L‐lysine Control of Albumin Reabsorption by the Renal Proximal Tubule Prevents the Development of Salt‐Sensitive Hypertension
Authors: Levchenko Vladislav , Palygin Oleg , Bukowy John D. , Cowley Allen , El‐Meanawy Ashraf , Staruschenko Alexander 
Published: June 2021

Salt‐induced hypertension is associated with renal and cardiovascular complications and is one of the leading causes of CKD. It is widely accepted that albuminuria is a diagnostic precursor of kidney injury. Despite the significance of renal and cardiovascular diagnostic utility of albuminuria, the events leading to the excessive filtration of albumin into the urine are not well understood. In our study, we want to determine potential mechanism contributing to the development of albuminuria and to attempt restoring albumin balance by inhibiting tubular protein reabsorption.Dahl salt‐sensitive (SS) rats, a widely used model of salt‐induced hypertension, were used to test our hypotheses. When fed a high salt (HS ‐ 8% of NaCl) diet, animals develop progressive elevation in urinary albumin followed by an increase in mean arterial pressure (MAP). Our recent studies using intravital imaging analyses of the kidneys revealed increased loading of proximal tubules (PT) with filtered albumin during the early stages of hypertension (Endres et a., AJP: Renal, 2017). Further progression of the disease is strongly correlated with significant PT damage as indicated by the impaired albumin reabsorption, increased prevalence of granular casts, and necrosis of PT epithelial cells.To prevent PT albumin overload and further development of kidney damage an inhibitor of PT protein reabsorption, L‐Lysine (17 mg/ml), was added to the drinking water on a HS diet. Treatment of SS rats with L‐lysine significantly reduced the progression of salt‐induced hypertension (MAP was 165±4 vs 133±2 mmHg after 14 days on HS in control vs L‐Lysine treated animals). L‐lysine also significantly attenuated the development of albuminuria and promoted serum albumin balance in hypertensive animals (24 hrs Alb/Cre ratios were 1.50±0.25 vs 13.28±2.14 and 6.91±1.07 in SS rats fed a low salt vs HS and HS treated with L‐Lysine, respectively; serum Alb values were 2.98±0.07 vs 2.46±0.08 and 2.86±0.05 g/dL for the same groups). Additionally, we have assessed glomerular injury using a novel automated scoring algorithm that is able to quantify spatial clustering of glomerular injury in histological sections.We conclude that damage to the PT, an essential regulator of albumin handling in the body, contributes to the progression of albuminuria and CKD. Specifically, the salt‐induced increase of renal albumin triggers activation of PT transport and further promotes PT damage due to excessive metabolic load and oxidative stress. The pathological changes in PT function strongly correlate with both elevated urinary albumin and the reduction of serum albumin during the development of hypertension in SS rats. The inhibition of PT reabsorption by L‐lysine restores albumin balance and diminishes the development of salt‐sensitive hypertension and kidney injury. Dietary supplement of L‐lysine could be used as a drug therapy to decrease microalbuminuria, thereby alleviating the symptoms of CKD, preventing or delaying the development of hypertension.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.