Acute kidney injury: an increasing global concern

doi:10.1016/S0140-6736(13)60647-9

The Lancet

Volume 382, Issue 9887, 13–19 July 2013, Pages 170-179

https://doi.org/10.1016/S0140-6736(13)60647-9 Get rights and content

Summary

Despite an increasing incidence of acute kidney injury in both high-income and low-income countries and growing insight into the causes and mechanisms of disease, few preventive and therapeutic options exist. Even small acute changes in kidney function can result in short-term and long-term complications, including chronic kidney disease, end-stage renal disease, and death. Presence of more than one comorbidity results in high severity of illness scores in all medical settings. Development or progression of chronic kidney disease after one or more episode of acute kidney injury could have striking socioeconomic and public health outcomes for all countries. Concerted international action encompassing many medical disciplines is needed to aid early recognition and management of acute kidney injury.

Introduction

Until recently, an absence of consensus meant that several different definitions of acute renal failure were in standard use, and wide variation existed in estimates of disease prevalence (1–25%) and mortality (15–60%).1, 2 To resolve this confusion, several definitions and classification systems of acute renal failure have been proposed.³ All systems were based on reports that even small absolute increases in serum creatinine are linked to poor short-term and long-term prognosis.4, 5 In parallel, the change of the term acute renal failure to acute kidney injury, which encompasses the entire spectrum of disease from small changes in function to requirement for renal replacement therapy (RRT), created a new descriptive system and extended the number of potentially affected patients.

The most recent definition of acute kidney injury retains the Acute Kidney Injury Network (AKIN) and Risk, Injury, Failure, Loss, and End-stage kidney disease (RIFLE) staging criteria, and is proposed by the Kidney Diseases: Improving Global Outcomes (KDIGO) clinical practice guidelines workgroup.⁶ The KDIGO criteria stage patients according to changes in serum creatinine and urine output, rather than changes in glomerular filtration rates, apart from in children younger than 18 years (for whom an acute decrease in estimated glomerular filtration rate to less than 35 mL/min per 1·73 m² is included in the stage 3 criteria). Both serum creatinine and urine output criteria are important predictors and the use of RIFLE without assessment of urine output underestimates the incidence and grade of acute kidney injury and can delay diagnosis.⁷

Key messages

•
Incidence of acute kidney injury is steadily increasing in low-income and high-income countries; however, the distribution of causes differs dependent on the location
•
Presence of more than one comorbidity results in high severity of illness scores in every medical setting of acute kidney injury
•
Pre-existing chronic kidney disease is a potent risk factor for acute kidney injury
•
Development or progression of chronic kidney disease after one or more episode of acute kidney injury has substantial socioeconomic and public health effects in high-income and low-income countries

In this Series, we review the increasing incidence of acute kidney injury and complexity behind prevention and management, focusing on differences between high-income and low-income countries.

Section snippets

High-income countries

Incidence of acute kidney injury steadily increased between 1988 and 2003.8, 9, 10 Disease reporting in administrative databases suggests a prevalence of about 2% of patients in hospitals in the USA.9, 10 However, incidence of acute kidney injury in patients with acute myocardial infarction declined between 2000 and 2008, despite a rising prevalence of risk factors, and probably because of an increased awareness of the disease and increasingly effective prevention.¹¹ Variety in incidence is

Overview

The causes of acute kidney injury are traditionally grouped into three categories: prerenal, renal (with direct intrinsic kidney damage), and postrenal. In prerenal disease, renal hypoperfusion leads to a decreased glomerular filtration rate as an adaptive response to various extrarenal insults such as volume depletion, systemic hypotension, significant renal vascular stenosis or thrombosis, severe systolic or diastolic cardiac failure, and activation of the neurohumoral axis increasing renal

Risk factors

Several comorbidities, including diabetes mellitus, cardiovascular disease, chronic liver disease, cancer, and complex surgery have been associated with development of acute kidney injury in community, hospital, and critical care settings.8, 33

Crush syndrome is a reperfusion injury that occurs after ischaemia of skeletal muscle caused by prolonged continuous pressure. After release from the pressure, severe volume depletion and circulatory failure can develop, leading to large amounts of

Pathophysiology

About two-thirds of acute tubular necrosis is caused by renal ischaemia-reperfusion injury or sepsis, and a third is caused by direct or indirect nephrotoxicity. Tubular and vascular changes, alongside interstitial inflammation, are responsible for the acute decrease in glomerular filtration rate.

Pathophysiological mechanisms of acute kidney injury, including molecular and cellular mechanisms have been described in several reviews.37, 38 The disease also has distant effects on the

Diagnosis

Causal diagnosis of acute kidney injury relies on a combination of a patient's history, clinical examination, assessment of kidney function, renal imaging, renal biopsy and, potentially, measurement of biomarkers of structural damage.³

After diagnosis and management of life-threatening complications, such as hyperkalaemia, intractable volume overload, severe acidosis, and uraemic serositis, a diagnosis of post-obstructive acute kidney injury should first be excluded by imaging of the kidney and

Non-dialytic management

Identification and correction of potentially reversible causes of kidney damage such as volume depletion and avoidance of nephrotoxins are of paramount importance. Drug doses should be adjusted on the basis of assessment of renal function, preferably with timed urinary clearances.⁵¹ Iodine, and to a lesser extent, gadolinium contrast media are potentially nephrotoxic and should be avoided when possible. The preventive and eventual therapeutic role of volume expansion, diuretics, vasoactive

Prognosis

Acute kidney injury is associated with several complications, including fluid overload, electrolyte abnormalities, and coagulopathy. Fluid overload is associated with increased risk of death,80, 81 although this association might also reflect severity of illness. Acute kidney injury exerts direct effects on other organs and systems, and contributes to multiorgan failure in critically ill patients.³⁹ Although the severity and outcome of an episode of acute kidney injury are predicted by its

Costs

Existing studies about costs associated with acute kidney injury are restricted to calculations of the costs of procedures and early admission to hospitals but did not include long-term costs. Costs attributable to acute kidney injury increase as the definition broadens and with the severity of the disease. Data from 23 hospitals in MA, USA,⁹⁶ in 2 years show that acute kidney injury, compared with non-acute injury, resulted in higher hospital resource use, with median direct hospital costs

Conclusions

Although our understanding of the causes and mechanisms of acute kidney injury is improving, the disease's occurrence and short-term and long-term complications are difficult to prevent. These problems impose an enormous socioeconomic burden, especially in low-income countries. An important concern is that even small acute changes in kidney function can lead to complications, chronic kidney disease, end-stage renal disease, and death. A concerted multinational and multidisciplinary effort is

Future perspectives

The definition of acute kidney injury needs to be standardised in clinical trials through implementation of an international definition and classification, as proposed by the recently published KDIGO acute kidney injury guideline group.

Multinational epidemiological studies are needed to assess incidence, prevalence, and causes of acute kidney injury, especially in low-income countries. Databases generated should include traditional markers of kidney function and new serum and urinary biomarkers

Search strategy and selection criteria

We searched PubMed and Embase for articles published between Jan 1, 2000, and Jan 31, 2013 without language restrictions with the search terms “AKI” and “acute kidney injury” as the first set of search terms with “epidemiology”, “causes”, “risk factors”, “clinical approach”, “prevention and management”, “prognosis”, and “costs”. We primarily included publications from the previous 5 years and articles that assessed developing countries, global health issues, and socioeconomic aspects of acute

References (101)

F Liaño et al.
Epidemiology of acute renal failure: a prospective, multicenter, community-based study
Kidney Int
(1996)
R Bellomo et al.
Acute kidney injury
Lancet
(2012)
S Naicker et al.
Epidemiology of acute kidney injury in Africa
Semin Nephrol
(2008)
SK Mishra et al.
Malaria and acute kidney injury
Semin Nephrol
(2008)
L Andrade et al.
Leptospiral nephropathy
Semin Nephrol
(2008)
PK Li et al.
Acute kidney injury: global health alert
Kidney Int
(2013)
MT James et al.
Glomerular filtration rate, proteinuria, and the incidence and consequences of acute kidney injury: a cohort study
Lancet
(2010)
ME Grams et al.
The distant organ effects of acute kidney injury
Kidney Int
(2012)
LS Chawla et al.
Acute kidney injury and chronic kidney disease: an integrated clinical syndrome
Kidney Int
(2012)
JL Vincent et al.
ICU nephrology: the implications of cardiovascular alterations in the acutely ill
Kidney Int
(2012)

A Lassnigg et al.

Clin Nephrol

(2004)

Cited by (743)

A National audit of the care of patients with acute kidney injury in England and Wales in 2019 and the association with patient outcomes
2024, Clinical Medicine, Journal of the Royal College of Physicians of London
Acute kidney injury (AKI) is a common complication of hospitalisations. This national audit assessed the care received by patients with AKI in hospital Trusts in England and Wales.
Twenty four hospital Trusts across England and Wales took part. Patients with AKI stage2/3 were identified using the UK Renal Registry AKI master patient index. Data was returned through a secure portal with linkage to hospital episode statistic mortality and hospitalisation data. Completion rates of AKI care standards and regional variations in care were established.
989 AKI episodes were included in the analyses. In-hospital 30-day mortality was 31-33.1% (AKI 2/3). Standard AKI interventions were completed in >80% of episodes. Significant inter-hospital variation remained in attainment of AKI care standards after adjustment for age and sex. Recording of urinalysis (41.9%) and timely imaging (37.2%) were low. Information on discharge summaries relating to medication changes/re-commencement and follow-up blood tests associated with reduced mortality. No quality indicators relating to clinical management associated with mortality. Better communication on discharge summaries associated with reduced mortality.
Outcomes for patients with AKI in hospital remain poor. Regional variation in care exists. Work is needed to assess whether improving and standardising care improves patient outcomes.
Timing of renal replacement therapy in patients with sepsis-associated acute kidney injury: A systematic review and meta-analysis
2024, Australian Critical Care
The objective of this study was to evaluate the clinical efficacy of early and delayed renal replacement therapy (RRT) in patients with sepsis-associated acute kidney injury (AKI).
We searched three databases (PubMed, Web of Science, and Cochrane) for randomised controlled trials and cohort studies published up to March 28, 2022, and manually searched for relevant references. We included data from adults older than 18 years of age with sepsis-associated AKI. The Newcastle–Ottawa Scale and the Cochrane Risk of Bias tool were used for quality assessment. The primary outcome was 28-day mortality. Relative risk (RR), mean difference (MD), and 95% confidence interval (CI) were used for meta-analysis.
There were a total of 3648 patients from four randomised controlled trials and eight cohort studies. The pooled results indicated that compared to delayed RRT, early RRT had a lower 28-day mortality (RR: 0.72; 95% CI: 0.59–0.88; P = 0.001; I² = 76%), and this result was robust according to sensitivity analysis, and no significant difference in 90-day mortality (RR: 0.80; 95% CI: 0.64–1.00; P = 0.05; I² = 82%),180-day mortality (RR: 1.07; 95% CI: 0.93–1.23; P = 0.36; I² = 0%), length of intensive care unit stay (MD − 0.94; 95% CI −2.43–0.55; P = 0.22; I² = 0%), length of hospital stay (MD − 1.02; 95% CI −4.21–2.17; P = 0.53; I² = 0%), and RRT dependence was found among survivors at 28 days (RR: 1.21; 95% CI: 0.73–2.00; P = 0.47; I² = 0%). Subgroup analysis of 28-day mortality showed that patients with sepsis-associated AKI who received early RRT at Kidney Disease: Improving Global Outcomes stage 2 or Sequential Organ Failure Assessment score ≤12 had a better chance of survival.
Early RRT may be beneficial to the 28-day short-term survival rate of patients with sepsis-associated AKI in Kidney Disease: Improving Global Outcomes stage 2 and having Sequential Organ Failure Assessment score less than or equal to 12 but has no significant effect on long-term survival, length of intensive care unit stay, the total length of hospital stay, and 28-day RRT dependence of survivors. These results still need to be confirmed by more large-scale randomised controlled studies.
Perioperative acute kidney injury: The renoprotective effect and mechanism of dexmedetomidine
2024, Biochemical and Biophysical Research Communications
Dexmedetomidine (DEX) is a highly selective and potent α2-adrenoceptor (α2-AR) agonist that is widely used as a clinical anesthetic to induce anxiolytic, sedative, and analgesic effects. In recent years, a growing body of evidence has demonstrated that DEX protects against acute kidney injury (AKI) caused by sepsis, drugs, surgery, and ischemia-reperfusion (I/R) in organs or tissues, indicating its potential role in the prevention and treatment of AKI. In this review, we summarized the evidence of the renoprotective effects of DEX on different models of AKI and explored the mechanism. We found that the renoprotective effects of DEX mainly involved antisympathetic effects, reducing inflammatory reactions and oxidative stress, reducing apoptosis, increasing autophagy, reducing ferroptosis, protecting renal tubular epithelial cells (RTECs), and inhibiting renal fibrosis. Thus, the use of DEX is a promising strategy for the management and treatment of perioperative AKI. The aim of this review is to further clarify the renoprotective mechanism of DEX to provide a theoretical basis for its use in basic research in various AKI models, clinical management, and the treatment of perioperative AKI.
Enhancing leptospirosis control with nanosensing technology: A critical analysis
2024, Comparative Immunology, Microbiology and Infectious Diseases
Leptospirosis is a serious health problem in tropical areas; thus, animals shed leptospires in the environment. Humans are accidental hosts infected through exposure to contaminating bacteria in the environment. One health strategy can be applied to protect and eliminate leptospirosis because this cooperates and coordinates activities between doctors, veterinarians, and ecologists. However, conventional methods still have limitations. Therefore, the main challenges of leptospirosis control are the high sensing of detection methods to screen and control the pathogens. Interestingly, nano sensing combined with a leptospirosis detection approach can increase the sensitivity and eliminate some limitations. This article reviews nanomaterial development for an advanced leptospirosis detection method, e.g., latex beads-based agglutination test, magnetic nanoparticles enrichment, and gold-nanoparticles-based immunochromatographic assay. Thus, nanomaterials can be functionalized with biomolecules or sensing molecules utilized in various mechanisms such as biosensors. Over the last decade, many biosensors have been developed for Leptospira spp. pathogen and others. The evolution of biosensors for leptospirosis detection was designed for high efficiency and might be an alternative tool. In addition, the high-sensing fabrications are useful for leptospires screening in very low levels, for example, soil or water from the environment.
N6-methyladenosine (m6A) methylation in kidney diseases: Mechanisms and therapeutic potential
2023, Biochimica et Biophysica Acta - Gene Regulatory Mechanisms
The N6-methyladenosine (m6A) modification is regulated by methylases, commonly referred to as “writers,” and demethylases, known as “erasers,” leading to a dynamic and reversible process. Changes in m6A levels have been implicated in a wide range of cellular processes, including nuclear RNA export, mRNA metabolism, protein translation, and RNA splicing, establishing a strong correlation with various diseases. Both physiologically and pathologically, m6A methylation plays a critical role in the initiation and progression of kidney disease. The methylation of m6A may also facilitate the early diagnosis and treatment of kidney diseases, according to accumulating research. This review aims to provide a comprehensive overview of the potential role and mechanism of m6A methylation in kidney diseases, as well as its potential application in the treatment of such diseases. There will be a thorough examination of m6A methylation mechanisms, paying particular attention to the interplay between m6A writers, m6A erasers, and m6A readers. Furthermore, this paper will elucidate the interplay between various kidney diseases and m6A methylation, summarize the expression patterns of m6A in pathological kidney tissues, and discuss the potential therapeutic benefits of targeting m6A in the context of kidney diseases.
Circular RNA hsa_circ_0005519 contributes to acute kidney injury via sponging microRNA-98-5p
2024, BMC Nephrology

View all citing articles on Scopus

View full text

SeriesAcute kidney injury: an increasing global concern

Summary

Introduction

Section snippets

High-income countries

Overview

Risk factors

Pathophysiology

Diagnosis

Non-dialytic management

Prognosis

Costs

Conclusions

Future perspectives

Search strategy and selection criteria

Kidney Int

Lancet

Semin Nephrol

Semin Nephrol

Semin Nephrol

Kidney Int

Lancet

Kidney Int

Kidney Int

Kidney Int

Kidney Int

Lancet

J Am Coll Cardiol

J Am Coll Cardiol

Kidney Int

Lancet

Kidney Int Suppl

Kidney Int

Am J Kidney Dis

Ann Thorac Surg

Am J Kidney Dis

Kidney Int

Kidney Int

Am J Kidney Dis

Am J Kidney Dis

Am J Kidney Dis

Acute renal failure in critically ill patients: a multinational, multicenter study

JAMA

Acute kidney injury, mortality, length of stay, and costs in hospitalized patients

J Am Soc Nephrol

Minimal changes of serum creatinine predict prognosis in patients after cardiothoracic surgery: a prospective cohort study

J Am Soc Nephrol

KDIGO Clinical Practice Guidelines for Acute Kidney Injury

Kidney Int Suppl

A comparison of RIFLE with and without urine output criteria for acute kidney injury in critically ill patients

Crit Care

Incidence and outcomes in acute kidney injury: a comprehensive population-based study

J Am Soc Nephrol

Declining mortality in patients with acute renal failure, 1988 to 2002

J Am Soc Nephrol

Incidence and mortality of acute renal failure in Medicare beneficiaries, 1992 to 2001

J Am Soc Nephrol

Trends in the incidence of acute kidney injury in patients hospitalized with acute myocardial infarction

Arch Intern Med

Acute kidney injury in critically ill patients classified by AKIN versus RIFLE using the SAPS 3 database

Intensive Care Med

Acute kidney injury in children and its potential consequences in adulthood

Blood Purif

Worldwide demand for critical care

Curr Opin Crit Care

The contrasting characteristics of acute kidney injury in developed and developing countries

Nat Clin Pract Nephrol

Acute kidney injury in dengue fever using Acute Kidney Injury Network criteria: incidence and risk factors

Trop Doct

A unifying hypothesis and a single name for a complex globally emerging infection: hantavirus disease

Eur J Clin Microbiol Infect Dis

Incidence and etiology of acute kidney injury in southern India

Indian J Pediatr

Incidence of acute kidney injury in hospitalized children

Indian Pediatr

Paediatric acute kidney injury in a tertiary hospital in Nigeria: prevalence, causes and mortality rate

PLoS One

Analysis of the prerenal contributions to acute kidney injury

Contrib Nephrol

Septic acute kidney injury: the culprit is inflammatory apoptosis rather than ischemic necrosis

Series
Acute kidney injury: an increasing global concern