Acute Kidney Injury (AKI)
KDIGO Definition of AKI
AKI is diagnosed if any one of the following is present:
- Increase in Serum Creatinine-≥0.3 mg/dL (26.5 μmol/L) within 48 hours
- Relative Increase in Creatinine-≥1.5 times baseline within previous 7 days
- Reduced Urine Output—<0.5 mL/kg/hr for 6 hours
KDIGO Staging of AKI
|
Stage |
Serum Creatinine Criteria |
Urine Output Criteria |
|
Stage 1 |
1.5–1.9 × baseline OR increase ≥0.3 mg/dL |
<0.5 mL/kg/hr for 6–12 hr |
|
Stage 2 |
2.0–2.9 × baseline |
<0.5 mL/kg/hr for ≥12 hr |
|
Stage 3 |
≥3 × baseline OR Cr ≥4 mg/dL OR dialysis initiation |
<0.3 mL/kg/hr ≥24 hr OR anuria ≥12 hr |
Important ICU Point: Creatinine is influenced mainly by muscle mass and tubular secretion, whereas BUN is heavily influenced by protein intake, catabolism, liver function, GI bleeding, and volume status. Therefore, abnormal BUN or creatinine alone does not necessarily indicate AKI.
|
Finding |
Likely Cause |
|
↑ BUN with normal creatinine |
GI bleed, steroids, high-protein intake, catabolic state |
|
↑ Creatinine with stable GFR |
Trimethoprim, Cimetidine, Dolutegravir |
|
Low creatinine despite CKD |
Elderly, cachexia, cirrhosis, amputees |
|
Very low BUN |
Advanced liver disease, malnutrition |
|
BUN rises disproportionately more than creatinine |
Upper GI bleed, corticosteroids, dehydration, high protein intake |
|
Low creatinine in pregnancy |
Increased GFR (physiological) |
Acute Kidney Disease (AKD)
Acute Kidney Disease (AKD) is the period between Acute Kidney Injury (AKI) and Chronic Kidney Disease (CKD).
The concept was introduced because many patients recover partially after AKI but continue to have abnormal kidney function for weeks to months before either recovering completely or progressing to CKD.
Diagnostic Criteria for AKD
AKD is present if any of the following persist for 7–90 days:
Reduced GFR-GFR <60 mL/min/1.73 m²
OR
Increase in Serum Creatinine-Creatinine >50% above baseline
OR
Structural Kidney Damage
Examples:
- Persistent proteinuria
- Hematuria
- Abnormal imaging
- Persistent tubular injury
Comparison of RIFLE and AKIN Criteria for Acute Kidney Injury
|
Stage |
RIFLE Criteria |
AKIN Criteria |
|
Stage 1 |
Risk Serum creatinine ↑ 1.5 × baseline or GFR ↓ >25% Urine output <0.5 mL/kg/hr for 6 hr |
Stage 1 Serum creatinine ↑ ≥0.3 mg/dL within 48 hr or 1.5–2 × baseline Urine output <0.5 mL/kg/hr for 6 hr |
|
Stage 2 |
Injury Serum creatinine ↑ 2 × baseline or GFR ↓ >50% Urine output <0.5 mL/kg/hr for 12 hr |
Stage 2 Serum creatinine ↑ >2–3 × baseline Urine output <0.5 mL/kg/hr for ≥12 hr |
|
Stage 3 |
Failure Serum creatinine ↑ 3 × baseline or serum creatinine ≥4 mg/dL with acute rise ≥0.5 mg/dL or GFR ↓ >75% Urine output <0.3 mL/kg/hr for 24 hr or anuria for 12 hr |
Stage 3 Serum creatinine ↑ >3 × baseline or serum creatinine ≥4 mg/dL with acute rise ≥0.5 mg/dL or initiation of RRT Urine output <0.3 mL/kg/hr for 24 hr or anuria for 12 hr |
|
Outcome Category 1 |
Loss Persistent complete loss of kidney function >4 weeks |
Not included |
|
Outcome Category 2 |
End-Stage Kidney Disease (ESKD) Complete loss of kidney function >3 months |
Not included |
Classification of AKI
|
Type of AKI |
Pathophysiology / Characteristics |
Common Causes / Examples |
|
Prerenal AKI |
Problem occurs before the kidney due to reduced renal perfusion. Kidney structure is initially normal. Accounts for 40–60% of AKI cases. |
Hypovolemia, Hemorrhage, Dehydration, Heart Failure, Cirrhosis, Septic Shock, -Drugs Affecting Renal Perfusion
|
|
Intrinsic (Renal) AKI |
Due to structural damage within the kidney involving tubules, interstitium, glomeruli, or renal vasculature. |
Acute Tubular Necrosis (ATN), Acute Interstitial Nephritis (AIN), Glomerulonephritis, Vasculitis, Thrombotic Microangiopathy |
|
Postrenal AKI |
Due to urinary tract obstruction causing impaired urine outflow. Usually reversible if obstruction is relieved early.For obstruction to produce azotemia,both kidneys must be involved because one normally functioning kidney is sufficient to maintain a near-normal GFR. |
Benign Prostatic Hyperplasia (BPH), Ureteric Obstruction, Urinary Stones, Blood Clots, Malignancy |
Acute Tubular Necrosis (ATN) vs Acute Interstitial Nephritis (AIN)
|
Feature |
Acute Tubular Necrosis (ATN) |
Acute Interstitial Nephritis (AIN) |
|
Definition |
Acute kidney injury caused by injury and necrosis of tubular epithelial cells |
Acute kidney injury caused by immune-mediated inflammation of renal interstitium and tubules |
|
Pathogenesis |
Ischemic or toxic tubular epithelial injury causing cell death and tubular obstruction |
Hypersensitivity reaction causing interstitial inflammation and edema |
|
Onset |
Usually after hypotension, shock, or nephrotoxin exposure |
Days to weeks after exposure to offending agent |
|
Common Causes |
Ischemia, sepsis, shock, major surgery, nephrotoxins |
Drugs (most common), infections, autoimmune diseases |
|
Drug Causes |
Aminoglycosides, Amphotericin B, Cisplatin, Vancomycin, Radiocontrast, Myoglobin, Hemoglobin |
PPIs, Penicillins, Cephalosporins, Rifampicin, Sulfonamides, NSAIDs, Fluoroquinolones |
|
Infection-Related Causes |
Sepsis |
Streptococcal infections, EBV, CMV, Tuberculosis, Leptospirosis |
|
Autoimmune Causes |
Rare |
Sjögren syndrome, SLE, Sarcoidosis, IgG4 disease |
|
Urine Output |
Oliguric or non-oliguric |
Usually non-oliguric |
|
Classic Triad |
Absent |
Fever + Rash + Eosinophilia(Present in <10–15% cases) |
|
Peripheral Eosinophilia |
Uncommon |
Common |
|
Flank Pain |
Rare |
Occasionally present |
|
Characteristic Urinary Cast |
Muddy brown granular casts |
WBC casts |
|
WBC Casts |
Rare |
Common |
|
Pyuria |
Mild |
Common |
|
Hematuria |
Mild |
Common |
|
Nephrotic Proteinuria |
Rare |
Can occur with NSAID-induced AIN |
|
Role of Biopsy |
Rarely required |
Gold standard diagnosis |
|
Prednisone Regimen |
Not indicated |
Commonly 0.5–1 mg/kg/day for 1–2 weeks then taper |
|
Most Important Urine Finding |
Muddy brown granular casts |
WBC casts and sterile pyuria |
Clinical Manifestations
1. Urinary Manifestations
Oliguria
- Urine output <0.5 mL/kg/hour for >6 hours (KDIGO)
- Typically <400–500 mL/day in adults
Anuria
- Urine output <100 mL/day
Non-Oliguric AKI
Urine output:
- 400–500 mL/day
Seen in:
- Drug-induced ATN
- Contrast nephropathy
- Aminoglycoside toxicity
- Some forms of AIN
Patients may appear deceptively stable despite worsening renal function.
Polyuric Phase
Occurs during recovery from ATN.With partialobstruction, damage to the kidney may impair the ability to concentrate urine,resulting in a polyuric state (acquired nephrogenic diabetes insipidus).
Features:
- Large urine volumes
- 3–6 L/day or more
Causes:
- Tubular dysfunction
- Impaired concentrating ability
Risks:
- Hypovolemia
- Hypokalemia
- Hypernatremia
2. Volume Overload
- Pedal edema
- Sacral edema in bedridden patients
- Generalized swelling
- Weight Gain
Often earliest sign of fluid retention.
Daily weight monitoring is important.
1 L retained fluid ≈ 1 kg weight gain.
- Pulmonary Edema
- Pleural Effusions
- Hypertension
3. Cardiovascular Manifestations
- Hypertension
- Hypotension
Seen in:
- Sepsis
- Hemorrhage
- Dehydration
- Cardiogenic shock
Usually represents the cause rather than the consequence of AKI.
- Arrhythmias(Usually due to:Hyperkalemia)
- Heart Failure(due to Volume overload)
- Uremic Pericarditis
4. Respiratory Manifestations
- Pulmonary Edema
- Respiratory Compensation for Metabolic Acidosis—Kussmaul Respiration
Features:Deep/Rapid/Labored breathing
Represents compensatory hyperventilation.
Pleural Effusions
5. Gastrointestinal Manifestations
Usually due to uremia.
- Anorexia
- Nausea and Vomiting
- Metallic Taste
- Uremic Fetor(Characteristic ammonia-like odor of breath.
- Caused by: Breakdown of urea in saliva)
- Gastrointestinal Bleeding
Mechanisms:
- Platelet dysfunction
- Gastritis
- Stress ulcers
Manifestations:
- Hematemesis
- Melena
6. Neurological Manifestations
Neurological symptoms correlate with severity of uremia.
Early Symptoms
- Fatigue
- Weakness
- Malaise
- Poor concentration
Cognitive Dysfunction
Features:
- Confusion
- Disorientation
- Delirium
Uremic Encephalopathy
Asterixis
Seizures
Coma
7. Electrolyte Manifestations
- Hyperkalemia
- Hyponatremia
- Hyperphosphatemia
- Hypocalcemia
8. Metabolic Acidosis Manifestations
Due to:
- Reduced hydrogen ion excretion
- Reduced ammoniagenesis
9. Hematological Manifestations
Platelet Dysfunction
Uremia causes:Qualitative platelet defects
Manifestations:
- Easy bruising
- Epistaxis
- GI bleeding
- Bleeding from catheter sites
10. Dermatological Manifestations
Usually seen in severe uremia.
Pallor
Due to:
- Anemia
- Chronic illness
Pruritus
Uremic Frost
Rare.White crystalline deposits of urea on skin.
Diagnostic Approach
Urine Dipstick
Assess:Protein—Blood—Leukocytes—Nitrites—Glucose
Urine Microscopy
|
Urinary Sediment / Cast |
Associated Condition / Significance |
|
Bland Sediment |
Seen in Prerenal AKI and Postrenal (Obstructive) AKI |
|
Muddy Brown Granular Casts |
Classic for Acute Tubular Necrosis (ATN); most characteristic urinary finding |
|
White Blood Cell (WBC) Casts |
Suggest Acute Interstitial Nephritis (AIN) or Pyelonephritis |
|
Red Blood Cell (RBC) Casts |
Highly suggestive of Glomerulonephritis or Vasculitis |
|
Fatty Casts (Oval Fat Bodies) |
Suggest Nephrotic Syndrome |
Crystals
|
Crystal |
Condition |
|
Uric acid |
Tumor lysis syndrome |
|
Oxalate |
Ethylene glycol poisoning |
|
Acyclovir crystals |
Drug nephropathy |
|
Sulfonamide crystals |
Drug nephropathy |
Fractional Excretion of Sodium (FENa)
FENa=(Plasma Na×Urine CrUrine Na×Plasma Cr )×100
Interpretation
<1%Suggests:Prerenal AKI
2% Suggests:ATN
Limitations
Unreliable in:
- Diuretic use
- CKD
- Sepsis
- Contrast nephropathy
Fractional Excretion of Urea
Preferred when on diuretics.
|
FEUrea |
Suggests |
|
<35% |
Prerenal |
|
>50% |
ATN |
BUN:Creatinine Ratio
|
Ratio |
Suggestion |
|
>20:1 |
Prerenal AKI |
|
10–15:1 |
ATN |
Not highly specific.
Imaging
Renal Ultrasound
Recommended in most unexplained AKI.
Looks for:
- Hydronephrosis
- Obstruction
- Kidney size
Doppler Studies
When vascular disease suspected.
CT Scan
If obstruction, trauma, or vascular lesion suspected.
Avoid contrast when possible.
Step 10: Special Serologic Workup
When intrinsic renal disease is suspected.
Autoimmune Panel
ANA Suggests:SLE
Anti-dsDNA-Lupus nephritis
ANCA
- GPA
- MPA
Anti-GBM Antibody
- Goodpasture syndrome
Complement Levels
Low C3/C4 suggests:
- Lupus nephritis
- Post-infectious GN
- MPGN
- Cryoglobulinemia
Infection Screen
- HBV
- HCV
- HIV
Monoclonal Protein Testing
- SPEP
- UPEP
- Serum free light chains
For:
- Multiple myeloma
- Cast nephropathy
Kidney Biopsy
Indications
When diagnosis remains uncertain and results will change management.
Common indications:
Suspected Glomerulonephritis
- RBC casts
- Active urine sediment
Unexplained AKI
Suspected AIN
When diagnosis uncertain
Nephrotic Syndrome
With AKI
Systemic Vasculitis
Biomarkers of AKI
Emerging markers:
- NGAL
- KIM-1
- TIMP-2
- IGFBP7
- Cystatin C
|
Feature |
Prerenal AKI |
ATN |
AIN |
|
Urine sediment |
Bland |
Muddy brown casts |
WBC casts |
|
FENa |
<1% |
>2% |
Variable |
|
FEUrea |
<35% |
>50% |
Variable |
|
Urine osmolality |
>500 |
<350 |
Variable |
|
Proteinuria |
Mild |
Mild |
Mild-Moderate |
|
Hematuria |
Minimal |
Mild |
Present |
|
Eosinophilia |
No |
No |
May occur |
|
Definitive treatment |
Restore perfusion |
Supportive care |
Remove offending drug ± steroids |
Management of AKI
Hypovolemia
Preferred fluids:Balanced crystalloids
Evidence suggests lower risk of worsening kidney injury compared with large-volume normal saline.
Fluid Challenge
Typical: 500 mL crystalloid over 15–30 min
Then reassess:BP—HR—MAP—Lactate—Urine output
Dynamic Assessment
Avoid blind fluid loading.
Use:
- Passive leg raising
- Stroke volume variation
- Pulse pressure variation
- Echocardiography
- IVC assessment
Vasopressors-Norepinephrine
Target:MAP ≥65 mmHg
Higher targets may be needed in chronic hypertension.
Management of Postrenal AKI
Goal:Rapid decompression.(Foley catheterization,Ureteric stent,Percutaneous nephrostomy)
Post-Obstructive Diuresis
May produce:200 mL/hour urine
Monitor:
- Fluid balance
- Potassium
- Magnesium
- Sodium
Replace approximately 50–75% of urinary losses initially.
Fluid Management
In normovolemic or edematous patients, restrict fluid intake (∼1500 mL/d) and sodium intake (<2 g/d).
Acute Interstitial Nephritis (AIN)
Steroid RegimenPrednisolone:
0.5–1 mg/kg/day Often for: 1–2 weeks Then taper Best outcomes occur when started early.
Glomerulonephritis
Management depends on etiology.
Examples:
ANCA Vasculitis
Treatment:
- High-dose steroids
- Rituximab
- Cyclophosphamide
Anti-GBM Disease
Treatment:
- Steroids
- Cyclophosphamide
- Plasma exchange
Lupus Nephritis
Treatment:
- Steroids
- Mycophenolate
- Cyclophosphamide
Avoid Further Kidney Injury
Stop nephrotoxins:
Drugs
- NSAIDs
- ACE inhibitors
- ARBs
- Aminoglycosides
- Amphotericin B
- Cisplatin
- Tacrolimus
- Cyclosporine
Contrast Exposure
Avoid unnecessary contrast.
If essential:
- Use lowest dose
- Use iso-osmolar/low-osmolar contrast
- Adequate hydration
Drug Dose Adjustment
|
Penicillins |
Cephalosporins |
Carbapenems |
|
Penicillin G |
Cefazolin |
Meropenem |
|
Ampicillin |
Cefuroxime |
Imipenem-Cilastatin |
|
Amoxicillin |
Cefotaxime |
Ertapenem |
|
Amoxicillin-Clavulanate |
Cefepime |
Doripenem |
|
Piperacillin-Tazobactam |
Ceftazidime |
Glycopeptide |
|
|
Ceftolozane-Tazobactam |
Vancomycin |
|
|
Ceftazidime-Avibactam |
Teicoplanin |
|
Sulfonamides |
Other Antibiotics |
Fluoroquinolones |
|
Trimethoprim-Sulfamethoxazole (Co-trimoxazole) |
|
Ciprofloxacin |
|
Aminoglycosides |
Daptomycin |
Levofloxacin |
|
Gentamicin |
Colistin (Polymyxin E) |
Ofloxacin |
|
Amikacin |
Polymyxin B |
|
|
Tobramycin |
Tigecycline?? |
|
|
Streptomycin |
Aztreonam |
|
Diuretics in AKI
Diuretics DO NOT improve:Mortality—Renal recovery—Need for dialysis
They are used only for:Volume overload.
Furosemide
Bolus:40–80 mg IV
Can escalate:160–200 mg IV
Infusion:5–20 mg/hour
Bicarbonate Therapy
Consider when: pH <7.1
Especially if:
- Hyperkalemia
- Severe acidosis
Not routinely indicated.
Nutrition in AKI-AKI is highly catabolic.
- Energy–25–30 kcal/kg/day
- Protein
Non-Dialysis AKI—0.8–1.0 g/kg/day
Dialysis Patients—1.3–1.7 g/kg/day
CRRT Up to:—2–2.5 g/kg/day due to amino acid losses.
Kidney Replacement Therapy (Dialysis)
|
Indication |
Details |
|
A |
Acidosis refractory to treatment |
|
E |
Electrolyte abnormality (especially hyperkalemia) |
|
I |
Intoxication (dialyzable toxins) |
|
O |
Overload (pulmonary edema) |
|
U |
Uremia |