Dietary Modulation of Urinary MCP-1 in ADPKD

Open Labeled , Randomized, Controlled, Crossover Trial on the Effect of a Carbohydrate Restricted Plant Dominant Diet on MCP-1 Mediated Inflammatory Signaling in Autosomal Dominant Polycystic Kidney Disease

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.

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