Dietary Modulation of Urinary MCP-1 in ADPKD

Official title

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

Overview

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

• Behavioral Carbohydrate 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.
• Behavioral usual diet
  Participants continue their habitual diet without specific dietary intervention or structured nutritional guidance.

Primary outcome measures

• Change in Urinary MCP-1/Creatinine Ratio [Time frame: Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)]

Secondary outcome measures (4)

• Association Between Carbohydrate Intake and MCP-1 [Time frame: Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)]
• Association Between Change in HOMA-IR and MCP-1 [Time frame: Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)]
• Dietary Adherence and MCP-1 Response [Time frame: Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)]
• Change in Metabolic and Biochemical Parameters (Safety Outcomes) [Time frame: Baseline and End of each 12-week study period (weeks 0,12, 18 and 30)]

Eligibility criteria

Inclusion criteria

• Age ≥18
• Diagnosis of ADPKD based on established clinical or genetic criteria (PKD 1/PKD2)
• Estimated glomerular filtration rate (eGFR) between 45 and 90 mL/min/1.73 m²
• Mayo Imaging Classification class 1C-1E based on MRI-derived height-adjusted total kidney volume.
• Stable kidney function, defined as no acute kidney injury and no decline in eGFR >20% within the preceding 3 months
• Stable antihypertensive and chronic medications for at least 4 weeks prior to enrollment
• Ability and willingness to adhere to the prescribed dietary intervention
• Ability to provide written informed consent

Exclusion criteria

• eGFR <45 mL/min/1.73 m² or requirement for dialysis
• History of kidney transplantation
• Significant albuminuria, defined as urine albumin to creatinine ratio (UACR) >300 mg/g
• Poorly controlled or unstable diabetes mellitus (e.g., HbA1c >8% or clinically significant glycemic variability or frequent hypoglycemia)
• Use of Tolvaptan at the time of screening or within the study period
• Current adherence to a ketogenic or carbohydrate restricted diet
• Unintentional weight loss >5% within the preceding 3 months
• Active infection, inflammatory disease, or malignancy that may influence inflammatory markers
• Current use of systemic corticosteroids or immunosuppressive therapy
• Active or symptomatic nephrolithiasis
• Serum bicarbonate <20 mmol/L
• Pregnancy or breastfeeding
• Known eating disorder or condition limiting adherence to dietary interventions
• Participation in another interventional study within the previous 3 months
• Any condition that, in the opinion of the investigators, would interfere with study participation or interpretation of results

Criteria are shown verbatim from the registry (in English). Final eligibility is always assessed by the study center.

Healthy volunteers: No

Study design

Allocation

Randomized

Model

Crossover

Masking

Single blind

Primary purpose

Basic science

Study locations

Center list to be confirmed — check the primary protocol.

Publications

• Maroni BJ, Steinman TI, Mitch WE. A method for estimating nitrogen intake of patients with chronic renal failure. Kidney Int. 1985 Jan;27(1):58-65. doi: 10.1038/ki.1985.10. PMID 3981873
• D'Alessandro C, Torreggiani M, Lippi F, Avesani C, Cupisti A, Piccoli GB. A Requiem for a Standardized Calculation of Ideal Body Weight in Chronic Kidney Disease? J Ren Nutr. 2026 May;36(3):373-380. doi: 10.1053/j.jrn.2025.12.007. Epub 2026 Jan 15. PMID 41547473
• Bouillanne O, Morineau G, Dupont C, Coulombel I, Vincent JP, Nicolis I, Benazeth S, Cynober L, Aussel C. Geriatric Nutritional Risk Index: a new index for evaluating at-risk elderly medical patients. Am J Clin Nutr. 2005 Oct;82(4):777-83. doi: 10.1093/ajcn/82.4.777. PMID 16210706
• Ryu H, Park HC, Kim H, Heo J, Kang E, Hwang YH, Cho JY, Lee KB, Oh YK, Oh KH, Ahn C. Bioelectrical impedance analysis as a nutritional assessment tool in Autosomal Dominant Polycystic Kidney Disease. PLoS One. 2019 Apr 4;14(4):e0214912. doi: 10.1371/journal.pone.0214912. eCollection 2019. PMID 30947248
• Cederholm T, Jensen GL, Correia MITD, Gonzalez MC, Fukushima R, Higashiguchi T, Baptista G, Barazzoni R, Blaauw R, Coats A, Crivelli A, Evans DC, Gramlich L, Fuchs-Tarlovsky V, Keller H, Llido L, Malone A, Mogensen KM, Morley JE, Muscaritoli M, Nyulasi I, Pirlich M, Pisprasert V, de van der Schueren MAE, Siltharm S, Singer P, Tappenden K, Velasco N, Waitzberg D, Yamwong P, Yu J, Van Gossum A, Comp PMID 30181091
• Irazabal MV, Rangel LJ, Bergstralh EJ, Osborn SL, Harmon AJ, Sundsbak JL, Bae KT, Chapman AB, Grantham JJ, Mrug M, Hogan MC, El-Zoghby ZM, Harris PC, Erickson BJ, King BF, Torres VE; CRISP Investigators. Imaging classification of autosomal dominant polycystic kidney disease: a simple model for selecting patients for clinical trials. J Am Soc Nephrol. 2015 Jan;26(1):160-72. doi: 10.1681/ASN.2013101 PMID 24904092
• Matthews DR, Hosker JP, Rudenski AS, Naylor BA, Treacher DF, Turner RC. Homeostasis model assessment: insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia. 1985 Jul;28(7):412-9. doi: 10.1007/BF00280883. PMID 3899825
• Charles K, Lewis MJ, Montgomery E, Reid M. The 2021 Chronic Kidney Disease Epidemiology Collaboration Race-Free Estimated Glomerular Filtration Rate Equations in Kidney Disease: Leading the Way in Ending Disparities. Health Equity. 2024 Jan 12;8(1):39-45. doi: 10.1089/heq.2023.0038. eCollection 2024. PMID 38250300

Identifiers

NCT: NCT07651397 · 0090-26-ASF

Primary sources (government registries)

• ClinicalTrials.gov (US NIH)

View this study on ClinicalTrials.gov ↗