Caloric Restriction for Polycystic Kidney Disease

Overseen By Emily Andrews

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of Colorado, Denver

Must not be taking: Weight loss drugs

Disqualifiers: Diabetes, Smoking, Cardiovascular disease, others

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

Compensation: Varies

Number of Visits: 12

Duration: 24 months

126 Participants Needed

Trial Summary

What is the purpose of this trial?

This clinical trial will determine whether a daily-caloric restriction-based weight loss intervention can slow kidney growth in adults with autosomal dominant polycystic kidney disease who are overweight or obese. The study will also evaluate changes in abdominal fat by magnetic resonance imaging. Blood and fat samples will provide insight into biological changes that may contribute to any observed benefits of the intervention.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you regularly use medications that affect weight, appetite, or energy metabolism, you may need to be weight stable to participate.

What data supports the effectiveness of the treatment Daily caloric restriction for Polycystic Kidney Disease?

Research shows that reducing food intake can slow the growth of kidney cysts in animal models of polycystic kidney disease. In humans, daily caloric restriction has been linked to weight loss and slower kidney growth, suggesting it may help manage the disease. ^{1 2 3 4 5}

Is caloric restriction safe for humans?

Caloric restriction appears to be safe for humans, especially for those who are overweight or obese, as it promotes weight loss and improves metabolic health. However, the long-term safety and effects of caloric restriction in conditions like polycystic kidney disease are still uncertain and require more research. ^{1 3 4 6 7}

How does daily caloric restriction differ from other treatments for polycystic kidney disease?

Daily caloric restriction is unique because it focuses on reducing food intake to slow the growth of kidney cysts, unlike other treatments that are mainly supportive or pharmacological. This approach works by affecting nutrient signaling pathways and has shown promising results in slowing disease progression in preclinical models. ^{1 3 4 8 9}

Research Team

Kristen Nowak, PhD, MPH

Principal Investigator

University of Colorado, Denver

Eligibility Criteria

Adults aged 18-65 with autosomal dominant polycystic kidney disease (ADPKD), overweight or obese, and not currently in weight loss programs can join. They must have internet for video chats, no recent smoking or major surgeries, and their kidneys should be functioning above a certain level.

Inclusion Criteria

Ability to provide informed consent

I am between 18 and 65 years old.

My kidneys are larger than normal, as shown by a recent scan.

Exclusion Criteria

I have diabetes.

You have a problem with drinking too much alcohol or being dependent on it.

I have untreated high cholesterol.

Timeline

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants undergo a 2-year daily caloric restriction-based behavioral weight loss intervention with a 30% reduction in caloric intake and increased physical activity

24 months

Regular group-based sessions

Follow-up

Participants are monitored for changes in kidney growth, abdominal adiposity, and various biomarkers

24 months

Baseline, 12-month, and 24-month assessments

Extension

Optional continuation of monitoring and assessment of long-term effects

Long-term

Treatment Details

Interventions

• Daily caloric restriction

Trial Overview The trial is testing if eating fewer calories each day helps slow down kidney growth in overweight ADPKD patients compared to standard advice. It includes checking belly fat by MRI and analyzing blood and fat samples for biological changes.

Participant Groups

Group I: Standard Advice Control Experimental Treatment 1 Intervention

The standard advice control group will receive an initial consultation with a registered dietician regarding current clinical recommendations for ADPKD without subsequent counseling sessions.

Group II: Daily Caloric Restriction Experimental Treatment 1 Intervention

The daily caloric restriction group will participate in a 2-year, group-based, behavioral weight loss intervention based on a 30% reduction in caloric intake and increased physical activity.

Who Is Running the Clinical Trial?

University of Colorado, Denver

Lead Sponsor

Trials

1,842

Recruited

3,028,000+

Mayo Clinic

Collaborator

Trials

3,427

Recruited

3,221,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Findings from Research

Recent evidence suggests that specific dietary regimens, such as caloric restriction, intermittent fasting, and ketogenic diets, may help slow the progression of autosomal dominant polycystic kidney disease (ADPKD) by influencing nutrient signaling in the kidneys.

The review highlights the potential for these dietary interventions to not only impact kidney health but also provide systemic metabolic benefits, with ongoing human clinical trials expected to provide further insights.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Dietary Interventions in Autosomal Dominant Polycystic Kidney Disease. Pickel, L., Iliuta, IA., Scholey, J., et al.[2023]

A 23% reduction in food intake significantly slowed the progression of autosomal-dominant polycystic kidney disease (ADPKD) in a mouse model, without causing malnutrition or other side effects, indicating a potential dietary intervention for patients.

This dietary restriction effectively suppressed key mTOR signaling pathways involved in cyst growth, suggesting that mild changes in nutrient intake could be a safer and more effective alternative to pharmacological mTOR inhibitors for managing ADPKD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

A mild reduction of food intake slows disease progression in an orthologous mouse model of polycystic kidney disease. Kipp, KR., Rezaei, M., Lin, L., et al.[2021]

Food restriction (FR) in mouse models of autosomal dominant polycystic kidney disease (ADPKD) significantly slows disease progression by reducing cyst area, renal fibrosis, inflammation, and injury in a dose-dependent manner.

The beneficial effects of FR are linked to the suppression of the mTOR pathway and activation of the LKB1/AMPK pathway, suggesting that dietary interventions could be a novel therapeutic approach for managing ADPKD in patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Food Restriction Ameliorates the Development of Polycystic Kidney Disease. Warner, G., Hein, KZ., Nin, V., et al.[2018]

Daily caloric restriction (DCR) and intermittent fasting (IMF) were both feasible for overweight or obese patients with autosomal dominant polycystic kidney disease (ADPKD), with DCR leading to greater weight loss and better adherence.

In a mouse model of ADPKD, only DCR resulted in significant weight loss and slowed cyst growth, suggesting that caloric restriction may be an effective therapeutic strategy for managing ADPKD progression.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Weight loss and cystic disease progression in autosomal dominant polycystic kidney disease. Hopp, K., Catenacci, VA., Dwivedi, N., et al.[2023]

In a study of Han:SPRD-cy rats, a low-protein diet (8% casein) significantly reduced tubular epithelial remodeling and interstitial pathology compared to a normal-protein diet (20% casein), indicating that dietary protein restriction can slow the progression of polycystic kidney disease.

The low-protein diet led to notable decreases in interstitial fibrosis, cellularity, and macrophage infiltration, suggesting that it effectively reduces inflammation and tissue damage in the kidneys of these rats.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Renal remodelling in dietary protein modified rat polycystic kidney disease. Bankovic-Calic, N., Eddy, A., Sareen, S., et al.[2006]

Recent research highlights the potential of dietary modifications as a strategy to prevent or slow the progression of polycystic kidney disease (PKD), alongside emerging drug treatments like vasopressin-receptor agonists.

The review summarizes current evidence on how specific nutrients and dietary patterns may influence cyst growth and disease progression in PKD, suggesting that evidence-based dietary interventions could play a significant role in managing the condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Diet and Polycystic Kidney Disease: Nutrients, Foods, Dietary Patterns, and Implications for Practice. Lambert, K., Gardos, R., Coolican, H., et al.[2023]

Dietary interventions like caloric restriction, intermittent fasting, and ketogenic diets show potential in managing autosomal dominant polycystic kidney disease (ADPKD) by improving metabolic health and reducing oxidative stress, but clinical evidence supporting their effectiveness is limited.

Patients with ADPKD are encouraged to follow personalized dietary guidelines focusing on weight management and specific nutritional restrictions, as the long-term safety and efficacy of these dietary strategies and supplements remain uncertain and require further clinical research.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Polycystic Kidney Disease Diet: What is Known and What is Safe. Chebib, FT., Nowak, KL., Chonchol, MB., et al.[2023]

A low-fat diet significantly slows the progression of renal injury in both male and female pcy mice, as evidenced by reduced kidney weights and serum urea nitrogen levels over a 130-day study.

Diets rich in n-3 fatty acids, particularly flaxseed oil, are more effective in mitigating renal fibrosis compared to diets high in n-6 fatty acids or other n-3 sources, indicating that the type of dietary fat plays a crucial role in kidney health.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Modulation of renal injury in pcy mice by dietary fat containing n-3 fatty acids depends on the level and type of fat. Sankaran, D., Lu, J., Bankovic-Calic, N., et al.[2019]

In a study using a murine model of polycystic kidney disease (PKD), early dietary protein restriction significantly reduced cyst growth, with low protein diets leading to an 11% lower percentage of cyst area and a 46% lower total cyst area compared to normal protein diets.

The type of dietary oil (sunflower seed oil vs. fish oil) did not affect disease progression, suggesting that the amount of protein in the diet is more critical for managing PKD than the type of fat consumed.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Effects of dietary protein restriction and oil type on the early progression of murine polycystic kidney disease. Aukema, HM., Ogborn, MR., Tomobe, K., et al.[2019]

References

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

Dietary Interventions in Autosomal Dominant Polycystic Kidney Disease. [2023]

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

A mild reduction of food intake slows disease progression in an orthologous mouse model of polycystic kidney disease. [2021]

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

Food Restriction Ameliorates the Development of Polycystic Kidney Disease. [2018]

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

Weight loss and cystic disease progression in autosomal dominant polycystic kidney disease. [2023]

5. Germany pubmed.ncbi.nlm.nih.gov

Renal remodelling in dietary protein modified rat polycystic kidney disease. [2006]

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

Diet and Polycystic Kidney Disease: Nutrients, Foods, Dietary Patterns, and Implications for Practice. [2023]

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

Polycystic Kidney Disease Diet: What is Known and What is Safe. [2023]

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

Modulation of renal injury in pcy mice by dietary fat containing n-3 fatty acids depends on the level and type of fat. [2019]

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

Effects of dietary protein restriction and oil type on the early progression of murine polycystic kidney disease. [2019]