Acute Kidney Injury

30-Second Snapshot

Defining and Staging AKI

AKI is diagnosed when any oneof these is true: SCr rises ≥0.3 mg/dL within 48 hours, SCr rises ≥1.5x baseline (known or presumed within the prior 7 days), or urine output drops below 0.5 mL/kg/hr for 6 hours. Before you stage it, correct volume status and rule out obstruction, because both can fake the numbers.

KDIGO is the system to know.RIFLE and AKIN exist too (older, RIFLE adds Loss and ESKD outcome categories) but KDIGO is what's actually used clinically because it's been validated across populations and its stage correlates with mortality, cost, and length of stay.

Pathophysiology - Three Buckets

Everything about AKI sorts into where the problem sits relative to the nephron. This is the single most important organizing idea in the whole chapter, because treatment is completely different in each bucket.

Prerenal: autoregulation trying (and failing) to save you

Normally the afferent arteriole dilates and the efferent arteriole constricts to keep glomerular pressure stable even when renal blood flow drops. That's autoregulation, and it's mediated by prostaglandins (afferent dilation) and angiotensin II (efferent constriction). This is exactly why NSAIDs and ACEi/ARBs are dangerous in a volume-depleted patient: NSAIDs kill the prostaglandin-driven afferent dilation, ACEi/ARBs kill the angiotensin II-driven efferent constriction. Either one alone removes the kidney's safety valve. Both together (the classic "double whammy," and a diuretic on top makes a "triple whammy") can tank GFR fast in someone who's dry.

Intrinsic: ATN vs AIN, different mechanism entirely

Acute tubular necrosis (ATN)is direct injury to tubular epithelial cells from prolonged ischemia or nephrotoxins (aminoglycosides, amphotericin B, IV contrast, myoglobin from rhabdomyolysis, uric acid from tumor lysis). Cells slough off and clog the tubule with debris, cutting off flow entirely in that nephron. This is a toxic/ischemicmechanism, not allergic.

Acute interstitial nephritis (AIN)is completely different: it's a hypersensitivity reaction in the space between tubules, most often triggered by a drug (beta-lactams, NSAIDs, PPIs, thiazides, even furosemide). It's immune-mediated, so the fix is stopping the trigger, not supporting perfusion.

Postrenal: only matters if it's bilateral

A single obstructed ureter usually doesn't cause AKI, because the other kidney compensates and SCr stays normal. You only see AKI with bilateralobstruction, or unilateral obstruction in someone with a single functioning kidney. Always rule this out early with a bladder scan or renal ultrasound since it's the most reversible category if caught fast.

Clinical Presentation

Presentation depends entirely on the cause and setting. Outpatients often show up with vague, nonspecific complaints; hospitalized patients get caught earlier because labs are drawn constantly.

The four phases, if the injury runs its full course

Diagnosis and Workup

History, physical exam (volume status first), labs, and imaging if the cause isn't obvious. No single test makes the diagnosis alone.

Why SCr and BUN aren't enough by themselves

• SCr lags GFR by 1-2 days,so early on it overestimates how much function is left. It's also thrown off by muscle mass, so a frail elderly patient with low muscle can have a "normal" SCr despite real injury.
• BUNis affected by protein intake, catabolic states (steroids, sepsis, thyrotoxicosis), and GI bleeding (blood is a protein load), so it's a poor stand-alone marker, but it's genuinely useful for typing prerenal AKI when paired with creatinine as a ratio.
• Cystatin Cis produced by all nucleated cells at a constant rate and isn't affected by muscle mass, so it's the better call in a frail, low-muscle-mass patient where you suspect SCr is underestimating injury. It's affected by obesity, smoking, and inflammation instead.

Fractional excretion of sodium (FENa), the workhorse calculation

Putting it together

Urinalysis and casts, worth memorizing cold

Prevention Strategies

Prevention beats treatment here because there is no drug that reverses established AKI. The whole strategy is identifying at-risk patients and protecting them before injury happens.

• IV fluidsare the mainstay for hemodynamic instability from volume depletion and for preventing contrast-induced AKI. KDIGO recommends isotonic crystalloids over colloids, and balanced solutions (like lactated Ringer's) may edge out normal saline, likely because normal saline's chloride load can cause its own kidney stress.
• Glycemic controlmatters in both directions. Target 140-180 mg/dL in critically ill patients per ADA and Surviving Sepsis Campaign guidance; both hyper- and hypoglycemia independently worsen outcomes.
• Electronic alertsfor rising creatinine or nephrotoxin exposure improve early detection and reduce cumulative nephrotoxin exposure in hospitalized patients.
• Stop the nephrotoxins you can stop.NSAIDs, unnecessary contrast, aminoglycosides where an alternative exists. This is the single most pharmacist-relevant intervention in the whole chapter.

Treatment, by Category

There is no cure for AKI once it's established. Management is supportive: correct the underlying driver, treat complications, and give the kidney time and the right conditions to heal.

Loop diuretics: symptom control only, never a treatment for AKI itself

Furosemide and other loop diuretics are commonly used to manage fluid overloadin established AKI and are often used before starting KRT to buy time. But they increase urine output without improving hard outcomeslike mortality or need for dialysis. KDIGO explicitly recommends limiting their use to fluid overload management and specifically againstusing them to treat the AKI itself, since more urine doesn't mean a healthier kidney.

Diuretic resistance in AKI

Diuretic resistance is common in AKI patients and has identifiable, fixable causes. Recognizing the mechanism tells you which fix actually works.

Complications to Watch For

These cluster hardest during the oliguric phase and are what actually kill patients, not the creatinine number itself.

Kidney Replacement Therapy (Dialysis)

Deciding when to start KRT is a judgment call, not a single lab trigger. Waiting until the patient is symptomatic increases risk, but starting too early exposes patients to unnecessary catheter and procedural risk. Remember the mnemonic for indications:

Intermittent vs continuous, and why it matters clinically

CRRT comes in variants (CVVH, CVVHD, CVVHDF) that differ in how they clear fluid and solute, but the shared advantage is gradual, gentler solute removal that critically ill patients tolerate better than the rapid shifts of IHD.

Medication Dosing Considerations in AKI

This is a uniquely pharmacist-relevant part of the chapter and shows up constantly in practice, not just on exams.

• AKI is not CKD, and CKD dosing tables don't transfer cleanly.AKI patients often have moreresidual nonrenal clearance than a CKD patient with the same measured creatinine clearance, meaning standard CKD-based dose reductions can leave an AKI patient subtherapeutic, not just at risk of toxicity.
• Volume of distribution changes.Edema and fluid shifts expand the Vd for water-soluble drugs (think vancomycin, aminoglycosides), which can mean a higher loading dose is still appropriate even while maintenance dosing gets reduced.
• Four phases of AKI (onset, extension, maintenance, recovery) each call for reassessment.A dose that's right during the oliguric phase may be wrong a week later in the diuretic phase as clearance changes again. This isn't a "set it and forget it" dosing problem.
• Drug clearance during RRT depends on the drug's own properties(molecular weight, protein binding, Vd, sieving coefficient) as much as on the RRT modality itself. Smaller, less protein-bound, lower-Vd drugs clear more readily through the filter.
• Therapeutic drug monitoringfor narrow-therapeutic-index renally cleared drugs (vancomycin, aminoglycosides) should happen whenever turnaround time allows, because both the kidney function and the RRT prescription are moving targets.

Monitoring - What, When, Why

Patient Counseling - What You'll Actually Say

High-Yield Recall Sheet