The clinical practice guidelines established in 2012 by the KDIGO Acute Kidney Injury Work Group were designed to provide information and assist decision-making in this condition
Anja Bienholz MD
Andreas Kribben MD
Department of Nephrology,
University Hospital Essen,
Acute kidney inury (AKI) is a life-threatening disease with poor outcome, incomplete understanding of pathogenesis and rare causal therapeutic options, which causes high morbidity, mortality and treatment costs. AKI occurs with an incidence of about 3000 per 1 million inhabitants and affects up to two-thirds of patients receiving intensive care. The incidence of AKI can be compared to that of acute lung injury or severe sepsis.(1)
Even small rises in serum creatinine are associated with increased 30-day mortality, as Lassnigg et al showed in patients after heart surgery.(2) But AKI not only increases short-term mortality, but also causes a stage-dependent decrease in patient survival that can be observed for at least ten years following AKI.(3) Lastly, patients recovering from AKI remain at an increased risk for recurrence development of chronic kidney disease and progression to end-stage renal disease.(4)
The clinical practice guidelines established in 2012 by the Kidney Disease: Improving Global Outcomes (KDIGO) Acute Kidney Injury Work Group(5) were designed to provide information and assist decision-making with focus on risk assessment, prevention and treatment of AKI. The guidelines incorporate the best information available from February 2011. This article gives an overview regarding selected statements of these guidelines.
Definition of AKI
As a consistent further development of RIFLE and AKIN criteria, a new definition of AKI has been established. AKI is defined by at least one of the following criteria:
- Increase in serum creatinine by at least 0.3mg/dl (26.5μmol/l) within 48 hours
- Increase in serum creatinine to at least 1.5-times baseline, which has been detected, or is presumed to have existed within the prior week
- Decrease in urine volume to <0.5ml/kg/h for at least six hours.
Table 1 shows the staging for AKI. Three stages of AKI were defined depending on serum creatinine and/or urine output. Definition and staging of AKI are important parts of the clinical practice guidelines, as treatment should follow stage-orientated steps.
Prevention and treatment
In order to successfully apply stage-orientated actions, possible triggering events (exposures) and encouraging factors (susceptibilities) for AKI have to be identified (see Table 2 for examples). The interaction of both creates the individual risk profile of each patient.
Actions that are appropriate in all patients with an increased risk for AKI include avoidance of nephrotoxic medication, optimisation of volume status, haemodynamic monitoring, regular monitoring of serum creatinine, urine volume and blood glucose levels, as well as substitution of procedures involving intravascular iodinated contrast medium by alternatives if possible and feasible. With increased severity of AKI, additional measures such as diagnostic actions, changes in drug dosing, admission to intensive care units or introduction of renal replacement therapy, might become appropriate.
The KDIGO AKI Working Group has created a timeline model for risk assessment in AKI (Figure 1). This model includes determination of the cause of AKI whenever possible and risk stratification for exposures and susceptibilities (Table 2).
Both should be checked before and after exposure to possible triggers of AKI. Patients who already suffer from AKI should be evaluated as early as possible in order to determine the cause of AKI, especially as they might be reversible in early stages, and should be managed in a stage-orientated fashion. Causes of AKI that might be directly influenced by specific treatment in early stages include reduced renal perfusion, acute glomerulonephritis, vasculitis, interstitial nephritis, thrombotic microangiopathy and urinary tract obstruction.
In accordance with the long-term effects of AKI on mortality and chronic kidney disease, the model also includes a recommendation to screen patients three months after the onset of AKI for recovery, new onset or progression of chronic kidney disease. Thereafter, these patients should be treated as either patients with chronic kidney disease or as patients with an increased risk for chronic kidney disease.
In the initial treatment for expansion of intravascular volume in patients at risk or with AKI who do not suffer from haemorrhagic shock, KDIGO guidelines suggest the use of isotonic crystalloid solutions instead of colloids. This suggestion is based on the lack of evidence for superiority of colloid solutions. By contrast, there are observations that specific hyperoncotic colloids, that are generally associated with higher costs, might even increase incidence for AKI.(7) A crucial point in treatment of AKI is ideal volume management. Ideal volume management includes assurance of sufficient volume supply in early phases and avoidance of volume overload as urine output declines.(8)
Providing sufficient nutrition – preferentially enteral – to provide catabolism is also suggested. Restriction of protein intake in order to delay initiation of renal replacement therapy is refused.
It is recommended to abandon diuretics in the prevention and treatment of AKI, with the exception of patients with volume overload. This guideline is mainly based on evidence concerning the most commonly prescribed loop diuretic, furosemide. There is some evidence for loop diuretics to decrease oxygen consumption in the loop of Henle,(9) to promote wash-out of necrotic fragments, and to reduce renovascular resistance and increase renal blood flow by inhibition of the prostaglandin dehydrogenase.(10) However, considering systematic reviews, there is no evidence that application of furosemide in prevention or treatment of AKI can reduce its incidence or severity.(11,12) The use of loop diuretics still plays an important role in the treatment of volume overload and ventilatory limitations, but lacks any benefit for the kidney itself.
Contrast-media induced AKI
The old definition for contrast media-induced nephropathy has been abolished. Instead, forms of contrast media-induced AKI are included in the general definition and staging of AKI.
Contrast media-induced AKI is one of the most common reasons for hospital-acquired AKI being associated with rising mortality and costs.(13) The guidelines suggest that all patients should undergo screening for pre-existing limitations of kidney function before intravenous application of iodinated contrast media. This could be done by a standardised questionnaire identifying risk factors (Table 2). Intravenous volume expansion with NaCl 0.9% or sodium bicarbonate solutions is recommended for all patients receiving contrast media.
The KDIGO guidelines also suggest the application of N-acetylcysteine (NAC) in patients at increased risk of contrast-induced AKI. This suggestion is not based on evidence for any benefit of NAC, but simply refers to the fact that NAC is cheap and has few adverse side effects. Because the guidelines are based on information available from February 2011, results of the ACT trial and the consecutive meta-analysis were not incorporated.(14) More than 13,000 patients were evaluated in this study, the largest of its kind so far, which did not show any evidence for protective effects of NAC in contrast media-induced AKI. In our opinion, NAC should not be used for prevention of contrast media-induced AKI.
Renal replacement therapy
Life-threatening changes in fluid, electrolyte and acid–base balance are emergency indications for the initiation of renal replacement therapy. Renal replacement therapy should be performed with regard to the clinical context and should not be based on single laboratory measurements (for example, serum creatinine or blood urea nitrogen). It is suggested to withdraw renal replacement when no longer needed, but to avoid accelerating this process by application of diuretics.
Continuous renal replacement therapy should be preferred in haemodynamically unstable patients. No further preference for intermittent or continuous methods is given. The use of regional citrate anticoagulation is suggested in patients undergoing continuous renal replacement therapy, as long as patients do not have contraindications and sufficient monitoring is ensured. Regional citrate anticoagulation can reduce bleeding risks. If continuous monitoring of ionised and overall calcium levels is guaranteed, regional citrate anticoagulation seems to be a safe treatment option, even in patients with insufficient liver function.(15)
The new KDIGO guidelines for AKI still do not clarify the intensity of renal replacement therapy that should be administered in AKI. Ronco et al published a study in 2000 that showed a correlation between survival time and increasing doses of continuous haemofiltration.(16) This result could not be confirmed in the larger cohorts of the ATN trial(17) and the ANZICS RENAL study.(18) The unfavourable performance of more intensified regimes might be due to more frequent hypotension and electrolyte imbalances. The recommendation to deliver a Kt/V of 3.9 per week in intermittent of extended renal replacement therapy is eventually consistent with data from patients suffering from chronic kidney disease.(19)
To summarise, the 2012 KDIGO guidelines for AKI include a revised definition with three severity stages. In prevention and treatment of the disease susceptibilities and exposures are of crucial importance. Being aware of long-term effects on mortality and development of chronic kidney disease, assessment of prognosis and patients’ follow-up have been brought into focus. Optimisation of fluid management is pivotal in AKI. Nevertheless, diuretics are without benefit for the kidney and renal function itself. Clear advantages do not exist for any kind of renal replacement modality, but regional citrate anticoagulation seems a practical option in continuous renal replacement therapy.
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- Lassnigg A et al. Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study. J Am Soc Nephrol 2004;15(6):1597–605.
- Hobson C et al. Acute kidney injury is associated with increased long-term mortality after cardiothoracic surgery. Circulation 2009;119(18):2444–53.
- Macedo E, Bouchard J, Mehta R. Renal recovery following acute kidney injury. Curr Opin Crit Care 2008;14(6):660–5.
- KDIGO AKI Working Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Kidney Int Suppl 2012;2:1–138.
- KDIGO AKI Working Group. KDIGO Clinical Practice Guideline for Acute Kidney Injury. Online Appendices A-F;2012.
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- Ludens J et al. Enhancement of renal blood flow by furosemide. J Pharmacol Exp Ther 1968;163:456–60.
- Ho K, Sheridan D. Meta-analysis of furosemide to prevent or treat acute renal failure. Br Med J 2006;333:420.
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- ACT Investigators. Acetylcysteine for prevention of renal outcomes in patients undergoing coronary and peripheral vascular angiography: Main results from the randomized acetylcysteine for contrast-induced nephropathy trial (ACT). Circulation 2011;124:1250–9.
- Saner F et al. Efficacy and safety of regional citrate anticoagulation in liver transplant patients requiring post-operative renal replacement therapy. Nephrol Dial Transplant 2011;27(4):1651–7.
- Ronco C et al. Effects of different doses in continuous veno-venous haemofiltration on outcomes of acute renal failure: a prospective randomised trial. Lancet 2000;356(9223):26–30.
- Palevsky P et al. Intensity of renal replacement therapy in acute kidney injury: perspective from within the Acute Renal Failure Trial Network Study. Crit Care 2009;13(4):310.
- Renal Replacement Therapy Study Investigators et al. Intensity of continuous renal-replacement therapy in critically ill patients. N Engl J Med 2009;361(17):1627–38.
- Eknoyan G et al. Effects of dialysis dose and membrane flux in maintenance hemodialysis. N Engl J Med 2002;347(25):2010–19.