Acute kidney injury

PRIMER Acute kidney injury John A. Kellum 1, Paola Romagnani2, Gloria Ashuntantang3, Claudio Ronco Alexander Zarbock6 and Hans-Joachim Anders 7 ✉ , 4,5 Abstract | Acute kidney injury (AKI) is defined by a sudden loss of excretory kidney function. AKI is part of a range of conditions summarized as acute kidney diseases and disorders (AKD), in which slow deterioration of kidney function or persistent kidney dysfunction is associated with an irreversible loss of kidney cells and nephrons, which can lead to chronic kidney disease (CKD). New biomarkers to identify injury before function loss await clinical implementation. AKI and AKD are a global concern. In low-income and middle-income countries, infections and hypovolaemic shock are the predominant causes of AKI. In high-income countries, AKI mostly occurs in elderly patients who are in hospital, and is related to sepsis, drugs or invasive procedures. Infection and trauma-related AKI and AKD are frequent in all regions. The large spectrum of AKI implies diverse pathophysiological mechanisms. AKI management in critical care settings is challenging, including appropriate volume control, nephrotoxic drug management, and the timing and type of kidney support. Fluid and electrolyte management are essential. As AKI can be lethal, kidney replacement therapy is frequently required. AKI has a poor prognosis in critically ill patients. Long-term consequences of AKI and AKD include CKD and cardiovascular morbidity. Thus, prevention and early detection of AKI are essential. ✉e-mail: hjanders@ med.uni-muenchen.de https://doi.org/10.1038/ s41572-021-00284-z Acute kidney injury (AKI) describes a sudden loss of kidney function that is determined on the basis of increased serum creatinine levels (a marker of kidney excretory function) and reduced urinary output (oliguria) (a quantitative marker of urine production) and is limited to a duration of 7 days (Table 1)1. AKI is part of a variety of functional kidney conditions, which are summarized as acute kidney disease and disorders (AKD) and can range from mild and self-limiting to severe and persistent. AKD can occur without ever meeting the criterion of rapid onset of AKI, for example when kidney dysfunction evolves slowly1, or AKD can continue after an AKI event has ended, for example, when kidney dysfunction does not resolve or when structural damage to the kidney persists. By definition, AKD persisting for >3 months is referred to as chronic kidney disease (CKD). Of note, AKI and AKD frequently occur in patients with precedent CKD (Fig. 1). As the diagnostic markers serum creatinine and urine output level measure loss of kidney function and not injury, AKI can be seen as a misnomer. In the absence of injury markers, individuals with episodes of transient volume depletion can meet the diagnostic criteria of AKI without injury being present. A few hours of volume depletion in an otherwise healthy human may have no long-term health implications. Similarly, renin– angiotensin system inhibitors or other drugs that affect glomerular filtration may result in small changes in NATURE REVIEwS | DISeASe PRIMeRS | Article citation ID: (2021) 7:52 0123456789();: serum creatinine levels that are not indicative of kidney injury2. However, AKI persisting despite volume therapy probably indicates structural damage to the kidney3. Unfortunately, direct assessment of kidney damage, apart from biopsy, is not possible with existing technology; hence, numerous urinary biomarkers are in use or have been proposed as indicators of glomerular or tubular cell injury4. A consensus statement published in 2020 suggested that damage biomarkers should be integrated into the definition of AKI to augment its classification (Table 2)5. Importantly, both functional impairment (serum creatinine level elevation and/or urine output decline) and presence of biomarkers indicating structural damage are associated with marked increases in mortality in the appropriate clinical context, for example, in cases of critical illness in which they increase hospital mortality 3–7-fold6–9, whereas the same changes may not have long-term health implications in other settings, such as in marathon runners10. Given that the kidney provides life-sustaining functions, severe AKI can be lethal; hence, appropriate management including kidney replacement therapy (KRT), if needed, is essential. In this Primer, we discuss the epidemiology of AKI in different economic settings, as well as the pathophysiology and diagnosis of AKI applied to a variety of settings, such as infections, sepsis, surgery, trauma, nephrotoxic medications, and heart disease, including its long-term consequences. Other causes of AKI or AKD, such as 1 Primer Table 1 | Criteria for defining AKI, AKD, CKD and NKD1,5,50,198 AKI AKD CKD NKD* Duration ≤7 days <3 months >3 months NA Functional criteria Increase in sCr by ≥50% within 7 days or increase in sCr by ≥0.3 mg/dl (26.5 µmol/l) within 2 days or oliguria for ≥6 hours AKI or GFR <60 ml/min/ 1.73 m2 or decrease in GFR by ≥35% over baseline or increase in sCr by >50% over baseline GFR < 60 ml/ min/1.73 m2 GFR ≥ 60 ml/min/1.73 m2, stable GFR (no decrease by 35% within 3 months), stable sCr (no increase by 50% within 3 months or increase by 0.3 mg/dl within 2 days), no oliguria for ≥6 hours AND/OR OR OR OR AND Structural criteria Not defined Elevated marker of kidney damage (albuminuria, haematuria or pyuria are most common) Elevated marker of kidney damage (albuminuria is most common) No marker of kidney damage AKD, acute kidney diseases and disorders; AKI, acute kidney injury; CKD, chronic kidney disease; GFR, glomerular filtration rate; NKD, no kidney diseases; sCr, serum creatinine level. *NKD implies no functional or structural criteria according to the definitions for AKI, AKD or CKD. Hepatorenal syndrome Impaired kidney perfusion and function in patients with advanced liver failure as a consequence of marked abnormalities in arterial and venous circulation, as well as overactivity of endogenous vasoactive systems. hepatorenal syndrome, glomerulonephritis, acute forms of glomerulonephritis or thrombotic microangiopathies (which can present as AKI), kidney transplantation or neonatal circumstances11–14, are not discussed in detail. We detail current approaches and cornerstones of AKI management, summarize how AKI and its long-term effects affect patients’ quality of life and highlight ongoing and future initiatives to improve care for patients with this disorder. Epidemiology Incidence The global burden of AKI-related mortality exceeds by far that of breast cancer, heart failure or diabetes15, with mortality remaining high during the past 50 years. In general, the incidence of AKI is reported as either community-acquired or hospital-acquired AKI. In high-income countries (HIC), AKI is predominantly hospital-acquired, whereas community-acquired AKI is more common in lower-income settings15 (...truncated)