Acute Kidney Injury

Acute kidney injury (AKI) is an abrupt decline in kidney function occurring over hours to days. KDIGO defines AKI as any one of: a rise in serum creatinine (SCr) of at least 26.5 μmol/L (0.3 mg/dL) within 48 hours; a rise in SCr to at least 1.5 times a known or presumed baseline within the prior 7 days; or a urine output under 0.5 mL/kg/hour for 6 hours.^[1] This is a functional, lab/output-based definition rather than a single disease — AKI is the final common pathway for a wide range of underlying processes, and the point of the workup is always to identify which one is present, not simply to note that the creatinine has risen.

AKI matters enormously to pharmacists for a reason that is different from most other conditions in this library: a very large share of AKI is directly caused or precipitated by medications, and a meaningful fraction of that is preventable at the point of prescribing or counselling. The combination of a RAAS inhibitor (ACE inhibitor or ARB), a diuretic, and an NSAID — the "triple whammy" — impairs the kidney's own autoregulatory response to volume depletion and is a well-documented, common, and avoidable cause of AKI, especially during an intercurrent illness with vomiting, diarrhea, fever, or reduced oral intake.^[2] Sick-day medication counselling, nephrotoxin recognition, and renal dose adjustment are core, everyday pharmacist responsibilities that directly determine whether a patient develops AKI at all.

AKI is frequently clinically silent in its early stages — many cases are first identified on routine bloodwork rather than through symptoms, which is exactly why at-risk patients need proactive monitoring rather than a wait-for-symptoms approach.^[1]

Symptoms and signs, when present

• Reduced urine output (oliguria) or no urine output (anuria) — though a substantial proportion of AKI is non-oliguric and detected only by rising creatinine.
• Edema and rapid weight gain from volume overload.
• Fatigue, nausea, vomiting, and anorexia from accumulating uremic toxins.
• Confusion or altered mental status (uremic encephalopathy) at more severe or prolonged AKI.
• Pruritus, and — at the more severe end — a pericardial friction rub (uremic pericarditis) or an unexplained bleeding tendency (uremic platelet dysfunction).
• Symptoms pointing to the specific mechanism: flank pain and reduced stream (obstruction), a new rash and fever (drug-induced interstitial nephritis), or hematuria with edema and hypertension (glomerulonephritis).

• Age 65 years or older — reduced renal reserve and blunted thirst response.
• Pre-existing chronic kidney disease or a prior episode of AKI — the single strongest risk factor, and a group in whom a further insult is poorly tolerated.
• Diabetes mellitus, heart failure, and cirrhosis — each reduces effective circulating volume or renal reserve through a different mechanism.
• Sepsis and critical illness generally.
• Major surgery, especially cardiac and major vascular surgery.
• Volume depletion from any cause — vomiting, diarrhea, fever, poor oral intake, aggressive diuresis, or heat exposure.
• Concurrent use of the "triple whammy" (ACE inhibitor or ARB, plus a diuretic, plus an NSAID) — a common, largely avoidable combination that impairs the kidney's autoregulatory response to reduced perfusion.^[2]
• Exposure to a direct nephrotoxin — iodinated contrast media, aminoglycosides, vancomycin, amphotericin B, cisplatin and other platinum chemotherapy, or calcineurin inhibitors (see Drug Tables).
• Known or newly diagnosed urinary tract obstruction risk — benign prostatic hyperplasia, pelvic malignancy, nephrolithiasis, or a single functioning kidney.
• Multiple myeloma (cast nephropathy) and other paraproteinemias.
• Malnutrition and hypoalbuminemia, which reduce effective circulating volume and alter drug protein binding.

KDIGO staging criteria

Stage is assigned by whichever criterion — serum creatinine or urine output — indicates the more severe category.^[1]

AKI that persists beyond 7 days is reclassified under KDIGO's expanded framework as acute kidney disease (AKD) — the same underlying principles of cause-finding and nephrotoxin avoidance still apply, but the follow-up timeline shifts toward long-term renal recovery assessment.

History

• Timeline of the creatinine rise or oliguria, and the best available estimate of baseline renal function.
• Every new medication, herbal/supplement, and over-the-counter product in the preceding weeks, with specific attention to NSAIDs (including OTC cold/flu combination products), recent iodinated contrast exposure, and any RAAS inhibitor/diuretic/SGLT2 inhibitor use during an intercurrent illness.
• Volume losses (vomiting, diarrhea, poor intake, excessive diuresis, hemorrhage) and volume-overload symptoms (heart failure, cirrhosis with ascites).
• Urinary symptoms suggesting obstruction — hesitancy, weak stream, or a history of prostate disease or pelvic malignancy.
• Systemic features suggesting glomerulonephritis/vasculitis — rash, joint pain, hemoptysis, recent infection.

Physical examination

• Volume status: jugular venous pressure, skin turgor, mucous membranes, peripheral edema, and postural blood pressure/heart rate change.
• A palpable bladder or suprapubic fullness suggesting outlet obstruction.
• Rash or purpura (drug-induced interstitial nephritis, vasculitis) and signs of the underlying illness driving hypoperfusion (sepsis, heart failure, cirrhosis).

Laboratory and urine studies

• Serum creatinine trend and electrolytes — potassium is the single most urgent value to review at every check.
• Venous or arterial blood gas when acidosis is a concern.
• Urinalysis with microscopy: muddy brown granular casts suggest acute tubular necrosis; red cell casts suggest glomerulonephritis; white cells and eosinophils suggest acute interstitial nephritis; crystals may point to a specific toxin or cast nephropathy.
• Urine sodium and creatinine to calculate the fractional excretion of sodium (FeNa) — under 1% supports a prerenal process, over 2% supports an intrinsic one; use the fractional excretion of urea instead if the patient is on a diuretic, since diuretics invalidate the FeNa calculation.
• Creatine kinase if rhabdomyolysis is suspected.

Imaging

Renal ultrasound to exclude obstruction — obtain promptly whenever the cause is unclear, when a risk factor for obstruction is present, or when the patient is anuric; postrenal AKI is fully reversible if caught early, so this should not be deferred. Avoid additional iodinated-contrast imaging unless it is genuinely necessary for the clinical question (see Choose Initial Treatment for contrast-associated AKI prevention).

• Identify and reverse the specific underlying cause (prerenal, intrinsic, or postrenal) as promptly as possible.
• Restore and maintain adequate renal perfusion without producing volume overload.
• Immediately identify and hold every nephrotoxic or renally-active exposure.
• Prevent and treat the complications that actually cause harm — hyperkalemia, metabolic acidosis, fluid overload, and uremia.
• Adjust the dose of every renally-cleared medication to the current level of kidney function, reassessed frequently as that function changes.
• Minimize progression to chronic kidney disease, and identify patients who need structured post-AKI follow-up.

• Daily weights and strict, documented intake/output monitoring for every patient with active AKI.
• Adequate caloric and protein intake — unlike chronic kidney disease, AKI is not an indication for routine dietary protein restriction; malnutrition worsens outcomes.
• Individualized restriction of dietary potassium, phosphate, and sodium guided by actual lab values rather than applied reflexively to every patient.
• Avoid additional iodinated-contrast imaging unless it will genuinely change management; use ultrasound or non-contrast imaging where diagnostically adequate.
• Renal replacement therapy (intermittent hemodialysis or continuous renal replacement therapy, chosen largely by hemodynamic stability) as the definitive supportive intervention when a red-flag complication is present — this is itself a non-pharmacologic treatment.
• Early mobilization and physiotherapy once the patient is hemodynamically stable.
• A structured medication reconciliation at every encounter specifically flagging nephrotoxic and renally-cleared drugs for review.

Pregnancy

Preeclampsia/HELLP syndrome, acute fatty liver of pregnancy, and postpartum hemorrhage are important obstetric-specific causes of AKI and should be considered alongside the standard prerenal/intrinsic/postrenal framework. Because normal pregnancy increases glomerular filtration rate, a serum creatinine within the usual non-pregnant "normal" range can already represent significant renal impairment in pregnancy — interpret creatinine against a pregnancy-adjusted expectation, not the standard reference range. ACE inhibitors and ARBs are independently contraindicated in pregnancy for teratogenicity, separate from any AKI consideration, and should already be avoided. Use contrast studies only when clinically necessary, applying the same eGFR-based framework above.

Breastfeeding

Hemodialysis and standard emergency AKI medications — calcium gluconate, insulin/dextrose, sodium bicarbonate, and furosemide — are all considered compatible with breastfeeding at usual doses. Hold any maternal medication that is independently contraindicated in lactation per its own product information, separate from the AKI indication.

Pediatrics

Hemolytic uremic syndrome — classically following Shiga toxin-producing E. coli (STEC) gastroenteritis — is an important pediatric cause of AKI. A key pharmacist teaching point: antibiotics and antimotility agents are generally avoided in suspected STEC-associated bloody diarrhea, since some evidence suggests they may increase the risk of progression to hemolytic uremic syndrome. Pediatric AKI staging uses weight-based urine output thresholds and age-appropriate eGFR equations rather than the adult criteria above; all dosing must be individualized under pediatric or pediatric nephrology direction rather than extrapolated from adult figures in this chapter.

Older adults

Reduced renal reserve, blunted thirst response, and polypharmacy combine to make older adults both more likely to develop AKI and less able to tolerate it. Proactively review and deprescribe non-essential nephrotoxic medications, and reinforce sick-day counselling specifically in this group.

Pre-existing chronic kidney disease (AKI-on-CKD)

This is the highest-risk group for both developing AKI and for incomplete recovery afterward — reduced renal reserve means a smaller insult produces a larger relative decline, and distinguishing a true acute event from expected CKD progression can be difficult without a reliable recent baseline. Apply more conservative thresholds for nephrotoxin exposure and diuretic dosing, and prioritize this group for post-AKI nephrology follow-up given the elevated risk of progression to end-stage kidney disease.

During active AKI

Check serum creatinine at least daily (more frequently in severe or rapidly evolving AKI), and monitor urine output continuously if catheterized or in a critical-care setting. Check electrolytes — potassium above all — at least daily, along with a blood gas whenever acidosis is a concern. Track daily weights and cumulative fluid balance throughout.

After recovery

KDIGO recommends a structured follow-up evaluation around 3 months after an AKI episode to confirm renal recovery and screen for new or worsening chronic kidney disease — even a single AKI episode is an independent risk factor for CKD progression and for a further AKI episode, so this follow-up should not be skipped simply because the creatinine has returned toward normal at discharge.^[1] Refer to nephrology for incomplete renal recovery, KDIGO Stage 3 AKI, or pre-existing CKD.

Medication reconciliation

Confirm explicitly, at the point of clinical recovery, that every medication placed on hold is formally resumed — a well-documented gap is a drug that stays "on hold" indefinitely after discharge simply because no one restarted it. Reassess the dose of each resumed RAAS inhibitor, diuretic, or renally-cleared drug against current renal function rather than automatically restarting the pre-AKI dose. Reinforce sick-day medication counselling for the next illness before the patient leaves the encounter.

1. Confirm every nephrotoxin — including over-the-counter NSAIDs and herbal/supplement products — is genuinely and completely held, not merely reduced.
2. Reassess volume status directly: both inadequate resuscitation and iatrogenic volume overload can each perpetuate AKI, and the correct next step depends on which is actually present.
3. Re-examine for a missed cause. Obtain a renal ultrasound if one has not already been done, to exclude obstruction. Reconsider an intrinsic cause — acute interstitial nephritis, glomerulonephritis, or vasculitis — especially if the urinalysis showed white cells, eosinophils, or red cell casts.
4. Persistent oliguria or a still-rising creatinine despite addressing the presumed cause is an indication to involve nephrology, not to continue the same supportive measures indefinitely.
5. If a specific complication (hyperkalemia, metabolic acidosis, fluid overload, or uremia) becomes refractory to medical therapy, initiate renal replacement therapy without further delay — do not wait for a fixed creatinine or urea threshold, since the complication itself is the indication.
6. AKI persisting beyond 7 days is reclassified as acute kidney disease under the expanded KDIGO framework — shift toward a longer-term renal recovery and nephrology follow-up plan rather than continuing to manage it as an acute inpatient problem alone.

• Continuing the "triple whammy" — an ACE inhibitor or ARB, a diuretic, and an NSAID together — through an acute dehydrating illness without holding any of the three.^[2]
• Using low-dose ("renal-dose") dopamine believing it protects the kidneys — not supported by evidence and no longer recommended.^[1]
• Prescribing prophylactic N-acetylcysteine for contrast-associated AKI prevention — current Canadian guidance explicitly does not recommend it.^[3]
• Withholding medically necessary contrast imaging out of AKI fear in a patient with an eGFR over 30 and no other major risk factor — this delays diagnosis without a meaningful renal benefit.^[3]
• Using a diuretic to try to convert oliguric AKI to non-oliguric AKI, or to "treat" AKI itself rather than genuine volume overload.^[1]
• Missing an obstructive (postrenal) cause by not ordering a renal ultrasound — this category is fully reversible if caught promptly.
• Forgetting to renally dose-adjust — or forgetting to hold entirely — a drug cleared by the kidney once AKI is recognized.
• Continuing metformin in a patient who develops AKI, given the lactic acidosis risk.
• Discharging a patient after an AKI episode without a documented plan for resuming every held medication and rechecking renal function.
• Using hydroxyethyl starch solutions for volume resuscitation.
• Assuming a "normal" serum creatinine excludes significant kidney injury in a patient with reduced muscle mass, or in pregnancy, where a materially lower baseline is expected.

How to use this table: Doses are adult doses and require patient-specific confirmation (renal/hepatic function, weight, allergy history). Pediatric dosing is weight-based per the current product monograph unless stated. Drug pricing is intentionally omitted. Select any drug name to open its complete Pharmasist Drug Database page.

Sick-Day Medications — Hold Temporarily During Acute Illness (SADMANS)

During an acute illness with vomiting, diarrhea, fever, or reduced oral intake for about 24 hours, hold the medications below for 1 to 3 days until the patient is eating, drinking, and feeling well, then resume them. Continuing these through a dehydrating illness is a common, preventable cause of AKI.

Nephrotoxic Drugs — Avoid or Use With Extreme Caution in AKI

Hold whenever possible once AKI is recognized; where a listed agent is genuinely required, use the lowest effective dose/duration with close renal monitoring.

Supportive and Emergency Therapy in AKI

For volume resuscitation, hemodynamic support, and the acute complications of AKI. See the Potassium Disturbances chapter for the full hyperkalemia stabilization sequence.

General principles for renal dose adjustment in AKI

• Estimate renal function using the institution's standard method (commonly Cockcroft-Gault for drug dosing purposes) and reassess it frequently — unlike stable chronic kidney disease, renal function in AKI can change materially within a single day.
• Loading doses are typically not reduced for renal impairment — they are based on volume of distribution, not clearance. Maintenance dose or dosing interval is what usually needs adjustment.
• Use therapeutic drug monitoring wherever available for narrow-therapeutic-index, renally-cleared drugs — vancomycin, aminoglycosides, and digoxin are the most common examples — rather than adjusting by estimated function alone.
• Consult the product monograph or an institutional renal dosing reference for each individual drug; do not extrapolate one drug's adjustment to another in the same class.
• Reassess every renally-cleared drug's dose again as AKI resolves — a dose reduced for AKI that is never increased back once renal function recovers is a common, preventable source of underdosing.