- Rapid Reference 🚀
- Definition & significance of AKI
- Causes of AKI
- Tests to evaluate the cause of AKI
- Approach to oliguria
- Management of AKI
- Questions & discussion
- PDF of this chapter (or create customized PDF)
- Supplemental media
approach to AKI:
- Electrolytes including Ca/Mg/Phos.
- Creatine Kinase.
- Consider renal imaging (ultrasound, or review of recent abdominal CT scan).
- Additional labs as indicated:
- Drug levels (e.g., vancomycin, aminoglycoside, cyclosporine).
- Uric acid, if concern for tumor lysis syndrome.
- Treat any identifiable cause(s).
- Discontinue nephrotoxins.
- Dose-adjust renally cleared medications.
- D/C PRN potassium orders (hold potassium unless K<3.0 mM).
- Optimize hemodynamics:
- Target euvolemia (may require fluid resuscitation or diuresis).
- Defend the MAP.
- Hold antihypertensives if soft Bp (especially negative inotropes).
- Consider bicarbonate for uremic metabolic acidosis.
- Treat hyperkalemia if present.
- 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.
- Indications for dialysis:
- Hyperkalemia, acidosis, or volume overload refractory to medical management.
- Uremic symptoms (e.g., pericarditis, encephalopathy).
furosemide stress test (FST):
definition & significance of AKI
- The KDIGO classification shown above is currently the favored definition of AKI.
- AKI is a powerful predictor of mortality. The figure above was obtained from hospitalized patients, but similar curves occur for AKI in a variety of contexts (e.g., ICU patients, septic patients).(23355628)
- It's unclear whether AKI causes this mortality or if this is simply a marker for underlying problems (or, most likely, both). Regardless, patients with AKI deserve serious consideration because they represent a high-risk population.
- These definitions aren't perfect:
- Cutoffs are somewhat arbitrary. For example, I can't find any good evidence to support why 0.5 cc/kg/hr is the cutoff to define oliguria (some newer literature suggests that 0.3 cc/kg/hr may have a higher specificity).(29156029)
- Prognosis varies dramatically across each stage of AKI (as shown below).
more detailed understanding of types & prognosis
- Prognosis depends on changes in urine output and creatinine (figure above).(25568178) Some specific types bear mention:
- (1) Isolated oliguria (low urine output with stable creatinine).
- These patients rarely required 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.
- Oliguria should be taken seriously and evaluated adequately. However, <12 hours of oliguria isn't necessarily a disaster – especially if the creatinine remains stable.
- (2) Non-oliguric renal failure (elevated creatinine with normal urine output)
- The vast majority of these patients (99.7% overall) won't require dialysis.
causes of AKI
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.
- Aminoglycosides, Colistimethate (Colistin).
- Acyclovir, ganciclovir, valacyclovir, valganciclovir, foscarnet.
- Indinavir, cidofovir, tenofovir.
- Beta-lactams esp. nafcillin (can rarely cause interstitial nephritis).
- ACE-inhibitors, Angiotensin receptor blockers (ARBs).
- Cardiac medications:
- 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.
- Calcineurin inhibitors (cyclosporine, tacrolimus, sirolimus).
- Chemotherapeutics (carboplatin, cisplatin, ifosfamide, methotrexate, mitomycin).
- Intravenous immunoglobulin (IVIG).
- Inflammatory bowel disease medications (mesalamine, sulfasalazine).
- Bisphosphonates (pamidronate, zoledronic acid).
- Antiepileptics (topiramate, zonisamide).
- Sodium chloride (0.9% or 3% in large quantity).
tests to evaluate the cause of AKI
- Electrolytes (including Ca/Phos/Mg).
- Creatinine Kinase.
- Interpretation shown above.
- If urinalysis suggests glomerulonephritis or acute interstitial nephritis, consult nephrology to review the urine microscopy and consider renal biopsy.
- Additional labs if indicated
- Relevant drug levels (e.g. vancomycin, aminoglycoside, cyclosporine, tacrolimus).
- Tumor lysis labs if malignancy (lytes, calcium, phosphate, uric acid).
- Renal & bladder ultrasound
- Main role is exclusion of hydronephrosis, but 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 abdominal CT scan was recently done for another reason, this may be adequate to exclude hydronephrosis.
tests not to order
- Urine electrolytes & fractional excretion of sodium (FENa).
- Urine eosinophils has poor performance for diagnosing acute tubulointerstitial nephritis.(24052222)
approach to oliguria
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. In thin patients, this is often fast and easy.
- Placement and trouble-shooting of a Foley catheter (via flushing) is a reasonable alternative. Most obstructions that cause oliguria are located in the urethra and may be managed with Foley placement (unilateral ureteral obstruction shouldn't cause oliguria, due to urine production from the contralateral kidney).
#2: hemodynamic evaluation
- Perform a brief chart review focusing on vital sign trends, new medications added (e.g. antihypertensives), cardiac history.
- The focus of this evaluation is generally on volume status, but other factors should be considered as well (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.
- If the patient is hypertensive this argues against hypovolemia, making fluid administration less likely to help.
- Note of caution: volume challenge isn't very helpful for new-onset oliguria in the ICU:
- Genuine hypovolemia is most often encountered among patients being initially admitted to the hospital (e.g. due to gastroenteritis and poor oral intake).
- It's pretty uncommon for ICU patients to suddenly develop hypovolemia without an obvious cause (e.g. hemorrhage or negative fluid balance on recorded I/O's). On the contrary, most ICU patients will tend to retain fluid and develop hypervolemia during their ICU stay.
#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 hours with an infusion of norepinephrine or phenylephrine (e.g. to MAP >75 mm). If this stimulates urine output, then maintain 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 previously in this chapter.
#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 (e.g. additional IV fluids) is unlikely to help.
- More on the furosemide stress test here.
management of AKI
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:
dose-adjust renally cleared medications
- Note that calculations of the glomerular filtration rate (GFR) based on creatinine level will be misleading in the context of 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).
- Pharmacist consultation can be helpful with this.
avoid giving potassium
- Discontinue potassium supplementations and potassium-sparing diuretics.
- In the absence of digoxin toxicity or hypomagnesemia, moderate hypokalemia is generally well tolerated.
- In acute kidney injury, it may be wise to avoid potassium supplementation unless the potassium is substantially reduced (e.g. <3 mM).
- If you're worried about the risk of Torsade de Pointes, make sure that the magnesium level isn't low. Giving magnesium is safer than giving potassium in this context.
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.
- In terms of renal outcomes, vasopressin might have a small advantage over other vasopressors, particularly among patients with tachycardia and systemic vasodilation.(27483065)
- 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 out of 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 net 1-2 liters positive per day this will rapidly become a major 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.
treatment of acidosis
- Nephrologists have used bicarbonate to stave off dialysis for decades. More recently, the BICAR-ICU trial demonstrated that bicarbonate use in the ICU for treatment of 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 the 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 (this is roughly equivalent to a bicarbonate level over ~17 mEq/L).(29910040)
- Formulation & route of bicarbonate depend on the clinical scenario and severity of acidosis:
- 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) will 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 a 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). Depending on the severity, 650-1300 mg may be given twice or three times daily.
- Dialysis is the second-line therapy for acidosis, in situations where bicarbonate is ineffective or contraindicated.
- 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 who is 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, Ca (may be preferable for patients on dialysis).
- May impair absorption of some drugs from the gut.
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questions & discussion
To keep this page small and fast, questions & discussion about this post can be found on another page here.
- Failing to fully evaluate AKI in the ICU. 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 specific therapy (e.g. Foley catheter obstruction, glomerulonephritis). Finding these patients is a bit like hunting for a needle in a haystack.
- Measurement of urine electrolytes and calculation of fractional excretion of sodium (FENa) isn't helpful.4–6
- Blind assumption that any patient with oliguria requires a fluid bolus.
- Fluid selection:
- Things I don't really think are nephrotoxic
- Furosemide stress test
- The importance of MAP: Vasopressors and Athos 3 with Mink Chawla (EMCrit 201).
- Low-volume resus trial: CLASSIC trial (Segun Olusanya via TheBottomLine)
Elderly F sent from NH after no urine output x 18h. Also, Foley replaced 18h ago… Not sure this is a win but definitely a quick ED diagnosis! @ACEP_EUS @ultrasoundpod @DavidPigottMD #FOAMus #UABWOTW pic.twitter.com/GSCP2r1Cf9
— UAB Emergency Ultrasound (@UAB_Sono) April 16, 2018
Don't assume that every Foley catheter is functioning properly! Prompt recognition of a dysfunctional Foley catheter is essential.
[Night-shift Pearl] 85 y/o with severe sepsis. Her clinical condition improved after 12 hours and 2 L of fluids. She had anuria, and her urinary output was literally 0??? Wait… where is the Foley catheter inserted? @MartinQuirosMD #FOAMed #POCUS pic.twitter.com/EZFkKsPWPL
— Yale Tung Chen (@yaletung) July 12, 2019
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