Acute kidney injury

doi:10.1016/S0140-6736(19)32563-2

The Lancet

Volume 394, Issue 10212, 23–29 November 2019, Pages 1949-1964

https://doi.org/10.1016/S0140-6736(19)32563-2 Get rights and content

Summary

Acute kidney injury (AKI) is defined by a rapid increase in serum creatinine, decrease in urine output, or both. AKI occurs in approximately 10–15% of patients admitted to hospital, while its incidence in intensive care has been reported in more than 50% of patients. Kidney dysfunction or damage can occur over a longer period or follow AKI in a continuum with acute and chronic kidney disease. Biomarkers of kidney injury or stress are new tools for risk assessment and could possibly guide therapy. AKI is not a single disease but rather a loose collection of syndromes as diverse as sepsis, cardiorenal syndrome, and urinary tract obstruction. The approach to a patient with AKI depends on the clinical context and can also vary by resource availability. Although the effectiveness of several widely applied treatments is still controversial, evidence for several interventions, especially when used together, has increased over the past decade.

Introduction

Acute kidney injury (AKI) is a syndrome. It is an important complication in patients admitted to hospital (10–15% of all hospitalisations)¹ and in patients in the intensive care unit (ICU) where its prevalence can sometimes exceed 50%.² Despite its complexity, AKI is traditionally seen as a single disease or classified according to semi-anatomical categories (ie, pre-renal, intrinsic, and post-renal AKI) in reference to the kidney (panel 1).

This simplistic taxonomy is now giving way to more specific syndromic descriptions including among others hepatorenal,⁸ cardiorenal,⁹ nephrotoxic,¹⁰ and sepsis-associated AKI.¹¹ This increased specificity is because of increasing evidence that these syndromes have a unique pathophysiology and treatment.

Another major challenge to AKI diagnosis and treatment is that specific syndromes often coexist as illustrated by the overlaps shown in figure 1. Because AKI often arises as part of other syndromes (ie, heart failure, liver failure, and sepsis), which themselves cause substantial morbidity and mortality, it is easy to overlook the significance of AKI as both a marker of disease severity and a determinant of short-term and long-term outcomes.

In patients with septic shock, 60-day mortality is three to five times greater in those who develop AKI.¹⁵ Although this mortality could be a function of greater sepsis severity in patients with severe AKI, the syndrome itself might independently increase mortality by leading to electrolyte and acid-base disorders, fluid accumulation, and metabolic dysfunction, impairing neutrophil function and reducing the patient's ability to clear infection.¹⁶

Thus, the early and rapid diagnosis and treatment of AKI is an important part of the overall management of patients with the various syndromes that cause or are associated with AKI. By contrast, management of the original disorder, in some cases, might help to resolve the secondary AKI syndrome. Although some aspects might not be modifiable, there is evidence that some causes of AKI can be mitigated in some settings.17, 18

Section snippets

Consensus definitions and epidemiology

Different terms and different criteria for AKI have been used previously making it impossible to reach accurate conclusions on the epidemiology of this syndrome. International consensus criteria were first introduced by the Acute Dialysis Quality Initiative,⁴ and subsequently modified by the AKI Network,⁵ and finally by Kidney Disease Improving Global Outcomes (KDIGO)⁶ as shown in table 1 and panel 2. Through use of standard criteria, estimates of incidence and prevalence of AKI, and

Clinical presentation

Kidney disease is usually a silent condition. Except for urinary tract obstruction, it does not cause pain or any specific signs or symptoms. Patients can therefore present in two ways. First, a patient might present with an acute illness such as sepsis,²⁵ or be exposed to a condition known to be associated with AKI such as major surgery.²⁶ Importantly, such patients might not present to the ICU and it is therefore essential that clinicians working outside the ICU are aware of the clinical

The pathophysiology of AKI

AKI is a loose collection of syndromes. Thus, its pathophysiology varies according to the myriad of conditions associated with its development.⁷⁶ In addition, the pathophysiology of AKI secondary to uncommon immunological diseases of the kidney parenchyma (glomerulonephritis) or direct infection of the renal parenchyma (pyelonephritis) is complex.77, 78 The same applies to acute (but also uncommon) vascular events, which can cause parenchymal injury, and to obstructive disease of the urinary

Distant organ effects of AKI

In many conditions, the presence of AKI can induce dysfunction or damage of distant organs. This effect on distant organs can be the case in cardiorenal syndrome type 3 (cardiac disease precipitated by or contributed to by AKI), in which the heart is affected with myocardial contractility defects and inflammatory infiltrates in the cardiac tissue. Another example is represented by the multiple interactions with the lungs.109, 110 The effect of acute or chronic uraemia on brain physiology and

Prevention of AKI

The first principle of AKI prevention is to treat its cause or trigger. The second principle is to ensure that further insults are avoided. Systemic haemodynamics should be optimised so that, irrespective of the trigger, further damage does not occur and adequate renal perfusion and perfusion pressure are maintained. If intravascular volume is compromised, it must be rapidly restored by administration of intravenous fluids.

The extent of fluid administration and whether a degree of fluid

Clinical and pharmacological management

Once AKI is both advanced and established, the focus of management should remain on delivering the same interventions used to prevent its development.¹³³ However, an additional focus of medical management should be directed to the prevention or rapid treatment of complications. Such management might vary in complexity from fluid restriction to the initiation of extracorporeal RRT. Nutritional support is an accepted standard of care. However, no level 1 studies exist to define what optimal

AKI as a risk factor for CKD

Over the past decade, multiple studies have shown a strong epidemiological link between AKI and the subsequent development of CKD.167, 168, 169, 170, 171, 172 The additional risk of end-stage kidney disease after AKI has been estimated at an additional 0·4 extra cases per 100 person-years, and the additional risk of CKD after AKI has been estimated at ten extra cases per 100 person-years.¹⁷¹ If the link between AKI and CKD is causal, the public health consequences of AKI in terms of CKD and

Post-AKI care

Patients with AKI tend to have worse medium-term to long-term outcomes than other patients who did not develop AKI.180, 181 This observation suggests the opportunity to improve care by close follow-up of patients who have one or more episodes of AKI during hospital or ICU admissions.¹⁸² These patients seem particularly fragile and might require specific medical interventions.¹⁸³ Of course, this extension of care will require additional resources and might be challenging to do in many

Conclusion

AKI is undergoing substantial evolution in terms of definition and classification, understanding of pathophysiological mechanisms, and interaction with other disciplines and organ systems. Epidemiology describes an increasing incidence partly due to a more thorough clinical evaluation and detection. New biomarkers and advanced diagnostic techniques represent an important advancement in the field, leading to implementation of timely and effective preventive and protective measures.

The management

Search strategy and selection criteria

We searched PubMed and MEDLINE for original research papers, reviews and systematic reviews, meta-analyses, editorials, and commentaries published between Jan 1, 2014, and June 30, 2019, using the following search terms: “acute kidney injury”, “acute renal failure”, “continuous hemofiltration”, “continuous renal replacement therapy”, and “haemodialysis”. We combined the terms “continuous hemofiltration”, “continuous renal replacement therapy”, and “haemodialysis” with “acute kidney injury” and

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