Acute Kidney Injury in the Critically Ill

Stephanie Davidson, ACNP-BCVanderbilt University Medical Center

Medical Intensive Care Unit

Objectives

• Brief pathophysiology review• Name the 3 types of acute kidney injury• Review contrast nephropathy and its treatments• Discuss necessary diagnostic tests• Discuss treatment modalities for the 3 types of acute

kidney injury

Epidemiology

• Acute Kidney Injury (AKI) – occurs in up to 20% of ICU patients– 25% will require RRT– 5% of general hospital population

• AKI is usually multifactorial– Sepsis– Hypotension– Drugs

• Mortality rate up to 80%

Pathophysiology• Blood flows from renal arteries and is delivered to

the glomeruli• Glomeruli form ultrafiltrate delivered to renal

tubules– Nearly free of protein and blood elements

• Tubules reabsorb and secrete solute and/or water from ultrafiltrate

• Final tubular fluid (urine) leaves kidneys and drains into renal pelvis to ureters, bladder, then urethra

Pathophysiology• Urine volume indicated kidney perfusion• Urine specific gravity and osmolality

(concentrating ability) indicate tubular function

Definition

• Lack of consensus definition in the past• Acute Dialysis Quality Initiative (ADQI) created

– RIFLE criteria– Graded risks of injury– Has been validated in variety of critically ill populations

• Acute Kidney Injury Network (AKIN)– Modified RIFLE criteria– Diagnostic and staging criteria for injury– Acute Kidney Injury to describe all levels of injury

Bellomo et al.,Critical Care 2004, 8:R204-R212 

RIFLE Criteria

Creatinine/GFR UOP

Risk 1.5-fold ↑ in Cr OR GFR ↓ by 25%

< 0.5 ml/kg/hr x 6 hrs

Injury 2-fold ↑ in Cr OR GFR ↓ by 50%

< 0.5 ml/kg/hr x 12 hrs

Failure 3-fold ↑ in Cr ORGFR ↓ by 75%

< 0.5 ml/kg/hr x 24 hrs OR Anuria x 12 hrs

Loss Complete loss of function > 4 weeks (needs RRT)

ESRD Complete loss of function > 3 months

OR

AKIN Criteria

• Based on abrupt (48 hr) increases• ⬆ Cr of ≥ 0.3 mg/dl from baseline OR• ⬆ in Cr of ≥ 50% OR• Oliguria ( < 0.5mg/kg/hr x 6 hrs or more) ✴✴Exclude obstruction if UOP is basis for diagnosis✴✴Optimize volume status, then apply criteria

Mehta, R, et al. Crit Care, 2007; 11:R31

Risk Factors for AKI

• age > 75 yrs• chronic kidney disease (CKD, eGFR < 60

mls/min/1.73m2)• Cardiac failure• Atherosclerotic peripheral vascular disease• Liver disease• Diabetes mellitus• Nephrotoxic medications

Complications of AKIMetabolic CV Neuro Heme GI Infectious

Metabolic acidosis

Fluid overload

Neuropathy

Anemia N&V UTI

Hyper K+ HTN Dementia Coag anomalies

GI bleeding IV catheter sepsis

Hypo Ca++ Arrhythmias Seizures Pneumonia

Hyperphos Pericarditis

hyper uremic

Marini, J & Wheeler, A, Critical Care Medicine, 2010

Types of AKI• Pre-renal

– Hypoperfusion (shock, cirrhosis, CHF)– Volume depletion (GI bleed, dehydration)

• Intra-renal– Acute interstitial nephritis (drug induced)– Acute tubular necrosis – Tumor Lysis Syndrome

• Post renal– obstruction

Tests and Formulas

• FENa - fractional excretion of sodium• Can help differentiate prerenal from ATN

– Measures percentage of filtered Na that is excreted– If <1%: prerenal, if >1%: ATN

– Not accurate if pt has received diuretics– (PCr x UNa)/ (PNa x UCr) x 100%

– Na = mEq/L Cr = mg/dl

• Feurea – fractional excretion of urea– Better estimation if pt has had diuretics– (serumCr x urineUrea)/ (serumUrea x urineCr) x 100%

– all units in mg/dl

Tests and Formulas

• Urine to plasma creatinine ratio– Estimates tubular water resorption– Creatinine in filtrate is equal to that of plasma– Urine Cr increases as water, not Cr, is reabsorbed

Prerenal AKI

Postrenal AKI

ATN AIN

Etiology Dehydration, hypoperfusion

Obstruction Ischemia, nephrotoxins

Allergic rxn; drug rxn

Serum BUN:Cr ratio

> 20:1 > 20:1 < 20:1 < 20:1

Urine Na (mEq/L)

< 20 Variable > 20 Variable

FeNa < 1% Variable > 1% Variable

Urine osms(mosm/kg)

>500 < 400 250 - 300 Variable

Urinary sediment

Hyaline casts Nml or red cells, white cells, or crystals

Muddy brown casts, renal tubular casts

White cells, white cell casts, +/- eosinophils

Common Diagnostics

• Urinalysis• Serum BUN/Cr• Urine Na+

• FENa or FEurea

• Urine osmolality• Urine to plasma Cr ratio• Urine volume

• Renal ultrasound– Gold standard– Will show obstructions,

hydronephrosis, kidney size

• Consider CT abd/pelvis• Consider 24 hr urine

collection

Prerenal Failure• R/T hypoperfusion and incomplete compensatory mechanisms• Causes:

– Hypovolemia: dehydration, hemorrhage, diuretics, GI losses– Edematous states: cirrhosis, CHF– Renal artery stenosis, hepatorenal syndrome, compartment

syndrome with elevated intraabdominal pressures• Results:

– Kidney is normal: glomeruli, tubules and interstitium intact– Untreated can lead to ischemia– Can occur is MAP <60 for >30minutes; worse if patient is

hypoxic

Compensatory Mechanisms

Prerenal Treatment• Treat underlying problem

– GI losses– CHF/cirrhosis (intravascularly dry)

• Attempt to reverse oliguria– Fluid challenge– Over 20-30 min; repeat if needed monitor UOP– Use crystalloid solution, 15-30ml/kg x1– Avoid if pt has s/s volume overload– Lasix challenge: one dose of 1mg/kg

• Consider invasive monitoring– CVP

Intrarenal Failure

Tubular Disorders

Interstitial Nephritis

Glomerulonephritis and small vessel vasculitis

ATN

• Sudden decline in GFR, accumulation of nitrogenous wastes, and dysregulation of electrolytes and acid-base balance

• Causes:– Prerenal if delayed treatment– Hypotension– Sepsis– Tumor lysis syndrome– Nephrotoxic substances

• Drugs: aminoglycosides, amphotericin, cyclosporine, ACEi, NSAIDs• Ethylene glycol/methanol

Prerenal AKI

Postrenal AKI

ATN AIN

Etiology Dehydration, hypoperfusion

Obstruction Ischemia, nephrotoxins

Allergic rxn; drug rxn

Serum BUN:Cr ratio

> 20:1 > 20:1 < 20:1 < 20:1

Urine Na (mEq/L)

< 20 Variable > 20 Variable

FeNa < 1% Variable > 1% Variable

Urine osms(mosm/kg)

>500 < 400 250 - 300 Variable

Urinary sediment

Hyaline casts Nml or red cells, white cells, or crystals

Muddy brown casts, renal tubular casts

White cells, white cell casts, +/- eosinophils

ATN Treatment

• Treat underlying cause– Sepsis, hypotension, ischemia, drugs

• Avoid volume overload• Nonoliguric renal failure has better outcomes than

oliguric• Monitor for hyperkalemia and treat• Monitor acid-base status (BMP)

ATN Treatment

• Consult nephrology– Courtesy and evaluate for possible RRT

• Monitor for AEIOU of HD– A = acidosis/alkalosis– E = electrolyte disturbances– I = Intoxications (methanol, ethylene glycol, salicylate)– O = overload (volume)– U = uremia– If any of these exist or are refractory, pt may need dialysis

Tattersall, J., et al, Neph. Dial. Transplant (2011). 26(7):2082-2086

-Decision when to start hemodialysis is difficult and cannot be guided by a single objective measure-Delaying until patient is symptomatic could increase risk of harm and/or death

Contrast-Induced Nephropathy• Evaluate risk vs. benefit of test • Occurs within 72 hrs of contrast given• Can resolve within 5 days• Prevent with fluid

– 0.9% saline: 1mL/kg x 12 hrs pre and post procedure– Isotonic bicarb: same dosing– No consensus on which is better

• No evidence for NAC (mucomyst)• Consider holding ACE-I/ARB and metformin prior to

contrast

AIN

• Drug induced allergic reaction in the renal interstitium• Common drugs: PCN, cephalosporins, sulfonamides,

quinolones, rifampin, thiazides, furosemide, NSAIDs, allopurinol, cimetidine

• Oliguria and rising serum creatinine often only indicators– ¼ of patients will have eosinophilia– ⅔ of patients will have eosinophiluria

• Discontinue offending drug, consider steroids

Marini, J & Wheeler, A, Critical Care Medicine, 2010

Prerenal AKI

Postrenal AKI

ATN AIN

Etiology Dehydration, hypoperfusion

Obstruction Ischemia, nephrotoxins

Allergic rxn; drug rxn

Serum BUN:Cr ratio

> 20:1 > 20:1 < 20:1 < 20:1

Urine Na (mEq/L)

< 20 Variable > 20 Variable

FeNa < 1% Variable > 1% Variable

Urine osms(mosm/kg)

>500 < 400 250 - 300 Variable

Urinary sediment

Hyaline casts Nml or red cells, white cells, or crystals

Muddy brown casts, renal tubular casts

White cells, white cell casts, +/- eosinophils

Post Renal Failure

• Less than 10% of AKI cases• High suspicion if abrupt stop in flow or decreased UOP• Causes:

– Renal calculi/clots– Prostatic hypertrophy– Ureteral stone– Rhabdomyolysis• Check renal ultrasound- hydronephrosis, renal obstruction• Consider CT of abd/pelvis• Treat underlying cause

Prerenal AKI

Postrenal AKI

ATN AIN

Etiology Dehydration, hypoperfusion

Obstruction Ischemia, nephrotoxins

Allergic rxn; drug rxn

Serum BUN:Cr ratio

> 20:1 > 20:1 < 20:1 < 20:1

Urine Na (mEq/L)

< 20 Variable > 20 Variable

FeNa < 1% Variable > 1% Variable

Urine osms(mosm/kg)

>500 < 400 250 - 300 Variable

Urinary sediment

Hyaline casts Nml or red cells, white cells, or crystals

Muddy brown casts, renal tubular casts

White cells, white cell casts, +/- eosinophils

Outcomes and Prognosis• AKI patients associated with

– Increased hospital and long term mortality– Longer hospital LOS– Increased costs

• AKI patients requiring HD– Extremely high risk for CKD – 10% may go on to develop ESRD

**Importance to have post-discharge follow up with nephrologist

Waikar, S. & Bonventre, J., Harrison’s Principles of Internal Medicine, 2012.

ReferencesBellomo, R, et al. Acute renal failure-definition, outcome measures, aminal

models fluid therapy and information technology needs: the Second International Consensus Conference of the Acute Dialysis Quality Initiative (ADQI) Group. Crit Care 2004; 8:R 204.Erdbruegger, U. and Okusa, M. (2012). Etiology and diagnosis of acute tubular necrosis and prerenal disease. Retrieved from www.uptodate.com. Esson, M. and Schrier, R. (2002). Diagnosis and Treatment of Acute Tubular

Necrosis. Annals of Internal Medicine, 137: 744-752 Fink, M., Abraham, E., Vincent, J.L., and Kochanek, P. (2005). Textbook of Critical Care (5th ed.). Philadelphia, PA: Elsevier Saunders. Levin, A, et al. Improving outcomes from acute kidney injury: report of an initiative. Am J Kidney Dis. 2007; 50:1.

ReferencesLewington, A. and Kanagasundaram, S. (2011). Summary of clinical practice guidelines for acute kidney injury. Retrieved from www.renal.org/Clinical/GuidelinesSection/AcuteKidneyInjury.aspxMcPhee, SJ and Papadakis M. (2008). Current Medical Diagnosis and Treatment. Tierney Jr, Lawrence (Ed.). New York, NY: McGraw Hill Medical. Neesh, P., Nadim, M., An overview of drug-induced acute kidney injury. Critical Care Medicine, 2008; 36: No 4 (suppl). Palevsky, P. (2012). Definition of acute kidney injury (acute renal failure). Retrieved from www.uptodate.com. Post, T. and Rose, B. (2012). Diagnostic approach to the patient with acute or chronic kidney disease. Retrieved from www.uptodate.com. Ricci, A., Cruz, D., and Ronco, C. (2008). The RIFLE criteria and mortality in acute kidney injury: A systematic review. Kidney International, 73, 538- 546

ReferencesTattersall, J., et al. When to start dialysis: updated guidance following publication of the Initiating Dialysis Early and Late (IDEAL) Study. Nephrol. Dial. Transplant (2011) 26(7). 2082-2086.Waikar S.S., Bonventre J.V. (2012). Chapter 279. Acute Kidney Injury. In Longo

D.L., Fauci A.S., Kasper D.L., Hauser S.L., Jameson J, Loscalzo J (Eds), Harrison's Principles of Internal Medicine, 18e. Retrieved August 16, 2014 fromhttp://accessmedicine.mhmedical.com/content.aspx?bookid=331&Sectio nid=40727068.