Renal & Liver Function

Tissue inhibitors of metalloproteinases (TIMPs) are tissue inhibitors of the MMPs family and are widely distributed in tissues and body fluids. They covalently bind to MMPs and inhibit their activity. The TIMP family has four proteins, TIMP1, TIMP2, TIMP3 and TIMP4. TIMP-1 is a 28KD glycoprotein that can be produced by many different types of cells. It is an important inhibitor of MMPs and specifically binds to the carboxy-terminal end of the catalytic region of MMPs' zymogen or activated enzyme to form a complex, thereby specifically inhibiting the hydrolytic activity of MMPs. In addition to inhibiting MMPs, TIMP-1 also plays an important role in tissue dynamic balance.

Bile acid is the most abundant of the four main human bile acids, and its derivatives, glycine cholic acid and taurine cholic acid, are the main human bile acids. Bile salts secreted by the liver into bile are powerful emulsifiers. After bile flows through the upper part of the small intestine, bile salts emulsify fats and help them be digested and absorbed. After the fatty acids and glycerides of the emulsified fat droplets are absorbed by the lower part of the small intestine, bile salts are also reabsorbed. They return to the liver and are reused, so bile salts circulate between the liver and small intestine. Bile salts are not only particularly important for the absorption of fats but also for all fat-soluble nutrients. When there is a defect in bile salt production or secretion due to certain diseases, undigested and unabsorbed fat appears in feces. At this time, fat-soluble vitamins A, D, E, K cannot be completely absorbed, which can lead to nutritional deficiencies in vitamin A.

Glycine cholic acid (CG) is a cholesterol metabolite and a conjugated bile acid formed by the combination of cholic acid and glycine. Its relative molecular mass is 465.6. It is one of the main components of bile acid and mainly exists in serum in a protein-bound form. CG has gradually become a more sensitive and specific indicator for the diagnosis of liver diseases. The analysis of CG combined with other indicators can provide more evidence for the diagnosis, treatment and prognosis of liver diseases. CG is a very important indicator in the screening and follow-up of intrahepatic cholestasis of pregnancy. The degree of damage to mothers and infants varies with the degree of increase in CG value during pregnancy, and the higher the CG value, the greater the harm. The level of glycine cholic acid is significantly increased in patients with liver cancer. It is particularly significant for early diagnosis of cirrhosis. It helps diagnose and evaluate the efficacy of various types of hepatitis. In patients with cholelithiasis accompanied by jaundice, serum CG is significantly increased due to biliary and gallbladder excretion dysfunction; when there is obstructive liver disease, CG levels increase by 10-20 times, and serum bile acids also increase in drug-induced cholestasis.

Chenodeoxycholic acid (CDCA) is one of the most widely used drugs for the treatment of gallstones in the world. Its chemical formula is C24H40O4 and it is a colorless needle-shaped crystal. It is almost insoluble in water, soluble in ethanol and ice acetic acid, and slightly soluble in chloroform. It can be used to reduce the saturation of cholesterol in bile. After most patients take CDCA (when CDCA accounts for 70% of bile salts), lipids recover into micelles, and cholesterol is in an unsaturated state, so that cholesterol in stones dissolves and falls off. High doses of CDCA (10-15mg/kg per day) can inhibit cholesterol synthesis and increase bile secretion in patients with cholelithiasis, but the secretion of bile salts and phospholipids remains unchanged.

Prealbumin (PA), also known as transthyretin (TTR), has a molecular weight of about 55kD and a plasma half-life of 1.9 days. It is a glycoprotein synthesized by liver cells and is named because it migrates before albumin during electrophoresis. The physiological function of PA is to repair tissues and act as a transport protein. Due to the short half-life of PA (1.9 days), which is shorter than other plasma proteins expressed and released by the liver, it is a sensitive indicator for reflecting nutritional status and liver function, and is also a sensitive negative acute-phase reaction protein.

Neutrophil gelatinase-associated lipocalin (NGAL), also known as human lipocalin 2 (Lipocalin 2, Ln2), is a member of the human lipocalin family and consists of 178 amino acid residues. NGAL is a small molecule protein expressed in neutrophils and epithelial cells in some tissues and organs, including renal tubules. Its expression in the kidney will significantly increase due to kidney damage caused by different reasons, and it will be released into urine and blood. Its level can increase within 2 hours after kidney injury. Studies have shown that the range of NGAL in urine of healthy people is 0.7-9.6 ng/mL, and that in plasma is 3-106 ng/mL. The level of NGAL increases sharply after kidney injury, so NGAL is used as an early sensitive biomarker for kidney injury. NGAL in blood and urine reflects the presence, severity and progression of chronic kidney disease. The level of NGAL may also moderately increase in infections and certain cancers.

Beta-2-microglobulin (β2-MG) is the β chain (light chain) part of human lymphocyte antigen (HLA) on the cell surface. It has a molecular weight of 11.8kD and is a single-chain polypeptide composed of 99 amino acids. It is mainly produced by lymphocytes, platelets, and polymorphonuclear leukocytes. β2-Microglobulin can be freely filtered from the glomerulus and 99.9% is absorbed in the proximal renal tubule and degraded into amino acids in lysosomes in renal tubular epithelial cells for the body to use. Therefore, under normal circumstances, the excretion of β2-microglobulin is very small. Elevated blood β2-microglobulin can reflect a decrease in glomerular filtration rate (GFR) and an increase in synthesis in the body, while elevated urinary β2-microglobulin can reflect impaired renal tubular function and increased GFR.

Retinol binding protein 4 (RBP4) is a newly discovered adipokine that is expressed and secreted in adipose tissue and participates in the occurrence of insulin resistance. It belongs to the retinol binding protein (RBP) family and is a serum retinol binding protein. It is the most important extracellular transport protein responsible for binding and transporting retinol in the blood. Retinol binding protein (RBP) is a plasma protein that binds and transports vitamin A. After vitamin A binds to it in the form of trans-retinol, it becomes a water-soluble substance, which is transported from the liver to extracellular tissues and protects it from oxidation. RBP is a transport protein for vitamin A in the blood, synthesized by the liver, and widely distributed in blood, cerebrospinal fluid, urine, and other body fluids. The determination of retinol binding protein can detect early renal tubular damage and sensitively reflect the degree of damage to the proximal renal tubules. It can also be used as an indicator for early liver damage and monitoring treatment.

Cystatin C (CYSC) is an alkaline glycosylated secretory protein that belongs to the cysteine protease inhibitor family. It has a molecular weight of 13.3kDa. All nucleated cells can produce CYSC, and its production rate is constant. Its secretion and excretion are not affected by any external factors such as gender, age, and diet. The kidney is the only organ that clears CYSC from circulation, and the rate of CYSC generation and its content in the blood are relatively stable and less affected by other factors. Therefore, CYSC is an ideal and reliable endogenous marker for reflecting early changes in glomerular filtration rate (GFR). The FDA has pointed out that this indicator has higher sensitivity and specificity than blood urea nitrogen (BUN) and creatinine (Cr), and emphasizes that this item should be promoted globally. Under normal circumstances, the concentration of CYSC in serum and plasma is 0.51-1.09mg/L (reference range). When renal function is impaired, the concentration of CYSC in the blood changes with changes in glomerular filtration rate. When renal failure occurs, the concentration of CYSC in the blood can increase more than ten times with a decrease in glomerular filtration rate; if renal tubular function is impaired while glomerular filtration rate is normal, it will hinder the absorption and decomposition of CYSC in renal tubules, resulting in an increase in concentration of more than 100 times in urine.

Alpha-1-microglobulin (a1-MG) is a glycoprotein composed of 184 amino acids with a molecular weight of about 31,000 daltons (with a sugar content of about 20%). Due to its covalently bound brown-yellow auxiliary base, 3-hydroxykynurenine, it appears brown-yellow. Free α1-MG in the blood can freely pass through the glomerular filtration membrane and is 95%-99% reabsorbed and metabolized in the proximal renal tubule, with only trace amounts excreted in the final urine. The determination of serum α1-MG can be used as a sensitive indicator for reflecting impaired renal tubular reabsorption function.