CONTENTS
- Rapid Reference: Approach to AKI 🚀
- Definition & significance of AKI
- Causes of AKI
- Evaluation of the cause of AKI
- Tests to evaluate the cause of AKI
- Approach to oliguria
- Furosemide stress test
- Management of AKI
- Related/miscellaneous
evaluation of the cause of AKI
labs
- Basic labs:
- Electrolytes (including Ca/Phos/Mg).
- Creatinine Kinase.
- Urinalysis (table below; if urinalysis suggests glomerulonephritis or acute interstitial nephritis, consult nephrology to review the urine microscopy).
- Additional labs:
- Relevant drug levels (e.g., vancomycin, aminoglycoside, cyclosporine, tacrolimus).
- Uric acid if concern for tumor lysis syndrome. 📖
renal & bladder ultrasound
- The primary role is the exclusion of hydronephrosis. However, this may provide additional information (e.g., scarred or polycystic kidneys).
- Immediate bedside ultrasonography may expedite diagnosis (don't forget to look at the bladder).
- If an abdominal CT scan was recently done for another reason, this is adequate to exclude hydronephrosis.
management of AKI
treat any identifiable cause(s) 📖
medication management
potassium
- D/C potassium supplementation, potassium-sparing diuretics, or PRN potassium orders (hold potassium unless K<3.0 mM). 📖
- Treat hyperkalemia if present. 📖
phosphate
- Renal diet in severe AKI.
- Consider phosphate binder if phosphate >6 mg/dL. 📖
- In hypocalcemia: calcium carbonate or calcium acetate (~600 or ~667 mg TID with meals).
- Otherwise: sevelamer 800 mg TID with meals.
acidosis management
- Consider bicarbonate for uremic metabolic acidosis. 📖
hemodynamic optimization 📖
- Defend the MAP.
- Hold antihypertensives if soft Bp (especially negative inotropes).
KDIGO criteria for acute kidney injury (assigned based on most worrisome feature)
- Stage I AKI
- Cr 1.5-1.9 times baseline.
- Cr increase >0.3 mg/dL.
- Urine output <0.5 ml/kg/hr for 6-12 hours.
- Stage II AKI
- Cr 2-2.9 times baseline.
- Urine output <0.5 ml/kg/hr for 12-24 hours.
- Stage III AKI
- Cr >3 times baseline.
- Cr >4 mg/dL.
- Initiation of dialysis.
- Urine output <0.3 ml/kg/hr for >24 hours.
- Anuria >12 hours.
more detailed understanding of types of AKI
- Prognosis depends on changes in urine output and creatinine (figure above). (25568178) Some specific types bear mention:
- Isolated oliguria (low urine output with stable creatinine).
- These patients rarely require dialysis, unless oliguria is profound (Stage 3).
- This may often represent “pre-renal” renal failure – the kidney is compensating for hypoperfusion by reducing urine output, but is continuing to function adequately.
- ⚠️ Be careful, however, because sometimes patients maintain a stable creatinine from a dilutional effect due to receiving lots of intravenous fluid. In that situation, creatinine may overestimate the renal function.
- Oliguria should be taken seriously and evaluated adequately. However, <12 hours of oliguria isn't necessarily a disaster – especially if the creatinine remains stable.
- Non-oliguric renal failure (elevated creatinine with normal urine output)
- The vast majority of these patients (99.7% overall) won't require dialysis.
pre-renal: disorders of perfusion
- Shock of any etiology (e.g., hypovolemic shock, cardiogenic shock).
- Hepatorenal syndrome.
- Congestive nephropathy (systemic congestion impairs venous outflow).
- Abdominal compartment syndrome.
- Hypertensive emergency.
- Thrombotic thrombocytopenic purpura & hemolytic uremic syndrome.
intrinsic renal failure
- Nephrotoxic medications (listed below).
- Cellular lysis (rhabdomyolysis, hemolysis, tumor lysis syndrome).
- Acute glomerulonephritis.
- Acute tubulointerstitial nephritis (ATIN).
- Acute tubular necrosis (ATN).
post-renal: Urologic obstruction
- Prostate obstruction.
- Occluded or malpositioned Foley catheter.
- Nephrolithiasis.
cardiovascular medications
- Direct:
- ACE inhibitors and angiotensin receptor blockers (ARBs).
- Triamterene.
- Indirect:
- For patients with borderline cardiac output, medications that reduce cardiac output may be nephrotoxic (e.g., beta-blockers, diltiazem).
- For patients with borderline hypotension, antihypertensives may be nephrotoxic.
antibiotics
- Aminoglycosides.
- Beta-lactams rarely cause interstitial nephritis (especially penicillins such as nafcillin, piperacillin, and ampicillin).
- Colistimethate (Colistin).
- Sulfonamides.
- Vancomycin.
antifungals
- Amphotericin.
- Pentamidine. (31665764)
antivirals (not exhaustive)
- Acyclovir, ganciclovir, valacyclovir, valganciclovir (crystal deposition).
- Cidofovir.
- Foscarnet.
- Indinavir.
- Tenofovir.
chemotherapy (not exhaustive)
- Many newer biologics and small-molecule inhibitors (not listed individually).
- Bevacizumab.
- Busulfan.
- Carboplatin.
- Checkpoint inhibitors.
- Cisplatin.
- Cyclophosphamide
- Ifosfamide.
- Methotrexate.
- Mitomycin.
- Oxaliplatin.
miscellaneous
- Antiepileptics (topiramate, zonisamide).
- Bisphosphonates (pamidronate, zoledronic acid).
- Immunosuppressives:
- Calcineurin inhibitors (cyclosporine, tacrolimus).
- mTOR inhibitors (sirolimus, everolimus).
- Inflammatory bowel disease medications (mesalamine, sulfasalazine).
- Intravenous immunoglobulin (IVIG).
- Mannitol.
- NSAIDs. (39230007)
- Urine electrolytes & fractional excretion of sodium (FENa).
- Urine eosinophils have poor performance for diagnosing acute tubulointerstitial nephritis. (24052222)
significance of oliguria
- Oliguria is a subset of acute kidney injury defined by low urine output (<0.3-0.5 ml/kg/hr for several hours, or roughly <500 ml/day). (29156029)
- Although oliguria has traditionally often been interpreted as a surrogate for hypovolemia, this is not accurate. Oliguria can be caused by any type of renal failure (if sufficiently severe).
This is intended merely as a rough conceptual schema to oliguria, not a rigid protocol. For example, if evaluation reveals the presence of a specific diagnosis (e.g., septic or cardiogenic shock), then further treatment will be aimed at that problem. The main issue is to put some thought into this rather than reflexively administering fluids.
#1: exclude obstruction
- Obstruction is rare, but this is a must-not-miss diagnosis.
- 🥇 The gold standard is bedside ultrasonography of the bladder and kidneys.
- 🥈 Simply performing a bladder ultrasound is probably adequate since this may evaluate for urethral obstruction. Unilateral ureteral obstruction shouldn't cause oliguria due to urine production from the contralateral kidney
- 🥉 Trouble-shooting the Foley catheter (via flushing) is reasonable, but not infallible.
#2: hemodynamic evaluation
- Perform a brief chart review focusing on vital sign trends, new medications added (e.g., antihypertensives), and cardiac history.
- Evaluation generally focuses on volume status, but other factors should also be considered (e.g., cardiac output).
- If the patient is hypertensive, this suggests the presence of intrinsic renal failure (rather than shock or hypovolemia).
#3a: volume challenge?
- Indicated for total-body hypovolemia.
- The best indications for providing fluid are one of the following:
- (1) Input/output trends showing that the patient is substantially net negative over the past day (e.g., salt-wasting nephropathy or aggressive diuresis).
- (2) Clinical history of nausea/vomiting, diarrhea, and poor oral intake combined with echocardiogram showing hypovolemia.
- (3) POCUS suggesting volume depletion.
- If the patient is hypertensive, this argues against hypovolemia, making fluid administration less likely to help.
#3b: vasopressor challenge?
- Although a MAP >65 mm is adequate for most patients, some patients with chronic hypertension may require a higher blood pressure to perfuse their kidneys adequately.
- If there is concern that the MAP is too low, then the blood pressure can be raised for a couple of hours with an infusion of norepinephrine or phenylephrine (e.g., to MAP >75 mm). If this stimulates urine output, the higher MAP should be maintained.
#3c: inotrope challenge?
- If there is evidence of poor cardiac output and concern for cardiogenic shock, it may be reasonable to trial an inotrope.
- Improved urine output following inotrope initiation confirms a diagnosis of cardiogenic shock. In this case, continue to treat the cardiogenic shock as discussed here: 📖.
#3d: furosemide stress test
- This is a validated test of renal function, which predicts the likelihood of persistent renal failure and dialysis. (24053972, 25655065, 29344743, 29673370)
- If the patient fails the furosemide stress test, this suggests significant intrinsic renal failure. In this situation, further hemodynamic manipulation is unlikely to help. This can help support a decision to stop giving the patient fluids.
- (More about the furosemide stress test in the next section)
definition of a furosemide stress test
- Administration of a defined dose of furosemide:
- 1 mg/kg for patients who are furosemide naive.
- 1.5 mg/kg for patients with prior exposure to furosemide.
- Monitoring urine output
- >200 ml within two hours indicates adequate response.
significance
- Failure to respond to a furosemide stress test suggests renal failure (with an increased risk of requiring hemodialysis). 🌊
- Please note that failure to respond doesn't exclude the possibility of renal recovery – especially if other resuscitative steps are available to improve renal function (e.g., improvement in blood pressure and/or perfusion).
clinical utility of a furosemide stress test?
- (1) The oliguric patient: Will additional hemodynamic manipulation help?
- A furosemide stress test may be useful to obtain a concept of whether the patient has intractable intrinsic renal failure.
- Failure to respond to furosemide implies that the kidneys are less likely to respond to hemodynamic manipulation (e.g., volume administration) and more likely to progress toward dialysis. Thus, a fluid-conservative strategy might be more beneficial.
- Response to a furosemide stress test reveals that the kidneys are functional. Therefore, hemodynamic manipulations to maintain urine output (e.g., volume administration, inotropes, vasopressors) may be more likely to succeed.
- (2) A patient who is volume overloaded and requires diuresis:
- Using the dose of furosemide prescribed in the furosemide stress test can help interpret the patient's response more rigorously.
Renal failure in the ICU is generally multifactorial. Treatment involves identifying and addressing all contributory factors (e.g., nephrotoxins as listed above). In addition, a variety of supportive therapies are important.
- Note that calculations of the glomerular filtration rate (GFR) based on creatinine level will be misleading in acute kidney injury.
- Formulas for the GFR only work in steady-state (equilibrium) conditions. This usually isn't the case in acute kidney injury.
- For example, with complete cessation of renal function, the creatinine will often increase by roughly ~1 mg/dL daily. So, if a patient's creatinine increases from 0.7 mg/dL to 1.7 mg/dL, their GFR may be extremely low (much lower than the calculated GFR).
maintain an adequate MAP
- MAP >65 mm is usually the target MAP for patients in AKI. MAP >80 mm may improve renal outcomes in some patients, especially those with chronic hypertension. (27230984)
- When in doubt, consider a vasopressor challenge: give the patient pressor to increase the MAP and determine whether this improves urine output.
- Regarding renal outcomes, vasopressin might have a slight advantage over other vasopressors, particularly among patients with tachycardia and systemic vasodilation. (27483065)
maintain euvolemia
- Generally avoid fluids.
- Non-oliguric AKI generally isn't due to hypoperfusion and shouldn't be an indication for extra fluids.
- Fluid should be given only if, after thoughtful assessment, there is evidence of hypovolemia (more on this above).
- If fluids are used, choose the best one.
- For patients with hypovolemia and uremic acidosis, the fluid of choice is isotonic bicarbonate (D5W with 150 mEq/L sodium bicarbonate). More on this below.
- For patients with hypovolemia and normal serum bicarbonate, the fluid of choice is a balanced crystalloid (e.g., lactated Ringers or plasmalyte). Avoid normal saline. (27230984, 29485926, 29485925) Contrary to popular dogma, lactated Ringers or plasmalyte are entirely safe in hyperkalemia (whereas normal saline is unsafe).
- Avoid volume overload.
- Overload may cause renal intra-capsular edema (swelling within the kidney that impairs perfusion, a bit like compartment syndrome). Furthermore, increased central venous pressure impairs renal perfusion by hampering venous blood flow from the kidney (a.k.a. congestive nephropathy). Among patients with marked systemic venous congestion, diuresis may often improve renal function!
- Basic steps to avoid volume overload include avoiding maintenance fluid or repeated fluid boluses.
- Follow fluid balance (inputs vs. outputs) and avoid ongoing volume accumulation or total net gain of more than a few liters. For example, if the patient is running a net of 1-2 liters positive per day, this will rapidly become a significant problem.
- Diuresis (furosemide with or without a thiazide) should be used to prevent or treat volume overload. Patients with renal failure may require prodigious diuretic doses. If this isn't effective, dialysis may be needed to control the volume status.
bicarbonate vs. dialysis
- Nephrologists have used bicarbonate to stave off dialysis for decades. More recently, the BICAR-ICU trial demonstrated that bicarbonate use in the ICU to treat anion-gap metabolic acidosis does indeed avoid dialysis. (29910040) It's not entirely clear whether bicarbonate actually improves renal function or whether it merely improves acidosis. Regardless, avoidance of dialysis is a meaningful patient-centered outcome.
- Sodium bicarbonate is generally the first-line therapy for uremic acidosis. The exact target level isn't clear, but shooting for a pH >7.2 may be reasonable (often equivalent to a bicarbonate level over ~17 mEq/L). (29910040)
- Dialysis is the second-line therapy for acidosis in situations where bicarbonate is ineffective or contraindicated.
formulations & route of bicarbonate:
- Isotonic bicarbonate is useful for patients with volume depletion (D5W with 150 mEq/L sodium bicarbonate). The problem with isotonic bicarbonate is that for patients who are euvolemic or hypervolemic, it provides a substantial volume load.
- Hypertonic bicarbonate ampules (50 ml ampules of 1 mEq/ml bicarbonate) are great for patients with hyponatremia. For example, two ampules (100 mEq/L) typically increase the bicarbonate and sodium by ~3 mEq/L. Ampules should be pushed slowly over ~10 minutes each to avoid rapid swings in pH. The problem with this strategy is that for patients with baseline sodium over ~140 mEq/L, it may cause hypernatremia.
- Oral bicarbonate tablets can be used for patients with mild acidosis to prevent worsening over time.
- Each 650 mg tablet contains 7.6 mEq of sodium bicarbonate (which isn't much).
- 1300 mg BID or TID provides 30 or 45 mEq bicarb daily, respectively.
- Potential indications:
- Acidosis refractory to IV bicarbonate.
- Electrolyte abnormalities (typically diuresis-refractory hyperkalemia).
- Fluid overload refractory to diuretics.
- Uremic symptoms (e.g., delirium, asterixis, pericardial effusion).
- Early versus late initiation of dialysis remains controversial. The best indication for earlier dialysis may be a patient progressively accumulating fluid and developing severe volume overload. As discussed above, even in the absence of frank pulmonary edema, systemic congestion may directly harm the kidneys, perpetuating renal dysfunction.
- Initiate phosphate binder if phosphate is >6 mg/dL.
- Calcium acetate (PHOSLO)
- 667 mg tablets, start with two tablets TID with meals
- Useful in patients with hypocalcemia. Avoid in hypercalcemia or vitamin D intoxication.
- Sevelamer (RENAGEL)
- Start at 800 mg PO TID with meals, double dose if needed.
- Nonabsorbable resin avoids problems with Mg and Ca (may be preferable for patients on dialysis).
- May impair absorption of some drugs from the gut.
clinical findings:
- Clinical context:
- GFR is usually <10-15 ml/min.
- Acute renal failure carries a higher risk than chronic renal failure.
- Movement disorders:
- Myoclonus and asterixis (“negative myoclonus”). Myoclonus has an extensive differential diagnosis 📖. In the absence of an alternative explanation for myoclonus, this may be highly suggestive of uremic encephalopathy.
- Tremor.
- Muscle spasms (including spontaneous carpopedal spasm). (Louis 2021)
- Delirium.
- Seizures.
lumbar puncture
- Not indicated to evaluate uremic encephalopathy, but may be needed to exclude alternative diagnoses.
- Protein may be mildly elevated (>100 mg/dL), occasionally with a mild pleocytosis. (Louis 2021)
EEG
- Background slowing may occur.
- GPDs 📖 (generalized periodic discharges) with triphasic morphology may appear.
- NCSE (nonconvulsive status epilepticus) may occur – and this is important to recognize since treatment may cause dramatic improvement. (Louis 2021)
neuroimaging findings:
- Three patterns may be seen:(31589567)
- (1) Basal ganglia involvement may be the most common:
- Basal ganglia hyperintensities are seen.
- “Lentiform fork sign” – bright rim highlights the medial and lateral edges of the putamen (figure below).
- (2) Posterior Reversible Encephalopathy Syndrome (PRES): Uremia may promote the development of PRES, especially in combination with hypertension.📖
- (3) Acute toxic leukoencephalopathy.
differential diagnosis
- The differential diagnosis is broad, including other causes of delirium as discussed here: 📖
- Accumulation of renally cleared medications should be carefully considered.
- NCSE (nonconvulsive status epilepticus).
- PRES (posterior reversible encephalopathy syndrome).
- Metabolic disturbances (e.g., severe electrolyte abnormalities).
management
- Evaluate and treat for any/all coexisting causes of delirium.
- Uremic encephalopathy generally responds well to dialysis, but this response may be delayed for some days (e.g., the first dialysis run may cause transient worsening). (Louis 2021)
- Dialysis disequilibrium syndrome usually occurs following initiation of dialysis among patients with severe baseline azotemia.
- Symptoms vary from nausea and mild headache to delirium and seizures.
- The central pathophysiology appears to be a rapid reduction in blood urea nitrogen levels, causing osmotic shifts that result in cerebral edema.
- The differential diagnosis is similar to the differential diagnosis of uremic encephalopathy (listed above).
- Management:
- Use of dialysate with higher sodium concentration may avoid osmotic shifts.
- In patients with persistent and severe symptoms, hypertonic saline may be considered to reverse cerebral edema. (Louis 2012)
hemodialysis (hemodialyzer machine)
IHD (intermittent hemodialysis)
- Diffusion promotes solute clearance.
- Urea, creatinine, and potassium usually leave blood.
- Bicarbonate and usually calcium enter the blood.
- Sodium may enter or leave (to equilibrate with dialysate).
- Convection (via ultrafiltration) allows for volume removal.
- High blood flow rate (~350-400 ml/min) and high dialysate flow rate (500-800 ml/min). (Schmidt 2024)
SLED (sustained low-efficiency dialysis) 🛷
- May be used as a PIRRT (prolonged intermittent renal replacement therapy).
- The blood flow rate is lower than with IHD (150-250 ml/min), as is the dialysate flow rate (100-200 ml/min). (Schmidt 2024)
- Typically, a slow hemodialysis session is performed over 8-12 hours daily. (Vincent 2024)
- The primary advantage of SLED is that it may allow for patient mobilization during the day.
- SLED is rarely used, usually in response to resource constraints. (Irwin 2023)
UF (ultrafiltration)
- Isolated ultrafiltration is performed, which solely removes fluid.
- Used for patients with isolated volume overload.
dialysate composition
- Potassium level: 1-4 mM.
- 1 mEq/L used for severe hyperkalemia (does carry the risk of arrhythmias due to rapid potassium clearance). (Irwin 2023)
- Bicarbonate:
- Usually 33-35 mM.
- 40 mEq/L may be used for chronic hypercapnia, or severe acidosis.
- Calcium:
- Usually 2.5 mM.
- 3-3.5 mM may be used to avoid hypocalcemia (especially with acidosis correction). (Irwin 2023)
CRRT (continuous renal replacement therapies using a hemofilter)
SCUF (slow continuous ultrafiltration)
- Fluid removal with minimal solute clearance.
- Similar to ultrafiltration (used for volume removal).
CVVH (continuous venovenous hemofiltration)
- CVVH = SCUF plus replacement fluid. Convection is used to achieve solute clearance and fluid removal.
- Ultrafiltrate is generated at 1-4 liters/hour and replaced with RF (replacement fluid). This creates high volumes of ultrafiltrate (~48-96 liters/day). (Irwin 2023)
- Convective clearance removes small and middle-sized molecules (<5000 Da), including cytokines. (Schmidt 2024)
CVVHD (continuous venovenous hemodialysis)
- This is purely dialysis, causing solute clearance via diffusion.
- The blood flow rate is slower than IHD (~100-250 ml/min), but the major difference is that the dialysate flow rate is much slower (25-30 ml/min, or ~1-2 liters/hour). This causes complete equilibration of solutes with the dialysate. (Irwin 2023)
- Effectively clears small molecules (<100 Da).
CVVHDF (continuous venovenous hemodiafiltration)
- This combines dialysis (diffusive clearance) and filtration (convective clearance).
- Dialysate is infused at 1-2 liters/hour.
- Replacement fluid is added at 1-2 liters/hour.
- May be unnecessarily complex (newer CVVHD machines are adequate and more straightforward). (Irwin 2023)
anticoagulation with CRRT
- Heparin is often necessary (e.g., bolus of 1000-2000 IU, followed by 10 IU/kg/hr to target an aPTT of 1.5-2 times normal). (Irwin 2023)
- Regional citrate anticoagulation limited to the CRRT circuit is recommended for patients without contraindications by the KDIGO-AKI Clinical Practice Guidelines. (Irwin 2023)
- Advantages of regional citrate anticoagulation may include prolonged filter life, lower transfusion requirement, and reduced incidence of hemorrhagic complications. (Vincent 2024)
- Ionized calcium must be monitored carefully, especially in patients with hepatic dysfunction (who may accumulate citrate, leading to reduced ionized calcium levels with elevated anion gap metabolic acidosis). Other risks include hypernatremia and hypomagnesemia.
electrolyte monitoring and adjustments
- Hypophosphatemia is common, but this may be mitigated by adding phosphate to dialysate.
dose of CRRT
- CRRT is dosed in terms of the effluent flow rate, with a range of 20-35 ml/kg/hr.
- Effluent reaches equilibrium with the blood, so the effluent rate equals the clearance rate.
- A minimum dose of 20-25 ml/kg/hr should be delivered. (Schmidt 2024)
- Risk of inadequate dosing: poor metabolic control of acidosis or uremia.
- Risk of excessive dosing: micronutrient deficiency, excessive clearance of medications.
selection of IHD vs. CRRT
advantages of CRRT
- [1] CRRT promotes greater hemodynamic stability (avoiding hypotension may promote renal recovery).
- [2] CRRT is superior for volume management. (CRRT is capable of slowly and continuously removing volume, which may achieve much higher amounts of fluid removal when multiple across 24 hours. Alternatively, IHD leads to intra-dialytic fluid accumulation.)
- [3] CRRT is preferred for patients with ICP elevation:
- Less fluctuation in cerebral perfusion pressure and intracranial pressure.
- Recommended by KDIGO guidelines for patients with cerebral edema.
- [4] CRRT is preferred in ALF (acute liver failure):
- IHD may cause rapid clearance of water and solutes, causing elevated intracranial pressure.
- EASL (European Association for the Study of the Liver) and KDIGO-AKI recommend CRRT instead of IHD.
- Hyperammonemia may be an indication for dialysis in the context of acute liver failure to avoid intracranial pressure crises (discussed further: 📖).
- [5] CRRT can be safely utilized in severe hyponatremia:
- IHD will immediately increase the sodium to a normal level. It is often impossible to reduce the dialysate sodium concentration to <130 mM.
- CRRT may avoid rapid sodium shifts by adjusting the dialysate fluid (table below). An alternative strategy is to run a separate infusion of hypotonic fluid independent of the dialysate. (34218456)
- [6] Rhabdomyolysis or tumor lysis syndrome.
- CRRT may be more effective than IHD for clearance of hyperphosphatemia.
advantages of IHD
- Preferred for intoxications due to more rapid toxin clearance.
- Preferred for extreme hyperkalemia.
- May facilitate physical therapy.
- May facilitate off-unit testing or procedures.
criteria for discontinuation of CRRT in acute kidney injury
Criteria utilized in the ATN study:
- Urine output >30 ml/hour.
- Six-hour timed urine collection utilized to calculate creatinine clearance:
- Creatinine Clearance = (Urine [Cr])x(Urine volume)/(Plasma [Cr])(360 minutes)
- Creatinine clearance <12 ml/min: continue CRRT.
- Creatinine clearance 12-20 ml/min: Individualize ongoing CRRT.
- Creatinine clearance >20 ml/min: Discontinue CRRT. (18492867)
There are two methods to estimate GFR based on vancomycin clearance.
method #1: single compartment model
- Baseline assumptions:
- Vancomycin clearance = 0.82(creatinine clearance). (19933799) Various studies have reported a ratio between 0.75-0.9, so 0.82 seems reasonable.
- Volume of distribution = 0.7 L/kg. This factor is subject to greater variation between studies, but 0.7 L/kg seem to be a reasonable figure that is often quoted in pharmacokinetic textbooks.
- Vancomycin is modeled using single-compartment pharmacokinetics.
- Based on these assumptions, GFR (creatinine clearance) may be estimated based on the concentration at two time points, the time elapsed between measurements, and the patient's weight:
- GFR in ml/min = 14*ln(C2/C1)*(wt in kg)/(Δ time in hours)
method #2: Creighton equation
- The elimination constant (Kel) of vancomycin is linearly related to the creatinine equation based on the following equation: (6732213)
- Kel (/hr) = 0.00083(Creatinine clearance in ml/min) + 0.0044
- Kel = ln (C2/C1)/(Δ time in hours)
- This equation is widely cited in pharmacokinetic literature and has been the basis of some studies on vancomycin pharmacokinetics. (32166646) However, when various authors try to replicate this equation, the results are somewhat variable.
comparison of methods
- The online calculator below will estimate GFR using both methods.
- For weights around 70 kg, the results are similar. For higher weights, the 1-compartment model will produce a higher GFR (since it's calculating an absolute creatinine clearance). Alternatively, the Creighton equation yields the same GFR regardless of weight (effectively calculating a GFR corrected for body surface area).
Follow us on iTunes
The Podcast Episode
Want to Download the Episode?
Right Click Here and Choose Save-As
To keep this page small and fast, questions & discussion about this post can be found on another page here.
- Failing to evaluate AKI in the ICU fully. Most cases of AKI will resolve without specific intervention (e.g., with treatment of underlying sepsis). However, occasionally, a specific issue is identified which requires particular therapy (e.g., Foley catheter obstruction, glomerulonephritis). Finding these patients is like hunting for a needle in a haystack.
- Measurement of urine electrolytes and calculating fractional excretion of sodium (FENa) isn't helpful. (27236480, 26689284, 27670788)
- Blind assumption that any patient with oliguria requires a fluid bolus.
Guide to emoji hyperlinks 
= Link to online calculator.
= Link to Medscape monograph about a drug.
= Link to IBCC section about a drug.
= Link to IBCC section covering that topic.
= Link to FOAMed site with related information.
= Link to supplemental media.
References
- 23355628 Wang HE, Jain G, Glassock RJ, Warnock DG. Comparison of absolute serum creatinine changes versus Kidney Disease: Improving Global Outcomes consensus definitions for characterizing stages of acute kidney injury. Nephrol Dial Transplant. 2013 Jun;28(6):1447-54. doi: 10.1093/ndt/gfs533 [PubMed]
- 24052222 Muriithi AK, Nasr SH, Leung N. Utility of urine eosinophils in the diagnosis of acute interstitial nephritis. Clin J Am Soc Nephrol. 2013 Nov;8(11):1857-62. doi: 10.2215/CJN.01330213 [PubMed]
- 24053972 Chawla LS, Davison DL, Brasha-Mitchell E, Koyner JL, Arthur JM, Shaw AD, Tumlin JA, Trevino SA, Kimmel PL, Seneff MG. Development and standardization of a furosemide stress test to predict the severity of acute kidney injury. Crit Care. 2013 Sep 20;17(5):R207. doi: 10.1186/cc13015 [PubMed]
- 25568178 Kellum JA, Sileanu FE, Murugan R, Lucko N, Shaw AD, Clermont G. Classifying AKI by Urine Output versus Serum Creatinine Level. J Am Soc Nephrol. 2015 Sep;26(9):2231-8. doi: 10.1681/ASN.2014070724 [PubMed]
- 25655065 Koyner JL, Davison DL, Brasha-Mitchell E, Chalikonda DM, Arthur JM, Shaw AD, Tumlin JA, Trevino SA, Bennett MR, Kimmel PL, Seneff MG, Chawla LS. Furosemide Stress Test and Biomarkers for the Prediction of AKI Severity. J Am Soc Nephrol. 2015 Aug;26(8):2023-31. doi: 10.1681/ASN.2014060535 [PubMed]
- 26689284 Pahwa AK, Sperati CJ. Urinary fractional excretion indices in the evaluation of acute kidney injury. J Hosp Med. 2016 Jan;11(1):77-80. doi: 10.1002/jhm.2501 [PubMed]
- 27230984 Ichai C, Vinsonneau C, Souweine B, et al.; Société française d’anesthésie et de réanimation (Sfar); Société de réanimation de langue française (SRLF); Groupe francophone de réanimation et urgences pédiatriques (GFRUP); Société française de néphrologie (SFN). Acute kidney injury in the perioperative period and in intensive care units (excluding renal replacement therapies). Ann Intensive Care. 2016 Dec;6(1):48. doi: 10.1186/s13613-016-0145-5 [PubMed]
- 27236480 Legrand M, Le Cam B, Perbet S, Roger C, Darmon M, Guerci P, Ferry A, Maurel V, Soussi S, Constantin JM, Gayat E, Lefrant JY, Leone M; support of the AZUREA network. Urine sodium concentration to predict fluid responsiveness in oliguric ICU patients: a prospective multicenter observational study. Crit Care. 2016 May 29;20(1):165. doi: 10.1186/s13054-016-1343-0 [PubMed]
- 27483065 Gordon AC, Mason AJ, Thirunavukkarasu N, Perkins GD, Cecconi M, Cepkova M, Pogson DG, Aya HD, Anjum A, Frazier GJ, Santhakumaran S, Ashby D, Brett SJ; VANISH Investigators. Effect of Early Vasopressin vs Norepinephrine on Kidney Failure in Patients With Septic Shock: The VANISH Randomized Clinical Trial. JAMA. 2016 Aug 2;316(5):509-18. doi: 10.1001/jama.2016.10485 [PubMed]
- 27670788 Ostermann M, Joannidis M. Acute kidney injury 2016: diagnosis and diagnostic workup. Crit Care. 2016 Sep 27;20(1):299. doi: 10.1186/s13054-016-1478-z [PubMed]
- 29156029 Kunst G, Ostermann M. Intraoperative permissive oliguria – how much is too much? Br J Anaesth. 2017 Dec 1;119(6):1075-1077. doi: 10.1093/bja/aex387 [PubMed]
- 29344743 Matsuura R, Komaru Y, Miyamoto Y, Yoshida T, Yoshimoto K, Isshiki R, Mayumi K, Yamashita T, Hamasaki Y, Nangaku M, Noiri E, Morimura N, Doi K. Response to different furosemide doses predicts AKI progression in ICU patients with elevated plasma NGAL levels. Ann Intensive Care. 2018 Jan 17;8(1):8. doi: 10.1186/s13613-018-0355-0 [PubMed]
- 29485925 Semler MW, Self WH, Wanderer JP, Ehrenfeld JM, Wang L, Byrne DW, Stollings JL, Kumar AB, Hughes CG, Hernandez A, Guillamondegui OD, May AK, Weavind L, Casey JD, Siew ED, Shaw AD, Bernard GR, Rice TW; SMART Investigators and the Pragmatic Critical Care Research Group. Balanced Crystalloids versus Saline in Critically Ill Adults. N Engl J Med. 2018 Mar 1;378(9):829-839. doi: 10.1056/NEJMoa1711584 [PubMed]
- 29485926 Self WH, Semler MW, Wanderer JP, Wang L, Byrne DW, Collins SP, Slovis CM, Lindsell CJ, Ehrenfeld JM, Siew ED, Shaw AD, Bernard GR, Rice TW; SALT-ED Investigators. Balanced Crystalloids versus Saline in Noncritically Ill Adults. N Engl J Med. 2018 Mar 1;378(9):819-828. doi: 10.1056/NEJMoa1711586 [PubMed]
- 29673370 Lumlertgul N, Peerapornratana S, Trakarnvanich T, Pongsittisak W, Surasit K, Chuasuwan A, Tankee P, Tiranathanagul K, Praditpornsilpa K, Tungsanga K, Eiam-Ong S, Kellum JA, Srisawat N; FST Study Group. Early versus standard initiation of renal replacement therapy in furosemide stress test non-responsive acute kidney injury patients (the FST trial). Crit Care. 2018 Apr 19;22(1):101. doi: 10.1186/s13054-018-2021-1 [PubMed]
- 29910040 Jaber S, Paugam C, Futier E, et al.; BICAR-ICU Study Group. Sodium bicarbonate therapy for patients with severe metabolic acidaemia in the intensive care unit (BICAR-ICU): a multicentre, open-label, randomised controlled, phase 3 trial. Lancet. 2018 Jul 7;392(10141):31-40. doi: 10.1016/S0140-6736(18)31080-8 [PubMed]
- 31262415 Co I, Gunnerson K. Emergency Department Management of Acute Kidney Injury, Electrolyte Abnormalities, and Renal Replacement Therapy in the Critically Ill. Emerg Med Clin North Am. 2019 Aug;37(3):459-471. doi: 10.1016/j.emc.2019.04.006 [PubMed]
- 31589567 de Oliveira AM, Paulino MV, Vieira APF, McKinney AM, da Rocha AJ, Dos Santos GT, Leite CDC, Godoy LFS, Lucato LT. Imaging Patterns of Toxic and Metabolic Brain Disorders. Radiographics. 2019 Oct;39(6):1672-1695. doi: 10.1148/rg.2019190016 [PubMed]
- 31665764 Goswami E, Ogden RK, Bennett WE, Goldstein SL, Hackbarth R, Somers MJG, Yonekawa K, Misurac J. Evidence-based development of a nephrotoxic medication list to screen for acute kidney injury risk in hospitalized children. Am J Health Syst Pharm. 2019 Oct 30;76(22):1869-1874. doi: 10.1093/ajhp/zxz203 [PubMed]
- 31777389 Ronco C, Bellomo R, Kellum JA. Acute kidney injury. Lancet. 2019 Nov 23;394(10212):1949-1964. doi: 10.1016/S0140-6736(19)32563-2 [PubMed]
- 34213593 Pickkers P, Darmon M, Hoste E, Joannidis M, Legrand M, Ostermann M, Prowle JR, Schneider A, Schetz M. Acute kidney injury in the critically ill: an updated review on pathophysiology and management. Intensive Care Med. 2021 Jul 2:1–16. doi: 10.1007/s00134-021-06454-7 [PubMed]
- 34518967 Ramírez-Guerrero G, Baghetti-Hernández R, Ronco C. Acute Kidney Injury at the Neurocritical Care Unit. Neurocrit Care. 2022 Apr;36(2):640-649. doi: 10.1007/s12028-021-01345-7 [PubMed]
- 39230007 Barreto EF, Gaggani AM, Hernandez BN, Amatullah N, Culley CM, Stottlemyer B, Murugan R, Ozrazgat-Baslanti T, Bihorac A, Kellum JA, Kashani KB, Rule AD, Kane-Gill SL; MEnD-AKI Study Group. The Acute Kidney Intervention and Pharmacotherapy (AKIP) List: Standardized List of Medications That Are Renally Eliminated and Nephrotoxic in the Acutely Ill. Ann Pharmacother. 2024 Sep 4:10600280241273191. doi: 10.1177/10600280241273191 [PubMed]