Abstract
The kidney proximal tubule is a key organ for human metabolism. The kidney responds to stress with altered metabolite transformation and perturbed metabolic pathways, an ultimate cause for kidney disease. Here, we review the proximal tubule's metabolic function through an integrative view of transport, metabolism, and function, and embed it in the context of metabolome-wide data-driven research. Function (filtration, transport, secretion, and reabsorption), metabolite transformation, and metabolite signaling determine kidney metabolic rewiring in disease. Energy metabolism and substrates for key metabolic pathways are orchestrated by metabolite sensors. Given the importance of renal function for the inner milieu, we also review metabolic communication routes with other organs. Exciting research opportunities exist to understand metabolic perturbation of kidney and proximal tubule function, for example, in hypertension-associated kidney disease. We argue that, based on the integrative view outlined here, kidney diseases without genetic cause should be approached scientifically as metabolic diseases. Expected final online publication date for the Annual Review of Physiology, Volume 86 is February 2024. Please see http://www.annualreviews.org/page/journal/pubdates for revised estimates.
| Original language | English |
|---|---|
| Journal | Annual Review of Physiology |
| Volume | 86 |
| Pages (from-to) | 405-427 |
| Number of pages | 23 |
| ISSN | 0066-4278 |
| DOIs | |
| Publication status | Published - Feb 2024 |
Keywords
- AKI
- CKD
- SGLT2
- amino acids
- diabetes
- fatty acid metabolism
- gluconeogenesis
- glycolysis
- ketone body metabolism