Tubular function in acute kidney injury

Acute kidney injury (AKI) is characterized by a sudden loss of kidney function, defined by consensus as an increase in serum creatinine and a reduction in urine output. However, current assessments underestimate tubular dysfunction, which can occur during injury. Evidence shows that functional tubular alterations are associated with progression to chronic kidney disease and an increased risk of AKI. The proximal convoluted tubule, responsible for reabsorbing sodium, glucose, and bicarbonate (among other key processes) undergoes mitochondrial damage, oxidative stress, and loss of transporters in AKI, leading to electrolyte imbalances. The loop of Henle, crucial for urine concentration, exhibits reduced activity and develops resistance to diuretics. Meanwhile, the distal tubule impairs potassium excretion and urinary acidification, causing hyperkalemia and acidosis. In different clinical contexts associated with AKI, functional alterations occur in the tubular epithelium. In cardiorenal syndrome, linked to hypoperfusion and neurohormonal activation, there is an increase in sodium and water reabsorption, worsening congestion and tubular damage. In contrast, sepsis-associated AKI involves systemic inflammation and oxidative stress, directly damaging tubular cells, reducing solute reabsorption, and promoting fibrosis. Tubular regeneration is crucial for recovery, but severe or repeated injuries lead to fibrosis and contribute to chronic kidney impairment. Identifying tubular alterations improves our understanding of complete nephron involvement in AKI, guiding the development of strategies to mitigate kidney damage during acute events associated with AKI.