NSAIDs and Renal Toxicity

Question 1

how do NSAIDS cause renal toxicity?

Answer 1

NSAIDS inhibit cyclooxygenase (COX). COX is required for prostaglandin synthesis. without prostaglandin synthesis (in diseased states), the reverse of prostaglandins happen:

1. vasoconstriction of afferent arteirole
2. renin inhibition
3. increased tubular Na reabsorption.

patients with low EABV are reliant on prostaglandins. If the prostaglandins are inhibited by NSAIDS, it can cause pre-renal AKI and acute tubular necrosis (ATN)

Question 2

normally, the kidneys rely on __ autoregulation and __ feedback to maintain renal perfusion.

there are times where these forces are inadequeate (ex/ reduced EABV).

Answer 2

normally, the kidneys rely on myogenic autoregulation and tubuloglomerular feedback to maintain renal perfusion.

there are times where these forces are inadequeate (ex/ reduced EABV). Due to hypovolemia, CHF, cirrhosis etc.

Question 3

normally, the kidneys rely on myogenic autoregulation and tubuloglomerular feedback to maintain renal perfusion.

there are times where these forces are inadequeate (ex/ reduced EABV). Due to hypovolemia, CHF, cirrhosis etc.

in these cases, where renal autorefulation is inadequate, prostaglandins are released. they increase blood flow to the kidney _______ to return blood flow back to normal. they also inhibit tubular ___resoprtion and increase ____ release.

Answer 3

in these cases, where renal autorefulation is inadequate, PROSTAGLANDINS are released. they increase BLOOD flow to the kidney by DILATING the AFFERNET ARTERIOLE to return blood flow back to normal. they also inhibit tubular NA+ resoprtion and increase RENIN release.

Question 4

3 functions of renal prostaglandins

Answer 4

• prostaglandins are important in renal disease and are stimulated by decreased EABV.
  1. afferent vasodilation
  2. Inhibits tubular Na+ resorption
  3. increase renin release

Question 5

prostaglandins are important in renal disease and are stimulated by __ __.

Answer 5

prostaglandins are important in renal disease and are stimulated by decreased EABV.

Question 6

NSAIDS inhibit ____ (COX). COX is required for ___ synthesis. without ____ synthesis (in diseased states), the reverse happen:

1. __ of afferent arteirole
2. __ inhibition
3. increased tubular __ reabsorption.

Answer 6

NSAIDS inhibit cyclooxygenase (COX). COX is required for prostaglandin synthesis. without prostaglandin synthesis (in diseased states), the reverse of prostaglandins happen:

1. vasoconstriction of afferent arteirole
2. renin inhibition
3. increased tubular Na reabsorption.

Question 7

NSAIDS + low EABV/predisposition can lead to –> __ __ –> __ __ __

Answer 7

NSAIDS + low EABV/predisposition can lead to –> pre-renal AKI –> Acute tubular necrosis

Question 8

Why should you not give ACEis and NSAIDS at the same time?

Answer 8

ACEis and ARBS reduce intraglomerular pressure and hyperfiltation by blocking angiotensin II which results in dilation of efferent arteriole.

If someone is on ACEis, and we give them NSAIDS, it will cause vasocontriction of the afferent arteriole. since the efferent arteriole is already vasodilated from ACEi, reducing afferent blood flow is a double wammy in terms of overall reduced blood flow to the kidneys. Can result in AKI

Question 9

T/F you cannot give NSAIDS in someone with CKD

Answer 9

TRUE. giving someone with CKD (on ACEis) NSAIDS will have a high likelyhood of precipitating to ACUTE KIDNEY INJURY

Question 10

Question 11

How do NSAIDS cause hyperkalemia

Answer 11

recall that kidneys secrete K+ at CCD hrough the principle cells. regulated by aldosterone which causes K+ secretion.

Recall that NSAIDS inhibit the release of renin, so there will be decreased renin in the body. there will then be decreased aldosterone activation and less K+ secretion. More K+ will stay in the PC/in the blood, causing hy[erkalemia

LOW GFR WILL ALSO EXACERBATE HYPERKALEMIA

Question 12

3 hallmark side effects of NSAIDS

Answer 12

1. hyperkalmiea
2. hypertension
3. Edema

Question 13

How do NSAIDS cause hypertension and edema?

Answer 13

=

NSAIDS → reduced inhibition of tubular sodium reabsorption → increased tubular sodium reabsorption → increased sodium retention → worsening HTN

Question 14

Why can you not give NSAIDS to someone in CHF and cirrhosis (think side effects)

Answer 14

• someone in CHF is probably on ACEis which, when combined with NSAIDS, cause acute kidney injury
• also, CHF and Cirrhosis patients often have ascites/edema due to back flow, and NSAIDS will exacerbate this issue because it increases Na+ and water reabsoprtion.

Question 15

other important condiitons that are exacerbated by NSAIDS:

1. acute intersitial nephritis– mechanism due to allergy to NSAIDS. can occur at any point. Can occur to anyone.
2. nsaids are known to be a cause of nephortic syndrome, and is assocaited with minimal change disease and membranous glomerulopathy.

Answer 15