MODELOS DE INNOVACIÓN

Acute kidney injury (AKI), also known as acute renal failure (ARF), is an abrupt decrease in kidney function that occurs over hours to days.21 _{This is in contradistinction}

to chronic kidney disease (CKD), where renal function declines over the course of months to years. In 2004, the Acute Dialysis Quality Initiative (ADQI) published the first AKI consensus definition, with the goal of standardizing disease recognition and endpoints for clinicians as well as for research studies, including clinical trials.22 _The

RIFLE criteria (an acronym that stands for risk, injury, failure, loss, and end-stage renal disease [ESRD]) used acute changes in serum creatinine (SCr) and urine output (UO), readily available measurements, to define three progressive levels of renal dysfunction (R, I, and F) and two clinical outcomes (L, E). Subsequent consensus definitions would use the term AKI, a more inclusive term that underscores the importance of the injury and consequent change in the renal function. Through this lens, the 2007 definitions of the Acute Kidney Injury Network (AKIN)23 focused on the initial injury previously deemed risk, injury, and failure of the RIFLE classification, terming them stage 1, 2, and 3 AKI. Loss and end stage kidney disease in the RIFLE system were removed along with the partial reliance on glomerular filtration rate (GFR). Additionally, the AKIN criteria included small changes in SCr (>26.5 umol/L increase in 48 hours[h]) in the definition of stage 1 AKI.

Several large observational trials confirmed the validity of the RIFLE and AKIN revised criteria, as increasing severity of AKI was associated with increasing risk of death.24,25 _{Despite high incidence and significant effect on outcomes, a concern}

remained that AKI was underdiagnosed owing to inconsistent screening practices and the tendency for these criteria to miss AKI that occurs before arrival at an acute care setting. The Kidney Disease Improving Global Outcomes (KDIGO) clinical practice guidelines for AKI present the most recent consensus definitions, which again attempt

definition emphasizes AKI risk assessment and evaluation while extending criteria to include a rise in SCr of 50% or greater over the presumed baseline within seven days of assessment. The association of AKI defined by these criteria with adverse outcomes has now been validated in a large number of clinical studies.3,28 Table 1 summarizes the RIFLE, AKIN, and KDIGO criteria for AKI.

Table 1. AKI definitions: RIFLE, AKIN, and KDIGO criteria for AKI Clasification Definition for

AKI Stage Serum Creatinine criteria for AKI staging UO criteria

RIFLE

Increase in SCr

≥50% within 7 d Risk To ≥1.5 times baseline <0.5ml/kg/h for >6 h Injury To ≥2 times baseline <0.5ml/kg/h for >12 h Failure mmol/L increase to at least 354 To ≥3 times baseline or ≥44

mmol/L <0.3ml/kg/h for >24 h or anuria ≥12 h AKIN Increase in SCr ≥26.5 mmol/L or ≥50% within 48 h 1 Increase of ≥26.5 mmol/L or to

1.5–2 times baseline <0.5ml/kg/h for >6 h 2 To 2–3 times baseline <0.5ml/kg/h for >12 h 3 mmol/L increase to at least 354 To ≥3 times baseline or ≥26.5

mmol/L or initiation of RRT <0.3ml/kg/h for >24 h or anuria ≥12 h KDIGO Increase in SCr ≥26.5 mmol/L within 48 h or ≥50% within 7 d

1 Increase in SCr ≥26.5 mmol/L within 48 h or to 1.5–2 times

baseline <0.5ml/kg/h for >6 h 2 To 2–3 times baseline <0.5ml/kg/h for >12 h 3 To ≥3 times baseline or to at least _{354 mmol/L or initiation of RRT} <0.3ml/kg/h for >24 h or anuria _{≥12 h}

AKI: Acute Kidney Injury; AKIN: Acute Kidney Injury Network; d: days; h: hours; KDIGO: Kidney Disease Global Outcomes; RIFLE: Risk Injury Failure Loss ESRD; RRT: renal replacement therapy; SCr: serum creatinine; UO: urine output.

Consensus definitions for AKI have been critical to move the AKI clinical research field forward, but have significant limitations because they use SCr and UO for the detection of kidney injury. SCr is a marker of GFR and consequently is a late marker of kidney injury (for example [e.g.], by the time SCr rises, injury has long occurred), and it has been suggested that SCr production may be affected by sepsis.29 _{UO may reflect a}

number of states including AKI, such as volume depletion and dehydration.30 _Numerous

studies have focused on identifying more sensitive and specific biomarkers of AKI to aid in earlier detection and better prognostication. These include urinary biomarkers of tubular injury such as kidney injury molecule-1 (KIM-1) and neutrophil gelatinase-

associated lipocalin (NGAL), as well as markers of glomerular filtration, such as cystatin C, which is less dependent on muscle mass than SCr.31

A few recent studies have shown that tissue inhibitor of metalloproteinases-2 (TIMP-2) and insulin-like growth factor-binding protein 7 (IGFBP7) are specific biomarkers of structural renal damage in critically ill patients.32,33 TIMP-2 and IGFBP7 are protective molecules involved in G1 cell-cycle arrest that moderate apoptotic, angiogenic34, inflammatory35 and ischaemic processes.36Since renal cell arrest usually occurs 24–48 h before SCr rises due to a signifcant fall in the GFR, TIMP-2 and IGFBP7 are thought to be earlier AKI biomarkers than SCr. TIMP-2 and IGFBP7 are detectable in urine. Previous studies in unselected ICU populations have shown that when analysed together as the index [TIMP-2]·[IGFBP7], they perform better than SCr, urine and plasma NGAL, plasma cystatin-C and KIM-1 for early detection of AKI and improved risk stratification for renal and general outcomes.32,33,37 UO and SCr are increasingly being complemented by these novel biomarkers that can rapidly and specifically recognise AKI. Thus, future definitions of AKI may soon include such biomarkers.