Acute kidney injury (AKI) was classified using the Kidney Disease: Publisher: La incidencia de la lesión renal aguda en la población. La injuria renal aguda (IRA) es una condición común, sobre todo en pacientes therapies for the treatment of critically ill patients with acute kidney injury (AKI). Acute renal failure (ARF) is an independent risk factor associated with increased mortality during sepsis. Recent consensus definitions have allowed the.

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Functional use of the new acute kidney injury biomarkers. New criteria for the diagnosis of acute kidney injury. Source of acute kidney injury biomarkers. Acute kidney injury in the critically ill represents an independent risk factor of morbidity and mortality in the short and long terms, with significant rrnal impacts in terms of public health qki.

However these new biomarkers display sensitive features that may threaten their full capacity of action, which focus specifically on their additional contribution in the early approach of the situation, aaki the lack of specific validated treatments for acute kidney agkda. This review aims to analyze the strengths and weaknesses of these new tools in the early management of acute kidney injury. This phenomenon may partly explain our acceptance or rejection of the use of new biomarkers in the diagnosis of acute kidney injury AKI.

AKI in critically ill patients is an independent risk factor that increases morbidity and mortality in the short and long term, with a tremendous financial impact in terms of health costs. There has been numerous preventive or curative strategies for AKI that have been either ineffective or insufficiently validated to be routinely recommended.

Some processes, such as endothelial dysfunction, 9 myocardial remodeling, 10 epigenetic factors 11 and increased oxidative stress, 12 are factors that could explain the increased risk of morbidity and mortality that persists long after the AKI episode. Another reason that may explain the negative outcome of AKI patients is the late recognition of kidney injury leading to delayed interventions. In this context, there are various limitations of serum creatinine sCr: The latter may differ over time, sometimes up to 48 h, especially in patients in intensive care units ICU.

This was well demonstrated in a secondary analysis of the EPANIC study, in which patients participated and which showed that a reduction in production of sCr positively correlated with the length of stay in the ICU, probably due to loss of muscle mass. The other parameter of AKI is oliguria, which is neither sensitive nor specific, since it could occur as a result of a kidney injury, but may also reflect an adaptive physiological response to either intracellular dehydration or hypovolemia.

The most recent biomarkers promise: The availability of these new biomarkers and the evaluation of simultaneous combinations of functional and tissue damage biomarkers may help stratify patients into 4 subgroups: This new approach has been recognized and recently incorporated to the definition of AKI in Australia and New Zealand regional practice guides, without clarifying what kind of biomarker to use or its cutoff value. New AKI biomarkers vary in their source, in their function, in their distribution and in the time of their release after kidney injury Fig.

Some biomarkers, as for example NGAL, reflect the severity of the triggering disease rather than being specific to the kidney injury. NGAL is a gelatinase-associated human neutrophil that exists as a 25 kDa monomer, as a 45 kDa homodimer and as a gelatinase it conjugates with a kDa heterodimeric conformation. The marker increases 2—4 h after the kidney damage occurs. The NGAL has been associated with a probable kidney protective effect, since it is released by nephron segments where they can form a complex with siderophores that binds to iron; thus, the iron released by the damaged tubular cells is chelated which prevents the formation of hydroxyl radicals and superoxide anions.

NGAL levels also rise in experimental sepsis and systemic inflammation models, suggesting that the release into the urinary system is the response of the kidney to a systemic infection or to the local urogenital infection.

Cystatin C is a 13 kDa protein produced by all nucleated cells that is released into the plasma at a constant rate, regardless of sex, race, muscle mass and hydration level. It circulates in plasma and it is not bound to any protein, is freely filtered through the glomerulus and is fully reabsorbed by megalin-mediated endocytosis at proximal tubule cells level. Diabetes, high doses of corticosteroids, hypertriglyceridemia, hyperbilirubinemia or rheumatoid factor may affect the analysis of Cys-C.

Consequently, increased urinary Cys-C values during AKI reflects decreased reabsorption at proximal tubule level.


It appears in urine 12—24 h after kidney damage. Lseion is a cell membrane glycoprotein whose mRNA levels increase more than any other gene after kidney injury.

The 90 kDa soluble ectodomain is part of the dependent metalloproteinase complexes and it is released into the tubule by epithelial cells making it readily detectable in urine.


During kidney injury, KIM-1 can facilitate remodeling of the injured epithelium. It appears 12 to 24 h after kidney damage. IL is an 18 kDa proinflammatory cytokine produced mainly by activated neutrophils, mononuclear cells, macrophages and non-immune cells, including the proximal tubule cells. It is an agudw ischemic AKI mediator. It appears 6—24 xguda after kidney damage.

NAG is a large-sized protein approximately kDa that originates in the lysosomes of proximal tubule cells.

Its high molecular weight prevents glomerular filtration and, therefore, it is unlikely that high urinary avuda come from a non-renal source. NAG is correlated with histological evidence of renal proximal tubule damage. However, urinary NAG has been shown to be a sensitive marker of tubular injury, and its specificity can be reduced by a low threshold for the release of the tubular enzyme.

False positive values have been reported during diabetes, rheumatoid arthritis and hyperthyroidism. In clinical practice, after AKI there is activation of cell division and cell proliferation in order to repopulate the denuded tubular epithelium. These phenomena occur 24—48 h before the increase in sCr which occurs after a significant drop in the GFR, and the early detection could undoubtedly facilitate new therapeutic and protective strategies, as suggested by the latest KDIGO guidelines.

The combination of these 2 biomarkers seems to be highly predictive of patients who ultimately develop moderate to severe AKI within the next 12—24 h. The international agdua Sapphire study, conducted in critically ill patients, showed that the increase in performance by the combination of these biomarkers was AKI-specific i.

These cutoff points between 0.

Los microARN en el riñón: nuevos biomarcadores de la lesión renal aguda

The most notable properties of these urinary biomarkers, and for which they were selected from more than biomarkers, include: The combination of two or more biomarkers an other clinical data is an attractive strategy to refine current diagnostic capacity. Despite great advances in this field, it should be noted that there are different methodological problems in AKI biomarker research; including the following: These 2 markers, sCr and oliguria, as already mentioned, are affected by external factors.

Studies vary in the cutoff points chosen renao set thresholds for positive and negative predictive AKI-related events. There lesio uncertainty about the exact laboratory method, test platform and sampling conditions, and whether biomarker levels should be normalized in relation to urinary creatinine. Like creatinine, several novel AKI biomarkers are themselves not specific for kidney pathologies and can be influenced by common comorbid conditions, such as sepsis. Most of the biomarkers show a reflect a dynamic pattern of molecular and cellular events occurring during the clinical or subclinical AKI renql.

It is therefore likely that a panel of different biomarkers and multiple measurements combined is better than a single test. The general concept is that in AKI at least a part of the kidney tissue can be protected by early detection and intervention. This may be especially true in the early stages of the renal injury, which would prevent further damage and would preserve renal functional reserve.

There is a need for AKI biomarkers that rapidly detect changes that allow the identification of subclinical kidney zki. Early detection of such patients would allow a stratification by risk according to increased biomarkers or a combination of them that could ultimately help in validating preventive strategies and future therapies.

Beyond early diagnosis and risk stratification, biomarkers have improved our understanding of the pathophysiological mechanisms associated with AKI. This change in our global vision of the pathophysiological mechanism of AKI will without doubt in the near future help us in the therapeutic design of alternative strategies and in focusing on patients most likely to benefit from these strategies with an individualized approach driven by the biomarkers, a diagnosis and personalized treatment.

The assessment of the kidney prognosis, and specifically kidney recovery after AKI, are issues that have recently arisen with direct implications for all health systems. The objective is prevention of progression rensl CKD, either by reducing the level of the injury or facilitating the healing and recovery of the damaged kidney and the control of risk factors. The injury, however, reduces the functioning renal mass and functional reserve. This process is key for the development of CKD.

The validation of biomarkers is insufficient to recommend its clinical use until now, 13,16,17,42 and some results have even been disappointing. One of the reasons for these negative results may be based in erroneous population of patients studied.


The type of ICU patients who may require the use of these biomarkers is still unknown. The population of interest could theoretically influence the diagnostic performance of the tests, 44 as well as their clinical relevance. Future efforts in this area should probably focus on evaluating the best current biomarkers in well-defined groups with high pretest likelihood of AKI and in contexts in which biomarkers can alter the clinical decision making.

It is important to identify patients at high risk of AKI, especially if this provides an opportunity to intervene. Ideally, the test to identify high risk patients should be as reliable as possible to avoid ai negative and false positive results.

Based on the experience from other clinical areas, the unselected use of biomarkers such as prostate specific antigen PSA or d -dimer in an unselected population produces a high number of false positive results and elsion potentially lead to harmful and unnecessary interventions. The results are more solid in pediatric cohorts without comorbidities suffering from a disease with a defined onset of AKI, such as for example in children after heart surgery.

Biomarkers in acute kidney injury: Evidence or paradigm?

It is generally assumed that an earlier diagnosis of AKI would translate directly into an earlier RRT and a better outcome for the patient. Unfortunately, there is currently no evidence that this actually happens, since there is no specific treatment for AKI. To date, there are no interventions beyond treatment of the underlying disease, attention to detail and good health care eenal prevent progression of AKI or induce recovery.

Although it may seem appealing to know which patient will need RRT, it is very unlikely that this information will change clinical practice, especially since there is no evidence that early RRT is more beneficial.

The efficacy of a specific intervention based on increased biomarkers has not been demonstrated. The only intervention study using biomarkers to guide treatment was negative. Therefore, the claim that the use of biomarkers benefits patients and improves the outcome remains unproven. It has been difficult to identify which patients would benefit more with the use of the biomarkers in situations in which the outcome lwsion seems predictable based on standard parameters, such as clinical diagnosis and oliguria.

Clearly in this situation, there is little additional benefit, just as with an application in patients with low risk of AKI, which leads to a useless use of the biomarkers, with an unnecessary increase in health care costs.

Probably the analogy between the 2 conditions crumbles when potential interventions are considered. AMI has specific treatments. Yet even if a reliable biomarker showed AKI early, there would be no currently specific treatments that could be offered for the treatment of tubular ischemia or septic nephropathy.

While the results regarding the ability of biomarkers to improve the predictive value of AKI 47—50 are contradictory and have not yet made the transition to clinical routine, recent publications of the Acute Dialysis Quality Initiative ADQI 20 should be noted, which promote lesioj search for early identification of damage aguds risk of AKI, especially in those patients in whom sCr is negative and biomarkers akl positive; the promotion is based on the potential for the latter to transform the manner of diagnosis and treatment of AKI.

However, these same recommendations, together with the KDIGO AKI guidelines, 4 clearly state that so far sCr and diuresis represent the best markers lesin clinical applicability of AKI for use in diagnosis and monitoring.

The ADQI proposes 4 possible combinations between functional and tissue damage biomarkers: Future efforts in this area should probably focus on evaluating the best current biomarkers in well-defined groups with high likelihood aji AKI and in contexts in which biomarkers can alter clinical decision making.

The authors declare no conflict of interest. Nefrologia English Version renall This review aims to analyze the strengths and weaknesses of these new tools agusa the early management of acute kidney injury.

Biomarkers, Acute kidney injury. This phenomenon may partly explain our acceptance or rejection of the use of new biomarkers in the diagnosis of acute kidney injury AKI. Another reason that may explain the negative outcome of AKI patients is the late recognition of kidney injury leading to delayed interventions.

Disagreement, dogmatism, and belief polarization. J Philos,pp. J Am Soc Nephrol, 16pp.