Nephrotoxic nephritis

　　1. The reasons why toxic renal substances are prone to cause kidney damage

　　1. The kidney blood flow is large. One fourth to one fifth of the total blood flow in the body flows through the kidneys, about 1000 to 1200 ml per minute. Toxic substances enter the kidney with blood flow, which must lead to renal damage.

　　2. Due to the countercurrent multiplication mechanism of the kidney, the concentration of toxic substances in the medulla and renal papilla is increased, so the lesions in the medulla and renal papilla are significant in toxic nephropathy.

　　3. Toxic substances are reabsorbed and excreted by renal tubular epithelial cells, so the concentration of toxic substances in the lumen of renal tubules or in renal tubular epithelial cells is increased, which can directly damage renal tubular epithelial cells.

　　4. The total area of glomerular capillary endothelium is much larger than that of other organs in the body, so immune complexes are prone to deposit in the glomerulus and cause immune renal damage. The mesangial proliferation and deposition of immune substances are caused by the phagocytosis and clearance of toxins by mesangial cells. In addition, when toxic substances pass through the three different filtration membranes of the glomerulus, toxins or immune complexes are deposited in the glomerulus.

　　2. Drug damage

　　Many substances have potential renal toxicity, common endogenous ones include hypercalcemia, hyperphosphatemia, hyperuricemia, and hyperoxaluria, which can all cause interstitial-tubular disease of the kidney. Exogenous ones include heavy metals (lead, cadmium, mercury, gold, uranium, copper, bismuth, thallium, arsenic, lithium, zinc, etc.), chemical toxins (including organic solvents, hydrocarbons, pesticides, disinfectants, and coal tar, etc.), and drugs; almost all drugs have renal toxicity (including antibiotics, antipyretics and analgesics, metal preparations, contrast agents, diuretics, traditional Chinese medicine, and others). Clinically, more common nephrotoxic drugs include:

　　1. Drugs that directly damage the kidneys. Aminoglycoside antibiotics (such as gentamicin, kanamycin, streptomycin, etc.), cefalosporins, polymyxins, vancomycin, bacitracin, purpurin, amphotericin B, tetracyclines, demeclocycline, sulfonamides, gold preparations, penicillamine, ethylenediaminetetraacetic acid (EDTA); indomethacin, ibuprofen, phenacetin, paracetamol, salicylates; methotrexate; contrast agents, and others.

　　2. Drugs that manifest as allergic renal damage include: penicillin class, cefalosporin class, sulfonamides, rifampicin, aminobenzoic acid, furosemide, thiazide diuretics, azathioprine, allopurinol, trimethadione, phenytoin sodium, phenobarbital, and others.

　　3. Drugs that manifest as crystalline nephropathy or obstructive urinary tract nephropathy include: sulfonamide drugs.

　　4. Biological toxins (toxins of animal and plant origin), including bee venom, snake venom, raw fish bile, mushroom toxins, and pollen, etc.

　　5. Physical factors such as radiation, heatstroke, electric shock, and others.

　　1. Nephrotic syndrome caused by infection

　　The main reasons for the decline in resistance to infection are mainly due to:

　　1. Large amounts of IgG are lost in the urine.

　　2. The lack of factor B (component of the alternative complement pathway) leads to a defect in the immune调理 function against bacteria.

　　3. During malnutrition, the body's non-specific immune response ability is weakened, causing damage to the body's immune function.

　　4. Large amounts of transferrin and zinc are lost in the urine. Transferrin is essential for maintaining normal lymphocyte function, and the concentration of zinc ions is related to thymus hormone synthesis.

　　5. Local factors. Pleural effusion, ascites, and severe edema caused by skin swelling can lead to the dilution of local body fluid factors, weakened defense function, and are all susceptible factors for patients with nephrotic syndrome. Before the advent of antibiotics, bacterial infection was one of the main causes of death in patients with nephrotic syndrome. Severe infections mainly occur in children and the elderly, and are less common in adults. Common clinical infections include: primary peritonitis, cellulitis, respiratory tract infections, and urinary tract infections. Once the diagnosis of infection is established, immediate treatment should be administered.

　　Secondly, hypercoagulability and venous thrombosis

　　Nephrotic syndrome exists in a hypercoagulable state, mainly due to changes in coagulation factors in the blood. This includes a decrease in factors IX and XI, and an increase in factors V, VIII, X, fibrinogen, beta-thromboglobulin, and platelet levels. The adhesion and aggregation of platelets are enhanced. Antithrombin III and antifibrinolytic activity are reduced. Therefore, the increase in procoagulant and procoagulation factors, the decrease in anticoagulant and anticoagulation factors, and the damage to the fibrinolysis mechanism are the reasons for the hypercoagulable state in nephrotic syndrome. The use of antibiotics, hormones, and diuretics is a worsening factor for venous thrombosis, with hormones acting through coagulation proteins, while diuretics increase blood viscosity by concentrating the blood.

　　In nephrotic syndrome, the risk of renal vein thrombosis increases when plasma albumin is less than 2.0g/dl. Most believe that thrombosis first forms in small veins, then extends, eventually involving the renal vein. Renal vein thrombosis can occur in up to 50% of patients with membranous nephropathy, and in other pathological types, the incidence rate is 5% to 16%. Acute-type patients with renal vein thrombosis may present with sudden onset of flank pain, hematuria, leukocyteuria, increased urine protein, and decreased renal function. Chronic-type patients may have no symptoms, but post-thrombotic renal congestion often aggravates proteinuria or results in poor response to treatment. Due to thrombus detachment, extrarenal embolic symptoms are common, and pulmonary embolism may occur. It may also be accompanied by tubular dysfunction, such as glycosuria, aminoaciduria, and tubular acidosis. Definitive diagnosis requires renal venography. Non-invasive examinations such as Doppler ultrasound, CT, and IMR are also helpful for diagnosis. Elevated plasma beta-thromboprotein suggests potential thrombosis, and increased blood alpha2-antifibrinolytic protein is also considered a sign of renal vein thrombosis. The incidence rate of peripheral deep vein thrombosis is about 6%, commonly occurring in the deep veins of the lower legs, with only 12% presenting with clinical symptoms, and 25% detectable by Doppler ultrasound. The incidence rate of pulmonary embolism is 7%, with 12% still asymptomatic. Other venous involvement is rare. Arterial thrombosis is less common, but in children, despite the relatively low incidence of thrombosis, arterial involvement is as common as venous involvement.

　　3. Acute renal failure:

　　Acute renal failure is the most serious complication of nephrotic syndrome and often requires dialysis treatment. Common causes include:

　　1. Hemodynamic changes: nephrotic syndrome often has hypoproteinemia and vascular lesions, especially in elderly patients with renal arteriosclerosis, who are very sensitive to decreases in blood volume and blood pressure. Therefore, after acute hemorrhage, vomiting, diarrhea, fluid loss, surgical injury, ascites, excessive diuresis, and the use of antihypertensive drugs, blood pressure can further decrease, leading to a sudden decrease in renal perfusion, thereby reducing glomerular filtration rate, and due to acute ischemia, tubular epithelial cell swelling,变性 and necrosis, leading to acute renal failure.

　　2. Renal interstitial edema: hypoproteinemia can cause peripheral tissue edema, which can also lead to renal interstitial edema. Renal interstitial edema compresses the renal tubules, increasing the hydrostatic pressure in the Bowman's capsule of the proximal tubules, and decreasing GFR.

　　3. Drug-induced acute interstitial nephritis.

　　4. Bilateral renal vein thrombosis.

　　5. Vasoconstriction: some patients with nephrotic syndrome show increased renin concentration during hypoproteinemia, which causes vasoconstriction of the renal arteries, leading to a decrease in GFR. This condition is more common in the elderly with vascular lesions.

　　6. Concentrated protein casts block the distal renal tubules: it may be one of the mechanisms involved in the acute renal failure of nephrotic syndrome.

　　7. During nephrotic syndrome, renal glomerular epithelial foot processes are widely fused, slit pores disappear, resulting in a significant reduction in the effective filtration area.

　　8. Rapid progressive glomerulonephritis.

　　9. Ureteral obstruction.

　　4. Renal tubular dysfunction

　　The renal tubular function of nephrotic syndrome is reduced, which is more common in children. The mechanism is considered to be the large reabsorption of filtered proteins by the renal tubules, which damages the tubular epithelial cells. It is often manifested as glycosuria, aminoaciduria, hyperphosphaturia, tubular nephrogenic hypokalemia, and hyperchloremic acidosis. The presence of multiple renal tubular dysfunction often indicates a poor prognosis.

　　5. Abnormalities in bone and calcium metabolism

　　In nephrotic syndrome, the VitD-binding protein (Mw65000) and VitD complexes in the blood circulation are lost in urine, resulting in a decrease in blood 1,25(OH)2VitD3 levels, leading to poor intestinal calcium absorption and bone tolerance to PTH, so nephrotic syndrome often presents with hypocalcemia, and sometimes fibrocystic osteitis caused by osteomalacia and hyperparathyroidism. The bone malnutrition that occurs in renal failure associated with the progression of nephrotic syndrome is generally more severe than that caused by uremia without nephrotic syndrome.

　　6. Endocrine and metabolic abnormalities

　　Nephrotic syndrome loses thyroid-binding globulin (TBG) and corticosteroid-binding globulin (CBG) in urine. Clinically, thyroid function may be normal, but serum TBG and T3 are often decreased, and free T3 and T4, TSH levels are normal. Due to the decrease in CBG and 17-hydroxycorticosterone in the blood, the ratio of free to bound cortisol can change, and the tissue response to pharmacological doses of cortisol is different from normal. Due to the loss of ceruloplasmin (Mw151000), transferrin (Mw80000), and albumin from the urine, nephrotic syndrome often has decreased serum copper, iron, and zinc concentrations. Zinc deficiency can cause impotence, taste disturbance, difficult wound healing, and impaired cell-mediated immunity. Continuous reduction in transferrin can cause refractory anemia with small cell hypochromia in clinical treatment. In addition, severe hypoproteinemia can lead to persistent metabolic alkalosis due to a decrease of 10g/L in plasma protein, which leads to a corresponding decrease of 3mmol/L in plasma bicarbonate.

　　The clinical manifestations of toxic nephropathy vary due to different pathogenesis, and the common manifestations are:

　　1. Symptom complex of tubular dysfunction

　　Distal tubular dysfunction is manifested as nephrogenic diabetes insipidus: polydipsia, polyuria, seen in lithium, fluorides, demeclocycline-induced nephrotic kidney disease; renal tubular acidosis: hyperchloric acidosis, electrolyte and water balance disorders (such as hypokalemia or hyperkalemia, hyponatremia, hypocalcemia, polyuria, polydipsia, etc.); renal osteodystrophy: rickets or osteomalacia, renal calcification or renal calculi, etc., seen in nephrotic kidney disease caused by amphotericin B toxicity.

　　2. Acute renal failure syndrome

　　Mild cases may only have trace amounts of urinary protein, red and white blood cells in urine, and casts, oliguria or anuria with azotemia. Severe cases may present with typical acute renal failure syndrome, which is seen in aminoglycoside antibiotics, nephrotic kidney disease caused by inorganic mercury toxicity.

　　3. Acute allergic interstitial nephritis

　　Systemic allergic manifestations such as fever, rash, lymphadenopathy, joint pain, increased eosinophils in blood, increased eosinophils in urine, and also massive proteinuria presenting as nephrotic syndrome, or hematuria. In severe cases, acute renal failure may occur, which is seen in various drugs, especially in penicillin group, sulfonamides, antituberculosis drugs, and other toxicities.

　　4. Chronic renal failure syndrome

　　临床表现与其他原因引起的中毒性肾病相似，有时停止接触毒物后肾功能仍持续缓慢恶化，见于慢性铅中毒肾病。

　　Clinical manifestations are similar to those caused by other reasons, and sometimes the renal function continues to deteriorate slowly after stopping contact with the toxic substance, which is seen in chronic lead poisoning nephritis.

　　5. Nephritis and Nephrotic Syndrome

　　1. Stop contacting the toxic substance.

　　2. Promote the excretion of toxins, which can be done by intravenous infusion, the use of detoxifying drugs, and dialysis treatment when necessary. Those with small molecular weight, less protein binding, and uniform distribution in the body can be excreted through hemodialysis. Those with high protein binding are more effective with peritoneal dialysis. Plasma exchange therapy should be used with caution.

　　3. Symptomatic treatment.

　　4. Take measures according to the type of kidney damage. For example, in the case of acute drug-induced allergic interstitial nephritis, which presents as nephrotic syndrome, and there are no contraindications, adrenal cortical hormones, immunosuppressants, or adrenal cortical hormone pulse therapy can be used. Patients with renal failure can be treated with peritoneal dialysis or hemodialysis.

　　For suspected kidney disease patients, blood routine, urine routine, Doppler ultrasound of both kidneys, renal pelvis venography; renal scan; renal biopsy (electron microscopy report); urine test; renal function test, etc. should be performed.

　　Food Therapy Prescriptions:

　　1. A crucian carp weighing about 250 grams, open the abdomen to remove the internal organs and clean it, stuff it with 10 grams of minced garlic, wrap it with clean white paper, soak it with water, and then roast it in bran. Eat the fish and garlic together; if possible, eat one a day. Suitable for chronic nephritis and malnutrition edema.

　　2. 30 grams of glutinous rice and 20 grams of Shuizhi, 10 white fruits (shell removed), cook to make porridge. Take 1 dose daily, with a course of 10 days. This porridge has the effect of invigorating the spleen and kidneys, and consolidating and condensing essence.

　　3. One pig kidney, 20 grams each of Dangshen, Huangqi, and Shuizhi. Cut the pig kidney open, remove the fascia and clean it, then cook it with the medicine to make a soup for consumption. This recipe is suitable for the recovery period of chronic nephritis and patients with spleen and kidney Qi deficiency.

　　1. Stop contacting the toxic substance.

　　2. Promote the excretion of toxins, which can be done by intravenous infusion, the use of detoxifying drugs, and dialysis treatment when necessary. Those with small molecular weight, less protein binding, and uniform distribution in the body can be excreted through hemodialysis. Those with high protein binding are more effective with peritoneal dialysis. Plasma exchange therapy should be used with caution.

　　3. Symptomatic treatment.

　　4. Take measures according to the type of kidney damage. For example, in the case of acute drug-induced allergic interstitial nephritis, which presents as nephrotic syndrome, and there are no contraindications, adrenal cortical hormones, immunosuppressants, or adrenal cortical hormone pulse therapy can be used. Patients with renal failure can be treated with peritoneal dialysis or hemodialysis.