Heavy metal toxicity nephropathy

Introduction to heavy metal toxic nephropathy Heavy metal nephropathy (heavymetalnephropathy) is an acute, chronic kidney injury caused by prolonged exposure to metals. Heavy metal toxic kidney disease is closely related to occupational exposure and environmental exposure to heavy metals. Because most heavy metals have nephrotoxicity. Kidney damage caused by heavy metals is related to individual quality, heavy metal concentration and length of contact. The renal damage can be acute or chronic, and glomeruli and renal tubules can be involved. basic knowledge The proportion of illness: the incidence rate is about 0.005% Susceptible people: no specific population Mode of infection: non-infectious Complications: anemia, jaundice, gout

Causes of heavy metal toxic nephropathy

Due to long-term occupational exposure, environmental pollution, misuse and application of heavy metal preparations, heavy metals are absorbed into the body through the digestive tract, respiratory tract or skin, causing kidney damage. Heavy metal protein conjugates are reabsorbed by proximal tubules after glomerular filtration. Protein is decomposed here, heavy metals are released and toxic effects occur. Among other factors related to small tube heavy metal damage, the most important may be the affinity of heavy metals with the kidney, half-life and the toxicity of heavy metals themselves.

Heavy metal toxicity (25%):

Most heavy metals have direct toxic effects and are closely related to the dose. When urine containing heavy metals flows through the proximal convoluted tubules, the proximal convoluted tubule cells become the main target organ for heavy metal toxicity, and the proximal convoluted tubules reabsorb and excrete, thus making the tubules Epithelial cells undergo vacuoles and degeneration and necrosis.

Renal tubular dysfunction (15%):

The direct toxic effects of heavy metals cause renal tubular dysfunction or acute tubular necrosis, or hemolytic uremic syndrome caused by hemolysis, slowing the flow of urine through dense plaques, increasing urinary sodium, activating renin, angiotensin System, leading to renal vasospasm, renal ischemia, and kidney damage through intracellular calcium ion accumulation, phosphatase activation, arachidonic acid product production, oxygen free radical production, etc., such as heavy metal lead toxic nephropathy, lead After absorption by the human body, the concentration of kidney and bone is the highest, and the high concentration of blood lead is consistent with recent lead exposure, while the normal blood lead concentration does not exclude lead exposure in the past, nor does it exclude the increase of lead load in the body. After the filtered plasma ligand-bound lead is filtered through the glomerulus, it is mainly reabsorbed in the proximal tubule, and the lead excretion in the kidney is also transported through the renal tubule. The lead can pass freely through the luminal surface and the basal plane of the tubular cell membrane. In the cytoplasm, lead and a protein combine to form an insoluble metalloprotein complex, which precipitates in the nucleus to form a characteristic eosinophilic inclusion body visible by optical microscopy. Some characteristics of the protein has been recognized, this protein is rich in glutamic acid, aspartic acid, glycine, toxic effects of lead are mainly inhibits mitochondrial oxidative phosphorylation.

Immune damage (20%):

Certain heavy metals, such as mercury, gold, etc., can damage kidney tissue, altering its antigenicity, producing autoantibodies, and causing glomerular immune damage.

Drinking alcohol may enhance the nephrotoxicity of lead. The nephrotoxicity of the two may have synergistic effects. The blood lead level and tubular function may be seen in patients with chronic alcoholism.

It is currently believed that potential or clinically significant lead poisoning can develop into chronic renal failure, and epidemiological evidence supporting this understanding is:

(1) Chronic renal failure is high in the composition ratio of death in lead exposure population.

(2) The follow-up results of children with acute lead poisoning in Queensland, Australia, mostly died of chronic renal failure.

(3) The incidence of chronic renal failure is high in people who drink illegally brewed whiskey (such as the use of a cooler containing a large amount of lead) in the southern United States, but the results of several years of biological monitoring of occupational lead contacts have failed to verify the above. Evidence, the interpretation of the aforementioned contradictory findings, suggests that lead toxicity may be enhanced by other risk factors such as other metals, drugs, alcohol, and individual quality.

Pathophysiological studies suggest that lead also has a hypertensive effect, that lead can reduce renal perfusion, while peripheral resistance increases; acute stimulation of the amount of cells in the juxtaglomerular can be increased by lead; and can cause increased alpha-adrenergic activity The relationship between lead and arterial hypertension is complex. At present, it is believed that lead-induced hypertension may be through a calcium-dependent mechanism because calcium and phosphorus in the diet are associated with lead reabsorption.

Heavy metal toxic kidney disease prevention

The key to heavy metal poisoning is prevention, avoiding exposure to various heavy metals that are easy to cause acute toxic liver and kidney dysfunction, and can effectively prevent the occurrence of this disease. Once symptoms appear, stop contact immediately. Acute poisoning should be immediately gastric lavage, and antidote should be applied. And emergency dialysis treatment, efforts to prevent systemic and renal damage increased and lead to acute death.

Heavy metal toxic kidney disease complications Complications anemia jaundice gout

The clinical manifestations of toxic nephropathy caused by heavy metals are complicated. In addition to the typical renal damage manifestations, mainly complicated with systemic diseases such as toxic encephalopathy, anemia, jaundice, liver damage, etc., lead kidney disease often accompanied by gout, accounting for about 50% of the incidence.

Symptoms of heavy metal toxic nephropathy Common symptoms Polyuria abdominal pain Kidney damage Isotonic urinary hypertension

The clinical manifestations of toxic nephropathy caused by heavy metals are complex, both systemic and typical renal damage, which are described as follows:

1. Kidney performance

(1) Prerenal renal insufficiency: often occurs before renal tubular necrosis, due to direct or indirect effects of heavy metals, causing peripheral circulatory failure, renal vasospasm leading to renal insufficiency, clinical manifestations of glomerular filtration rate decreased, Serum creatinine and urea nitrogen are elevated, but renal tubular function is generally normal.

(2) acute tubular necrosis (ATN): due to the direct toxicity of heavy metals, hemoglobin tube type blocked small lumen, renal ischemia and other factors can cause acute tubular necrosis (ATN), clinical manifestations of acute renal failure and obvious renal tubules Dysfunction, such as decreased osmolality, increased urinary sodium, and decreased urine specific gravity.

(3) Chronic renal tubular insufficiency: This is a common manifestation of chronic nephrotoxicity caused by low-dose heavy metals, mainly due to proximal convoluted tubule dysfunction, clinical appearance of low molecular proteinuria, renal glucosuria, amino aciduria, phosphate urine, etc. The performance of Fanconi syndrome.

(4) Chronic interstitial nephritis: mainly seen in the acute sequelae of acute toxic injury or late stage of chronic tubular injury, clinical manifestations are more insidious, clinical polyuria, nocturia, polydipsia and other symptoms, often in the presence of chronic renal failure Only discovered.

(5) Nephrotic syndrome: caused by immunological damage caused by heavy metals on glomeruli, caused by mercury, cadmium, gold, etc., clinically mainly characterized by massive proteinuria, hypoalbuminemia, with or without With edema and hyperlipidemia, renal function is more normal.

2. Extrarenal performance

Extrarenal manifestations vary with the type of heavy metals. Common headaches, fever, stomatitis, gastroenteritis, abdominal pain, pneumonia, pulmonary edema, rash, muscle paralysis, toxic encephalopathy, anemia, jaundice, liver damage, etc.

Such as chronic lead poisoning, its clinical main features is a potential, progressive disease, early difficult to find through the general renal function test indicators, lead kidney disease, renal blood flow decreased, glomerular filtration rate decreased, there are varying degrees Hypertension and hyperuricemia, 50% of cases have gout attacks, some cases have microalbuminuria, hyperkalemia and renal tubular acidosis, normal urine sediment, with tubule degeneration, interstitial fibrosis and calcification, slow The development of chronic renal failure, it is currently believed that potential or clinical symptoms of lead poisoning can develop into chronic renal failure.

In children with acute lead poisoning and experimental animals, proximal tubule dysfunction is characterized by classic Fanconi syndrome. In adult chronic lead nephropathy, renal biopsy can show non-specific tubulointerstitial lesions, visible interstitial sclerosis, lymphatic Cell infiltration, tubule atrophy and dilatation, vascular disease and even severe arteriosclerosis, non-specific vascular damage are associated with the development of hypertension. In the first few years of lead poisoning, only a few cases showed eosinophilic deposition in the proximal tubule.

Chronic renal failure occurs after long-term lead exposure, and there is no history of acute episodes of lead poisoning. Diet, stress and other factors can cause slow release of bone lead deposition and promote the progression of renal damage. There is no reliable method for examination. Predicting and judging that lead-nephropathy has entered an irreversible stage, lead urinary acetylglucosaminidase (NAG) and lysozyme (LYS) excretion increased, and still higher than normal or only slightly reduced after lead exposure The length of lead exposure was positively correlated with the level of urinary NAG excretion. These results indicate that long-term occupational lead exposure leads to an increase in urinary enzyme excretion, while persistent lysosomal urinary tract suggests chronic tubulointerstitial damage.

In patients with chronic lead poisoning, arterial hypertension is common, workers exposed to lead for a long time, chronic renal failure and other diseases associated with arterial hypertension (heart failure, cerebrovascular accidents, etc.) are significantly increased. Experimental studies have confirmed chronic High-dose exposure to lead-induced hypertension, such as patients with chronic renal failure, increased lead exposure during EDTA movement testing, and lead hypertension in patients with essential hypertension without chronic renal failure undergoing EDTA movement test Not more than 3.14mol/24h, the above studies suggest that lead plays a role in the pathogenesis of some essential hypertension.

Examination of heavy metal toxic kidney disease

Urine check

Proteinuria, low molecular proteinuria, may have hematuria, hemoglobinuria and tubular urine, elevated urinary enzymes such as NAG, urinary microproteins such as RBP, 1-MG, 2-MG, urinary calcium, urine Phosphorus rises, urine sugar is positive, amino acid urine, urine is alkaline.

2. Renal function test

The endogenous creatinine clearance rate is reduced, blood urea nitrogen, creatinine, and uric acid are elevated. The nuclear chromatogram is often a parabolic kidney map with a decrease in GFR.

3. Biochemical examination

May have hypokalemia, acidosis, high urinary calcium, high urine phosphorus, elevated blood SGPT, increased jaundice index.

4. Determination of various heavy metal contents

Those who have the conditions for urine aluminum, urinary cadmium, urine gold, etc., to determine the type and content of heavy metal poisoning.

5. Image inspection

X-ray or B-ultrasound can be found in renal calcification and kidney stones.

6. Renal biopsy

(1) When acute tubular necrosis is caused by direct toxic effects and renal ischemic tubular damage, light microscopy shows degeneration of proximal tubule epithelial cells, necrosis, dilatation of the lumen, interstitial congestion around the tubules, edema, inflammatory cell infiltration .

(2) Chronic interstitial nephritis, a large number of lymphocytes and plasma cells infiltrated in the renal interstitial, interstitial fibrosis, tubular dilatation or atrophy; severe cases of diffuse fibrosis throughout the kidney; renal blood vessels and glomeruli are involved.

(3) In the presence of nephrotic syndrome, membranous or proliferative glomerular changes can be seen by light microscopy, thickening of the basement membrane under electron microscope or deposition of electron dense deposits on the surface of the mesentery. Immunofluorescence indicates IgG, IgM, C3 granular system Membrane or capillary wall deposition.

Diagnosis and diagnosis of heavy metal poisoning nephropathy

Diagnostic criteria

For the history of exposure to certain heavy metals, there are clinically abnormal urine tests, changes in renal function, urine glucose positive, amino aciduria, urinary calcium, elevated urinary phosphorus and extrarenal manifestations of heavy metal poisoning, and determination of certain heavy metals in urine. Patients with a content above the normal value can be diagnosed.

For example, the diagnosis of lead-nephropathy, due to the non-specificity and diversity of symptoms of lead-nephropathy, clinical diagnosis is difficult, for patients with chronic renal failure with a history of occupational lead exposure, the diagnosis of lead-nephropathy should be considered, because lead exposure may be non-professional The diagnosis of lead kidney disease should also be considered if the following manifestations are observed: 1 Gout occurs after renal failure. 2 Gout occurs after hypertension, and chronic renal failure occurs relatively quickly.

The increase of lead discharge in EDTA mobile test can affirm the diagnosis of lead nephropathy. The test method is to give 1-2 EDTA to the subject, and add 5% glucose solution 250-500ml for 4h, and measure the urinary lead excretion within 24h. For non-contact persons without lead storage, the urine lead emission is generally not more than 3.14 mol/24h. In individuals with chronic renal failure, urine can be collected for 3 to 4 days. If the individual has no lead exposure, the urine lead emission is also It should not be greater than 3.14mol. X-ray fluorescence analysis has recently been used to determine the lead load of individuals. This method can be used to determine the bone lead content. Kidney biopsy or urine sediment examination can also find eosinophilic inclusion bodies in the proximal tubule nucleus to help establish diagnosis. .

Differential diagnosis

1. Idiopathic Fanconi syndrome: no history of heavy metal exposure, mainly due to defects in multiple reabsorption functions of congenital renal proximal convoluted tubules, causing glucose, amino acids in glomerular filtrate There is an obstacle to the absorption of calcium, phosphorus and sodium bicarbonate.

2. Idiopathic urinary calcium hyperplasia: renal tubular reabsorption of calcium ability, resulting in increased urinary calcium excretion, easy to cause urinary calculi and osteoporosis, primary tubular defects, due to intestinal calcium absorption, kidney The small tube reabsorbs due to excessive load.

3. Drug-induced interstitial nephritis: history of abuse of painkillers and nephrotoxic antibiotics (gentamicin, amphotericin B, cyclosporine A, etc.), manifested as proteinuria, hematuria, etc., severe cases may appear acute kidney Functional failure.

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