Acute Kidney Injury/Rhabdo

Question 1

Functions of the Kidney

Answer 1

Regulation of ionic composition
Sodium, potassium, calcium, chloride, phosphate

Regulation of blood pH, osmolarity, and glucose
Regulation of blood volume

Conserving or eliminating water
Regulation of blood pressure
Secreting renin

Release of erythropoietin & calcitriol

Excretion of wastes
Nitrogenous waste products (ammonia, uric acid, urea, creatinine, and amino acids), excess quantities of salts and water

Question 2

Major Function of the Kidney

Answer 2

Filter blood plasma and separate wastes from the useful chemicals

Eliminates the wastes in urine while returning the useful chemicals to the bloodstream

Question 3

Renal Corpuscle

Answer 3

Component of each nephron
Site where blood filtration begins
Passive process by high hydrostatic pressure of the glomerular capillaries

Consists of:
Glomerulus (cluster of capillaries)
Bowman’s capsule
Two-layered capsule that encloses the glomerulus

Blood flows into the glomerulus via the afferent arterioles → water and solutes pass through the capillary endothelium, through the basement membrane, and through the epithelium → Bowman’s space → renal tubule

Remaining blood leaves the glomerulus through efferent arterioles

Question 4

Glomerular Filtration Rate (GFR)

General and dependent on

Answer 4

The volume of fluid filtered by the kidneys in a minute
Measure of your kidney function

Dependent upon:
The net filtration pressure
Vasodilation of the afferent arterioles mediated by prostaglandins
Vasoconstriction of the efferent arterioles mediated by angiotensin II

Available surface area for filtration
Filtration membrane permeability

Question 5

Renin-angiotensin-aldosterone system (RAAS) plays a central role in the regulation of renal blood flow

Answer 5

Angiotensin II vasoconstricts the glomerular arterioles; greater effect on the efferent arterioles than the afferent arterioles → increased glomerular filtration pressure

Increased circulating volume from the affects of aldosterone → increased blood pressure and renal perfusion

Angiotensin II stimulates the release of antidiuretic hormone (ADH), which will reabsorb water from the collecting ducts → increased circulating blood volume and renal perfusion

Question 6

Renal Tubule

Answer 6

Duct that leads away from the glomerular capsule
Divided into 4 regions:
Proximal convoluted tubule (PCT)
Nephron loop
Distal convoluted tubule (DCT)
Collecting duct
Each has a unique absorptive properties

Question 7

Acute Kidney Injury (AKI)

general and epi

Answer 7

Characterized by abrupt deterioration in kidney function (within 48 hours) based on an elevation in serum creatinine level with or without reduction in urine output

Spectrum of injury from mild to advanced → requiring renal replacement therapy

Often reversible

Classified as pre-renal, intrinsic/intra-renal, or post-renal

Epidemiology:
7% of hospitalized patients
2/3 of ICU patients → Mortalityis 50%‒70% in AKI associated withsepsis and multiple organ failure

Previously referred to as acute renal failure (ARF) and acute renal insufficiency

Question 8

AKI

Staging Criteria

Answer 8

Kidney Disease: Improving Global Outcomes (KDIGO) criteria for AKI

Stage 1
≥ 0.3 mg/dL increase in serum creatinine within 48 hours,or
Increase in serum creatinine > 1.5–1.9 times baseline in the past 7 days,or
Urine volume/urine output < 0.5 mL/kg/hr for 6–12 hours

Stage 2
Serum creatinine 2.0‒2.9 times baseline,or
Urine volume/urine output < 0.5 mL/kg/hr for ≥ 12 hours

Stage 3
Serum creatinine 3 times baseline,or
Serum creatinine ≥ 4 mg/dL,or
Initiation of renal replacement therapy,or
Decrease in estimatedGFR
< 35 mL/min/1.73 m2in individuals < 18 years of age,or
Urine volume/urine output < 0.3 mL/kg/hr for ≥ 24 hours,or
Anuria for ≥ 12 hours

DONT MEMORIZE

Multiple staging systems for AKI
Staging is based on serum creatinine, urine output, and/or changes in GFR
Kidney Disease: Improving Global Outcomes (KDIGO) criteria is the currently preferred staging system

Other staging systems:
Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) classification system
The Acute Kidney Injury Network (AKIN) criteria
International Renal Interest Society (IRIS) guidelines for AKI (Grade I-V)

Question 9

AKI

RF

Answer 9

Older age >75 years
Hypovolemia – dehydration or blood loss
Nephrotoxic drugs
Rhabdomyolysis
Sepsis

Chronic disease:
Diabetes mellitus
Liver failure
Heart failure
Kidney disease (acute on chronic kidney injury)

Question 10

AKI

Pre-renal Causes

Answer 10

Most common type of AKI
70% of community-acquired cases

Caused by decreased renal perfusion
Reduced circulating volume (GI losses, blood loss, diuretic use, osmotic diuresis – DKA, insensible loss – burns)
Reduced cardiac output (heart failure)
Systemic vasodilation (septic shock)

Medications
ACE inhibitors, ARBs, NSAIDs
Obstruction of the renal artery (thrombosis/embolus, stenosis, or aneurysm)

Question 11

Question 12

Pre-renal cause

NSAIDs

Answer 12

Vasodilation of the afferent arterioles mediated by prostaglandins
NSAIDs block the production of prostaglandins → vasoconstriction and possible AKI

Vasoconstriction of the efferent arterioles mediated by angiotensin II
ACEi/ARBs block the effects of angiotensin II (vasoconstriction) → vasodilation of the efferent arterioles (renal protective)
In patients with renal artery stenosis, the introduction of an ACEi/ARBs can lead to a drop in glomerular filtration pressure

Question 13

AKI

Intrinsic/Intra-renal Causes

Answer 13

Caused by direct damage to the glomeruli and/or tubulointerstitial structures

Acute tubularnecrosis(ATN)
Damage to the tubular cells
Caused by a lack of blood flow to the kidneys and nephrotoxic agents

Acute interstitial nephritis
Inflammatory cell infiltration into the kidney interstitium

Caused by medications,infections, orautoimmune diseases
Vascular disease
Atherosclerosis and vasculitis
Glomerular disease
Glomerulonephritis (presents withhematuria) or nephrotic syndrome(presents withproteinuria)

Question 14

AKI

Post-renal Causes

Answer 14

Caused by inadequate drainage of urine distal to the kidneys (obstruction) leading to back pressure on the kidneys and hydronephrosis
May occur at any point in its course from therenal pelvisto theurethra

Causes of obstruction
Urinary calculi
Benign prostatichyperplasia (BPH) or prostate cancer
Bladder outlet obstruction
Urethral stricture
Gynecologic tumors (ovarian cancer, uterinefibroids,cervical cancer)

A single stone will lead to AKI in a patient with 1 functioning kidney, but unlikely in patients with 2 functioning kidneys

Question 15

Effects of AKI on Electrolytes & Acid-Base Balance

Answer 15

Hyperkalemia
Due to decreased renal excretion ofpotassium
Increases theprobability ofcardiac arrhythmias

Hyperphosphatemia
Due to decreased renal excretion ofphosphate

Metabolic acidosis
Inability of thekidneysto excreteacids
Exacerbateshyperkalemia
Increases theprobabilityofcardiac arrhythmias

Question 16

Hyperkalemia

Question 17

AKI

Labs

Answer 17

Urinalysis – proteinuria, hematuria, casts

Urine output
Oliguria < 400 mL per day of urine
Anuria < 100 mL per day of urine

CBC with differential
CMP
Compare current BUN/creatinine to prior results
Electrolyte imbalances
Other lab tests to further evaluate underlying cause

Question 18

AKI

imaging

Answer 18

Doppler US to evaluate for renal artery stenosis
Non-contrast CT scan of abdomen and pelvis to rule out obstruction

Question 19

AKI

Biopsy

Answer 19

Reserved for patients in whom prerenal and postrenal causes of AKI have been excluded

Question 20

AKI

Tx

Answer 20

Based on the etiology of AKI

Stop any offending agents (medications) if identified as the cause of AKI

Adjust all essential medications for renal dosing
Avoid iodinated contrast media and gadolinium

If prerenal withhypovolemia
Treat withIV fluids (isotonic solution - normal saline or Lactated Ringer’s)

Ifprerenal with fluid overload treat withdiuretics

If postrenal with obstruction
Foley catheter to relieveurinary retention
Specialist consultation to treat underlying conditions (urology or gynecology)

Question 21

AKI

Tx electrolyte imbalance

Answer 21

Treat electrolyte and acid-base imbalances urgently

Hyperkalemia
≥ 6.5 mEq/L (severe)
If EKG changes are present
Calcium gluconate 10 mL of 10% solution given IV over 5 minutes to reduce the risk of cardiac arrhythmias
Insulin and dextrose given IV to shift potassium out of circulation and into the cells
Loopdiureticsto allow for renal loss ofpotassium
Sodium polystyrene sulfonate (Kayexalate) can be given to lower potassium levels gradually

Metabolic acidosis
Treat with oral or IVsodium bicarbonate

Question 22

Rhabdomyolysis

general and causes

Answer 22

Condition characterized by muscle necrosis and the release of intracellular contents into circulation (especially myoglobin)
Prompt recognition and treatment are vital because severe disease can be associated with life-threatening acute kidney injury (AKI) and electrolyte imbalances

Causes:
Any form of muscle damage can result in rhabdomyolysis
Broadly divided into three categories:
Traumatic or muscle compression
Non-traumatic exertional
Non-traumatic, non-exertional

Question 23

Rhabdo

Traumatic or muscle compression

Answer 23

Crush injuries
Victims of prolonged restraint, torture, or physical abuse
Surgical procedure with prolonged muscle compression
Acute lower-limb compartment syndrome
High-voltage electrical injury

Question 24

Rhabdo

Non-traumatic exertional causes

Answer 24

Extreme exertion or exertion under conditions in which muscle oxygenation is impaired

Marked physical exertion when one or more of the following risk factors is present:
Patient with the sickle cell trait
Patient is physically untrained
Exertion occurs in extremely hot, humid conditions (heatstroke)
Normal heat loss through sweating is impaired (anticholinergic medications or heavy football equipment)

Pathologic hyperkinetic states:
Grand mal seizures
Delirium tremens (DTs): severe type of withdrawal from alcohol
Psychotic agitation
Amphetamine overdose

Question 25

rhabdo

Nontraumatic, non-exertional causes

Answer 25

Prolonged immobilization
Alcohol use

Drug use
Illicit: heroin, cocaine, LSD, methadone
Prescription: statins, colchicine, daptomycin

Toxins
Snake venom, mushroom poisoning, carbon monoxide

Infections
Viral – influenza A & B, coxsackievirus

Inflammatory myopathies (dermatomyositis)

Electrolyte abnormalities
Hypokalemia
Hypophosphatemia

Question 26

Electrolyte balance

intra/extracellular fluid

Answer 26

Intracellular fluid
Potassium (K⁺) – main cation
Magnesium (Mg2⁺)
Proteins
Phosphates (HPO₄²-/H₂PO₄-) – main anion
Electrically balance the intracellular cations along with the negatively chargedproteins

Extracellular fluid
Sodium (Na⁺) – main cation
Controls ECF volume and water distribution in the body – water follows sodium
Calcium (Ca²⁺)
Chloride (Cl-) and Bicarbonate (HCO₃-):
Chloride is the most abundant anion in the ECF
Anions balance the extracellular cations

Question 27

rhabdo

Patho

Answer 27

Muscle injury

Influx of extracellular sodium and calcium into the myocytes; water follows sodium distorting the integrity of the intracellular space

↑ intracellular calcium causes a sustained myofibril contraction → ATP depletion within these cells

Activation of lipases and proteases → damage of the myocyte cellular membrane

Release of intracellular components (creatine kinase (CK), myoglobin, potassium, phosphate) that enter the bloodstream

Myoglobinuria and electrolyte abnormalities cause end-organ complications
Most common systemic complication is renal failure

Question 28

Rhabdo

S/Sx
Triad

Answer 28

Clinical presentation is variable

Classic triad - Present in < 10% of patients
Weakness
Myalgia
Tea-colored urine

Muscle pain
Affects proximal muscle groups, such as shoulders, thighs, lower back, and calves

Oliguria (output of < 500 mL/day) or anuria (output of 0-100 mL/day)

Other signs and symptoms based on the inciting event and complications

Fever is present in patients with infection
Altered mental status in cases of intoxication

Question 29

rhabdo

labs

Answer 29

Suspected based on history and clinical signs and symptoms

Labs (confirmatory)
↑creatine kinase (CK)
Key biomarker for rhabdomyolysis
>5x the upper limit of normal
Elevated at 12 hours after insult
Peaks at 24‒72 hours
Back to normal in about 5 days

↑ Myoglobin
Hard to detect in serum due to shorthalf-life
Red-to-brown urine without genitourinary symptoms
Suspect myoglobinuria → positive test for blood on the urine dipstick, but no RBCs on microscopic examination

Electrolyte abnormalities
Hyperkalemia: serum potassium (K+) level > 5.0 mEq/L
Hyperphosphatemia
Hyperuricemia: release of purines from the damaged muscle
Hypocalcemia: results from hyperphosphatemia

Metabolicacidosis
↑ lactic acid from damaged/ischemic muscles

↑ LDH due to tissue damage

Acute renal injury
↑ BUN and creatinine

Myoglobin is cytotoxic to nephrons and scavenges nitric oxide leading to worsening renal injury

Question 30

rhabdo

ECG

Answer 30

Electrocardiography (ECG)
To look for cardiac dysrhythmias (secondary to electrolyte abnormalities)

Possible findings ofhyperkalemia
Peaked T waves
Flattened to loss of P waves
Wide QRS interval
Sine wave pattern

Possible finding withhypocalcemia
QT prolongation

Question 31

rhabdo

Tx

Answer 31

Initial approach
Airway, breathing, circulation (ABC) assessment for all patients with trauma history
Exclude and treat other potential injuries (compartment syndrome, vascular compromise, fractures, dislocations, and wounds)

Removal of offending agents (if medication is suspected)

Aggressive intravenous fluid resuscitation
Lactated Ringer’sor saline (0.9%‒0.45%)
Caution for fluid overload in the anuric patient

Manage electrolyte abnormalities

Question 32

Rhabdo

monitoring

Answer 32

CK levels every 6 hours until levels are consistently decreasing

Basic metabolic panel at least every 4 hours to monitor
Electrolyte abnormalities
Renal function

Hourly urine output (urinary catheterization may be necessary)

Electrocardiogram and cardiac monitoring if K+is > 6.0 mEq/L

Question 33

Rhabdo

Key points

Answer 33

The classic triad of symptoms (myalgias, muscle weakness, and tea-colored urine) is present in<10% of cases

Myoglobinuria → positive test for blood on the urine dipstick, but no RBCs on microscopic examination

A CK level of>5 times the upper limit of normal is typically required for diagnosis

Treatment is supportive with IV hydration as well as concurrent treatment of the inciting cause and any resulting complications

Question 34