the kidneys normally receive 25% of all cardiac output
roles of prostaglandins in the kidneys:
vasodilatory actions:
mainly prostacyclins, PGE2, PGD2 - will act as vasodilators in the afferent arteriole, increasing renal perfusion, with distribution of the cortex flow to the nephrons in the renal medullary region
this is a counter regulation of mechanisms, such as the renin-angiotensin-aldosterone system and that of the sympathetic nervous system to ensure adequate renal perfusion
PGE2 will also inhibit the transport of sodium and chloride in the ascending loop of Henle and in the collecting ducts, by means of stimulating of the EP1 receptor, leading to natriuresis
PGE2 exerts an antagonistic action on the antidiuretic hormone (ADH) receptors, also promoting diuresis
NSAID cyclooxygenase (COX) enzyme inhibition prevents the above actions of prostaglandins resulting in reduce renal perfusion, medullary ischaemia, reduced natriuresis, reduced diuresis and thus may potentially cause salt and water retention
mechanisms of NSAID AKI:
haemodynamically mediated due to inadequate renal perfusion
risk factors:
volume depletion (eg. diuretics or dehydration) + ACEIs + NSAIDs
high dose NSAIDs in the elderly
systemic arterial hypertension, which causes an even higher activation of the renin-angiotensin-aldosterone system (RAAS) and the sympathetic nervous system, leading to vasoconstriction; and the inhibition of prostaglandin synthesis causes the loss of the compensatory mechanism of renal vasodilation
comorbidities that lead to a decrease in effective arterial volume, such as nephrotic syndrome with a high level of proteinuria, liver cirrhosis, especially in those with ascites, heart failure and lupus nephritis.
immune related acute interstitial nephritis, which may manifest as nephrotic proteinuria
in the future this could potentially be diagnosed by finding the protein CXCL-9 in the urine
4)
long-term NSAID use can lead to chronic kidney disease (CKD)
this is mainly dose dependent in those with co-morbidities
in patients without renal disease, young and without comorbidities, NSAIDs are not greatly harmful however care should be given in chronic use
most of the side effects of NSAIDs are related to COX-1 inhibition, individuals with previously compromised renal function are the most affected by the time-dependent use of non-selective NSAIDs rather than Cox-2 inhibitors
however, the action of COX-2 is associated with water and electrolytic maintenance in the renal environment, which worsens its effects under dehydration, low renal perfusion or previously existing renal damage.