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 acute kidney injury (∼ 60% of cases)
- Hypotension: e.g., sepsis, dehydration, cardiogenic shock (decreased cardiac output), anaphylactic shock
- Renal artery stenosis
- Drugs affecting glomerular perfusion: e.g., cyclosporine, tacrolimus, NSAIDs , ACE inhibitors
Avoid coadministering 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 acute kidney injury (∼ 35% of cases)
Intrinsic causes include any disease that leads to severe direct kidney damage.
- Acute tubular necrosis (causes ∼ 85% of intrinsic AKIs): most commonly caused by sepsis, infection, ischemia, and/or nephrotoxins
- Glomerulonephritis (e.g., rapidly progressive glomerulonephritis)
Acute tubulointerstitial nephritis
Postrenal acute kidney injury (∼ 5% of cases)
- Congenital malformations (e.g. posterior urethral valves)
- Acquired obstructions
- 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+, 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 (e.g., Na+), water, and/or urea; (depending on the location of injury along the tubular system) → increased Na+ and H2O in the urine → decreased urine osmolality
- Bilateral urinary outflow obstruction (e.g., stones, BPH, neoplasia, congenital anomalies) → increased retrograde hydrostatic pressure within renal tubules → decreased GFR and compression of the renal vasculature → acidosis, fluid overload, and increased BUN, Na+, and K+.
- A normal GFR can be maintained as long as one kidney functions normally.
Four phases of AKI (some patients may not undergo all phases)
Initiating event (kidney injury)
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- May be asymptomatic.
- Oliguria or anuria
- Signs of volume depletion (in prerenal AKI caused by volume loss)
- Signs of fluid overload (from Na+ and H2O retention)
- Signs of uremia
- 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).
Subtypes and variants
Acute tubular necrosis
- Epidemiology: causes ∼ 85% of intrinsic AKIs
- Ischemic: Injury occurs secondary to decreased renal blood flow.
- Toxic: Injury occurs directly due to nephrotoxic substances.
- Other: sepsis, infections
- Pathophysiology: necrotic proximal tubular cells fall into the tubular lumen → debris obstructs tubules → decreased GFR → sequence of pathophysiological events similar to prerenal failure (i.e., activation of RAAS; see “Pathophysiology” above)
- Clinical features: same as AKI (see “Clinical features” and four phases of AKI above)
Diagnostics (see “Diagnostics” below)
- Blood findings: azotemia, hyperkalemia, and metabolic acidosis
- Urinary findings
- Urinary sediment
- Management: See “Treatment” below.
Renal cortical necrosis
- Definition: rare cause of AKI caused by acute generalized ischemic necrosis of the renal cortex in both kidneys
- Etiology: septic shock, disseminated intravascular coagulation (DIC); , hemolytic uremic syndrome (HUS), obstetric complications; (e.g., abruptio placentae, septic abortion, postpartum hemorrhage)
- Pathophysiology: vasospasms and microvascular injury with vascular thrombosis → prolonged severe renal ischemia → diffuse; and/or patchy destruction of the renal cortex
- Clinical features: flank pain, CVA tenderness and signs of AKI (see also “Clinical features” above and shock)
- Management: Dialysis can improve outcomes (see “Treatment” below).
- Prognosis: high mortality rates without treatment
- 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|| || |
- 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
Blood test findings
- Elevated serum creatinine concentration; and rapidly rising serum creatinine level
- BUN:creatinine ratio < 15:1.
- Markedly elevated serum CPK level (10,000–100,000) in rhabdomyolysis
- Hyperkalemia, metabolic acidosis; , hyperphosphatemia, hypocalcemia, hyperuricemia, and/or dyslipidemia (especially hypertriglyceridemia) may be seen.
- Low Hb (anemia) due to decreased EPO
- 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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|Urine sodium concentration (mEq/L)|| || |
|Urine osmolality (mOsm/kg)|| || || |
|Urine sediments|| |
Consequences of acute and chronic renal failure (MAD HUNGER): Metabolic Acidosis, Dyslipidemia, High potassium, Uremia, Na+/H2O retention, Growth retardation, Erythropoietin failure (anemia), Renal osteodystrophy.
- 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 chronic renal failure. Treat early!
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