Analgesic nephropathy

　　I. Etiology

　　Analgesic addiction caused by long-term abuse of analgesics due to diseases such as rheumatic fever, rheumatoid arthritis, migraine, dysmenorrhea, etc. When analgesics and non-steroidal anti-inflammatory drugs are taken for several years to several decades, and the cumulative dose exceeds 1-2 kg, the disease can occur. The cumulative dose exceeding 6 kg can affect the kidneys in 50%-80% of cases.

　　II. Pathogenesis

　　The pathogenesis of analgesic nephropathy is mainly due to the accumulation of some components in the compound analgesics, such as acetaminophen, in the renal medulla, and the generation of excessive reactive oxygen species during the metabolic process involving the cytochrome P-450 system, while also inhibiting prostaglandin synthesis. The aforementioned biochemical effects of analgesics can lead to the following changes:

　　1. Decreased renal blood flow:Analgesics, as inhibitors of prostaglandin synthase (cyclooxygenase), can reduce the synthesis of prostaglandins by the kidneys, causing vasoconstriction of the renal small blood vessels, especially in the medulla, leading to a decrease in renal blood flow and a decrease in glomerular filtration rate, resulting in ischemic renal papillary necrosis.

　　2. Direct toxic effects on renal tubules:Long-term and high-dose use of analgesics can inhibit the activity of enzymes in renal tubular epithelial cells, directly producing toxic effects on renal tubular epithelial cells.

　　3. Allergic reactions:The use of analgesics may cause local allergic reactions in the renal tissue, leading to renal damage.

　　4. Renal vascular sclerosis:Analgesics can cause sclerosis of the small blood vessels in the renal medulla, which may lead to renal papillary necrosis. The cortical lesions of chronic interstitial nephritis in this disease are secondary to the obstruction of the tubules in the necrotic area of the medulla, and in some cases may not depend on renal papillary necrosis. Apoptosis may be involved in the occurrence of chronic interstitial nephritis in this disease.

　　In clinical prospective studies, it has been confirmed that compound preparations containing propyphenazone still have carcinogenic effects.

　　1. Kidney stones and chronic renal insufficiency: About 60% of patients with this disease have associated urinary tract infections. If there is persistent or recurrent infection, kidney stones may occur. In the late stage, chronic renal insufficiency may occur, with significant renal tubular dysfunction in a few patients, presenting as oliguria type renal failure.

　　2. The main complications of the gastrointestinal system are gastric and duodenal bulb ulcers, gastrointestinal bleeding, gastric perforation, and pyloric stenosis, etc.

　　3. The main complications of the cardiovascular system are cardiac enlargement, heart failure, and malignant hypertension, etc.

　　In addition, it can make the skin appear bronze and cause nervousness, depression, and psychological disorders.

　　I. Renal manifestations

　　This disease is more common in neurotic females aged 40 to 60, with a ratio of 3:1 to 6:1 between females and males. The onset is relatively hidden, and there are usually no obvious symptoms in the early stage. Polyuria and increased nocturia may occur. With the progression of the disease, nephrotic syndrome or renal tubular acidosis may occur, and 50% to 75% of patients have hypertension, which may manifest as malignant hypertension. This may be related to the reduction of medullary antihypertensive substances and the increased activity of renin, angiotensin, and the sympathetic nervous system.

　　The prominent characteristics of this disease are asymptomatic pyuria and renal papillary necrosis. Acute renal papillary necrosis manifests as sudden gross hematuria, renal colic, and severe azotemia. Chronic renal papillary necrosis may not have obvious clinical manifestations. About 60% of patients have associated urinary tract infections. Patients with persistent or recurrent urinary tract infections may develop kidney stones. In the late stage, chronic renal insufficiency may occur, with significant renal tubular dysfunction. A few patients may present with oliguria type renal failure. If the medication is continued, the renal lesions will continue to develop, leading to uremia. About 8% of patients may develop transitional cell carcinoma of the urinary tract, manifested as persistent or intermittent asymptomatic microscopic or gross hematuria.

　　II. Extrarenal manifestations

　　Long-term use of analgesics not only causes kidney damage but can also cause damage to other organs, with the main manifestations as follows.

　　1. Gastrointestinal symptoms:Patients may experience decreased appetite, and in severe cases, gastric and duodenal bulb ulcers may occur, which can lead to gastrointestinal bleeding, gastric perforation, and pyloric stenosis and other complications.

　　2. Cardiovascular system:Cardiac enlargement, heart failure, and cardiovascular symptoms caused by hypertension, such as dizziness, headache, chest tightness, palpitations, and orthopnea may occur.

　　3. Skin changes:Due to the deposition of the metabolite 3-amin-7-ethoxyphenazone of phenacetin in the skin, the skin can become bronze.

　　4. Premature aging manifestations:Increased facial skin wrinkles, skin pigmentation, and graying of hair.

　　5. Mental and neurological symptoms:More common in women aged 40-60, characterized by tension, depression, and psychological disorders.

　　This disease is caused by long-term abuse of analgesic drugs, leading to chronic tubulointerstitial damage and (or) renal papillary necrosis when the cumulative dose exceeds 1-2 kg. Therefore, the key to prevention lies in early detection, timely discontinuation of medication, and active symptomatic treatment, so as to protect renal function and improve the prognosis. Once infection and other complications are found, low-toxicity or non-toxic antibiotics should be actively selected for treatment to control the development and progression of the disease and prevent renal failure.

　　1. Urine examination

　　Urine routine examination may have leukocytes, showing sterile pyuria, with obvious microscopic hematuria or gross hematuria, hematuria often suggests the presence of stones, urinary tract tumors, interstitial cystitis, renal papillary necrosis, or malignant hypertension, atypical red blood cells suggest glomerular damage, generally mild proteinuria can be seen, 24h urine protein quantification

　　2. Renal tubular function test

　　Urine concentration and dilution test function is poor, amino acids, bicarbonate in urine increase, urine pH>6, urine titratable acid decreases, urine N-acetyl-β-D-glucosaminidase (NAG) concentration increases, urine retinol-binding protein (RBP) concentration increases.

　　3. Renal biopsy examination

　　Pathological changes are mainly manifested as chronic interstitial nephritis, and under the microscope, there is diffuse infiltration of lymphocytes and monocytes in the renal interstitium, accompanied by fibrosis, tubular degeneration, atrophy, intimal thickening of renal small arteries, lumen stenosis, vascular sclerosis, ischemic atrophy of glomeruli, periglomerular fibrosis, renal papillary necrosis and calcification foci may occur, and the specific pathological change of analgesic kidney disease is superficial capillary sclerosis of the urinary tract mucosa, which can be observed as a uniform thickening of the capillary basement membrane after iodine acid Schiff (Schiff) staining.

　　4. Imaging examination

　　Early manifestations of urinary tract X-ray examination are dilated renal pelvis, blunted renal calyceal cup mouth, and typical manifestations of renal papillary necrosis in the late stage. Renal pelvis and calyceal filling defects, allowing contrast medium to enter the renal parenchyma and surround the renal papilla to form a typical annular shadow. Renal venography can also show kidney shrinkage, cortical atrophy, renal papillary necrosis in some cases, and renal calcification visible on abdominal film.

　　5. Ultrasound examination

　　It can be found that there is a typical annular calcification of renal papilla around the renal sinus.

　　What foods are good for the body for analgesic kidney disease patients:Kidney disease is recommended to eat chicken, peach, scallion, soybean, pork, chestnut, huoxiang, kidney, bizi ren, oyster yellow, deer tenderloin, deer fetus, deer tail, deer penis, deer horn glue, sea dog kidney, cow kidney, sheep kidney, cow penis, black bean, prepared rehmannia, salt, wuling shen, chicken kidney, duck kidney, quail, starling, chicken kidney herb, deer mouth bead herb.

　　I. Treatment

　　The key to the treatment of this disease lies in early diagnosis, timely discontinuation of medication, and protection of renal function.

　　1. Maintain a certain urine output:The fluid intake of the patient should be ensured to maintain urine output above 2000ml/d, so as to increase drug excretion, reduce the concentration of drugs in the renal medulla, and alleviate renal damage.

　　2. Prevention and treatment of infection:Attention should be paid to preventing the occurrence of infection to avoid exacerbating renal damage, and low-toxic or non-toxic antibiotics should be actively chosen once infection is found.

　　3. Treatment of chronic renal insufficiency:For those with chronic renal insufficiency, dietary control and drug treatment should be given, non-dialysis therapy such as aldehyde oxidized starch, intravenous infusion of essential amino acids, rhubarb preparations, etc., should be adopted, and dialysis treatment or kidney transplantation should be performed if necessary.

　　4. Correction of electrolyte and acid-base imbalance:For those with water, electrolyte imbalance and acidosis, 5% sodium bicarbonate (Sodium Bicarbonate) 125-250ml/d should be given for 1-3 days, and attention should be paid to replenishing blood volume.

　　5. Symptomatic and supportive therapy:Antihypertensive therapy should be actively adopted, and enzyme inhibitors such as Captopril (25mg, 3 times a day, oral) should be used. Enalapril (10mg, once a day, oral); or Benazepril (Lotensin), 5-10mg, once a day, oral, etc., should be used to avoid or use diuretics as little as possible. When urinary tract obstruction occurs due to renal papillary necrosis, antispasmodic and fluid replacement therapy should be given, and if ineffective, surgical removal of necrotic tissue is required.

　　6. Treatment of urinary tract obstruction:The cause of obstruction should be removed in time, if caused by blood clots, alkali drugs can be given (250ml of 5% sodium bicarbonate intravenous infusion), for those caused by stones, ultrasonic lithotripsy or surgical treatment should be performed. In emergency situations, stenting surgery should be performed above the obstruction. When obstruction is combined with infection, effective antibiotic treatment should be chosen. If urinary tract obstruction has caused renal failure or anuria, dialysis treatment can be given to improve the patient's condition before removing the obstructive factors.

　　II. Prognosis

　　If the disease is discovered early, the prognosis is good if the medication is stopped in time and active treatment is given. If chronic renal insufficiency has occurred, it is difficult to reverse.