Novel Concepts in Nephron Sodium Transport: A Physiological and Clinical Perspective

The kidneys play a critical role in maintaining total body sodium (Na⁺) balance across a wide range of dietary intake, accomplished by a concerted effort involving multiple Na⁺ transporters along the nephron. Furthermore, nephron Na⁺ reabsorption and urinary Na⁺ excretion are closely linked to renal blood flow and glomerular filtration such that perturbations in either of them can modify Na⁺ transport along the nephron, ultimately resulting in hypertension and other Na⁺-retentive states. In this article, we provide a brief physiological overview of nephron Na⁺ transport and illustrate clinical syndromes and therapeutic agents that affect Na⁺ transporter function. We highlight recent advances in kidney Na⁺ transport, particularly the role of immune cells, lymphatics, and interstitial Na⁺ in regulating Na⁺ reabsorption, the emergence of potassium (K⁺) as a regulator of Na⁺ transport, and the evolution of the nephron to modulate Na⁺ transport.