creation date: 2025-10-02 17:18
tags: Pathologies
Acute Kidney Injury
Background
Definitions
Acute kidney injury (AKI) refers to an abrupt decrease in kidney function. This results in retention of waste products and dysregulation of electrolytes and volume.
AKI was formerly referred to as acute renal failure.
Pathogenesis
The pathophysiology of AKI is divided into three categories which have different causes but may be associated with each other and have overlapping mechanisms of injury.
Pre-renal
These conditions result in reduce blood flow to the kidney. This could range from systemic hypoperfusion to selective hypoperfusion of the kidney. This ultimately results in hypoxia and cell death, thus damaging the kidney.
Intrinsic renal (intrarenal)
Intrinsic renal conditions are those which affect the glomerulus or tubules. These conditions often involve ischemia or toxins.
The exact pathophysiology varies based on disease. Injured tubules can necrose and clump together causing casts that can further decrease filtration and secretion. Inflammation can damage the interstitial. Glomerular injury vary significantly but revolves around damage to the glomerular structure.
It should be noted that pre-renal causes, if prolonged, can cause cellular damage consistent with intrinsic renal etiologies.
Post-renal
The most common post-renal causes include obstruction which lead to congestion and urinary backflow to the kidneys. This increases intra-trubular pressure and thus decreases GFR.
Obstructions that are more proximal usually does not result in bladder distension while more distal obstructions can cause bladder distension and possibly post-void volume (if bladder outlet is obstructed).
Notably, unilateral obstructions, if gradual enough, may not present as AKI due to compensation by the contralateral kidney.
Etiology
Pre-renal
Characterized by decreased renal perfusion
- Hypervolemia (eg. cardiorenal syndrome, hepatorenal syndrome) - reduced effective circulating volume
- Hypovolemia (eg. hemorrhage, burns, GI fluid loss)
- Hypotension from decreased cardiac output (eg. cardiogenic shock, PE, ACS)
- Hypotension from systemic vasodilation (eg. septic shock)
- Renal vasoconstriction (eg. NSAIDs, iodinated contrast)
- Glomerular efferent arteriolar vasodilation (eg. ACE inhibitors, ARBs) - reduces GFR by decreasing glomerular pressure
Intrinsic renal - Acute tubular necrosis (eg. from ischemia or drugs) (85% of AKI)
- Nephrotoxins include myoglobin, uric acid, vancomycin, contrast
- Acute interstitial nephritis (eg. type 1 or 4 hypersensitivity, medications)
- Glomerulonephritis
- Intratubular obstruction
Post-renal - Renal/uretral calculi
- Tumours, blood clots, neurogenic bladder causing ureteral outlet obstruction
- Urethral obstruction
Clinical Presentation
Signs & Symptoms
Many patients in early or mild AKI may have no clinical symptoms.
Patients who are symptomatic present with signs of diminished kidney function. Signs would also depend on the etiology. Generally, this includes:
- Decreased urine output
- Hypertension
- Edema
For pre-renal causes:
- Hypotension, tachycardia, dehydration
- Possible signs of fluid overload
Post-renal causes:
- Distension of bladder
- Flank/bladder pain
Kidney dysfunction may also manifest as:
- Electrolyte imbalnaces
- Uremia
- Acidosis
AKI typically progresses through four phases:
Initiation
- Symptoms of underlying insult to kidney
Oligo-anuria - Urine output drops with decrease in eGFR
- Accumulation of weight due to fluid overload
- Electrolyte imbalances
Polyuria - Healing begins with eGFR increase
- Urine output increases
Recovery - Return to baseline
History & Physical Exam
History can elucidate the etiology. Care review of concurrent illnesses and potentially nephrotoxic medications is integral.
Additionally, timing of onset can be used to determine precipitating event. Serum creatinine generally lags behind kidney injury by 24-48 hours.
Physical exam should investigate possible etiology. Special notice should be given to volume status for hemodynamically mediated AKI (prerenal).
Urine output can give an idea of severity of AKI and whether dialysis is necessary.
Risk factors
Diagnosis
Criteria
The diagnosis of AKI can be made with one of the following criteria:
- Increase in serum creatinine by ≥26.5 mcmol/L within 45 hours
- Increase in serum creatinine to ≥1.5 times baseline in the prior 7 days
- Urine volume <0.5 mL/kg/hr for 6 hours
It should be noted that the urine volume output criteria requires exclusion of urinary tract obstruction, hypovolemia, or other easily reversible causes of reduced urine output.
Staging
AKI is staged if any one of the criteria for a given stage is met.
Stage 1:
- Increase in serum creatinine to 1.5-1.9x baseline
- Increase in serum creatinine by ≥26.5 mcmol/L
- Reduction in urine volume to <0.5 mL/kg/hr for 6-12 hours
Stage 2:
- Increase in serum creatinine to 2.0-2.9x baseline
- Reduction in urine volume to <0.5 mL/kg/hr for ≥12 hours
Stage 3:
- Increase in serum creatinine to 3.0x baseline
- Increase in serum creatinine by ≥353.6 mcmol/L
- Reduction in urine volume to <0.5 mL/kg/hr for ≥24 hours
- Anuria for ≥12 hours
- Initiation of kidney replacement therapy
- In patients <18 years, decrease of eGFR to <35 mL/min/1.73m2
Work-up
Initial laboratory testing includes:
- Urinalysis
- Blood tests
- Serum creatinine
- Electrolytes
- Glucose
- Blood urea nitrogen
- Serum calcium
- CBC with differential
If etiology is not apparent:
- Renal ultrasound and bladder scan for post-renal obstructions
- Hydronephrosis and hydroureter suggests obstruction
- Urine sodium, creatine, and osmoality
- FeNa <1% with normal urine osmolality suggests pre-renal
- FeNa >2% with decreased urine osmolality suggests intra-renal
Pre-renal and renal causes can also be differentiated with IV bolus of fluid, in which pre-renal should correct itself.
If the patient is at risk of multiple myeloma, further workup may be warranted.
Differential
The differential diagnosis consist of varying etiologies that may lead to AKI. Additionally, excessive protein ingestion or dietary supplementation can result in elevated creatinine levels.
Red Flags / Complications
Many complications of AKI are associated with increased mortality. Some complications are directly related to AKI but others are related to the underlying causes which may be difficult to assess.
Common complications include:
- Hyperkalemia (and sequalae)
- Metabolic acidosis
- Hyperphosphatemia
- Fluid overload resulting in pulmonary edema
Other organ-related complications include:
- Cardiovascular: HF secondary to fluid overload
- Gastrointestinal symptoms
- Neurologic symptoms of uremia
Management
Triage
Following initial evaluation and staging, decision should be made whether:
- Emergency department referral is needed
- Outpatient nephrology referral is needed if outpatient
- Assessment of indications for urgent kidney replacement therapy
Subacute kidney injury refers to a form of kidney injury which develops slower and is milder than true AKI. In these cases, outpatient management is sufficient but failure to improve or complex etiology with risk of complications should warrant nephrology referral.
In patients where fluid and electrolyte abnormalities put them at risk of life-threatening complications, kidney replacement therapy should be initiated.
- Hypervolemia with pulmonary edema
- Severe hyperkalemia
- Signs of uremia
- Severe metabolic acidosis and hypervolemia
- Acute poisoning
Treatment
Elimination of potential insults
Medications
If possible, medications that can affect the kidney should be discontinued during the acute phase of AKI:
- NSAIDs
- ACE inhibitors and ARBs
- Nephrotoxins (eg. aminoglycosides, pip-tazo, chemotherapy)
Dosing will likely need to be reviewed and adjusted, especially for drugs that are cleared by the kidney.
Hypotension
Low blood pressure can precipitate or complicate AKI and as such identification and correction should be done to reduce kidney injury.
Contrast
Avoid using contrast unless used for an emergency. Dialysis may be necessary to prevent iodinated contrast-induced nephropathy.
Obstructions
Obstructions can be removed based on the type. This could include:
- Urethral stenting
- Catheterization
- Surgery
Volume management
An assessment of volume status should be performed. Hypovolemic patients should receive fluid therapy.
It should be noted that fluid overload is a cause of increased mortality and as such fluid should be administered with care. Fluid therapy should also be avoided in patients with pulmonary edema or anuria.
In hypervolemic patients, diuretics can be used to relieve the effects. A common option is:
- Furosemide 80 mg IV
- Adjunct: thiazide diuretic if effect insufficient
Management of electrolyte imbalances
A number of electrolytes imbalances can occur during AKI. These are discussed in depth separately.
- Hyperkalemia
- Hyperphosphatemia
- Hypocalcemia
- Hypomagnesemia and hypermagnesemia
Management acid-base disturbances
Acid-base disturbances are complications of AKI or sometimes a result of an underlying cause.
Metabolic acidosis
In cases were correction of etiology can resolve metabolic acidosis (eg. diabetic ketoacidosis), treatment should begin there.
In patients who are oliguric or anuric, and are volume overloaded with severe acidosis (pH <7.1), kidney replacement therapy is indicated. If the patient is not volume overloaded with no indications for KRT, then bicarbonate can be used instead.
Metabolic alkalosis
In the minority of cases, metabolic alkalosis may be present. Treatment consist of IV sodium chloride infusion.
Management of uremia
During care, assessment of uremic symptoms should be done for possible nonemergency dialysis. It should be noted that due to the nonspecific nature of symptoms of uremia, other causes should be ruled out before KRT is initiated.
Otherwise, dialysis is indicated for:
- Uremic symptoms
- Severe electrolyte imbalances that cannot be corrected
- Severe overload refractory to diuretics
- Intoxications
- Acidosis
Management of nutrition
Nutritional support for AKI patients who are critically ill generally consist of:
- Restriction of potassium, phosphorous, and sodium
- Adequate protein, nutrients, and energy
It should be noted that protein energy wasting is common which may require patients to consume higher levels of protein.