-
what is the definition of acute renal failure?
- Serum creatinine increase of 0.5mg/dL from baseline
- or
- a value >1.5mg/dL
-
What is MOST IMPORTANT in prevention and management of ARF?
hydration
-
Which two drugs cause BUN rise but not SCr rise? What is the mechanism?
- corticosteroid use
- tetracycline therapy
- can cause protein catabolism and increase ureagenesis and BUN as a result of tissue breakdown.
- GFR is unchanged.
-
What kind of renal failure can tetracycline cause? why? What would be the lab change?
- pseudo renal failure
- can cause protein catabolism and increase ureagenesis and BUN as a result of tissue breakdown.
- BUN increase but SCr remain the same
-
What kind of renal failure can corticosteroid therapy cause? What would be the lab change?
- pseudo renal failure can cause protein catabolism and increase ureagenesis and BUN as a result of tissue breakdown.
- BUN increase but SCr remains the same
-
Which two drugs cause SCr rise but not BUN? What is the mechanism?
- trimethoprim
- cimetidine
- competitively inhibit secretion of creatinine into proximal tubular lumen, therefore increase SCr
-
What kind of renal failure can cimetidine cause? What would be the lab change?
- pseudo renal failure
- competitively inhibit secretion of creatinine into proximal tubular lumen, therefore increase SCr
- SCr increase but BUN remains the same
-
What kind of renal failure can tetracycline cause? What would be the lab change?
- pseudo renal failure
- competitively inhibit secretion of creatinine into proximal tubular lumen, therefore increase SCr
- SCr increase but BUN remains the same
-
What is pre-renal failure?
- diminshed renal blood flow as a result of intravascular depletion, decreased effective circulating volume to the kidneys, agents that impair renal blood flow
- before the kidneys
-
What is intrinsic (renal) failure?
- damage to the renal parenchyma
- tubular disease, glomerular disease, vascular disease and interstitial disease
-
what is obstructive (post renal) failure?
- urinary tract obstruction
- prostatic hypertrophy
- prostate cancer
- cervical cancer
- retroperitoneal disorders
-
What are implicated drugs for pre-renal failure?
- diuretics
- NSAIDs
- ACE-i
- radiocontrast media
- cyclosporine
- tacrolimus
-
What are the lab findings for pre-renal failure?
- low urine volume
- low sodium excretion
- low/high osmolality and specific gravity (not realy good subjective findings)
-
What is a treatment option for pre-renal failure?
d/c the offending agent
-
What are examples of intrinsic renal failure?
- acute tubular necrosis
- acute and chronic interstitial nephritis
- thrombotic microangiopathy
-
What kind of renal failure is acute tubular necrosis?
what are implicated drugs?
what are the findings?
- intrinsic renal failure
- aminoglycosides, amphotericin B, cisplatin, radiocontrast media, cocaine, IV immunoglobulin
- finding: oliguria, abnormal urinary casts
-
what is the clinical presentation of aminoglycoside nephrotoxicity?
- gradual increase of SCr (and decrease of CrCl) after 6-10 days of therapy
- non-oliguric: maintain urine volume >500 ml/d (patient is still urinating, no decrease volume of urine)
- potential renal Mg and K wasting (high Mg and K in urinalysis)
-
What is the pathogenesis of AG nephrotox?
- cellular dysfunction and death due to release of lysosomal enzymes, reactive oxygen species, altered cellular metabolism, altered cell fluidity
- Proximal tubular epithelial cell damage leads to obstruction of the tubular lumen & backleak of the glomerular filtrate across the damaged tubular epithelium
- Catatonic charge: facilitates binding of filtered aminoglycoside to renal tubular epithelial cell membranes
-
What are the risk factors of AG nephrotox?
- dosing: large dose, prolong therapy, trough >2mg/L, recent past therapy with AG
- synergistic toxicity: cyclosporine, amphotericin B, vancomycin, diuretic
- predisposing conditions: preexisting renal insufficiency, increased age, poor nutrition, shock, gram negative bacteria, liver disease, hypoalbuminemia, obstructive jaundice, dehydration and K or Mg deficiencies
-
How do you prevent AG nephrotox?
- avoid use if possible
- QD dosing when possible
- avoid volume depletion
- limit total AG used
- avoid concomitant thearpy with other nephrotox drugs (i.e. vanco)
- administer agent that decreases binding to phospholipids in kidney: polyaspartic acid, daptomycin, antioxidant
-
what are agents that may help dcrease binding to phospholipids in kidney?
- polyaspartic acid
- daptomycin
- antioxidants
-
How do you manage AG nephrotox?
- d/c or revise dosing in Scr incrase of more than 0.5mg/dL
- if possible, d/c other nephrotoxic drugs
- adequate hydration and stabilize hemodynamics (electrolytes)
-
Is renal failure due solely to AG reversible?
Yes, usually!
-
Radiographic contrast media
what is the clinical presentation?
range of toxicity?
lab changes? when does this resolve?
- toxicity ranges from transient to irreversible
- Scr: Scr rises and peaks between 2-5 days (or as early as 24-72 hrs) after exposure. this resolves 4-10 days
- oliguria: urine volume <500ml/d presents in 50% of cases
-
radiographic contrast media mostly causes nephrotox in which patient population?
most common in diabetic pts with pre-existent renal insufficiency
-
what is pathogenesis of radiographic contrast media for nephrotox?
- direct tubular toxicity (intrinsic way of nephrotox)
- renal ischemia (compromised hemodynamics)
- ----systemic hypotension assoc with contrast inj (overall, renal perfusion is DECREASED)
- ----vasoconstriction
- ----dehydration
- ---- increased blood viscosity
-
what are the risk factors of radiographic contrast media for nephrotox?
- pre-existent renal insufficiency (i.e. diabetic nephropathy)
- conditions associated with decreased blood flow: CHF, dehydration, miltiple myeloma
- large doses: >300ml of 300mg/L
- older agents: high osmolality is worse
-
How do you prevent radiographic contrast media nephrotox? (also any meds to hold and how/when do you hold?)
- assess for risk factors
- use smallest adequate dose
- correct dehydration
- hydrate patient (before and after!): 0.45% NS at 100ml/hr, 4 hours prior and 8-12 hours after
- hold/dc other nephrotox drugs (24-72 hrs before): ACEI, ARB, NSAID, diuretic
- hold metformin 48h prior to CM: only reinitiate when renal fxn is normal
- possible protective agent: dopamine, theophylline, fenoldopam, prostaglandin E, CCB (dihydro)
-
how do you manage radiographic contrast media nephrotox?
- no specific therapy
- care is supportive (hydrate)
- dialysis as needed
- avoid infection and bleeding
-
What is the clinical presentation of cisplatin and carboplatin?
when does it manifest, lab changes etc?
- manifest early
- peak Scr occur at 10-12 days after initiation with recovery by 21 days
- hypomagnesemia (may be severe)
- hypocalcemia and hypokalemia
-
When there is Mg, Ca and K imbalance how do you treat?
treat Mg first and Ca and K usually follow
-
What is the pathogenesis of cisplatin and carboplatin nephrotox?
proximal tubular damage and necrosis
-
Risk factors for cisplatin and carboplatin nephrotox?
- high dose: 200mg/m2older age
- dehydration
- renal irradiation
- concurrent use with AG
- alcohol abuse
-
Which is more nephrotox? cisplatin vs carboplatin, and why?
- cisplatin is more toxic
- carboplatin is more soluble and chemically stable
-
How do you prevent cisplatin and carboplatin nephrotox?
reduce dose and frequency of use
- aggressive saline hydration is important and should be administered to ALL patients
- * 1-4L/24h for cisplatin
- * hypertonic saline used to inc Cl level and dec conversion of cisplatin to reactive platinum species
- * up to 3L/24h for carboplatin
- * furosemide diuresis for volume homeostasis
- * mannitol used to enhance drug dilution
- Amifostine (renal-protective)
- - prodrug and metabolized to sulfhydrol donor
- - administer 15 min prior to cisplat use
-
Is cisplatin and carboplatin nephrotox reversible?
- yes, partially reversible with time and supportive care
- however, progressive chronic RF by cumulative toxicity may not be reversible. some may need chronic dialysis support
-
how do you manage cisplatin and carboplatin nephrotox?
- aggressive hydration
- dialysis
- correct Mg concentration
- (hypocalcemia and hypokalemia may be hard to reverse if hypomagnesemia is not corrected)
-
what is clinical presention of amphotericin B nephrotox?
- decrease in K, Na, Mg
- impaired urine concentrating ability
- distal renal tubular acidosis (increase aciditiy in kidney)
- increase SrCr and BUN
-
what is pathogenesis of amphotericin B nephrotox?
- direct tubular epithelial cell toxicity with increased tubular permeability and necrosis
- arterial vasoconstriction (kind of like pre-renal)
-
what are risk factors for amphotericin B nephrotox?
- baseline renal insufficiency
- increase daily dose (>35mg, >7days)
- diuretic use
- volume depletion
- concomitant administration of other nephrotoxin
- rapid infusion
-
how do you prevent amphotericin B nephrotox?
- limit cumulative dose
- adminsiter liposomal formulation (lipid based allow for increase dose for longer time with less toxicities)
- avoid concomitant nephrotoxin
- hydrate with high sodium diet and 1L IV 0.9% NaCl daily
- pretreat with CCB may be useful (not clinically validated)
-
how do you manage amphotericin B nephrotox?
adminsiter liposomal formulation (lipid based allow for increase dose for longer time with less toxicities)
- d/c therapy (and substitute with anther antifungal)
- focus on prevention
-
is amphotericin B nephrotox irreversible?
some may improve gradually but some may be irreversible
-
when is foscarnet used?
for CMV
-
what is the prevalence of nephrotox for foscarnet?
66%
-
what is the mechanism of foscarnet nephrotox?
how do you treat?
- complex of Ca+ and foscarnet forms and the crystals precipitate in renal glomeruli to cause crystalline glomerulonephritis.
- this develops large pores and necrosis
- may also precipitate in tubules and lead to tubular necrosis
- administer appropriate dose after vigorously pre-hydrating the patient (IV)
-
which agents cause osmotic nephrosis?
- mannitol
- dextran
- IV immunoglobulin
-
Why does renal function decrease in osmotic nephrosis?
how do you prevent?
- due to hypertonic and osmotically active nature of the agents (mannitol, dextran, IV Ig)
- prevent: dilute solution, decrease infusion rate
- hydroxyethylstarch (HES): plasma volume expander,
-
what are risk factors for ACEi and ARB nephrotox?
- severe artherosclerotic renal artery stenosis with SCr >1.6 mg/dL
- patients with decreased renal blood flow (CHF, volume depleted from excess diuresis or GI fluid loss, hepatic cirrhosis, nephrotic syndrome)
- primary renal disease (diabetic nephropathy, Scr >30mg/dL)
-
what is a clinical presentation of ACEi and ARB nephrotox?
increase in SCr
-
what is pathogenesis of ACEi and ARB nephrotox?
- dilates efferent arteriole and reduces glomerular capillary hydrostatic pressure
- ultimately decreases glomerular ultrafiltration and GFR
-
how do you prevent ACEi and ARB nephrotox?
- inpatient: administer low doses of short acting ACEi (i.e. captopril TID) then gradually up-titrate the dose to convert to longer acting agent
- outpatient: start on low dose of long acting ACEi with gradual dose titration
- monitor SCr and K (hyperkalemia)
- ensure hydration (avoid dehydration, hold/dec diuretic prior, counsel on drinking water, not juice etc.)
-
how do you manage ACEi and ARB nephrotox?
- if increase in SCr is <20%: continue
- if increase in SCr is >30%: dec dose by 50% (hold dose in outpatient)
- if patient is on lowest possiblel dose and SCr is increasing for >4wk then d/c
- treat any K+ abnormality
- correct volume depletion if necessary
- hydralazine and nitrate combo to reduce afterload in CHF
-
is damage due to ACEi and ARB nephrotox reversible?
yes, given that flow was not impaired for too long.
-
what is the clinical presentation of NSAIDs nephrotox? how fast does it occur? what is the prevalence?
- renal failure within days of initiation (esp with short acting NSAIDs)
- prevalence up to 40%
- low urine volume
- low sodium concentration in urine
- granular casts may be present in urine
- urine sediment is usually unchanged from baseline
-
what is the first line for osteoarthritis?
- Tylenol
- NOT NSAIDs because no inflammation
-
what is the first line for rheumatoic arthritis?
- NSAID
- because all inflammation
-
do you d/c NSAID if you have kidney stones?
- Nope but you must monitor
- you can give Vicodin
-
what is pathogenesis of NSAIDs nephrotox?
impair renal function by decreasing synthesis of vasodilatory prostaglandins from arachidonic acid so causes vasoconstriction
-
what are risk factors of NSAIDs nephrotox?
- pre-existing renal insufficiency
- medical problems associated with high plasma renin activity
- systemic lupus erythematosus
- artherosclerotic CV disease
- diuretic therapy
- elderly (due to concomitant use of drugs)
- increased doses and prolonged therapy
-
how do you prevent NSAIDs nephrotox?
- low dose and short term therapy (3-5 days)
- recognize high risk patients
- use analgesics with less prostaglandin inhibition (APAP, ASA, nabumetone)
- MONITOR (K, Na, BUN, SCr): baseline and q 3-6mo
- Sulindac may be assoc with less renal tox
-
how do you manage NSAIDs nephrotox?
- d/c therapy
- supportive therapy (volume repletion, treat K abnormality)
-
what do you ask patients using NSAID to prevent renal tox?
- do you see physician often?
- what other medicines do you use?
- use Tylenol if it is possible
-
what is the presentation of cyclosporine and tacrolimus nephrotox? when does it occur?
- usually occurs within 6-12 mo of therapy
- increase in SCr and BUN
- HTN, hyperkalemia, sodium avidity, hypomagnesemia may occur
-
what is the pathogenesis of cyclosporine and tacrolimus nephrotox?
- vasoconstriction and injury to glomerular afferent arterioles
- direct tubular toxicity
-
what are risk factors for cyclosporine and tacrolimus nephrotox?
- increased length of exposure
- older age
- high initial doses
- renal graft rejection
- hypotension
- infection
- concomitant nephrotox drugs
-
how do you prevent cyclosporine and tacrolimus nephrotox?
- this is really difficult
- MONITORING: mostly renal function, not necessarily drug level (this is important because patient is usually on these drugs for a long time)
- CCB may antagonize vasoconstrictor effect of cyclosporine
- decreased doses
-
how do you manage cyclosporine and tacrolimus nephrotox?
- dose reduction or d/c
- treat contributing illness
- d/c interacting drugs
- change of therapy if possible
-
what is the main mechanism of acute interstitial nephritis based on? what kind of renal toxicity is this?
- mainly allergic mechanism
- intrinsic renal
-
what are the implicated drugs for acute interstitial nephritis?
- antibiotics: PCN, cephalo, sulfonamides, amphotericin B
- cocaine
- NSAIDs
- diuretics
- lithium
- ranitidine
- omeprazole
- captopril
- phenytoin, valproic acid
- streptokinase
- 5-ASA
- allopurinol
- rifampin
-
what are the findings in acute interstitial nephritis?
- fever, rash, arthralgia, abnormal urinary cast, WBC and RBC in urine, proteinuria, eosinophilia, eosinophiluria
- (damage in kidneys so all these "uria")
-
how do you treat acute interstitial nephritis?
- d/c offending agent
- if renal failure persists, steroid therapy may be beneficial
- irreversible damage occurs if offending agent is used for >1mo, persistent ARF, delayed response to steroids and increased interstitial granulomas
-
when does penicillin induced acute interstitial nephritis occur? what are symptoms?
- 17 days after initiation
- fever, maculopapular rash, eosinophilia, pyruia, hematuria, low level proteinuria, oliguria
-
when does NSAIDs induced acute interstitial nephritis occur? what is the clinical presentation?
- delayed onset (5.4 mo)
- usually in older patients
- common s&s of allergic reaction is uncommon
- proteinuria >3.5 g/d (higher than PCN-induced)
-
how do you prevent acute interstitial nephritis?
- idiosyncratic in nature
- no specific preventative means known
- recognize s&s early
-
how do you manage acute interstitial nephritis?
- no prospective treatments known
- prednisone 0.5-1mg/kg for 1-4 wk: this is allergic mediated so prednisone may work here unlike other renal toxicity
-
what is lithium-induced chronic interstitial nephritis? when does it usually occur? what is the clinical presentation?
- impaired ability to concentrate urine
- occurs 10 years after treatment
- polydipsia, polyuria
- ATN is common
- patient is usually asymptomatic (if the patient is on lithium, assess hydration during every visit as possible)
- rise in BUN or SCr
- hypertension
- urinalysis (moderate proteinuria, few RBC and WBC, granular cast)
-
what is the pathogenesis of chronic interstitial nephritis induced by lithium?
- impaired ability to concentrate urine is the result of dose related decrease in collecting duct response to anti diuretic hormone
- common during lithium toxicity
-
Is chronic interstitial nephritis induced by lithium reversible?
- irreversible in most cases bbecause takes 10 years to manifest
- damage has already been done
-
what are the risk factors for chronic interstitial nephritis induced by lithium?
- elevated lithium concentration
- dehydration
- concomitant neuroleptics, ACEi
-
how do you prevent chronic interstitial nephritis induced by lithium?
- maintain therapeutic Li concentration
- avoid dehydration
- MONITOR
-
how do you manage chronic interstitial nephritis induced by lithium?
- treat symptoms
- d/c lithium if possible (check with the psych)
- hydrate
-
renal tubular obstruction is what kind of renal toxicity?
post renal
-
what are the implicated drugs in post renal obstruction?
acyclovir, sulfonamide, methotrexate, indinavir, triamterene, high dose vitamin C, methysergide
-
what are the findings in post renal obstruction?
urinary RBC, WBC and crystals
-
how do you treat post renal obstruction?
- d/c offending agent
- volume replacement (IV fluids)
- alkalinization of urine (increase elimination by IV sodium bicarbonate)
-
what kind of renal toxicity is acute uric acid nephropathy?
when does it occur?
why does renal failure occur here?
what is an important lab finding?
how do you prevent?
- post renal
- after chemotherapy
- RF occurs due to obstruction by tissue degradation products
- urine uric acid to creatinine ratio is >1
- pretreat with hydration, urine alkalinization (with sodium bicarbonate IV) and allopurinol may prevent uric acid precipitation
-
what kind of renal toxicity is drug induced rhabdomyolysis?
what does this lead to?
can this lead to renal failure?
what are the risk factors?
- post-renal
- leads to intratubular precipitation of myoglobin
- if severe, this can cause acute RF.
- statins (alone or in combo) with gemfibrozil, niacin, other CYP3A4 inhibitor
- pressure necrosis (coma) so make sure to rotate patient
- abuse of CNS stimulant
-
how does extrarenal urinary tract obstruction occur?
- calculi or retroperitoneal fibrosis can cause ureteral obstruction
- bladder dysfunction with urinary outflow obstruction may result (BPH)
- anticholinergics drugs may cause as well
-
what is nephrolothiasis?
how is GFR affected?
what are the clinical presentation?
what are the causative agents?
- formation of kidney stones. abnormal crystal precipitation in renal collection system
- GFR usually does not decrease
- flank pain, hematuria, infection, urinary tract obstruction with renal insufficiency
- triamterene, sulfadiazine, indinavir, allopurinol, magnesium trisilicate aluminum hydroxide, laxative abuse (all these meds require counseling "drink plenty of water")
-
what are the implicated drugs for CRF?
which ones are reversible and which irreversible?
what are the findings of CRF?
how do you treat?
- reversible: 5-ASA, ifosfamide
- irreversible: lithium, cyclosporine
- also chronic analgesic abuse, cisplatin
- slow and progressive elevation of SCr, electrolyte disturbance, proteinuria
- d/c offending agent
-
what are the implicated drugs for nephrotic syndrome?
what are the findings?
how do you treat?
is this reversible?
- NSAIDs, captopril, gold, penicillamine, interferon
- edema, proteinuria, hypoalbuminuria
- d/c offending agent
- irreversible injury is common
-
What are the most common nephrotoxic agents?
I C 3A Clair
- indinavir
- cyclosporin
- amphotericin B
- aminoglycoside
- acyclovir
- cisplatin
- lithium
- ACEi
- interleukin 2
- IV radiocontrast media
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