Kidney Effects of Potassium Additives in Health and Disease

Potassium homeostasis is maintained primarily by the kidney, yet potassium is increasingly recognized not only as a regulated electrolyte but also as a key determinant of renal physiology and kidney health. Experimental, epidemiologic, and clinical evidence supports a reciprocal relationship in which kidney function governs potassium balance, whereas dietary potassium intake and plasma potassium concentration influence renal sodium transport, blood pressure regulation, and susceptibility to kidney injury. Both potassium deficiency and excess are associated with adverse cardiorenal outcomes, emphasizing the importance of maintaining potassium within an optimal physiologic range. Evidence suggests that the kidney adapts to changes in potassium availability through coordinated feedforward and feedback mechanisms, including a putative gut-kidney signaling axis and nephron-intrinsic potassium-sensing pathways. Along the nephron, inwardly rectifying potassium channels function as extracellular potassium sensors that couple changes in potassium concentration to alterations in epithelial transport and metabolism. Recent studies have identified potassium-responsive signaling pathways in the proximal tubule that regulate sodium transport, cellular growth, and kidney injury during potassium deficiency. In the distal convoluted tubule, related mechanisms regulate the thiazide-sensitive sodium-chloride cotransporter through the renal "potassium switch," linking potassium balance to sodium handling and blood pressure control. These mechanistic advances have renewed interest in potassium supplementation and potassium-containing additives as therapeutic interventions. Epidemiologic and emerging clinical data suggest that physiologically appropriate potassium intake, particularly from potassium-rich diets or bicarbonate/citrate-containing supplements, may provide cardiovascular and renal benefits. However, because impaired potassium excretion increases susceptibility to hyperkalemia in advanced chronic kidney disease, potassium supplementation and restriction should be individualized according to kidney function and patient risk.