The term "acute kidney injury" refers to a sudden loss of renal excretory function, a slow deterioration of renal function, or persistent renal dysfunction with irreversible loss of renal cells and nephrons, which can lead to chronic kidney disease (CKD). Acute kidney injury (AKI) mainly occurs in elderly patients and is associated with sepsis and endotoxemia. Studies have shown that bacterial endotoxins can induce sepsis. In the azotemia phase of chronic renal insufficiency, especially in the uremia phase, the level of endotoxin in the blood of patients increases significantly, indicating that endotoxin plays a role in the development of chronic renal insufficiency. Previous experimental studies have proved that the early target organ of endotoxin is the kidney. The renal vascular resistance increases about 6 times within a short period after animal injection of endotoxin, so it is believed that endotoxin can affect the kidney in the early stage and induce the occurrence of functional renal failure. Currently, there is no direct assessment of kidney injury with existing techniques other than biopsy. Endotoxin may become a powerful diagnostic tool for renal disease if new biomarkers can be identified before renal function is lost.
Figure 1. Pathogenic associations between gut dysbiotic microbiota and development of diabetic kidney diseases from the gut-kidney axis. (Lin J R, et al., 2022)
As well as maintaining a dynamic balance of body fluids and electrolytes, osmotic pressure, and pH, the kidneys also excrete metabolic waste and secrete hormones, and biologically active molecules. However, AKI disrupts homeostasis, leading to disturbances in the main function of the kidneys (maintaining homeostasis), and can be fatal in severe cases. According to statistics, the mortality rate associated with AKI has far exceeded that of breast cancer, heart failure, or diabetes. Endotoxin is a kind of lipopolysaccharide (LPS), derived from the outer membrane of Gram-negative bacteria, which can promote the Schwartzman reaction in the body, and cause fibrin precipitation and vascular embolism in the capillaries around the renal tubules through the action of vasoactive substances, and even renal tubules. The experiment revealed that short-term renal function damage appears rapidly in rats after a certain amount of LPS is injected into their tail veins, along with a series of morphological changes, suggesting that LPS is capable of modulating renal function and causing nephropathy. In addition, the endotoxin levels in the plasma of uremic patients tend to be significantly higher than normal. Several urinary biomarkers are currently being used or have been proposed to assess glomerular or tubular cell injury. It has been proven that endotoxin is closely related to kidney disease. The Limulus test method can be used to accurately and timely detect endotoxin in patients' blood, and timely prevent and treat endotoxemia, which can reduce renal damage or prevent renal failure.
Unlike other acute organ failures, AKI does not present immediately with overt symptoms, so diagnosis requires specific technical assessment. It has been confirmed that endotoxin has a wide range of biological activities on the body, and is related to various pathophysiological processes and inflammation of kidney diseases, so its detection has extremely important clinical significance. For the determination of urine endotoxin, urine samples are usually drawn from clean urine or catheterization, and diluted appropriately with sterile pyrogen-free saline before testing. The urine limulus test detects endotoxin quickly and conveniently, which is beneficial to judge the occurrence of kidney disease clinically.
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