Acute Kidney Injury

Ahmed A. Albassam, Ph.D.

Associate Professor
College of Pharmacy, Prince Sattam Bin Abdulaziz
University
 Learning Objectives

1. Define acute kidney injury (AKI) according to the Kidney Disease

Improving Global Outcomes (KDIGO) initiative
2. Discuss epidemiology and etiology of AKI as it applies to a patient
case
3. Determine patient-appropriate treatment and prevention strategies
of AKI
4. Review clinical basic for AKI patients
 Acute Kidney Injury

3 6
A clinical syndrome defined by a sudden reduction in kidney function as
evidenced by changes in:

• Serum creatinine (Scr)

• Blood urea nitrogen (BUN)
• Urine output (UOP)
 Definitions
Anuria
• Absence of urine formation and excretion
• UOP < 50 ml/day

Oliguria
• Diminished urine formation and excretion
• UOP < 500 ml/day

Nonoliguria
• Urine is of poor quality (contains little waste) although
• adequate volume
• UOP > 500 ml/day
Classification of AKI

RIFLE (Risk, Injury, Failure, Loss of Kidney Function, and End-Stage Renal Disease)
AKIN (Acute Kidney Injury Network)
KDIGO (Kidney Disease Improving Global Outcomes (KDIGO)
 KDIGO Definition of AKI
AKI is present when:

• Increase in Scr by 0.3 mg/dL within 48 hours

• Increase in Scr by 1.5x baseline within prior 7days
• Decrease in urine volume to < 0.5 ml/kg/hr x 6 hours
 Epidemiology
• Associated with increased length of stay, ventilator days and
outpatient follow-up
• Intensive care unit (ICU) patients > Hospitalized > Community
• Risk factors depend on setting
• ICU – sepsis, surgery, multiorgan failure, hypotension
• Hospitalized – volume depletion, sepsis, hypotension, radiocontrast dyes
• Community – chronic conditions, elderly, sepsis,
• dehydration, infection
• DRUGS are a risk factor in each setting
Etiology

https://www.wikidoc.org/index.php/Acute_kidney_injury_pathophysiolog
 Prerenal AKI
• Hypoperfusion of undamaged renal parenchyma +/-hypotension
• Causes
• Hypovolemia
• Decreased circulating blood volume/cardiac output
• Decreased renal autoregulation
• Effects of NSAIDs, ACEIs, ARBs
 Intrinsic Renal AKI
Glomerular Damage Interstitial Damage
• Least common • Acute interstitial nephritis (AIN)
• Inflammatory (nephritis, glomerulonephritis) • Drugs (non-steroidal anti-inflammatory drugs,
• Autoimmune disease antibiotics)
• Infection
Vascular Damage
Tubular Damage
• Occlusion in renal artery/vein (thrombosis )
• Inflammation (vasculitis) • Most common in hospitalized and ICU
patients (acute tubular necrosis)
• Ischemia
• Exogenous Toxins (drugs such as
aminoglycosides, radiocontrast dyes)
• Endogenous toxins (myoglobin, hemoglobin,
uric acid, ..)
 Intrinsic Renal AKI

Initiation Maintenance Recovery

1. Ischemic Injury
Remove toxin Diuretic phase
2. Tubular necrosis Or
Ischemia
3. Inflammatory response Monitor Fluid balance
Weeks to months
4. Decreased UOP/GFR
 Postrenal AKI
• Obstruction at any level within urinary collection system
• Bladder outlet (prostate)
• Ureteral (malignancy, nephrolithiasis)
• Renal tubular (drugs)

• Obstruction>>> Upstream pressure>>> Decrease GFR

• Clinical consequence once remove obstruction =diuresis

• Monitor fluid balance
 Clinical Presentation
Symptoms
• Change in urinary habits (cola-colored urine, UOP)
• Sudden weight gain
• Severe abdominal or flank pain

Signs
• Serum creatinine (Scr) ↑
• BUN ↑
• Urine output ↓
• Glomerular filtration rate (GFR)
 Clinical Presentation
• Scr cannot be used alone to diagnose AKI because it is insensitive to rapid
changes in glomerular filtration rate (GFR)

• The use of BUN in AKI is very limited because urea production and renal
clearance are heavily influenced by extrarenal factors such as critical illness,
volume status, protein intake, and medications

• Urine output measured over a specified period of time allows for short-term
assessment of renal function, but its utility is limited to cases in which it is
significantly decreased

• The fractional excretion of sodium( FENa ) is one of the better diagnostic

parameters to differentiate the cause of AKI
 Clinical Presentation
Signs
• Urinalysis
• Urine chemistry
 Treatment of AKI
Goals of treatment include:

1. Minimizing the degree of

insult to the kidney

2. Reducing extrarenal
complications

3. Speed up recovery of renal

function

4. Restoration of renal function

to pre-AKI baseline
 Treatment of AKI
Non-pharmacologic Therapy
• DISCONTINUE nephrotoxic agents
• Rehydration
• Oral vs. intravenous
• IV Normal Saline (bolus, continuous infusion)
• Monitor: edema, blood pressure, electrolyte balance, blood glucose, UOP
• Renal Replacement Therapy (RRT)
• Acid-base abnormalities
• Electrolyte imbalance
• Intoxications
• Salicylates, lithium, methanol, ethylene glycol, theophylline, phenobarbital
• Fluid Overload
• Uremia
 Treatment of AKI

• Intermittent hemodialysis (IHD)

• Transport process where solute passively
diffuses down concentration gradient from
one fluid compartment (blood or dialysate)
into the other

• Continuous Renal Replacement Therapy

(CRRT)
• Involves either dialysis (diffusion-based
solute removal) or filtration (convection-
based solute and water removal) that
operate in a continuous mode
 Treatment of AKI
IHD Disadvantages
Advantages • Venous access
• Readily available • Hypotension
• Rapid removal (3-4 hr) • Drug dose adjustments
• Scheduled

CRRT
Advantages Disadvantages
• Hemodynamically unstable patients • Availability of equipment
• Superior clearance of larger molecular • Nursing care
weight molecules • Thrombosis
• Drug dose adjustments
 Treatment of AKI-Pharmacologic Therapy
Mannitol (Aridol®)
• MOA: Increases osmotic pressure of glomerular filtrate inhibits tubular
reabsorption of water & electrolytes diuresis
• Dose: 12.5-25 gm IV over 3 to 5 minutes
• Onset of action: 1-3 hours
• Pregnancy category: C
• Monitoring: fluid I & O, renal function, serum electrolytes, urine and serum
osmolality
• Clinical Pearls
• Use 1-2 doses and assess patient response
• May cause renal dysfunction
• Little nonrenal clearance hyperosmolar state
 Treatment of AKI
Loop Diuretics
Furosemide (Lasix®)
• MOA
• Inhibits reabsorption of Na+ and Cl- in ascending loop of Henle by interfering with chloride-binding co-
transport system
• Inhibits reabsorption of Na+ and Cl- in proximal & distal tubule
• Increases excretion of water, Na+, Cl-, Mg++, Ca++
• Dose: 40 to 80 mg IV
• Onset of action: ~ 5 minutes
• Pregnancy category: C
• Monitoring: fluid In & Out, serum electrolytes, BP, renal function
• Clinical Pearls
• Hearing loss with high dose or rapid IV administration
• Max infusion rate 4 mg/min
 Loop Diuretics

Drug Chemical Equivalent Routes Bioavailability Preg

Structure Dose Categ
Furosemide Sulfonamide 40 mg IV IM PO 50% C
Bumetanide Sulfonamide 1 mg IV IM PO 80% C
Torsemide Sulfonamide 20 mg PO 80% B
Ethacrynic Phenoxyacetic 50 mg IV PO 100% B
Acid acid
 Treatment of AKI
Diuretic Resistance
• Causes
• Excessive sodium intake/increased sodium resorption
• Reduction in number of functioning nephrons
• Reduced renal blood flow
• Reduced oral bioavailability of furosemide
• Extensive protein binding
• Treatment
• Increase dose
• Continuous infusion vs. intermittent infusion
• Combination therapy with thiazide diuretic
• IV chlorothiazide, PO metolazone
 Treatment of AKI
Electrolyte Management
• Hyperkalemia
• Life-threatening cardiac arrhythmias
• Dietary potassium restriction
• Drug causes
• PO potassium replacement, IV fluids, PO phosphorus replacement,
sulfamethoxazole/trimethoprim
• Hypernatremia
• Dietary sodium restriction
• Drug causes
• IV metronidazole, ampicillin, piperacillin, fluconazole
 Treatment of AKI
Electrolyte Management
• Hyperphosphatemia
• More common with significant tissue destruction
• NOT removed by dialysis
• Dietary phosphorus restriction
• Oral phosphate binders may be necessary
• Hypermagnesemia
• Uncommon
• NOT removed by dialysis
• Dietary magnesium restriction
 Treatment of AKI
Nutrition
• Why important?
• 42% AKI patients with malnutrition have increase mortality & length of stay
• Results in insulin resistance, hypertriglyceridemia, protein catabolism,
negative nitrogen balance
• KDIGO goals
• Caloric goal
• 20-30 kcal/kg/day
• Protein goal
• 0.8-1 g/kg/day (no dialysis)
• 1-1.5 g/kg/day (RRT)
 Monitoring of AKI

ICU Patient Hospitalized Patient

• Daily weight • Daily weight
• I & O’s every shift • I & O’s every shift
• BP, HR, MAP (continuous) • BP, HR every shift
• Labs • Labs
• Chemistry panel • Chemistry panel
• Q 12h or daily • Blood glucose
• Blood glucose • Q 4h, Q 6h or prior to meals & at
• Q 1h, Q 2h, Q 4h bedtime
• Nutrition • Nutrition
• Enteral preferred • Enteral preferred
• Drug therapy • Drug therapy
 Prevention of AKI
• Hydration, Hydration, Hydration
• Inpatient setting → Isotonic crystalloid
• Normal saline, lactated ringer’s
• Outpatient setting → Optimize daily fluid intake
• Maintain ~ 2 L/day
• AVOID nephrotoxic agents
• Consider Drug Therapy
Prevention of AKI
 Clinical Pearls of AKI
• Don’t rely solely on CrCl to indicate patients’ renal function
• Discontinue ANY potential nephrotoxic agent
• Adjust and monitor drug dosing and scheduling
• Patient factors
• Residual drug clearance
• Fluid accumulation effecting volume of distribution
• Presence of multisystem organ failure
• RRT or not
• Drug factors
• Pharmacokinetics of the individual drug(s)
• Therapeutic drug monitoring on or off RRT
• Daily assessment
Drug Causes of AKI
 Summary
1. History and physical
2. Laboratory monitoring
3. Determine cause of AKI
4. Remove cause
5. Volume status of patient fluid vs Diuresis
6. Await renal recovery