9%, demonstrating its effectiveness in preventing kidney stones by alkalinizing urine without reported adverse effects.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Empiric use of potassium citrate reduces kidney-stone incidence with the ketogenic diet. McNally, MA., Pyzik, PL., Rubenstein, JE., et al.[2021]

A low-protein diet (0.6-0.8 g/kg ideal body weight/day) supplemented with keto acids is safe and helps preserve residual renal function (RRF) in patients undergoing peritoneal dialysis, as shown in a study of 60 stable patients followed for one year.

In contrast, patients on a low-protein diet without keto acids and those on a high-protein diet experienced a significant decline in RRF, indicating that keto acids may play a crucial role in maintaining kidney function during dialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Better preservation of residual renal function in peritoneal dialysis patients treated with a low-protein diet supplemented with keto acids: a prospective, randomized trial. Jiang, N., Qian, J., Sun, W., et al.[2013]

In a study of 85 patients with chronic kidney disease (CKD), a low-protein diet (LPD) that replaced animal protein with soy protein showed significantly better nephro- and cardioprotective effects compared to a conventional LPD with animal protein over 12 months.

The soy protein diet resulted in less decline in kidney function, lower increases in left ventricular hypertrophy and blood pressure, and better maintenance of lean body mass, indicating it may be a more effective dietary strategy for managing CKD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Soy protein as part of a low-protein diet is a new direction in cardio- and nephroprotection in patients with 3B-4 stages of chronic kidney disease: prospective, randomized, controlled clinical study]. Milovanova, LY., Taranova, MV., Volkov, AV., et al.[2022]

Citations

1. England pubmed.ncbi.nlm.nih.gov

The effect of a ketogenic diet on weight loss in CKD: a randomized controlled trial in obese stage G1-3a CKD patients. [2023]

2. United States pubmed.ncbi.nlm.nih.gov

No additional benefit of prescribing a very low-protein diet in patients with advanced chronic kidney disease under regular nephrology care: a pragmatic, randomized, controlled trial. [2023]

3. United States pubmed.ncbi.nlm.nih.gov

The Effects of Restricted Protein Diet Supplemented With Ketoanalogue on Renal Function, Blood Pressure, Nutritional Status, and Chronic Kidney Disease-Mineral and Bone Disorder in Chronic Kidney Disease Patients: A Systematic Review and Meta-Analysis. [2022]

4. Switzerland pubmed.ncbi.nlm.nih.gov

Ketoanalogue Supplementation in Patients with Non-Dialysis Diabetic Kidney Disease: A Systematic Review and Meta-Analysis. [2022]

5. Switzerland pubmed.ncbi.nlm.nih.gov

Long-Term Effects of Ketoanalogues on Mortality and Renal Outcomes in Advanced Chronic Kidney Disease Patients Receiving a Low-Protein Diet. [2021]

6. Switzerland pubmed.ncbi.nlm.nih.gov

Very Low-Calorie Ketogenic Diet: A Safe and Effective Tool for Weight Loss in Patients With Obesity and Mild Kidney Failure. [2020]

7. United States pubmed.ncbi.nlm.nih.gov

Hypercalcemia in Children Using the Ketogenic Diet: A Multicenter Study. [2021]

8. United States pubmed.ncbi.nlm.nih.gov

Effects of a supplemented hypoproteic diet in chronic kidney disease. [2022]

9. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Effects of keto/amino acids and a low-protein diet on the nutritional status of patients with Stages 3B-4 chronic kidney disease]. [2022]

10. United States pubmed.ncbi.nlm.nih.gov

Empiric use of potassium citrate reduces kidney-stone incidence with the ketogenic diet. [2021]

11. England pubmed.ncbi.nlm.nih.gov

Better preservation of residual renal function in peritoneal dialysis patients treated with a low-protein diet supplemented with keto acids: a prospective, randomized trial. [2013]

12. Russia (Federation) pubmed.ncbi.nlm.nih.gov

[Soy protein as part of a low-protein diet is a new direction in cardio- and nephroprotection in patients with 3B-4 stages of chronic kidney disease: prospective, randomized, controlled clinical study]. [2022]