Autosomal Dominant Polycystic Kidney Disease (ADPKD)
Conditions
Brief summary
Autosomal dominant polycystic kidney disease (ADPKD) is characterized by progressive cyst growth and declining kidney function. Inflammatory pathways, including those mediated by monocyte chemoattractant protein-1 (MCP-1), are increasingly recognized as contributors to disease progression. Metabolic alterations in cystic epithelial cells may influence inflammatory signaling, suggesting a potential role for dietary interventions targeting metabolic pathways. This study is a prospective, randomized, open-label crossover trial designed to evaluate the effect of a carbohydrate restricted, plant dominant dietary intervention on urinary MCP-1 levels in adults with ADPKD. Participants will be randomized to one of two sequences: dietary intervention followed by usual diet, or usual diet followed by dietary intervention, with a washout period between study phases. Each study period will last 12 weeks. The primary objective is to assess within subject differences in urinary MCP-1/creatinine ratio between the dietary intervention and usual diet conditions. Secondary outcomes include measures of metabolic parameters, insulin resistance, dietary adherence, and safety. This study aims to explore whether a structured dietary approach may influence intrarenal inflammatory activity in ADPKD and provide preliminary data to inform future interventional studies.
Interventions
BEHAVIORALCarbohydrate Restricted, Plant Dominant Diet
A structured dietary intervention targeting approximately 20% of total daily energy intake from carbohydrates (range 15-25%), with a plant dominant composition. Energy and protein intake are prescribed based on adjusted body weight. The intervention is not ketogenic and is not intended to induce nutritional ketosis. Participants receive individualized dietary counseling and ongoing support from a registered dietitian.
BEHAVIORALusual diet
Participants continue their habitual diet without specific dietary intervention or structured nutritional guidance.
Sponsors
Assaf-Harofeh Medical Center
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
SINGLE (Investigator)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
Healthy volunteers
No
Inclusion criteria
1. Age ≥18 2. Diagnosis of ADPKD based on established clinical or genetic criteria (PKD 1/PKD2) 3. Estimated glomerular filtration rate (eGFR) between 45 and 90 mL/min/1.73 m² 4. Mayo Imaging Classification class 1C-1E based on MRI-derived height-adjusted total kidney volume. 5. Stable kidney function, defined as no acute kidney injury and no decline in eGFR \>20% within the preceding 3 months 6. Stable antihypertensive and chronic medications for at least 4 weeks prior to enrollment 7. Ability and willingness to adhere to the prescribed dietary intervention 8. Ability to provide written informed consent
Exclusion criteria
1. eGFR \<45 mL/min/1.73 m² or requirement for dialysis 2. History of kidney transplantation 3. Significant albuminuria, defined as urine albumin to creatinine ratio (UACR) \>300 mg/g 4. Poorly controlled or unstable diabetes mellitus (e.g., HbA1c \>8% or clinically significant glycemic variability or frequent hypoglycemia) 5. Use of Tolvaptan at the time of screening or within the study period 6. Current adherence to a ketogenic or carbohydrate restricted diet 7. Unintentional weight loss \>5% within the preceding 3 months 8. Active infection, inflammatory disease, or malignancy that may influence inflammatory markers 9. Current use of systemic corticosteroids or immunosuppressive therapy 10. Active or symptomatic nephrolithiasis 11. Serum bicarbonate \<20 mmol/L 12. Pregnancy or breastfeeding 13. Known eating disorder or condition limiting adherence to dietary interventions 14. Participation in another interventional study within the previous 3 months 15. Any condition that, in the opinion of the investigators, would interfere with study participation or interpretation of results
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change in Urinary MCP-1/Creatinine Ratio | Baseline and End of each 12-week study period (weeks 0,12, 18 and 30) | Urinary MCP-1 levels will be measured in first morning urine samples and normalized to urine creatinine (MCP-1/creatinine ratio). For each study period, two samples will be collected within the final week (2-5 days apart), and the mean value will be used. The primary outcome is the within subject difference in MCP-1/creatinine ratio between the dietary intervention and usual diet conditions. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Association Between Carbohydrate Intake and MCP-1 | Baseline and End of each 12-week study period (weeks 0,12, 18 and 30) | Mean carbohydrate intake during each study period will be calculated from repeated dietary assessments. The association between carbohydrate intake and urinary MCP-1/creatinine ratio will be evaluated to explore a potential dose response relationship. |
| Association Between Change in HOMA-IR and MCP-1 | Baseline and End of each 12-week study period (weeks 0,12, 18 and 30) | The association between changes in insulin resistance (HOMA-IR) and changes in urinary MCP-1/creatinine ratio will be evaluated within individuals across study conditions. |
| Dietary Adherence and MCP-1 Response | Baseline and End of each 12-week study period (weeks 0,12, 18 and 30) | Dietary adherence will be defined as the proportion of dietary assessments in which carbohydrate intake falls within the target range (15-25% of total energy intake). The association between adherence and urinary MCP-1/creatinine ratio will be evaluated. |
| Change in Metabolic and Biochemical Parameters (Safety Outcomes) | Baseline and End of each 12-week study period (weeks 0,12, 18 and 30) | Changes in selected metabolic and biochemical parameters, including serum bicarbonate, LDL cholesterol, and estimated glomerular filtration rate (eGFR), will be assessed between study conditions to evaluate the safety of the dietary intervention. |
Contacts
CONTACTELAD NIZRI, MD
Outcome results
None listed