Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5224_Библиотеки_им_академика_М_И_Перельмана.pdf
314 V. Pota and M. Bell
Table 26.1 Incidence of AKI in different settings
Setting AKI incidence (%) References
Cardiac surgery 5–42 Wang (2017) [12]
13 Hu (2016) [13]
Vascular surgery 4–68 Hobson (2018) [17]
Sepsis 51 Vincent (2006) [23]
45 Gordon (2016) [24]
Trauma 24 Sovik (2019) [33]
Burn 38 Folkestad (2020) [34]
Covid-19 32–57 Gupta (2021) [37]
26 Kolhe (2020) [38]
45 Silver (2021) [39]
Conclusion
Acute kidney injury (AKI) is indeed a severe complication for patients in the
intensive care unit (ICU), and its incidence rate is often correlated with the cause
of hospitalization in the ICU, such as sepsis, trauma, or specific perioperative
settings like cardiovascular surgery or major abdominal surgery.
The increasing incidence of AKI has significant ramifications for healthcare
services, not only in terms of the immediate cost of therapy but also due to the
long-term consequences of AKI. These consequences may include the development
of chronic kidney disease, end-stage renal disease, and cardiovascular disease, all of
which can impose substantial financial burdens on healthcare systems.
Table 26.1 would typically
contain data
AKI across diff erent clinical settings, which helps healthcare providers and
policymakers understand the scope and impact of AKI in different patient
populations.
illustrating the varying incidence rates of
References
1. Koeze J, Keus F, Dieperink W, et al. Incidence, timing and outcome of AKI in critically ill
patients varies with the definition used and the addition of urine output criteria. BMC Nephrol.
2017;18:70. https://doi.org/10.1186/s12882-017-0487-8.
Levey AS,
2.
Levin A, Mehrotra R, Palevsky PM, Perazella MA, Tong A, Allison SJ, Bockenhauer D, Briggs
JP, Bromberg JS, Davenport A, Feldman HI, Fouque D, Gansevoort RT, Gill JS, Greene EL,
Hemmelgarn BR, Kretzler M, Lambie M, Lane PH, Laycock J, Leventhal SE, Mittelman M,
Morrissey P, Ostermann M, Rees L, Ronco P, Schaefer F, St Clair Russell J, Vinck C, Walsh
SB, Weiner DE, Cheung M, Jadoul M, Winkelmayer WC. Nomenclature for kidney function
and disease: report of a kidney disease: improving global outcomes (KDIGO) consensus
conference. Kidney Int. 2020;97(6):1117–29.
Epub 2020 Mar 9
Eckardt KU, Dorman NM, Christiansen SL, Hoorn EJ, Ingelfinger JR, Inker LA,
https://doi.org
/10.1016/j.kint.2020.02.010.
26 Global Epidemiology and Outcomes of Acute Kidney Injury 315
3. Hoste EAJ, Kellum JA, Selby NM, Zarbock A, Palevsky PM, Bagshaw SM, Goldstein SL,
Cerdá J, Chawla LS. Global epidemiology and outcomes of acute kidney injury. Nat Rev
Nephrol. 2018;14(10):607–25. https://doi.org/10.1038/s41581-018-0052-0.
4. The World Bank
org/
5. Yang L, et al. Acute kidney injury in China: a cross-sectional survey.
71.
6. Xu X, et al. Epidemiology and clinical correlates of AKI in Chinese hospitalized adults. Clin J
Am Soc Nephrol. 2015;10:1510–8.
7. Mehta RL, Cerdá J, Burdmann EA, Tonelli M, García-García G, Jha V, ... Remuzzi
G. International Society of Nephrology’s 0by25 initiative for acute kidney injury (zero preventable deaths by 2025): a human rights case for nephrology. Lancet. 2015;385(9987):
2616–43.
8. Cerd. J, Bagga A, Kher V, Chakravarthi RM. The contrasting characteristics of acute kidney
injury in developed and developing countries. Nat Clin Pract Nephrol 2008; 4: 138–153
9. Massoth C, Zarbock A, Meersch M. Acute kidney injury in cardiac surgery. Crit Care Clin.
2021;37(2):267–78. https://doi.org/10.1016/j.ccc.2020.11.009. Epub 2021 Feb 13. PMID:
33752855.
10. Hoste EAJ, Vandenberghe W. Epidemiology of cardiac surgery-associated acute kidney injury.
Best Pract Res Clin Anaesthesiol. 2017;31(3):299–303. https://doi.org/10.1016/j.bpa.2017.11.
001. Epub 2017 Nov 8
11. Englberger L, et al. Clinical accuracy of RIFLE and acute kidney injury network (AKIN)
criteria for acute kidney injury in patients undergoing cardiac surgery. Crit Care. 2011;15:R16.
12. Wang Y, Bellomo R. Cardiac surgery-associated acute kidney injury: risk factors, pathophysiology and treatment. Nat Rev Nephrol. 2017;13(11):697–711.
2017.119. Epub 2017 Sep 4. PMID: 28869251.
13. Hu J, Chen R, Liu S, Yu X, Zou J, Ding X. Global incidence and outcomes of adult patients with
acute kidney injury after cardiac surgery: a systematic review and meta-analysis. J Cardiothorac
Vasc Anesth. 2016;30(1):82–9. https://doi.org/10.1053/j.jvca.2015.06.017 . Epub 2015 Jun 10.
14. Chakos A, Wilson-Smith A, Arora S, et al. Long term outcomes of transcatheter aortic valve
implantation (TAVI): a systematic review of 5-year survival and beyond. Ann Thorac Surg.
2017;6:432–43.
15. Azzalini L, Kalra S. Contrast-induced acute kidney injury-definitions, epidemiology, and
implications. Interv Cardiol Clin. 2020;9(3):299–309. https://doi.org/10.1016/j.iccl.2020.02.
001. Epub 2020 May 7. PMID: 32471671.
16. Yoon S, Whisenant BK, Bleiziffer S, et al. Transcatheter mitral valve replacement for
degenerated bio-prosthetic valves and failed annuloplasty rings. J Am Coll Cardiol. 2017;70:
1121–31.
17. Hobson C, Lysak N, Huber M, Scali S, Bihorac A. Epidemiology, outcomes, and management
of acute kidney injury in the vascular surgery patient. J Vasc Surg. 2018;68(3):916–28. https://
doi.org/10.1016/j.jvs.2018.05.017. Epub 2018 Jun 28. PMID: 30146038; PMCID:
PMC6236681
18. Huber M, Ozrazgat-Baslanti T, Thottakkara P, Efron PA, Feezor R, Hobson C, et al. Mortality
and cost of acute and chronic kidney disease after vascular surgery. Ann Vasc Surg. 2016;30:
72–81.e1–81.e2.
19. Group AKIW. Kidney disease: improving global outcomes (KDIGO) – clinical practice
guideline for acute kidney injury. Kidney Int Suppl. 2012;2:1–138.
20.
Aspelin P, Aubry P, Fransson SG, et al. Nephrotoxic effects in high-risk patients undergoing
angiography. N Engl J Med. 2003;348:491–9.
21.
Tsai TT,
kidney injury in
NCDR Cath-PCI registry. JACC Cardiovasc Interv. 2014;7:1–9.
Patel UD, Chang TI, et al. Contemporary incidence, predictors, and outcomes of acute
(2017) How we classify countries The World Bank http://www.worldbank.
Lancet. 2015;386:1465–
https://doi.org/10.1038/nrneph.
patients undergoing percutaneous coronary interventions: insights from the
316 V. Pota and M. Bell
22. Singer M, Deutschman CS, Seymour CW, Shankar-Hari M, Annane D, Bauer M, Bellomo R,
Bernard GR, Chiche JD, Coopersmith CM, Hotchkiss RS, Levy MM, Marshall JC, Martin GS,
Opal SM, Rubenfeld GD, van der Poll T, Vincent JL, Angus DC. The third international
consensus definitions for sepsis and septic shock (Sepsis-3). JAMA. 2016;315(8):801–10.
https://doi.org/10.1001/jama.2016.0287. PMID: 26903338; PMCID: PMC4968574.
23. Vincent JL, Sakr Y, Sprung CL, Ranieri VM, Reinhart K, Gerlach H, Moreno R, Carlet J, Le
Gall JR, Payen D. Sepsis occurrence in acutely ill patients investigators. Sepsis in European
intensive care units: results of the SOAP study. Crit Care Med. 2006;34(2):344–53.
24. Gordon AC, Mason AJ, Thirunavukkarasu N, Perkins GD, Cecconi M, Cepkova M, Pogson
DG, Aya HD, Anjum A, Frazier GJ, Santhakumaran S, Ashby D. Brett SJ; VANISH investigators. Effect of early vasopressin vs norepinephrine on kidney failure in patients with septic
shock: the VANISH randomized clinical trial. JAMA. 2016;316(5):509–18. https://doi.org/10.
1001/jama.2016.10485.).
25. Bagshaw SM, Uchino S, Bellomo R, et al. Septic acute kidney injury in critically ill patients:
clinical characteristics and outcomes. Clin J Am Soc Nephrol. 2007;2:431–9. [PubMed:
17699448.
26. Uchino S, Kellum JA, Bellomo R, Doig GS, Morimatsu H, Morgera S, Schetz M, Tan I,
Bouman C, Macedo E, Gibney N, Tolwani A, Ronco C. Beginning and ending supportive
therapy for the kidney (BEST kidney) investigators. Acute renal failure in critically ill patients:
a multinational, multicenter study. JAMA. 2005;294(7):813–8. https://doi.org/10.1001/jama.
294.7.813.
27. Hoste EA, Bagshaw SM, Bellomo R, Cely CM, Colman R, Cruz DN, Edipidis K, Forni LG,
Gomersall CD, Govil D, Honoré PM, Joannes-Boyau O, Joannidis M, Korhonen AM,
Lavrentieva A, Mehta RL, Palevsky P, Roessler E, Ronco C, Uchino S, Vazquez JA, Vidal
Andrade E, Webb S, Kellum JA. Epidemiology of acute kidney injury in critically ill patients:
the multinational AKI-EPI study. Intensive Care Med. 2015;41(8):1411–23. https://doi.org/10.
1007/s00134-015-3934-7. Epub 2015 Jul 11
28. Liu J, Xie H, Ye Z, Li F, Wang L. Rates, predictors, and mortality of sepsis-associated acute
kidney injury: a systematic review and meta-analysis. BMC Nephrol. 2020;21(1):318. https://
doi.org/10.1186/s12882-020-01974-8. PMID: 32736541; PMCID: PMC7393862.
29. Sood MM, Shafer LA, Ho J, et al. Early reversible acute kidney injury is associated with
improved survival in septic shock. J Crit Care. 2014;29:711–7.
30. Peerapornratana S, Manrique-Caballero CL, Gómez H, Kellum JA. Acute kidney injury from
sepsis: current concepts, epidemiology, pathophysiology, prevention and treatment. Kidney Int.
2019;96(5):1083–99.
31. Gameiro J, Fonseca JA, Neves M, Jorge S, Lopes JA. Acute kidney injury in major abdominal
surgery: incidence, risk factors, pathogenesis and outcomes. Ann Intensive Care. 2018;8(1):22.
https://doi.org/10.1186/s13613-018-0369-7. PMID: 29427134; PMCID: PMC5807256.
32. O’Connor ME, Kirwan CJ, Pearse RM, Prowle JR. Incidence and associations of acute kidney
injury after major abdominal surgery. Intensive Care Med. 2016;42(4):521–30. https://doi.org/
10.1007/s00134-015-4157-7. Epub 2015 Nov 24.
33. Søvik S, Isachsen MS, Nordhuus KM, Tveiten CK, Eken T, Sunde K, Brurberg KG, Beitland
S. Acute kidney injury in trauma patients admitted to the ICU: a systematic review and metaanalysis. Intensive Care Med. 2019;45(4):407–19. https://doi.org/10.1007/s00134-019-05535-
y. Epub 2019 Feb 6. PMID: 30725141.
34. Folkestad T, Brurberg KG, Nordhuus KM, Tveiten CK, Guttormsen AB, Os I, Beitland
S. Acute kidney injury in burn patients admitted to the intensive care unit: a systematic review
and meta-analysis. Crit Care. 2020;24(1):2. https://doi.org/10.1186/s13054-019-2710-4. PMID:
31898523; PMCID: PMC6941386.
Cheng Y,
35.
disease is associated with in-hospital death of patients with COVID-19. Kidney Int. 2020;97:
829–38. https://doi.org/10.1016/j.kint.2020.03.005.).
Luo R, Wang K, Zhang M, Wang Z, Dong L, Li J, Yao Y, Ge S, Xu G. Kidney
26 Global Epidemiology and Outcomes of Acute
36. Yang X, Yu Y, Xu J, Shu H, Xia J, Liu H, Wu Y, Zhang L, Yu Z, Fang M, et al. Clinical course
and outcomes of critically ill patients with SARS-CoV-2 pneumonia in Wuhan, China: a singlecentered, retrospective, observational study. Lancet Respir Med. 2020;8:475–81.
37. Gupta S, Coca SG, Chan L, Melamed ML, Brenner SK, Hayek SS, Sutherland A, Puri S,
Srivastava A, Leonberg-Yoo A, et al. AKI treated with renal replacement therapy in critically ill
patients with COVID-19. J Am Soc Nephrol. 2021;32:161–76.
38. Kolhe NV, Fluck RJ, Selby NM, Taal MW. Acute kidney injury associated with COVID-19: a
retrospective cohort study. PLoS Med. 2020;17:e1003406.
39. Silver SA, Beaubien-Souligny W, Shah PS, Harel S, Blum D, Kishibe T, Meraz-Munoz A,
Wald R, Harel Z. The prevalence of acute kidney injury in patients hospitalized with COVID-19
infection: a systematic review and meta-analysis. Kidney Med. 2021;3, 83–98.e1.
Kidney Injury 317
Chapter 27
Definition, Staging Criteria of Acute Kidney
Injury, and Controversies
Marisa Palmieri and Marco Fiorentino
Introduction
Acute kidney injury (AKI) represents a sudden and often reversible decline in kidney
function, posing significant risks of morbidity and mortality. Accurate staging of
AKI is paramount for effective clinical management and prognostication. Current
definitions and staging criteria primarily rely on changes in serum creatinine and
urine output, yet ongoing debates persist regarding their limitations, especially
concerning baseline creatinine and the potential role of novel biomarkers in risk
assessment. The clinical implications of AKI staging in risk stratification and
treatment strategies are crucial for prognostication and patient outcomes. This
necessitates innovative approaches that consider AKI subphenotypes based on
individual patient characteristics and biomarkers. The identification of AKI
subphenotypes holds promise in enhancing risk prediction and treatment strategies,
ultimately leading to more targeted and effective interventions aimed at improvi ng
long-term outcomes among critically ill patients.
Supplementary Information The online version contains supplementary material available at
https://doi.org/10.1007/978-3-031-66541-7_27.
M. Palmieri · M. Fiorentino (
Nephrology, Dialysis and Transplantation Unit, Department of Precision and Regenerative
Medicine and Ionian Area (DiMePRe-J), University of Bari “Aldo Moro”, Bari, Italy
e-mail: marco.fiorentino@uniba.it
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2024
A.
Cotoia et al. (eds.), Nutrition, Metabolism and Kidney Support,
https://doi.org/10.1007/978-3-031-66541-7_27
✉)
319
320 M. Palmieri and M. Fiorentino
AKI Definition and Staging
Acute kidney injury (AKI) is a clinical syndrome characterized by a rapid and
usually revers ible decline of kidney function, associated with increased length of
hospital stay and costs of hospitalization and worse short- and long-term outcomes in
critically ill patients [1]. Several definitions of AKI have been proposed in the last
decades in order to provide a standardized staging system useful in both the clinical
evaluation and management of patients with AKI [ 2 ]. Increasing serum creatinine
and oliguria still represent the main diagnostic criteria for AKI, although several
proposed classifications have made significant changes in the last years, as reported
in Table 27.1. In 2002, the Acute Dialysis Quality Initiative (ADQI) was created in
order to develop consensus and evidence-based guidelines for the prevention,
diagnosis, and treatment of AKI. RIFLE criteria defined different stages of AKI
(Risk, Injury, and Failure; and Loss; and End-stage kidney disease) according to the
glomerular filtration rate (GFR) and/or urine output [3].
In 2004, the Acute Kidney Injury Network (AKIN) was set up, with the primary
goal to review AKI definitions [4]. A report by the AKIN proposed the foll owing
criteria for defining AKI: an abrupt impairment of kidney function defined as an
absolute increase in serum creatinine of 0.3 mg/dL or more (26.5 μmol/L or more)
within 48 h or an increased serum creatinine of 1.5-fold from baseline or a reduction
in urine output defined as lower than 0.5 mL/kg/h for more than 6 h [4]. The main
difference between the two AKI classifications is related to the timing of changes in
serum creatinine (48 h instead of 7 days); furthermore, the AKIN classification
avoided the use of GFR in assessing and staging AKI, since it is unreliable in the
Table 27.1 Comparison between RIFLE, AKIN, and KDIGO classifications
RIFLE AKIN KDIGO
Criteria
Risk ≥1.5-fold sCr
Injury ≥ two-fold
Failure ≥ three-fold sCr
GFR glomerular filtration
Creatinine
definition Criteria
increase from
baseline or GFR
decline ≥25%
increase from
baseline or GFR
decline ≥50%
increase
baseline or
increase to
≥4 mg/dl
decline ≥75%
sCr
from
or GFR
Stage 1 ≥0.3 mg/dl
Stage 2 ≥ two-fold
Stage 3 ≥ three-fold
rate, RRT renal replacement therapy, sCr serum creatinine
Creatinine
definition Criteria
increase or
≥1.5-fold sCr
increase from
baseline within
48 h
increase from
baseline
increase from
baseline or
to
increase
≥4 mg/dl
RRT initiation
Stage 1 ≥0.3 mg/dl
Stage 2 2–2.9 times
sCr
sCr
Stage 3 ≥3 times
or
Creatinine
definition
increase
within 48 h or
1.5–1.9 times
baseline
within 7 days
baseline
within 7 days
baseline
within
or
increase to
≥4 mg/dl or
RRT initiation
7 days
Urine
output
<0.5 ml/
kg/h for
>6h
<0.5 ml/
kg/h for
12 h
<0.3 ml/
kg/h for
24 h or
anuria
27 Definition, Staging Criteria of Acute Kidney Injury, and Controversies 321
setting of critically ill patients. In addition, the AKIN report suggested the use of
such criteria after adequate volume status optimization and after excluding urinary
tract obstructions when considering oliguria as diagnostic criteria [5].
In 2012, the Kidney Disease Improving Global Outcomes (KDIGO) guidelines
for AKI were relea
sed, proposing to define AKI as any of the following criteria [
6]:
increase in serum creatinine by 0.3 mg/dL or more within 48 h or more than 1.5 times
baseline within the last 7 days or reduction in urine output less than 0.5 mL/kg/h for
6 h. In addition, KDIGO guidelines recommended a staging system based on
severity of serum creatinine and urine output impairments, as follows:
• Stage 1: increase in serum creat inine by 1.5–1.9 times baseline, or increase by
0.3 mg/dL, or decreased urine output to <0.5 mL/kg/h for 6–12 h.
• Stage 2: increase in serum creatinine from 2 to 2.9 times baseline, or decreased
urine output to <0.5 mL/kg/h for ≥ 12 h.
• Stage 3: increase in serum c reatinine more than three times baseline, or increased
serum creatinine ≥ 4 mg/dL, or decreased urine output to <0.3 mL/kg/h for
≥ 24 h, or anuria for ≥ 12 h, or initiation of renal replacement therapy (RRT).
AKI Etiology
There are several potential causes of AKI, and for many years, AKI diagnosis and
management were related to the etiological classification in three categories: prerenal
(functional) AKI, renal (intrinsic/organic) AKI, and post-renal (obstructive) AKI
(Table 27.2). The majority of AKI cases are related to prerenal causes, in which renal
hypoperfusion associated with low intravascular volum e or decreased arterial pressure can result in a reduced GFR without significant parenchymal damag e
[7]. Autoregulatory mechanisms can partially compensate for the reduction of
renal perfusion to maintain GFR. However, in patients with preexisting chronic
Table 27.2 Etiopathology of AKI
Prerenal AKI (functional)
Hypovolemia related to severe volume depletion (abuse of diuretics, dehydration, hemorrhages)
Systemic vasodilatation (sepsis)
Vascular obstruction (renal artery stenosis)
Drugs (NSAID medications, RAS inhibitors)
Intrinsic/Organic AKI
Glomerular damage (acute
Vascular damage (e.g., vasculitis, malignant hypertension, bilateral renal arterial stenosis,
hemolytic uremic syndrome, renal vein thrombosis)
Tubular damage (persistent ischemia as complication of shock, nephrotoxic drugs, endogenous
toxins as myoglobin, hemoglobin)
Post-renal A
Extrarenal obstruction
Internal obstruction (blood clots, calculi)
obstructive)
KI (
glomerulonephritis,
(prostate hypertrophy or cancer)
lupus nephritis, vasculitis)
322 M. Palmieri and M. Fiorentino
kidney disease, these mechanisms are impaired, increasing the susceptibility to
develop acute-on-chronic kidney disease [8]. Elderly or sick patients may experience
prerenal AKI due to specific drugs (NSAIDs, RAAS inhibitors) or even slight
hypoperfusion. Renal blood flow can also be compromised by conditions such as
heart failure, hemorrhages, or dehydration, resulting in a reduction of circulating
blood volume. Severe or prolonged hypoperfusion can lead to tubular epithelial cell
9]
injury, resulting in intrinsic (organic) AKI [
Sepsis is a primary p
triggers an inflammatory cascade, endothelia l dysfunction, and metabolic
reprogramming, which are underlying mechanisms of sepsis-associated AKI
[10]. Intrinsic AKI encompasses a wide spectrum of injuries primarily affecting
the kidney, involving glomeruli, intrarenal vessels, and/or tubules [11]. Acute tubular necrosis (ATN) is the most common type of organic AKI, driven mainly by
persistent renal hypoperfusion. Contrast-induced acute kidney injury (CI-AKI) is
another leading cause of hospital-acquired AKI, particularly following intra-arterial
administration of iodinated contrast media [ 12]. Prevention strategies for CI-AKI
include the use of lower doses of contrast medium and intravenous hydration in
high-risk patients.
Finally, acute obstructions of urinary flow may lead to post-renal AKI, causing
increased intratubular pressure and reduced GFR. The main causes of post-renal AKI
are extrarenal or intrarenal obstructions occurring at any level of the excretory
system [13]. This traditional etiological classification may not encompass all potential clinical presentations in AKI patients, as significant histological data are often
unavailable to confirm the exact cause of AKI. Additionally, in diseases like sepsis,
multiple factors may contr ibute to the development of AKI, complicating
interpretation [14].
recipitating factor of AKI in critically ill patients, as it
.
Subclinical AKI and AKI Biomarkers
Although serum creatinine and urine output are widely used in the diagnosis of AKI,
they are markers of functional impairment, and, consequently, they do not allow
timely and accurate identification of AKI at early phases [13]. Serum creatinine
values are in fluenced by various factors such as age, gender, diet, muscle mass, renal
function history, medications affecting secretion, and concentration changes due to
fluid balance variations during ICU stays. Establishing a specific baseline serum
creatinine for patients is often challenging, leading to misclassification of AKI cases
[14]. Similarly, urine output assessment can be difficult without a urinary catheter
and can be significantly affected by hypovolemia, diuretics, and adjustments
according to body weight, potentially impacting AKI incidence due to fluid overload
and differences between actual and ideal body weight [15]. Consequently, these
criteria are insufficient to describe the broad clinical spectrum of AKI in critical care
settings and cannot identify conditions characterized by a severe risk for AKI or its
early phases. Over the last decade, numerous investigations have aimed to discover
27 Definition, Staging Criteria of Acute Kidney Injury, and Controversies 323
and validate AKI biomarkers capable of identifying early kidney injury, a concept
termed “subclinical AKI” [16]. Potential AKI biomarker s have been identified,
leading to the development of a new conceptual AKI model that involves progression from a baseline condition of normal or high-susceptibility kidneys (e.g.,
reduced renal functional reserve or chronic kidney disease) to early acute kidney
stress, kidney damage, and kidney dysfunction [17]. Using these biomarkers may
offer a more precise approach compared to traditional markers like serum creatinine
and urine output, transitioning from a clinical/biochemical diagnosis to a molecular
diagnosis of AKI [
18]. The clinical integration and routine use of AKI biomarkers
may aid in identifying patients at high risk of AKI development and/or experiencing
kidney stress. Early recognition of kidney stress/injury and monitoring of progression to severe and clinical AKI are crucial endpoints in managing critically ill
patients, as exposure to specific insults (infections, nephrotoxic agents, etc.) can
result in tubular or glomerular damage, leading to maladaptive repair and
AKI-to-
CKD transition.
Various molecules, i
ncluding neutrophil gelatinase-associated lipocalin (NGAL),
interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and liver-type fatty acid
binding protein (L-FABP), have been identified as potential AKI biomarkers, detectable in both serum and urine, and associated with early AKI prediction [19, 20].Associations with the need for dialysis, renal recovery, progression to CKD, and mortality
have also been reported, though further studies are required [19, 2
espite exten-
0]. D
sive preclinical application and publications, the translation of AKI biomarkers into
routine clinical practice has not been successful [21, 22].
In recent
years, the US Food and Drug Administration authorized the use of two
urinary cell-cycle arrest biomarkers, tissue metalloproteinase-2 (TIMP-2), and insulin-like growth factor-binding protein 7 (IGFBP7) [
23]. The combination of these
biomarkers has shown the ability to predict the development of moderate to severe
AKI within the next 12 h. Elevated levels of these biomarkers indicate kidney stress
or early injury, conditions that may still be transient with high chances of renal
recovery if kidney stress resolves [
24].
The increase in TIMP-2* IGFBP7 levels
precedes the rise in typical markers of kidney dysfunction, enabling the early
detection of high-risk patients and the application of KDIGO bundle measures to
prevent progression to clinical AKI [
25]. The integration of such biomarkers into the
AKI classification has been proposed, with the identification of a stage 1S characterized by subclinical AKI (normal serum creatinine and urine output with positive
biomarkers). Implementation of biomarker-guided risk-stratified measures based on
the KDIGO bundle has been shown to reduce the incidence and severity of AKI,
especially in the context of cardiac-associated AKI [
26].
Additionally, specific
biomarkers may represent a molecular signature for a particular type of insult,
allowing for improved characterization of the causative role of specific pathogenic
factors. Finally, AKI biomarkers are useful in identifying conditions of incomplete
recovery after AKI, characterized by maladaptive repair and progression to CKD.
324 M. Palmieri and M. Fiorentino
Subphenotyping AKI
The integration of classical functional markers and novel mark ers of kidney damage
or stress plays a pivotal role in identifying specific AKI phenotypes. Proper interpretation of all available pathophysiological information enables physicians to better
understand AKI pathophysiology, tailor appropriate treatment, and predict outcomes
based on treatment response [27]. AKI exhibits high heterogeneity in terms of
etiology, timing of injury, duration, severity, and rate of renal recovery and can
occur in the context of multi-organ dysfunction. Therefore, KDIGO criteria and
classical etiological distinctions in prerenal, intrinsic, and obstructive AKI may not
adequately describe this variability [28]. Creatinine trajectories during the course of
AKI have been proposed to identify AKI subphen otypes, delineating different rates
of renal recovery and long-term outcomes. The duration of AKI episodes has also
been linked to different subphenotypes, with a high risk for sustained decline in
eGFR or renal failure in those with persistent AKI [29]. This risk was also evident in
patients developing AKI outside the ICU, with around a fivefold increased all-cause
mortality in patients with AKI duration >48 h and without renal recovery [
tionally, novel biomarkers of non-recovery after AKI (e.g., C-C motif chemokine
ligand 14, CCL14) can stratify patients at high risk of persistent AKI [31]. Biomarkers of endothelial activation and inflammation, although not specific to AKI, are
relevant in other critical syndromes like sepsis. Functional evaluations such as the
furosemide stress test could aid in assessing the integrity of renal tubular function
and AKI risk and progression [
recently to subphenotype AKI. Unsupervised clustering analyses, such as latent
class analysis (LCA), have identified different AKI subphenotypes based on various
clinical characteristics and outcomes. These subphenotypes may respond differently
to treatments, highlighting the necessity for tailored approaches. For instance, in a
single-center retrospective cohort study, Andrew et al. identified 12 AKI trajectories
using latent class mixed modeling among patients following cardiac surgery, including 4 high-risk phenotypes characterized by a high risk for death compared to other
subphenotypes [
ferent variables in critically ill patients with AKI and identifying 2 AKI
subphenotypes (AKI-SP1 and AKI-SP2) characterized by different clinical conditions and outcomes [
condition’s heterogeneity. However, leveraging AKI subphenotypes can help identify genetic risk factors associated with specific patient subgroups [34
research should focus on novel approaches to identify subphenotypes or treatable
traits, as successfully done in other medical fields like cancer and lung diseases,
leading to more targeted and effective treatments [
Bhatraju et al. applied a similar methodology, analyzing 29 dif-
29].
33]. Genetic studies in AKI have been inconsistent due to the
32]. Innovative approaches have been proposed
35].
30].
].
Addi-
Soon,