Increased Ammoniagenesis as a Determinant of Progressive Renal Injury

Loss of renal mass evokes increased ammoniagenesis in surviving nephrons, which in turn enables net acid excretion by the kidney. However, this compensatory increase in ammonia production in surviving nephrons triggers the alternative complement pathway, thereby instigating progressive tubulointerstitial injury. Ammonia has recently been identified as a stimulus to renal growth. Enhanced renal growth may serve as a forerunner for renal injury. The growth-promoting properties of ammonia may provide another mechanism through which augmented ammoniagenesis may underlie the enhancement of renal growth and injury observed in such models as the remnant kidney, hypokalemic nephropathy, high protein feeding, experimental diabetes nephropathy, and dietary deficiency of antioxidants.