Trigger Warning: How Modern Diet, Lifestyle, and Environment Pull the Trigger on Autosomal Dominant Polycystic Kidney Disease Progression

Nutrients. 2024 Sep 27;16(19):3281. doi: 10.3390/nu16193281.

Abstract

Understanding chronic kidney disease (CKD) through the lens of evolutionary biology highlights the mismatch between our Paleolithic-optimized genes and modern diets, which led to the dramatically increased prevalence of CKD in modern societies. In particular, the Standard American Diet (SAD), high in carbohydrates and ultra-processed foods, causes conditions like type 2 diabetes (T2D), chronic inflammation, and hypertension, leading to CKD. Autosomal dominant polycystic kidney disease (ADPKD), a genetic form of CKD, is characterized by progressive renal cystogenesis that leads to renal failure. This review challenges the fatalistic view of ADPKD as solely a genetic disease. We argue that, just like non-genetic CKD, modern dietary practices, lifestyle, and environmental exposures initiate and accelerate ADPKD progression. Evidence shows that carbohydrate overconsumption, hyperglycemia, and insulin resistance significantly impact renal health. Additionally, factors like dehydration, electrolyte imbalances, nephrotoxin exposure, gastrointestinal dysbiosis, and renal microcrystal formation exacerbate ADPKD. Conversely, carbohydrate restriction, ketogenic metabolic therapy (KMT), and antagonizing the lithogenic risk show promise in slowing ADPKD progression. Addressing disease triggers through dietary modifications and lifestyle changes offers a conservative, non-pharmacological strategy for disease modification in ADPKD. This comprehensive review underscores the urgency of integrating diet and lifestyle factors into the clinical management of ADPKD to mitigate disease progression, improve patient outcomes, and offer therapeutic choices that can be implemented worldwide at low or no cost to healthcare payers and patients.

Keywords: chronic kidney disease; dietary guidelines; disease progression; nutrition; polycystic kidney disease.

Publication types

  • Review

MeSH terms

  • Diabetes Mellitus, Type 2 / etiology
  • Diet* / adverse effects
  • Disease Progression*
  • Humans
  • Life Style*
  • Polycystic Kidney, Autosomal Dominant* / etiology
  • Renal Insufficiency, Chronic / etiology
  • Risk Factors

Grants and funding

This research was funded by grants from the National Institutes of Health (R01DK109563 and R01DK124895) and the United States Department of Defense (W81XWH2010827) to T.W., gifts from the Amy P. Goldman Foundation to support research in T.W.’s laboratory, and a Daryl and Marguerite Erret Discovery Postdoctoral Fellow Award in Biomedical Research to M.M.