What Is the Relationship Between Arginine and Diabetes?

Diabetic nephropathy (DN) is a serious and most serious chronic complication caused by diabetes. Glomerulosclerosis caused by microvascular disease caused by diabetes is a characteristic of this disease and the main cause of death in patients with IDDM. Appearing infectious diseases such as pyelonephritis and renal papillary necrosis, and large vascular diseases such as renal arteriosclerosis, are not in the category of diabetic nephropathy.

Diabetes with nephropathy

This entry lacks an overview map . Supplementing related content makes the entry more complete and can be upgraded quickly. Come on!

Diabetic nephropathy (DN) is a serious and most serious chronic complication caused by diabetes. Glomerulosclerosis caused by microvascular disease caused by diabetes is a characteristic of this disease and the main cause of death in patients with IDDM. Appearing infectious diseases such as pyelonephritis and renal papillary necrosis, and large vascular diseases such as renal arteriosclerosis, are not in the category of diabetic nephropathy.

Chinese name

Diabetes with nephropathy

Foreign name

iabetic nephropathy, DN

Cause

Family susceptibility to genetic susceptibility DN

There are 3 modes

Major gene effect

English name: Diabetes mellitus with nephropathy

Chinese name: Diabetes with nephropathy

With the continuous improvement of diabetes treatment methods and technology, fewer and fewer patients die of acute complications of diabetes, such as ketoacidosis. Diabetic and nephropathy is mainly a major microvascular complication of diabetes, mainly referring to diabetic glomerulosclerosis, a type of glomerular disease with mainly vascular damage. Early asymptomatic, blood pressure can be normal or high. Its incidence increases with the duration of diabetes. In the early stage of diabetes, the kidney volume increases, and the glomerular filtration rate increases, showing a high filtration state. Later, interstitial proteinuria or microalbuminuria gradually appears, and continuous proteinuria, edema, hypertension, and small kidneys appear as the course of the disease increases. Reduced ball filtration rate, followed by renal insufficiency and uremia, is one of the main causes of death in diabetes. The incidence of type 1 diabetes with nephropathy is 30% to 40%. The incidence of type 2 diabetes is 20%. As the number of patients with type 2 diabetes increases year by year, the number of people with DN also increases accordingly. The degree of harm to society cannot be underestimated. The occurrence and development of diabetic nephropathy is slow. Once the renal damage is clinically persistent proteinuria, the course is difficult to reverse, and it often progresses to renal failure. Therefore, we must attach great importance to diabetic nephropathy and try to achieve early diagnosis and early treatment as much as possible to prevent and delay the occurrence and development of diabetic nephropathy.

The occurrence and development of DN are mainly caused by the interaction of genetic susceptibility and hyperglycemia (environmental factors). Environmental factors also include factors such as hyperlipidemia and hypertension, but hyperglycemia is more important.

1. Genetically susceptible DN has a family aggregation phenomenon. Whether in 1-DM or 2-DM patients, if the proband case is complicated by DN, the incidence of DN in siblings will increase significantly. Even if 1-DM patients have poor glycemic control, only 35% eventually develop into end-stage DN. Even if strict control of blood glucose is close to normal, DN has been proven to significantly improve or prevent DN, but it cannot completely prevent the occurrence and development of DN. So there are already clues suggesting that DN is genetically susceptible.

There are three types of susceptibility:

(1) Major gene effect: refers to the occurrence of DN due to the interaction between a major gene polymorphism (or mutation) and poor glycemic control.

(2) Moderate gene effects: refers to the interaction between several genetic polymorphisms (or mutations) and poor glycemic control, and the disease alleles of DN occur independently and appear. Additive effect. As for the overall effect of the effects of these alleles, it depends on their frequency of occurrence in the population; if the frequency of occurrence in the population is similar, each of them produces a more average effect; if a gene appears more frequently This allele has a major genetic effect, while several other alleles have a minor genetic effect.

(3) Polygenic effects or minor gene effects: DN occurs when many genetic polymorphisms (or mutations) interact with poor glycemic control. Each allele contributes to DN. Genetic susceptibility plays only a minor role

DN susceptibility genes are more studied in 1-DM. Most studies have shown that the frequency of angiotensin II type-1 receptor (AT1R) gene polymorphism (or mutation) in patients with DN is significantly higher than that in patients without combined DN that it may play a major genetic effect. As for the relationship between angiotensinogen (AGT) gene and angiotensin-converting enzyme (ACE) gene polymorphism (or mutation) and DN, no consensus has been reached. Some people use the TDT method to study the relationship between AGT and ACE gene polymorphisms (or mutations) and DN, and find that they are related to DN, and they think that they may play a small genetic effect. In 2-DM, a large Pima Indian family study found that the frequency of ATIR gene polymorphisms (or mutations) was significantly higher in patients with DN than in patients without combined DN, suggesting that it may play a major genetic effect; however, studies in other populations No consistent results were found. In addition, studies on the relationship between the frequency of gene polymorphisms (or mutations) such as AGT, ACE, kinin, and atrial natriuretic aldose reductase and DN have not reached a consistent conclusion. Because many parents of 2-DM patients with DN are no longer alive, it is difficult to use TDT to conduct family research and it is not possible to determine whether these genes exert a microgene effect.

2. In addition to the genetic development of hyperglycemia DN, hyperglycemia also plays a very important role. Strict control of blood glucose can significantly reduce the risk of DN. How hyperglycemia causes DN has not been fully elucidated. However, hyperglycemia can activate many local endocrine hormones (or cytokines) in the kidney. These substances are closely related to the occurrence and development of DN. Of course, the mechanism of DN also includes abnormal blood rheology, red blood cell oxygen dysfunction, and sorbitol bypass. Factors, but these factors are more or less related to local endocrine hormones (or cytokines) in the kidney.

(1) Renin angiotensin system (RAS): Studies have found that the level of angiotensin (AT II) in DM rats is significantly increased. The expression of ATlR in renal tissue is also significantly increased, and clinical and experimental studies have proved that Application of ACE inhibitors can effectively prevent the occurrence and development of DN.

(2) Local renal growth factors: Studies have shown that a variety of local renal growth factors are closely related to the occurrence and development of DN, such as insulin-like growth factor, platelet-derived growth factor, and transforming growth factor-B (TGF-). Etc. They can stimulate the proliferation of mesangial cells and increase the deposition of extra-mesenchymal matrix. Among them, there are more studies on TGF-1. Studies have shown that the expression of FGF-1 in the kidney tissue of DM rats is significantly increased, and the important thing is that it can be significantly decreased after the application of ACE inhibitors. Therefore, it is thought that it may play a key role in the pathogenesis of DN.

(3) Endothelin (ET): ET has a strong vasoconstrictive effect, of which ETI has the strongest effect. It is currently known to stimulate the proliferation of mesangial cells. Experimental studies have shown that the expression of ETI and its receptors in the kidney tissue of DM rats are significantly increased, and the use of ETI receptor antagonists can prevent and treat DN. In addition, in vitro studies have shown that TGF-1 can increase ETI expression in renal tubular cells.

(4) Nitric oxide (NO): NO has a strong vasodilator effect. It is synthesized by L-arginine as a donor under the action of NO synthase (NOS). There are two types of structural NOS and inducible NOS (INOS). The increase of INOs expression and NO content in early renal tissue of DM rats may be related to the increase of early renal blood flow. In the late stage of DM rats, the expression of INOS in the kidney tissue did not increase significantly. The expression of structural NOS and the content of NO were significantly decreased. Some people treated with L-arginine can prevent the occurrence of DN, while long-term application of NOS inhibitors can accelerate the development of Glomerular lesions in mice suggest that NO can prevent the occurrence and development of DN. The above studies suggest that NO can protect the glomerular lesions in DM rats at later stages. At the same time, many studies have shown that NO and AT and TGF-1 in kidney tissues can regulate each other.

The onset of diabetic nephropathy is insidious, slowly progressing, and there are not many symptoms related to early kidney disease. In the early stage of nephropathy, the kidneys are enlarged, the glomerular filtration function and microproteinuria can last for many years, and it is not easy to be noticed. Therefore, most patients with diabetic nephropathy are noticed when there is significant proteinuria or significant edema. The main clinical manifestations of this disease are as follows:

1. Proteinuria is the first clinical manifestation of diabetic nephropathy, which is intermittent at first and then persistent. Using radioimmunoassay to measure albumin or microalbumin in urine can diagnose proteinuria earlier and is beneficial for controlling the disease.

2. Edema, diabetic nephropathy, edema occurs mostly due to a large amount of proteinuria, this stage indicates that it has developed to the late stage of diabetic nephropathy. Clinical manifestations of renal dysfunction, such as decreased GFR, suggest a poor prognosis.

3. Hypertension appears later. At the stage of diabetic nephropathy, the blood pressure is increased, which may be closely related to the changes in the structure and function of diabetic renal resistance blood vessels. In addition, water and sodium retention is also a factor of hypertension. Deterioration is therefore essential to control high blood pressure.

4. Anemia Diabetic nephropathy patients with significant azotemia may have mild to moderate anemia. Anemia is an impediment to erythropoiesis, and treatment with iron is ineffective.

5. Renal dysfunction From the appearance of proteinuria to renal dysfunction, the interval varies greatly. If diabetes is well controlled, proteinuria can be maintained for many years without renal dysfunction. If not controlled, azotemia and renal insufficiency will occur. In addition, diabetic nephropathy is often accompanied by diabetic retinopathy.

From diabetes to kidney disease, it can be divided into 5 stages. Danish scholar Mogensen divides diabetes nephropathy into the following 5 stages:

Phase 1 (function change period): Also known as the period of hyperglycemia or increased filtration rate. In the early stage of diabetes, the glomerular filtration rate has increased. During this stage, renal blood flow gradually increased, the glomerular filtration rate increased, and serum creatinine and urea nitrogen were lower than normal people. At this stage, kidney volume increased by approximately 20%. Renal plasma flow increased, endogenous creatinine clearance increased by approximately 40%, renal histological changes, increased glomerular filtration rate, and increased kidney volume weight, glomerular and tubule volume. Increase related. Observation confirms that increased glomerular filtration rate in early diabetes is related to renal plasma flow. The high filtration of diabetes is related to the dilation of the arterioles and the contraction of the arterioles.

Phase 2 (early glomerular lesion phase): Also known as the resting phase, or the normal albuminuria phase. It often occurs in the course of insulin-dependent diabetes for 18 to 24 months. This period is characterized by the appearance of glomerular structural damage. First, the basement membrane is slightly thickened. After 2 to 3 years, the glomerular mesangial matrix begins to expand 3.5 to 5 years and the basement membrane is significantly thickened. This period of ultrafiltration still has increased urine microalbumin excretion rate after exercise, which is the only clinical evidence of this period.

Stage 3 (recessive nephropathy): or early diabetic nephropathy, which usually occurs 5 to 15 years after insulin-dependent diabetes. This period mainly damages the glomerular basement membrane charge barrier. When the heparin sulfate and sialic acid constituting the glomerular basement membrane components are reduced, the negative charge is correspondingly reduced, the charge barrier is destroyed, and albumin excretion is increased. Urinary protein showed intermittent proteinuria, and renal function began to decline. This is related to poor diabetes control, tissue hypoxia, and increased renal microcirculation filtration pressure, often promoted or induced by hypertension, hyperglycemia, urinary tract infections, and protein load. The glomerular filtration rate is still higher than normal at this stage. With the development of the disease, the urine microalbumin excretion rate (UAER) increases and gradually fixed at 20-200 g / min. Blood pressure may increase later in the period.

Stage 4 (diabetic nephropathy): Also known as persistent proteinuria or clinical diabetic nephropathy. At the peak of the disease, 15% to 20 years, 20% to 40% of insulin-dependent diabetes entered this period of 24h urine protein> 0.5g, if no measures are taken, the glomerular filtration rate will rapidly decline.

There may be a lot of proteinuria during this period, accompanied by hypoproteinemia, edema, and hyperlipoproteinemia. In addition to the loss of urine protein, hypoalbuminemia is related to dysregulation of protein metabolism and insufficient protein intake in diabetes itself. It is also clinically seen that plasma protein levels are higher than those caused by nephropathy when other reasons cause edema. This is due to the conversion of albumin to glycosylated albumin in diabetic patients, which passes through capillary membranes more easily than normal albumin. The prognosis of nephrotic syndrome caused by diabetes is more dangerous, and it quickly enters azotemia. Once the glomerular filtration rate decreases into azotemia, urine protein often decreases rapidly.

Stage 5 (Uremic Phase): End-stage renal disease (ESRD). 30% to 40% of insulin-dependent diabetes develops into end-stage renal disease 20 to 30 years after the onset of disease, at which time uremia manifestations and corresponding histological changes occur. Creatinine clearance is slightly higher than in non-diabetics. According to statistics, the average duration of insulin-dependent diabetes from diagnosis to clinical diabetic nephropathy is about 19 years, and the average duration of persistent proteinuria to death is 6 years. The total course of disease is about 25 years. Diabetic nephropathy has become the single most important cause of end-stage renal failure requiring dialysis or kidney transplantation in European and American countries

Among the above stages of diabetic nephropathy, patients before stage 3 have no obvious manifestations of renal damage clinically, and renal pathological changes can still be reversed. If effective treatment is performed in time, further development of diabetic nephropathy can be prevented. So stage 3 was called early or non-clinical stage of diabetic nephropathy. After entering stage 4, patients will not only have clinical manifestations of kidney damage, but renal pathological changes will be difficult to reverse. The disease will progress progressively and will eventually enter the uremia stage. Little is known about the natural history of nephropathy in non-insulin-dependent diabetes mellitus. Due to the insidious onset, as well as mixed factors such as hypertension and arteriosclerosis, half of the patients do not know they are sick. Often due to occasional blood glucose checks or other diseases, it is found to be low. It is estimated that the clinical nephropathy of this type of diabetes is 2.5% to 10%, which progresses to end-stage renal failure 5 to 10 years. Older patients progress more rapidly than younger patients. The glomerular hyperfiltration period is often uncertain, and 20% to 37% of the non-insulin-dependent diabetic patients diagnosed have an increased urine microalbumin excretion rate. Such a high microalbuminuria excretion rate may be a long-term misdiagnosis. Related glomerular filtration rate can be normal for many years during proteinuria

In addition, hypertension is more common in patients with diffuse glomerulosclerosis, renal arteriosclerosis, and renal failure. Partial nodular sclerosis has mild diastolic blood pressure rise, blood pressure fluctuates greatly in the early stage, and then continues to increase. Recent studies have found that with diabetic nephropathy, as the rate of urinary protein excretion increases, renal function damage increases, and abnormal blood pressure rhythms become more pronounced in diabetic patients. Renal disease causes a drop in nighttime blood pressure in diabetic patients. The possible reasons are:

(1) Water and sodium retention: With diabetic nephropathy, renal blood flow decreases, the glomerular filtration rate decreases, and the increase in water and sodium reabsorption of proximal renal tubules results in water and sodium retention.

(2) Relatively polyuria at night: Diabetes nephropathy patients have increased intramuscular glomerular pressure at night, accompanied by diurnal renal hemodynamic abnormalities and bulb tube imbalance, manifested as nocturnal polyuria.

(3) Impaired autonomic nerve function in patients with diabetic nephropathy: On the one hand, autonomic nerve damage can increase renal hemodynamic abnormalities by increasing the hydrostatic pressure of the glomerular transmembrane, on the other hand, it also participates in the occurrence of water and sodium balance disorders, thereby A circadian rhythm that affects blood pressure.

First of all, we must first understand how diabetes damages the kidney: diabetes can be damaged by different methods. The kidney damage can reach all the structures of the kidney, but only glomerulosclerosis is directly related to diabetes. It is also known as diabetic nephropathy. One of systemic microvascular complications. Therefore, once a diabetic patient has kidney damage and persistent proteinuria occurs, the condition often irreversibly progresses to end-stage renal failure. Diabetic nephropathy has now become the leading cause of death in diabetic patients.

Well, from the above, it can be understood that as long as there is kidney damage in diabetic patients, the condition will rapidly change. The prognosis of diabetic nephropathy is poor. Because its kidney disease is chronic progressive damage, clinical symptoms appear later. Generally, the duration of the disease is more than 10 years. As long as there is persistent proteinuria in diabetic nephropathy, its kidney function will decline irresistibly and progressively. About 25% of patients develop within 6 years, 50% within 10 years, and 75% develop end-stage renal failure within 15 years, from the appearance of proteinuria to death.

The prognosis of diabetic nephropathy is not good, so is there any way to limit diabetes to damage the kidneys? Experts warn that high blood sugar, high blood pressure and high protein diet can accelerate the continuous deterioration of renal function in patients with diabetic nephropathy. Smoking is a considerable risk factor for diabetic nephropathy.

The treatment of diabetic nephropathy should be a comprehensive treatment, with emphasis on prevention and early treatment. There should be such a concept that when patients have diabetes, while preventing diabetes, they must consider the prevention of diabetic nephropathy. Actively control blood sugar, regularly check the urinary albumin excretion rate, control blood pressure, and reduce urinary protein excretion.

1. Controlling the occurrence of diabetic nephropathy is affected by many factors, of which hyperglycemia is an extremely important factor. The relationship between elevated blood glucose and diabetic nephropathy is self-evident. Experimental and clinical studies confirm that good blood glucose control can significantly reduce the incidence of diabetic nephropathy. Therefore, controlling blood glucose is essential. A large number of clinical and animal experiments have proven that renal hypertrophy occurs in diabetes. After the high-filtration state, timely control of blood glucose, correction of metabolic disorders, renal hypertrophy and high-filtration state can be partially restored in the early glomerular filtration rate of diabetic nephropathy and increased glycated hemoglobin are consistent. Therefore, blood glucose control is the basic treatment for diabetic nephropathy. Treatment should take diabetes education, proper exercise of diet therapy, drug treatment and blood glucose monitoring and other means to make blood glucose control as close to normal as possible. For example, try to make glycosylated hemoglobin <7%, fasting blood glucose <6.0mmol / L, 2h postprandial blood glucose <8.0mmol / L, and pay attention to avoid the occurrence of hypoglycemia as much as possible. The main measures include diet and medication.

(1) Diet therapy for diabetic nephropathy: The diet therapy for diabetic nephropathy has its particularity. The total calorie intake should be determined according to the patient's height, weight and activity. In the composition of nutrition, special attention must be paid to protein intake. In diabetic nephropathy, the glomeruli are in a state of high filtration. An excessively high protein diet will continue this state of high filtration and aggravate changes in glomerular hemodynamics. Therefore, it is currently advocated to limit protein intake in the early stages of diabetic nephropathy. It is hoped that this will reduce the glomerular filtration load. Generally, a protein amount of 0.8g / (kg? D) is more suitable. For patients who have entered the clinical stage and have edema, proteinuria, and renal impairment, the intake of protein must be arranged according to the endogenous creatinine clearance. The protein intake of patients must be high-quality protein, that is, animal protein with high amino acid content must be the main ingredient.

(2) The choice of oral hypoglycemic drugs for diabetic nephropathy should consider its metabolic pathways: active metabolites of glibenclamide (glycemic hypoglycemic) and glipizide (damicon) are mainly excreted by the kidneys. When renal function is impaired, it is easy to cause hypoglycemia and should not be used. Gliquidone (glucosepine) is mainly metabolized in the liver. Only about 5% is excreted by the kidney when renal insufficiency is used. It is safe to use and the dosage range used can be the drug of choice for patients with diabetic nephropathy. Some of the metabolites of Glipizide (Meprida) are excreted by the kidneys, but the activity is weak and it is not easy to cause hypoglycemia. It is relatively safe. Biguanide oral hypoglycemic drugs should not be used for clinical stage diabetic nephropathy due to proteinuria, because it is It is excreted from the urine in its original form, which easily causes lactic acid accumulation and lactic acidosis. For patients with diabetic nephropathy who are poorly controlled with diet and oral hypoglycemic agents, insulin should be used as soon as possible to delay and delay the development of diabetic nephropathy. It should be emphasized that for patients with significant renal impairment, the insulin half-life in blood must be considered. Prolonged, followed by decreased appetite and reduced food intake, all of which require fine adjustments in the amount of insulin used to monitor blood glucose frequently to avoid hypoglycemia.

Attention should also be paid to improving insulin resistance and reducing hyperinsulinemia. Diabetic patients often have hyperinsulinemia due to insulin resistance and inappropriate treatment. Persistent hyperinsulinemia can stimulate arterial wall smooth muscle and endothelial cell proliferation; increase liver low-density lipoprotein production and promote arterial wall lipid deposition; damage Endogenous fibrinolytic systems, such as stimulating endothelial cells to produce plasminogen inhibitory factors, promote thrombosis; long-term hyperinsulinemia can increase blood pressure and weight can accelerate the occurrence and progression of arteriosclerosis and reduce hyperinsulinemia In addition to the proper use of oral hypoglycemic agents, supplementation with trace elements such as alum and chromium can also increase insulin sensitivity.

In recent years, the new drug rosiglitazone has been found to be a thiazinidinedione hypoglycemic agent. Its hypoglycemic effects include lowering plasma glucose and insulin levels and improving glucose tolerance; reducing plasma triacylglycerol and free fatty acid levels; reducing liver glycogenogenesis and stimulating glucose uptake by adipose tissue and skeletal muscle. Good medicine.

In addition, according to recent research results, non-enzymatic end-glycosylation products (AGE) of diabetes have an important role in the development of diabetic nephropathy, and AGE inhibitors are used to treat diabetic nephropathy.

Aminoguanidine: It is an AGE inhibitor, which can effectively prevent AGE production or inhibit AGE activity under high glucose conditions. Aminoguanidine selectively inhibits the formation of early products of non-enzymatic glycosylation of proteins by competing with glucose and binding to large proteins. According to research, aminoguanidine also prevents NO activation and regulates vascular dysfunction in early diabetes.

spirohydantoin inhibition: The clinical observation results have a slight effect on the prevention of diabetic retinopathy, peripheral neuropathy and nephropathy, and the effect is slow. Due to the short use time, it is not widely used yet to be evaluated objectively.

2. Control of hypertension Hypertension is a major factor in the occurrence and development of renal impairment in kidney patients, and it is a controllable factor. The same is true for diabetic nephropathy. Hypertension plays a very important role in the development of diabetic nephropathy. Therefore, controlling hypertension is the key to delaying the development of diabetic nephropathy. Control of hypertension must first limit the patient's intake of sodium salts, at the same time ban smoking, abstaining from alcohol, reduce weight, and exercise appropriately. This is the basis of treatment.

It is generally believed that the blood pressure of patients with diabetic nephropathy should be controlled below 17.5 / 11kPa. Relevant data show that when the blood pressure drops from 21.3 / 12.7kPa to 18.0 / 11.3kPa, the urinary protein excretion is significantly reduced. The rate of glomerular filtration decreases from 1ml / min to 0.35ml / min per month. The survival of patients with diabetic nephropathy The period was also significantly prolonged, with a cumulative mortality of 50% to 70% before 10 years of antihypertensive treatment and 18% after treatment. Clinical studies have proven that effective antihypertensive treatment can significantly prevent or delay the occurrence and development of many chronic diseases of diabetes. Studies show that active antihypertensive treatment can delay the progress of clinical diabetic nephropathy, especially when blood pressure has started to rise and has not yet reached clinical hypertension. Antihypertensive treatment should reduce average arterial pressure, restore blood pressure circadian rhythm, and reduce glomerular pressure. .

The choice of antihypertensive drugs is currently angiotensin-converting enzyme inhibitors, which can reduce the excretion of urinary protein and slow the decline of renal function. The mechanism is:

(1) Reduce the pressure of glomerular capillaries, thereby correcting the high filtration state and reduce proteinuria. Recently, ACEI is also believed to directly improve the selective filtering effect of glomerular capillaries.

(2) Inhibit the activity of cell growth factors such as transforming growth factor beta, and increase the sensitivity of skeletal muscle insulin to improve blood glucose control.

(3) Reduce the phagocytosis of macromolecular substances by mesangial cells, thereby reducing mesangial cell proliferation and tubulointerstitial fibrosis due to proteinuria.

(4) Promote the degradation of matrix metalloproteinases, so that the formed part of the cell matrix can be degraded. The role of ACEI is not only for lowering blood pressure, but also suitable for patients with diabetic nephropathy without hypertension, and it is convenient to take medicine. Its main side effect is cough. Currently, long-acting agents using angiotensin-converting enzyme inhibitors (ACEI) are popular. The drugs commonly used in the clinic are: Captopril (Kaibo Tong), Enalapril (Wing Ning Ding), Perindopril (Yashida), Benazepril (Luodinxin), Fosinopril Lee (Mono) and so on. It is worth noting that ACEI can cause hyperkalemia in patients with decreased renal function.

Angiotensin receptor antagonists are also gradually used in diabetic nephropathy. At present, the commonly used angiotensin type I receptor (AT) blockers do not have adverse effects such as cough because they have no effect on kinin; meanwhile, AT Higher angiotensin after receptor blockade can stimulate angiotensin II receptor (ATII), which can have antiproliferative effects and is therefore better than ACEI. However, some studies have shown that the renal protective effect of ACEI is caused by bradykinin, so it is not yet conclusive. Losartan is the first of the new AT class drugs. According to data from more than 4,000 patients, losartan is an effective antihypertensive drug at a dose of 50-100 mg / d and is well tolerated.

Calcium channel antagonists can reduce mean arterial pressure, can alleviate angina, and lower intracellular calcium can improve insulin resistance. Another class of drugs recommended for the treatment of diabetic nephropathy and hypertension. However, the effect of L-type calcium channel blockers on renal protection is not as clear as that of ACEI. Recent T-type calcium channel blockers can reduce protein and have better application prospects. Commonly used drugs are alpha-blocker prazosin and urapidil (nunidine) have no adverse effects on sugar and fat metabolism, and have good antihypertensive effect. Uladil (Bunidine) has a better antihypertensive effect than prazosin. This drug can be injected intravenously to treat severe hypertension. Such drugs have adverse effects of orthostatic hypotension, and care should be taken when applying them.

Indapamide (sodium catalysis) can increase the excretion of sodium in the urine, does not affect glucose metabolism and fat metabolism, has a dual effect of lowering blood pressure and diuresis, and has a synergistic effect with ACEI.

3. Dialysis and kidney transplantation Dialysis and kidney transplantation are the necessary measures for the treatment of renal failure. Most patients with diabetic nephropathy are associated with systemic arteriosclerosis, and vascular wall stiffness is difficult to establish and maintain for a short time. Peritoneal dialysis is an ideal choice for patients with diabetic nephropathy. Ambulatory continuous peritoneal dialysis can be used in operation without the need to establish vascular access. In general, regardless of hemodialysis and peritoneal dialysis, the survival rate of patients with diabetic nephropathy in maintaining dialysis is not as good as that of non-diabetic nephropathy patients. The main reason is that diabetic nephropathy with cardiovascular disease has increased significantly. When kidney function worsens, some serious complications such as pericarditis, colitis, bleeding tendency, and neurological diseases greatly shorten the survival time.

(1) Dialysis treatment: The timing of dialysis treatment for diabetic nephropathy is very important. First, it should be early and not later when the endogenous creatinine clearance min or blood creatinine is> 530 7lOmol / L (7mg / dl). .

(2) peritoneal dialysis therapy: peritoneal dialysis is one of the main treatments for end stage of diabetic nephropathy. Because peritoneal dialysis has the following advantages:

Avoid excessive circulation load and reduce heart load.

It can remove medium molecular weight toxins and effectively control the symptoms of uremia. It is better than hemodialysis in improving anemia, neuropathy and bone disease.

Since insulin can be absorbed from the peritoneum, adding insulin (per 4g glucose plus 1U insulin) directly to the peritoneal fluid can control hyperglycemia.

Increasing the osmotic pressure of peritoneal fluid can correct the excessive blood volume and effectively control blood pressure.

Does not require systemic heparinization, which can prevent retinal bleeding and affect vision.

The disadvantages of peritoneal dialysis are mainly prone to peritonitis, low immunity to diabetes, exit infections or tunnel mouth infections. Long-term peritoneal glucose overload can cause patients with obesity and hyperlipidemia, such as the loss of protein and amino acids in peritoneal fluid. bad. Long-term peritoneal dialysis failure is often caused by peritoneal sclerosis.

(3) Hemodialysis therapy: Hemodialysis is faster than peritoneal dialysis in removing toxins, controlling blood sugar and adjusting electrolytes. It is reported in the literature that diabetic patients have limb gangrene due to severe inadequate blood supply, and those who need amputees have less hemodialysis than peritoneal dialysis. However, hemodialysis has the following disadvantages:

Arteriosclerosis is more common in diabetic patients, and the vascular route for internal fistula is difficult.

Diabetes is often complicated by coronary heart disease and myocardial disease caused by myocardial metabolic disorder, which makes the cardiovascular system of patients with poor stability, so hypotension is prone to occur during hemodialysis. At this time, it is more likely to occur due to autonomic dysfunction.

Due to low intake and diabetic uremia due to long renal half-life and increased insulin effect, hypoglycemia can occur after hemodialysis.

Diabetic nephropathy without urine or oliguria for continuous hemodialysis, prone to hyperkalemia than other patients with kidney disease, especially in patients with ACEI.

(4) Kidney transplantation: It is the best way to treat diabetic nephropathy and uremia than dialysis. At present, the survival rate of living donor transplantation is similar to that of non-diabetic patients. The main causes of death from diabetic kidney transplantation are cardiac and cerebrovascular complications and infections. There are also more ureteral necrosis bladder leaks and neurogenic bladder than non-diabetic nephropathy. Therefore, in order to improve the survival rate and quality of life of diabetic kidney transplantation, we emphasize the treatment of cardiovascular complications before blood glucose control and dialysis as soon as possible.

Although dialysis and kidney transplantation are effective for the treatment of advanced diabetic nephropathy, the cost of treatment is large and the source of donor kidney is difficult. Therefore, the fundamental treatment of diabetic nephropathy lies in early control and delayed development, which needs to be paid great attention by clinicians. At present, clinical observation of kidney transplantation alone cannot prevent the recurrence of DN. For example, poor glycemic control may lead to glomerular sclerosis and lead to uremia again. In addition, other diabetic complications cannot be improved with kidney transplantation. Combined pancreas-kidney transplantation is now a commonly used and mature treatment due to the resolution of many technical issues. Compared with kidney transplantation alone, the survival rate of patients has improved significantly. According to a group of 31 IDDM patients, combined pancreas-kidney transplantation23 Follow-up for months: The results showed that all patients had glycated hemoglobin levels, creatinine levels returned to normal, other comorbidities improved, and the quality of life was significantly better than those of kidney transplantation alone. At present, the number of transplant patients in the world is about 1,000 in one year. The 1-year survival rate was 94%, the renal survival was 91%, the pancreatic survival was 67%, the 3-year survival rate was 89%, and the renal survival was 69%. The pancreatic survival was 64%.

Kidney or pancreas-kidney transplantation is the best choice for diabetic patients with ESRD. Compared with non-diabetes, the survival rate of grafts and the maintenance of renal function are all lower. In recent years, with the continuous development and progress of immunosuppressive agents, such as cyclosporine, mycophenolate mofetil (Xiaoxi), etc., more and more diabetic patients have received kidney transplantation, and the transplantation effect has also improved significantly. The high-risk factors for such patients receiving kidney transplantation include: existing macrovascular disease, left ventricular hypertrophy, and hypertension. At present, it is believed that existing cardiovascular problems need to be corrected before transplantation. Some foreign countries have coronary angiography for all diabetic patients who need renal transplantation. If coronary heart disease is present, first use bypass or vascular intervention to correct it.