Acute Kidney Injury

Exam 1, Dr.Wai

KDIGO

• clinical practice guidelines for acute kidney injury

abrupt decline in renal function)<48hrs)

KDIGo definition of acute kidney injury

Stage 1 acute kidney injury

• increase SCr > 0.3 mg/dL OR increase Scr 1.5-1.9x from baseline

• decrease in urine output <0.5ml/kg/hr for 6-12 hours

stage 2 acute kidney injury

• increase SCr 2-2.9x from baseline

• decrease in urine output <0.5ml.kg.hr for >12 hours

stage 3 acute kidney injury

• increase SCr >/= 3x from baseline OR SCr > 4mg/dl OR

• Need for renal replacement therapy (RRT)

• anuria for >12 hours

anuric or oliguric AKI

• patients have increased mortality in comparision to non-oliguric

• less likely to recover renal function

non-oliguric

• urine output >450ml/day

oliguric

• urine output 50-450ml/day

anuric

• urine output <50ml/day

azotemia

• increase in nitrogenous waste products

• BUN, creatinine

uremia

• urea in blood, clinical syndrome resulting from azotemia

• characterized by azotemia, nausea, vomiting, altered mental status

risk factors for AKI

• CKD, diabetes, heart or liver disease, albuminuria, major surgery, acute decompensated heart failure, sepsis, hypotension, volume depletion, medications, advanced age, male, african american

Pre-renal AKI

• decreased renal perfusion without damaged parenchymal tissue

intrinsic AKI

• structural kidney damage, most commonly the tubule from ischemic or toxic insult

• acute tubular necrosis, acute interstitial nephritis

Post renal AKI

• obstructive urine flow downstream from kidney

Stage 2

A 65 yo M with PMH of BPH and lung cancer on cisplatin presents to the ED with complaints of 9/10 abdominal pain. He has been taking ibuprofen “around the clock” for a week for the pain. CT abdomen/chest/pelvis with radiocontrast revealed acute pancreatitis. Two days into his hospital admission his urine output drops to 200 mL/day and his SCr 2.5 mg/dL (baseline 0.9).

Per KDIGO, what stage would you classify his AKI?

oliguric

A 65 yo M with PMH of BPH and lung cancer on cisplatin presents to the ED with complaints of 9/10 abdominal pain. He has been taking ibuprofen “around the clock” for a week for the pain. CT abdomen/chest/pelvis with radiocontrast revealed acute pancreatitis. Two days into his hospital admission his urine output drops to 200 mL/day and his SCr 2.5 mg/dL (baseline 0.9).

How would you classify his urine output?

fractional excretion of sodium (FENa)

• measures % filtered sodium excreted in urine

• used to differentiate etiology of AKI

• (urine sodium x serum creatinine / urine creatinine x serum sodium) x 100

• can be affected by recent diuretic use

(urine sodium x serum creatinine / urine creatinine x serum sodium) x 100

FENa equation

Pre-renal

FENa <1%

Pre-renal or intrinsic

FENa >1% and <2%

intrinsic

FENa >/= 2%

post renal

variable FENa, not a good indicator

intrinsic

Urine analysis for 60 y F with sudden decrease in urine output showed urine Na 62 and urine Cr 28. Blood work showed SCr 1.4 and SNa 132. What is the likely etiology?

pre-renal AKI

• systemic hypoperfusion- overdiuresis (most common)

• isolated renal hypoperfusion

overdiuresis

• most common diagnosis of systemic hypoperfusion pre renal aki

functional AKI

• subtype of pre-renal

• decrease in GFR due to decrease in glomerular hydrostatic pressure

• no direct damge to the kidney

• due to hemodynamic changes

Functional AKI

• diuretics, ACEI/ARB, NSAIDs, calcineurin inhbiitors can cayuse this AKI

loop diuretics

•  block active reabsorption of Na+, K+, Cl at the thick ascending loop of Henle

• cause functional AKI

• intravascular volume depletion → hypoperfusion→ decreased glomerular filtration

thiazide diuretics

• : block active reabsorption of Na+/Cl- at the distal convoluted tubule

• cause functional AKI

• intravascular volume depletion → hypoperfusion→ decreased glomerular filtration

ACEI/ARB

• cause functional pre-renal AKI

• inhibition of angiotensin II

  • vasodilation of efferent arteriole causes decreased intraglomerular rpessure and decreased GFR

  • may see increase in Scr, if SCr <30% then continue

30

when giving ACEI/ARB may see increase in Scr, if SCr <___% then continue

NSAIDs

• account for 37% of drug induced AKI cases

• both COX-1 and COX-2

• rare in healthy patients at therapeutic doses and short term use (7-10days)

• patients with hemodynamic instability and volume depletion at risk; renal perfusion is prostaglandin dependent

• avoid chronic use in high risk: hypoperfusion, age > 65, SCr 1.7, concomitant use with diuretics and ACEI/ARB

NSAID AKI MOA

Inhibits COX-1 and COX-2, which are enzymes that produce renal prostaglandins → vasoconstriction of afferent arteriole

decrease

NSAID effect on GFR

calcineurin inhibitors

• tacrolumus and cyclosporine → immunosuppressants used post transplant

• progression from reversible decrease in GFR to irreversible tubule interstitial injury and glomerulosclerosis

acute reversible nephrotoxicity of calcineurin inhibitors

• cause vasoconstriction of the afferent arteriole

hypercalcemia

• can cause functional AKI due to direct vasoconstriction and natriuresis induced volume contraction

hepatorenal syndrome

• can cause functional AKI

• acute renal failure in patients with severe liver disease

• may be mediated by renal prostaglandins

intrinsic AKI

• direct damage to kidney

• characterized by primary site of damage

tubules

• site of damage in acute tubular necrosis

acute tubular necrosis (ATN)

• most common intrinsic AKI

• ischemic 50%, nephrotoxins 35%

• tubular cells die

• slough into the tubular lumen forming casts, leads to increase in tubular pressure

tubular injury leads to

• loss of urine concentrating ability

• defective distal sodium reabsorption

• reduced GFR

endogenous cause of Acute tubular necrosis

• myoglobin

• hemoglobin

exogenous causes of acute tubular necrosis

• cyclosporine

• amino-glycosides

• radiocontrast media

• cisplatin

• amphotericin B

• foscarnet

• heavy metals

aminoglycoside

• can cause acute tubular necrosis

• incidence 10-25% on a therapeutic dose, typically occurs days 5-7

• critically ill patients incidence -58%

• full kidney function recover> tobramycin > amikacin

aminoglycoside ATN prevention/management

• 0.9% NaCl bolus or continuous infusion

radiocontrast media

• accounts for 10-13% cases of AKI

• develops within 24-48 hours after contrast, usually peaks between days 3-4 and recovers by day 7-10

• some irreversible oluguria AKI requiring dialysis

• etiology= renal ischemia + direct cellular toxicity

• renal ischemia from systemic hypotension and acute vasoconstriction form disrupted prostaglandins and release of vasoconstrictors

radiocontrast induced ATN prevention/management

• 0.9% NaCl pre and post contrast

cisplatin

• used as chemotherapy used in solid tumors

• AKI incidence 33%

• results in impaired tubular reabsorption and decreased urinary concentratoin ability, leading to Na, Mg, and H2O loss <24 hours

• SCr rises at day 3-4, and peaks at days 10-14, recovers by day 21

• kidney damage is dose related and cumulative with subsequent cycles → may become irreversible

management of cisplatin induced AKI

• 0.9% NaCl hydration, lower doses, use alternative like carboplatin

amphotericin B

• causes acute tubular necrosis

• nephrotoxicity incidence- 30% at cumulative doses of 240mg, 80% at doses of 5g

• mechanism

  • direct tubular epithelial cell toxicity from interaction with ergosterol in cell membrane leading to increased tubular cell membrane permeability, lipid peroxidation, and necrosis of proximal tubular cells

  • afferent arteriolar vasoconstriction, leading to reduction in renal blood flow and GFR, and ischemic tubular injury

• liposomal formulation has lower incidence of AKI because enhanced drug delivery and less interaction with tubular epithelial cells

management of amphotericin B induced ATN

• hydrate with 1L 0.9% NaCl before and during, reduce cumulative dose, slow infusion rate, avoid other nephrotoxic drugs

amphotericin B induced AKI monitoring

•   renal function, electrolytes (hypokalemia, hypomagnesemia, hypocalcemia, hyponatremia)

acute interstitial nephritis

• intrinsic AKI with damage to interstitium

85%

• acute tubular necrosis intrinsic AKI instance

10%

• acute intersittial nephritis intrinsic AKI instance

renal vasculature damage

• occulsion of major renal vessel (uncommon intrinsic AKI cause)

• atheroemboli

• thromboemboli

• renal artery thrombosis

acute glomerulonephritis

• 5% of intrinsic AKI

• circulating immune complexes deposit in the glomeruli and cause inflammatory reaction

• ability to filter fluid and solute into tubules while retaining protein and large molecules in intravascular space

immunosuppressants, plasma exchange

• acute glomerulonephritis treatment

acute interstitial nephritis (AIN)

• interstital damage intrinsic AKI

• hypersensitivity immune reaction caused by: drugs, infections, autoimmune diseases, idiopathic causes

• allergic hypersisitivty response

• can be cell mediated (most common) or humoral antibody mediated

acute interstitial nephritis symptoms

• fever

• maculopapular rash

• eosinophilia

• arthraligia

• oliguria

biopsy

acute interstitial nephritis usually required ___ for diagnosis

drug classes that may cause acute interstitial nephritis

• antimicrobials

• diureitcs

• anti-seizure

• NSAIDs

interstitial nephritis management

• reversible with removal of drug or treatment of underlying disorder

• corticosteroids: prednisone 1mg/kg/day for 4 weeks

prednisone 1mg/kg/day for weeks

• corticosteroid treatment for interstitial nephritis

post renal AKI

• caused by obstruction of urine flow

• may occur from pelvis to urethra

• most common causes: BPH, malignacy (prostate or cervical cancer)

foley catheter, ureteroscopy

• post renal AKI management

fluids

• treatment of AKI

• aggressive fluid replacement in dehydrated/volume depleted patients

• caution: CHF, cirrhosis, anuric

dialysis

• may consider ___ for emergent drug removal for treatment of AKI

indications for emergent dialysis

• A- acid base disturbances

• E- electrolyte disturbances

• I- intoxicants/drugs

• O- overload fluid

• U-uremic symptoms (encephalopathy, pericarditis, bleeding)

continuous renal replacement therapy (CRRT)

• hemodynamically unstable AKI-patients cannot tolerate rapid fluid volume removal

• runs continuously over 24 houts a day

• provides a slow consistent removal of solute and fluid over time

prevention of AKI

• assess risk factors:

• pre-existing renal disease

• hepatic disease

• diabetes mellitus

• dehydration

• age

• multiple nephrotoxic drugs

avoid these drugs (nephrotoxins) when possible to prevent AKI

• NSAIDS combined with ACEI or ARBs

• aminoglycosides

• herbals (generally, not regulated by FDA)

• phosphate based bowel preps (oral and enema)

• caution with combination of beta lactams and vancomycin

• proton pump inhibitors should be used with caution

fluid infusion

• prevention strategies with possible benefits to avoid AKI

• KDIGO recommends isotonic crystalloids over colloids

prevention strategies for AKI

• fluid infusion

• sodium bicarbonate infusion

• ascorbic acid

• N-acetylcysteine

cisplatin intrinsic ATN, radiocontrast intrinsic ATN, ibuprofen pre renal or functional AKI, BPH obstructive

 A 65 yo M with PMH of BPH and lung cancer on cisplatin presents to the ED with complaints of 9/10 abdominal pain. He has been taking ibuprofen “around the clock” for a week for the pain. CT abdomen/chest/pelvis with radiocontrast revealed acute pancreatitis. Two days into his hospital admission his urine output drops to 200 mL/day and his SCr 2.5 mg/dL (baseline 0.9).

what are some risk factors and underlying etiology?

urine sodium, SCr, serum Na, to calculate FENa

 A 65 yo M with PMH of BPH and lung cancer on cisplatin presents to the ED with complaints of 9/10 abdominal pain. He has been taking ibuprofen “around the clock” for a week for the pain. CT abdomen/chest/pelvis with radiocontrast revealed acute pancreatitis. Two days into his hospital admission his urine output drops to 200 mL/day and his SCr 2.5 mg/dL (baseline 0.9).

what additional info do you need to determine etiology of AKI?

stop nephrotoxic medicatinos, isotonic fluids (either 0.9% NaCl or lactated ringers)

 A 65 yo M with PMH of BPH and lung cancer on cisplatin presents to the ED with complaints of 9/10 abdominal pain. He has been taking ibuprofen “around the clock” for a week for the pain. CT abdomen/chest/pelvis with radiocontrast revealed acute pancreatitis. Two days into his hospital admission his urine output drops to 200 mL/day and his SCr 2.5 mg/dL (baseline 0.9).

how would you manage the AKI?

SCr, BUN, electrolytes, urine output

 A 65 yo M with PMH of BPH and lung cancer on cisplatin presents to the ED with complaints of 9/10 abdominal pain. He has been taking ibuprofen “around the clock” for a week for the pain. CT abdomen/chest/pelvis with radiocontrast revealed acute pancreatitis. Two days into his hospital admission his urine output drops to 200 mL/day and his SCr 2.5 mg/dL (baseline 0.9).

what should be monitored?:

stay hydrates, stop taking NSAIDs, ask MD for prescription pain meds if APAP doesn’t work

 A 65 yo M with PMH of BPH and lung cancer on cisplatin presents to the ED with complaints of 9/10 abdominal pain. He has been taking ibuprofen “around the clock” for a week for the pain. CT abdomen/chest/pelvis with radiocontrast revealed acute pancreatitis. Two days into his hospital admission his urine output drops to 200 mL/day and his SCr 2.5 mg/dL (baseline 0.9).

what should you counsel the patient?