Proximal Tubule Hypertrophy and Hyperfunction: A Novel Pathophysiological Feature in Disease States

The role of proximal tubules, a major component of the renal tubular structure located at the renal cortex, in healthy and diseased states has been examined extensively. Along with its physiological role in the reabsorption of various molecules, including electrolytes, amino acids and monosaccharides, transcellular transport of different hormones and regulation of homeostasis, pathological events affecting proximal tubules may underlie multiple disease states. Proximal tubular hypertrophy or hyper-functioning state, despite being a compensatory mechanism at first in response to various stimuli or alterations at tubular transport proteins, have shown to be critical pathophysiological events leading to multiple disorders, including diabetes mellitus, obesity, metabolic syndrome, congestive heart failure. Moreover, pharmacotherapeutic agents have primarily targeted proximal tubules, including sodium-glucose cotransporter-2, urate transporters and carbonic anhydrase enzyme. In this narrative review, we focus on the physiological role of proximal tubules in healthy states and the current understanding of the proximal tubular pathologies leading to disease states and potential therapeutic targets.