Endoplasmic reticulum stress inhibition limits the progression of chronic kidney disease in the Dahl salt-sensitive rat.

Endoplasmic reticulum stress inhibition limits the progression of chronic kidney disease in the Dahl salt-sensitive rat. Am J Physiol Renal Physiol. 2017 Jan 01;312(1):F230-F244 Authors: Yum V, Carlisle RE, Lu C, Brimble E, Chahal J, Upagupta C, Ask K, Dickhout JG Abstract Proteinuria is one of the primary risk factors for the progression of chronic kidney disease (CKD) and has been implicated in the induction of endoplasmic reticulum (ER) stress. We hypothesized that the suppression of ER stress with a low molecular weight chemical chaperone, 4-phenylbutyric acid (4-PBA), would reduce the severity of CKD and proteinuria in the Dahl salt-sensitive (SS) hypertensive rat. To induce hypertension and CKD, 12-wk-old male rats were placed on a high-salt (HS) diet for 4 wk with or without 4-PBA treatment. We assessed blood pressure and markers of CKD, including proteinuria, albuminuria, and renal pathology. Furthermore, we determined if HS feeding resulted in an impaired myogenic response, subsequent to ER stress. 4-PBA treatment reduced salt-induced hypertension, proteinuria, and albuminuria and preserved myogenic constriction. Furthermore, renal pathology was reduced with 4-PBA treatment, as indicated by lowered expression of profibrotic markers and fewer intratubular protein casts. In addition, ER stress in the glomerulus was reduced, and the integrity of the glomerular filtration barrier was preserved. These results suggest that 4-PBA t...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research