All the causes of increase creatinine

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An increased serum creatinine usually means a reduced glomerular filtration rate (GFR), but it can also rise without true kidney damage because of drugs, muscle breakdown, diet, or laboratory interference.

1. Reduced kidney blood flow: prerenal causes

The kidney itself may initially be structurally normal.

Volume loss / dehydration
- Vomiting, diarrhea
- Fever, sweating, burns
- Bleeding: gastrointestinal bleed, trauma, surgery, heavy menstrual bleeding
- Excess diuretics, poor fluid intake
Low blood pressure or shock
- Sepsis
- Hemorrhage
- Anaphylaxis
- Severe pancreatitis
Low effective circulating volume
- Heart failure or cardiogenic shock
- Advanced liver cirrhosis / hepatorenal syndrome
- Nephrotic syndrome
Reduced renal perfusion
- Renal artery stenosis
- Abdominal compartment syndrome
- NSAIDs, especially in dehydration, heart failure, cirrhosis, or chronic kidney disease
- ACE inhibitors / ARBs, particularly with bilateral renal artery stenosis, volume depletion, or severe heart failure

Washington Manual of Medical Therapeutics, p. 478.

2. Direct kidney damage: intrinsic renal causes

Tubular injury

Acute tubular necrosis (ATN)
- Prolonged shock, severe dehydration, sepsis, major surgery
- Ischemia
- Nephrotoxins:
  - Iodinated contrast in susceptible patients
  - Aminoglycosides
  - Amphotericin B
  - Cisplatin and other chemotherapy
  - Tenofovir
  - Calcineurin inhibitors: tacrolimus, cyclosporine
  - Ethylene glycol
  - Heavy metals
Pigment nephropathy
- Rhabdomyolysis: crush injury, prolonged immobilization, seizures, heat stroke, severe exercise, statins in rare cases
- Hemolysis
Tumor lysis syndrome
- Uric acid and phosphate crystal-related kidney injury

Glomerular disease

Acute or rapidly progressive glomerulonephritis
IgA nephropathy
Lupus nephritis
Post-infectious glomerulonephritis
Anti-GBM disease / Goodpasture syndrome
ANCA-associated vasculitis
Membranoproliferative glomerulonephritis
Infection-associated glomerulonephritis

Interstitial disease

Acute interstitial nephritis, often drug related:
- Penicillins, cephalosporins, sulfonamides
- NSAIDs
- Proton-pump inhibitors
- Rifampicin
- Some anticonvulsants
Pyelonephritis
Autoimmune disorders: Sjögren syndrome, sarcoidosis, SLE

Vascular disease

Malignant hypertension
Thrombotic thrombocytopenic purpura / hemolytic-uremic syndrome
Disseminated intravascular coagulation
Renal infarction or renal-vein thrombosis
Atheroembolic renal disease, often after vascular procedures
Scleroderma renal crisis
Vasculitis

3. Urinary tract obstruction: postrenal causes

Obstruction raises pressure upstream and lowers GFR.

Benign prostatic hyperplasia
Prostate cancer
Urethral stricture or blockage
Bladder tumor, stones, blood clots, neurogenic bladder
Bilateral ureteric stones
Pelvic, cervical, uterine, colorectal, or bladder cancer compressing ureters
Retroperitoneal fibrosis
Pregnancy-related ureteric obstruction
A single functioning kidney with obstruction of its ureter

A kidney ultrasound and bladder scan are often used to assess this category. The standard clinical approach classifies acute kidney injury into prerenal, intrinsic renal, and postrenal causes, as summarized in this AKI evaluation guide.

4. Chronic kidney disease causes

A persistently high creatinine can reflect chronic loss of kidney function from:

Diabetes mellitus
Long-standing hypertension
Chronic glomerulonephritis
Polycystic kidney disease
Reflux nephropathy or recurrent pyelonephritis
Chronic urinary obstruction
Chronic interstitial nephritis, including analgesic nephropathy
Autoimmune disease: lupus, vasculitis
Multiple myeloma / light-chain disease
Chronic calcineurin-inhibitor toxicity
Congenital kidney or urinary tract disorders
Previous severe or recurrent acute kidney injury

5. Raised creatinine without a true fall in GFR

These are important because they can mimic kidney injury.

Reduced tubular secretion of creatinine
- Trimethoprim
- Cimetidine
- Pyrimethamine
- Some salicylates
- Fenofibrate may also raise measured serum creatinine
Greater creatinine production
- Large muscle mass
- Intense exercise
- Creatine supplements
- Large cooked-meat meal
- Rhabdomyolysis
Laboratory assay interference
- Nitromethane can falsely elevate creatinine measured by the Jaffé method
- Some drugs and abnormal substances may interfere with particular assays
Normal physiologic variation
- Older age and low muscle mass can make creatinine deceptively low despite impaired GFR, while muscular people may have a higher baseline creatinine.

Cimetidine and trimethoprim can increase creatinine by blocking its tubular secretion without changing true GFR. Brenner and Rector's The Kidney, 2-Volume Set, p. 754-761.

Seek urgent medical assessment now if elevated creatinine is accompanied by:

Little or no urine
Breathlessness, leg swelling, or confusion
Severe vomiting/diarrhea or inability to drink
Fever with low blood pressure or suspected sepsis
Blood in urine, severe flank pain, or inability to pass urine
Muscle pain with dark cola-colored urine
Potassium elevation, chest symptoms, or severe weakness

Interpret creatinine with the baseline value, eGFR, urine output, urinalysis, medications, blood pressure, and renal ultrasound when obstruction is possible. A single mildly elevated value does not identify the cause by itself.

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