Analgesic nephropathy

Analgesic nephropathy Analgesic nephropathy (AN) is a chronic tubulointerstitial damage and/or renal papillary necrosis caused by long-term abuse of analgesic drugs, which is more than 1 to 2 kg. This disease is called analgesic nephropathy. Or chronic tubulointerstitial nephritis caused by analgesics. basic knowledge Proportion of disease: 1% of patients taking sedatives Susceptible people: no specific population Mode of infection: non-infectious Complications: kidney stones, urinary tract infection, gastrointestinal bleeding, pyloric obstruction, hypertension

Analgesic nephropathy

(1) Causes of the disease

Due to rheumatic fever, rheumatoid arthritis, migraine, dysmenorrhea and other diseases, long-term abuse of painkillers caused by painkillers, when taking painkillers and non-steroidal anti-inflammatory drugs for several years to decades, the cumulative amount exceeds When 1 to 2 kg, you can get sick. If the cumulative amount exceeds 6 kg, the kidney may be affected by 50% to 80%.

(two) pathogenesis

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

1. Renal blood flow reduction painkiller as a prostaglandin synthetase (epoxidase) inhibitor, which can reduce the synthesis of prostaglandins in the kidney, small blood vessels contract, especially the small blood vessels of the medulla contract, causing renal blood Decreased flow and decreased glomerular filtration rate lead to renal ischemic renal papillary necrosis.

2. Direct toxicity to renal tubules Long-term high-dose analgesics can inhibit the activity of renal tubular epithelial cells and directly produce toxic effects on renal tubular epithelial cells.

3. Allergic reactions Taking painkillers may cause local allergic reactions in kidney tissue, which may lead to kidney damage.

4. Small renal arteriosclerosis analgesics can cause small blood vessels in the renal medulla, which may lead to necrosis of the kidney. The cortical lesions of chronic interstitial nephritis in this disease are secondary to the obstruction of tubules in the medullary necrosis area. In some cases, Depending on renal papillary necrosis, apoptosis may be involved in the development of chronic interstitial nephritis.

It has been confirmed in clinical prospective studies that the combination preparation containing phenacetin is still carcinogenic.

Analgesic nephropathy prevention

The key to this disease is early detection, timely withdrawal and active symptomatic treatment to protect kidney function and improve prognosis. Once infection and other complications are found, low-toxic or non-toxic antibiotics should be actively used to control the development and aggravation of the disease. So as not to cause kidney failure.

Analgesic nephropathy complications Complications, kidney stones, urinary tract infection, gastrointestinal bleeding, pyloric obstruction, hypertension

1. Kidney stones and chronic renal insufficiency About 60% of patients with urinary tract infections, such as persistent or recurrent episodes may be complicated by kidney stones, chronic renal insufficiency in the late stage, a small number of patients have significant renal tubular dysfunction, manifested as Oliguria-type renal failure.

2. The main complications of the digestive tract are gastric and duodenal ulcer, gastrointestinal bleeding, gastric perforation and pyloric obstruction.

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

In addition, the skin can be made of bronze and mental stress, depression, and psychological disorders.

Analgesic nephropathy symptoms common symptoms polyuria azotemia nocturia increased appetite loss facial skin wrinkles increased hematuria palpitations chest dizziness dizziness

1. Kidney performance

The disease occurs in women with neuropathy from 40 to 60 years old. The ratio of female to male is 3:1 to 6:1. The onset is more insidious. There are no obvious symptoms in the early stage. There may be more urine and nocturia, as the disease progresses. Development may occur with sodium-deficient nephropathy or renal tubular acidosis, 50% to 75% of patients have high blood pressure, and may present with malignant hypertension, possibly with decreased medullary antihypertensive substances and renin, vascular tension It is related to the increased activity of the sympathetic nervous system.

The prominent features of this disease are aseptic pyuria and renal papillary necrosis. Acute renal papillary necrosis is characterized by sudden gross hematuria, renal colic and severe azotemia. Chronic renal papillary necrosis can have no obvious clinical manifestations. % of patients with urinary tract infection, persistent or recurrent urinary tract can be complicated by kidney stones, late renal dysfunction, significant renal tubular dysfunction, a small number of patients with oliguric renal failure, such as continued medication, then Renal lesions continue to develop, leading to uremia, and approximately 8% of patients may develop urinary tract transitional epithelial cancer, which is characterized by persistent or intermittent painless microscopic or gross hematuria.

2. Extrarenal performance

Long-term use of painkillers can not only cause kidney damage but also cause damage to other organs, mainly as follows.

(1) digestive tract symptoms: patients may have loss of appetite, severe cases of stomach and duodenal ulcer, can cause gastrointestinal bleeding, gastric perforation and pyloric obstruction and other complications.

(2) cardiovascular system: heart enlargement, heart failure and cardiovascular symptoms caused by high blood pressure, such as dizziness, headache, chest tightness, palpitations, sitting breathing, etc.

(3) Skin changes: Since the metabolite of phenacetin, 3-amino-7-ethoxyphenazine, is deposited on the skin, the skin can be bronzed.

(4) Premature aging performance: increased facial wrinkles, pigmentation of the skin, and gray hair.

(5) Mental and neurological symptoms: more common in women aged 40 to 60 years, manifested as mental stress, depression, and psychological disorders.

Analgesic nephropathy

Urine check

Urine routine examination may have white blood cells, aseptic pyuria, obvious microscopic hematuria or gross hematuria, hematuria often suggests stones, urothelial tumors, interstitial cystitis, renal papillary necrosis or malignant hypertension, abnormal red blood cell tips Small ball damage, generally seen mild proteinuria, 24h urine protein quantitative <2g, mainly low molecular proteinuria, sometimes up to the degree of kidney disease, proteinuria up to 3.0g / d, often mixed, small ball, Tubulous and 2-microglobulin urine, the latter is a marker of tubule proteinuria, urine cytology is conducive to the discovery of urinary tract tumors, urine sugar can be positive.

2. Renal tubular function test

Poor urine concentration dilution test function, urinary amino acid, bicarbonate increase, urine pH>6, urine titratable acid decreased, urine N-acetyl--D-glucosidase (NAG) concentration increased, urinary retinol The binding protein (RBP) concentration is elevated.

3. Kidney biopsy

Pathological changes were mainly caused by chronic interstitial nephritis. Microscopically, diffuse lymphocytes and mononuclear cells infiltrated with interstitial cells, accompanied by fibrosis, tubular degeneration, atrophy, intimal thickening of renal arterioles, and stenosis Small blood vessel sclerosis, glomerular ischemic atrophy, fibrosis around the ball, renal papillary necrosis and calcification can occur, specific pathological changes of painkiller nephropathy are superficial capillary hardening of urinary tract mucosa, with periodic acid Schiff staining showed a uniform thickening of the capillary basement membrane.

4. Image inspection

The early urinary tract X-ray examination showed a widening of the renal pelvis, dullness of the renal pelvis, and a typical manifestation of renal papillary necrosis in the late stage. The renal pelvis and renal pelvis were filled with defects, which caused the contrast agent to enter the renal parenchyma and surrounded the renal nipple. The annular shadow, intravenous pyelography can also show renal shrinkage, cortical atrophy, renal nipple necrosis in some cases, renal calcification in the plain plain.

5. Ultrasound examination can be found to have typical garland-like renal papillary calcification around the renal sinus.

Diagnostic identification of analgesic nephropathy

Diagnostic criteria

For long-term analgesics, patients with chronic renal failure who are complained of various physical discomfort should consider analgesic nephropathy, such as a history of long-term abuse of analgesics, with a cumulative amount greater than 1 to 2 kg, interstitial Clinical manifestations of nephritis and renal papillary necrosis, ie polyuria, nocturia, loss of sodium nephritis, renal tubular acidosis, aseptic pyuria with renal insufficiency; necrotic renal papillary tissue found in the urine; intravenous pyelography See the ring shadow of renal papillary necrosis; accompanied by fever, hematuria, acute low back pain, urinary tract cramps and urinary tract obstruction; renal biopsy suggests chronic tubulointerstitial inflammation with small sclerosis, ultrasound examination found typical around the renal sinus When the garland-like renal papilla is calcified, it can be diagnosed as an analgesic nephropathy.

Differential diagnosis

The disease should be differentiated from the following diseases.

1. Balkan nephropathy This disease is an epidemic of unknown cause. It occurs mostly in Yugoslavia, Bulgaria and other countries. It is more common in adults over 30 years old, often without edema, hypertension and fundus changes.

2. Chronic obstructive nephropathy This disease is caused by a variety of reasons, the clinical manifestations of renal insufficiency, urinary tract infection or extrarenal signs, B-ultrasound and X-ray examination can be found in urinary tract or tumor.

3. Patients with acute pyelonephritis often have fever, urinary tract irritation sign, positive renal pain, and positive urine culture in the middle.

4. Diabetic nephropathy patients have a history of diabetes for many years, kidney performance is mainly proteinuria, severe cases can be manifested as nephrotic syndrome and renal insufficiency, fundus examination with microaneurysms, renal biopsy can help identify.

5. Analgesic nephropathy Kidney papillary necrosis should be differentiated from reflux nephropathy (RN) renal papillary necrosis. The disease needs to be differentiated from tuberculosis, medullary sponge kidney and other diseases that cause medullary calcification.

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