Acute Kidney Injury Flashcards
acute kidney injury (AKI) - overview
*comprised of a wide spectrum of clinical syndromes characterized by an abrupt decrease in GFR
*resulting in the accumulation of nitrogenous waste products, including urea and creatinine, as well as other uremic middle molecules and inflammatory components
*decline in urine output can be variable
*no precise correlation exists between changes in sCr levels & GFR
relationship of GFR to steady-state serum creatinine & BUN
*elevation in serum creatinine is apparent only when GFR falls to about 70 mL/min
*early renal disease: slight elevations in sCr → substantial decline in GFR
*late renal disease: large elevations in sCR → small declines in GFR
most used indicators of renal function
*BUN and creatinine
*insensitive and late markers of renal dysfunction
*can also be affected by other confounding factors:
-elevated BUN: GI bleeding, steroids, etc
-elevated sCr: trimethoprim, rhabdomyolysis, etc
other conditions/medications that may increase serum creatinine
*rhabdomyolysis
*cimetidine
*trimethoprim
*probenacid
other conditions/medications that may increase BUN
*GI bleeding
*catabolic states
*high protein diet
*amino acid infusion/TPN
*tetracycline
*steroids
acute kidney injury (AKI) - definitions
*an acute or sustained increase in sCr by 0.5 (if baseline Cr < 2.5) OR an increase in sCr by 20% (if baseline Cr > 2.5)
*an abrupt (within 48 hrs) reduction of kidney function defined by an absolute increase sCr > 0.3 OR other
*RIFLE/AKIN criteria primarily used in research arena
RIFLE criteria for AKI
- renal risk
- renal injury
- renal failure
- renal LOSS
- ESRD (end-stage renal disease)
diagnostic approach to AKI
- review old records (establish a baseline Cr, previous urinalysis/imaging; plot Cr/urine output trend)
- thorough HPI & physical
- examination of URINALYSIS and urine studies
pre-renal acute kidney injury - defined
*clinical syndrome characterized by:
1. reduced renal perfusion
2. preserved renal parenchyma function
3. kidneys respond appropriately to reduced perfusion → Na+ and H2O retention, concentrated urine, LOW urine Na+
pre-renal AKI - pathophysiological mechanisms
*true intravascular hypovolemia
*decreased effective circulatory volume
*intrarenal vasoconstriction
*renal artery disease
autoregulation of GFR: what happens when there is decreased renal perfusion?
*2 mechanisms by which the kidney is able to adapt in order to maintain normal GFR, despite decreased renal perfusion:
- decreased renal perfusion → release of NO and prostaglandins → VASODILATION of AFFERENT arteriole → increased renal blood flow → increased Pgc to maintain GFR
- decreased renal perfusion → release of Ang II → VASOCONSTRICTION of EFFERENT arteriole → maintained GFR
effect of NSAIDs on autoregulation of GFR
*NSAIDs block prostaglandins → not able to vasodilate afferent arteriole → inability to increase renal blood flow to maintain GFR → DECREASE IN GFR
note - this is in patients with decreased renal perfusions on NSAIDs
effects of ACEi/ARBs on autoregulation of GFR
*ACEi/ARBs → inhibit the effect of Ang II on the efferent arteriole → inability to vasoconstrict the efferent arteriole → DECREASE IN GFR
note - this is in patients with decreased renal perfusions on ACEi or ARB
causes of pre-renal AKI: true volume depletion
*renal: diuretic use, diabetes insipidus, osmotic diuresis
*extra-renal: diarrhea, vomiting, pancreatitis, GI bleeding, surgery/trauma, blood loss, burns, third spacing, surgical drains
causes of pre-renal AKI: low effective circulation
*CHF
*cirrhosis
*shock/sepsis
causes of pre-renal AKI: intrarenal vasoconstriction
*hypercalcemia
*contrast dye
*cyclosporine
*tacrolimus
causes of pre-renal AKI: pharmacological
*NSAIDs
*ACEi / ARBs
recall:
1. NSAIDs block prostaglands, preventing vasodilation of the afferent arteriole; effectively, constrict the afferent arteriole → decreased GFR
2. ACEi/ARBs block angiotensin II’s effects, preventing vasoconstriction of efferent arteriole; effectively, dilate the efferent arteriole → decreased GFR
causes of pre-renal AKI: renal artery disease
*renal artery stenosis → decreased renal perfusion → decreased GFR
pre-renal AKI due to true volume depletion - clinical presentation
*history: extracellular fluid loss from skin, GI or renal source
-inquire about recent infections, fever, diarrhea, diuretic use, decreased hydration, orthostatic lightheadedness, thirst
*PE: signs of hypovolemia such as:
-orthostatic hypotension
-tachycardia
-dry mucous membranes
-decreased skin turgor
-no axillary moisture
-oliguria or concentrated urine
pre-renal AKI due to low effective circulation - clinical presentation
*history: heart failure, low cardiac output, cirrhosis
-inquire about SOB, PND, orthopnea, change in weight, edema
*PE: edema, third heart sound (S3 or S4), JVD, pulmonary crackles/effusion
pre-renal AKI diagnosis: serum chemistry findings
*elevated BUN and Cr
*BUN/Cr ratio > 20:1 (low urinary flow allows for increased urea absorption)
*monitor for complications of AKI (hyperkalemia, acidosis)
pre-renal AKI diagnosis: urinalysis
*normal/bland sediment (little to no protein, no blood, no WBCs, no other cellular elements)
pre-renal AKI diagnosis: fractional excretion of sodium (FEna)
*amount of filtered sodium that is actually excreted
*expected to be VERY LOW: FEna < 1%
*note - not helpful if pt is on a diuretic (use FEurea; should be < 35%)
recall: FEna = (Una x Pcr) / (Ucr x Pna) x 100
pre-renal AKI diagnosis: urine studies
*urine sodium: LOW (<20) due to increased proximal reabsorption of Na in response to hypovolemia
*urine Osm: HIGH (>500) due to increased concentration (reabsorption of water in effort to volume expand)
pre-renal AKI - treatment
*key = normalize the effective renal blood flow
*expedient treatment will help minimize the risk of progression of intrinsic renal failure
*if true volume depletion, give fluids
*if CHF, diurese
intrinsic (renal) AKI - defined
*primary lesion is in the kidney
*renal parenchyma is NOT intact; can be:
-vascular/microvascular
-glomerular
-interstitial
-tubular
*unlike pre-renal and post-renal causes, recovery is not expected to be as dramatic with removal of the culprit
acute tubular necrosis (ATN) - overview
*most common cause of intrinsic acute kidney injury in hospitalized patients
*a form of AKI described as acute damage to the renal tubules, usually due to ischemia associated with shock, IV contrast, or excess myoglobin
acute tubular necrosis (ATN) - clinical presentation
*nonspecific signs and symptoms of renal failure
*similar to prerenal symptoms (true volume depletion or low effective circulation)
*also look at:
-episodes of hypertension and recent surgeries
-recent contrast administration
-review meds for nephrotoxins
pre-renal AKI and ATN spectrum
*pre-renal AKI and ATN are two extremes of the same clinical spectrum
*3 causes that can lead to progression from pre-renal AKI to ATN:
1. ischemia: prolonged hypoperfusion, crush injury & trauma, septic shock, pancreatitis
2. endotoxins: uric acid, hemoglobin & myoglobin, immunoglobulin light chains
3. exotoxins: heavy metals (lead), ethylene glycol, contrast dye, antibiotics (ex. ampho)
pathophysiology of ischemic acute tubular necrosis (ATN)
*ischemic ATN is a progression of the prerenal state to a point at which compensatory mechanisms decompensate
1. overwhelming levels of AngII and endothelin-1 causes intense vasoconstriction → further reduction of perfusion
2. increase in inflammatory cytokines potentiates endothelial injury
3. congestion & obstruction of capillaries
4. disruption of actin cytoskeleton → loss of brush border
5. loss of polarity of epithelial cells → failure of tight junctions → backleak of tubular fluid, detached BM
6. apoptosis and necrosis of tubular epithelium
acute tubular necrosis (ATN) - phases
- initiation (OLIGURIC phase):
-inciting event damages tubular epithelial necrosis → blockage of tubular lumen by necrotic debris → reduction in GFR, vasoconstriction, resulting in prolonged ischemia - maintenance:
-ongoing renal failure
-creatinine usually increases slightly per day
*conversion from oliguria → nonoliguria does not improve mortality - recovery (POLYURIC PHASE):
-regeneration of tubular epithelium, but unable to reabsorb H2O and electrolytes
-gradual return of BUN/Cr to baseline or near-normal levels
ATN diagnosis: serum chemistries
*elevated BUN and creatinine
*BUN/Cr ratio < 20:1 (contrast to pre-renal, where ratio is greater than 20)
ATN diagnosis: urine studies
*FEna > 2%
*urine sodium > 40
*urine osmolarity < 350
ATN diagnosis: urine sediment
*classic “muddy brown cast” (GRANULAR CASTS)
ATN diagnosis: renal biopsy
*tubular injury
*flattened tubular epithelium
*sloughed cells
note - we typically do NOT biopsy these patients
acute tubular necrosis (ATN) - treatment
*largely supportive:
-attempt to improve renal perfusion, maintain SBP > 100, avoid nephrotoxic agents, remember to adjust doses of meds for Cr clearance < 10-15
*medical therapy:
-correct volume status, treat electrolyte disturbances, treat acidosis, consider dialysis
contrast urine and serum studies in pre-renal AKI vs. acute tubular necrosis (ATN)
*urine osmolarity (mOsm/kg)
-prerenal AKI: > 500
-ATN: < 350
*urine Na+ (mEq/L):
-prerenal AKI: < 20
-ATN: > 40
*FENa:
-prerenal AKI: < 1%
-ATN: > 2%
*serum BUN/Cr ratio:
-prerenal AKI: > 20:1
-ATN: < 20:1
contrast-induced nephropathy - overview
*subset of ATN injury frequently seen in hospital settings
*pathogenesis: IV contrast → vasoconstriction of renal arteries & direct tubular injury
*risk factors:
-underlying renal insufficiency
-diabetic nephropathy with renal insufficiency
-advanced heart failure
-states of hypoperfusion
-percutaneous coronary interventrions
-high total dose of contrast agent
contrast-induced nephropathy - clinical presentation
*AKI apparent within the first 24-48 hours after contrast study
*non-oliguric with mild decline in renal function
*patients occasionally require dialysis
differentiating contrast-induced nephropathy from atheroembolic disease
ATHEROEMBOLIC DISEASE has the following:
*presence of other embolic lesions (as on the toes) or livedo reticularis
*transient eosinophilia and hypocomplementemia
*onset of renal failure that may be delayed for days to weeks after the procedure
*protracted course with frequently little or no recovery of renal function
contrast-induced nephropathy - diagnosis
*similar to ATN (FENa > 2%, urine Osm < 350, urine Na+ > 40, serum BUN/Cr ratio < 20:1)
*history of recent contrast administration and characteristic rise in creatinine 24-48 hrs later
contrast-induced nephropathy - prevention
*avoid contrast, if possible, in high-risk individuals
*use of nonionic, low osmolal agents
*use lower doses of contrast
*avoid repetitive, closely spaced studies
*avoid volume depletion and NSAIDs
contrast-induced nephropathy - treatment
*VOLUME EXPAND:
-fluids prior to/during/after contrast administration
-ANY type of fluid suffices (saline)
-if volume expansion contraindicated (i.e. CHF), just hold diuretic
atheroembolic disease - overview
*cholesterol crystal embolization occurs when portions of an atherosclerotic plaque break off and embolize distally
*resulting in partial or total occlusion of multiple small arteries (or glomerular arterioles)
*leading to tissue or organ ischemia
*seen after manipulation of the aorta or other large arteries
atheroembolic disease - clinical presentation
*blue toe syndrome
*livedo reticularis
*GI manifestations
*renal failure
*CVA
atheroembolic disease - renal manifestations
*occurs primarily in older patients
*marked AKI with an acute onset, seen within 1-2 weeks of event
*sub-acute presentation: renal dysfunction occurs in staggered steps separated by periods of stable kidney function
atheroembolic disease - diagnosis
*urine: bland urine sediment
-eosinophiluria during active phase
-proteinuria is usually not a prominent feature
*eosinophilia & hypocomplementemia
*definitive dx: biopsy
-skin lesion (if present)
-kidney
pigment-induced ATN - overview
*subset of ATN injury
*seen with rhabdomyolysis:
-associated with marked elevations in CPK
-seen with trauma or statin therapy
pigment-induced ATN - clinical findings
*rapid rise in creatinine, often > 2 mg/L/day
*hyperkalemia
*hyperphosphatemia
*hyperuricemia
*urine dipstick positive for blood BUT NO RBC on urinalysis (picks up myoglobin)
causes of nephrotoxin drug-induced ATN
- aminoglycosides (gentamicin, tobramycin, amikacin)
- amphotericin B
- vancomycin
nephrotoxin drug-induced ATN due to aminoglycosides
*NON-OLIGURIC AKI [5-10 days post-exposure to drug]
*hypomagnesemia
*mechanism of injury: non-protein bound drug filters into glomerulus & cationic properties allow it to be taken into PT → accumulate in lysosomes and interfere with normal cells functions → cell death
*risk factors: high peak serum levels, cumulative dose
nephrotoxin drug-induced ATN due to amphotericin B
*mechanism of injury:
-direct binding to tubular epithelial cells creates PORES → Na+, K+, Mag wasting (directly)
-indirect mech: afferent arteriolar vasoconstriction
nephrotoxin drug-induced ATN due to vancomycin
*synergistic nephrotoxicity (worse when in conjunction with other nephrotoxic meds)
*independent risk factors for nephrotoxicity:
-use of concomitant nephrotoxic agents, age, duration of therapy, etc
acute interstitial nephritis (AIN) - overview
*defines a pattern of renal injury characterized histopathologically by inflammation and edema of the renal interstitium
*a type of intrinsic (renal) AKI
*most commonly caused by:
-drugs (antibiotics, NSAIDs, etc)
-infections (bacterial & viral)
-autoimmune disorders (sarcoid, TINU syndrome)
-idiopathic
acute interstitial nephritis (AIN) - clinical presentations
*nonspecific symptoms (except for drug-induced):
-malaise, anorexia, N/V
-acute or subacute onset
-s/s of AKI
*drug-induced AKI:
-onset within 3 weeks of first exposure or 3-5 days after second exposure
-classic symptoms: RASH, FEVER, EOSINOPHILIA
acute interstitial nephritis (AIN) - diagnosis
*clinical symptoms
*AKI improves with removal of offending agent
*peripheral eosinophilia
*urine is VARIABLE:
-white cells, white cells casts
-urine eosinophils
-sterile pyuria
*definitive = biopsy
acute interstitial nephritis (AIN) - treatment
- drug-induced:
*discontinue offending agent (expect improvement in 3-7 days)
*trial of corticosteroids - non-drug induced:
-treat underlying disease
acute glomerulonephritis & vasculitis - overview
*another cause of intrinsic AKI (rare)
*look at URINE:
-active sediment? RBC casts? proteinuria, hematuria?
-nephrotic vs. nephritic
3 causes of intrinsic (renal) AKI
- acute tubular necrosis (ATN)
- acute interstitial nephritis (AIN)
- acute glomerulonephritis & vasculitis
post-renal AKI - overview
*an impediment of urine flow due to structural or functional obstruction
*resulting in an increase in pressure proximal to obstruction
*obstruction can occur anywhere from the renal pelvis to the tip of the urethra
post-renal AKI - obstructive nephropathy
*when the kidney parenchyma itself if damaged
*functional or pathological changes in the kidney that results from urinary tract obstruction
*obstruction classified based on:
-duration (acute vs. chronic)
-level of obstruction (upper vs. lower tract)
-degree of obstruction (complete vs. partial)
-unilateral vs. bilateral
ureteral causes of post-renal AKI
*intrinsic: crystals, light chain casts, stones, blood clots, papillary necrosis, fungus balls, edema
*extrinsic: gravida uterus, uterine prolapse, uterine tumors, RP fibrosis, RP tumor, radiation therapy
bladder causes of post-renal AKI
*diabetes mellitus
*multiple sclerosis
*spinal cord injury
*anticholinergic agents
urethral causes of post-renal AKI
*posterior urethral valves
*BPH
*diverticula
*strictures
*tumors
*obstructed foley catheters
post-renal AKI - clinical presentation
*VARIABLE, depending on site, duration, and severity
*common symptoms:
-pain
-change in urine output
-palpable mass
-bladder symptoms
diagnosis of post-renal AKI - serum chemistries
*elevated BUN/Cr > 15:1
*FEna > 2-4%
*hyponatremia
*hyperkalemia
note - VARIABLE!!
diagnosis of post-renal AKI - urine studies
*bland sediment
*hematuria (stones, tumors)
*crystals
post-renal AKI - treatment
*relieve obstruction
*depends on level of obstruction & cause
post obstructive diuresis
*commonly seen after relief of severe bilateral obstruction
*polyuria:
-osmotic diuresis caused by retained urea
-volume overload
-tubular concentration defect
compare serum chemistries of pre-renal, intrinsic, and post-renal AKI
*BUN/Cr > 20:1 = prerenal
*BUN/Cr < 20:1 = intrinsic
*BUN/Cr > 25:1 and variable in post-renal
compare urinalysis of pre-renal, intrinsic, and post-renal AKI
*bland sediment: prerenal or post-renal
*epithelial cells & muddy brown casts: ATN
*RBC casts: glomerulonephritis
*WBCs, WBC casts, sterile pyuria: AIN
