**1. Introduction**

Classically, acute kidney injury (AKI) is defined as a decrease in the glomerular filtration rate (eGFR) in a period of less than 3 months accompanied by the retention of nitrogenous products and changes in the internal environment, and anuria or oliguria may or may not be present [1].

In 2004, the Acute Dialysis Quality Initiative (ADQI) group considered that staging the damage is important in the diagnosis of AKI because small increases in creatinine or decreased diuresis are associated with greater morbidity and mortality and longer hospital stay [2].

In the Acute Kidney Injury Network (AKIN) Classification System, the value of increased serum creatinine (sCr) greater than 0.3 mg/dl is added with greater diagnostic sensitivity and eliminates the Loss and ESRD stages [3]. The Kidney Disease Improving Global Outcomes (KDIGO) workgroup in 2012 [4] encompasses an elevation of sCr greater than 0.3 mg/dl or an increase greater than 50% above the baseline value in a period of 7 days; in each of the three stages, a range is placed in relation to the fold

increase in creatinine in relation to the basal range, and the other parameter that is taken into account is urine production [4]. Comparison of the KDIGO criteria, creatinine has greater predictive ability than urinary volume.

After reaching consensus on the definition of AKI by the Acute Disease Quality Initiative (ADQI) group, the AKI incidence in the general ward has been 20% [5], with rates increasing by approximately 10% per year [6]. The incidence of AKI in the intensive care unit (ICU) has been 30 to 50%, and 10% require kidney replacement therapy (KRT) [7, 8]. The hospital mortality of AKI has been 27.5% in those who did not require KRT and from 33 to 53% [9] in those who required KRT. This incidence has not changed over time probably due to more serious pathologies and increasingly long-living patients.

The development of AKI in the ICU is considered a predictor of mortality with a specificity of 71% and a sensitivity of 93% similar to the APACHE II score with a specificity of 75% and a sensitivity of 93% and where the relationship between AKI and mortality in the ICU is significant (odds ratio 3.99; 95% CI 2.125–7.481) [10].

### **2. Classification and biomarkers**

The KDIGO guidelines classify the severity of ARF into three stages according to functional 2os2rome (sCr and diuresis), one of which is the elevation of creatinine with respect to baseline, and if the baseline value is not known, the corresponding creatinine values are taken into account, depending on sex, age and race; another variable is the reduction in urinary 2os2rom as a function of time. It is known that creatinine is not the best marker of renal function, in addition to being a late marker, and can be interpreted in different clinical situations such as states of fluid overload (FO), and the creatinine value should be corrected by the FO. There are also drugs that affect the tubular secretion of creatinine (trimethoprim-sulfamethoxazole, cimetidine, and ranitidine) and changes in the rate of sCr production (muscle hypercatabolism, the elderly).

It is important to identify predisposing and susceptibility factors that may develop AKI, such as heart failure, diabetes mellitus, liver disease, chronic kidney disease (CKD), sepsis, emergency surgery, cardiac surgery, and the use of nephrotoxic drugs. The use of biomarkers in populations at clinical risk will allow the detection of subclinical AKI in those at risk of renal complications after exposure to a noxa and allow opportunities for preventive intervention strategies to improve clinical outcomes and reduce the need for KRT [11]. The ADQI consensus conference (**Table 1**) recommends a combination of damage and functional biomarkers (**Table 2**) to improve the diagnostic accuracy of AKI and has made it possible to modify the KDIGO classification in stage 1 AKI with three subcategories (1S, 1A, and 1B) and AKI stage 2 and 3 with subcategories (2 A biomarker negative, 2B biomarker positive) (recommendation grade B) [12, 13].

### **3. Considerations at the start of kidney replacement therapy**

The question of when to start KRT dates back 60 years, where Parsons F. et al. described a retrospective cohort of 17 patients with sepsis of surgical origin with AKI and who underwent intermittent hemodialysis with BUN values >180 mg/dl and had an 88% mortality. One year later, the same work group reported another cohort of 17 *Timing of Initiation of Kidney Replacement Therapy in Acute Kidney Injury… DOI: http://dx.doi.org/10.5772/intechopen.112156*


*The ADQI consensus conference recommends a combination of damage and functional biomarkers to improve the diagnostic accuracy of AKI and have allowed modification of the KDIGO classification in stage 1 AKI with three subcategories (1S, 1A, and 1B) and stages 2 and 3 from AKI with subcategories (2A biomarker negative and 2B biomarker positive) [12].*

#### **Table 1.**

*AKI classification.*


*Biomarkers are classified into glomerular filtration, tubular function, tubular damage, injury response, and cell regulation [12].*

*Urinary insulin-like growth factor-binding protein (IGFBP-7) and tissue inhibitor of metalloproteinase (TIMP-2), neutrophil gelatinase-associated lipocalin (NGAL), interleukin-6, interleukin-10, interleukin-18, Kidney Injury Molecule-1 (KIM-1), liver-type fatty acid-binding protein (L-FABP), Fractional Excretion of Sodium (FENa), and Fractional Excretion of Urea (FEUrea).*

#### **Table 2.**

*Biomarker IN AKI.*

patients with AKI due to sepsis with daily BUN increases of 30 mg/dl in which early intervention in dialysis treatment decreased mortality to 25% [14].

The KDIDO-2012 guideline recommends the Initiate KRT emergently when lifethreatening changes in fluid, electrolyte, and acid-base balance exist (Not Graded). The clinical context should be considered, and trends from laboratory tests should be evaluated, rather than single nitrogen values (Not Graded). These appraisals are far from being practical and we hope that, with the updated evidence of recent years and the forthcoming recommendations from the KDIGO, they will provide a clearer guideline [15].

The decision to start KRT should not only be based on kidney function or KDIGO stage, but many aspects mentioned below should also be evaluated (**Figure 1**).

The kidneys have a finite capacity; when the demands exceed the renal capacity in the context of AKI, an imbalance with non-renal organ dysfunction is generated. Renal demands and capacity should be assessed taking the following considerations:

#### **Figure 1.**

*Considerations at the start of kidney replacement therapy. To consider the initiation of KRT, patient comorbidities, severity of acute illness, severity of AKI, and the expressed will of the patient, family, human resources, and available machines and costs are taken into account [16].*


*Timing of Initiation of Kidney Replacement Therapy in Acute Kidney Injury… DOI: http://dx.doi.org/10.5772/intechopen.112156*

#### **Figure 2.**

*Kidney capacity and demand. The relationship of renal capacity and demands refers to the state of functional reserve of the kidneys. They are not able to withstand the severity of acute illness, fluid overload, and metabolic overload, where previous comorbid conditions may be a factor in a lower tolerance to the development of AKI [16].*

6. It is important to know the wishes of the patient and family, to evaluate with the medical team whether dialysis is part of a therapeutic plan of the multidisciplinary team and that it does not represent a futile measure, and to consider the availability of nursing staff, machines, and costs [16].
