RENAL 2- Babos- Drug induced renal injury and drugs in renal impairment

Aldosterone antagonist
spirolactone
ACEi
ARB
Renin antagonist: aliskiren
K sparing diuretics
Eplerenone

Mependine (demerol)

neuromuscular blockade
ototoxicity

Hydrophilicity
Low plasma protein binding
Ionized at physiologic pH

rapid loss of kidney function
hours to weeks
Defined by 50% increase in SCr (> 0.5 g/dL)

also called chronic renal insufficiency, progressive kidney disease
progressive loss of function
months to years
gradual replacement of normal kidney architecture with interstitial fibrosis

Pseudofailure/pseudoinjury
Prerenal azotemia
Acute functional renal failure
Intrinsic acute renal failure
Postrenal

drugs cause interference with measurement of BUN and/or creatinine (Case I)

inability to perfuse kidney
OFTEN A PERIOPERATIVE PROBLEM

altered renal hemodynamics lead to decreased filtration (Case II and III)

damage to glomerulus, tubules, interstitium

obstruction to outflow

DI at LDT, use thiazide for TX

Pseudofailure – medications increase measurement of BUN or serum creatinine
no harm to kidney
-BUN
Steroids
Tetracyclines
-Creatinine
FYI Cimetidine
Trimethoprim
Cephalosporins in older creatinine assay methods

Acute Functional Failure – alteration of hemodynamics leads to reduction in filtration
ACEI/ARB
NSAIDs
Radiocontrast media
FYI Cyclosporine
FYI Tacrolimus

INcrease vasodilation of Aff, due to PG
and constriction of efferent by A2

Dilate effernt and decrease filtration P. by PGi

Constrict affernt and dilate efferent
Worst case scenerio

Recognize high-risk patients

Hydration!

Use analgesics with less PG inhibition (acetaminophen, aspirin, non-acetylated salicylates NOTE: low dose aspirin is unlikely to be problematic!!)

Initiate ACEIs and Ang II blockers at low doses in high-risk patients

Monitor renal function in high-risk patients requiring NSAIDs or ACEIs

Make sure patient is hydrated at initiation
Consider withholding diuretic until Cr stable
Expect ↑Cr up to 25% initially
In CKD, if acute-on-chronic develops, hold and re-initiate when renal parameters stabilize
In high risk patients – go low go slow
Bilateral renal arterial stenosis, renal vessel dz, prerenal, concomitant NSAIDs
ADE: hyperkalemia; ACEI angioedema, cough

aggressive diuresis, antihypertensives, anesthesia, vasopressors, drugs that induce clots, radiocontrast

ATN: aminoglycosides, radiocontrast, platinum containing cytotoxics, amphotericin, PPI; ATN is most common, due in part to high O2 demand of tubules!!!
Glomerular damage: NSAIDs, Gold salts, lithium, phenytoin
Tubulointerstitial: phosphates
Allergic nephritis: NSAIDs, penicillins
Chronic interstitial nephritis: analgesics, cyclosporin

Tubule obstruction: methotrexate, statins, sulfonamides, ascorbic acid, indinavir, allopurinol

non-oliguric failure via ATN
Inhibit lysosomal hydrolases, causing phospholipidosis and rupture of lysosome

MONITOR TROUGH AND RENAL PARAMETERS
Cr change will not occur for DAYS after damage
Slow recovery may occur
Use lowest dose for shortest possible duration
Pulse-dosing?
HYDRATION!!!!!

acute functional renal failure and/or structural damage

Renal disease
High renin states
SLE
Concomitant nephrotoxins
ACEI/ARB

AVOID NSAIDs in high risk if possible!!!
Initiate ACEI/ARB with caution
Monitor renal indices in high risk or with other nephrotoxins

Acute functional renal failure, occasionally with acute tubular necrosis

Diabetes
Underlying renal insufficiency (GFR<60ml/min)

Increase in Scr in 2-5 days, decreased FeNa and UNa, possibly casts in urine

HYDRATION
N-acetylcysteine
Bicarbonate?
Use of non-ionic low osmolal agents?

N-acetylcysteine

Calcium oxalate and phosphate
Treat with hydration, thiazide diuretics
Struvite (Mg NH4+ PO4)
Tend to recur; lithotripsy
Urate
Will increase risk: probenecid
Cysteine
Drugs:
Sulfonamides, acyclovir, indinavir, methotrexate, triamterene, vitamin C