What Happens to the Kidneys in Acute Kidney Injury
In AKI, the kidneys experience a sudden loss of excretory function, resulting in an inability to eliminate waste products and maintain fluid and electrolyte balance, with pathophysiology ranging from ischemic tubular injury to direct nephrotoxic damage. 1
Functional Changes
The kidneys undergo an abrupt decline in glomerular filtration rate (GFR), manifesting as:
- Accumulation of nitrogenous waste products (elevated serum creatinine and blood urea nitrogen) due to impaired filtration capacity 1
- Loss of ability to regulate fluid balance, leading to volume overload and potential pulmonary edema 2
- Electrolyte dysregulation, including hyperkalemia, metabolic acidosis, and disturbances in sodium, chloride, and bicarbonate levels that worsen with increasing AKI severity 3
- Oliguria or anuria in many cases, though non-oliguric AKI also occurs frequently 2
Structural and Cellular Damage
The kidney tissue experiences varying degrees of injury depending on the etiology:
- Acute tubular necrosis (ATN) is the most common intrarenal pathology, caused by either ischemic injury or nephrotoxic exposures 4
- Loss of tubular cells and nephrons occurs with ongoing injury, which can become irreversible if AKI progresses to acute kidney disease (AKD) or chronic kidney disease (CKD) 1
- Ongoing cellular injury, repair, and regeneration may persist even after serum creatinine returns toward baseline, detectable through biomarkers, proteinuria, or loss of renal reserve 2
- Drug-associated AKI occurs in approximately 25% of critically ill patients, with each nephrotoxin administration presenting 53% greater odds of developing AKI 5
Hemodynamic Alterations
Renal perfusion becomes critically compromised:
- Decreased renal blood flow from hypovolemia, hypotension, or impaired cardiac output reduces oxygen delivery to tubular cells 6
- Loss of autoregulation in severe cases, making the kidneys vulnerable to even minor fluctuations in blood pressure 6
- Microvascular dysfunction and endothelial injury contribute to persistent ischemia even after macrovascular perfusion is restored 6
Progression and Recovery Patterns
The kidney's response to injury follows distinct trajectories:
- Incomplete recovery is common—even when serum creatinine returns to baseline, patients may have ongoing kidney damage evidenced by proteinuria, hypertension, or reduced renal reserve 2
- Loss of renal reserve occurs in many survivors, meaning the kidneys have diminished capacity to respond to future stressors despite apparently normal baseline function 2
- Transition to chronic disease happens when AKI persists beyond 3 months without resolution, meeting criteria for CKD 7
- Vulnerability to recurrent injury remains elevated even in patients who achieve apparent clinical recovery, with increased long-term risk of cardiovascular events, CKD progression, and mortality 2
Common Pitfalls in Understanding AKI Pathophysiology
Do not assume serum creatinine normalization equals complete kidney recovery—structural damage, proteinuria, and loss of renal reserve frequently persist despite creatinine returning to baseline 2. This is why the concept of AKD Stage 0B exists, recognizing ongoing kidney damage even with "normal" creatinine 2.
Avoid the oversimplified "prerenal, renal, postrenal" classification in isolation—AKI is typically multifactorial, with overlapping mechanisms including ischemia, nephrotoxicity, sepsis, and hemodynamic instability occurring simultaneously 4. While this classification helps establish differential diagnosis, real-world AKI rarely fits neatly into one category 2.
Do not overlook the dynamic nature of kidney injury—the kidneys undergo continuous processes of injury, repair, and adaptation throughout the AKI episode and recovery phase, requiring ongoing assessment beyond the acute period 2, 1.