Kidney damage in leptospirosis

　　1. Etiology

　　The pathogen Leptospira (abbreviated as leptospires) is the main cause of this disease. Leptospires have 12 to 18 spirals in shape, with hooks at both ends, showing active rotational movement and having strong penetrating ability. Leptospires can grow slowly under aerobic conditions in rabbit serum-containing culture medium, but the positive rate can be significantly increased if inoculated into sensitive animals (such as guinea pigs and hamsters). They can survive for 1 to 3 months under appropriate conditions in vitro and are very sensitive to cold, dryness, and general disinfectants. Currently, leptospires are mainly classified based on serological reactions. China has 18 serogroups and 70 serotypes, and in recent years, the application of monoclonal antibody technology for leptospira classification has been carried out, and the preliminary success has been achieved in the classification and identification of leptospires using DNA probes.

　　After the leptospires enter the human body through the skin, they can replicate through the lymphatic system or directly enter the blood circulation, producing toxins and causing systemic toxic blood symptoms. The invasive leptospires are widely distributed in various visceral organs in the human body, but the amount of leptospires in the organs is not completely consistent with the degree of organ damage. The leptospires themselves have no direct pathogenic effect, and the interaction between the leptospires and organ tissues is the main cause of tissue damage and capillary damage, leading to serious functional disorders of important organs with the progression of the disease.

　　Taking the leptospirosis with jaundice and hemorrhagic type as an example, the hemorrhagic tendency is not caused by a decrease in prothrombin or platelets, but is related to capillary damage caused by vascular endothelial injury. Pathological examination, such as vascular endothelial swelling, sarcoplasmic reticulum expansion, and mitochondria swelling, these initial responses of endothelial cell necrosis can appear in various organs, indicating that changes in the function and permeability of the endothelium have occurred before the necrosis of the endothelium. The necrosis of the actual liver cells and the mild inflammatory response suggest that the dysfunction of liver function is at the subcellular level of liver cells, caused by enzyme dysfunction. In the study of experimental acute renal failure, it is often found that there is significant ischemia or renal injury caused by toxins, which is related to the infection-related regulatory mechanism of the patient's leptospirosis sepsis and the enhanced local infection response of the whole body, also suggesting that leptospirosis is one of the renal-loving pathogens.

　　The transmembrane potential difference, water, and sodium-potassium permeability between the luminal side of the renal tubules and the lateral side of the epithelial cells were measured by the microperfusion technique of the renal tubules. Abnormalities in these indicators were found in the leptospirosis model animals, but they returned to normal after the addition of vasopressin, suggesting that the renal tubular urine concentration function in leptospirosis-related kidney disease is abnormal. In addition to the sodium reabsorption impairment in the proximal renal tubules, the decreased water permeability due to the weakened responsiveness of the medullary collecting ducts to vasopressin may also be an important reason.

　　2. Pathogenesis

　　In recent years, new views have been proposed on the pathogenesis of leptospirosis, believing that after leptospires enter the human body, they are phagocytosed and dissolved by macrophages, releasing a glycoprotein component, that is, leptospiral toxin, which has the effect of inhibiting Na-K-ATPase. This cellular-level action is closely related to the electrolyte imbalance, arrhythmia, and diarrhea in clinical leptospirosis. It is further proposed that Na-K-ATPase is the specific target of this toxin because the glycoprotein component of leptospires has the same affinity and inhibitory effect on all Na-K-ATPase isomers.

　　Recently, it has been found that the lipid peroxidation of the cell membrane plays an important role in the occurrence of vascular lesions in leptospirosis. There is also evidence that certain components of the outer membrane of renal tubular epithelial cells may directly participate in the induction and maintenance of the immune mechanism of leptospirosis interstitial nephritis.

　　The clinical manifestations of leptospirosis can be divided into influenza typhoid type, pulmonary hemorrhagic type, jaundice and hemorrhagic type, renal failure type, and meningoencephalitis type, among which the pulmonary hemorrhagic type can be divided into common pulmonary hemorrhagic type and diffuse pulmonary hemorrhagic type. The latter is dangerous, with a high mortality rate. Depending on the clinical type, the main complications are high fever, meningitis, jaundice, hemorrhage, acidosis, and renal failure.

　　The incubation period of leptospirosis is 1-2 weeks, the longest can reach 4 weeks. Early symptoms may include fever, myalgia (especially pain and tenderness in the gastrocnemius), general weakness, conjunctival congestion, and lymphadenopathy. It has characteristic

　　Kidney damage associated with leptospirosis can be accompanied by influenza typhoid type, jaundice and hemorrhagic leptospirosis. If it occurs alone, it is renal failure type. The clinical manifestations are mainly oliguria, proteinuria, a small number of leukocytes, red blood cells, casts in urine, and a few severe patients have progressive deterioration of the disease, showing anuria, acidosis, renal failure, uremia. Generally, kidney damage associated with leptospirosis has a good prognosis, and most patients recover through oliguria and polyuria phases.

　　1. Due to the continuous expansion of new epidemic areas, epidemic monitoring should be done in the south to monitor rodent density, rodent virus carriage rate, and susceptible populations, and in the north, pig feces and urine management should be done to prevent the overflow of pig feces and urine during the rainy season or flood season, which may cause the spread and epidemic of the disease. Most areas in China are prone to outbreaks and epidemics in the rainy and warm summer and autumn seasons. Humans are generally susceptible to leptospirosis.

　　2. Maintain food and personal hygiene to prevent the contamination of food by rodent excrement, and avoid touching rodents and their excrement with your hands. During animal experiments, prevent being bitten by large and small rats. Most rural areas in China have the habit of raising pigs, and it should be avoided to closely contact between humans and animals, pay attention to personal hygiene to prevent infection.

　　One, Routine examination

　　1, Blood routine:Blood leukocytes are slightly to moderately increased, mostly (10-20) × 10^9/L, and in cases of jaundice and hemorrhagic type, it can reach as high as 60 × 10^9/L. Neutrophils can account for 80% to 95%, and the erythrocyte sedimentation rate increases. When there is kidney damage, blood BUN and Scr increase.

　　2, Urinalysis:Early urine may contain a small amount of protein, red blood cells, white blood cells, and casts.

　　3, Blood biochemistry:When renal failure occurs, the blood potassium and sodium levels of patients are all lower than normal, and the serum potassium and sodium levels of some patients are lower than those of patients with simple acute tubular necrosis. The cause may be related to the enhanced potassium excretion by the adrenal cortex hormone.

　　Two, Specific diagnostic tests

　　1, Precipitation test (microscopic precipitation test):Using live bacteria of Leptospira standard strain as antigen, mixed with patient serum and observed under a microscope. If there is a specific antibody present, the agglutination phenomenon can be seen. This test is specific and is currently the most commonly used test for diagnosing the disease. It usually appears positive within 7 to 8 days after the onset and gradually increases, and its titer reaches above 1:400 or the titer of double serum increases by more than 4 times, which has diagnostic significance.

　　2, Enzyme-linked immunosorbent assay (ELISA):This method has high specificity and is more apparent than the positive appearance of the precipitation test and more sensitive. It is worth promoting in areas with conditions.

　　3, Monoclonal Antibodies (McAb):Production of Leptospira group-specific or serotype-specific McAb by hybridoma technology is much better than the currently used conventional immunodiagnostic serum products in terms of specificity, sensitivity, etc., and has a large production batch, is easy to standardize, and is a very valuable and promising specific diagnostic method.

　　One, Leptospirosis dietary recipes

　　1, Drug: 250 grams of fresh bamboo root.

　　Usage: Decoction, take 3 times a day, 1 dose per day.

　　2, Drug: 50 grams of Siegesbeckia whole grass.

　　Usage: Decoction, 1 dose per day, taken twice.

　　Two, What is the best to eat for kidney damage caused by Leptospirosis

　　Diet should be light, and attention should be paid to diet when the kidney function is damaged. It is necessary to consume an appropriate amount of sugar, protein, and inorganic salts, but it is imperative not to over-consume.

　　Three, What not to eat for kidney damage caused by Leptospirosis

　　1, When the kidney is damaged, many foods should not be consumed in excess, and water should not be consumed excessively.

　　2, Beans (red beans, mung beans, soybeans, broad beans, kidney beans, mung bean sprouts), and bean products (tofu, bean curd, soy milk).

　　3, Tofu products (tofu, tofu sticks, roasted bran), stone fruits (watermelon seeds, peanuts, walnuts, cashews, chestnuts) and others.

　　4, Processed canned foods, cured and smoked products, pickled vegetables, sauerkraut, salted vegetables, and instant foods.

　　5, High-potassium fruits (bananas, tomatoes, jujubes, oranges, tangerines, mangoes, persimmons, melons, grapefruits, star fruits).

　　6. High aluminum diet (tea, cheese, tea infusion, steamed cakes cooked in aluminum containers).

　　7. High purine diet (meat juice, beans, concentrated meat soup, lean meat, duck meat, brain, mushrooms, internal organs, sardines, eels, asparagus).

　　1. Treatment

　　The treatment for renal failure is the same as for hemorrhagic fever.

　　Generally, kidney disease related to leptospirosis occurs on the fourth day of the disease course, so if leptospirosis is suspected, penicillin G (Penicillin G) should be used immediately as the first choice, and the earlier it is used, the better the effect. This drug has a rapid killing effect on leptospirosis. The common dose is 400,000 units, intramuscular injection, once every 6 to 8 hours, for 7 to 10 days, and some patients may experience Herxheimer reaction (a reaction that worsens after treatment) after penicillin treatment. The Herxheimer reaction usually occurs within 0.5 to 4 hours after the first dose injection, characterized by sudden chills, high fever, or hyperpyrexia, followed by profuse sweating, rapid drop in fever, and in severe cases, hypotension or shock. To reduce or avoid the occurrence of Herxheimer reaction, the initial dose of penicillin should be small (50,000 to 200,000 units), and the dose should be increased after that. For those allergic to penicillin, doxycycline (doxycycline) can be used, and it is best to avoid drugs that damage the liver and kidney function, such as tetracycline, gentamicin, and others.

　　The main cause of ischemia-reperfusion injury is related to intracellular calcium overload caused by calcium ion influx, therefore, the use of calcium channel blocking drug verapamil by intravenous injection, combined with the administration of potent diuretics, in the treatment of acute renal failure related to leptospirosis, has the effects of improving glomerular filtration rate (GFR), reducing serum creatinine, and increasing urine output.

　　Regarding the application of dialysis in kidney failure related to leptospirosis, peritoneal dialysis can generally be used, but when there is severe azotemia or (and) intestinal paralysis, hemodialysis should be considered. If intravenous hyperalimentation can be used in combination, the effect will be better. If the patient has a tendency to hemorrhage, small-dose heparin or heparin-free dialysis can be used. For severe leptospirosis patients with poor liver and kidney function, the above treatment plan can also significantly reduce the mortality rate.

　　2. Prognosis

　　The prognosis of kidney disease related to leptospirosis is generally good, with most patients able to smoothly pass through the oliguria and polyuria periods and recover slowly.