Role of renin‐angiotensin system in acute kidney injury‐chronic kidney disease transition

Abstract

Acute kidney injury (AKI) can increase the risk of developing incident chronic kidney disease (CKD). The severity, frequency and duration of AKI are crucial predictors of poor renal outcome. A repair process after AKI can be adaptive and kidney recovers completely after a mild injury. However, severe injury will lead to a maladaptive repair, which frequently progresses to nephron loss, vascular rarefaction, chronic inflammation and fibrosis. Although different mechanisms underlying AKI‐CKD transition have been extensively discussed, no definite intervention has been proved effective to block or to retard the transition until recently. In CKD, renin‐angiotensin system (RAS) inhibitor has been proved effective to slow down disease progression. Furthermore, RAS needs to be highlighted again in AKI‐CKD transition because recent animal studies have shown the activation of intra‐renal RAS after AKI, and RAS blockade can reduce the ensuing CKD and mortality. In patients with the complete renal recovery after AKI, administration of RAS inhibitor is associated with reduced risk of subsequent CKD as well. In this article, we will demonstrate the role of RAS in AKI‐CKD transition comprehensively. We will then emphasize the promising effect of RAS inhibitor on CKD prevention in patients recovering from AKI based on evidence from the bench to clinical research. All of these discussions will contribute to the establishment of reliable monitoring and therapeutic strategies for patients with functional recovery from AKI who can be most easily ignored.

Inhibition of IRE1/JNK pathway in HK‐2 cells subjected to hypoxia‐reoxygenation attenuates mesangial cells‐derived extracellular matrix production

“…[27][28][29][30] The possible behind mechanisms include ER stress, incomplete or maladaptive tissue repair, driven fibrosis, inflammation and capillary rarefaction. 8,[31][32][33] The loss of nephron mass and the consequent nephron hyperfiltration can lead to the activation of the renin-angiotensin system, hypertension and the subsequent glomerulosclerosis. [34][35][36] Experimental models have shown that selective epithelial injury could drive capillary sparseness, interstitial fibrosis, glomerulosclerosis and CKD, substantiating a direct role for damaged TEC in disease progression.…”

Molecular Mechanisms of the Acute Kidney Injury to Chronic Kidney Disease Transition: An Updated View

“…Moreover, consequent to altered oxygen availability, tubular injury and necrosis cause tubular dysfunction, oliguria and reduced glomerular filtration via tubulo-glomerular feedback. Thus, after an ischemic injury, the loss of nephronic mass, with remnant nephron hyperfiltration, renin-angiotensin system (RAS) activation, systemic hypertension and subsequent glomerulosclerosis have been described to pave the way from AKI to CKD [18,19,20]. Regardless of the initial insult, evidence of tubular cell loss and replacement by collagen scars and infiltrating macrophages are associated with further renal functional loss and progression towards end stage renal failure.…”

New insights into the pathophysiological mechanisms underlying cardiorenal syndrome

“…Ang II also exerts direct effects on cardiomyocytes by inducing hypertrophy and apoptosis [28,29]. Interestingly, treatment with a RAAS inhibitor has been shown to protect against AKI and cardiac failure [30,31].…”