- Clinical science
Acute kidney injury (AKI) is a sudden loss of renal function with a consecutive rise in creatinine and blood urea nitrogen (BUN). It is most frequently caused by decreased renal perfusion (prerenal) but may also be due to direct damage to the kidneys (intrarenal or intrinsic) or inadequate urine drainage (postrenal). In AKI, acid-base homeostasis, as well as the fluid and electrolyte balance, is disturbed, and the excretion of substances, including drugs, within the urine is impaired. The main symptom of AKI is oliguria or anuria; in some cases, polyuria may occur as a result of disturbed tubular reabsorption. Diagnosis of AKI requires an increase in serum creatinine concentration and/or decrease in urine output. Specific investigations are guided by the suspected cause. Rapid evaluation, diagnosis, and treatment are necessary to prevent irreversible loss of renal function.
Prerenal (∼ 60% of cases)
Any condition leading to decreased renal perfusion
- Hypotension: e.g., sepsis, dehydration, cardiogenic shock, anaphylactic shock
- Renal artery stenosis
- Drugs affecting glomerular perfusion: e.g., cyclosporine, tacrolimus, NSAIDs , ACE inhibitors
Avoid co-administering ACE inhibitors and NSAIDs in patients with reduced renal perfusion (e.g., congestive heart failure, renal artery stenosis) because doing so can significantly decrease the glomerular filtration rate (GFR)!
Intrinsic (∼ 35% of cases)
Any disease causing severe direct kidney damage
- Acute tubular necrosis (causes ∼ 85% of intrinsic AKIs)
- Glomerulonephritis (e.g., rapidly progressive glomerulonephritis)
Prolonged prerenal failure leads to intrinsic failure because decreased renal perfusion causes tubular necrosis!
Postrenal (∼ 5% of cases)
- Congenital malformations
- Acquired obstructions: benign prostatic hyperplasia (BPH), iatrogenic/catheter-associated tumors, stones, bleeding
- Neurogenic bladder (e.g., multiple sclerosis, spinal cord lesions, or peripheral neuropathy)
- Decreased blood supply to kidneys (due to hypovolemia, hypotension, or renal vasoconstriction) ; → failure of renal vascular autoregulation to maintain renal perfusion → decreased GFR → activation of renin-angiotensin system → increased aldosterone release → increased reabsorption of Na+ and H2O → increased urine osmolality → secretion of antidiuretic hormone → increased reabsorption of H2O and urea
- Creatinine; is still secreted in the proximal tubules, so the blood BUN:creatinine ratio increases.
- Damage to a vascular or tubular component of the nephron → necrosis or apoptosis of tubular cells → decreased reabsorption capacity of electrolytes, water, and/or urea (depending on the location of injury along the tubular system)
- Acute tubular necrosis: necrotic debris obstructs tubules → decreased GFR → sequence of pathophysiological events similar to prerenal failure
- Renal obstruction (e.g., stones, BPH, neoplasia, congenital anomalies) → increased retrograde hydrostatic pressure within tubuli → decreased GFR and compression of the renal vasculature → acidosis, fluid overload, and increased BUN, Na+, and K+.
- A normal GFR can be maintained if the other kidney's function is normal.
Phases of AKI
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Hours to days
Oliguric or anuric phase
Generally < 2 weeks
∼ 3 weeks
Up to 2 years
- May be asymptomatic.
- Oliguria or anuria
- Signs of volume depletion (in prerenal AKI caused by volume loss)
- Orthostatic or frank hypotension and tachycardia
- Reduced skin turgor
- Signs of fluid overload
- Signs of renal obstruction (in postrenal AKI)
- Fatigue, confusion, and lethargy
- In severe cases: seizures or coma
- Affected individuals have a higher risk of secondary infection throughout all phases (most common reason for fatalities).
- Causes ∼ 85% of intrinsic AKIs
- Clinical features: same as for AKI (See “Clinical features” above.)
- Blood findings: azotemia, hyperkalemia, and metabolic acidosis
- Urinary sediment: muddy brown granular casts, epithelial cell casts, free renal tubular epithelial cells (due to denudation of the tubular basement membrane)
- Management: see “Treatment” section below.
- Prognosis: After 1–3 weeks, most patients with ATN will experience tubular re-epithelization and full recovery.
- Definition: AKI after IV administration of iodinated contrast medium
- Risk factors
- Clinical features/diagnostics: See “Clinical features” above and “Diagnostics” below.
- Always evaluate kidney function before administering a contrast agent.
- Use a low dose and low concentration of contrast medium.
- The patient should discontinue nephrotoxic substances before administration.
- Ensure hydration: isotonic NaCl before and after administration of contrast medium
- Acetylcysteine (no clear recommendations .)
- The diagnosis of AKI requires an acute increase in serum creatinine and/or decrease in urine output (see the criteria for different stages in the table below); therefore, renal function tests should be done in every patient with suspected AKI
- Additional laboratory investigations and imaging should be guided by the suspected cause.
|Stages of AKI by Kidney Disease Improving Global Outcomes (KDIGO, 2012)|
|Stage||Serum creatinine||Urine output|
|1|| || |
|2|| || |
|3|| || |
- Blood test findings
Urine test findings
- Normal urinalysis
- Low urine sodium concentration (< 20 mEq/L)
Low fractional excretion of sodium (FeNa < 1%)
- The fractional excretion of sodium reveals how much filtered sodium is excreted in the urine.
- FENa= (V*UNa)/(GFR*PNa), using plasma and urine sodium concentrations (PNa and UNa), urine flow rate (V), and GFR or
- FENa= (SCr*UNa)/(SNa*UCr), using serum sodium (SNa), urine sodium; (UNa), serum creatinine; (SCr), and urine creatinine (UCr).
- High urine osmolality (> 500 mosm/kg) and specific gravity (> 1.010)
- Hyaline casts due to hypovolemia resulting in concentrated urine: hyaline casts are a nonspecific finding that may also be seen in healthy individuals
- Blood test findings
- Urine test findings
- Biopsy: in suspected
- Blood test findings
- Urine test findings
- Imaging: high post-void residual volume and bilateral hydronephrosis on renal ultrasound or noncontrast CT scan
Comparison of diagnostic findings in different types of AKI
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Fractional excretion of sodium
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|Urine sodium concentration (mEq/L)|| || |
|Urine osmolality (mOsm/kg)|| || || |
|Urine sediments|| |
- Treat the underlying cause.
- Patient should discontinue use.
- Adjust dosages of medications cleared by the kidney (e.g., amiodarone, digoxin, cyclosporin, tacrolimus, antibiotics, chemotherapeutic agents).
- Monitor and manage changes in pH, water, and electrolyte balance.
- Assess uremic signs and symptoms (e.g., anorexia, nausea, vomiting, metallic taste, altered mental status) daily
- Perform dialysis if necessary. (See .)
- Postrenal: Remove outflow obstructions with Foley catheter insertion, an indwelling bladder catheter, nephrostomy, or stenting.
The longer the underlying cause, the greater the chance that AKI progresses to renal failure. Treat early!
Consequences of renal failure (MAD HUNGER): Metabolic Acidosis, Dyslipidemia, High potassium, Uremia, Na+/H2O retention, Growth retardation, Erythropoietin failure (anemia), Renal osteodystrophy.