Acute Kidney Injury

Nephrotoxin Associated AKI

Nephrotoxic Associated Acute Kidney
Injury
 Kidney is susceptible to nephrotoxins due to
high perfusion and high concentration of the
toxins
 All parts of the
kidney(tubules,interstitium,vasculature) may
be affected by toxins of various kinds
 RFs : Older Age, Chronic Kidney Disease, and
occurrence of Prerenal Azotemia
Exogenous Nephrotoxins

 Contrast Agents
 A Leading cause of AKI
 Causes AKI by :
▪ Perturbing renal microvasculature
▪ Direct Cytotoxic damage to the tubular cells
▪ Precipitation and obstruction of tubular lumen
 Occurs most commonly in the setting of CKD,
more severe in CHF associated CKD, or
coincidenting with ischemia associated AKI
 Clinical Course
 Self Limiting : Creatinine rise 1-2 days after
exposure to contrast, peak in days 3-5, resolve by
day 7
 Severe : may require dialysis
 Antimicrobials
 Aminoglycosides ( Gentamycin) : Filtered at the
glomerulus, and accumulate in the tubules and cortex.
Causes AKI usually 5-7 days after therapy,usually with
Hypomagnesemia
 Amphotericin B(Antifungal) : Causes renal
vasoconstriction by increasing TGF and direct tubular
damage. Occurs with hypomagnesemia, hypocalcemia,
and polyuria
 Vancomycin
 Acyclovir(Obstructive)
 Chemotherapeutic Agents
 Several chemotherapeutic agents, the most
frequent being Cisplatin, may cause AKI
 Accumulates in lumen of Proximal tubules, causes
tubular necrosis and apoptosis
Toxins
- Ethylene Glycol (Autofreeze), and Melamine
Endogenous Nephrotoxins

 Myoglobin and Hemoglobin

 Myoglobin may be released due to muscle injury,
such as crush injury, muscle ischemia or
infections.Hemolysis may be released due to
massive hemolysis
 They may be directly toxic to proximal tubular
cells, or accumulate in the distal tubule by
precipitating with Uromodulin
 Uric Acid
 Most commonly accumulate due to Tumor lysis
syndrome (Cytotoxic treatment), release of uric
acid,accumulate in tubular lumen
POSTRENAL AKI
POSTRENAL AKI

 Occurs due to any obstruction in the

unidirectional path of urine, causing high
retrograde hydrostatic pressure, and
interferes with glomerular filtration
DIAGNOSTIC EVALUATION

 History and Physical Exam

 AKI is currently defined as a rise of ScR, by more
than 0.3 mg/dL in 1-2 days, or a decrease in urine
output to 0.5 mL/kg/hour for more than 6 hours.
 A serial blood test showing continuously rising
ScR, is very evident of AKI
 May be differentiated from CKD through
radiology(Contracted kidney on USG) or the
common normocytic anemia and secondary
hyperparathyroidism
 History and Physical Exam
 Suspect Pre-renal Azotemia if :
▪ History of : Diarrhea,Vomiting,use of Diuretics, NSAIDs, or ACE
Inhibitors
▪ PE : Hypotension, Tachycardia, Decreased JVP, Decreased Skin
Turgor,Dry Mucous Membrane
Suspect Post-Renal AKI if :
- History of Nephrolithiasis,Prostatic Disease
- PE : Ureteric : Colicky flank pain radiating to groin, Abdominal
fullness and suprapubic pain Bladder, Nocturia and Urinary
Hesitancy : Prostatic
- Needs Radiologic Imaging for definitive diagnosis
 History and Physical Exam
 Careful review of all drug and toxic exposures ,and
history of diseases such as crush syndrome, or
tumor lysis syndrome must be acquired to rule out
nephrotoxic associated AKI
 Urine Analysis
 Output Levels : Decreasing output shows a
decreased prognosis
▪ Preserved Urine Output : Common in Aminoglycoside or
Cisplatin toxicity
▪ Oligouria : More severe Kidney Injury (<400 mL/hour)
▪ Anuria : Severe disease ( Renal Artery Occlusion,
Complete Urinary Tract Obstruction)
 Urine Analysis
 Proteinuria
▪ Light (<1g/dL) : Ischemia or Nephrotoxin
▪ Severe(>3.5g/dL) : Damage to glomerular membrane,
Glomerulonephritis