Prerenal physiology

Reduced effective renal perfusion can lower filtration before structural injury occurs. Causes include volume depletion, impaired circulation, and altered glomerular hemodynamics. Prerenal physiology and structural injury can coexist or evolve over time.

BUN may rise disproportionately, but protein intake, catabolism, gastrointestinal bleeding, liver function, and medications confound the BUN:creatinine ratio. Sodium, potassium, chloride, and bicarbonate vary with the illness and treatment. There is no maximum creatinine that defines prerenal AKI.

Low urine sodium or a low fractional excretion of sodium can support sodium avidity in selected patients. They are not proof of fluid responsiveness or a mandate to give fluids [6,11].

Intrinsic kidney injury

Injury may involve tubules, glomeruli, interstitium, or vessels. Creatinine and BUN can rise as filtration falls; potassium may rise and bicarbonate may fall. Sodium and chloride are variable. Metabolic acidosis can have a normal or increased anion gap.

Urine findings help localize injury: granular casts and tubular epithelial cells support tubular injury; dysmorphic red cells or red cell casts suggest glomerular bleeding. Pyuria or white cell casts suggest inflammation but are not specific for acute interstitial nephritis. Quantify albuminuria or proteinuria when appropriate [10].

Drugs can cause hemodynamic changes, tubular injury, interstitial nephritis, or crystal injury. Review exposure, timing, dose, and concurrent illness; a creatinine rise alone does not establish structural drug toxicity [5].

Postrenal obstruction

Obstruction in the collecting system, ureters, bladder outlet, or urethra can impair filtration. Renal artery obstruction is a vascular cause, not postrenal urinary obstruction. The BMP pattern depends on severity and duration and is not diagnostic [4].

Consider bladder retention, catheter malfunction, stones, malignancy, or neurogenic bladder. Use a bladder assessment and appropriate imaging. A normal initial ultrasound does not exclude every obstruction, particularly early or nondilated obstruction. An infected obstructed system, anuria, or severe complications requires urgent specialist assessment [4].

Rhabdomyolysis pattern

Muscle injury may cause a marked CK rise, hyperkalemia, hyperphosphatemia, and early hypocalcemia; findings vary with timing and severity. A heme-positive urine dipstick with few red cells can suggest pigmenturia. CK and phosphorus are separate tests, not BMP components.

Assess the cause, volume status, urine output, and complications promptly. Give isotonic crystalloid when indicated with repeated reassessment, particularly when oliguria or congestion limits safe fluid administration. Routine bicarbonate or mannitol to prevent rhabdomyolysis-associated AKI is not supported by the cited guideline; bicarbonate may have a separate indication, such as selected severe acidemia [7].

AKI after iodinated contrast

A creatinine rise following contrast is contrast-associated AKI; temporal association alone does not prove contrast caused it. Hypotension, sepsis, congestion, embolic disease, and other exposures may contribute. There is no diagnostic sodium, potassium, or anion-gap pattern [8].

For intravenous contrast, prevention is individualized to AKI status, kidney function, and the risk of volume overload. Isotonic saline prophylaxis is used in selected high-risk patients when appropriate. N-acetylcysteine is not recommended for routine prophylaxis. Metformin is not a nephrotoxin; withholding decisions relate to AKI or severe kidney dysfunction and lactic-acidosis risk, following the applicable contrast protocol [8].

AKI in cirrhosis and HRS-AKI

Cirrhosis with ascites increases the risk of several AKI phenotypes, including hypovolemia, sepsis-associated injury, drug injury, and HRS-AKI. Hyponatremia may coexist but does not diagnose HRS. BUN production can be reduced by liver disease, so a high BUN:creatinine ratio is not a required HRS pattern [9].

Use contemporary HRS-AKI criteria and evaluate volume status and competing causes. Vasoconstrictor therapy with carefully titrated albumin is used after HRS-AKI is established, with close respiratory and volume monitoring. Do not start HRS treatment solely because sodium is below a numerical threshold [9].

Cardiorenal physiology

Heart failure can affect kidney function through venous congestion, impaired forward flow, neurohormonal activation, and treatment effects. Both reduced and preserved ejection fraction can be relevant.

Sodium may fall with impaired water excretion. Potassium may be low with diuretics or high with reduced excretion and medications. Diuretics can cause metabolic alkalosis; shock can produce lactic acidosis. Respiratory acidosis is a separate acid-base process and does not explain a low bicarbonate by itself.

Interpret the creatinine trend alongside perfusion, congestion, urine output, treatment response, and relevant cardiac assessment. A rise during decongestion does not automatically require fluids or establish structural tubular injury [11].

Fractional excretion of sodium (FeNa)

Formula: FeNa (%) = 100 × (urine sodium × serum creatinine) / (serum sodium × urine creatinine). Use compatible units and samples obtained close together.

A low FeNa suggests sodium avidity; a higher value may reflect reduced sodium reabsorption. Traditional thresholds below 1% and above 2% are contextual clues. FeNa performs best in selected oliguric patients without CKD or recent diuretic exposure; it is less reliable in broader populations. Low FeNa can occur in intrinsic disease, and diuretics can raise it despite reduced effective perfusion [6].

Fractional excretion of urea (FeUrea)

Formula: FeUrea (%) = 100 × (urine urea × serum creatinine) / (serum urea × urine creatinine). Match urea or urea-nitrogen units consistently.

A value below 35% has been studied as a clue to reduced effective perfusion, including in some patients receiving diuretics [3]. It is not a definitive separator of prerenal and intrinsic AKI and is not uniformly reliable in sepsis, CKD, or diuretic-treated patients. Interpret it with the clinical course and other findings [11].

When to obtain urine electrolytes

Order selectively when the result could clarify a specific question. Recognize diuretic, CKD, and sepsis confounding. Persistent oliguria after substantial fluid administration requires reassessment for congestion, intrinsic injury, or obstruction; it is not evidence that more fluid is automatically needed [6,11].

When to examine urine sediment

Microscopy is useful in unexplained AKI and suspected glomerular, tubular, interstitial, or crystal disease. Urine eosinophils neither establish nor exclude AIN. Interpret casts and cells as clues alongside the history and other tests [5,10].

When to obtain kidney and bladder imaging

Evaluate obstruction when retention, anuria, stones, pelvic or retroperitoneal disease, catheter problems, or unexplained AKI make it plausible. The BMP cannot exclude obstruction. Interpret a residual volume and ultrasound in the clinical context rather than treating one cutoff as diagnostic [4].

When to consider kidney biopsy

Discuss biopsy with nephrology when unexplained AKI or suspected glomerular, interstitial, vascular, or paraprotein-related disease could change treatment. Normal complement does not establish lupus or membranoproliferative disease, and negative serologies do not exclude every treatable lesion [5,10,11].

Warning 1: Urine indices are not definitive

Neither FeNa nor FeUrea proves a mechanism or predicts that fluids are safe. Use trends, sediment, perfusion, congestion, and the exposure history [3,6,11].

Warning 2: Rhabdomyolysis can evolve

Creatinine may lag muscle injury. Monitor the clinical course and complications, and individualize fluids. A high CK alone is not an instruction for unlimited fluids or routine urine alkalinization [7].

Warning 3: An osmolal gap requires context

With sodium in mmol/L and glucose and BUN in mg/dL, a common calculated osmolality is 2 × sodium + glucose/18 + BUN/2.8. Compare with measured osmolality and account for relevant alcohols or other osmoles.

An elevated gap is not specific for toxic alcohol exposure, and a normal gap does not exclude it, especially later in the course. If exposure is plausible, obtain urgent toxicology guidance; do not rely on the gap alone [11].

Warning 4: Severe hyponatremia needs prompt assessment

Assess symptoms, acuity, and the cause. Severe hyponatremia in cirrhosis does not by itself diagnose HRS-AKI or justify immediate vasoconstrictor treatment. Plan correction carefully and evaluate the AKI phenotype [9].