Acute Kidney Injury
Clinical Snapshot
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.
Recognize the Condition
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]
The three mechanistic categories
Every AKI presentation is prerenal, intrinsic, or postrenal — identifying which one is present is the entire point of the initial workup.
Prerenal
Reduced renal blood flow without direct kidney damage — volume depletion, hypotension, heart failure, cirrhosis, or hemodynamically-mediated drug effects (RAAS inhibitors, NSAIDs, diuretics). Usually rapidly reversible if perfusion is restored promptly; the most common category overall.
Intrinsic
Direct damage to the kidney parenchyma — acute tubular necrosis (prolonged ischemia or a direct nephrotoxin), acute interstitial nephritis (frequently drug-induced), glomerulonephritis or vasculitis, or contrast-associated injury. Recovery is often slower and less complete than prerenal AKI.
Postrenal
Obstruction to urine flow anywhere from the renal pelvis to the urethra — benign prostatic hyperplasia, pelvic malignancy, nephrolithiasis (especially with a single functioning kidney), or a blocked catheter. Fully reversible if relieved promptly; specifically and urgently treatable, so it must never be missed.
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).
Risk Factors
- 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.
Red Flags & Refer
Escalate to urgent nephrology involvement, and prepare for dialysis, for any of the following — these are complications treated by their presence, not by waiting for a fixed creatinine or urea number.[1]
- Refractory hyperkalemia not controlled by standard medical therapy (see the Potassium Disturbances chapter for the acute stabilization sequence).
- Severe or refractory metabolic acidosis.
- Fluid overload unresponsive to diuretics, particularly with pulmonary edema and respiratory compromise.
- Overt signs of uremia — a pericardial friction rub, uremic encephalopathy, or an otherwise unexplained bleeding tendency.
- KDIGO Stage 3 AKI, or anuria persisting beyond 12 hours.
- A rapidly rising creatinine that continues to climb despite apparently correcting the presumed cause.
- Suspected obstruction (anuria, flank pain, a palpable bladder, known obstructive risk factors) — obtain urgent renal ultrasound and urology involvement; this is a reversible cause and delay causes permanent damage.
- Features suggesting glomerulonephritis or vasculitis (hematuria, proteinuria, red cell casts, systemic symptoms such as rash, arthralgia, or hemoptysis) — needs urgent nephrology assessment and often a kidney biopsy to guide immunosuppressive treatment.
- Rhabdomyolysis with a markedly elevated creatine kinase and myoglobinuria.
Assessment & Diagnosis
KDIGO staging criteria
Stage is assigned by whichever criterion — serum creatinine or urine output — indicates the more severe category.[1]
| Stage | Serum creatinine criteria | Urine output criteria |
|---|---|---|
| 1 | 1.5–1.9 times baseline, or an increase of ≥26.5 μmol/L (≥0.3 mg/dL) | <0.5 mL/kg/hour for 6–12 hours |
| 2 | 2.0–2.9 times baseline | <0.5 mL/kg/hour for ≥12 hours |
| 3 | 3.0 times baseline, or an increase to ≥353.6 μmol/L (≥4.0 mg/dL), or initiation of renal replacement therapy | <0.3 mL/kg/hour for ≥24 hours, or anuria for ≥12 hours |
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).
Treatment Targets
- 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.
Choose Initial Treatment
Treat the specific cause — there is no single "AKI drug"
Immediately hold every nephrotoxic and renally-active drug in every patient with new or worsening AKI, before the specific cause is even confirmed (see Drug Tables) — this single step prevents ongoing injury regardless of the underlying mechanism.
Prerenal — restore perfusion. Use a balanced crystalloid (e.g., lactated Ringer's) in preference to 0.9% sodium chloride for volume resuscitation where feasible; large-volume 0.9% saline resuscitation is associated with more hyperchloremic metabolic acidosis. Do not use hydroxyethyl starch solutions for volume expansion — associated with an increased risk of AKI and need for renal replacement therapy.[1] If hypotension persists despite adequate fluid resuscitation (fluid-refractory vasodilatory shock), start norepinephrine as the first-line vasopressor, titrated to a mean arterial pressure target per institutional protocol.
Do not use low-dose ("renal-dose") dopamine with the intent of preventing or treating AKI — this is a long-standing but unsupported practice; it does not improve renal outcomes and carries its own arrhythmia risk.[1]
Do not use diuretics to prevent AKI, to treat AKI itself, or to convert oliguric AKI to non-oliguric AKI — none of these uses improves outcomes. Reserve diuretics strictly for managing genuine volume overload once it is present.[1]
Intrinsic — remove the causative nephrotoxin immediately; treat the specific process identified (e.g., urgent nephrology-directed immunosuppression for glomerulonephritis or vasculitis; supportive care and drug discontinuation for most drug-induced acute interstitial nephritis, with corticosteroids sometimes used under specialist direction for cases that do not improve).
Postrenal — urgent urology or nephrology referral for relief of the obstruction (urinary catheterization, nephrostomy, or ureteric stenting as appropriate). This category is fully reversible if treated promptly and permanently damaging if it is not — do not delay.
eGFR >30 mL/min/1.73m² — proceed with the clinically indicated contrast study; no specific prophylaxis is needed.
eGFR ≤30 mL/min/1.73m², or established AKI — this is an individualized decision balancing the risk of worsening AKI against the diagnostic/therapeutic benefit of the study and the risk of a missed or delayed diagnosis without it. For intra-arterial iodinated contrast specifically, some centres use intravenous hydration (0.9% sodium chloride or 1.26% sodium bicarbonate) per local protocol; the evidence for hydration before intravenous contrast is insufficient to mandate it, and the choice is left to institutional/practitioner judgment.[3]
Do not routinely use N-acetylcysteine, statins started specifically for this purpose, or any of theophylline, ascorbic acid, allopurinol, fenoldopam, or natriuretic peptides for contrast-associated AKI prophylaxis — none of these is recommended in current guidance. Do not preferentially select an iso-osmolar contrast agent for this purpose either; agent choice should instead be based on cost and availability.[3]
Do not routinely discontinue an ACE inhibitor, ARB, or diuretic purely because of an upcoming contrast study — this is a distinct situation from sick-day illness-related holding below.[3]
Metformin and contrast: hold metformin at the time of, or immediately before, iodinated contrast administration in a patient with an eGFR ≤30 mL/min/1.73m² or with established AKI. Do not restart it for at least 48 hours, and only once kidney function has been reassessed as stable (creatinine risen less than 25% from baseline). Do not routinely stop metformin for contrast exposure in a patient with an eGFR over 30.[3]
During any acute illness with vomiting, diarrhea, fever, or significantly reduced oral intake for roughly 24 hours or longer, temporarily hold the SADMANS medications — Sulfonylureas, ACE inhibitors/ARBs/ARNI, Diuretics, Metformin, Another RAAS agent is not a separate class (mnemonic covers ACEi/ARB together), NSAIDs, and SGLT2 inhibitors — for 1 to 3 days until the patient is eating, drinking, and feeling well again, then resume them.[4][5] Low-dose ASA (81 mg) for cardiovascular prophylaxis does not need to be held. Advise patients specifically to avoid OTC cough/cold/flu products and analgesics containing ibuprofen, naproxen, or decongestants during this period, and to seek medical attention if not improving after 3 days.[5] A patient on a diuretic for heart failure should be advised to check with their care team before pausing it, given the risk of decompensation, rather than stopping it unilaterally.[5]
Non-Pharmacologic Treatment
- 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.
Special Populations
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.
Monitoring & Follow-Up
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.
Common Errors to Avoid
- 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.
Clinical Decision Algorithm
Drug Tables
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.
| Medication class | Examples | Why it is held when unwell/dehydrated | When to resume |
|---|---|---|---|
| ACE inhibitors / ARBs / ARNI | ramipril, losartan, candesartan, sacubitril/valsartan | Impairs the kidney's autoregulatory response to reduced perfusion during volume depletion — increases prerenal AKI risk. | Once eating/drinking normally and feeling well; check with a healthcare provider first if held for a heart failure indication. |
| Diuretics | furosemide, hydrochlorothiazide, indapamide, spironolactone | Compounds volume depletion during illness, increasing prerenal AKI risk. | Once eating/drinking normally; if used for heart failure, contact the care team before pausing rather than stopping unilaterally. |
| SGLT2 inhibitors | empagliflozin, dapagliflozin, canagliflozin | Osmotic diuresis compounds volume depletion; also carries euglycemic diabetic ketoacidosis risk during acute illness. | Once eating/drinking normally and feeling well. |
| NSAIDs (including OTC) | ibuprofen, naproxen, diclofenac, celecoxib; also OTC cold/flu combination products | Direct hemodynamically-mediated nephrotoxicity, most dangerous in combination with an ACE inhibitor/ARB and a diuretic (the "triple whammy"). | Once eating/drinking normally. Low-dose ASA 81 mg for cardiovascular prophylaxis does not need to be held. |
| Metformin | metformin | Risk of lactic acidosis if renal function worsens during the illness. | Once eating/drinking normally; consider restarting at a lower dose for a few days if nausea or diarrhea are still resolving. |
| Sulfonylureas | gliclazide, glyburide, glimepiride | Reduced oral intake during illness raises the risk of hypoglycemia on an unchanged dose. | Once eating/drinking normally; check blood glucose more frequently during the illness itself. |
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.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Aminoglycosides | Use: Reserve for situations where no less nephrotoxic alternative is adequate | Acute tubular necrosis, especially with prolonged courses or pre-existing volume depletion | Additive nephrotoxicity with vancomycin, amphotericin B, or iodinated contrast; ototoxicity risk increases with loop diuretics | Also see <a href="/drug-database/tobramycin">tobramycin</a> and <a href="/drug-database/amikacin">amikacin</a>. Use extended-interval dosing with levels wherever possible; avoid entirely if an equally effective alternative exists. |
| Vancomycin | Dosing: Per current therapeutic drug monitoring protocol, renally adjusted | Acute tubular necrosis/AKI, risk increased with higher trough targets and longer courses | Markedly increased AKI risk when combined with piperacillin-tazobactam | Dose and monitor by current therapeutic drug monitoring practice; reassess renal function frequently during therapy. |
| Amphotericin B (conventional) | Use: Reserve conventional formulation for situations where a lipid formulation is unavailable or not indicated | Dose-dependent nephrotoxicity, renal tubular acidosis, hypokalemia, hypomagnesemia | Additive nephrotoxicity with other nephrotoxic drugs | A lipid formulation substantially reduces nephrotoxicity where available and clinically appropriate. |
| NSAIDs / COX-2 inhibitors | Use in AKI: Avoid; use acetaminophen for analgesia instead where appropriate | Hemodynamically-mediated AKI by impairing prostaglandin-dependent renal autoregulation | Markedly increased AKI risk in combination with an ACE inhibitor/ARB and a diuretic ("triple whammy") | Avoid entirely once AKI is present, not only during a sick-day illness. See <a href="/drug-database/naproxen">naproxen</a>, <a href="/drug-database/diclofenac-potassium">diclofenac</a>, and <a href="/drug-database/celecoxib">celecoxib</a>. |
| Iodinated contrast media | Use: Proceed when clinically indicated; individualize prophylaxis only at eGFR ≤30 | Contrast-associated AKI, disproportionately in patients with an eGFR ≤30 mL/min/1.73m² or additional risk factors | Additive nephrotoxicity with other agents on this list | See Choose Initial Treatment for the current (2022 CAR) prevention framework — N-acetylcysteine is no longer recommended. |
| Calcineurin inhibitors | Dosing: Per current therapeutic drug monitoring protocol | Dose-dependent nephrotoxicity, both acute (vasoconstrictive) and chronic | Levels raised by many CYP3A4 inhibitors, increasing nephrotoxicity risk | Also see <a href="/drug-database/cyclosporine">cyclosporine</a>. Dose by therapeutic drug monitoring; do not adjust empirically without a level. |
| Platinum chemotherapy | Use: Per oncology protocol, with mandated hydration | Direct tubular toxicity, often dose-limiting | Additive nephrotoxicity with other agents on this list | Pre- and post-treatment IV hydration is standard practice specifically to reduce this risk. |
| Piperacillin-tazobactam | Use: Per antimicrobial stewardship guidance; avoid the vancomycin combination where a suitable alternative exists | Associated with an increased AKI risk, particularly when combined with vancomycin | Markedly increased AKI risk in combination with vancomycin | Consider an alternative combination when both agents would otherwise be used together in an at-risk patient. |
| Acyclovir, high-dose IV | Use: Per current dosing guidance, with mandated hydration | Crystal nephropathy from renal tubular precipitation, particularly with rapid infusion or inadequate hydration | Additive nephrotoxicity with other agents on this list | Ensure adequate hydration and infuse over the recommended duration rather than as a rapid bolus. |
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.
| Drug | Dosage | Adverse effects | Drug interactions | Comments |
|---|---|---|---|---|
| Lactated Ringer's injection (balanced crystalloid) | Adults: Titrated IV to restore euvolemia/perfusion, guided by clinical response | Fluid overload if over-administered | None significant | Preferred over 0.9% saline for larger-volume resuscitation given a lower risk of hyperchloremic metabolic acidosis. |
| Sodium chloride 0.9% injection | Adults: Titrated IV to restore euvolemia/perfusion, guided by clinical response | Hyperchloremic metabolic acidosis with large volumes; fluid overload if over-administered | None significant | A reasonable alternative to a balanced crystalloid when one is unavailable. |
| Norepinephrine | Adults: Titrated IV infusion to a mean arterial pressure target per institutional protocol | Arrhythmia; peripheral or digital ischemia at high doses or with extravasation | Caution with other vasoactive/arrhythmogenic drugs | First-line vasopressor for fluid-refractory vasodilatory shock. Do not substitute low-dose dopamine for presumed renal protection. |
| Furosemide | Adults: IV bolus or infusion, titrated to urine output/volume status per institutional protocol | Ototoxicity at high IV doses; electrolyte depletion | Additive ototoxicity with other ototoxic drugs; additive nephrotoxicity with aminoglycosides | Use strictly for genuine volume overload, not to prevent, treat, or convert oliguric AKI. |
| Calcium gluconate | Adults: 10 mL of a 10% solution IV over 2-5 minutes; may repeat once after 5 minutes depending on ECG | Tissue necrosis if extravasated; bradycardia if infused too fast | Incompatible with sodium bicarbonate-containing solutions | First step for AKI with hyperkalemia and ECG changes — stabilizes the cardiac membrane but does not lower potassium. |
| Sodium bicarbonate | Adults: Per institutional protocol, guided by blood gas | Sodium/volume overload; can unmask hypocalcemic tetany | Incompatible with calcium-containing solutions | Reserve for severe metabolic acidosis; give calcium first if hypocalcemic. Renal replacement therapy is often the definitive treatment. |
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.
References
- KDIGO Clinical Practice Guideline for Acute Kidney Injury — Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group. Kidney Int Suppl 2012;2(1):1-138
- Canadian Society of Nephrology Commentary on the 2012 KDIGO Clinical Practice Guideline for Acute Kidney Injury — American Journal of Kidney Diseases (James MT, Levin A, Tonelli M, et al.; Canadian Society of Nephrology). Am J Kidney Dis 2013;61(5):673-685
- Canadian Association of Radiologists Guidance on Contrast Associated Acute Kidney Injury — Canadian Association of Radiologists Journal (Macdonald DB, Hurrell C, Costa AF, et al.). Can Assoc Radiol J 2022;73(3):499-514
- Consensus Recommendations for Sick Day Medication Guidance for People With Diabetes, Kidney, or Cardiovascular Disease: A Modified Delphi Process — American Journal of Kidney Diseases (Watson KE, Dhaliwal K, Robertshaw S, et al.; PAUSE Medication Safety Advisory Panel). Am J Kidney Dis 2023;81(5):564-574
- Protecting the Kidneys When Unwell and Dehydrated (Sick-Day Medication List) — RxFiles Academic Detailing, College of Pharmacy and Nutrition, University of Saskatchewan. RxFiles Academic Detailing, September 2025
Professional reference only. Apply clinical judgment and verify patient-specific decisions against current authoritative guidance and product information.