Gagal Ginjal Akut

01Pathophysiology

AKI represents a rapid decline in the glomerular filtration rate (GFR) over hours to days, leading to accumulation of waste products (urea, creatinine) and failure to regulate fluid, electrolyte, and acid-base balance.

Prerenal AKI accounts for the majority of cases and results from decreased renal perfusion without structural damage to the nephron. The kidney itself is intact but underperfused. Common causes include hemorrhage, dehydration, septic shock, heart failure with low cardiac output, and hepatorenal syndrome in cirrhosis. Because the tubules are still functioning, the kidney avidly reabsorbs sodium and water in an attempt to restore circulating volume. This is why $FENaFENa$ is less than 1% and urine osmolality is high (concentrated urine). The BUN rises disproportionately to creatinine because urea reabsorption in the proximal tubule is flow-dependent and enhanced during low-flow states, producing a BUN-to-creatinine ratio greater than 20:1. If perfusion is not restored promptly, prerenal AKI progresses to intrinsic injury through ischemic damage to the tubular epithelium.

Intrinsic renal AKI involves direct structural damage to the kidney parenchyma. The most common subtype is acute tubular necrosis (ATN), which can be ischemic (prolonged prerenal insult) or nephrotoxic (aminoglycosides, contrast dye, myoglobin from rhabdomyolysis, cisplatin). In ATN, necrotic tubular epithelial cells slough off and form muddy brown granular casts in the urine. These cells also obstruct the tubular lumen and cause backleak of filtrate into the interstitium, both of which reduce effective GFR. Because the damaged tubules lose their ability to reabsorb sodium, $FENaFENa$ exceeds 2% and the urine is dilute (isosthenuric). Other intrinsic causes include acute interstitial nephritis (AIN), typically drug-induced (NSAIDs, penicillins, proton pump inhibitors), characterized by the triad of fever, rash, and eosinophilia with white blood cell casts and urine eosinophils. Glomerulonephritis presents with red blood cell casts and proteinuria, pointing to glomerular inflammation.

Postrenal AKI results from bilateral urinary tract obstruction (or unilateral in a solitary kidney). Common causes include benign prostatic hyperplasia (the most common cause in elderly men), bilateral ureteral stones, pelvic malignancy, and neurogenic bladder. Obstruction raises intratubular pressure, which opposes filtration pressure at the glomerulus, thereby reducing GFR. The key concept is that obstruction must be bilateral to cause AKI, because a single functioning kidney can maintain adequate filtration.

02Classification and Clinical Manifestation

KDIGO Staging of AKI

Classification by Anatomic Location

A critical nuance: glomerulonephritis produces a low $FENaFENa$ similar to prerenal disease because the intact tubules downstream of the damaged glomerulus still reabsorb sodium normally. Do not assume low $FENaFENa$ always equals prerenal.

03Diagnostic Workup

Summary Table

The first step in evaluating AKI is confirming the diagnosis by documenting a rise in serum creatinine that meets KDIGO criteria. Once AKI is confirmed, the priority is to determine the category: prerenal, intrinsic, or postrenal.

Renal ultrasound is the best initial imaging test and should be obtained in every patient with unexplained AKI. Its primary role is to detect bilateral hydronephrosis, which indicates postrenal obstruction. It is non-invasive, readily available, and does not require contrast. If hydronephrosis is found, the next step is relieving the obstruction (Foley catheter for bladder outlet obstruction, percutaneous nephrostomy or ureteral stent for ureteral obstruction).

If the ultrasound is normal (no obstruction), the next step is to differentiate prerenal from intrinsic AKI using urinalysis with microscopy and $FENaFENa$.

The fractional excretion of sodium is calculated as:

$$FENa=\frac{U_{Na}\times P_{Cr}}{P_{Na}\times U_{Cr}}\times 100FENa\; =\; \backslash frac\{U\_\{Na\}\; \backslash times\; P\_\{Cr\}\}\{P\_\{Na\}\; \backslash times\; U\_\{Cr\}\}\; \backslash times\; 100$$

A indicates the tubules are intact and reabsorbing sodium avidly, pointing to prerenal disease. A $FENa>2\mathrm{\%}FENa\; >\; 2\backslash \%$ indicates tubular damage and favors intrinsic AKI (ATN). One important caveat: in patients receiving diuretics, $FENaFENa$ becomes unreliable because diuretics increase urinary sodium excretion even in prerenal states. In these patients, use the fractional excretion of urea ($FEUreaFEUrea$) instead. A suggests prerenal physiology.

Urine microscopy is the most informative non-invasive test for categorizing intrinsic AKI. Muddy brown granular casts confirm ATN. RBC casts confirm glomerulonephritis. WBC casts suggest pyelonephritis or AIN. Hyaline casts are nondiagnostic and can be seen in prerenal states.

Renal biopsy is reserved for cases where the etiology of intrinsic AKI remains unclear after a full non-invasive workup, particularly when glomerulonephritis or vasculitis is suspected and a tissue diagnosis would change management (e.g., initiation of immunosuppression).

04Management and Treatment

Summary Table

Prerenal AKI is managed with aggressive volume resuscitation using isotonic crystalloid (normal saline or lactated Ringer). The expected response is a drop in creatinine and return of urine output within 24-72 hours. If creatinine does not improve with volume repletion, consider that the insult has progressed to ATN. All nephrotoxic medications should be held immediately. ACE inhibitors and ARBs reduce efferent arteriolar tone and further decrease GFR in the setting of hypoperfusion, so they must be discontinued during AKI. NSAIDs reduce prostaglandin-mediated afferent arteriolar dilation and are similarly harmful.

Intrinsic AKI from ATN is largely managed with supportive care. There is no pharmacologic therapy that accelerates tubular recovery. The tubular epithelium regenerates over 1-3 weeks if no further insult occurs. During this recovery phase, monitor electrolytes closely and avoid additional nephrotoxins.

Acute interstitial nephritis typically resolves after withdrawing the causative drug. If renal function does not begin improving within 5-7 days of drug withdrawal, corticosteroids (prednisone 1 mg/kg/day tapered over several weeks) may hasten recovery.

Indications for emergent dialysis can be remembered with the mnemonic AEIOU:

Before resorting to dialysis for hyperkalemia, stabilize the myocardium with IV calcium gluconate (which does not lower potassium but protects the heart), then shift potassium intracellularly with IV insulin plus dextrose, inhaled albuterol, and IV sodium bicarbonate if acidotic. To truly remove potassium from the body, use loop diuretics (if the patient still makes urine), sodium polystyrene sulfonate (Kayexalate), patiromer, or sodium zirconium cyclosilicate. Dialysis is the definitive removal method when these measures fail.

For postrenal AKI, the next best step after confirming hydronephrosis on ultrasound is immediate decompression. If the obstruction is at the bladder outlet (BPH), a Foley catheter is placed. If obstruction is at the level of the ureters (stones, external compression), a percutaneous nephrostomy tube or ureteral stent is required. After relief, watch closely for postobstructive diuresis, a phenomenon where massive polyuria (liters per hour) occurs due to accumulated solute and fluid. These patients require careful IV fluid replacement, typically replacing 50-75% of urine output with half-normal saline to prevent secondary hypovolemia and electrolyte disturbances.

05Differential Diagnosis and Distractors

06Traps and High-Yield Pearls

The single most common trap with AKI questions is failure to distinguish prerenal from intrinsic disease. The vignette will describe a patient who initially had a prerenal insult (dehydration, hemorrhage, sepsis) but has now progressed to ATN after prolonged hypoperfusion. Students pick "continue IV fluids" because the original etiology was prerenal, but the muddy brown casts and $FENa>2\mathrm{\%}FENa\; >\; 2\backslash \%$ in the question stem are telling you the damage has already occurred. Once ATN is established, further aggressive fluid resuscitation does not reverse the injury and can cause volume overload. The correct answer shifts to supportive care and, if needed, dialysis.

Another frequent error involves $FENaFENa$ interpretation in patients on diuretics. If the vignette mentions furosemide or any other diuretic, the $FENaFENa$ will be artificially elevated even in prerenal states. When you see diuretics in the stem, switch your thinking to $FEUreaFEUrea$ (less than 35% supports prerenal).

Watch for the postrenal setup in an elderly male with BPH symptoms (hesitancy, weak stream, nocturia) who presents with bilateral hydronephrosis. The next best step is Foley catheter placement, not further imaging or nephrology consultation. Test-writers want to see that you recognize obstruction and act immediately to relieve it.

For rhabdomyolysis, the classic trap is a urine dipstick positive for blood with no red blood cells on microscopy. This discordance occurs because the dipstick reacts with both hemoglobin and myoglobin. The correct next step is checking serum CK, and the treatment is aggressive IV normal saline to maintain urine output above 200-300 mL/hr, which prevents myoglobin from precipitating in the tubules.

Finally, remember that AIN is a clinical diagnosis driven by the temporal relationship between a new medication and renal dysfunction, accompanied by fever, rash, and eosinophilia. The most commonly tested offenders are NSAIDs, beta-lactam antibiotics, sulfonamides, and proton pump inhibitors. The next best step is stopping the drug, not biopsy.

The core competency being tested across AKI questions is your ability to categorize the injury by location (prerenal, intrinsic, postrenal), use the correct laboratory markers to differentiate them, and identify the appropriate next step in management for each category.