Residency · Residency · Internal Medicine
Acute Kidney Injury: Classification, Workup, and Management
Overview
Acute kidney injury (AKI) is a sudden decline in kidney function defined by rises in serum creatinine and/or decreases in urine output. It occurs in 10-15% of hospitalized patients and up to 50% of ICU patients. AKI is associated with increased mortality, prolonged hospital stays, and increased risk of progression to chronic kidney disease. Prevention and early recognition are critical because no specific pharmacotherapy reverses established AKI.
Classification
KDIGO Staging
| KDIGO Stage | Creatinine Criteria | Urine Output Criteria |
|---|---|---|
| 1 | Rise ≥0.3 mg/dL in 48h OR 1.5-1.9x baseline in 7 days | <0.5 mL/kg/h for 6-12 hours |
| 2 | 2.0-2.9x baseline | <0.5 mL/kg/h for ≥12 hours |
| 3 | ≥3.0x baseline OR ≥4.0 mg/dL OR initiation of RRT | <0.3 mL/kg/h for ≥24h OR anuria ≥12h |
Stage 1 is defined by a creatinine rise of 0.3 mg/dL or more within 48 hours, or a rise to 1.5-1.9 times baseline within 7 days, or urine output below 0.5 mL/kg/h for 6-12 hours. Stage 2 requires creatinine at 2.0-2.9 times baseline or urine output below 0.5 mL/kg/h for 12 or more hours. Stage 3 is defined by creatinine at 3.0 times baseline or above, or an absolute value of 4.0 mg/dL or higher, or initiation of renal replacement therapy, or urine output below 0.3 mL/kg/h for 24 or more hours, or anuria for 12 or more hours.
Etiologic Categories
Pre-renal AKI accounts for 60-70% of cases and results from decreased renal perfusion due to dehydration, hemorrhage, heart failure, sepsis, hepatorenal syndrome, or medications such as NSAIDs and ACE inhibitors/ARBs. Intrinsic renal AKI (25-30%) involves parenchymal damage and includes acute tubular necrosis (ATN) from ischemic or nephrotoxic insults (the most common intrinsic cause), acute interstitial nephritis (AIN) from drugs such as PPIs, antibiotics, and NSAIDs, glomerulonephritis including rapidly progressive GN, and vascular causes such as renal artery thrombosis, atheroembolic disease, and thrombotic microangiopathy. Post-renal AKI (5-10%) results from obstruction by BPH, kidney stones, pelvic malignancy, or retroperitoneal fibrosis.
<image>Etiologic classification of acute kidney injury showing pre-renal, intrinsic renal (ATN, AIN, GN, vascular), and post-renal causes with key examples for each category</image>
Diagnostic Workup
Initial Assessment
The evaluation begins with a comprehensive medication review focused on nephrotoxins (NSAIDs, aminoglycosides, contrast, ACE inhibitors/ARBs), volume status assessment (orthostatics, skin turgor, JVP, edema), and Foley catheter placement or bladder scan to rule out urinary retention.
Laboratory Studies
A basic metabolic panel establishes the creatinine trend, BUN, and identifies electrolyte derangements such as hyperkalemia and metabolic acidosis. Urinalysis with microscopy is essential and often underutilized: muddy brown granular casts indicate ATN, WBC casts and eosinophils suggest AIN, RBC casts and dysmorphic RBCs point to glomerulonephritis, and a bland sediment is consistent with pre-renal or post-renal causes.
The fractional excretion of sodium (FENa) helps differentiate pre-renal (below 1%, reflecting avid sodium retention) from intrinsic renal causes (above 2%, indicating ATN). An important caveat is that FENa is unreliable in patients on diuretics, in which case the fractional excretion of urea (FEUrea) should be used instead: below 35% suggests pre-renal, while above 50% suggests intrinsic renal disease.
Additional laboratory studies are guided by clinical suspicion and include CK for rhabdomyolysis, LDH and haptoglobin for hemolysis, complement, ANCA, and anti-GBM if glomerulonephritis is suspected, and serum and urine protein electrophoresis if myeloma cast nephropathy is a consideration.
Imaging
Renal ultrasound is the first-line imaging study to evaluate for hydronephrosis (obstruction) and kidney size. Small echogenic kidneys suggest underlying CKD, though normal-sized kidneys do not exclude it. CT without contrast is obtained if stone disease is suspected.
<image>Urine microscopy findings in acute kidney injury showing muddy brown granular casts of ATN, white blood cell casts of AIN, and red blood cell casts of glomerulonephritis</image>
Management
General Principles
The cornerstone of management is treating the underlying cause: volume resuscitation for pre-renal AKI, obstruction relief for post-renal, and discontinuation of nephrotoxins. Hemodynamics should be optimized to maintain adequate mean arterial pressure (65 mmHg or above). NSAIDs, aminoglycosides, and ACE inhibitors/ARBs should be held during the acute episode. Medications must be dose-adjusted for reduced GFR. Close monitoring of electrolytes, acid-base status, fluid balance, and urine output is essential.
Fluid Management
Pre-renal AKI requires IV crystalloid resuscitation, with balanced crystalloids preferred. Fluid overload must be avoided in oliguric or anuric patients. "Renal dose" dopamine has no proven benefit and this practice should be abandoned.
Indications for Renal Replacement Therapy (RRT)
Absolute indications for emergent dialysis include refractory hyperkalemia, severe metabolic acidosis (pH below 7.1) unresponsive to bicarbonate, refractory volume overload or pulmonary edema, uremic complications (encephalopathy, pericarditis, bleeding), and certain toxic ingestions (methanol, ethylene glycol, lithium, salicylates). The STARRT-AKI trial demonstrated no benefit to early initiation of RRT based on biochemical thresholds alone in critically ill patients without urgent indications; the accelerated strategy led to more RRT without a mortality benefit.
<image>Algorithm for management of acute kidney injury showing stepwise approach from initial assessment through volume optimization, nephrotoxin removal, and indications for renal replacement therapy</image>
Specific AKI Etiologies
Contrast-associated AKI is managed with pre-hydration using isotonic crystalloid and holding metformin; notably, the risk is often overstated in patients with eGFR above 30. Rhabdomyolysis requires aggressive IV crystalloid resuscitation targeting urine output of 200-300 mL/h, with no proven role for bicarbonate or mannitol. Acute interstitial nephritis is managed by discontinuing the offending drug; the role of corticosteroids is debated but they may accelerate recovery if started early. Tumor lysis syndrome is treated with rasburicase, aggressive hydration, and allopurinol prophylaxis.
Prevention
Prevention strategies include avoiding nephrotoxins when possible, providing adequate pre-procedural hydration for contrast studies, using balanced crystalloids over 0.9% saline (the SMART trial showed lower composite of death, new RRT, or persistent renal dysfunction), and holding ACE inhibitors/ARBs perioperatively in high-risk settings (though practice varies).
Clinical Pearls
A bland urinalysis with rising creatinine should prompt consideration of pre-renal AKI, obstruction, or myeloma cast nephropathy. FENa is only useful in oliguria and is unreliable in non-oliguric AKI. Creatinine is a lagging indicator, with a rise reflecting injury that occurred 24-48 hours prior. ATN typically recovers in 1-3 weeks if the insult is removed; persistent AKI beyond 3 weeks should prompt reconsideration of the diagnosis. Post-obstructive diuresis after catheter placement can cause significant volume depletion and requires close monitoring with appropriate replacement. Even mild AKI (Stage 1) is independently associated with long-term CKD, cardiovascular events, and mortality.
References
- Kellum JA, et al. KDIGO Clinical Practice Guideline for AKI. Kidney Int Suppl. 2012;2(1):1-138.
- STARRT-AKI Investigators. Timing of Initiation of RRT in AKI. N Engl J Med. 2020;383:240-251.
- Semler MW, et al. Balanced Crystalloids versus Saline in Critically Ill Adults (SMART). N Engl J Med. 2018;378:829-839.
- Perazella MA, Coca SG. Traditional Urinary Biomarkers in the Assessment of Hospital-Acquired AKI. Clin J Am Soc Nephrol. 2012;7:167-174.
- Ronco C, Bellomo R, Kellum JA. Acute Kidney Injury. Lancet. 2019;394:1949-1964.
