Treatment approaches for AKI vary according to the type of insult. The underlying illness requires treatment.
General therapy includes intervention in electrolyte and acid/base abnormalities and optimization of volume status, either by replacing volume in the volume-contracted patient or by fluid removal (either diuresis or renal replacement therapy) in patients with volume overload.
Sodium and volume restriction are generally required along with limiting potassium and phosphorus intake.
Dose adjustment of medications is likely required in all cases and should not be overlooked. Patients with AKI should not be given potentially nephrotoxic drugs unless there is no alternative. Electrolyte and acid-base balance should be monitored and optimized. Early involvement by a nephrologist may be valuable;[112]Balasubramanian G, Al-Aly Z, Moiz A, et al. Early nephrologist involvement in hospital-acquired acute kidney injury: a pilot study. Am J Kidney Dis. 2011 Feb;57(2):228-34.
http://www.ncbi.nlm.nih.gov/pubmed/21195518?tool=bestpractice.com
however, automated electronic alerts to identify AKI have not improved outcomes.[113]Wilson FP, Shashaty M, Testani J, et al. Automated, electronic alerts for acute kidney injury: a single-blind, parallel-group, randomised controlled trial. Lancet. 2015 May 16;385(9981):1966-74.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4475457
http://www.ncbi.nlm.nih.gov/pubmed/25726515?tool=bestpractice.com
Prerenal renal failure
Prerenal azotemia is managed with techniques to improve the hemodynamic status of the patient.
The volume-contracted patient requires volume expansion with crystalloid or colloid to restore euvolemia.
Crystalloid (normal saline or balanced solutions, such as Ringer's lactate [Hartmann's solution]) or colloid (considered in cases of significant hypoalbuminemia) fluids are infused, along with packed red blood cells if there is significant anemia.[5]Sharfuddin AA, Weisbord SD, Palevsky PM, et al. Acute kidney injury. In: Taal MW, Chertow GM, Marsden PA, et al, eds. Brenner and Rector's the kidney. 9th ed. Philadelphia, PA: Saunders; 2012.[114]Flamm SL, Wong F, Ahn J, et al. AGA clinical practice update on the evaluation and management of acute kidney injury in patients with cirrhosis: expert review. Clin Gastroenterol Hepatol. 2022 Dec;20(12):2707-16.
https://www.cghjournal.org/article/S1542-3565(22)00829-1/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/36075500?tool=bestpractice.com
In the US, the Food and Drug Administration (FDA) issued safety labeling changes in July 2021 for solutions containing hydroxyethyl starch (HES) stating that HES products should not be used unless adequate alternative treatment is unavailable.[115]Food and Drug Administration. Labeling changes on mortality, kidney injury, and excess bleeding with hydroxyethyl starch products. Jul 2021 [internet publication].
https://www.fda.gov/vaccines-blood-biologics/safety-availability-biologics/labeling-changes-mortality-kidney-injury-and-excess-bleeding-hydroxyethyl-starch-products
Solutions containing HES are associated with adverse outcomes including kidney injury and death, particularly in critically ill patients and those with sepsis.[116]Lewis SR, Pritchard MW, Evans DJ, et al. Colloids versus crystalloids for fluid resuscitation in critically ill people. Cochrane Database Syst Rev. 2018 Aug 3;8:CD000567.
https://www.doi.org/10.1002/14651858.CD000567.pub7
http://www.ncbi.nlm.nih.gov/pubmed/30073665?tool=bestpractice.com
[117]Zarychanski R, Abou-Setta AM, Turgeon AF, et al. Association of hydroxyethyl starch administration with mortality and acute kidney injury in critically ill patients requiring volume resuscitation: a systematic review and meta-analysis. JAMA. 2013 Feb 20;309(7):678-88.
http://www.ncbi.nlm.nih.gov/pubmed/23423413?tool=bestpractice.com
In view of the serious risks posed to these patient populations, the Pharmacovigilance Risk Assessment Committee of the European Medicines Agency in February 2022 recommended suspending HES solutions for infusion in Europe.[118]European Medicines Agency. PRAC recommends suspending hydroxyethyl-starch solutions for infusion from the market. Feb 2022 [internet publication].
https://www.ema.europa.eu/en/news/prac-recommends-suspending-hydroxyethyl-starch-solutions-infusion-market-0
The US National Kidney Foundation states that crystalloids are preferred over colloids for most patients with acute kidney injury, and recommends that hydroxyethyl starches are avoided.[111]Moore PK, Hsu RK, Liu KD. Management of acute kidney injury: core curriculum 2018. Am J Kidney Dis. 2018 Jul;72(1):136-48.
https://www.ajkd.org/article/S0272-6386(17)31141-1/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/29478864?tool=bestpractice.com
All fluid resuscitation should be performed by a clinician with expertise in this area, with close patient monitoring.
Vasopressors are recommended if hypotension is severe, to augment blood pressure while optimizing the patient's volume status.[5]Sharfuddin AA, Weisbord SD, Palevsky PM, et al. Acute kidney injury. In: Taal MW, Chertow GM, Marsden PA, et al, eds. Brenner and Rector's the kidney. 9th ed. Philadelphia, PA: Saunders; 2012. A common goal of vasopressors in this setting is to keep the mean arterial pressure (MAP) >60 mmHg. (MAP is the diastolic pressure plus one third of the pulse pressure, where the pulse pressure is the systolic pressure minus the diastolic pressure.)
Management is often difficult if renal hypoperfusion results from impaired cardiac function due to poor left or right ventricular systolic function. It requires optimization of cardiac output and volume status by use of inotropes, diuretics, or renal replacement therapy as indicated by the clinical scenario, along with close monitoring of renal function and urine production during therapy.[5]Sharfuddin AA, Weisbord SD, Palevsky PM, et al. Acute kidney injury. In: Taal MW, Chertow GM, Marsden PA, et al, eds. Brenner and Rector's the kidney. 9th ed. Philadelphia, PA: Saunders; 2012.[114]Flamm SL, Wong F, Ahn J, et al. AGA clinical practice update on the evaluation and management of acute kidney injury in patients with cirrhosis: expert review. Clin Gastroenterol Hepatol. 2022 Dec;20(12):2707-16.
https://www.cghjournal.org/article/S1542-3565(22)00829-1/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/36075500?tool=bestpractice.com
Vasopressors and inotropic agents should be used only with appropriate hemodynamic monitoring in place.
Renal replacement therapy may be needed if severe acid/base, electrolyte, or uremic complications are present while the underlying cardiac or volume issues are treated. The use of diuretics may be helpful to manage volume in patients with ineffective circulating volume and prerenal AKI. Diuretic-unresponsive volume overload, increased potassium, severe metabolic acidosis, or uremic symptoms are indications to proceed to renal replacement therapy by means of dialysis or filtration.[5]Sharfuddin AA, Weisbord SD, Palevsky PM, et al. Acute kidney injury. In: Taal MW, Chertow GM, Marsden PA, et al, eds. Brenner and Rector's the kidney. 9th ed. Philadelphia, PA: Saunders; 2012.
Intrinsic renal failure
Management of intrinsic renal failure varies according to etiology.
Volume expansion is required when coexisting prerenal azotemia exists. It is unclear whether a chloride-sparing intravenous fluid strategy improves outcomes in critically ill patients.[86]Yunos NM, Bellomo R, Hegarty C, et al. Association between a chloride-liberal vs chloride-restrictive intravenous fluid administration strategy and kidney injury in critically ill adults. JAMA. 2012 Oct 17;308(15):1566-72.
http://www.ncbi.nlm.nih.gov/pubmed/23073953?tool=bestpractice.com
[87]Young P, Bailey M, Beasley R, et al. Effect of a buffered crystalloid solution vs saline on acute kidney injury among patients in the intensive care unit: the SPLIT randomized clinical trial. JAMA. 2015 Oct 27;314(16):1701-10.
http://www.ncbi.nlm.nih.gov/pubmed/26444692?tool=bestpractice.com
Larger randomized studies remain necessary to alter practice.[87]Young P, Bailey M, Beasley R, et al. Effect of a buffered crystalloid solution vs saline on acute kidney injury among patients in the intensive care unit: the SPLIT randomized clinical trial. JAMA. 2015 Oct 27;314(16):1701-10.
http://www.ncbi.nlm.nih.gov/pubmed/26444692?tool=bestpractice.com
Generally, patients with volume overload require sodium restriction. The amount of sodium restriction depends on the clinical setting. Volume overload may be managed with diuretics when responsive.
In cases of drug-induced AKI or interstitial nephritis, offending drugs should be stopped when possible, followed by consideration for corticosteroids.
Management of acute glomerulonephritis, vasculitis, and thrombotic microangiopathies may require corticosteroids, cytotoxic agents, or other immune-modifying drugs depending on the specific diagnosis, often determined by renal biopsy and serology studies.[119]Walters GD, Willis NS, Cooper TE, et al. Interventions for renal vasculitis in adults. Cochrane Database Syst Rev. 2020 Jan 13;1(1):CD003232.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD003232.pub4/full
http://www.ncbi.nlm.nih.gov/pubmed/31927782?tool=bestpractice.com
The management of acute glomerulonephritis requires a nephrologist consultation, particularly regarding the use of cytotoxic and immune-modifying agents. Doses and protocols for many of the drugs used vary by center. The Kidney Disease: Improving Global Outcomes (KDIGO) clinical practice guideline for glomerulonephritis can be consulted.
KDIGO clinical practice guideline for glomerulonephritis
Opens in new window
There is no specific therapy for acute tubular necrosis aside from maintaining volume status and controlling electrolyte and acid/base abnormalities. Nephrotoxins should be removed or minimized. Renal replacement therapy is generally required if there is severe acidosis, volume expansion refractory to diuretics, hyperkalemia, or uremia.
Obstructive renal failure
Bladder catheter placement should be done in all cases of AKI if bladder outlet obstruction cannot be quickly ruled out by ultrasound.
Urologic, radiologic, or surgical assistance for ureteral stenting, urinary diversion, debulking procedures, or other case-specific requirements may become necessary.
Renal replacement therapy is generally required if there is severe acidosis, volume overload unresponsive to diuretics, or electrolyte or uremic complications while the underlying obstructive issue is being addressed.
Renal replacement therapy
Renal replacement therapy is indicated for refractory severe hyperkalemia, acidosis, volume overload, or uremia.
Conventional hemodialysis is often used when the indications for dialysis arise. Other modes of renal replacement include sustained low-efficiency dialysis (SLED), extended daily dialysis (EDD), rapid-start peritoneal dialysis, or continuous renal replacement therapy (CRRT).[120]Dalbhi SA, Alorf R, Alotaibi M, et al. Sustained low efficiency dialysis is non-inferior to continuous renal replacement therapy in critically ill patients with acute kidney injury: a comparative meta-analysis. Medicine (Baltimore). 2021 Dec 23;100(51):e28118.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8702221
http://www.ncbi.nlm.nih.gov/pubmed/34941056?tool=bestpractice.com
[121]Blake PG, Jain AK. Urgent start peritoneal dialysis: defining what it is and why it matters. Clin J Am Soc Nephrol. 2018 Aug 7;13(8):1278-9.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6086705
http://www.ncbi.nlm.nih.gov/pubmed/30018049?tool=bestpractice.com
Arteriovenous and venovenous techniques may be used, although the most frequent approach is continuous venovenous treatment through a large double lumen catheter placed into the central venous system, such as the internal jugular or femoral vein. Major commonly used modalities include continuous venovenous hemofiltration (CVVH), continuous venovenous hemodialysis (CVVHD), and continuous venovenous hemodiafiltration (CVVHDF).[122]Palevsky PM, Zhang JH, O'Connor TZ, et al; VA/NIH Acute Renal Failure Trial Network. Intensity of renal support in critically ill patients with acute kidney injury. N Engl J Med. 2008 Jul 3;359(1):7-20.
https://www.nejm.org/doi/full/10.1056/NEJMoa0802639
http://www.ncbi.nlm.nih.gov/pubmed/18492867?tool=bestpractice.com
[123]Tolwani AJ, Campbell RC, Stofan BS, et al. Standard versus high-dose CVVHDF for ICU-related acute renal failure. J Am Soc Nephrol. 2008 Jun;19(6):1233-8.
https://jasn.asnjournals.org/content/19/6/1233.full
http://www.ncbi.nlm.nih.gov/pubmed/18337480?tool=bestpractice.com
[124]Bellomo R, Cass A, Cole L, et al; RENAL Replacement Therapy Study Investigators. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009 Oct 22;361(17):1627-38.
https://www.nejm.org/doi/10.1056/NEJMoa0902413
http://www.ncbi.nlm.nih.gov/pubmed/19846848?tool=bestpractice.com
[125]Chertow GM, Burdick E, Honour M, et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005 Nov;16(11):3365-70.
http://jasn.asnjournals.org/cgi/content/full/16/11/3365
http://www.ncbi.nlm.nih.gov/pubmed/16177006?tool=bestpractice.com
CRRT is mostly used in hemodynamically unstable patients or those in whom aggressive ultrafiltration within the conventional 4- to 6-hour treatment of hemodialysis would not be tolerated. Such patients include septic patients requiring vasopressors, or patients with severe heart failure with volume overload and a blood pressure that would not support conventional hemodialysis. Despite improved hemodynamic stability, studies have shown that CRRT or more intensive/frequent dialysis in critically ill patients with AKI confers no increased benefit with respect to other complications or mortality.[123]Tolwani AJ, Campbell RC, Stofan BS, et al. Standard versus high-dose CVVHDF for ICU-related acute renal failure. J Am Soc Nephrol. 2008 Jun;19(6):1233-8.
https://jasn.asnjournals.org/content/19/6/1233.full
http://www.ncbi.nlm.nih.gov/pubmed/18337480?tool=bestpractice.com
[124]Bellomo R, Cass A, Cole L, et al; RENAL Replacement Therapy Study Investigators. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med. 2009 Oct 22;361(17):1627-38.
https://www.nejm.org/doi/10.1056/NEJMoa0902413
http://www.ncbi.nlm.nih.gov/pubmed/19846848?tool=bestpractice.com
[125]Chertow GM, Burdick E, Honour M, et al. Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol. 2005 Nov;16(11):3365-70.
http://jasn.asnjournals.org/cgi/content/full/16/11/3365
http://www.ncbi.nlm.nih.gov/pubmed/16177006?tool=bestpractice.com
Early dialysis appeared to reduce mortality compared with a delayed strategy in one small single-center randomized trial of critically ill patients with AKI, but subsequent meta-analyses found no clear mortality benefit associated with early initiation of renal replacement therapy.[72]Mercado MG, Smith DK, Guard EL. Acute kidney injury: diagnosis and management. Am Fam Physician. 2019 Dec 1;100(11):687-94.
https://www.aafp.org/pubs/afp/issues/2019/1201/p687.html
http://www.ncbi.nlm.nih.gov/pubmed/31790176?tool=bestpractice.com
[126]Zarbock A, Kellum JA, Schmidt C, et al. Effect of early vs delayed initiation of renal replacement therapy on mortality in critically ill patients with acute kidney injury: the ELAIN randomized clinical trial. JAMA. 2016 May 24-31;315(20):2190-9.
https://jamanetwork.com/journals/jama/fullarticle/2522434
http://www.ncbi.nlm.nih.gov/pubmed/27209269?tool=bestpractice.com
[127]Gaudry S, Hajage D, Schortgen F, et al. Initiation strategies for renal-replacement therapy in the intensive care unit. N Engl J Med. 2016 Jul 14;375(2):122-33.
http://www.ncbi.nlm.nih.gov/pubmed/27181456?tool=bestpractice.com
[128]Fayad AI, Buamscha DG, Ciapponi A. Timing of kidney replacement therapy initiation for acute kidney injury. Cochrane Database Syst Rev. 2022 Nov 23;11(11):CD010612.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD010612.pub3/full
http://www.ncbi.nlm.nih.gov/pubmed/36416787?tool=bestpractice.com
[129]Gaudry S, Hajage D, Benichou N, et al. Delayed versus early initiation of renal replacement therapy for severe acute kidney injury: a systematic review and individual patient data meta-analysis of randomised clinical trials. Lancet. 2020 May 9;395(10235):1506-15.
https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(20)30531-6/fulltext
http://www.ncbi.nlm.nih.gov/pubmed/32334654?tool=bestpractice.com
Peritoneal dialysis has generally been thought ineffective in AKI and hypercatabolic states, although some studies suggest comparable effectiveness in appropriate subjects. In developing countries, high-volume peritoneal dialysis (HVPD) provides an alternative form of therapy in selected cases.[130]Ponce D, Balbi AL. Peritoneal dialysis in acute kidney injury: a viable alternative. Perit Dial Int. 2011 Jul-Aug;31(4):387-9.
http://www.ncbi.nlm.nih.gov/pubmed/21799052?tool=bestpractice.com
[131]Ponce D, Berbel MN, Regina de Goes C, et al. High-volume peritoneal dialysis in acute kidney injury: indications and limitations. Clin J Am Soc Nephrol. 2012 Jun;7(6):887-94.
http://www.ncbi.nlm.nih.gov/pubmed/22461532?tool=bestpractice.com
[132]Liu L, Zhang L, Liu GJ, et al. Peritoneal dialysis for acute kidney injury. Cochrane Database Syst Rev. 2017 Dec 4;(12):CD011457.
https://www.cochranelibrary.com/cdsr/doi/10.1002/14651858.CD011457.pub2/full
http://www.ncbi.nlm.nih.gov/pubmed/29199769?tool=bestpractice.com
[133]Cullis B, Al-Hwiesh A, Kilonzo K, et al. ISPD guidelines for peritoneal dialysis in acute kidney injury: 2020 update (adults). Perit Dial Int. 2021 Jan;41(1):15-31.
https://journals.sagepub.com/doi/full/10.1177/0896860820970834
http://www.ncbi.nlm.nih.gov/pubmed/33267747?tool=bestpractice.com