Renal function renin-angiotensin system

NSAIDs can cause renal insufficiency when administered to patients whose renal function depends on prostaglandins. Patients with chronic renal insufficiency or left ventricular dysfunction, the elderly, and those receiving diuretics or drugs that interfere with the renin-angiotensin system are particularly susceptible. Decreased glomerular filtration also may cause hyperkalemia. NSAIDs rarely cause tubulointerstitial nephropathy and renal papillary necrosis. 

The ANF hormones, which derive from higher-molecular-weigth precursors (atriopeptigens), have diuretic properties, i.e. an administration of ANF in the rat increases diuresis and natriuresis (the release of Arg-vasopressin is inhibited) and at the same time the vessels are dilated, apparently by inhibition of catecholamines and angiotensin II. In addition, it has been shown that under volume loading the ANF peptides are released from the atria and develop their effects as hormones in renal, vascular, and other tissues. They can be considered as functional antagonists of the renin-angiotensin system. 

Wong, P.Y., Talamo, R.C., Williams, G.H. Kaliikrein-kinin and renin-angiotensin systems in functional renal failure of cirrhosis of the iiver. Gastroenterology 1977 73 1114-1118... 

The pathophysiology of ciclosporin-induced hypertension is complex and not yet fully elucidated. Increased systemic vascular resistance subsequent to altered vascular endothelium function, renal vasoconstriction with reduced glomerular filtration and sodium-water retention, and/or increased activity of the sympathetic nervous system were suggested, while only a minor role or none was attributed to the renin-angiotensin system (10). However, hypertension often occurs before changes in renal function or sodium balance can be demonstrated, and ciclosporin nephrotoxicity alone does not explain ciclosporin-associated hypertension (8,11). 

Rondeau E, Paillard F, Peraldl MN, Violet l,Tasse S, Dussaule JC, Ardaillou R, Sraer JD. Role of the renin-angiotensin system on the renal functional reserve In renal transplant recipients. Kidney Int 1993 44 165-172. 

Workman RJ, Shaff Ml, Jackson RV, Diggs J, Erazer MG, Briscoe C. Relationship of renal hemodynamic and functional changes following intravascular contrast to the renin-angiotensin system and renal prostacyclin in the dog. Invest Radiol 1983 18 160-166. 

Despite these findings, the pathophysiological mechanisms by which AA induce renal interstitial fibrosis remain hypothetic. In the Wistar rat model, pathways leading to interstitial fibrosis seem to be independent of the renin-angiotensin system (RAS), as suggested by experiments where functional and structural renal impairments were not modified eifher... 

The earlier discussion on renal hypertension briefly dealt with the renin-angiotensin system (RAS) (Fig. 10-1). Before considering the several drugs on the market, as well as some others under active consideration, that do or may interfere in some manner with either ACE or renin, it will be useful to survey briefly some present understanding of what the RAS is and what its functions might be. It should be pointed out at the outset that much about this complex system is still not known. 

Many tissues (e.g., brain, pituitary, blood vessels, heart, kidney, and adrenal gland) express mRNAs for renin, angiotensinogen, and/or ACE, and can produce renin, angiotensinogen, ACE, and Angl, 11, and 111. These local renin-angiotensin systems may influence vascular, cardiac, and renal function and structure. 

Marked decreases in blood pressure may affect renal function, and in addition, the renin-angiotensin system plays an important role in the maintenance of the glomerular filtration rate when renal artery pressure is... 

Experiments in animals have found that proliferation of vascular smooth muscle cells can be inhibited by calcitriol administration (Mitsuhashi et al. 1991). An over-active renin-angiotensin system (RAS) can impair renal function and deteriorate cardiovascular health (Li 2012), and down-regulation of RAS activity is one of the key mechanisms proposed for calcitriol (Li et al. 2002). Evidence to support this mechanism has been primarily obtained from animal experiments for example, treatment with calcitriol has been shown to down-regulate RAS and to improve cardiac function in la-hydroxylase knockout mice (Zhou et al. 2008), and in salt-sensitive rats with cardiac hypertrophy (Bae et al. 2011, Choi et al. 2011). However, a recent randomized controlled trial in patients with chronic kidney disease did not find improvements in left ventricular mass index or diastolic function by treatment with paricalcitol (active vitamin D analogue) (Thadhani et al. 2012). 

The role of concomitant medication is not clear due to the lack of good clinical studies [9]. It is recommended to stop nonsteroidal anti-inflammatory drugs, metformin for the risk of lactic acidosis with decreasing renal function, and diuretics. Usually, diuretics used for long-term treatment of hypertension and inhibitors of the renin-angiotensin system should not be discontinued. 

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