Caloric Restriction for Polycystic Kidney Disease
(EXPLORE Trial)
Recruiting in Palo Alto (17 mi)
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Academic
Recruiting
Sponsor: University of Colorado, Denver
Must not be taking: Weight loss drugs
Disqualifiers: Diabetes, Smoking, Cardiovascular disease, others
No Placebo Group
Trial Summary
What is the purpose of this trial?The proposed research is a pilot study assessing kidney oxidative metabolism and insulin sensitivity after a 2-year weight loss intervention in those with autosomal dominant polycystic kidney disease who are overweight or obese.
Do I have to stop taking my current medications for the trial?
The trial does not specify if you must stop taking your current medications. However, if you regularly use medications that affect weight, appetite, food intake, or energy metabolism, you may be excluded from participating.
What data supports the idea that Caloric Restriction for Polycystic Kidney Disease is an effective treatment?
The available research does not provide specific data supporting the effectiveness of Caloric Restriction for Polycystic Kidney Disease. Instead, it focuses on protein restriction and its effects on chronic kidney conditions. One study mentions that protein restriction has less effect on adult polycystic kidney disease compared to other kidney diseases. Another study highlights the risk of malnutrition with low-protein diets, suggesting that caloric supplements might be necessary. Overall, the research does not directly support Caloric Restriction as an effective treatment for Polycystic Kidney Disease.
12345What safety data exists for caloric restriction in treating polycystic kidney disease?
The safety data for caloric restriction in treating polycystic kidney disease (PKD) is primarily derived from studies on dietary interventions in animal models and human case series. Food restriction has been shown to slow disease progression in mouse models of PKD, with no specific safety concerns reported. A retrospective case series study on ketogenic dietary interventions in PKD patients suggests feasibility and safety, though detailed safety outcomes are not specified. In a study involving overweight or obese PKD patients, daily caloric restriction (DCR) was found to be more effective and better tolerated than intermittent fasting, with no major safety issues reported. Additionally, a study on meal replacements in hemodialysis patients, which included caloric restriction, found the approach to be safe and effective for weight loss, with no significant safety concerns noted. Overall, while these studies suggest that caloric restriction can be safe, more comprehensive clinical trials are needed to fully establish its safety profile in PKD patients.
678910Eligibility Criteria
This trial is for overweight or obese adults aged 18-65 with autosomal dominant polycystic kidney disease (ADPKD) and a body-mass index of 25-45 kg/m^2. Participants must have internet access, not be in other weight loss programs, and have a certain level of kidney function. Exclusions include serious heart conditions, recent significant weight changes, diabetes, substance abuse issues, major psychiatric disorders, inability to undergo MRI scans, smoking history within the past year.Inclusion Criteria
Ability to provide informed consent
I am between 18 and 65 years old.
Not currently participating in or planning to participate in any formal weight loss or physical activity program, or another interventional study
+6 more
Exclusion Criteria
My heart's rhythm is irregular or I have a serious heart condition.
I have lost more than 5% of my weight in the last 3 months, not due to childbirth.
I have diabetes.
+13 more
Trial Timeline
Screening
Participants are screened for eligibility to participate in the trial
2-4 weeks
Baseline Assessment
Participants undergo baseline assessments including PET/CT scan and hyperinsulinemic-euglycemic clamp
1-2 weeks
1 visit (in-person)
Treatment
Participants in the caloric restriction group undergo a 2-year behavioral weight loss intervention
24 months
Regular group sessions (frequency not specified)
Follow-up
Participants are monitored for changes in renal oxygen consumption and insulin sensitivity
4 weeks
Participant Groups
The study tests how daily caloric restriction over two years affects kidney oxidative metabolism and insulin sensitivity in ADPKD patients compared to standard advice control. It's designed as a pilot study where participants are given specific dietary interventions to follow.
2Treatment groups
Experimental Treatment
Group I: Other: Standard Advice ControlExperimental Treatment1 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 RestrictionExperimental Treatment1 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.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
University of Colorado- Anschutz Medical CampusAurora, CO
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Who Is Running the Clinical Trial?
University of Colorado, DenverLead Sponsor
Nutrition Obesity Research CenterCollaborator
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Collaborator
Nutrition Obesity Research CenterCollaborator
References
Adequate protein dietary restriction in diabetic and nondiabetic patients with chronic renal failure. [2022]To evaluate whether a dietary protein restriction is useful for slowing the progression of chronic renal failure (CRF) in diabetic and nondiabetic patients and to analyze the possible risk of malnutrition after such a dietary regimen.
Effect of changes in daily protein intake on renal function in chronic renal insufficiency: differences in reaction according to disease entity. [2018]Protein restriction is advocated in patients with chronic renal insufficiency (CRI) in an attempt to slow down further renal function deterioration, with the most obvious effect in patients with chronic glomerulonephritis (GN) and diabetic nephropathy, and much less in other disease entities, such as adult polycystic kidney disease (APKD), tubulointerstitial nephritis (TIN) and nephrosclerosis (NS). The mechanism by which protein restriction slows down the progression of renal failure remains unclear. Decline of hyperfiltration has been implicated. Whether long-term protein restriction in patients with CRI is associated with a decrease in hyperfiltration is not clear. We studied the effects of prolonged protein intake variation (isocaloric diets in 4-week periods of low (goal: 30-40 g protein daily) and high protein intake (goal: 80-90 g daily) on renal function in 51 patients with CRI. Patients were divided into subgroups according to the underlying renal disease (GN, n = 17; APKD, n = 9; TIN, n = 12; NS, n = 13). Glomerular filtration rate (GFR) and effective renal plasma flow (ERPF) were measured at the end of each study period. Overall, GFR rose from 39 (9-90) to 46 (9-100) ml/min/1.73 m2 (median and ranges, p
Caloric supplements for patients on low-protein diets? [2018]Protein-calorie malnutrition (PCMN) in patients suffering from chronic renal failure treated with a low-protein diet (LDP) is generally considered to be the major adverse effect of such a diet. One cause of PCMN might be that these protein-restricted diets do not supply enough energy, although all of them are supposed to provide at least 35 kcal/kg body weight (BW). In order to test this hypothesis, we analyzed the hypothetical protein and energy intake of a patient on different LPDs. The food intake of such a patient was simulated by analyzing the average composition of 28 complete daily menus. The daily menus simulating 9 dietary schedules (0.3 g protein/kg BW; n = 6; 0.6 g protein/kg BW; n = 3) were taken from 5 different German cookery books. Our analysis revealed that only 2 schedules supplied enough energy. All others were deficient in energy by about 500 kcal/day. The deficiency occurred to the same extent in schedules for diets providing 0.3 and 0.6 g of protein/day. Therefore we conclude that PCMN in patients on LPDs is often due to an insufficient energy supply. The use of less protein-restricted diets does not necessarily prevent PCMN, as also these diets may be low in calories. Thus the use of caloric supplements, e.g. wine or polysaccharides, and correct dietary counseling by a skilled dietitian are recommended.
Optimizing Diet to Slow CKD Progression. [2021]Due to the unique role of the kidney in the metabolism of nutrients, patients with chronic kidney disease (CKD) lose the ability to excrete solutes and maintain homeostasis. Nutrient intake modifications and monitoring of nutritional status in this population becomes critical, since it can affect important health outcomes, including progression to kidney failure, quality of life, morbidity, and mortality. Although there are multiple hemodynamic and metabolic factors involved in the progression and prognosis of CKD, nutritional interventions are a central component of the care of patients with non-dialysis CKD (ND-CKD) and of the prevention of overweight and possible protein energy-wasting. Here, we review the reno-protective effects of diet in adults with ND-CKD stages 3-5, including transplant patients.
Low-protein diets in renal disease. [2019]End-stage renal disease is a major cause of morbidity and mortality in the U.S. population and a significant contributor to national health-care expenditures. In recent years, a growing body of literature has accumulated from studies in animals and humans to suggest that dietary protein restriction can significantly retard the progression of chronic renal insufficiency. This article reviews the relevant literature and outlines the questions that remain for future investigation.
Food Restriction Ameliorates the Development of Polycystic Kidney Disease. [2018]Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by the accumulation of kidney cysts that ultimately leads to loss of renal function and kidney failure. At present, the treatment for ADPKD is largely supportive. Multiple studies have focused on pharmacologic approaches to slow the development of the cystic disease; however, little is known about the role of nutrition and dietary manipulation in PKD. 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, renal fibrosis, inflammation, and injury in a dose-dependent manner. Molecular and biochemical studies in these mice indicate that FR ameliorates ADPKD through a mechanism involving suppression of the mammalian target of the rapamycin pathway and activation of the liver kinase B1/AMP-activated protein kinase pathway. Our data suggest that dietary interventions such as FR, or treatment that mimics the effects of such interventions, may be potential and novel preventive and therapeutic options for patients with ADPKD.
Ketogenic dietary interventions in autosomal dominant polycystic kidney disease-a retrospective case series study: first insights into feasibility, safety and effects. [2023]Our laboratory published the first evidence that nutritional ketosis, induced by a ketogenic diet (KD) or time-restricted diet (TRD), ameliorates disease progression in polycystic kidney disease (PKD) animal models. We reasoned that, due to their frequent use for numerous health benefits, some autosomal dominant PKD (ADPKD) patients may already have had experience with ketogenic dietary interventions (KDIs). This retrospective case series study is designed to collect the first real-life observations of ADPKD patients about safety, feasibility and possible benefits of KDIs in ADPKD as part of a translational project pipeline.
Weight loss and cystic disease progression in autosomal dominant polycystic kidney disease. [2023]Progression of autosomal dominant polycystic kidney disease (ADPKD) is modified by metabolic defects and obesity. Indeed, reduced food intake slows cyst growth in preclinical rodent studies. Here, we demonstrate the feasibility of daily caloric restriction (DCR) and intermittent fasting (IMF) in a cohort of overweight or obese patients with ADPKD. Clinically significant weight loss occurred with both DCR and IMF; however, weight loss was greater and adherence and tolerability were better with DCR. Further, slowed kidney growth correlated with body weight and visceral adiposity loss independent of dietary regimen. Similarly, we compared the therapeutic efficacy of DCR, IMF, and time restricted feeding (TRF) using an orthologous ADPKD mouse model. Only ADPKD animals on DCR lost significant weight and showed slowed cyst growth compared to ad libitum, IMF, or TRF feeding. Collectively, this supports therapeutic feasibility of caloric restriction in ADPKD, with potential efficacy benefits driven by weight loss.
Protein restriction and malnutrition in renal disease: fact or fiction? [2007]The protein and energy requirements of chronic renal failure (CRF) patients are similar to normal subjects and evidence indicates that both nephrotic and nonnephrotic CRF patients can activate normal homeostatic responses allowing them to achieve a neutral nitrogen balance when dietary protein intake is restricted. The benefits of low-protein (and phosphorus) diets (LPDs) include the amelioration of uremia symptoms and some of its metabolic complications and possibly a slowing of the rate of progression of renal failure. When LPDs are prescribed, patients should be monitored to assess dietary compliance and to ensure nutritional adequacy. Recent evidence that the protein intake of patients with progressive CRF decreases when they consume unrestricted diets should not be interpreted as an argument against the use of LPDs. Rather, it is a persuasive argument to restrict dietary protein intake in order to minimize complications of renal failure while maintaining nutritional status.
Meal replacements as a strategy for weight loss in obese hemodialysis patients. [2018]Introduction There is currently limited evidence on the use or safety of meal replacements as part of a low- or very-low-calorie diet in patients with renal insufficiency; however, these are occasionally used under dietetic supervision in clinical practice to achieve the desired weight loss for kidney transplant. This case series reports on the safety and efficacy of a weight loss practice utilizing meal replacements among hemodialysis patients, who needed to lose weight for kidney transplant. Methods Five hemodialysis patients were prescribed a modified low-calorie diet (950 kcal and 100 g protein per day) comprising three meal replacements (Optifast® ), one main meal, and two low-potassium fruits per day. Dietary requirements and restrictions were met for all participants. Dialysis prescriptions, weight (predialysis and postdialysis), interdialytic weight gain, biochemistry, and medications were monitored during the study period for up to 12 months. Findings Participants were aged between 46 and 61 years, and the median time on the low-calorie diet was 364 days. Phosphate binders were temporarily ceased for one participant for reasons unrelated to this program and no other safety concerns were recorded. The low-calorie diet resulted in energy deficits ranging from 1170 kcal to 2160 kcal, and all participants lost weight (median 7% [range 5.2%-11.4%]). The most dramatic weight change appeared to occur by week 12, and declining adherence led to erratic weight change thereafter. Discussion This modified low-calorie diet was safe and effective to use in this population. Meal replacements are a useful weight loss strategy in hemodialysis patients, therefore, offering an alternative to usual weight loss protocols.
Dietary Interventions in Autosomal Dominant Polycystic Kidney Disease. [2023]Autosomal dominant polycystic kidney disease (ADPKD) is characterized by the progressive growth of renal cysts, leading to the loss of functional nephrons. Recommendations for individuals with ADPKD to maintain a healthy diet and lifestyle are largely similar to those for the general population. However, recent evidence from preclinical models suggests that more tightly specified dietary regimens, including caloric restriction, intermittent fasting, and ketogenic diets, hold promise to slow disease progression, and the results of ongoing human clinical trials are eagerly awaited. These dietary interventions directly influence nutrient signaling and substrate availability in the cystic kidney, while also conferring systemic metabolic benefits. The present review focuses on the importance of local and systemic metabolism in ADPKD and summarizes current evidence for dietary interventions to slow disease progression and improve quality of life.
Renal remodelling in dietary protein modified rat polycystic kidney disease. [2006]Dietary protein restriction slows progression of the Han:SPRD-cy rat model of polycystic kidney disease. We undertook studies to examine the relative changes in interstitial and tubular pathology as a result of feeding an 8% casein (LP) diet to Han:SPRD-cy rats. Archival tissue from a previous study comparing LP and 20% casein (NP) diets was examined morphometrically after immunohistochemical or histochemical staining for apoptosis, proliferation antigens, interstitial fibrosis, and macrophage infiltration. Expression of common extracellular matrix genes was measured by Northern analysis. Animals fed LP diet demonstrated reduced tubular epithelial remodelling compared with animals fed NP diet by both proliferating cell nuclear antigen-positive cells (57.5 vs. 71.6 cells/mm epithelium, P=0.007) or apoptosis (31.2 vs. 35.6 cells/mm epithelium, P=0.006). Interstitial pathology demonstrated that LP feeding was associated with proportionately greater reductions in interstitial fibrosis (0.3 vs. 1.3 ml/kg body weight, P=0.003), interstitial cellularity (361 vs. 604 cells/high-power field, P=0.0002), and interstitial macrophages (67 vs. 149 cells/high-power field, P=0. 0002). Northern analysis only revealed significantly lower levels of monocyte chemoattractant protein mRNA (P=0.04) in animals fed the LP diet. Dietary protein restriction modifies both tubule and interstitium, with significant impact upon interstitial inflammation and fibrosis in the Han:SPRD-cy rat.