What Is Uremia?

Chronic renal failure refers to a clinical syndrome composed of a series of symptoms and metabolic disorders that result from the gradual and irreversible decline of kidney function caused by various kidney diseases, and is referred to as chronic renal failure. The end stage of chronic renal failure is commonly referred to as uremia. Uremic is not an independent disease, but a clinical syndrome common to various advanced kidney diseases. It is a syndrome composed of a series of clinical manifestations that appear when chronic renal failure enters the end stage.

Zhou Yuchao	(Attending physician)	Army Nephrology Institute, Nanjing General Hospital of Nanjing Military Region
Cheng Zhen	(Deputy Chief Physician)	Army Nephrology Institute, Nanjing General Hospital of Nanjing Military Region
Wu Yan	(Deputy Chief Physician)	Army Nephrology Institute, Nanjing General Hospital of Nanjing Military Region

Western Medicine Name: Uremia
English name: uremia
Affiliated Department: Internal Medicine-Nephrology

Disease site: kidney
The main symptoms: Metabolic acidosis
Contagious: Non-contagious
Whether to enter health insurance: Yes

Clinical manifestations of uremia

Uremic disorders of water, electrolyte and acid-base metabolism

Metabolic acidosis and water and electrolyte balance disorders are the most common.

(1) Metabolic acidosis During the period of chronic renal failure and uremia, acidic products metabolized by the human body such as phosphoric acid and sulfuric acid are retained due to renal excretion disorders, and "uremia acidosis" may occur. In mild chronic acidosis, most patients have fewer symptoms, but if arterial blood HCO3 <15 mmol / L, obvious loss of appetite, vomiting, weakness, and deep breathing can occur.

(2) Disorders of water and sodium metabolism, mainly manifested as water and sodium retention, or hypovolemia and hyponatremia. During renal insufficiency, the kidney's ability to adapt to excessive sodium load or excess capacity gradually decreases. Patients with uremia who improperly restrict water can cause an overload of the volume. Subcutaneous edema (eyelids, lower limbs) or body fluid (thorax, abdominal cavity) of varying degrees are common. Cardiac insufficiency (expressed by chest tightness, decreased activity tolerance, or even failure to lie flat at night) and cerebral edema. On the other hand, when the patient has a large amount of urine and excessively restricts water, or is accompanied by gastrointestinal symptoms such as vomiting and diarrhea, it is easy to cause dehydration. Too much capacity is clinically common. Therefore, patients with uremia should pay attention to proper control of water intake (in addition to drinking water, including soup, porridge, fruits and other watery foods), and avoid excessive amounts during diagnosis and treatment. Rehydration to prevent heart failure and pulmonary edema.

(3) Disturbance of potassium metabolism: When the GFR drops to 20-25ml / min or lower, the kidney's ability to excrete potassium gradually decreases, and hyperkalemia is prone to occur at this time; especially when excessive potassium intake, acidosis, infection, When trauma and gastrointestinal bleeding occur, hyperkalemia is more likely to occur. Severe hyperkalemia (serum potassium> 6.5mmol / L) is dangerous and requires timely treatment and rescue (see Management of hyperkalemia). Sometimes hypokalemia can also occur due to insufficient potassium intake, excessive gastrointestinal loss, application of potassium-releasing diuretics, and other factors. Hyperkalemia is more common clinically, so patients with uremia should strictly limit the intake of foods high in potassium, and should regularly review blood potassium.

(4) Disorders of calcium and phosphorus metabolism, mainly manifested as excessive phosphorus and calcium deficiency. In chronic renal failure, the kidney produces 1,25- (OH) 2D3, which reduces the absorption of calcium in the intestine; the target organs resist 1,25- (OH) 2D3, which reduces the reabsorption of calcium by the renal tubules. Phosphatemia can increase the calcium-phosphorus product, promote the deposition of calcium phosphate salts, cause ectopic calcification, and reduce blood calcium. Food is rich in phosphorus, and the blood phosphorus concentration is adjusted by the intestinal absorption of phosphorus and renal excretion. When the glomerular filtration rate decreases and the urinary phosphorus excretion decreases, the blood phosphorus concentration gradually increases, and hyperphosphatemia further inhibits the synthesis of 1,25- (OH) 2D3, which worsens hypocalcemia. Parathyroid glands compensate for the secretion of more PTH to maintain blood calcium. Causes secondary hyperparathyroidism (referred to as parathyroidism).

Disorders of protein, sugar, fat and vitamins

Protein metabolism disorders in CRF patients generally manifest as accumulation of protein metabolites (azotemia), including urea, guanidine compounds, creatinine, amines, indole, phenols, and medium molecular substances.

Urea is excreted by the kidneys. Urea accumulation in the body during uremia may be related to fatigue, anorexia, vomiting, inattention, decreased body temperature, and bleeding tendency; under normal circumstances, arginine is mainly metabolized to urea in the liver, Guanidine acetate and creatinine, urea and creatinine accumulation during uremia, and arginine can be broken down into methylguanidine and guanidinoarginine through other routes. Among them, methylguanidine is the most toxic small molecule substance, and its accumulation in the body can reach 70 to 80 times the normal value, which is related to many clinical symptoms such as weight loss, shortened red blood cell life, vomiting, diarrhea, and lethargy. Amine fatty amines can cause myoclonus, flutter-like tremor and hemolysis; polyamines (spermine, cadaverine, putrescine) can cause anorexia, nausea, vomiting and proteinuria, and can promote red blood cell lysis and inhibit red blood cells The production of auxin promotes the occurrence of pulmonary edema, ascites and cerebral edema in renal failure.

Impaired glucose metabolism is mainly manifested in impaired glucose tolerance and hypoglycemia, the former is more common, the latter is rare. Hyperlipidemia is quite common, most patients show mild to moderate hypertriglyceridemia, and a few patients show mild hypercholesterolemia, or both. Vitamin metabolism disorders are quite common, such as increased serum vitamin A levels, vitamin B6, and folic acid deficiency.

Cardiovascular manifestations of uremia

Cardiovascular disease is one of the major complications and the most common cause of death in patients with CKD. Especially in the stage of end-stage renal disease (ie, the uremia stage), the cardiovascular disease mortality rate has further increased (accounting for 45% -60% of the cause of uremia death). Recent studies have found that cardiovascular adverse events and atherosclerotic cardiovascular disease in patients with uremia are about 15-20 times higher than in the general population.

People with chronic renal failure may suffer from heart failure, arrhythmia, and myocardial damage due to the effects of renal hypertension, acidosis, hyperkalemia, sodium-water retention, anemia, and toxic substances. Due to urea (probably also Uric acid) can also cause aseptic pericarditis, patients with pain in the anterior heart, pericardial friction sounds during physical examination. In severe cases, cellulose and bloody exudates appear in the pericardial cavity. Vascular calcification and atherosclerosis also play important roles in cardiovascular disease.

Respiratory symptoms of uremia

The breath exhaled by the patient has a urine smell, which is due to the decomposition of urea in the saliva by the bacteria to form ammonia; shortness of breath and shortness of breath when there is too much fluid; the patient breathes slowly and deeply during acidosis, and the particularity of acidosis can be seen in severe Kussmaul breathing (deep breathing). Excessive body fluids and cardiac insufficiency can cause pulmonary edema or pleural effusion; increased alveolar capillary permeability and pulmonary congestion caused by uremic toxins can cause "uremia pulmonary edema". At this time, lung x-ray examination can appear " "Butterfly wing" sign, prompt diuresis or dialysis can quickly improve the above symptoms; cellulose pleurisy is inflammation caused by urea stimulation; lung calcification is caused by the deposition of calcium phosphate in the lung tissue.

Gastrointestinal symptoms of uremia

The earliest symptoms of digestive system in uremia patients are loss of appetite or indigestion. Anorexia, nausea, vomiting or diarrhea may occur when the condition worsens. The occurrence of these symptoms may be related to the decomposition of urea into ammonia by the urease of the bacteria in the intestine, which stimulates the gastrointestinal mucosa and causes inflammation and multiple superficial small ulcers. In addition, nausea and vomiting are also related to dysfunction of the central nervous system. Gastrointestinal bleeding is also more common, and its incidence is significantly higher than that of normal people, mostly due to gastric mucosal erosion or peptic ulcer.

Blood system performance of uremia

CRF patients' blood system abnormalities are mainly manifested as renal anemia and bleeding tendency. Most patients generally have mild to moderate anemia, and the cause is mainly due to erythropoietin deficiency, so it is called renal anemia; if accompanied by factors such as iron deficiency, malnutrition, and bleeding, it can worsen the degree of anemia. Patients with advanced CRF have abnormal platelet function and tend to bleed, such as subcutaneous or mucosal bleeding points, ecchymosis, gastrointestinal bleeding, and cerebral hemorrhage.

Neuromuscular symptoms of uremia

Early symptoms may include insomnia, inattention, and memory loss. In uremia, there may be indifferent reactions, delirium, convulsions, hallucinations, coma, and mental disorders. Peripheral neuropathy is also common, and sensory neurological disorders are more pronounced. The most common is the loss of sensation in sock-like distribution of limbs. It may also have numbness, burning or pain in the limbs, dullness or disappearance of deep reflexes, and neuromuscular Increased excitability, such as muscle tremors, cramps, restless leg syndrome, etc. The occurrence of these symptoms is related to the following factors: accumulation of certain toxic substances may cause degeneration of nerve cells; electrolyte and acid-base balance disorders; cerebral vasospasm caused by renal hypertension, hypoxia and capillary permeability Increased, can cause degeneration of cerebral nerve cells and cerebral edema. Patients with primary dialysis may develop dialysis imbalance syndrome, nausea, vomiting, headache, convulsions, etc., mainly due to imbalance of intra- and extra-cellular fluid osmotic pressure, cerebral edema, and increased intracranial pressure after hemodialysis.

Uremia bone disease

Renal osteodystrophy (i.e., renal osteopathy) is quite common, including fibrocystic osteitis (high turnover bone disease), osteogenesis (adynamic bone disease), osteomalacia (low turnover bone disease), and bone Osteoporosis. About 35% of patients with abnormal bone X-rays were found before dialysis, but bone pain, inconvenience of walking, and spontaneous fractures were relatively rare (less than 10%). About 90% of bone biopsy (bone biopsy) can detect abnormalities, so early diagnosis depends on bone biopsy.

Fibrocystic osteitis is mainly caused by excessively high PTH, which is prone to dissolution of bone salts and rib fractures. X-ray examination showed the manifestations of skeletal cystoid defects (such as phalanges, ribs) and osteoporosis (such as spine, pelvis, femur, etc.).

The occurrence of poor osteogenesis is mainly related to the relatively low blood PTH concentration and insufficient osteogenic factors, so it is not enough to maintain bone regeneration; dialysis patients, such as long-term excessive use of active vitamin D, calcium and other drugs or dialysate calcium If it is too high, the blood PTH concentration may be relatively low.

Diagnosis of uremia

Uremic is not a separate disease but a group of clinical syndromes. In the end stage of chronic renal failure, the three major functions of the kidney are lost, and a series of symptoms and metabolic disorders appear, thereby forming uremia. The diagnosis of uremia depends not only on the serum creatinine level, but also on the clinical manifestations of the above systems.

In the early stages of chronic renal insufficiency, there are only clinical symptoms of the primary disease, and only a decrease in creatinine clearance can be seen in the examination. These patients with uremia compensatory stage often have sudden deterioration of renal function under stress and uremia symptoms (ie, the clinical manifestations of the various systems described above). They are clinically referred to as reversible uremia. Elimination of irritants, renal function can often return to the compensatory period. If the disease progresses to a "healthy" nephron that cannot meet the minimum requirements of the body, even if there is no stress factor, uremia symptoms will gradually appear. The damage to each system of the above-mentioned uremia may not always be manifested. In different patients, the symptoms of uremia may not be the same, and the timing of the occurrence of the symptoms of each system may not be the same.

Uremia test

1. Routine blood test for uremia, hemoglobin is generally under 80g / L, most of them are only 40 ~ 60g / L, it is positive cell angiochromic anemia, when patients with chronic blood loss, malnutrition, can also show small cells Low pigmented anemia. Leukocytes change less and can increase leukocyte counts during acidosis and infection. The number of platelets is low or normal, but the function is reduced, and the red blood cell sedimentation rate is often accelerated due to anemia and hypoproteinemia.

2. Urine routine examination Urine changes in patients with uremia vary greatly with the primary disease. The common points are: the urine osmotic pressure is reduced, most morning urine is below 450mOsm / kg, the specific gravity is low, most is below 1.018, and it is fixed between 1.010 and 1.012 in severe cases. In the concentrated dilution test, the nocturia volume is greater than the daily urine volume, and the specific gravity of each urine does not exceed 1.020, and the difference between the highest and lowest urine specific gravity is less than 0.008. The urine output decreases below 1000ml / day. When the creatinine clearance rate drops to 1.0 2.0ml / second, the urine can be anaemic. Urinary protein is + +++. In the late stage, because most of the glomeruli have been destroyed, urine protein has decreased. The urine sediment examination can have a variety of red blood cells, white blood cells, epithelial cells and granular casts. If you can find thick, short, homogeneous, waxy casts with cracks on the edges, it is meaningful for diagnosis.

3. Renal function test During the period of renal insufficiency compensation, although the renal creatinine clearance rate has decreased, but the serum creatinine has not increased; during the azotemia stage, although the serum creatinine has increased, the patient has no clinical symptoms of uremia. There is no metabolic acidosis; in the uremia period, when the renal creatinine clearance rate is <25ml / min, blood creatinine will be significantly increased, accompanied by metabolic acidosis.

4. Plasma protein decreased in blood biochemical examination. The total protein is usually below 60g / L, and the decrease of albumin is usually more obvious, mostly lower than 30g / L. Blood calcium is low, often around 2mmol / L, and blood phosphorus is usually higher than 1.7mmol / L. Blood potassium and blood sodium depend on the condition.

5. Other inspections

(1) X-ray examination: X-ray examination of the abdomen can be performed on patients with uremia. The purpose is to observe the size and shape of the kidneys, and whether there are stones in the urinary system. A lateral abdominal film can show the presence or absence of atherosclerosis. In the case of severe renal insufficiency, due to the poor function of the renal excretion contrast agent, the contrast agent is not developed after injection, so it is generally not suitable for angiography.

(2) The radionuclide nephrogram and kidney scan can help to understand the size, blood flow, secretion and excretion function of the kidneys on both sides.

(3) Renal ultrasound and CT can help determine the location, size, and thickness of the kidney, and the presence or absence of fluid, stones, and tumors in the renal pelvis. Usually, the kidneys of patients with uremia shrink and the cortex becomes thin. However, the kidneys of patients with uremia caused by secondary causes such as diabetes, lupus, and vasculitis may not shrink significantly, but the echo of the lower cortex of the B ultrasound is enhanced.

Ultrasound examination of the kidney has the advantages of economy, convenience, non-invasiveness, fastness, etc. It can judge the size of the kidney, cortical echo, etc., and is widely used in clinical practice.

Treatment of uremia disease

Renal replacement therapy is needed when chronic renal insufficiency progresses to the uremia phase.

There are often some patients who have entered the uremia period, but have been delayed, are unwilling to receive dialysis treatment, and are always worried about dialysis side effects, costs and so on. Many patients also hope that traditional Chinese medicine treatment will "cure" uremia and get rid of dialysis. In fact, dialysis works instead of the kidneys. When the patient enters the uremia period, the kidneys of the patient should be damaged by more than 90%. If you continue to delay without taking alternative treatment, the toxins will remain in the body and will bring other organs in the body Irreversible damage to the heart, digestive system, bones, blood system, etc. And uremia is a disease that cannot be cured by drug treatment. There is no so-called "magic panacea" that can cure uremia. Therefore, patients with uremia should not hesitate to take renal replacement therapy, that is, dialysis treatment.

For patients with relatively stable uremia

These patients are relatively stable. Although renal replacement therapy needs to be started as soon as possible, there is no indication for emergency dialysis. Such patients need to actively prepare for dialysis while taking medication and diet control. For example, pre-dialysis related education by medical staff will enable patients to fully understand the necessity and limitations of renal replacement therapy, and choose a suitable dialysis method (hemodialysis or peritoneal dialysis) based on their own conditions, family environment, work conditions, and economic conditions ); Patients planning to undergo hemodialysis need to perform ostomy surgery 1 to 3 months in advance, and contact the hemodialysis center for long-term dialysis treatment. For patients preparing for peritoneal dialysis, the peritoneal dialysis tube should be inserted 2 to 4 weeks in advance.

Uremia Urgency

Common uremia emergencies include:

Hyperkalemia In the case of uremia, the kidney's ability to excrete potassium decreases, and hyperkalemia is prone to occur at this time; especially when excessive potassium intake, acidosis, infection, trauma, gastrointestinal bleeding, etc., occur disease. Severe hyperkalemia (serum potassium> 6.5mmol / l) may cause cardiac arrest, life-threatening, and need to be rescued in time: Calcium to counteract the toxicity of hyperkalemia to myocardium, 10% calcium gluconate 10 ~ 20ml is usually added, etc Measure the amount of hypertonic glucose and push it slowly and quietly for no less than 5 minutes. If the arrhythmia does not improve after 5 minutes of injection or it is effective but recurs quickly, it can be re-injected; Sodium lactate or sodium bicarbonate can promote potassium ions into the cells, antagonize the inhibition of potassium on the heart, and increase urinary potassium excretion; The combined application of glucose and insulin (4g glucose: 1U insulin) can promote the transfer of potassium into cells; oral or injection of potassium excretion diuretics (furosemide, torasemide, etc.) to promote renal potassium excretion; oral cation exchange resin, Promote the excretion of potassium from the intestinal tract; High potassium is very serious (> 6.5mmol / l), and when the above treatment is not effective, hemodialysis treatment can be used to reduce blood potassium. Patients with heart failure, pulmonary edema, and uremia have decreased or even lost their kidneys' ability to regulate water and sodium balance, and their urine output is reduced, which can easily lead to volume overload. In severe cases, heart failure, pulmonary edema, and life-threatening. Its preventive and treatment measures include: Control the water intake so that the amount of water is less than the amount of water, and diuretics are necessary when necessary; Ultrafiltration dehydration treatment for hemodialysis; Cardiac and tube expansion treatments. Metabolic acidosis has a blood pH of <7.2, carbon dioxide binding power <13mmol / l, and has clinical manifestations of metabolic acidosis (appetite loss, vomiting, weakness, deep breathing, etc.). Treatment measures: intravenous sodium bicarbonate: 5% sodium bicarbonate solution intravenous drip; hemodialysis to correct acid-base balance disorders. Toxin levels are high, blood creatinine 707umol / l, urea nitrogen 28.6mmol / l, when symptoms of uremia are obvious, emergency hemodialysis is required to remove toxins; when severe complications such as pericarditis and gastrointestinal bleeding occur. When emergency dialysis is needed in the above situation, the blood flow channel needs to be established through central venous intubation. Dialysis imbalance syndrome may occur in patients with first dialysis, so the first dialysis time is short, usually about 2 hours.

Hemodialysis and peritoneal dialysis

Hemodialysis: The patient's blood is introduced into the dialysis machine through the vascular channel, and the material is exchanged between the dialysis membrane and the dialysate in the dialyzer, and the purified blood is returned to the body to discharge waste, correct electrolytes, The purpose of acid-base disorders. If reasonable dialysis can be maintained for a long time, many patients can survive for more than 10 to 20 years.

Since hemodialysis requires the use of a hemodialysis machine, it is necessary to go to the hospital 2 to 3 times a week for about 4 hours each time. The advantage is that there is less waste accumulated in the body after each hemodialysis and there is a fixed time to return each week. Treatment is performed in the hospital. If the condition changes, it can be treated in a timely manner. There is a professional medical staff to operate during the dialysis process, no need to do it yourself.

Disadvantages are also obvious: each time a needle is needed; anemia is more serious; blood pressure will be affected before and after dialysis, which is unfavorable for patients with cardiovascular disease and diabetes; strict diet control is required; discomfort is more likely to occur before dialysis; dialysis time cannot be arbitrarily changed; infection The risks of hepatitis B and C are greatly increased.

Peritoneal dialysis: A special fluid called "peritoneal dialysis fluid" is poured into the abdominal cavity through a "peritoneal dialysis tube". At this time, one side of the peritoneum is blood containing metabolic waste and excess water, and the other side is dry. With static peritoneal fluid, metabolic waste and excess water in the blood will run through the peritoneum into the peritoneal fluid. After 3-4 hours of retention (8-10 hours at night), remove these waste-containing peritoneal fluid from the abdominal cavity, and then inject new peritoneal fluid. This can be replaced 3-4 times a day, and the toxins and excess water in the body can be continuously discharged. After education and training, patients and their families can master peritoneal dialysis and then perform peritoneal dialysis at home. If you use a fully automatic peritoneal dialysis machine, you can perform dialysis during sleep every night, and you can work and study normally during the day.

Advantages of peritoneal dialysis:

Protection of residual renal function is better than hemodialysis: peritoneal dialysis is the closest treatment to physiological conditions. There is no sudden change in hemodynamics, body fluid capacity, and biochemistry during dialysis, thereby reducing dialysis due to unstable internal environment. Complications such as cardiovascular disease, hypertension, hypotension, and arrhythmia. It will not cause kidney ischemia during treatment, which is beneficial to protect residual renal function.

Wide range of application: peritoneal dialysis has good cardiovascular stability and is the preferred dialysis method with severe cardiovascular disease, cerebrovascular disease, diabetes, and elderly patients; dialysis has fewer dietary restrictions, and patients have better nutritional status. Children's growth and development have little impact, and avoid the pain of hemodialysis; abdominal dialysis does not require arteriovenous fistulas, which avoids arteriovenous fistula occlusion due to peripheral vascular disease in patients with diabetes.

(3) High dialysis efficiency: It has a good ability to remove medium molecular toxins, 2 microglobulin and phosphorus. Therefore, peritoneal dialysis can improve the symptoms of uremia and improve anemia and neuropathy better than hemodialysis.

There is less chance of hepatitis B and C infection.

The degree of dialysis bone disease in long-term dialysis is better than hemodialysis.

Dialysis can be performed at home without going to the hospital, which does not affect work, study and travel. The cost of treatment is low and the quality of life is high.

Disadvantages of peritoneal dialysis: Because peritoneal dialysis requires an intraperitoneal tube to be built into the abdominal cavity, and frequent operations such as changing the peritoneal fluid during dialysis, if the patient or family members do not strictly control the aseptic operation, they are prone to infection and cause peritonitis. However, with the improvement of peritoneal dialysis devices, the education and training of patients by dialysis specialists and nurses, and the improvement of living and living sanitary conditions, the incidence of peritoneal dialysis infection has been greatly reduced.

Peritoneal dialysis has been used to maintain the lives of patients with uremia for more than thirty years. In Hong Kong and some European countries, 80% of uremia patients live, work and study under peritoneal dialysis.

However, no matter hemodialysis or peritoneal dialysis, it can only replace the role of the kidneys in removing metabolic waste, maintaining water, electrolytes, and acid-base balance. It cannot replace another important function of the kidney, namely endocrine functions, such as EPO, active vitamin D3. And so on. Therefore, patients with maintenance hemodialysis or peritoneal dialysis still need to use EPO, calcitriol and other drugs depending on the condition. It is not what some patients think is "no medication is needed for dialysis."

Kidney transplantation is the most reasonable and effective treatment method for uremia patients. However, due to the lack of donors, kidney transplantation cannot perform its proper therapeutic effect. There are only more than 5,000 kidney transplant recipients in the country each year. Only about one in 150 waiting patients may get a kidney transplant. The shortage of donors has become a bottleneck restricting organ transplantation. Therefore, most patients with uremia need long-term maintenance hemodialysis or peritoneal dialysis. According to agency statistics, there are about 100,000 patients on dialysis in China, about 90% of patients on hemodialysis, and only 10% of patients on dialysis. ^[1-3]