# Nutrient intake and renal cancer: molecular pathways and mechanistic insights into the protective role of dietary components

## TL;DR

This review explores how diet affects kidney cancer by focusing on specific molecular pathways and biochemical interactions in the kidney.

## Contribution

The paper introduces a kidney-specific framework linking dietary components to renal cancer through gut-kidney axis and metabolic pathways.

## Key findings

- Dietary components like fermentable fibers and phytochemicals modulate the renal microenvironment.
- Short-chain fatty acids influence renal carcinogenesis via gut-kidney axis and metabolic signaling.
- Nutritional metabolites interface with VHL-HIF and mTOR circuits in kidney cancer progression.

## Abstract

Renal cell carcinoma involves specialized metabolic transformations centered on proximal tubule biology, yet its interface with nutrient intake is frequently interpreted within a generalized oncological framework. This review contextualizes dietary influences within the kidney-specific physiological environment, emphasizing the role of renal filtration dynamics and oxygen-sensing mechanisms in shaping nutrient–tumor interactions. We discuss mechanistic and experimental evidence suggesting that dietary components—particularly fermentable fibers and plant-derived phytochemicals—may function as context-dependent biochemical modulators within the renal microenvironment. Special attention is given to short-chain fatty acids generated by gut microbial fermentation, which may act as distal modulators along the gut–kidney axis and influence metabolic and inflammatory signaling relevant to renal carcinogenesis. By relating circulating nutritional metabolites to proximal tubule metabolic sensitivity and VHL–HIF–dependent regulation, this review aims to bridge systemic nutritional metabolism with metabolic reprogramming characteristic of kidney cancer. Overall, this kidney-centric perspective reframes nutrition from a broad health factor to a context-dependent molecular modulator within renal metabolic pathways, specifically identifying nutritional signals as biochemical modulators—such as short-chain fatty acids—that directly interface with the oncogenic microenvironment through the VHL-HIF and mTOR circuits.

Infographic showing a kidney at the center surrounded by illustrations and text panels about dietary influences on kidney health, including gut-kidney immunomodulation, oxidative stress from processed food, metabolic engineering, angiogenesis, cell proliferation, fiber-rich foods, and key molecular pathways such as AMPK, PI3K/Akt/mTOR, HIF-1α, and NF-κB.