Medical School · Year 2 · Renal · includes a quiz and discussion video

Lecture 8: Acute Kidney Injury

Unit 2.1: Renal System

Learning Objectives

By the end of this lecture, students will be able to:

1. Define acute kidney injury and its diagnostic criteria
2. Classify AKI by etiology (prerenal, intrinsic, postrenal)
3. Describe the pathophysiology of acute tubular necrosis
4. Differentiate causes of AKI using clinical and laboratory findings
5. Explain the management principles for AKI
6. Describe indications for renal replacement therapy

Definition and Epidemiology

Acute kidney injury, formerly termed acute renal failure, describes a rapid decline in kidney function occurring over hours to days. The terminology shift from "failure" to "injury" reflects the spectrum of severity and the recognition that even modest kidney injury carries prognostic significance.

The Kidney Disease: Improving Global Outcomes (KDIGO) criteria provide standardized definitions for AKI diagnosis and staging. AKI is defined by an increase in serum creatinine of at least 0.3 mg/dL within 48 hours, or an increase to at least 1.5 times baseline within 7 days, or urine output less than 0.5 mL/kg/hour for 6 hours or more. These criteria intentionally capture both laboratory and clinical manifestations.

KDIGO staging classifies AKI severity into three stages with prognostic implications. Stage 1 represents creatinine rise of 1.5 to 1.9 times baseline or increase of at least 0.3 mg/dL, or urine output less than 0.5 mL/kg/hour for 6 to 12 hours. Stage 2 represents creatinine rise of 2.0 to 2.9 times baseline or urine output less than 0.5 mL/kg/hour for 12 hours or more. Stage 3 represents creatinine rise of 3 times baseline or more, or absolute creatinine of 4.0 mg/dL or more, or requirement for renal replacement therapy, or urine output less than 0.3 mL/kg/hour for 24 hours or more, or anuria for 12 hours or more.

The epidemiology of AKI varies by clinical setting. Community-acquired AKI occurs in 5 to 7 percent of hospital admissions. Hospital-acquired AKI affects 10 to 15 percent of all hospitalized patients. In intensive care units, AKI incidence reaches 30 to 60 percent. Mortality increases substantially with AKI severity, reaching 20 to 50 percent for stage 3 AKI.

Beyond acute mortality, AKI carries important long-term consequences. Survivors face 2 to 3-fold increased risk of developing or accelerating chronic kidney disease. Risk of progression to end-stage renal disease increases, and cardiovascular events are more common in the years following AKI. These outcomes underscore the importance of both prevention and follow-up care.

<image>Panel A: KDIGO diagnostic criteria showing creatinine rise of 0.3 mg/dL or more in 48 hours, or 1.5x baseline in 7 days, or urine output less than 0.5 mL/kg/hr for 6 or more hours. Panel B: Three KDIGO stages with creatinine and urine output criteria for each stage, color-coded by increasing severity. Panel C: AKI incidence bar graph by clinical setting showing community-acquired (5-7%), hospital-acquired (10-15%), and ICU (30-60%). Panel D: Outcomes showing short-term mortality increasing by stage and long-term risks including CKD progression, ESRD, and cardiovascular events.</image>

Classification of Acute Kidney Injury

AKI is traditionally classified by the anatomical location of the insult, which guides both diagnostic workup and management. The three categories—prerenal, intrinsic, and postrenal—have distinct mechanisms and implications.

Prerenal AKI, accounting for 55 to 60 percent of cases, results from decreased renal perfusion without intrinsic kidney damage. The tubules remain functional and respond appropriately by maximally conserving sodium and water. Common causes include true hypovolemia from hemorrhage, gastrointestinal losses, or inadequate fluid intake. Effective hypovolemia despite normal or elevated total body volume occurs in heart failure, where cardiac output is insufficient, and in cirrhosis, where splanchnic vasodilation reduces effective circulating volume. Renal hypoperfusion from medications that interfere with renal autoregulation—particularly NSAIDs and ACE inhibitors—can precipitate prerenal AKI, especially in patients whose baseline kidney function depends on prostaglandin-mediated afferent dilation or angiotensin-mediated efferent constriction. Renal artery stenosis or thrombosis represents a vascular cause of reduced perfusion.

Intrinsic AKI, comprising 35 to 40 percent of cases, involves structural damage to the kidney parenchyma. The injury may involve the tubules (acute tubular necrosis from ischemia or nephrotoxins), the interstitium (acute interstitial nephritis, typically drug-induced), the glomeruli (rapidly progressive glomerulonephritis, vasculitis), or the vessels (thrombotic microangiopathy, atheroembolic disease, malignant hypertension). Acute tubular necrosis is by far the most common form, often developing when prerenal hypoperfusion is prolonged or severe.

Postrenal AKI, representing 5 to 10 percent of cases, results from obstruction to urine flow. For obstruction to cause AKI, it must be bilateral (affecting both kidneys) or occur in a patient with a solitary functioning kidney. Unilateral obstruction in a patient with two normally functioning kidneys typically does not cause significant creatinine elevation because the contralateral kidney compensates. Causes include prostatic obstruction (benign or malignant), bladder stones or clots, neurogenic bladder, bilateral ureteral obstruction from stones, tumor, or retroperitoneal fibrosis.

<image>Panel A: Prerenal AKI (55-60%) showing decreased blood flow entering the kidney with causes including hypovolemia, heart failure, cirrhosis, NSAIDs/ACEi, and renal artery disease. Panel B: Intrinsic AKI (35-40%) showing damage within kidney parenchyma subdivided by structure with tubules (ATN), interstitium (AIN), glomeruli (GN), and vessels (TMA/atheroemboli). Panel C: Postrenal AKI (5-10%) showing obstruction beyond the kidney with causes by level including BPH, prostate cancer, bladder outlet obstruction, and bilateral ureteral stones or tumor. Panel D: Central kidney cross-section with arrows to each region and notation that bilateral obstruction or solitary kidney is required for postrenal AKI.</image>

Prerenal Acute Kidney Injury

Prerenal AKI represents the kidney's functional response to inadequate perfusion. Understanding this pathophysiology is essential because prerenal AKI is reversible if perfusion is restored before ischemic injury develops, but can progress to established tubular necrosis if hypoperfusion persists.

When renal blood flow decreases, glomerular filtration rate falls in parallel. However, tubular function remains intact, and the kidney mounts an appropriate physiological response. The renin-angiotensin-aldosterone system activates, producing sodium retention via increased proximal and collecting duct reabsorption. ADH levels rise, promoting water retention. Sympathetic nervous system activation supports blood pressure and cardiac output while enhancing sodium retention. The urine becomes maximally concentrated and nearly sodium-free as the kidney attempts to restore effective circulating volume.

Compensatory mechanisms help maintain GFR during moderate hypoperfusion. Prostaglandins dilate the afferent arteriole, maintaining inflow despite reduced perfusion pressure. Angiotensin II constricts the efferent arteriole, maintaining glomerular capillary pressure and filtration despite reduced flow. These compensatory mechanisms are directly antagonized by NSAIDs (which block prostaglandin synthesis) and ACE inhibitors or ARBs (which reduce angiotensin II). Administering these medications to patients with marginal renal perfusion can precipitate acute prerenal AKI.

Hepatorenal syndrome represents a special form of prerenal physiology in advanced cirrhosis with portal hypertension. Splanchnic vasodilation from nitric oxide and other mediators reduces effective circulating volume despite total body volume overload. The kidneys respond with intense vasoconstriction and sodium avidity. Type 1 hepatorenal syndrome progresses rapidly with doubling of creatinine over two weeks, carrying poor prognosis without liver transplantation. Type 2 develops more gradually and is associated with refractory ascites. Treatment involves splanchnic vasoconstrictors (terlipressin, midodrine, octreotide) combined with albumin to expand effective circulating volume, though liver transplantation remains definitive therapy.

<image>Panel A: Kidney with reduced blood flow showing intact tubules with concentrated urine, sodium avidity, and preserved cell structure representing functional prerenal response. Panel B: Compensatory mechanisms with prostaglandin dilating the afferent arteriole and angiotensin II constricting the efferent arteriole to maintain GFR. Panel C: Drug-induced prerenal AKI showing NSAIDs blocking afferent prostaglandin dilation and ACEi/ARBs blocking efferent angiotensin II constriction, with crossed-out arrows at each compensation point. Panel D: Hepatorenal syndrome showing cirrhotic liver with portal hypertension, splanchnic vasodilation, decreased effective circulating volume despite ascites, and intense renal vasoconstriction.</image>

Acute Tubular Necrosis

Acute tubular necrosis (ATN) represents the most common cause of intrinsic AKI, resulting from injury to tubular epithelial cells. Two general mechanisms produce ATN: ischemic injury from prolonged hypoperfusion, and direct nephrotoxic injury from drugs, pigments, or toxins.

Ischemic ATN develops when prerenal hypoperfusion is severe or prolonged enough to cause tubular cell death rather than merely reduced function. Surgical procedures with hypotension, septic shock, cardiogenic shock, and severe hemorrhage are common precipitants. The proximal tubule S3 segment and the medullary thick ascending limb are particularly vulnerable because of their high metabolic rates and the relatively hypoxic medullary environment.

Nephrotoxic ATN results from direct injury by various agents. Aminoglycoside antibiotics accumulate in proximal tubular cells over several days of therapy, causing dose- and duration-dependent toxicity typically manifest as non-oliguric AKI with concentrating defect. Amphotericin B produces tubular and arteriolar damage. Iodinated contrast media cause vasoconstriction and direct tubular toxicity, with creatinine rising within 24 to 48 hours and peaking at 3 to 5 days. Pigments including myoglobin from rhabdomyolysis and hemoglobin from intravascular hemolysis precipitate in tubules and generate reactive oxygen species. Cisplatin and other chemotherapeutic agents cause cumulative tubular damage.

The pathophysiology of ATN involves four overlapping phases. During initiation, ATP depletion from ischemia or toxin exposure leads to cytoskeletal disruption, loss of cell polarity, and detachment of cells from the basement membrane. During extension, ongoing hypoxia and inflammation amplify injury. During maintenance, GFR remains depressed through several mechanisms: tubular debris and casts obstruct the lumen, backleak of filtrate through the damaged epithelium returns it to the blood, and afferent arteriolar constriction reduces filtration. During recovery, surviving tubular cells proliferate and redifferentiate to restore epithelial integrity.

<image>Panel A: Two pathways to ATN showing ischemic causes (prolonged prerenal with hypotension, shock, surgery) and nephrotoxic causes (aminoglycosides, contrast, pigments, chemotherapy). Panel B: Four phases of ATN along a timeline showing initiation (ATP depletion, cytoskeletal disruption), extension (ongoing hypoxia and inflammation), maintenance (depressed GFR), and recovery (tubular cell proliferation). Panel C: Mechanisms of GFR decline during the maintenance phase including tubular obstruction by debris and casts, backleak of filtrate through damaged epithelium, and afferent vasoconstriction. Panel D: Nephron diagram identifying vulnerable segments (S3 proximal tubule and medullary thick ascending limb) with explanation of their high O2 demand in the hypoxic medullary environment.</image>

Specific Forms of Intrinsic AKI

Several specific causes of intrinsic AKI deserve individual attention because of their distinct presentations and management considerations.

Contrast-induced AKI develops predictably after iodinated contrast exposure, with creatinine rising within 24 to 48 hours and peaking at 3 to 5 days. Risk factors include pre-existing CKD (the strongest predictor), diabetes, volume depletion, large contrast volumes, and concurrent nephrotoxins. Prevention through adequate hydration before and after contrast exposure is the cornerstone; minimizing contrast volume, using iso-osmolar agents, and holding concurrent nephrotoxins also reduce risk. Most cases resolve spontaneously, though some patients require temporary or permanent dialysis.

Rhabdomyolysis releases massive amounts of myoglobin from damaged skeletal muscle. Causes include trauma, crush injury, prolonged immobilization, seizures, extreme exertion, and certain drugs and toxins including statins and cocaine. Laboratory findings include markedly elevated creatine kinase (often exceeding 10,000 U/L), hyperkalemia, hyperphosphatemia, hypocalcemia (from calcium precipitation in damaged muscle), and hyperuricemia. Urinalysis shows positive blood on dipstick (detecting myoglobin) but few or no red blood cells on microscopy. Treatment centers on aggressive intravenous fluid resuscitation to maintain urine output and dilute myoglobin; some advocate alkalinization to reduce myoglobin precipitation, though evidence is limited. Compartment syndrome requires monitoring and possible fasciotomy.

Tumor lysis syndrome occurs when rapidly proliferating tumors, particularly hematologic malignancies with high tumor burden, undergo massive cell death after chemotherapy initiation. Released intracellular contents produce hyperkalemia, hyperphosphatemia (with secondary hypocalcemia), and hyperuricemia. Uric acid and calcium phosphate precipitate in the tubules, causing obstruction. Prevention with hydration, allopurinol, or rasburicase (recombinant uricase) is preferred; established tumor lysis syndrome may require dialysis for electrolyte control.

Acute interstitial nephritis, discussed below, represents an important intrinsic cause with different pathophysiology and treatment than ATN.

<image>Panel A: Contrast nephropathy showing creatinine rise timeline (24-48 hour onset, peak at 3-5 days), risk factors (pre-existing CKD, diabetes, volume depletion), and prevention strategies (hydration, minimize contrast, hold nephrotoxins). Panel B: Rhabdomyolysis showing damaged muscle releasing myoglobin, laboratory findings (CK greater than 10,000, elevated K+ and phosphate, low Ca2+, positive urine blood but no RBCs on microscopy), and treatment with aggressive IV fluids. Panel C: Tumor lysis syndrome showing lysing tumor cells releasing K+, phosphate, and uric acid, with precipitation in tubules and prevention/treatment (hydration, allopurinol, rasburicase). Panel D: Aminoglycoside nephrotoxicity showing proximal tubule accumulation over 5-7 days, non-oliguric AKI pattern, and risk factors (dose, duration, dehydration).</image>

Acute Interstitial Nephritis

Acute interstitial nephritis (AIN) represents an allergic or immunologically mediated inflammatory reaction within the kidney interstitium, distinct from the ischemic or toxic injury of ATN. Drugs cause 70 to 75 percent of cases, with infections accounting for 5 to 10 percent and autoimmune conditions making up the remainder.

Drug-induced AIN can occur with virtually any medication but is particularly associated with certain classes. Beta-lactam antibiotics (penicillins, cephalosporins) were historically the most common cause. Proton pump inhibitors have emerged as an increasingly recognized cause, often with insidious onset after prolonged exposure. NSAIDs produce a unique form with nephrotic-range proteinuria in addition to interstitial inflammation. Sulfonamides, quinolones, and allopurinol are other important causes. The reaction is idiosyncratic rather than dose-dependent, occurring in susceptible individuals after variable exposure periods typically ranging from 1 to 3 weeks.

The classic clinical triad of fever, rash, and eosinophilia is present in fewer than 30 percent of cases, making clinical diagnosis challenging. AKI of variable severity develops, often non-oliguric. Patients may report flank pain or exhibit features of the systemic hypersensitivity reaction.

Urinalysis shows sterile pyuria (white blood cells without bacteria), and white blood cell casts may be seen. Urine eosinophils were historically considered helpful but have poor sensitivity and specificity. Gallium scanning may show renal uptake. Definitive diagnosis requires kidney biopsy demonstrating interstitial inflammation with edema and tubulitis, often with eosinophils.

Management centers on withdrawing the offending agent, which is sufficient for recovery in many cases. The role of corticosteroids remains debated; observational data suggest faster recovery with steroids, particularly if started early, but randomized controlled trial evidence is lacking. Prognosis is generally favorable with early recognition and drug withdrawal, though delayed diagnosis may lead to interstitial fibrosis and permanent kidney damage.

<image>Panel A: Causative agents by category showing drugs (beta-lactams, PPIs, NSAIDs, sulfonamides) as most common, infections (pyelonephritis, viral), and autoimmune causes (sarcoidosis, Sjogren syndrome, TINU syndrome). Panel B: Classic triad of fever, rash, and eosinophilia with notation that the complete triad is present in fewer than 30% of cases. Panel C: Urinalysis findings showing sterile pyuria, WBC casts, and possible eosinophils (low sensitivity), alongside kidney biopsy histology with interstitial inflammation, edema, and eosinophilic infiltrate. Panel D: Management algorithm showing removal of offending agent, observation for improvement, and consideration of corticosteroids if no improvement occurs.</image>

Other Intrinsic Causes

Several additional intrinsic causes of AKI present with distinct clinical features and require specific diagnostic approaches and treatments.

Rapidly progressive glomerulonephritis (RPGN) describes the clinical syndrome of rapid GFR loss with an active urine sediment (red blood cells, red cell casts, proteinuria) and crescent formation on biopsy. Three immunological patterns exist. Anti-GBM disease (Goodpasture syndrome when lungs are also involved) produces linear IgG staining along the glomerular basement membrane. Immune complex disease (lupus nephritis, IgA nephropathy, post-infectious) shows granular immune deposits. Pauci-immune glomerulonephritis (typically ANCA-associated vasculitis—granulomatosis with polyangiitis or microscopic polyangiitis) shows few or no immune deposits. Treatment involves aggressive immunosuppression, and plasma exchange is indicated for anti-GBM disease and severe ANCA-associated disease.

Atheroembolic disease occurs when cholesterol crystals from atherosclerotic aortic plaques shower into the renal vasculature. Triggers include vascular procedures (catheterization, vascular surgery) and anticoagulation. Unlike contrast nephropathy, the onset is often delayed (days to weeks) and the course is progressive or stepwise rather than peaking and recovering. Systemic findings include livedo reticularis, blue toe syndrome, and evidence of distal emboli. Laboratory findings may include eosinophilia, low complement, and eosinophiluria. Biopsy shows characteristic cholesterol clefts. Treatment is supportive; prognosis is often poor.

Thrombotic microangiopathy encompasses conditions characterized by endothelial injury, microthrombi formation, and microangiopathic hemolytic anemia. Thrombotic thrombocytopenic purpura (TTP) results from ADAMTS13 deficiency, producing a clinical pentad of microangiopathic hemolytic anemia, thrombocytopenia, neurological changes, renal impairment, and fever. Hemolytic uremic syndrome (HUS) in children typically follows Shiga toxin-producing E. coli infection. Atypical HUS results from complement dysregulation. Laboratory findings include schistocytes on blood smear, thrombocytopenia, elevated LDH, and low haptoglobin. Treatment depends on the specific etiology: plasma exchange for TTP, supportive care for typical HUS, and complement inhibition (eculizumab) for atypical HUS.

<image>Panel A: RPGN showing glomerulus with crescents classified by immunofluorescence pattern (linear for anti-GBM, granular for immune complex, pauci-immune for ANCA), associated diseases, and treatment with immunosuppression plus or minus plasma exchange. Panel B: Atheroembolic disease showing aortic plaque with cholesterol crystal emboli traveling to kidney, skin findings (livedo reticularis, blue toes), delayed onset after vascular procedure, and characteristic cholesterol cleft on biopsy. Panel C: Thrombotic microangiopathy showing endothelial injury leading to microthrombi and blood smear with schistocytes. Panel D: TMA differential showing TTP (ADAMTS13 deficiency, treated with plasma exchange), typical HUS (Shiga toxin, supportive care), and atypical HUS (complement dysregulation, eculizumab).</image>

Postrenal Acute Kidney Injury

Postrenal AKI results from obstruction to urine flow at any level from the renal pelvis to the urethra. Because humans have two kidneys, bilateral obstruction (or obstruction of a solitary functioning kidney) is required for significant creatinine elevation.

Lower urinary tract obstruction at the bladder outlet is most commonly caused by benign prostatic hyperplasia in older men, with prostate cancer being another important cause. Neurogenic bladder from diabetes, spinal cord injury, or medications can produce functional outlet obstruction. Urethral strictures and blood clots may also obstruct flow. Patients often report urinary symptoms including hesitancy, weak stream, and incomplete emptying. Physical examination may reveal a distended, palpable bladder.

Upper urinary tract obstruction at the level of the ureters requires bilateral involvement or a solitary kidney. Nephrolithiasis with bilateral or sequential obstruction can cause AKI. Malignancy may obstruct ureters through direct invasion or external compression from retroperitoneal tumors or lymphadenopathy. Retroperitoneal fibrosis, whether idiopathic or associated with medications, malignancy, or infection, can encase the ureters. Papillary necrosis from analgesic abuse, sickle cell disease, or diabetes can obstruct the collecting system.

Clinical features depend on the level and acuteness of obstruction. Complete obstruction produces anuria; partial obstruction may cause alternating polyuria and oliguria or normal output. Acute obstruction, particularly with stones, often causes severe flank pain, while chronic obstruction may be painless. Upper tract obstruction does not cause bladder distension.

Diagnosis relies on imaging. Ultrasound is the initial test of choice, showing hydronephrosis (dilation of the collecting system). However, early obstruction may not yet produce visible dilation, and retroperitoneal fibrosis may prevent dilation despite obstruction. CT provides detailed anatomical information about the cause. Bladder scan reveals elevated post-void residual in lower tract obstruction.

Treatment involves relieving obstruction. For lower tract obstruction, bladder catheterization (urethral or suprapubic) provides immediate relief. For upper tract obstruction, nephrostomy tubes or ureteral stents decompress the system. Post-obstructive diuresis may occur after relief of prolonged obstruction as the kidney excretes accumulated solute and water; monitoring and fluid replacement prevent hypovolemia.

<image>Panel A: Urinary tract anatomy with obstruction sites highlighted at the urethra (stricture), bladder outlet (BPH, prostate cancer, neurogenic bladder), and bilateral ureters (stones, tumor, retroperitoneal fibrosis), noting bilateral obstruction or solitary kidney is required. Panel B: Diagnostic imaging showing ultrasound with hydronephrosis revealing dilated renal pelvis and calyces. Panel C: Management by obstruction level showing Foley catheter for lower tract obstruction and nephrostomy tube or ureteral stent for upper tract obstruction. Panel D: Post-obstructive diuresis showing massive urine output after obstruction relief, risk of hypovolemia, and need for fluid monitoring and replacement.</image>

Diagnostic Approach

Distinguishing between categories of AKI guides management and prognosis. A systematic approach incorporating history, physical examination, and laboratory evaluation is essential.

The history provides crucial clues. Recent hypotension, surgery, or volume loss suggests prerenal or ischemic ATN. New medications, particularly antibiotics, NSAIDs, and PPIs, raise concern for nephrotoxic ATN or AIN. Contrast exposure within the preceding 24 to 72 hours suggests contrast nephropathy. Muscle trauma, immobilization, or seizure suggests rhabdomyolysis. Urinary symptoms suggest obstruction. Systemic illness with rash, arthralgias, or respiratory symptoms may indicate glomerulonephritis or vasculitis.

Physical examination assesses volume status and searches for systemic findings. Signs of volume depletion (orthostatic hypotension, tachycardia, dry mucous membranes, poor skin turgor) support prerenal etiology. Distended bladder suggests lower tract obstruction. Skin findings may indicate vasculitis (palpable purpura), atheroemboli (livedo reticularis, blue toes), or drug reaction (rash).

Laboratory indices help distinguish prerenal from intrinsic AKI, particularly ATN. In prerenal AKI, tubular function is intact and the kidney avidly retains sodium: fractional excretion of sodium (FENa) is typically less than 1 percent, urine sodium is less than 20 mEq/L, urine osmolality exceeds 500 mOsm/kg, and BUN:creatinine ratio exceeds 20:1 (reflecting enhanced urea reabsorption). In ATN, tubular dysfunction impairs sodium reabsorption: FENa exceeds 2 percent, urine sodium exceeds 40 mEq/L, urine osmolality is typically less than 350 mOsm/kg, and BUN:creatinine ratio approximates 10 to 15:1.

Important caveats limit the utility of FENa. Diuretics increase sodium excretion and may elevate FENa despite prerenal physiology; in this setting, fractional excretion of urea (FEUrea less than 35% suggests prerenal) is more reliable. Contrast nephropathy and pigment nephropathy (myoglobin, hemoglobin) may show low FENa despite intrinsic injury because of vasoconstriction. Patients with CKD have elevated baseline FENa.

Urinalysis and sediment examination provide critical diagnostic information. A bland sediment (few cells, hyaline casts only) suggests prerenal AKI or obstruction. Muddy brown granular casts are characteristic of ATN, representing degenerating tubular cells. White blood cell casts suggest interstitial nephritis or pyelonephritis. Red blood cell casts indicate glomerulonephritis. Proteinuria with hematuria suggests glomerular disease.

<image>Panel A: History and physical assessment starting from AKI detection, with hypotension suggesting prerenal/ATN, medications suggesting ATN/AIN, contrast exposure suggesting contrast nephropathy, and urinary symptoms suggesting obstruction. Panel B: Ultrasound branch showing hydronephrosis indicating postrenal AKI and absence of hydronephrosis prompting continued workup. Panel C: Laboratory indices table comparing prerenal versus ATN with FENa (less than 1% vs greater than 2%), urine Na (less than 20 vs greater than 40 mEq/L), urine osmolality (greater than 500 vs less than 350 mOsm/kg), and BUN:Cr ratio (greater than 20 vs 10-15), including FENa limitations with diuretics, contrast, pigments, and CKD. Panel D: Urine sediment findings showing bland sediment (prerenal/obstruction), muddy brown granular casts (ATN), WBC casts (AIN), and RBC casts (glomerulonephritis).</image>

Management of Acute Kidney Injury

Management of AKI focuses on identifying and treating the underlying cause, preventing further injury, managing complications, and providing supportive care while awaiting recovery.

For prerenal AKI, treatment involves restoring renal perfusion. Volume depletion requires crystalloid resuscitation with isotonic saline or balanced solutions. Cardiogenic shock may require inotropic support. Hepatorenal syndrome is treated with albumin and vasoconstrictors. Offending medications (NSAIDs, ACE inhibitors) should be held during the acute episode.

For intrinsic AKI, treatment depends on the specific cause. ATN is largely supportive, as there is no specific therapy to accelerate tubular recovery. Drug-induced AIN requires withdrawal of the offending agent; corticosteroids are sometimes used but evidence is limited. Glomerulonephritis and vasculitis require immunosuppressive therapy appropriate to the specific diagnosis. Rhabdomyolysis treatment centers on aggressive fluid resuscitation.

For postrenal AKI, obstruction must be relieved promptly. Bladder catheterization addresses lower tract obstruction. Nephrostomy or ureteral stenting addresses upper tract obstruction. Post-obstructive diuresis requires careful monitoring and fluid replacement to prevent hypovolemia.

General management principles apply to all AKI. Nephrotoxins should be avoided or dose-adjusted. Drug dosing must be adjusted for reduced GFR. Hyperkalemia is managed with dietary restriction, potassium binders, and dialysis if severe. Metabolic acidosis may require bicarbonate supplementation. Volume overload is treated with diuretics if the patient is responsive, or dialysis if refractory. Uremia with symptoms (pericarditis, encephalopathy, bleeding) requires dialysis.

<image>Panel A: Prerenal management showing IV fluids for hypovolemia, inotropes for cardiogenic shock, vasoconstrictors plus albumin for hepatorenal syndrome, and holding NSAIDs/ACEi. Panel B: Intrinsic AKI management showing cause-specific treatments with supportive care for ATN, drug removal plus or minus steroids for AIN, immunosuppression for GN, and aggressive fluids for rhabdomyolysis. Panel C: Postrenal management showing Foley catheter for outlet obstruction, nephrostomy or ureteral stent for upper tract obstruction, and monitoring for post-obstructive diuresis. Panel D: General measures for all AKI types including avoiding nephrotoxins, adjusting drug doses, managing hyperkalemia (restriction, binders, dialysis), treating acidosis, managing volume, and dialysis for uremia.</image>

Renal Replacement Therapy

Renal replacement therapy (dialysis) becomes necessary when conservative management cannot control the complications of AKI or when uremic toxicity develops. The traditional indications are remembered by the mnemonic AEIOU.

Acidosis that is severe (pH less than 7.1 to 7.2) and refractory to bicarbonate therapy indicates dialysis. The acidosis of AKI reflects inability to excrete the daily fixed acid load and may be compounded by lactic acidosis from underlying illness.

Electrolyte abnormalities, particularly hyperkalemia, may require dialysis when medical therapy (calcium, insulin/glucose, albuterol, diuretics, binders) fails to control the level or when life-threatening ECG changes persist. Refractory hyperphosphatemia and other electrolyte disturbances may also factor into the decision.

Intoxication with dialyzable toxins (methanol, ethylene glycol, lithium, salicylates, certain medications) may warrant emergent dialysis even before significant AKI develops.

Overload of volume that is refractory to diuretic therapy—manifesting as pulmonary edema, respiratory compromise, or severe hypertension—indicates dialysis. Patients with oliguric or anuric AKI who cannot achieve negative fluid balance with diuretics require ultrafiltration.

Uremia with clinical manifestations including pericarditis (detected by rub or pericardial effusion), encephalopathy (confusion, asterixis, seizures), or bleeding diathesis mandates dialysis regardless of absolute laboratory values.

The optimal timing of dialysis initiation for AKI without these urgent indications remains debated. Recent trials have not shown benefit from early, preemptive dialysis compared to waiting for conventional indications. Individual patient factors including trajectory, catabolic state, and likelihood of recovery guide decisions.

Modalities include intermittent hemodialysis, which provides efficient solute removal in hemodynamically stable patients, and continuous renal replacement therapy (CRRT), which is better tolerated in hemodynamically unstable patients and allows gentle, continuous fluid and solute removal.

<image>Panel A: AEIOU mnemonic for dialysis indications showing A for refractory Acidosis (pH less than 7.1-7.2) and E for refractory Electrolyte abnormalities (hyperkalemia with ECG changes). Panel B: AEIOU continued showing I for Intoxication with dialyzable toxins (methanol, ethylene glycol, lithium, salicylates) and O for volume Overload (pulmonary edema refractory to diuretics). Panel C: U for Uremia with clinical manifestations (pericarditis, encephalopathy, bleeding diathesis) mandating dialysis regardless of laboratory values. Panel D: Modality comparison showing intermittent hemodialysis (efficient, 3-4 hours, 3x weekly, for stable patients) versus CRRT (gentle, continuous, for hemodynamically unstable patients), with note that benefit of early or preemptive dialysis is not proven.</image>

Recovery and Outcomes

The clinical course of AKI varies based on etiology, severity, and patient factors. Understanding typical recovery patterns helps set expectations and guide follow-up.

Prerenal AKI reverses rapidly, often within 24 to 48 hours, once perfusion is restored. If correction is delayed and ATN develops, recovery takes longer.

ATN typically follows a triphasic course. The oliguric phase, lasting days to weeks, features low urine output and rising creatinine. Not all ATN is oliguric; non-oliguric ATN (preserved urine output) generally carries better prognosis. The diuretic phase follows as tubular function recovers; urine output increases, sometimes dramatically, but concentrating ability remains impaired and electrolyte abnormalities may occur. The recovery phase sees gradual normalization of creatinine, though return to baseline is not universal. Many patients retain some degree of permanent kidney damage.

Long-term outcomes after AKI extend well beyond the acute hospitalization. Patients who experience AKI have increased risk of developing CKD, and those with pre-existing CKD face accelerated progression. Risk of end-stage renal disease requiring chronic dialysis increases. Cardiovascular morbidity and mortality are elevated in AKI survivors. These observations underscore the importance of nephrology follow-up after discharge, with monitoring of kidney function, proteinuria, and cardiovascular risk factors.

Prevention of AKI in high-risk settings is preferable to treatment. Strategies include maintaining adequate volume status, avoiding nephrotoxins when possible, using alternatives to iodinated contrast when feasible, and adjusting drug dosing for renal function.

<image>Panel A: Typical ATN course showing oliguric phase (days to weeks, low urine output, rising creatinine), diuretic phase (increasing urine output, concentrating defect, electrolyte disturbances), and recovery phase (creatinine improving, may not return to baseline). Panel B: Comparison of oliguric versus non-oliguric ATN showing better prognosis with non-oliguric presentation. Panel C: Long-term outcomes showing AKI episode leading to increased risk of CKD development and progression, ESRD, cardiovascular events, and mortality. Panel D: Follow-up and prevention checklist including nephrology referral, monitoring GFR and proteinuria, cardiovascular risk assessment, avoiding nephrotoxins, and prevention strategies for high-risk settings.</image>

Summary

• AKI is defined by creatinine rise of 0.3 mg/dL in 48 hours, 1.5× baseline in 7 days, or urine output less than 0.5 mL/kg/hr for 6 hours
• Classification by anatomy: prerenal (55-60%), intrinsic (35-40%), postrenal (5-10%)
• Prerenal AKI reflects decreased perfusion with intact tubular function; FENa less than 1%, BUN:Cr greater than 20
• ATN results from ischemic or nephrotoxic tubular injury; FENa greater than 2%, muddy brown casts
• AIN is typically drug-induced; the classic triad of fever, rash, and eosinophilia is present in less than 30%
• Postrenal AKI requires bilateral obstruction; ultrasound shows hydronephrosis
• Diagnosis integrates history, volume status, laboratory indices, and urine sediment
• Management: treat the underlying cause, avoid nephrotoxins, adjust drug dosing, manage complications
• Dialysis indications (AEIOU): Acidosis, Electrolytes, Intoxication, Overload, Uremia
• Long-term outcomes include increased risk of CKD, ESRD, and cardiovascular events

Key Terms

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