Acute Kidney Injury Treatment & Management
- Author: Biruh T Workeneh, MD, PhD; Chief Editor: Vecihi Batuman, MD, FACP, FASN more...
Measures to correct underlying causes of acute kidney injury (AKI) should begin at the earliest indication of renal dysfunction. Serum creatinine does not rise to abnormal levels until a large proportion of the renal mass is damaged, because the relationship between the glomerular filtration rate (GFR) and the serum creatinine level is not linear, especially early in disease. Indeed, the rise of serum creatinine may not be evident before 50% of the GFR is lost.
It cannot be overstated that the current treatment for AKI is mainly supportive in nature; no therapeutic modalities to date have shown efficacy in treating the condition. Therapeutic agents (eg, dopamine, nesiritide, fenoldopam, mannitol) are not indicated in the management of AKI and may be harmful for the patient.
Maintenance of volume homeostasis and correction of biochemical abnormalities remain the primary goals of treatment and may include the following measures:
Correction of fluid overload with furosemide
Correction of severe acidosis with bicarbonate administration, which can be important as a bridge to dialysis
Correction of hyperkalemia
Correction of hematologic abnormalities (eg, anemia, uremic platelet dysfunction) with measures such as transfusions and administration of desmopressin or estrogens
Furosemide can be used to correct volume overload when patients are still responsive; this often requires high intravenous (IV) doses. Furosemide plays no role in converting an oliguric AKI to a nonoliguric AKI or in increasing urine output when a patient is not hypervolemic. However, response to furosemide can be taken as a good prognostic sign.
Hyperkalemia in patients with AKI can be life-threatening. Approaches to lowering serum potassium include the following:
Decreasing the intake of potassium in diet or tube feeds
Exchanging potassium across the gut lumen using potassium-binding resins
Promoting intracellular shifts in potassium with insulin, dextrose solutions, and beta agonists
In AKI, the kidneys are especially vulnerable to the toxic effects of various chemicals. All nephrotoxic agents (eg, radiocontrast agents, antibiotics with nephrotoxic potential, heavy metal preparations, cancer chemotherapeutic agents, nonsteroidal anti-inflammatory drugs [NSAIDs]) should be avoided or used with extreme caution. Similarly, all medications cleared by renal excretion should be avoided, or their doses should be adjusted appropriately.
A 2013 study indicated that triple therapy using nonsteroidal anti-inflammatory drugs (NSAIDs) with 2 antihypertensive medications—a diuretic along with an angiotensin-converting enzyme (ACE) inhibitor or an angiotensin-receptor blocker (ARB)—significantly increases the risk of hospitalization for AKI, particularly in the first 30 days of treatment with these drugs.
The retrospective, case-controlled study involved a cohort of 487,372 users of antihypertensive drugs between 1997 and 2008. During a mean follow-up of almost 6 years, 2215 cases of acute kidney injury were identified (incidence rate of 7 per 10 000 person-years), and each was compared with up to 10 matched controls.[40, 41]
Nephrology consultation should be sought early in the course of AKI. A nephrologist can help to optimize management and avoid the preventable complications of AKI.
The rationale for vasodilator therapy in AKI is that improved renal perfusion may reduce renal damage. Strong evidence in support of this approach is lacking, however.
A meta-analysis of 16 randomized studies concluded that the vasodilator fenoldopam reduces the need for renal replacement therapy and lowers the mortality rate in patients with AKI. However, larger trials need to be conducted before the use of fenoldopam can be recommended.
Dopamine in small doses (eg, 1-5 mcg/kg/min) causes selective dilatation of the renal vasculature, enhancing renal perfusion. Dopamine also reduces sodium absorption; this enhances urine flow, which helps to prevent tubular cast obstruction. However, most clinical studies have failed to establish this beneficial role of low-dose dopamine infusion, and one study demonstrated that low-dose dopamine may worsen renal perfusion in patients with AKI.
Dietary changes are an important facet of AKI treatment. Restriction of salt and fluid becomes crucial in the management of oliguric renal failure, wherein the kidneys do not adequately excrete either toxins or fluids.
Because potassium and phosphorus are not excreted optimally in patients with AKI, blood levels of these electrolytes tend to be high. Restriction of these elements in the diet may be necessary, with guidance from frequent measurements. In the polyuric phase of AKI, potassium and phosphorus may be depleted, so that patients may require dietary supplementation and IV replacement.
Calculation of the nitrogen balance can be challenging, especially in the presence of volume contraction, hypercatabolic states, GI bleeding, and diarrheal disease. Critically ill patients should receive at least 1 g/kg/day protein but should avoid hyperalimentation, which can lead to an elevated blood urea nitrogen (BUN) level and water loss resulting in hypernatremia.
Dialysis, especially hemodialysis, may delay the recovery of patients with AKI. Most authorities prefer using biocompatible membrane dialyzers for hemodialysis. Indications for dialysis (ie, renal replacement therapy) in patients with AKI are as follows:
Volume expansion that cannot be managed with diuretics
Hyperkalemia refractory to medical therapy
Correction of severe acid-base disturbances that are refractory to medical therapy
Severe azotemia (BUN >80-100)
Timing and intensity
Great controversy exists regarding the timing of dialysis. Older studies suggested decreased mortality with early, versus late, initiation of dialysis, but timing of dialysis initiation has not been assessed in large, randomized, controlled trials. Approaches vary widely at present.
The Acute Renal Failure Trial Network (ATN) Study found that increasing the intensity of dialysis (either intermittent or continuous) did not improve clinical outcomes (morbidity/mortality). The best evidence suggests that patients with dialysis-dependent AKI should receive at least 3 hemodialysis treatments per week with a delivered Kt/V value of 1.2, or continuous hemodialysis (continuous venovenous hemodialysis or hemofiltration) of 20 mg/kg/h (prescribed).
There seems to be no difference in outcome between the use of intermittent hemodialysis and continuous renal replacement therapy (CRRT), but this question is currently under investigation. CRRT may have a role in patients who are hemodynamically unstable and who have had prolonged renal failure after a stroke or liver failure. Such patients may not tolerate the rapid shift of fluid and electrolytes caused during conventional hemodialysis.
Peritoneal dialysis is not frequently used in patients with AKI. Nevertheless, it can technically be used in acute cases and probably is tolerated better hemodynamically than is conventional hemodialysis.
Prevention of Contrast-Induced Nephropathy
In patients undergoing imaging studies with contrast, prophylactic administration of IV fluid has been shown to decrease the incidence of contrast nephropathy. Although controversy exists regarding the ideal fluid, normal saline and isotonic NaHCO3 have proved to be effective. A normal saline solution of 1 mL/kg/h administered 12 hours before the procedure and then 12 hours after the procedure is recommended for most patients.
In patients who are at high risk for volume overload—in particular, those with chronic heart failure who have a left ventricular ejection fraction of less than 40%—isotonic NaHCO3 solution should be administered before and after the procedure. It can be prepared by mixing 3 ampules of NaHCO3 in a liter of 5% dextrose in water (D5W) and can be given at a rate of 3 mL/kg/h for 1 hour prior to the procedure, with the rate decreased to 1 mL/kg/h during the procedure and for 6 hours afterward.
Another prophylactic agent, used with varying success, is oral N -acetylcysteine at a dosage of 1200 mg every 12 hours. This is administered to high-risk patients the day before a contrast study is performed and is continued the day of the procedure. N -acetylcysteine appears to provide only borderline benefit. Diuretics, nonsteroidal anti-inflammatory drugs (NSAIDs), and possibly angiotensin-converting enzyme (ACE) inhibitors should be withheld near the time of the procedure.
A meta-analysis found that statin treatment before coronary angiography can reduce contrast-induced AKI. Risk was 3.91% in the statin group versus 6.98% in the control group. On subanalysis, benefit was highly significant benefit in patients whose GFR was ≥60 ml/min (relative risk [RR] 0.40, P <0.0001).
A meta-analysis of intensive statin therapy before coronary angiography and percutaneous coronary intervention reported that in patients with acute coronary syndrome (ACS), statin treatment significantly reduced the incidence of contrast-induced AKI (RR 0.37, P<0.0001). In patients without ACS, however, only a nonsignificant positive trend was seen (RR 0.65, P=0.07).
Renal recovery in most cases is not complete, with the kidneys remaining vulnerable to the nephrotoxic effects of all therapeutic agents. Therefore, agents with nephrotoxic potential are best avoided.
Renal recovery is usually observed within the first 2 weeks, and many nephrologists tend to diagnose patients with end-stage (ie, irreversible) renal failure 6-8 weeks after the onset of AKI. It is always better to check these patients periodically, because some patients may regain renal function much later.
Prevention of Perioperative Nephropathy
Remote ischemic preconditioning (RIPC) is a novel investigative method for preventing perioperative AKI. The rationale is that producing ischemia in a patient’s extremity immediately before surgery will stimulate the release of endogenous protective molecules, thereby reducing the likelihood that the surgery will precipitate AKI.
In a randomized trial in 240 patients who were undergoing on-pump coronary bypass grafting and were at moderate to high risk for perioperative AKI, 37.5% of patients who received RIPC developed AKI within 72 hours after surgery, compared with 52.5% of controls (P = 0.02). In patients who developed AKI, 5.8% who had received RIPC required renal replacement therapy versus 15.8% of those in the control arm (10% absolute risk reduction).
In this study, remote ischemia was induced by inflating a blood pressure cuff to 200 mm Hg on one upper extremity for 5 minutes; this was repeated twice, for a total of three cycles. Control patients received three cycles of blood pressure cuff inflation to 20 mm Hg for 5 minutes.
A review of randomized, controlled trials of pharmacologic measures used to protect renal function perioperatively found no reliable evidence that any of the following interventions are effective :
Dopamine and its analogues
Calcium channel blockers
Angiotensin-converting enzyme (ACE) inhibitors
Atrial natriuretic peptide (ANP)
Specific hydration fluids
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|Stage||GFR** Criteria||Urine Output Criteria||Probability|
|Risk||SCreat† increased × 1.5
GFR decreased >25%
|UO‡ < 0.5 mL/kg/h × 6 h||High sensitivity (Risk >Injury >Failure)|
|Injury||SCreat increased × 2
GFR decreased >50%
|UO < 0.5 mL/kg/h × 12 h|
|Failure||SCreat increased × 3
GFR decreased 75%
SCreat ≥4 mg/dL; acute rise ≥0.5 mg/dL
|UO < 0.3 mL/kg/h × 24 h
anuria × 12 h
|Loss||Persistent acute renal failure: complete loss of kidney function >4 wk||High specificity|
|ESKD*||Complete loss of kidney function >3 mo|
|*ESKD—end-stage kidney disease; **GFR—glomerular filtration rate; †SCreat—serum creatinine; ‡UO—urine output
Note: Patients can be classified by GFR criteria and/or UO criteria. The criteria that support the most severe classification should be used. The superimposition of acute on chronic failure is indicated with the designation RIFLE-FC; failure is present in such cases even if the increase in SCreat is less than 3-fold, provided that the new SCreat is greater than 4.0 mg/dL (350 µmol/L) and results from an acute increase of at least 0.5 mg/dL (44 µmol/L).
|Stage||Serum Creatinine Criteria||Urine Output Criteria|
|1||Increase of ≥0.3 mg/dL (≥26.4 µmol/L) or 1.5- to 2-fold increase from baseline||< 0.5 mL/kg/h for >6 h|
|2||>2-fold to 3-fold increase from baseline||< 0.5 mL/kg/h for >12 h|
|3*||>3-fold increase from baseline, or increase of ≥ 4.0 mg/dL (≥35.4 µmol/L) with an acute increase of at least 0.5 mg/dL (44 µmol/L)||< 0.3 mL/kg/h for 24 h or anuria for 12 h|
|*Patients who receive renal replacement therapy (RRT) are considered to have met the criteria for stage 3 irrespective of the stage they are in at the time of RRT.|