Hypercalcemic nephropathy
Introduction
Introduction to hypercalcemia nephropathy Hypercalcemic nephropathy (hypercalcemicnephropathy) refers to hypercalcemia (serum calcium >2.8mmol / L) caused by renal damage and functional changes, mainly as tubulointerstitial lesions. Renal concentrating dysfunction is the most significant and the first dysfunction of hypercalcemia. basic knowledge The proportion of illness: 0.005%--0.007% Susceptible people: no specific population Mode of infection: non-infectious Complications: renal diabetes insipidus renal glycosuria pyelonephritis uremia keratopathy dysphagia ataxia
Cause
Cause of hypercalcemia nephropathy
Primary hyperparathyroidism (65%):
Primary hyperparathyroidism is the most common cause of hypercalcemia, accounting for approximately 50% of all hypercalcemia cases, and approximately 250/1 million patients with primary hyperparathyroidism each year, although it can occur in any Age, but most common in old age and women. Eighty-five percent of patients had a single benign adenoma in the parathyroid gland, and four of the parathyroid glands in other patients had hyperplasia. A glandular cancer was extremely rare. The biochemical feature of patients with primary hyperparathyroidism was PTH,1. 25(OH)2D3 rises and its results, PTH stimulates osteoclast ablation, reduces urinary calcium excretion and causes high blood calcium, PTH increases urinary phosphorus excretion and bicarbonate excretion, causes hyperchloric acidosis, increases urine cAMP is excreted and many patients have elevated blood alkaline phosphatase. Primary hyperparathyroidism can also be manifested as one of multiple endocrine syndromes, including hyperparathyroidism, pituitary adenomas that secrete prolactin or growth hormone, and islet cell tumors that secrete insulin or progesterone. Type II includes parathyroidism, thyroid myeloma, and pheochromocytoma, both of which are autosomal dominant.
Hypercalcemia caused by malignant tumors (9%):
It is the second leading cause of hypercalcemia. Hypercalcemia in patients with cancerous tumors may be related to most stress symptoms, such as nausea, vomiting, and mental confusion. It is recommended to use intensive measures to reduce blood calcium to improve symptoms. Some tumors are more likely to cause hypercalcemia, the most common is lung squamous cell carcinoma and breast cancer. Breast cancer patients often only have high blood calcium when the cancer is widely transferred to the bone. Other cancers include myeloma, T cell lymph. Tumor, head and neck squamous cell carcinoma, renal cell and ovarian cell carcinoma, less hypercalcemia such as lung swine cell carcinoma, stomach, colon, and female germ tumor.
Thyrotoxicosis (8%):
The incidence of past survey results is 10% to 20%. After measuring ionized calcium, the possibility is higher. Usually it is moderately high blood calcium, asymptomatic. Some patients may have hyperparathyroidism. Phosphorus in patients with thyrotoxicosis usually Will increase, and the blood phosphorus of patients with hyperparathyroidism decreased, after treatment for thyrotoxicosis, high blood calcium will return to normal.
No exercise (5%):
Commonly seen in adolescents with rapid and completely unrecognized bones, such as paraplegia, quadriplegia, and bedridden after fracture, high urinary calcium is more common than hypercalcemia, high blood calcium can be maintained for several months, intravenous administration, intensive treatment Bisphosphonates, glucocorticoids or CT are beneficial.
Sarcoma-like and other granulomatous diseases (3%):
High blood calcium can be found in sarcoma-like disease, tuberculosis, histoplasmosis, cocciform fungal disease, candidiasis and sputum poisoning. Among them, sarcoma-like disease is the most common, and high blood calcium is often moderate, less than 120mg/ L, high urinary calcium is more common, often occurs renal calcinosis and soft tissue calcification, the cause is related to granulomatous tissue production 1,25 (0H) 2D3, sarcoma-like macrophages, granuloma cells can make 25 (OH) D3 transformation Into 1,25(OH)2D3, sporadic cytomegalovirus infection caused by acquired immunodeficiency syndrome (abbreviation: AIDS) can also occur high blood calcium, associated with granulomatous lesions, treatment can be expanded, calcium-limited, Use steroids if necessary.
Vitamin poisoning (2%):
Can cause high blood calcium, high urinary calcium, and high blood calcium caused by sarcoma-like disease, patients may have high blood phosphorus, renal dysfunction, renal calcium deposition, soft tissue calcium deposition, high blood calcium duration caused by vitamin D Longer than the time it takes to use its active products, it can last for several months. Therefore, if hypercalcemia is severe, vitamin D poisoning requires steroid treatment and increased sensitivity to vitamin D: sudden infant hypercalcemia, granulomatosis , sarcoidosis, tuberculosis, histoplasmosis, coccidioidomycosis. Vitamin A rarely causes high blood calcium, which is common in the abuse of vitamins. Vitamin A poisoning can cause calcification of the spinal ligament, osteophyte formation, sparse bone, removal of vitamin A and corticosteroids can effectively treat hypercalcemia.
Drug factor (5%):
(1) thiazide diuretics: occasionally cause moderately high blood calcium, blood calcium is almost always less than 110mg / L, but the role of thiazide drugs can be superimposed on primary hyperparathyroidism or other causes of high blood calcium.
(2) Lithium carbonate: 5% of high blood calcium caused by occupation of drugs, the mechanism is unknown, PTH level is inappropriately elevated, suggesting that the calcium regulation point of inhibiting PTH secretion changes, stopping lithium treatment, can restore blood calcium.
Renal failure (3%):
Most patients with renal failure have hypocalcemia. Hypercalcemia can cause renal failure, especially sarcoma-like disease, milk alkali syndrome, vitamin D poisoning or myeloma patients. Hypercalcemia caused by acute renal failure occurs in polyuria. Period, most patients have rhabdomyolysis, the cause is unknown, high blood calcium occasions in patients with chronic renal failure, and secondary hyperparathyroidism or aluminum poisoning, aluminum poisoning often accompanied by low-operation type of bone softening, iPTH is not significant Elevated, characterized by lower alkaline phosphatase.
Pathogenesis
The main effect of hypercalcemia on the kidney is to reduce renal blood flow and glomerular filtration rate, possibly caused by catecholamine release, causing glomerular vasoconstriction; due to calcium, renal tubular permeability to water is reduced. Inhibition of the medullary Na-K pump, which reduces the reabsorption of Na, reduces the osmotic pressure of the medulla hyperosmolar area, and reduces the sensitivity of the distal convoluted tubule to diuretic hormone, thereby affecting water reabsorption and degrading renal enrichment function. In addition, calcium salts can be deposited in the kidneys and cause renal interstitial lesions. The pathophysiological changes of this disease are:
1. Water reabsorption disorder: The membrane structure of renal tubular epithelial cells is tight during hypercalcemia, which reduces the permeability of the distal convoluted tubules to water, reduces water reabsorption, and inhibits the activity of Na-K-ATPase in the medullary sputum. The reabsorption of Na is reduced, the osmotic pressure of the medulla hyperosmotic zone is reduced, and the water reabsorption is reduced.
2. Acid-base balance disorders: hypercalcemia caused by hyperparathyroidism often occurs with metabolic acidosis, while hypercalcemia with no increase in parathyroid hormone often causes metabolic alkalosis due to hypercalcemia Causes damage to the distal tubule, which causes the distal tubule to secrete H, and the ability to produce ammonia is reduced, which can lead to metabolic acidosis. Hypercalcemia can also stimulate gastric acid secretion and osteolysis, and the alkaline substance is released into the extracellular fluid. It also promotes the reabsorption of bicarbonate, thus causing metabolic alkalosis.
3. Nitrogenemia and renal insufficiency: Hypercalcemia directly causes renal microvascular contraction, or increases catecholamine release, resulting in decreased renal blood flow, azotemia, long-term hypercalcemia nephropathy due to renal parenchymal damage CRF .
4. Hypertension: The mechanism of hypertension in this disease may be related to high blood calcium causing neuromuscular excitability changes, causing vascular smooth muscle contraction or increasing the release of vasopressor substances.
Prevention
Hypercalcemia nephropathy prevention
In the treatment of primary disease and rapid control of high blood calcium, peritoneal dialysis and hemodialysis can be used in patients with high calcium crisis and renal failure. Attention to control infection and prevention and treatment of complications can effectively prevent the progression of the disease.
Complication
Hypercalcemia nephropathy complications Complications renal diabetes insipidus renal glycosuria pyelonephritis uremic keratopathy dysphagia dysfunctional ataxia
The disease is not effective in the treatment of antidiuretic hormone, and may be complicated by renal diabetes insipidus. The elderly with long-term disease appear amino aciduria, renal glucosuria, proteinuria, renal calcification, urinary calculi, often complicated with pyelonephritis, late GFR decline, nitrogen blood Symptoms and uremia, the special signs of systemic manifestations are chronic conjunctivitis, corneal calcification ring, band keratopathy, can be combined with tongue muscle atrophy, olfactory dysfunction, hoarseness, difficulty swallowing, ataxia, hypercalcemia The disease can excite the gastric gland secretion and ulcer disease, which can cause stomach bleeding and perforation. When the blood calcium concentration increases rapidly more than 3.7mmol/L, it can be accompanied by hypercalcemia crisis.
Symptom
Hypercalcemia nephropathy symptoms common symptoms polyuria stun stun skin itching dehydration urine collapse convulsion peptic ulcer nausea dysphagia
Early manifestations of polyuria, nocturia, polydipsia, decreased urine specific gravity and osmotic pressure, and even renal diabetes insipidus, vasopressin treatment is ineffective, amino acid urinary, renal glycosuria, proteinuria, renal calcification, Urinary calculi, often associated with pyelonephritis, late decline in GFR, azotemia and uremia.
Systemic manifestations include dehydration, hypokalemia, hyponatremia, hypomagnesemia, renal tubular acidosis, pruritus, chronic conjunctivitis, and corneal calcification, band keratopathy, which is a special form of hypercalcemia. Signs, can be combined with tongue muscle atrophy, olfactory dysfunction, hoarseness, difficulty swallowing, ataxia, hypercalcemia can excite gastric gland secretion and ulcer disease, can cause gastric bleeding and perforation, the disease is secreted by parathyroid hormone Increased can be accompanied by multiple stones, peptic ulcer, pancreatitis and so on.
When the blood calcium concentration increases rapidly by more than 3.7mmol/L, a hypercalcemic crisis can occur, and the mortality rate is 60%. The patient has severe polyuria, dehydration, sharp increase in blood pressure, sharp deterioration of renal function, and headache. , nausea, vomiting, abdominal cramps, convulsions, lethargy, convulsions, stupor, coma, ventricular tachycardia or ventricular fibrillation.
Laboratory tests can be found hypercalcemia, hypophosphatemia, hyperchloremia, increased BUN and serum creatinine, decreased creatinine clearance, increased urinary calcium (hypercalciuria), above 0.1 mmol/(kg·24h) ), males are higher than 7.49mmol/24h, females are higher than 6.24mmol/24h, proteinuria is mostly mild, mainly low molecular proteinuria, sometimes visible red blood cells, white blood cells, cell casts, occasionally calcium casts.
Imaging studies can reveal kidney stones or kidney calcification.
According to clinical manifestations and laboratory tests, such as increased blood calcium concentration, increased urinary calcium (hypercalciuria), sometimes seen in the urine, red blood cells, white blood cells, cell casts, occasionally calcium casts, and clinical features of renal damage Urine, nocturia, amino aciduria, renal glucosuria, proteinuria, renal calcification, urinary tract stones, often associated with pyelonephritis, late GFR decline, azotemia and uremia; or systemic specific signs of chronic conjunctiva Inflammation, corneal calcification ring, band keratopathy; also tongue muscle atrophy, olfactory sensation, hoarseness, difficulty swallowing, ataxia, stomach bleeding and perforation, rapid increase in serum calcium concentration and hypercalcemia Hypercalcemic crisis, patients with severe polyuria, dehydration, sharp increase in blood pressure, sharp deterioration of renal function, headache, nausea, vomiting, abdominal cramps, convulsions, lethargy, paralysis, stupor, coma, ventricular heartbeat Overspeed or ventricular fibrillation; at this time, the disease can generally be diagnosed, and patients with renal failure may be difficult to diagnose because blood calcium has been reduced.
Examine
Examination of hypercalcemia nephropathy
1. Blood test: Hypercalcemia, hypophosphatemia, hyperchloremia, hypokalemia, hyponatremia, hypomagnesemia, renal tubular acidosis, increased BUN and serum creatinine, and decreased creatinine clearance, Serum alkaline phosphatase levels increased and serum PTH increased.
2. Urine examination: increased urinary calcium (hypercalciuria), higher than 0.1mmol / (kg · 24h), male is higher than 7.49mmol / 24h, female is higher than 6. 24mmol / 24h, proteinuria is mostly mild It is mainly composed of low molecular proteinuria, sometimes red blood cells, white blood cells, cell casts, and occasionally calcium casts.
Imaging examination can be found in kidney stones or renal calcification. The pathological changes in the acute phase of this disease are mainly in the medulla. In the short-term persistent hypercalcemia, the medullary ascending branch rapidly occurs, and the distal tubules and collecting duct epithelial cells are swollen and degenerated. , necrosis, shedding, basal membrane calcification of tubular epithelial cells, obstruction of renal tubules by necrotic tissue, the mechanism of which is abnormal increase of intracellular and mitochondrial calcium concentration, tubular basal membrane calcification and structural destruction cause adjacent interstitial inflammatory infiltration and proliferation, necrotic cells The shedding causes tubule atrophy, obstruction, secondary dilatation, and stress damage to the proximal tubule segment of the injured site. Calcium deposits in the necrotic and damaged areas cause characteristic renal calcification seen by radiographic examination. The ball is also affected, showing glomerular and vascular calcification, glomerular glass-like changes with fibrosis around the ball, calcium deposition in the glomerular capillaries and interstitial vessels is associated with progressive damage to the kidney, chronic tubules visible in the chronic phase Typical changes in interstitial nephropathy, tubular atrophy, interstitial fibrosis and mononuclear cell infiltration, formation of kidney stones and their Further exacerbated plug nephropathy tubulointerstitial damage, renal biopsy visibility above characteristic changes.
Diagnosis
Diagnosis and diagnosis of hypercalcemia nephropathy
The disease can be complicated by renal diabetes insipidus, so it should be differentiated from other related diseases that cause polyuria.
1. Diabetes insipidus: Diabetes insipidus is caused by the lack of ADH. ADH can increase the permeability of the distal convoluted tubules and collecting ducts, thus promoting the reabsorption of water. If for some reason, the secretion of ADH is insufficient, far-reaching The water in the small tube and the collecting tube can not be absorbed, so the urine volume is greatly increased. The total urine volume in 24 hours is 4-8L, and the maximum is 40L, which is clinically called diabetes insipidus.
Diabetes insipidus can be divided into idiopathic and secondary. The former has no obvious cause in clinical, some of which may be related to heredity; more than 50% of the latter are often in or near the sella (craniopharyngeal tube) Tumor, chromoblastoma, glioma, pineal tumor, yellow lipoma, etc.), inflammation (encephalitis, meningitis, tuberculosis, syphilis, etc.), cerebrovascular disease, granuloma (such as eosinophilic granuloma, Yellow lipoma, sarcoidosis, etc., craniocerebral trauma (concussion, skull base fracture), hypothalamic-neuronal system surgery, etc., clinically associated with visual impairment, hemianopia, increased intracranial pressure or other Nervous system performance.
According to typical performance, general diagnosis is not difficult, but must be differentiated from mental polyuria and renal diabetes insipidus (Table 1).
2. Diabetes: Polyuria is one of the main symptoms of diabetes. In diabetes, due to elevated blood sugar, glomerular filtration glucose increases, the original urine contains increased sugar, and the osmotic concentration in the renal lumen increases, limiting the reabsorption of water. Therefore, polyuria, polydipsia is also one of the important reasons for polyuria, in addition to polyuria often accompanied by polydipsia, polydipsia, polyphagia, weight loss, fatigue, female patients may have genital itching, their urine daily Not more than 5000ml, characterized by high urine specific gravity and urine sugar positive. Symptoms, random blood glucose 11.1mmol/L, or more than two fasting blood glucose 7.77mmol/L, can be diagnosed as diabetes, and this disease is not Increased blood sugar can be identified.
3. Primary aldosteronism: Primary aldosteronism is caused by adrenal cortical tumors, hyperplasia caused by increased aldosterone secretion, acting on the distal renal tubules, and the action of sodium and potassium excretion, the increase of blood sodium stimulates the thirst center Causes polydipsia, polydipsia causes polyuria; on the other hand, it can also cause potassium loss due to renal potassium loss, affecting renal tubular concentrating function and causing polyuria, clinical manifestations of polydipsia, polyuria and nocturia, high Blood pressure, hypokalemia, muscle fatigue, weakness, severe cases can cause flaccid paralysis, blood potassium is often less than 3mmol / L, blood sodium is slightly elevated, blood pH is high, blood and urine 24h aldosterone emission increased, renin The activity is reduced, and imaging examination can make a diagnosis of adenoma.
