Partial ureteral obstruction (PUO) is a major clinical problem in the daily urologic practice that is treatable and often reversible. It may be acute or chronic, unilateral or bilateral/solitary kidney [1]. PUO leads to the development of renal cell apoptosis, interstitial inflammation, renal fibrosis and loss in renal function, if not treated [2]. The hazardous effects of renal obstruction may persist even after the relief of obstruction, hindering the recoverability of the renal function [3]. Several medications have been shown to enhance the recoverability of the renal function after the relief of PUO, such as selenium, vitamins A, C and E, N-acetylcysteine, melatonin, calcium channel blockers, ß-blockers and lipid-lowering agents [4].

Renin-angiotensin system (RAS) is involved in the pathophysiology of PUO due to the substantial vasoconstriction of the renal vascular bed [5]. Renin enzyme stimulates the conversion of angiotensinogen into angiotensin I which is subsequently converted into angiotensin II by angiotensin-converting enzyme (ACE). Angiotensin II eventually induces alterations in renal hemodynamics, apoptosis, inflammation and fibrosis [6]. RAS can be blocked at different levels by renin inhibitors, ACE inhibitors or angiotensin receptor blockers (ARB). ACE inhibitors and ARB have been clinically used to recover the unfavorable functional and histological changes after relief of PUO [7].

Renin inhibition, however, has been shown to be more effective than ACE inhibitors or ARB in blocking the function of RAS, as these agents may cause a compensatory increase in renin release which might decrease their potential effects [8]. Aliskiren, which is a direct renin inhibitor, has been proven to offer more benefits in the control of hypertension and cardiovascular disorders than ACE inhibitors or ARB [9]. The renoprotective effect of aliskiren has been previously evaluated in many experimental studies, such as renal ischemia/reperfusion injury and drug-induced nephropathy [9].

In the article entitled “Functional and Molecular Evaluation of Using Aliskiren during Acute and Chronic Partial Ureteral Obstruction in Rat Solitary Kidney”, the effect of aliskiren on the renal function during acute and chronic PUO in rat solitary kidney has been discussed [10].

Oxidative stress is a condition related to the imbalance between the increased production of oxygen-derived oxidants, commonly known as reactive oxygen species (ROS), and the antioxidant defenses in the body, results in an increased rate of cellular damage. Overexpression of ROS in PUO can denature proteins, lipids, carbohydrates and other molecules, thus cause apoptosis, inflammation and fibrosis [11].

The mechanism of the kidney damage during PUO is complex and has not been fully understood, but it has been suggested that PUO may induce mechanical stretching of the tubular epithelial cells which secrete pro-apoptotic factors and induce apoptosis of these cells. B-cell lymphoma (BCL)-2, which is a regulatory protein that inhibits apoptosis, has been found to be down-regulated in obstructive nephropathy in rats, but losartan (ARB) up-regulates its expression to attenuate renal tubular cell apoptosis [12]. BCL-2 expression is down-regulated during acute and chronic PUO.

Renal tubular cell apoptosis promotes secretion of exosomes, chemokines and cytokines such as interleukin (IL)-6, that initiate inflammation. During acute and chronic PUO, there is significant up-regulation of IL-6 expression [13]. Inflammation triggers macrophage and monocyte recruitment to the tubulointerstitium which in turn, produces transforming growth factor (TGF)-β1. TGF-β1 is the main factor that activates fibroblasts and induces tissue fibrosis and scarring. TGF-β1 expression is up-regulated during acute and chronic PUO [14].

Tubulointerstitial fibrosis and scarring are eminent features of PUO which emerge when TGF-β1 stimulates the migration and proliferation of fibroblasts and promotes the synthesis and accumulation of extracellular matrix (ECM) proteins such as collagen type I, III and IV, fibronectin and laminin [15]. Collagen type I and fibronectin are indices of tubulointerstitial fibrosis that accumulate during acute and chronic PUO.

During PUO, antioxidant enzyme activity diminishes, ROS production increases, lipid peroxidation occurs and malondialdehyde (MDA) activity increases, as a result. The vascular endothelial cells are affected by the ischemic condition during PUO and increase nitric oxide (NO) formation [16].

Aliskiren administration has been proven to inhibit renal tubular cell apoptosis via up-regulation of BCL-2 expression during acute and chronic PUO. It has also been found to attenuate the inflammatory response during acute and chronic PUO through down-regulation of IL-6 expression. Li et al. also stated that aliskiren inhibits the inflammatory responses, especially IL-1β expression, in the complete bilateral ureteral obstruction in rats [17].

It has been documented that aliskiren down-regulates TGF-β1 expression during acute and chronic PUO. Choi et al. concluded that aliskiren has both anti-inflammatory and antifibrotic effects in a complete uilateral ureteral obstruction (UUO) in a mouse model via down-regulation of TGF-β1 [18].

Aliskiren has been shown to alleviate tubulointerstitial fibrosis via down-regulation of the expression of collagen type I and fibronectin during acute and chronic PUO. The combination of aliskiren and other agents such as ARB and mizoribine, has provided increased protection against renal inflammation and fibrosis in complete UUO in rats [19,20].

Aliskiren has also been found to recover antioxidant enzymes, such as glutathione (GSH) and superoxide dismutase (SOD) to scavenge ROS [21]. Lipid peroxidation has been reduced by aliskiren and MDA activity has been diminished. Aliskiren has been confirmed to attenuate the effects of tacrolimus on MDA in tacrolimus-induced nephrotoxicity in rats [22]. Aliskiren administration has been verified to reduce NO activity during acute PUO and chronic PUO.

Additionally, aliskiren administration for chronic PUO has been shown to offer more renoprotective effects compared to its administration for acute PUO [10].

Aliskiren ameliorates the deterioration of the renal function during acute and chronic PUO. Yet, further studies should be performed before endorsing the use of aliskiren in the clinical practice for the management of obstructive uropathy.