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

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial explores whether reducing daily calories can slow kidney growth in individuals with polycystic kidney disease (a condition where cysts develop in the kidneys) who are overweight or obese. The study also examines changes in belly fat using MRI scans and collects blood and fat samples to understand the diet's biological effects. Participants will either follow a calorie-restricted diet with physical activity or receive standard diet advice. This trial may suit someone diagnosed with polycystic kidney disease, who struggles with weight, and has internet access. As an unphased trial, it offers a unique opportunity to contribute to understanding the impact of diet on kidney health.

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 prior data suggests that this caloric restriction intervention is safe for individuals with polycystic kidney disease?

Research has shown that reducing daily calorie intake by about 30% is generally safe for weight loss in people with obesity. Studies have also examined this method for individuals with autosomal dominant polycystic kidney disease (ADPKD) and found it effective for weight loss. Beyond weight loss, these studies aim to determine if eating fewer calories can slow kidney growth in people with ADPKD.

Reducing calories is a common weight loss strategy, and many people tolerate it well. The reviewed studies did not report any serious side effects. However, some individuals might experience mild hunger or fatigue, which is normal when consuming fewer calories.

Participating in such a trial typically involves monitoring by healthcare professionals, which helps manage any potential issues. It is important to consult a healthcare provider to determine if this dietary change suits individual health needs. ^{1 2 3 4 5}

Why are researchers excited about this trial?

Researchers are excited about daily caloric restriction as a treatment for polycystic kidney disease (PKD) because it offers a lifestyle-based approach, rather than relying solely on medication. Unlike traditional treatments that often focus on managing symptoms with drugs like tolvaptan, this method emphasizes reducing caloric intake by 30% and increasing physical activity. This approach could potentially slow disease progression by targeting metabolic changes, offering a new avenue for improving patient outcomes. Additionally, it empowers patients to take an active role in their health management, which could lead to broader benefits beyond the kidney condition itself.

What evidence suggests that daily caloric restriction might be an effective treatment for polycystic kidney disease?

Research has shown that eating fewer calories each day might help slow kidney growth in people with autosomal dominant polycystic kidney disease (ADPKD). Studies with mice have found that reducing food intake by 10% to 40% can decrease the size of kidney cysts. In humans, being overweight or obese is linked to faster kidney growth in ADPKD patients, suggesting that weight loss might help. This trial will compare daily caloric restriction, involving a 30% reduction in caloric intake, with standard advice control. Although tolvaptan is an approved treatment to slow kidney disease progression, it can be expensive. Reducing daily calorie intake offers a possible alternative that could be both effective and more affordable. ^{1 2 6 7 8}

Who Is on the Research Team?

Kristen Nowak, PhD, MPH

Principal Investigator

University of Colorado, Denver

Are You a Good Fit for This Trial?

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

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

Not currently participating in or planning to participate in any formal weight loss or physical activity program, or another interventional study

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 for a Trial Participant

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

What Are the Treatments Tested in This Trial?

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.

How Is the Trial Designed?

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+

Published Research Related to This Trial

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]

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]

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 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]

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]

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]

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]

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]

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]

Citations

1. clinicaltrials.gov clinicaltrials.gov/study/NCT03342742

Study Details | NCT03342742 | Daily Caloric Restriction ... The investigators have novel preliminary data that overweight and obesity are independently associated with substantially faster kidney growth in ADPKD patients ...

2. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC4849816/

Food Restriction Ameliorates the Development of Polycystic ... Here, we show that food restriction (FR) effectively slows the course of the disease in mouse models of ADPKD. Mild to moderate (10%–40%) FR reduced cyst area, ...

3. reporter.nih.gov reporter.nih.gov/project-details/11098556

Daily Caloric Restriction in Overweight and Obese Adults with ... To date, tolvaptan is the only approved intervention to slow kidney disease progression in patients with ADPKD. However, tolvaptan is constrained by high cost ...

4. clinicaltrials.gov clinicaltrials.gov/study/NCT04907799

NCT04907799 | Daily Caloric Restriction in ADPKD This clinical trial will determine whether a daily-caloric restriction-based weight loss intervention can slow kidney growth in adults with autosomal ...

5. sciencedirect.com sciencedirect.com/science/article/pii/S2589004221016679

Weight loss and cystic disease progression in autosomal ... We demonstrate the feasibility of daily caloric restriction (DCR) and intermittent fasting (IMF) in a cohort of overweight or obese patients with ADPKD.

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC11108253/

Polycystic Kidney Disease Diet: What is Known and ... Daily caloric restriction (approximately 30%) is a standard approach to weight loss in obesity. Clinical studies on caloric restriction in patients with ADPKD ...

7. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8760407/

Weight loss and cystic disease progression in autosomal ... Thus, it is plausible that weight loss, caloric restriction, and/or periods of fasting may be beneficial in slowing ADPKD progression in humans.

8. pkdcure.org pkdcure.org/resources/adpkd-weight-loss-study-findings/

ADPKD Weight Loss Study Findings The major takeaway from this work is that both dietary interventions are feasible and result in clinically significant weight loss. Additionally ...