Acute Kidney Injury and Its Damages You Need To Know

Contact: Audrey Hu Whatsapp/hp: 0086 13880143964 Email: audrey.hu@wecistanche.com

Fabian Aleg & Philip Earnhard

Introduction

Acute kidney injury (AKl) is a syndromic disease defined by acute deterioration in renal function [1. An alternative terminology is "acute renal impairment"; the term "acute kidney failure" has not been used in the English-speaking world for years because it is misleading. The two parameters that are used as surrogate markers for kidney function are serum creatinine and diuresis. The time window for this acute deterioration is a maximum of 7 days, and there are 3 degrees of severity of AKI(Acute kidney injury) (Tab.1). These criteria were published in 2012 in the international guidelines of Kidney Disease: Improving Global Outcomes(KDIGO)【1】 and solved the previously existing definitions according to RIFLE -Lrisk/injury/failure/loss of kidney function/end-stage kidney disease"[2]) and AKIN (Acute Kidney Injury Network) criteria [3] (see Table 1), these diagnostic criteria have become established and are currently valid despite some limitations. Essentially, there are 3 criticisms of the current diagnostic criteria:

• Neither the serum creatinine nor the diuresis corresponds to that glomerular filtration rate (GFR), which would be the most meaningful correlate of renal function.

• To make matters worse, the serum creatinine only increases， when half of the nephrons fail so that the diagnosis of AKI(Acute kidney injury) can often be made too late or not at all.

• Another limitation is the lack of a baseline serum creatinine, which is not uncommon in everyday clinical practice and is a prerequisite for diagnosing and evaluating the severity of AKI(Acute kidney injury).

  
  

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Despite all these limitations, the current criteria are widely accepted. The results of many epidemiological studies have contributed to this, which show that these diagnostic criteria correlate well with the kinetic outcome and are therefore clinically relevant. Large studies show that the mortality of patients with AKI(Acute kidney injury) is significantly higher than those of patients without AKI(Acute kidney injury) and that the mortality increases， the more severe the AKI(Acute kidney injury) is【4】. For example, the mortality of critically ill patients with AKI(Acute kidney injury) in sepsis is about 50%[5]. However, AKI(Acute kidney injury) also has an impact on the long-term prognosis. 10 years after surviving an AKI(Acute kidney injury) episode, the mortality rate of these patients is comparative to control patients' significantly higher 【6】. In addition, AKI(Acute kidney injury) leads to a higher risk of chronic kidney disease (chronic kidney disease, CKD) including the need for dialysis [7], hypertension [8] and cardiovascular events such as heart failure and stroke [9]. Thus, AKI(Acute kidney injury) is a relevant prognostic factor.

Due to the lack of recovery from AKI(Acute kidney injury) in some patients and the scarce data that AKI(Acute kidney injury) leads to CKD[7], there are recent efforts to define renal recovery more precisely. Persistent AKI has been defined as CKD after 3 months according to KDIGO criteria [10]. Experts now advise naming AKI(Acute kidney injury) that lasts longer than 7 days but shorter than 3 months as "acute kidney disease" (AKD) [11]. Initial data show that this persistent impairment of kidney function is associated with an unfavorable prognosis [ 12].

*Note: Acute renal injury is an acute deterioration in renal function within 7 days. The surrogate markers that represent renal function are serum creatinine and diuresis.

Table 1 Diagnostic criteria for acute kidney injury (AKI) according to Kidney Disease: Improving Global Outcomes (KDIGO; [1])

Epidemiology

The incidence of AKI(Acute kidney injury) varies greatly depending on the clinical context. Thus, AKI(Acute kidney injury) with an incidence of 14% is relatively rare in outpatients in primary care practices【13】. In the inpatient setting, however, it is relatively common and occurs in 3-20% of patients 【14】. AKI(Acute kidney injury) is particularly common in critically ill patients with sepsis and affects about 50% of all patients in this population [15]. These data indicate that incidence correlates with disease severity. Typical risk factors for the occurrence of AK have been investigated and identified in large epidemiological studies. These include pre-existing CKD, age over 65 years, arterial hypertension, diabetes mellitus, previous cardiovascular diseases such as heart failure, coronary artery disease, and peripheral arterial occlusive disease [16].

*Note: Risk factors for AKI(Acute kidney injury) are age >65 years, arterial hypertension, diabetes mellitus, and pre-existing cardiovascular disease.

Pathogenesis

The AC includes a heterogeneous group of different diseases or conditions that can lead to AKI(Acute kidney injury). Conceptually, these are divided into 3 categories, based on the "place of origin", - prerenal AKI(Acute kidney injury), - intrarenal AKI(Acute kidney injury), - postrenal AKI(Acute kidney injury). Typical causes of the prerenal genesis of AKI(Acute kidney injury) are volume deficiency, cardiac pump failure, or shock; Intrarenal causes are, for example, acute glomerulonephritis or acute interstitial nephritis, while postrenal AKI(Acute kidney injury) is triggered by urinary obstruction (see Table 2).

Tab. 2 Ursachen für eine akute Nierenschädigung (AKI)

*Note: Conceptually, AKI(Acute kidney injury) is divided into prerenal, intrarenal and postrenal Like the triggers, the pathogenesis of AKI(Acute kidney injury) is not uniform. Depending on the trigger-volume deficiency, cardiogenic shock, severe sepsis-other pathomechanisms are assumed. A mild form is the purely hemodynamic AKI(Acute kidney injury), in which there is a functional deterioration of the kidney function without structural damage. This AKI(Acute kidney injury) often resolves quickly after rapid correction of the trigger, This form is the prerenal AKI(Acute kidney injury) in the actual sense since there are no cellular changes in the kidneys. If the trigger for the AKI(Acute kidney injury) is more pronounced or lasts longer, it can lead to the destruction of tubular epithelial cells, the so-called acute tubular necrosis. come. The name is not necessarily exact, since it is currently still uncharted whether the tubular epithelial cells actually perish through necrosis or some other type of cell death Depending on the trigger, tubular cells are caused by a lack of oxygen and nutrients and/or inflammatory mediators. The dying tubular epithelial cells also activate present and migrating immune cells; a sterile inflammatory reaction contributes to tissue damage and can lead to a vicious circle of even more dying cells and even more inflammation [17]. , which do not always easily explain the sometimes complete loss of function of the kidneys (see Fig.1).

*Note: Acute tubular necrosis, ie the death of tubular epithelial cells, often occurs in AKI(Acute kidney injury).

Fig. 1 8 Examples of acute kidney injury (AKI) histology: a rapid-progressive Glomerulonephritis (RPGN) in ANCA (antineutrophil cytoplasmic antibody) vasculitis with the destruction of the Glomeruli.b AKI in severe septic shock; the glomeruli appear largely normal, and the tubular epithelial cells also show only very discrete changes, despite the presence of severe AKI. (With kind permission, © Professor Wolfgang Schneider, Charité, Universitätsmedizin Berlin; all rights reserved)

Diagnosis

The diagnosis of AKI(Acute kidney injury) is made by an increase in serum creatinine or decreased diuresis. On the one hand, to find clues for the cause of the AKI(Acute kidney injury) or to recognize the following AKI(Acute kidney injury)， diagnostic measures are helpful. In the kinetic examination, the determination of blood pressure, heart rate, and the clinical signs of volume depletion or expansion is particularly helpful. Inflammation of the skin and joints can indicate a systemic disease, signs of heart failure can indicate a cardiorenal genesis and livedo reticularis, and a blue toe on cholesterol embolism. Further blood tests are useful in patients with no obvious trigger of AKI(Acute kidney injury) and depend on the kinetic context. These include 【18】∶- differential blood count, - fragment oocytes, calcium, - creatine kinase, - lactate dehydrogenase, - haptoglobin, - amylase and lipase, protein electrophoresis with immunofixation, - complements C3/C4, - hepatitis and HIV serology,

Urine analysis is an important diagnostic tool. Relevant proteinuria (subnephrotic to nephrotic) with nephritic sediment indicates possible glomerulonephritis, whereas a normal urine status indicates a functional genesis of the AKI(Acute kidney injury). Some laboratories also perform urine protein differentiation. High selective excretion of alpha-1-microglobulin indicates tubular damage. Urine microscopy is highly dependent on the examiner. Some studies also prove its advantage in patients in the intensive care unit [19], but the data situation is inconsistent overall. It is definitely recommended for patients with suspected glomerulonephritis [11]. Determining the fractional excretions of urea and sodium can be helpful in differentiating prerenal AKI(Acute kidney injury) from acute tubular necrosis (ATN) with unremarkable urine sediment [20]. here too the data situation is inconsistent. Imaging of the kidneys is necessary for any AKI(Acute kidney injury) to determine renal morphology and identify possible urinary obstruction【21. Sonography lends itself to this because it is cheap and easily available. Alternative examination methods are computed tomography (CT) and magnetic resonance imaging (MRT. The evaluation of renal perfusion can be helpful, for example after major aortic intervention with possible renal perfusion failure or in the case of generalized arteriosclerosis. Doppler sonography is suitable for this. A renal biopsy is performed in critically ill patients due to the poor Biopsy should be considered in all other patients with unclear AKI(Acute kidney injury) without rapid recovery and/or nephritic sediment and proteinuria greater than 1 g per day.

*Note: Important aspects in the diagnosis of AKI(Acute kidney injury) are the determination of blood pressure, evaluation of volume balance, blood and urine tests and imaging of the kidneys.

New diagnostic strategies-electronic alerts and new biomarkers

Even in hospitals, AKI(Acute kidney injury) is often overlooked despite available information about creatinine increase and/or decrease in diuresis【14】. Therefore, electronic alert systems have been developed that automatically identify and report patients with AKI(Acute kidney injury) based on routine laboratory parameters. These so-called AKI(Acute kidney injury) alerts promise a reliable and early identification of patients with AKI(Acute kidney injury), but it is disputed whether this also leads to a kinetic benefit. In a prospective cohort study, in which an AKI alert in combination with a package of measures was successively introduced in various hospitals in Great Britain, the duration of AKI(Acute kidney injury) could be reduced [22]. However, in a multicentre, randomized, controlled study, no improved care was achieved with the help of an AKI(Acute kidney injury) alert [23].

*Note: New biomarkers and electronic AKI(Acute kidney injury) alerts could enable earlier and better diagnosis in the future.

A number of new biomarkers for AKI(Acute kidney injury) have been developed in recent years. Such new biomarkers in the urine can indicate an AKI(Acute kidney injury) at an early stage, and this is already at a time when the serum creatinine has not yet risen. There are also several biomarkers that correlate with the severity of the renal damage. The best-studied markers are currently KIM (Kidney injury molecule")-1 [24], IGFBPLinsulin-like growth factor binding protein"-7 [25], TIMPLtissue inhibitor of metalloproteinases")-2 [26] and NGAL (neutrophil gelatinase-associated lipocalin";[27] ). But here too it is still uncertain whether the use of these markers in clinical routine will bring any advantage. However, at least 2 monocentric studies could show that an early diagnosis based on IGFBP-7 and TIMP-2 in combination with the application of the KDIGO recommendations for supportive therapy (see below) could reduce the rate of severe AKI(Acute kidney injury) [28, 29]. However, there is currently a lack of data from larger studies, and accordingly, the new biomarkers continue to play a subordinate role in everyday clinical practice.

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