What do you know of diabetic nephropathy

Diabetic nephropathy (diabetic nephropathy, DN) is a serious and chronic complications of the biggest dangers caused by diabetes , glomerular sclerosis microvascular disease caused by diabetes caused , is characteristic of this disease . Is also a major cause of death in patients with IDDM . Diabetic patients with infectious diseases such as pyelonephritis, renal papillary necrosis, renal vascular disease such as atherosclerosis, is not a category of diabetic nephropathy. With the progress of diabetes treatment and technology, died of diabetes complications such as fewer patients with acute ketoacidosis , diabetes mellitus and cardiovascular disease and kidney disease has become the main cause of death in diabetic patients in recent years , resulting in residual reasons. Diabetic nephropathy occurs not only in type 1 diabetes. In recent years, found that Type 2 diabetes can also develop into diabetic nephropathy .
Signs and symptoms Edit this paragraph
Diabetic nephropathy insidious onset , slowly progressive , not much about the early symptoms of kidney disease . Early nephropathy and renal enlargement , glomerular filtration hyperthyroidism and microalbuminuria sustainable for many years , is not easy to be noticed , so most patients with diabetic nephropathy is significant proteinuria or party is aware of significant edema . The main clinical manifestations of this disease are as follows :
1 proteinuria of diabetic nephropathy is the first clinical manifestation , first as intermittent , after conversion to sustainability. By radioimmunoassay or micro albumin in urine albumin , earlier diagnosis can proteinuria , beneficial to control the disease.
2 diabetic nephropathy edema occurred more due to massive proteinuria and edema caused by this late stage has been developed to show that diabetic nephropathy . More associated with decreased GFR and other clinical manifestations of renal dysfunction , suggesting a poor prognosis.
3 hypertension appeared later . Multi- stage diabetic nephropathy when elevated blood pressure, diabetes may be associated with renal vascular resistance changes in the structure and function are closely related , in addition, sodium retention is one of the factors for hypertension . Hypertension can increase the development of worsening kidney disease and renal function , and therefore control of hypertension is essential.
4 anemia in patients with diabetic nephropathy significant azotemia , may have mild to moderate anemia. Anemia is a disorder of erythropoiesis , ineffective treatment with iron .
5 abnormal renal dysfunction intervals vary greatly from proteinuria appears to renal function, if diabetes is well controlled, multi proteinuria without renal dysfunction. If the control is not good , there will be azotemia , renal insufficiency. In addition , diabetic nephropathy is often accompanied by diabetic retinopathy.
From diabetic nephropathy progression to , and can be divided into five stages , diabetic nephropathy Danish scholar Mogensen will be divided into the following five :
A ( functional changes of ) : also known as the glomerular filtration rate or hyperthyroidism increased period of . Early diabetic glomerular filtration rate both increased , at this stage for several years . Gradually increased renal blood flow , increased glomerular filtration rate , serum creatinine and urea nitrogen is lower than normal . This period , kidney volume increased approximately 20% increase in renal plasma flow , creatinine clearance rate increased by about 40%, kidneys no histological changes . Glomerular filtration rate and renal volume , weight increase , increased glomerular and tubular volume related. Observation confirmed early diabetic glomerular filtration rate and renal plasma flow increased correlation . Diabetes, high filtration and afferent and efferent arteries artery contraction .
2 ( early glomerular lesions period ) : also known as resting phase , or normal albuminuria period . Often appear in insulin-dependent diabetes duration of 18 to 24 months. Period is characterized by glomerular structural damage occurs , the first is a mild thickening of the basement membrane , 2 to 3 years after the start of mesangial matrix expansion , 3.5 to 5 years of basement membrane thickening . This ultrafiltration still exists. Urine albumin excretion rate increases after exercise , is the only current clinical evidence.
3 ( recessive kidney period ) : or early diabetic nephropathy , often appear in the insulin- dependent diabetes mellitus 5 to 15 years. Current major damage to the glomerular basement membrane charge barrier . So that heparan sulfate and sialic acid constitutes the glomerular basement membrane components is reduced, then the corresponding decrease in negative charge , the charge barrier damage , albumin excretion . Urine protein was intermittent , somewhat heavier proteinuria and kidney function began to subside . This poorly controlled diabetes , tissue hypoxia, increased renal microcirculation filtration pressure related to or induced by the constant promotion of high blood pressure, high blood sugar , exercise, urinary tract infection and protein load. This period of glomerular filtration rate is still higher than normal , with the progression of the disease , urinary albumin excretion rate (UAER) and gradually increased fixed at 20 ~ 200μg/min, after the current phase of high blood pressure can occur .
4 ( diabetic nephropathy period ) : also known as persistent proteinuria or clinical stage diabetic nephropathy . Peak prevalence in the course of 15 to 20 years , 20 % to 40% of insulin- dependent diabetes to enter the , 24h urine protein > 0.5g, such measures are not taken , the glomerular filtration rate decreased rapidly.
This may have a lot of proteinuria , accompanied hypoalbuminemia, edema and hyperlipoproteinemia . Low albumin urinary protein loss in addition to outside hyperlipidemia , and diabetes itself insufficient protein and protein intake related metabolic disorders . Clinical plasma protein levels may also see the edema than the other causes kidney , which is due to changes in people with diabetes is albumin glycated albumin , which passes through the capillary membrane easier than normal albumin . Nephrotic syndrome caused by diabetes prognosis is more sinister , and rapid access to azotemia . Once azotemia , glomerular filtration rate , proteinuria often quickly reduced.
5 ( uremia ) : namely, end stage renal disease ( referred to as ESRD). Insulin- dependent diabetes mellitus in 30% to 40% develop in 20 to 30 years after the prevalence of end-stage renal disease, uremia appears manifestations and histological changes accordingly . Creatinine clearance rate is slightly higher than non- diabetics . According to statistics from insulin-dependent diabetes to enter clinical diagnosis of diabetic nephropathy an average of about 19 ​​years , persistent proteinuria to death an average of six years , with a total duration of about 25 years. In the United States and Europe has become the most important reason of diabetic nephropathy with end-stage renal failure requiring dialysis or a kidney transplant individual .
These diabetic nephropathy staging , three former patients no obvious clinical manifestations of kidney damage , kidney pathology can still be reversed , should be timely and effective treatment can prevent further development of diabetic nephropathy. So three formerly known as diabetic nephropathy and non- clinical stage . And upon entering 4 after kidney damage occurs not only in patients with clinical manifestations, pathological changes have been difficult to reverse , the progressive development of the disease , eventually entering uremia . Non- insulin-dependent diabetes know very little about the natural history of nephropathy due insidious onset , as well as the inclusion of factors such as hypertension and arteriosclerosis , half of the patients do not know that he is sick . Often due to occasionally check blood sugar or suffering from other diseases were found. This type of diabetes is estimated lower clinical nephropathy was 2.5 % to 10% , progression to end-stage renal failure five to 10 years, elderly patients compared to younger patients progress rapidly. Glomerular filtration often unsure of , an increase in non -insulin-dependent diabetic patients diagnosed in 20% to 37% has been fixed urine albumin excretion rate , such a high excretion rate of microalbuminuria and long-term misdiagnosis may related. Proteinuria and glomerular filtration rate may be normal during the years .
In addition , with regard to hypertension is more common in diffuse glomerulosclerosis , renal arteriosclerosis and renal failure . Part of tuberous sclerosis with mild diastolic blood pressure , early large fluctuations in blood pressure , increase was sustained after . Recent studies have found that diabetic kidney disease, with the increase in urinary protein excretion rate , increased kidney dysfunction , diabetes, blood pressure rhythm abnormalities are more obvious. Diabetic kidney disease resulting in nighttime blood pressure . Possible reasons are:
( 1 ) Shuinazhuliu : diabetic nephropathy patients with decreased renal blood flow , glomerular filtration rate , proximal tubular reabsorption of sodium and water increased, leading to sodium retention .
( 2 ) the relative nocturnal polyuria : increased pressure within the glomeruli nocturnal patients with diabetic nephropathy , renal hemodynamic abnormalities associated with circadian tube and balance disorders , manifested as nocturnal polyuria .
( 3 ) patients with diabetic nephropathy kidney autonomic dysfunction : autonomic nervous system dysfunction may aggravate renal blood flow abnormalities on the one hand by increasing glomerular transmembrane hydrostatic pressure , on the other hand is also involved in the occurrence of sodium and water balance disorders , thus affecting the circadian rhythm of blood pressure .
2 drug treatment edit this section
Treatment of diabetic nephropathy treatment should be comprehensive , emphasizing prevention and early treatment. Should have such a concept that when patients with diabetes , in the treatment of diabetes , we must consider the prevention of diabetic nephropathy. Positive control of blood glucose , urinary albumin excretion rate checked regularly to control blood pressure, reduce urinary protein excretion .
1 . The control of blood glucose in diabetic nephropathy occurs affected by many factors , including high blood sugar is extremely important factors . The relationship between hyperglycemia and diabetic nephropathy is self-evident , experimental and clinical studies have confirmed good blood glucose control can significantly reduce the incidence of diabetic nephropathy. Therefore , control of blood glucose is essential. Numerous clinical and animal experiments show that in diabetic renal hypertrophy and hyperfiltration state , the timely control of blood glucose , corrected metabolic disorders, renal hypertrophy and hyperfiltration state can be partially restored. Diabetic nephropathy increased glomerular filtration rate and elevated glycated hemoglobin is consistent . Therefore, controlling blood sugar is the basic treatment for diabetic nephropathy . Treatment should take diabetes education, diet , adequate exercise , medication and blood glucose monitoring and other means , as much as possible so that near-normal blood glucose control . If strive to make glycosylated hemoglobin < 7% , fasting plasma glucose <6.0mmol / L, 2h postprandial blood glucose <8.0mmol / L, taking care to avoid hypoglycemia . The main measures include diet therapy and medication.
( 1 ) dietary treatment of diabetic nephropathy : Diabetic nephropathy diet therapy has its particularity, the total calorie intake should be determined according to the patient height, weight and activity level . Nutritional composition , and pay special attention to protein intake. Diabetic nephropathy , glomerular filtration in the high state , high -protein diet will make this high filtration state continues , aggravating change glomerular hemodynamics. Therefore, it is advocated in the early stage of diabetic nephropathy to limit the intake of protein. Hoping to lighten the load of glomerular filtration . General 0.8g / (kg · d) of the protein is more appropriate. To have entered clinical stage , patients with edema, proteinuria , renal damage , shall in accordance with endogenous creatinine clearance rate to arrange protein intake . Patients must be of high quality protein intake of protein , essential amino acids that high levels of animal protein -based.
( 2 ) Select diabetic nephropathy oral hypoglycemic drugs should consider their metabolic pathways : glibenclamide ( glyburide ) , gliclazide ( gliclazide ) of the active metabolite is mainly excreted by the kidneys. Renal dysfunction, easily lead to low blood sugar, unfit for use. Gliquidone ( Gliquidon ) is mainly metabolized in the liver , only approximately 5% excreted by the kidney, renal insufficiency , the use of more secure , and high-dose range used as the drug of choice in patients with diabetic nephropathy . Glipizide ( glipizide ) part metabolites excreted by the kidneys , but the activity is weak, are unlikely to cause low blood sugar reactions , safer. Biguanide oral hypoglycemic drugs already in clinical proteinuria of diabetic nephropathy should not be used because it is excreted unchanged in the urine , could easily lead to the accumulation of lactic acid caused lactic acidosis. For with diet and oral hypoglycemic agents in diabetic nephropathy patients with poorly controlled , insulin as soon as possible to postpone , delay the onset of diabetic nephropathy and development. It should be emphasized that, for patients with significant renal impairment , taking into account the extension of the half-life in blood insulin , followed by patients with anorexia, eating less , these need to be refined to insulin dosage adjustments, frequent monitoring of blood glucose, avoid low glucose occurred.
Note also improve insulin resistance, reduce hyperinsulinemia. Diabetic patients often due to the presence of insulin resistance and hyperinsulinemia improper treatment caused lasting hyperinsulinemia can stimulate the arterial wall smooth muscle and endothelial cell proliferation ; increased hepatic LDL produce , promote arterial wall lipid calm ; damage endogenous fibrinolytic system such as stimulation of the endothelial cells produce inhibitors of plasminogen , and promote thrombosis ; term hyperinsulinemia can increase blood pressure and the onset and progression of weight gain can be accelerated atherosclerosis. In addition to reducing hyperinsulinemia appropriate use of oral hypoglycemic drugs, trace elements such as vanadium and chromium supplements may also increase insulin sensitivity.
In recent years, found that drug rosiglitazone thiazide TZDs as antidiabetic drugs . Its hypoglycemic effects include decreased plasma glucose and insulin levels , improve glucose tolerance ; decreased plasma triglycerides and free fatty acid levels ; reduce the role of hepatic gluconeogenesis and stimulate adipose tissue and skeletal muscle glucose uptake . Insulin resistance is better drugs .
Moreover, according to recent findings in diabetic non-enzymatic glycation end products (AGE) has an important role in the development of diabetic nephropathy , diabetic nephropathy using AGE inhibitor therapy .
① aminoguanidine : an AGE inhibitor, which under high glucose conditions can also be effective in preventing or inhibiting AGE AGE generating activity . Aminoguanidine competition through a combination of glucose and protein macromolecules , selective inhibition of non-enzymatic glycation of proteins formed early products. According to the research , but also to prevent NO activation aminoguanidine adjust early diabetic vascular dysfunction.
② aldose reductase (spirohydantoin): clinical observations preventing diabetic retinopathy , peripheral neuropathy, and nephropathy mild and slow onset . Due to the use of a short time, do not use a wide range of objective assessment to be made ​​.
2 Control Hypertension Hypertension is the occurrence of kidney patients with impaired renal function , the main factor in development, but is controllable factor. The same is true for diabetic nephropathy . Hypertension in the development of diabetic nephropathy play a very important role , therefore , control of hypertension , is the key to delaying the development of diabetic nephropathy . To limit the control of hypertension in patients with first intake of sodium , while smoking , drinking, weight loss, proper exercise , which is the basis of treatment.
Now generally believed that patients with diabetic nephropathy blood pressure should be controlled at 17.5/11kPa less. Relevant data show that blood pressure dropped from when 21.3/12.7kPa 18.0/11.3kPa, urinary protein excretion was significantly reduced, the rate of decline in glomerular filtration rate dropped from a monthly 1ml/min monthly 0.35ml/min, in patients with diabetic nephropathy survival was significantly prolonged antihypertensive treatment before l0 -year cumulative mortality rate was 50% to 70 % and 18% after treatment . Clinical studies have confirmed an effective antihypertensive treatment can prevent or significantly delay the onset of many chronic diseases and the development of diabetes . Studies have shown that active antihypertensive treatment can slow the progression rate of clinical diabetic nephropathy , especially in the blood pressure began to rise yet reached clinical hypertension is more obvious when , antihypertensive therapy should be to reduce mean arterial pressure , restore circadian blood pressure and reduce glomerular internal pressure .
Choice of antihypertensive drugs , angiotensin converting enzyme inhibitors currently preferred , it can reduce urinary excretion of protein , slowing the rate of decline in kidney function . The mechanism is :
( 1 ) reduced glomerular capillary pressure, thus correcting high filtration state also reduced proteinuria, ACEI can also believes that the recent improvement in the selectivity of the glomerular capillary filtration effect .
( 2 ) inhibition of cell growth factors such as transforming growth factor- β like activity, and improve glycemic control and may increase insulin sensitivity in skeletal muscle .
( 3 ) reduced mesangial cell phagocytosis of macromolecules , thus reducing the inter mesangial cell proliferation caused by proteinuria and tubulointerstitial fibrosis.

( 4 ) promote the degradation of matrix metalloproteinases that part of the extracellular matrix degradation has been formed . ACEI role not only for the buck , but not in patients with diabetic nephropathy with hypertension should also apply , and easy to medication, its main side effect is cough. Currently, the popular use of angiotensin -converting enzyme inhibitors (ACEI) long-acting formulations .