Toxicology – Acute Kidney Injury (AKI) in Poisoning

Definition

Acute kidney injury (AKI), historically called acute renal failure, is an abrupt decline in renal function resulting in impaired regulation of fluid, electrolytes, acid-base balance, and waste products.

Related terms:

• Azotemia: increased BUN and/or serum creatinine
• Acute tubular injury/necrosis (ATI/ATN): damage and dysfunction of renal tubular cells
• Acute interstitial nephritis (AIN): inflammatory injury involving the renal interstitium
• Nephrotic syndrome: heavy proteinuria associated with hypoalbuminemia, edema, and often hyperlipidemia

Major Mechanisms

Toxin-associated AKI can be divided into three broad categories:

1. Prerenal AKI – decreased renal perfusion

• Dehydration
• Vomiting or diarrhea
• Hemorrhage
• Hypotension or shock
• Drug-induced cardiac dysfunction
• Altered renal vascular tone

Examples of drugs that can impair renal perfusion include NSAIDs, ACE inhibitors, and calcineurin inhibitors.

2. Intrinsic Renal Injury – direct kidney damage

Important mechanisms include:

• Acute tubular injury
• Acute interstitial nephritis
• Glomerular injury
• Pigment nephropathy from rhabdomyolysis or hemolysis
• Crystal nephropathy

Representative nephrotoxic exposures include:

• Aminoglycosides
• Amphotericin B
• Cisplatin
• Cyclosporine
• Ethylene glycol
• Methotrexate
• Heavy metals
• Certain mushrooms
• Radiographic contrast in susceptible patients

3. Postrenal AKI – urinary obstruction

Possible causes include:

• Drug or metabolite crystallization
• Calcium or uric acid stones
• Anticholinergic urinary retention
• Other mechanical urinary obstruction

Risk Factors

The risk of toxin-associated AKI increases with:

• Pre-existing kidney disease
• Dehydration or hypovolemia
• Simultaneous exposure to several nephrotoxic agents
• Severe systemic poisoning
• Prolonged hypotension

Clinical Features

AKI may initially produce few symptoms.

Possible findings include:

• Reduced urine output
• Fluid retention
• Peripheral or pulmonary edema
• Hypertension
• Nausea and vomiting
• Weakness
• Confusion in severe uremia

Major complications include:

• Hyperkalemia
• Metabolic acidosis
• Fluid overload
• Uremia

Urine output can be reduced, normal, or occasionally increased, so normal urine production does not exclude AKI.

Toxicologic Clues

Certain findings can suggest the underlying exposure:

• Anion-gap metabolic acidosis + calcium oxalate crystalluria → ethylene glycol
• Rhabdomyolysis → sympathomimetics, prolonged coma/immobility, seizures, carbon monoxide, and several other toxic exposures
• Microcytic anemia + basophilic stippling → chronic lead exposure
• GI injury + renal failure → consider heavy metals and other systemic toxicants
• Tremor, neurologic abnormalities + renal dysfunction → consider lithium in the appropriate setting

These findings are clues rather than diagnostic by themselves.

Urinalysis and Urine Sediment

Urine microscopy can help determine the mechanism of renal injury.

Prerenal AKI

• Often relatively bland urine sediment
• Hyaline casts may occur

Acute tubular injury

• Muddy-brown granular casts
• Renal tubular epithelial cells

Glomerulonephritis

• Hematuria
• Proteinuria
• Red blood cell casts

Pigment nephropathy

• Urine dipstick positive for blood with few or no red blood cells on microscopy suggests myoglobin or free hemoglobin

Crystal nephropathy

• Calcium oxalate crystals may support ethylene glycol exposure in the appropriate clinical setting.
• Uric acid crystals can occur with uric acid nephropathy.

Laboratory Evaluation

Important tests may include:

• Serum creatinine and BUN
• Electrolytes
• Bicarbonate
• Calcium, magnesium, and phosphate
• Urinalysis with microscopy
• Urine output monitoring
• Creatine kinase when rhabdomyolysis is suspected
• ECG when hyperkalemia is possible
• Targeted toxicant concentrations when clinically indicated

Serial creatinine measurements are often more informative than a single value because creatinine may rise after the kidney injury has already occurred.

FENa and Other Urine Indices

Traditionally:

• Low fractional excretion of sodium (FENa) supports a prerenal process.
• Higher FENa may support intrinsic tubular injury.

However, these are supportive rather than definitive tests. Diuretics, chronic kidney disease, sepsis, and several other conditions can make FENa misleading.

Clinical context and urine sediment are therefore important.

Management

Treatment focuses on both the cause of AKI and its complications:

• Stop nephrotoxic substances when possible.
• Treat the underlying poisoning.
• Restore appropriate intravascular volume when hypovolemia is present.
• Maintain adequate renal perfusion.
• Carefully monitor fluid intake and urine output.
• Correct clinically important electrolyte and acid-base abnormalities.
• Treat rhabdomyolysis or other underlying causes when present.

A specific antidote should be given when one exists for the responsible toxicant.

Dialysis

Renal replacement therapy may be required for complications such as:

• Refractory hyperkalemia
• Severe metabolic acidosis
• Pulmonary edema or fluid overload
• Significant uremic complications

In toxicology, dialysis may also be indicated specifically to remove a dialyzable poison, such as lithium, methanol, ethylene glycol, or salicylate, even before conventional indications for dialysis develop.

Important Modern Correction

Older references sometimes recommend “renal-dose” dopamine to preserve kidney function.

This practice is no longer recommended because low-dose dopamine has not been shown to prevent or treat AKI and can cause adverse effects.

Loop diuretics may help manage volume overload, but they do not reverse intrinsic kidney injury or improve renal recovery simply by increasing urine output.

Key Points

• Toxin-related AKI may be prerenal, intrinsic renal, or postrenal.
• Muddy-brown granular casts → acute tubular injury.
• RBC casts → glomerular disease.
• Positive urine blood with few/no RBCs → consider myoglobinuria or hemoglobinuria.
• Hyperkalemia, metabolic acidosis, and fluid overload are major complications.
• Creatinine may lag behind the actual renal injury.
• FENa can support the diagnosis but should not be interpreted in isolation.
• Treat the underlying poisoning and discontinue nephrotoxins whenever possible.
• “Renal-dose” dopamine should not be used to prevent or treat AKI.