Abstract P026: The Accumulation Of Lysine In The Kidney Cortex Protects From Proximal Tubule Damage And Salt-Sensitive Hypertension.

Abstract

The kidneys are highly sensitive to metabolic changes. Metabolic phenotyping uncovered a number of pathways associated with high blood pressure and kidney diseases, which sheds light on the complex pathophysiology of hypertension and associated kidney injury. However, the mechanisms underlying the effects of dietary interventions on kidney function and associated changes in cellular metabolic intermediates remain incompletely understood. L-lysine, one of the essential amino acids, is necessary for many physiological functions. Among all organs, the kidney is a key organ in lysine turnover and metabolism, in particular for modified lysines. Our recent metabolomics study revealed that intrarenal levels of L-Lysine are reduced in Dahl salt-sensitive (SS) rats fed an HS diet. This finding provided further evidence that L-Lysine is critical for metabolic states in the kidney. Using a well-established SS rat model of hypertension and kidney injury, we found that administration of lysine at a concentration of 17mg/ml in drinking water counteracted the lysine deficit in kidneys, restored albumin balance, triggered diuresis, and diminished the development of salt-sensitive hypertension (133±2 vs. 165±4 (136±4 vs. 166±7), mmHg in L-Lysine treated rats vs. control rats male (female) after 14 (21) days of an 8 (4) % NaCl diet). HPLC analysis revealed a significant elevation of lysine in the renal cortex of treated rats. In contrast, the concentration of other amino acids, such as glycine and arginine, did not change with increasing blood pressure. Overall, dietary lysine supplementation of SS rats on the HS diet leads to significant protection of proximal tubule damage, shown by Kim-1 immunostaining. Also, it restores kidney function by the rapid excretion of the pathologically accumulated renal albumin and rebalancing megalin abundance. Moreover, the analyses of glomerular damage showed improvement for the lysine treated group. In conclusion, dietary L-Lysine supplementation significantly enhanced cardiorenal protection via acute inhibition of metabolic load and oxidative stress triggered by hypertension.