Acute Kidney Injury

Acute Kidney Injury (AKI)

AKI is a rapid decline in kidney function (hours to days), resulting in the accumulation of nitrogenous waste, electrolyte imbalance, and dysregulation of volume and acid-base status.

Conceptual continuum: AKI (0–7 days) → AKD (7–90 days) → CKD (≥90 days).

Important nuance: AKD is a broader concept than simply “AKI lasting 7–90 days.” AKD can occur with or without preceding AKI; the 7–90-day description is particularly useful when discussing persistent kidney dysfunction following AKI.

KDIGO Criteria 

AKI is diagnosed if any of the following are present:

• ↑ Serum creatinine (SCr) by ≥0.3 mg/dL within 48 hours
• ↑ SCr ≥1.5× baseline within 7 days
• Urine output (UO) <0.5 mL/kg/h for ≥6 hours

KDIGO Staging

Why Creatinine Is an Imperfect Marker

Serum creatinine is a functional marker, not a direct marker of structural renal injury.

After an acute fall in GFR, serum creatinine may take 24–48 hours or longer to substantially rise.

Creatinine is affected by:Muscle mass,Age,Sex

• Nutritional status,Liver disease,Volume status
• Creatinine production,Drugs affecting tubular secretion,Fluid resuscitation.

Dilutional effect in ICU patients

Large-volume fluid administration increases the volume of distribution of creatinine.

Therefore:

A massively fluid-resuscitated patient may have substantial AKI despite a deceptively modest serum creatinine rise.

Isolated Oliguria

Isolated oliguria refers to reduced urine output with a relatively stable serum creatinine.

• Oliguria: urine output <0.5 mL/kg/h or roughly <500 ml/day.
• It may represent an early sign of AKI, sometimes preceding the rise in serum creatinine.
• Oliguria Normal compensatory mechanism to conserve fluid(Kidney is compensating for hypoperfusion )

Non-Oliguric AKI

Non-oliguric AKI refers to rising serum creatinine despite preserved urine output, usually >0.5 mL/kg/h.

• Normal urine output does not exclude significant AKI.
• Many patients with intrinsic renal injury, particularly acute tubular injury (ATI), remain non-oliguric.
• It may also occur with AIN, glomerular disease, nephrotoxic injury, and partial urinary obstruction.
• Non-oliguric AKI generally has a better prognosis and lower likelihood of requiring KRT than severe oliguric/anuric AKI, although the underlying cause and AKI severity remain more important than urine output alone.

Etiological Classification

The classic approach divides AKI into:

1. Prerenal
2. Intrinsic renal
3. Postrenal

Prerenal AKI

Prerenal AKI results from reduced renal perfusion without initial structural parenchymal injury.

If prolonged/severe, prerenal injury can progress to ischemic acute tubular injury.

Causes

A. True intravascular volume depletion

• Hemorrhage,Vomiting,Diarrhea,Excessive diuresis
• Poor oral intake,Burns,Polyuria,Third-space losses

B. Reduced effective circulating volume

Total body fluid may actually be increased.

Examples:Heart failure,Cardiogenic shock

• Cirrhosis,Hepatorenal syndrome,Severe hypoalbuminemia

C. Systemic vasodilation / hypotension

• Sepsis,Septic shock
• Anaphylaxis,Vasodilator drugs

D. Altered renal autoregulation

Afferent arteriolar vasoconstriction

Examples:NSAIDs,Calcineurin inhibitors,Hypercalcemia

NSAIDs inhibit prostaglandin synthesis → afferent vasoconstriction → ↓GFR.

Efferent arteriolar vasodilation

Examples:ACE inhibitors,ARBs

Particularly important in:

• Bilateral renal artery stenosis
• Severe volume depletion
• Advanced heart failure

Venous Congestion and AKI

A common ICU misconception is:

AKI = give fluid.

This can be dangerous.

Elevated renal venous pressure can reduce effective filtration.

Seen particularly in:

• RV failure
• Severe TR
• Pulmonary hypertension
• Cardiorenal syndrome
• Fluid overload
• High intra-abdominal pressure

Therefore:

Congestive nephropathy may improve with decongestion rather than additional fluid.

Intrinsic Renal AKI

A useful classification is:

Acute Tubular Injury — ATI

Traditionally called acute tubular necrosis (ATN).

In many patients there may be severe tubular dysfunction without widespread frank tubular necrosis, so acute tubular injury is increasingly preferred.

ATI is one of the most important causes of intrinsic AKI in ICU patients.

Major mechanisms

Ischemic ATI

Occurs with:

• Septic shock
• Hemorrhagic shock
• Major surgery
• Cardiac surgery
• Prolonged hypotension
• Cardiac arrest

Nephrotoxic ATI

Causes include:

• Aminoglycosides
• Amphotericin B
• Cisplatin
• Some antivirals
• Pigment nephropathy
• Toxic alcohol–related crystal injury
• Tumor lysis–related crystal injury

Acute Interstitial Nephritis — AIN

Commonly drug related.

Drugs

• Beta-lactams
• PPIs
• NSAIDs
• Rifampicin
• Sulfonamides
• Some immune checkpoint inhibitors

Classic triad:

• Fever
• Rash
• Eosinophilia

But the complete triad is uncommon.

Urine may show:

• Pyuria
• WBC casts
• Mild proteinuria
• Hematuria

Urine eosinophils have poor diagnostic accuracy and should not be relied upon.

Definitive diagnosis when uncertain:

Kidney biopsy

Acute Glomerulonephritis

Think of GN when AKI occurs with:

• Hematuria
• Proteinuria
• Dysmorphic RBCs
• RBC casts
• Hypertension
• Edema

Major etiologies include:

• ANCA-associated vasculitis
• Anti-GBM disease
• Lupus nephritis
• Infection-related GN
• IgA nephropathy
• Cryoglobulinemic GN

High-yield urine finding

RBC casts → glomerulonephritis until proven otherwise.

Renal Vascular Causes

Important causes include:

• Renal artery thrombosis
• Renal artery embolism
• Renal vein thrombosis
• Atheroembolic disease
• Thrombotic microangiopathy
• Malignant hypertension
• Vasculitis
• Scleroderma renal crisis

Postrenal AKI

Results from obstruction of urinary outflow.

Causes

• BPH,Prostate cancer,Bladder tumor
• Urethral obstruction,Stones
• Blood clots,Retroperitoneal fibrosis
• Pelvic malignancy,Bilateral ureteric obstruction
• Obstructed solitary kidney

For AKI to develop, obstruction usually must involve:

Both kidney or a solitary functioning kidney

Exception:Bladder outlet obstruction affects drainage from both kidneys.

Phases of Acute Kidney Injury (AKI)

Laboratory Evaluation

• CBC
• Serum creatinine,Urea/BUN
• Electrolytes-sodium,Potassium,calcium,phosphate,magnesium
• Bicarbonate
• Urinalysis
• Urine microscopy

Depending on context:

• CK
• LDH
• Haptoglobin
• Peripheral smear
• ANA
• dsDNA
• C3/C4
• ANCA
• Anti-GBM
• Hepatitis serology
• HIV testing
• SPEP/UPEP/free light chains

Urinalysis and Urine Microscopy

Urinary Indices

Fractional Excretion of Sodium — FENa

FENa estimates the fraction of filtered sodium that is excreted.

Typical interpretation:

But this is not absolute.

Limitations of FENa

FENa <1% may occur despite intrinsic AKI in:

• Early sepsis-associated AKI
• Contrast-associated AKI
• Pigment nephropathy
• Acute GN
• Hepatorenal syndrome

FENa may be elevated despite prerenal physiology after:

• Diuretic administration
• CKD
• Sodium bicarbonate administration

Therefore:Do not diagnose prerenal AKI or ATI from FENa alone.

Fractional Excretion of Urea — FEUrea

Useful particularly when loop diuretics have altered sodium handling.

FEUrea <35% → suggests prerenal physiology

But FEUrea also has substantial limitations in critically ill patients.

Prerenal vs ATI 

These values are supportive rather than diagnostic.

In ICU patients, especially with sepsis, CKD and diuretic use, they are much less reliable.

Imaging

Renal Ultrasound

Useful to evaluate:

• Hydronephrosis
• Kidney size and cortocomedullary differentiation 
• Structural abnormalities
• Bladder distension
• Urinary obstruction

POCUS

Critical-care ultrasound can additionally assess:

• LV/RV function
• Lung B-lines
• Venous congestion(Vexus)
• Bladder(check Clots,Urine)—
• Hydronephrosis
• Ascites

This helps determine whether AKI occurs in the setting of:

Hypovolemia vs distributive shock vs cardiac dysfunction vs venous congestion.

Biomarkers of AKI

Investigational/emerging biomarkers include:

• NGAL
• KIM-1
• IL-18
• Cystatin C
• TIMP-2
• IGFBP7

TIMP-2 × IGFBP7

These are markers of tubular cell-cycle arrest and can help identify patients at increased risk for development of moderate/severe AKI.

The evolving KDIGO framework is placing increasing emphasis on combining functional changes with structural kidney-damage biomarkers, although their exact routine role varies by clinical setting. 

Approach to AKI in the ICU

History

Fluid loss

• Diarrhea,Vomiting,Bleeding,Poor intake
• Fever,Polyuria(
• Diuretics

Hemodynamic insults

• Shock,Sepsis,Surgery,Cardiac arrest,Major hemorrhage.

Drugs

Especially:

• NSAIDs
• ACEI/ARB
• Aminoglycosides
• Vancomycin
• Amphotericin
• Chemotherapy
• Calcineurin inhibitors

Contrast exposure

Assess temporal association but do not automatically attribute every post-contrast creatinine rise to contrast.

Systemic clues

• Rash + AKI → AIN/vasculitis
• Hemoptysis + AKI → pulmonary–renal syndrome
• Diarrhea + thrombocytopenia + AKI → HUS/TMA
• Muscle pain + dark urine → rhabdomyolysis
• Urinary retention → obstruction

Physical Examination

Look for both hypovolemia AND congestion.

Hypovolemia

• Dry mucosa,Tachycardia,Hypotension,Reduced capillary refill,Low JVP.

Congestion

• Elevated JVP,Peripheral edema,Pulmonary edema
• Ascites,Hepatomegaly

Other clues

• Skin rash → AIN/vasculitis
• Livedo reticularis → cholesterol emboli
• Purpura → vasculitis/TMA
• Bladder distension → obstruction

Chech for Foleys Leak,foleys obstruction

Management of AKI

Treat the Cause

Hemodynamic Optimization

If genuinely hypovolemic(“Oliguria = fluid bolus” is not a valid strategy) Give appropriate fluid resuscitation.

Generally prefer:Isotonic crystalloids

Balanced crystalloids are commonly preferred in many critically ill patients But fluid should be given because the patient is fluid responsive and likely to benefit, not simply because creatinine is elevated.

Vasopressors

If hypotension persists despite adequate initial fluid resuscitation:

Use vasopressors rather than continuing unlimited fluids.

In septic shock:

Norepinephrine is first-line vasopressor.

The goal is adequate systemic and renal perfusion rather than attempting to “force” urine production.

MAP Target—Initial MAP target ≈65 mmHg

Some patients with chronic hypertension may require individualized higher perfusion pressures target ≈80 mmHg.

Do not use urine output alone to determine the MAP target.

Nephrotoxin Stewardship

Review all medications daily.

Consider stopping or adjusting:

• NSAIDs
• ACE inhibitors
• ARBs
• Aminoglycosides
• Vancomycin
• Amphotericin B
• Calcineurin inhibitors
• Other renally eliminated medications

Dose-adjust drugs according to changing kidney function and, when applicable, the KRT modality.

This is a major focus of contemporary AKI prevention and management. 

ACEI/ARB in AKI

These drugs are not intrinsically nephrotoxic in the classic tubular-toxic sense.

However, they may worsen GFR when renal filtration depends strongly on angiotensin-II-mediated efferent arteriolar constriction, such as:

• Severe hypovolemia
• Hypotension
• Bilateral renal artery stenosis

They are therefore often temporarily withheld during severe hemodynamically mediated AKI.

Diuretics in AKI

• Loop diuretics do NOT treat the kidney injury itself.
• They may be used to:Manage volume overload.
• They should not be used simply to convert oliguric AKI into non-oliguric AKI with the expectation of improving renal recovery.
• A patient producing more urine after furosemide does not necessarily have improved GFR.

Furosemide Stress Test

• The furosemide stress test can help predict progression of early AKI in selected patients.
• Typical approach:1 mg/kg IV if loop-diuretic naïve or 1.5 mg/kg IV if recently exposed to loop diuretics.
• >200 mL urine over 2 hours This indicates a pre-renal etiology (hypoperfusion)
• <200 mL urine over 2 hours suggests intrinsic renal failure and increased risk of progression to severe AKI.
• This is primarily a prognostic/functional test, not treatment of AKI.

Albumin Followed by Furosemide in AKI

Albumin → furosemide is NOT routine treatment for AKI. It is a selective strategy for diuretic-resistant edema/fluid overload, particularly when significant hypoalbuminemia is contributing to poor loop-diuretic response.

Why combine albumin + furosemide?

• Furosemide is >95% albumin-bound in plasma. It must reach the kidney, undergo proximal tubular secretion, and enter the tubular lumen to inhibit the Na-K-2Cl cotransporter (NKCC2) in the thick ascending limb.
• In severe hypoalbuminemia: ↓ serum albumin → altered furosemide pharmacokinetics + reduced effective tubular delivery and hypoalbuminemic patients often also have:↓ effective circulating volume + increased sodium avidity + interstitial edema → diuretic resistance

When Should You Consider It?

The combination may be reasonable when there is:

AKI + clinically important fluid overload/edema + substantial hypoalbuminemia + inadequate response to an appropriately dosed loop diuretic.

Examples include selected patients with:

• Marked hypoalbuminemia
• Nephrotic syndrome with severe edema
• Cirrhosis with specific albumin indications plus volume overload
• Critically ill hypoalbuminemic patients with refractory edema

It is not indicated merely because serum creatinine is elevated or urine output is low.

How Is It Given?

20–25% albumin IV → followed by IV furosemide

For example, 25 g albumin may be administered, with IV furosemide given toward the end of or shortly after the albumin infusion. The furosemide dose should be based on prior loop-diuretic exposure and kidney function rather than using a fixed dose for everyone.

In AKI, substantially higher loop-diuretic doses may be required because less drug reaches the tubular lumen.

Important distinction

Concentrated albumin (20–25%) is generally the formulation considered when the objective is to mobilize interstitial edema.

Giving large volumes of 5% albumin to an already overloaded oliguric patient can aggravate fluid overload.

What Does the Evidence Show?

Meta-analyses suggest that adding albumin to furosemide can produce a short-term increase in urine output and natriuresis, with the effect appearing greater in patients with lower serum albumin and impaired kidney function. However, heterogeneity is substantial, and evidence does not establish improvement in mortality, renal recovery, or avoidance of dialysis.

Therefore:

Albumin + furosemide is a fluid-management strategy—not a treatment that reverses AKI.

“Renal-Dose” Dopamine

Do NOT use low-dose dopamine to prevent or treat AKI.

Although dopamine may increase renal blood flow and urine output, it has not demonstrated meaningful renal or mortality benefit.

Fenoldopam

Not recommended routinely for prevention or treatment of AKI.

Nutrition in AKI

Avoid unnecessary protein restriction simply to postpone dialysis.

Critically ill patients require adequate nutrition.

Protein requirements depend on:

• Catabolic state
• Critical illness severity
• Whether RRT is being used
• RRT modality

Patients receiving CRRT may have substantial amino-acid losses and often require higher protein intake than non-catabolic patients.

Metabolic Acidosis

• Bicarbonate therapy may be considered in selected patients with severe metabolic acidemia, particularly when significant AKI is present.
• initial objective in severe AKI-associated acidemia is often to get the patient safely above the dangerous acidemic range (e.g. >7.20) while treating the underlying cause.

Hypertonic bicarbonate(8.4% NaHCO₃ = 1 mEq/mL)

• Use if patient has hyponatremia too
• Ampules should be pushed slowly over ~10 minutes each to avoid rapid swings in pH. 

Oral sodium bicarbonate

• Useful for mild/persistent metabolic acidosis when rapid correction is unnecessary—more commonly in CKD or recovering/stable AKI than in severe ICU acidemia.
• 650 mg NaHCO₃ ≈ 7.7 mEq bicarbonate

Therefore:

650 mg BID → ~15.4 mEq/day

1300 mg BID → ~30.8 mEq/day

1300 mg TID → ~46 mEq/day

Kidney Replacement Therapy — KRT

Modern terminology increasingly favors:

Kidney Replacement Therapy (KRT) rather than RRT.

Modalities include:

• Intermittent hemodialysis — IHD
• Continuous kidney replacement therapy — CKRT/CRRT
• Sustained low-efficiency dialysis — SLED
• Peritoneal dialysis in selected settings

Absolute Indications for KRT

AEIOU

A — Acidosis

Severe metabolic acidosis refractory to appropriate medical therapy.

E — Electrolyte abnormalities Especially: Refractory/severe hyperkalemia

I — Intoxications

Selected dialyzable toxins.

Examples include:

• Lithium
• Methanol
• Ethylene glycol
• Salicylates

O — Overload

Severe fluid overload/pulmonary edema refractory to medical management.

U — Uremic complications

Examples:

• Uremic encephalopathy
• Uremic pericarditis
• Clinically important uremic bleeding

Do NOT Start Dialysis Based on Creatinine Alone

There is no universal:“Creatinine X mg/dL = dialysis.”

Similarly, isolated BUN elevation alone is usually insufficient.

Decision making should consider:

• Clinical condition
• Potassium
• Acid–base status
• Volume status
• Urine output
• Uremic manifestations
• Rate of deterioration
• Catabolic burden
• Overall trajectory

Early vs Delayed RRT

Several trials have addressed whether RRT should be started early before conventional indications develop.

ELAIN

Single-center study suggested mortality benefit from earlier RRT. 

However, subsequent larger multicenter trials did not confirm a routine mortality benefit.

IDEAL-ICU

In severe AKI with septic shock, early RRT did not establish the anticipated benefit over a delayed strategy. 

STARRT-AKI

No mortality advantage from accelerated initiation.

Furthermore, only 61.8% of patients in the standard strategy ultimately received RRT, meaning many patients avoided dialysis altogether. 

Practical conclusion

In severe AKI without an urgent indication, routinely starting RRT simply because the patient has reached a particular KDIGO stage is generally not supported.Monitor closely and initiate when clinical indications/trajectory justify it.

Drug Dosing During AKI

This is especially important in ICU practice.

AKI changes:

• Renal clearance
• Volume of distribution
• Protein binding

Critical illness additionally changes pharmacokinetics.

CRRT further removes many drugs.

Therefore drug dosing should consider:

Antibiotic principle

First—Creatinine-based eGFR calculations are unreliable in evolving AKI.Why?

Equations such as CKD-EPI assume that serum creatinine is at steady state:Creatinine production ≈ creatinine excretion

In AKI, GFR can fall abruptly, but serum creatinine takes time to accumulate.

For example:GFR suddenly falls → serum creatinine still near baseline → calculated eGFR appears relatively preserved

Thus, during rising creatinine, conventional eGFR generally overestimates the current GFR.

The reverse occurs during recovery:

GFR improves first → accumulated creatinine takes time to fall → eGFR may underestimate current renal function.

For AKI, follow serial creatinine + urine output + clinical trajectory. When a filtration estimate is specifically required, kinetic eGFR (KeGFR) can provide a more physiologically appropriate estimate during non-steady-state creatinine, although it also has limitations

Major GFR / Creatinine Clearance Equations

Second-Do not automatically reduce the loading dose merely because the patient has AKI.Loading dose depends mainly on:Loading dose ≈ Volume of distribution × desired concentration not renal clearance.

The maintenance dose/interval is then adjusted according to clearance and KRT.

Electrolyte Complications

• Hyperkalemia—reduce potassium intake,Consider scheduled sodium zirconium cyclosilicate in patients with borderline hyperkalemia to prevent ongoing rise in the potassium level.
• Hyperphosphatemia—Give phosphate binder(Calcium acetate,Sevelamer) if phosphate is >6 mg/dL.
• Hypocalcemia
• Hypermagnesemia
• Metabolic acidosis

Renal Recovery

• AKI may result in: Complete recovery or Partial recovery → AKD
• or Progression to CKD or Dialysis dependence
• AKI is therefore not always a transient event.

Survivors have increased long-term risks of:

• CKD
• Recurrent AKI
• Cardiovascular events
• Kidney failure
• Mortality

Follow-Up After AKI

Patients should have reassessment of kidney function after AKI.

Evaluate:

• Serum creatinine/eGFR
• Urinalysis
• Albuminuria/proteinuria when appropriate
• Blood pressure
• Medication dosing
• Need for ACEI/ARB reintroduction
• CKD development
• Recurrent AKI risk

Patients with severe or incompletely recovered AKI may need nephrology follow-up.

Kidney Biopsy in AKI — When Is It Indicated?

Kidney biopsy is NOT routine in AKI. Consider it when the cause remains uncertain and histology is likely to change management, especially when a potentially treatable intrinsic renal disease is suspected.

Other AKI staging Criteria

RIFLE Criteria (2004 – by ADQI group)

RIFLE Staging (based on GFR or Creatinine + Urine Output)

 2. AKIN Criteria (2007 – Acute Kidney Injury Network)

• Modified and simplified RIFLE
• Removed GFR criteria (hard to measure acutely)
• Added absolute rise in creatinine ≥0.3 mg/dL
• Must occur within 48 hours

AKIN Staging