Acute Kidney Injury

Moises Auron MD, FAAP FACP

Assistant Professor of Medicine and Pediatrics

January 28, 2010

 Outline
• Definition
• Etiology and Clinical Presentation
• Diagnosis
• Treatment
 Definition
• Acute Kidney Injury Network (AKIN)
– AKI - represent the entire spectrum of acute
renal failure
• RIFLE Classification
– three levels of injury (Risk, Injury, and Failure)
– two outcome measures (Loss and ESRD)

Critical Care. 2007, 11(2):R31

 RIFLE Criteria

Limitations:
• Change in creatinine may not
correlate with change in GFR
• Need to know baseline
creatinine.
• No correlation between U/O
and Screat levels
•Should exclude U obstruction

(Acute Dialysis Quality Initiative (ADQI) Group). Critical Care. 2004;8(4):R204-12.

• Abrupt (< 48 h) absolute increase in the
serum creatinine concentration of ≥0.3
mg/dL from baseline
• Increase in the serum creatinine ≥ 50 %
• Oliguria < 0.5 mL/kg per hour for > 6 hrs.

Critical Care. 2007, 11(2):R31

GFR and Creatinine

Dennen P. Crit Care Med 2010; 38(1):261–275

 Epidemiology
• Upon admission to hospital – 1%
• During hospitalization – 2-5%
• After Cardiopulmonary bypass. – 5-15%

Thadhani R. NEJM. 1996;334(22):1448-60

 Etiology
• Prerenal (40-80% cases)
– Volume depletion
• Blood loss: surgery, trauma, gastrointestinal or
genitourinary bleeding
• Gastrointestinal: vomiting, diarrhea
• Urinary (diuretics, diabetes insipidus)
• Cutaneous losses (burns, fever)
– Decreased Arterial Blood Pressure
• Low Cardiac output
• Cardio renal syndrome type 1
• Sepsis/shock
• Hepatorenal syndrome
• Drugs: ACEI, NSAIDS

Thadhani R. NEJM. 1996; 334:1448–1460

Etiology of low perfusion states

Abuelo JG. NEJM. 2007;357(8):797-805.

Hepatorenal Syndrome

Garcia-Tsao G. HEPATOLOGY 2008;48:2064-2077.

Gines P. N Engl J Med 2009;361(13):1279-90.
AKI in Cirrhosis

Garcia-Tsao G. HEPATOLOGY 2008;48:2064-2077.

Gines P. N Engl J Med 2009;361(13):1279-90.
Cardiorenal Syndrome Type 1

Shamseddin MK. Nat Rev Nephrol. 2009;5:641–649.

Ronco C. European Heart Journal e-pub Dec 25, 2009. doi:10.1093/eurheartj/ehp507
Sepsis and AKI

Schrier RW. NEJM 2004;351(2):159-69.

 Etiology
• Renal (5-15%)
– Vascular
• Thrombosis (arterial and venous)
– Cholesterol emboli (post-intervention)
• Renal artery stenosis
• Hemolytic-uremic syndrome
• Malignant hypertension
• Vasculitis (Wegener’s, SLE, PAN, MPA).
• Scleroderma
– Glomerular
• Acute glomerulonephritis: vasculitis, post-infectious (Streptococcus).
– Tubular and interstitial disease
• Acute tubular necrosis (ATN) – ischemia or injury from tubular nephrotoxins
• Nephrotoxic agents: aminoglycosides, amphotericin B, contrast agents
• Rhabdomyolysis
• Tumor lysis syndrome
• Acute interstitial mephritis – Eosinophiluria, drug hypersensitivity
• Nephrolithiasis

Thadhani R. NEJM. 1996; 334:1448–1460

http://path.upmc.edu/cases/case51/dx.html
Ischemic Acute Tubular Necrosis

Abuelo JG. NEJM. 2007;357(8):797-805.

Contrast Induced AKI

Abu Jawdeh BJ. J Hosp Med. 2009;4:500–506.

Solomon R. Radiol Clin N Am. 2009;47:783–788
Rhabdomyolysis

Bosch X. NEJM. 2009;361(1):62-72.

Etiology of AKI in the ICU

Dennen P. Crit Care Med 2010; 38(1):261–275

Acute interstitial nephritis

Needham E. Am Fam Physician 2005;72:1739-46.

 AKI and Metabolic Acidosis
• Anion Gap Metabolic Acidosis
– Normal osmolal gap: salicylate and
paraldehyde
– Increased osmolal gap: methanol,
ethanol, isopropyl alcohol and ethylene
glycol
• Ethylene-glycol: calcium oxalate crystals

http://www1.nasa.gov/centers/marshall/news/background/facts/renal.html
 Etiology
• Postrenal (10-30%)
– Bilateral urinary tract obstruction
• PUV (children)
• BPH
• Retroperitoneal malignancies
• Urethral strictures
• Nephrolithiasis
• Catheters
• Neurogenic bladder

Thadhani R. NEJM. 1996; 334:1448–1460

British Journal of Radiology.2002;75:177-179
Anderson RJ. Best Pract Res Clinical Anaesth. 2004;18(1):1–20.
Luyckx VA. Nat Clin Pract Nephrol. 2008;4(12): 664-71.
 Diagnosis

Anderson RJ. Best Pract Res Clinical Anaesth. 2004;18(1):1–20.

 Creatinine and drugs
• Inhibition of secretion of creatinine by the proximal tubule
– Cimetidine
– Trimethoprim
– Pyrimethamine
– Salicylates

• Modification of the production rate and the release of

creatinine:
– Corticosteroids
– Vitamin D metabolites

• Unclear:
– phenacemide

Andreev E. J Int Med 1999; 246: 247-52.

Diagnosis: Urinary Indices

Fe Urea % <35 50 – 65
Fe Uric Acid % <7 >15
Fe Lithium % <7 >20

Esson ML. Ann Intern Med. 2002;137:744-752.

Anderson RJ. Best Pract Res Clinical Anaesth. 2004;18(1):1–20.
 Calculation of FENa

                      UNa   x   PCr
FENa (%) =            x    100
                      PNa   x   UCr
Diagnosis: Urinary sediment
x400 x400

Perazella, MA. CJASN ePress. Jan 14 2010 as doi: 10.2215/CJN.06960909

Esson ML. Ann Intern Med. 2002;137:744-752.
 Diagnosis: Urinary sediment

Hansel stain

http://missinglink.ucsf.edu/lm/IDS_102_cases_glomerular/Nephritic_syndrome.htm
Kaye M. Kidney International (2008) 73, 980.
Diagnosis – Urinary microscopy

Perazella, MA. CJASN ePress. Jan 14 2010. DOI 10.2215/CJN.06960909

Kanbay M. Int Urol Nephrol. Nov 17 2009. DOI 10.1007/s11255-009-9673-3
 Diagnosis: Ultrasound
• R/O obstruction
• Assess renal size and
parenchyma
• Doppler (renal flow and
resistive index)
– Normal < 0.7
– High: intrarenal vascular
disease or arteriosclerosis,
ATN, urinary obstruction
and acute graft rejection.
Ikee R. Am J Kidney Dis 2005 Oct;46(4):603-9.
http://radiology.med.sc.edu/renalultrasound.htm
 Diagnosis: CT scan/MRI
• Nephrolithiasis (non-contrast)
• Pyelonephritis
• Renal vein thrombosis
• Assessment of renal arteries
– Avoid gadolinium in GFR < 30 ml/min/1.73m2
Biomarkers of AKI

Soni SS. Blood Purif 2009;28:165–174

 Biomarkers of AKI
• Cystatin C - cysteine protease inhibitor
synthesized by all nucleated cells. It is freely
filtered by the glomerulus, reabsorbed
completely by PCT and not secreted.
– Levels of cystatin C are not affected by gender, age,
race or muscle mass.
• IL-18 - proinflammatory cytokine induced in PCT
and is detected in urine following AKI.
– Early predictor of AKI in ARDS (AUC) 0.73.
– More specific for ischemic AKI and its levels are not
deranged in CKD, UTI or nephrotoxic AKI
Soni SS. Blood Purif 2009;28:165–174
 Biomarkers of AKI
• Kidney Injury Molecule-1 (KIM-1) - transmembrane
protein markedly overexpressed in PCT in response
to ischemic or toxic AKI.
– Urinary KIM-1 helped to distinguish ischemic AKI from
prerenal azotemia and CKD
• Neutrophil gelatinase-associated lipocalin (NGAL)
- 25-kD protein massively released from renal tubular
cells after injury
– Higher baseline NGAL - increased risk of worsening
residual renal function w/n 1 yr
Ronco C. Critical Care 2007, 11:173.
Bolignano D. Clin J Am Soc Nephrol. 2009;4: 337–344.
Soni SS. Blood Purif 2009;28:165–174.
NGAL as biomarker for AKI

Soni SS. Blood Purif 2009;28:165–174

 Prevention of CIN
• Minimize radiocontrast dose
• Isoosmolar radiocontrast media preferred
• I.V. NaHCO3 at 3 mL/kg/hr for 1 hour prior to
radiocontrast exposure, then 1 mL/kg/hr for 6 hours after
• I.V. N-acetylcysteine 1200 mg before procedure, then
1200 mg po bid for total 4 doses.
• If I.V. N-acetylcysteine not available, then P.O. N-
acetylcysteine 600-1200 mg po for 2 doses before and 2
doses after the procedure.
• If already on acute hemodialysis, consider CVVH 6
hours before and for 24 hours after the procedure

Abu Jawdeh BJ. J Hosp Med. 2009;4:500–506.

 General management of AKI
• Exclude prerenal causes
• Exclude postrenal causes (US; bladder scan; postvoid residual).
• Review urinary sediment
– muddy brown casts: ATN
– red blood cell casts: glomerulonephritis or vasculitis
– pyuria: acute interstitial nephritis
– Clear sediment or hyaline cast: prerenal or postrenal azotemia
• Evaluate urinary indices
• After confirmation of ATN notify nephrologist when serum creatinine
level is 2.0 mg/dL
• Anticipate dialysis
– oliguric ATN (urine volume < 400 mL/24 hr) - 85% of patients
– nonoliguric ATN (urine volume > 400mL/24 hr) - 30% to 40% of patients.
• Assess for differential diagnoses (ANCA, ANA, ESR, etc.)

Esson ML. Ann Intern Med. 2002;137:744-752.

 General management of AKI
• Avoid excessive fluid overload leading to
pulmonary edema.
• Avoid hypotension and maintain euvolemia.
• Treat hyperkalemia.
• Review patient’s medications - necessary dose
adjustments.
• Use enteral alimentation if possible
• Discuss timing for initiation and mode of renal
replacement with nephrologists

Esson ML. Ann Intern Med. 2002;137:744-752.

 Vasoactive drugs and AKI
• Norepinephrine - in hypotensive vasodilated
patients with AKI, restoration of BP within
autoregulatory values should occur promptly
with NE.
• Dopamine has no advantages over
norepinephrine.
• Epinephrine and phenylephrine may be similar in
efficacy to noradrenaline – limited data
– Epinephrine: associated with hyperglycemia,
hyperlactatemia, acidosis, and hypokalemia.
• Terlipressin - useful in hepatorenal syndrome

Bellomo R. Crit Care Med 2008; 36(Suppl):S179–S186

Indication for dialysis

Needham E. Am Fam Physician 2005;72:1739-46.

Hepatorenal Syndrome: Treatment

Garcia-Tsao G. HEPATOLOGY 2008;48:2064-2077.

Gines P. N Engl J Med 2009;361(13):1279-90.