elderly diabetic nephropathy
Introduction
Introduction to diabetic nephropathy in the elderly Diabetic nephropathy (DN) is caused by diabetic microangiopathy. Early manifestations of microalbumin excretion in the urine, followed by clinical proteinuria, and finally development of chronic renal insufficiency. End-stage renal disease is the leading cause of death from diabetes in the elderly. basic knowledge The proportion of illness: 0.087% Susceptible people: the elderly Mode of infection: non-infectious Complications: uremia heart failure arrhythmia coma
Cause
The cause of diabetic nephropathy in the elderly
(1) Causes of the disease
It is now clear that the occurrence and development of diabetic nephropathy is caused by the condensation of various factors, disorders of glucose metabolism, abnormal renal hemodynamics, various active cytokines and genetic factors play an important role in the occurrence of this disease.
(two) pathogenesis
Pathogenesis
(1) Genetics: For a long time, people have noticed the following chronic facts such as long-term uncontrolled blood glucose and kidney disease, and found the following facts, suggesting that there may be genetic factors.
Although 40% to 50% of IDDM patients can eventually develop significant clinical nephropathy, more than half of the patients do not have kidney disease for life without regard to glycemic control. This heterogeneity cannot be explained by differences in metabolic regulation. New cases of IDDM The annual incidence rate reached its peak in the course of 20 years, and the disease course showed a sharp decline after 30 years.
The occurrence and development of DN is inconsistent with the course of disease and the degree of metabolic control. Some diabetic patients never have kidney disease despite long-term loss of blood sugar, and about 5% of diabetic patients have severe DN in the short-term onset despite good glycemic control.
1 ACE gene genetic polymorphism and DN: It has been confirmed that the 287 bp insertion/deletion (I/D) polymorphism in the 16th intron of the angiotensin I converting enzyme (ACE) gene is associated with the onset of coronary heart disease, and the genotype DD is coronary heart disease. Independent risk factors for myocardial infarction. In recent years, a few studies have begun to pay attention to the relationship between ACE gene I/D polymorphism and microangiopathy such as DN. It has been confirmed that ACE gene I/D polymorphism can affect angiotensin II and vasodilatation. Peptides affect systemic and intravascular renal vasomotor and hemodynamic changes, which may increase renal perfusion pressure and GFR, thereby promoting the occurrence of kidney disease.
2 erythrocyte membrane Na+/Li+ reverse transport (SLC) activity: increased SLC activity on erythrocyte membrane is a marker of genetic susceptibility to essential hypertension. Many studies have reported that SLC activity in erythrocyte membrane of DN patients is significantly higher than that without renal disease. In patients with diabetes, Carr et al reported that IDDM patients found increased cell membrane SLC activity before nephropathy, and found that the glomerular filtration rate of patients with increased SLC activity was significantly increased, while the early stage of renal disease showed an increase in glomerular filtration rate. Erythrocyte SLC is a useful indicator for early detection of kidney disease in patients with NIDDM.
3N-acetyltransferase (NAT2) gene: Heparin sulfate proteoglycan (HS-PG) is a major component of the glomerular capillary basement membrane, mesangial and vascular wall glycosaminoglycans, which plays an important role in maintaining its structural integrity. Role, NAT2 is a key enzyme for HS-PG sulfation. NAT2 has genetic polymorphism, some are sensitive to hyperglycemia, and activity is easily inhibited, thereby inhibiting the synthesis of HS-PG and affecting the integrity of glomerular basement membrane. Sexuality, prone to proteinuria, other NAT2 gene expression of NAT2 is not susceptible to hyperglycemia and other factors, so it is not easy to appear proteinuria, it has been reported that the NAT2 gene point mutation can cause the acetylation process to slow down, and micro-white with IDDM patients Proteinuria is associated.
4 aldose reductase gene: hyperglycemia leads to the first key enzyme in the polyol active pathway is aldose reductase (AR), under the same hyperglycemia conditions, with high AR activity in diabetic patients including DN Chronic complications are susceptible, Hamado et al reported that the AR activity of erythrocytes in diabetic patients varies greatly. The AR activity of erythrocytes in diabetic patients with diabetic microvascular complications in a short period of time is significantly higher than that in patients with a disease course >25 years without significant complications of diabetes. The expression level of AR gene can partially affect the rate of production of polyol products. Therefore, it is speculated that the difference in AR activity caused by AR gene abnormality may be related to the occurrence of microvascular disease such as DN.
5 Other genetic factors: In addition to some of the above genetic factors or genes, scholars have explored other genetic factors, Ronningen studied 114 HLA-DR, -DQ genes and insulin genes in IDDM patients with a course of more than 15 years. No trace of albuminuria was found to be associated with the HLA class II antigen gene region, nor was it associated with insulin polymorphism. Individual studies reported collagen IVla gene HindIII digestion polymorphism and NIDDM with nephropathy and retina Complications are related. Mimura studies the relationship between erythrocyte Na+/K+-ATPase activity and DN in NIDDM.
It was found that the erythrocyte Na+/K+-ATPase with the microalbuminuria group was significantly lower than that of the unbound microalbuminuria group. In recent years, 5778 bp deletion of the mitochondrial gene was found in 5 patients with diabetes with muscle atrophy, nephropathy or chronic renal failure. And believe that this may be caused by the body's related tissue oxidative phosphorylation barrier.
The genetic mechanism of DN has not been elucidated. Scholars have studied from various angles and from various possible aspects of the pathophysiological process of renal pathology, and found some genetic factors, because diabetes is mostly multi-gene, multi-factor disease. Therefore, the genetic problem of kidney disease may also be the result of multi-gene, multi-factor comprehensive influence, find the main affected genes, find genetic susceptibility and early intervention to further improve the prognosis of diabetes.
(2) Biochemical metabolic disorders:
1 Polyol pathway: In the past 20 years, a large number of studies have proved that the activation of polyol pathway of glucose metabolism is one of the important pathogenesis of chronic complications of diabetes. The metabolic pathway of aldose reductase (AR) and sorbitol dehydrogenase In this pathway, AR uses NADPH as a coenzyme to reduce glucose to sugar alcohol-sorbitol, which is then oxidized by sorbitol dehydrogenase.
AR is the main rate-limiting enzyme in the polyol pathway. AR is widely distributed in various tissues and cells (such as liver, retina, crystal and adrenal gland, etc.). Various renal tissue cells such as glomerular basement membrane, mesangial cells, and epithelium Cells and podocytes are also rich in AR. The body is regulated by NADPH/NADP+ ratio and surrounding glucose concentration, which controls AR activity and affects the production rate of sorbitol and fructose. In the AR catalytic reaction, NADPH is required to provide hydrogen, and NADP+ inhibits AR activity. Role, hyperglycemia, NADPH increased>NADP+, AR activity increased, under normal circumstances, when blood glucose is normal, AR competes with hexokinase for glucose metabolism, due to the affinity of hexokinase for glucose (Km=0.1mmol/L) Higher than AR (Km=70mmol/L), AR activity inhibition, sorbitol production is rare, glucose is mainly metabolized by glycolysis pathway, hexokinase tends to be saturated when diabetes is hyperglycemic, and AR activity is increased to sorbitol production. A common feature of diabetes, which is easily damaged by tissues (such as crystals, nerves, retinas, and kidneys) is that its intracellular glucose levels are not regulated by insulin. In hyperglycemia, these tissues The intracellular glucose concentration is parallel to the blood glucose level, the hyperglycemia causes an increase in AR activity, and the polyol metabolic pathway is activated.
Polyol pathway activation accelerates the development of chronic complications of diabetes through a variety of mechanisms: 1 the concentration of sorbitol in the tissue cells increases, sorbitol is a very polar compound, unable to freely enter and exit the cell, thus causing it to accumulate in the cell, On the other hand, it causes cell osmotic edema, on the other hand, it destroys the integrity of cell structure and function, reduces inositol intake, increases loss, and thus affects the metabolism of phosphatidylinositol, and inositol diphosphate is converted to inositol triphosphate, resulting in Na+ Decreased activity of /K+-ATPase further aggravates the damage of cell metabolism and function, produces lesions, activates 2 sorbitol pathway, increases NADPH consumption, and reduces the production of reduced glutathione in NADPH to provide hydrogen, AR and glutathione Reductase competition utilizes NADPH. Once NADPH does not meet the needs, reduced glutathione production is reduced, intracellular redox imbalance, decreased antioxidant capacity, reduced free radical scavenging, impaired tissue and cell function; Sorbitol is further reduced to fructose by sorbitol dehydrogenase, and tissue protein fructose increases its harm Animal experiments reported that the expression of AR mRNA in kidney tissue of diabetic animals increased, the content of sorbitol was significantly higher than that of the control group, the decrease of inositol and the activity of Na+/K+-ATPase decreased, and the AR inhibitors could prevent and correct the above changes. Sorbinil treatment of STZ diabetic rats can significantly reduce urinary protein excretion, prevent or reduce GBM thickening. At present, most scholars believe that the activation of polyol pathway plays an important role in the development of DN. Early application of AR inhibitors for diabetes Chronic complications have a certain preventive effect. Once complications have occurred, tissue cells often have irreversible damage, the effect is not good, some scholars in China have reported that some Chinese medicines, such as quercetin and silybin, can also inhibit AR.
2 protein non-enzymatic glycation: non-enzymatic glycation of glucose molecules and proteins has been widely recognized, it plays a very important role in the etiology of a variety of chronic complications of diabetes, protein non-enzymatic glycation sugars (mainly For glucose, other fructose, galactose and triose, etc.), the nucleophilic addition polymerization process between the aldehyde group and the -amino group of the N-terminal free amino acid or lysine residue of various proteins, also known as the addition reaction or In the Maillard reaction, the glucose molecule first forms an unstable glycation product (Schiff reaction) with the protein amino acid, and its formation rate (K1) = dissociation rate (K-1), which can be reached in a few hours. In the early stage, the protein is not enzymatically glycated. The amount increases with the increase of blood glucose and the contact time of protein and glucose. When the blood glucose returns to normal, it can be reversed. However, in the case of persistent hyperglycemia, the early glycation products are further subjected to a slow chemical structure rearrangement (usually several weeks) to form a A relatively stable sugar-protein product, the Amadori product (ketoamine compound), the Amadori product is also reversibly balanced, generally after 4 weeks of equilibrium, Most of the Amadori products are dehydrated and rearranged to form complex glycation and products (AGEs) with complex and physiological transduction rates and accumulate in proteins with long half-life (such as collagen, crystal protein). And elastin, etc.) and on the blood vessel wall, and accumulate over time. Even if the hyperglycemia is effectively corrected, the glycated protein cannot return to normal.
Non-enzymatic glycation of proteins leads to physical and chemical properties, functional and structural changes of proteins, and promotes chronic complications of diabetes through a variety of pathways.
1 protein regulation function changes: such as hemoglobin saccharification, resulting in decreased binding to 2,3-diphosphoglycerol, oxygen shift curve left shift, tissue hypoxia, microvascular dilatation; antithrombin III glycosylation, its anticoagulant effect Reduced, resulting in hypercoagulable state of the blood, AR saccharification, its activity increased, involved in the activation of the polyol pathway; low-density lipoprotein (LDL) saccharification, decreased affinity with its receptor, LDL clearance decreased, resulting in plasma LDL concentration It rises, infiltrates into the blood vessel wall, and is cleared by the macrophage scavenger pathway to form foam cells and promote vascular complications.
2 Insoluble matrix proteins with long extravascular half-life (such as vascular matrix, glomerular basement membrane, neuromyelin, crystal protein and skin collagen) can be cross-linked by AGEs, cross-linked proteins to proteolytic enzymes Degradation resistance, clearance reduction, which may be related to thickening of blood vessel wall, reduction of elasticity and thickening of GBM; after cross-linking, the three-dimensional structure of the basement membrane itself is deformed, the degree of cross-linking between molecules is reduced by about 40%, and the pores in the membrane are enlarged. Increased permeability and increased protein filtration. In addition, the affinity of the glycated protein to the heparan sulfate, an important anionic proteoglycan component in the basement membrane, is reduced, and the clearance is increased. On the one hand, the charge barrier of the basement membrane is damaged, and the inhibitory group is lost. Membrane and mesangial hyperplasia cause the basement membrane and mesangial hyperplasia, eventually occlusion of the vascular lumen and expansion of the mesangial area.
3 Glycosylated vascular matrix proteins can capture extracellular soluble plasma proteins through AGEs, such as increased accumulation of cholesterol-rich LDL, causing local accumulation of LDL, promoting arteriosclerosis; capturing immunoglobulins such as IgG and albumin Increased can lead to progressive thickening of the capillary basement membrane and vascular occlusion.
4AGEs bind to specific AGEs receptors, causing increased release of cytokines such as interleukin-1 (IL-1) and tumor necrosis factor (TNF), which further stimulate the synthesis and release of collagenase and other cells in nearby mesothelial cells. Exoprotease cleaves AGE-protein degradation, but in long-term hyperglycemia, AGEs accumulate on matrix proteins, and AGEs-specific receptors on mononuclear macrophages, mesangial cells, and endothelial cell membranes In combination with AGEs, a large number of cytokines such as IL-1 and TNF are released, causing a series of metabolic changes, such as IL-1, which can proliferate fibroblasts, smooth muscle cells, mesangial cells and endothelial cells, and increase glomeruli. Collagen synthesis; TNF and insulin synergistically promote growth, increase the reactivity of target cells to other growth factors and stimulate platelet-derived platelet-derived growth factors, etc. These cytokines can damage endothelial cells and promote degradation of polyanionic proteoglycans. , the permeability of the blood vessel wall is increased.
5 Finally, non-enzymatic saccharification of protein can promote the increase of free radical production and participate in diabetic oxidative stress, which also accelerates the occurrence of chronic complications.
Non-enzymatic glycation of protein promotes the development of chronic complications of diabetes through a variety of pathways. Therefore, good glycemic control or the use of some compounds to block non-enzymatic glycation can reverse the above pathological process. Recently, it has been found that aminoguanidine is a non-toxic parent. Nucleus compounds can competitively inhibit the formation of AGEs, and further confirm that non-enzymatic glycation of proteins plays an important role in the development of DN.
3 lipid metabolism disorder: in addition to the main manifestations of glucose metabolism disorders, diabetic patients often have abnormal lipid metabolism, elevated blood cholesterol, TG, LDL and APOB, decreased or normal HDL and APOA1 levels, with DN, the above changes More obvious, abnormal lipid metabolism can damage the kidney and promote the development of glomerular sclerosis.
The possible mechanisms by which dyslipidemia damages the kidney and promote glomerular sclerosis are generally considered as follows:
1 glomerular lipid deposition, infiltration of glomerular mononuclear cells and macrophages phagocytic lipids increased, becoming foam cells.
2 Kidney tissue cholesterol and cholesterol ester content increased absolutely.
3 changes in fatty acid structure in the kidney (relative lack of essential fatty acids), increased release of renal vasoactive substances, increased glomerular capillary pressure.
4 Hyperlipidemia increases plasma viscosity and erythrocyte rigidity, altering glomerular hemorheology.
5 Recently, the role of cholesterol-rich LDL, especially oxidative modification (Ox-LDL) and glycated LDL, in glomerular sclerosis has been greatly valued. The metabolic pathway of LDL modified by oxidation and saccharification changes. The binding energy to APOB/APOE receptor is reduced, and the degradation of LDL clearance in plasma is reduced, resulting in an increase in LDL blood concentration. As a result, clearance by scavenger pathways such as monocytes and macrophages increases, and glomerular mesangial cells are reported. LDL, Ox-LDL and glycated LDL receptors are expressed, and the uptake of Ox-LDL and glycated LDL by mesangial cells is stronger than that of LDL. LDL not only stimulates mesangial cell proliferation, but also stimulates mesangial cells to produce extracellular matrix and mononuclear cells. Cellular chemokines directly infiltrate mononuclear macrophages, phagocytose LDL through the scavenger pathway, Ox-LDL and glycated LDL, etc., and become foam cells, and release various cytokines and growth factors, such as platelet-derived growth factors. CPDGF, IL-1 and transforming growth factor (TGF-) promote mesangial cells to further proliferate and synthesize matrix, and participate in glomerular sclerosis. In addition to LDL, diabetic patients are often accompanied by increased levels of Ox-LDL and glycated LDL.
6 In addition, it has been reported that patients with IDDM who have poor glycemic control or albuminuria often have elevated blood LP (). LP () is a large molecular glycoprotein with similar homology to plasmin. Competing with fibrinolytic enzymes to bind fibrin and fibrinogen, thereby inhibiting plasmin activity, leading to coagulation and thrombosis, and diabetic patients can significantly improve or restore normal lipid metabolism through good glycemic control.
(3) glomerular hemodynamic changes:
1 The effect of glomerular hemodynamic changes on the development of nephropathy: early glomerular filtration rate (GFR) of diabetic patients is significantly increased, especially in newly diagnosed IDDM patients, the GFR can be increased by 25% to 40% compared with normal people. %; similar phenomena can be seen in newly diagnosed NIDDM patients. In recent years, a large number of animal experiments have confirmed the use of angiotensin-converting enzyme (ACE) inhibitors, reducing glomerular hypertension and improving glomerular hemodynamics. Prevention of diabetic glomerular sclerosis strongly suggests that glomerular hemodynamic changes play an important role in the development of DN, and may even be the originating factor of DN. It is generally believed that sustained glomerular hyperfiltration, especially persistence Intraglomerular hypertension, mainly through the following two aspects of glomerular damage: 1 sustained glomerular hyperfiltration and glomerular high pressure can damage glomerular capillary endothelial cells, resulting in membrane permeability Increased, plasma macromolecular substance exudation of mesangial area increased, and the ability of mesangial cells to remove macromolecular substances decreased during diabetes, causing obstruction of the mesangial area, in addition, macromolecular substances accumulated in the mesangial area can be stabbed Mesangial cell proliferation, promote the increase of mesangial matrix, so that the mesangial area expands, accelerate glomerular sclerosis, 2 sustained glomerular capillary hypertension can stimulate the increase of collagen synthesis in glomerular filtration membrane epithelial cells, leading to GBM Thickening, but also stimulate the mesangial cell matrix production increased, and ultimately promote glomerular sclerosis, loss of glomerular function, residual glomerular compensatory high filtration, the formation of a vicious circle, and finally renal failure.
Prevention
Elderly diabetic nephropathy prevention
Primary prevention: Once the patient is diagnosed with diabetes or found to have impaired glucose tolerance (IGT), he should be actively treated to correct the IGT status in the body, prevent the occurrence of diabetes and the appearance of microalbuminuria.
Secondary prevention: Diabetic patients regularly perform urinary albumin, renal function (creatinine clearance), blood sugar and glycosylated hemoglobin, blood pressure, fundus examination, especially urinary albumin examination, which is helpful for early diagnosis of diabetic nephropathy. Some patients with DN early microalbuminuria can be reversed after active treatment. The treatment intervention at this stage can reduce and delay the occurrence of a large amount of proteinuria. Early active control of blood sugar can restore kidney hypertrophy and increase GFR. To normal; for diabetic nephropathy phase III (micro-albuminuria) intensive insulin therapy, strict control of hypertension and angiotensin-converting enzyme inhibitors, can delay the progression of kidney disease, reduce urinary albumin.
Tertiary prevention: entering the clinical diabetic nephropathy is a sign of irreversible kidney, but controlling glucose metabolism is conducive to reducing diabetes complications (such as cardiovascular, neurological, retinopathy and infection), may be to some extent to reduce slow renal disease development Progress and improve the quality of life are beneficial.
Complication
Elderly diabetic nephropathy complications Complications uremia heart failure arrhythmia coma
Complicated with uremia, heart failure, arrhythmia, infection, bleeding, coma and so on.
Symptom
Symptoms of Diabetic Nephropathy in the Elderly Common Symptoms Weakness, polyuria, glucosuria, water loss, immune dysfunction, hematuria, coma, oliguria, loss of appetite
The clinical manifestations of DN vary greatly, and there is no clinical symptom in the early stage. In the advanced stage, severe metabolic disorders of end-stage renal disease and systemic multi-system involvement may occur. The clinical manifestations mainly depend on the stage of DN disease and the degree of renal dysfunction.
Currently DN is divided into 5 phases:
Stage I: characterized by high glomerular filtration and mild renal enlargement, manifested as elevated GFR, increased hemodynamic changes in glomerular capillary vasospasm and increased intracapillary pressure, and elevated GFR 25% ~ 40%, up to 150ml / min, kidney volume increased by about 25%, but no obvious histopathological changes, no clinical symptoms, the current general clinical diagnosis can not be found, is the initial stage of diabetes.
Stage II: There is an increase in the amount of urinary protein excretion at rest. After exercise, there may be an increase in urinary protein excretion. The glomerulus begins to show structural damage, but it is reversible. In this period, GFR may be higher, more than 150ml. /min, some patients' blood pressure began to rise from the original basis. In this period, if early intervention is available, the structure and function of glomeruli can return to normal.
Stage III: manifested as an increase in persistent urinary albumin (UAE) (20-200 g/min), a highly selective proteinuria called early kidney disease, also known as the early DN, in which GFR gradually After returning to the normal level, the blood pressure can be slightly increased, but the level of hypertension is not reached. The increase of GFR and plasma flow in the early DN has a certain relationship with the blood sugar control state. After the blood sugar control, the two can be decreased. Some people find that a high protein diet is given. GFR can be increased, but GFR can be reduced after limiting the protein diet.
Stage IV: that is, in the stage of clinical nephropathy, before the application of early diagnostic indicators such as urinary microalbumin, the clinically diagnosed DN is mostly in this stage. This period is characterized by a progressive increase in clinical non-selective proteinuria, and the GFR gradually decreases. Histopathological changes gradually progress to glomerular sclerosis.
Patients with persistent or frequent proteinuria, from the UAE over 200g / min (or 300g / 24h) to a large number of proteinuria nephrotic syndrome performance, the clinical manifestations vary greatly, in addition to early proteinuria may be somewhat selective Mainly for non-selective proteinuria, diabetes patients from the onset of diabetes to proteinuria, urine protein increased by 5 to 20 times.
The proteinuria of DN often coexists with other chronic complications of diabetes such as retinopathy and macrovascular disease. Especially proteinuria (even persistent microalbuminuria) is a risk factor for coronary heart disease and retinopathy. It has predictive significance and is progressing. In diabetic nephropathy, retinopathy is often severe, parallel with the degree of proteinuria, but patients with retinopathy or even blindness due to retinopathy may have no proteinuria. Some people think that there is no diabetic nephropathy without retinopathy, if kidney Patients with dysfunction after careful examination of dilated sputum have not found diabetic retinopathy, other reasons should be considered, the appearance and extent of proteinuria may indicate prognostic significance, proteinuria more than 3g / d, is a sign of poor prognosis, such as the emergence of a large number of non-selection Sexual proteinuria predicts a period of renal failure within a few years.
Patients with clinical nephropathy often have edema, which is more common in mild edema of both lower extremities. A few cases of high body edema often suggest nephrotic syndrome. The causes of edema are not the same. Most patients with mild edema are unexplained and may be related to diabetes. Neuropathy vasomotor dysfunction is related to edema. Obvious edema is often associated with a decrease in plasma albumin caused by long-term massive proteinuria. In the later stage of clinical nephropathy, renal insufficiency may be associated with nitrogen retention, causing drainage disorders to aggravate edema. Period (renal failure period) transition phase.
Nephrotic syndrome is a special clinical type of DN clinical nephropathy. It is different from the small lesions in children or adults with chronic glomerulonephritis in clinical manifestations of nephrotic syndrome. The presence of nephrotic syndrome in diabetic patients is often clinical nephropathy. Later, it indicates that renal failure is coming.
With the continuous discharge of urinary protein, the blood pressure of most patients gradually increases, but severe hypertension is rare, and the original hypertensive patients can be aggravated. Conversely, if hypertension is not actively controlled, it can further aggravate kidney damage, so it is active and effective. It is important to control high blood pressure.
Stage V: uremia stage, diabetes protein clinical urinary period further development, the renal function gradually declines until the end stage is uremia stage, at this time, the renal sugar threshold is often significantly increased and the increase of urine sugar is not obvious, the clinical damage of the kidney The performance varies widely, and there are many systems involved. The severity of the lesions in each system can be different. The end-stage clinical manifestations of DN are similar to those of other kidney diseases, which are described as follows:
Water metabolism disorder
With the progress of DN, renal function is further damaged, the function of concentration and dilution is more reduced, the specific gravity of urine is fixed at 1.010~1.012, and the osmotic pressure is similar to plasma at 280mOsm/kg. It is called isotonic urine, and the patient's water regulation ability is obvious. Decreased, if the appetite is poor, the water intake is reduced, acidosis increases the respiratory rate, the water loss in the respiratory tract is increased, and accompanied by diarrhea, vomiting, etc., it is prone to dehydration, glomerular filtration rate is extremely reduced, urine The amount is decreasing day by day, blood urea nitrogen, creatinine rises rapidly.
2. Electrolyte metabolism disorder
Electrolyte disorders caused by DN in uremia are common and can occur together with dehydration and edema. Single or several electrolyte metabolic disorders can occur simultaneously.
(1) Sodium metabolism disorder: The blood sodium concentration in uremia is mostly normal, and most of them can still maintain the balance of intake and discharge. However, if the glomerular filtration rate is <25ml/min, the sensitivity of regulation decreases. Longer time can make the blood sodium level tend to be normal. At this time, there may be obvious sodium balance disorder, and sodium or sodium retention may occur. Because the patient's water excretion ability decreases earlier than the sodium excretion disorder, it is easier to dilute. Hyponatremia, patients with many neurological symptoms, such as apathy, slow response, fatigue, muscle spasm, convulsions, etc., can occur in severe cases of coma.
(2) Potassium metabolism disorder: When normal, the body's potassium salt is excreted by the kidneys except for a small amount of feces and sweat glands. The potassium salt in the glomerular filtration fluid is almost entirely from the proximal convoluted tubules under normal conditions. And the medullary sputum is reabsorbed, and the potassium excreted in the urine is mainly secreted by the distal convoluted tubule. If the potassium salt in the body is released from the tissue (such as infection, trauma, gastrointestinal bleeding), there is renal failure. The renal blood flow is greatly reduced. Due to the decrease of excretion ability, blood potassium can rise significantly, showing hyperkalemia. There may be fatigue in the clinic, muscle weakness, sputum reflex weakening or disappearing, sinus arrest, house conduction. Block arrhythmia, and even sudden cardiac arrest, DN is characterized by glomerular sclerosis, glomerular damage is predominant, hyperkalemia is more common in the terminal phase, and some cases are under-fed, long-term use of diuretics or accompanied In diarrhea, hypokalemia may occur, patients may experience burnout and weakness, sputum reflexes weaken or disappear, with abdominal distension, bowel sounds decrease, heart rate increases, but heart sounds blunt, and ventricular premature contraction or paroxysmal Heartbeat , Or ventricular flutter or fibrillation that produce - Adams syndrome.
(3) Calcium, phosphorus, magnesium metabolism disorders: blood calcium in most of DN uremia decreased, of which protein-binding calcium decreased significantly, blood phosphorus levels often rise, but due to the regulation of parathyroid hormone, blood Phosphorus concentration can still be maintained. High-phosphorus diet often causes a sharp increase in blood phosphorus. There are not many uremia patients with low-calcium hand-foot-foot sputum. Plasma magnesium ion concentration is related to sputum, and blood magnesium concentration is in chronic renal failure. The change is not large, a small number of patients are high, and the kidneys have a strong ability to excrete magnesium. However, when the kidney function is seriously damaged, the magnesium excretion is finally limited, resulting in inhibition of central nervous function and nerve and muscle joint transmission, resulting in reduced reflexes. May have muscle weakness, difficulty swallowing, lethargy, atrioventricular or intraventricular conduction block, and even respiratory center paralysis, coma or cardiac arrest.
3. Acidosis
The acidic metabolites accumulated in the body during renal failure are mainly sulfates, phosphates, sulfates mainly from the glomerulus, renal tubules are rarely reabsorbed, and phosphate is also glomerular filtration, renal tubular weight The effect of absorption, when the glomerular filtration rate drops to about 20%, almost every case has different degrees of acidosis, clinical manifestations of deeper breathing, decreased appetite, fatigue, weakness, myocardial contraction, blood pressure, etc. Because of the obstruction of hydrogen ion excretion by renal tubules, the number of hydrogen pumps (endostatic hydrogen ions into the lumen from renal tubular cells) is reduced, hydrogen ions are retained in the body, which consumes a large amount of alkali storage, while renal tubular cells produce ammonia (NH3). The ability to reduce acidosis, such as sugar metabolism is still seriously out of control, fat metabolism disorders, blood ketone body levels increased, acidosis is more serious than other causes of uremia acidosis, more complicated.
4. Protein, sugar, fat metabolism disorders
The total plasma protein value of DN uremia is often lower than normal. Chronic malnutrition, hemorrhage, urinary protein loss and metabolic disorders in the human body lead to protein synthesis, transformation and other dysfunctions are all causes, and uremia has obvious abnormal glucose metabolism. However, in general, patients have no symptoms of diabetes. In renal failure, the ability of the kidney to use and inactivate insulin decreases. The patient's insulin requirement is relatively reduced. If hypoglycemia occurs in patients with kidney disease, be alert to whether it has entered uremia, caused by uremia. The cause of hyperglycerolemia is not fully understood. It seems that the removal rate of blood triglyceride is slow, which is related to the incidence of cardiovascular complications. High HDL is often decreased with the increase of low density lipoprotein.
5. Endocrine dysfunction DN chronic renal failure can occur a variety of endocrine hormone metabolism abnormalities, these disorders can be summarized as:
1 Synthetic or secreted disorders: mainly renin, angiotensin, prolactin secretion, thyrotropin, testosterone, etc., decreased secretion, active vitamin D synthesis is also significantly reduced.
2 biological obstacles of hormones: tissue to insulin, testicular response to the reduction of progesterone is more obvious.
3 abnormal plasma protein binding: the decrease in T4 content caused by the decrease of thyroxine-binding globulin content, and the decrease of blood testosterone level may also be related to the decrease of protein binding.
4 metabolic disorders: Many hormones are affected by the degradation of the kidneys, so its half-life is prolonged, resulting in accumulation in the blood.
6. System performance of each obstacle
(1) Digestive system: Loss of appetite often occurs first, but the degree varies from person to person, with nausea, fullness in the abdomen, light taste and odorlessness, special metallic taste in the mouth, vomiting with the severity of the disease, sometimes due to dripping Loss of water, swelling of the oral mucosa, swollen gums, mostly dry tongue and smell of urine, the incidence of stomach and intestinal ulcers can be as high as 18% to 24%, can produce a small amount of hematemesis or black feces, a small number of patients can have constipation Or diarrhea, the incidence of pancreatitis is very high, reported to reach 8% to 19%.
(2) Neuropsychiatric system: Neuropsychiatric symptoms are common in uremia, retention of uremic toxins, imbalance of water and electrolytes, acid-base imbalance, drug application and hypertensive encephalopathy, etc. The sign increases the complexity of the symptoms of the nervous system. The central nervous system can be weak, memory loss, inattention, depression or impatience. A few cases are excited and multilingual, and they can also be seen and listened. Kind of hallucinations, late cases have drowsiness, apathy, gradually into a coma, peripheral nerves are more common in chronic renal insufficiency, involving sensory nerves and motor nerves, mostly symmetrical polyneuritis, patients often have numbness, burning , ant sense, etc., uremic myopathy manifested as muscle weakness, muscle fibrillation or muscle atrophy.
(3) Hematopoietic system: Anemia is one of the most common symptoms of DN chronic renal failure. Due to severe damage to the nephron, erythropoietin production is reduced and severe renal anemia is produced. The bone marrow is inhibited by certain toxic products and interferes. Proliferation and maturation of young red blood cells; poisons and metabolic disorders interfere with the microenvironment of stem cell growth, which weakens the effect of erythropoietin and leads to anemia. As Na+/K+-ATPase is inhibited by uremic toxins, the sodium salt in red blood cells is increased, affecting Erythrocyte fragility and easy to hemolyze, bleeding tendency is common in patients with uremia, mainly skin mucosa, manifested as subcutaneous ecchymosis, gingival, combined with submucosal hemorrhage, gastrointestinal bleeding, hemoptysis, blood in the stool, nosebleeds, bleeding The reason is more complicated, the blood vessel wall is affected by metabolic disorders and malnutrition, resulting in structural fragility, abnormal platelet function, and decreased platelet adhesion function.
(4) Cardiovascular system; cardiovascular disease is one of the important causes of death in patients with DN uremia. Hypertension is very common and has a certain relationship with the degree of renal dysfunction. Uremia myocardial damage is called uremic cardiomyopathy. The uremia patients have more common heart damage: cardiac hypertrophy, arrhythmia, heart failure, myocardial infarction, etc., in the end stage of uremia can produce cellulosic pericarditis.
(5) Respiratory system: DN uremia patients due to reduced immune function, susceptible to infection, bronchitis, bronchial pneumonia are more common, there may also be uremic interstitial pneumonia, pleurisy.
(6) skin and mucous membrane performance: skin color is often diffuse deep, accompanied by melanin deposition, dry skin, rough and itchy, the skin is easy to purulent infection.
(7) Abnormal immune function: DN uremia patients have different degrees of immune dysfunction, susceptible to a variety of infections, and there are many hepatitis B patients, the number of lymphocytes in the surrounding blood is reduced, and the blood immunoglobulin concentration is often low. Neutrophil phagocytosis is poor, movement, sterilization ability is also measured, and the thymus often shrinks.
(8) Water metabolism disorder: The time required for DN renal failure patients to discharge excess water is longer than that of normal people. As the glomerular filtration rate decreases, the urine concentration capacity decreases, polyuria and urination rhythm changes, and nocturia is more. When oliguria occurs and water persists, edema worsens and water intoxication and heart failure occur.
(9) Electrolyte metabolism disorder: DN chronic renal failure is prone to dilute hyponatremia, sodium balance regulation disorder, hypokalemia or hyperkalemia may occur due to decreased potassium metabolism; calcium, phosphorus, Magnesium metabolism disorders, often appear low calcium or high magnesium.
(10) Acidosis: The kidney is the main place for the excretion of fixed acid. In the DN renal failure, the body mainly accumulates sulfate and phosphate. They are mainly filtered out from the glomerulus, and the renal tubules are rarely reabsorbed. When the filtration rate drops to about 20%, almost every case has different degrees of acidosis.
(11) Protein, sugar, fat metabolism disorders: DN chronic renal failure, plasma total protein value is lower than normal, blood essential and non-essential amino acid levels are also lower than normal, uremia patients with blood reducing substances such as The accumulation of uric acid, creatinine and glucuronic acid causes abnormal glucose tolerance. Patients with uremia often have high blood TG, and the blood TG removal rate is slow.
Examine
Examination of diabetic nephropathy in the elderly
1. Microalbuminuria (UAER)
The UAER variation in the elderly is larger, in older men (11.4±2.6) g/min, female (8.2±2.2) g/min, other conditions such as diabetes out of control, ketoacidosis, urinary tract infection, nephritis, hypertension, etc. Causes transient or persistent microalbuminuria, so these conditions should be ruled out. About 80% of microalbuminuria IDDM patients and 20% of NIDDM patients progress to clinical stage renal disease within 10 years. In addition, the sensitivity of this index is about 78%. The specificity is about 98%, so persistent microalbuminuria is a good predictor of clinical nephropathy, especially IDDM clinical nephropathy. The microalbuminuria of DN is still reversible. At this stage, if it can intervene treatment, remove the unfavorable factors. The renal lesions may be reversed and recovered. Therefore, in recent years, a large number of studies have focused on the detection and determination of this period and before the period. WHO recommends that IDDM and all NIDDM patients with a disease duration of more than 5 years should be tested once a year for UAER, such as UAER. High, UAER should be measured 3 times in 6 months to determine whether it is early DN. The production of microalbuminuria is due to the change of negative charge on the glomerular basement membrane, plus the glomerulus, the high already existing in the capillaries. Filtration Highly selective small-molecule albuminuria, it is best to take 24h urine sample for determination of albuminuria, because albumin excretion is not continuous and uniform in one day, and it is best to repeat after a period of time to exclude certain factors. Such as urinary tract infections, etc., but the outpatients are inconvenient to take 24h of urine. After comparison, it is found that although the sensitivity of early DN is slightly lower than 12h urine, it can basically replace 24h urine for UAER measurement for the diagnosis of diabetes involvement. Staging, morning urine albumin concentration determination can be used first for routine screening of DN, for >30g / L can be further overnight 12h or 24h UAER determination.
2. Trace transferrin urine
In 1988, Bernard et al. suggested that microtransferrinuria could also be used as an early diagnostic indicator of DN. Some studies suggest that transferrin (TRF) excretion rate (TER) may be more sensitive than UAER, but it has not yet been used as a formal early diagnostic indicator. .
The relative molecular weight of TRF and albumin is 77000, but its load is less than albumin. At the very early stage of DN, the negative charge on the glomerular filtration membrane has been reduced, and the pore has not changed. It is not easy to filter out, and TRF has been filtered out. Therefore, several studies have reported that TRF is a good early diagnostic indicator of DN, which may be more sensitive than UAER. Domestic Qi Ying et al. compared urinary microalbumin and urinary micro transferrin. For the early diagnosis of DN, it was found that 43.4% of patients saw an increase in TER, while patients with elevated AER were only 32.9%.
3. Urine sialic acid
Sialic acid (SA), also known as N-acetylneuraminic acid (NANA), is one of the components of the glomerular capillary membrane, basement membrane and other cell membranes. The relative molecular weight is 309.3, mostly in the form of a combination of sialic acid. Divided into two types: sialic acid bound to glycoprotein is PSA, LSA is bound to glycolipid (mainly ganglioside), sialic acid is rich in glomerular capillary membrane and glomerular basement membrane, sialic acid Under normal circumstances, the barrier function of its charge on the basement membrane can prevent leakage of small molecules of albumin in plasma. In the early stage of DN, the sialic acid on the membrane is lost, destroying the charge barrier on the basement membrane, causing obvious sialic acid discharge in the urine. Increase, Japan's Ishikawa and domestic scholars and other studies confirmed the diagnostic value of urinary sialic acid in early DN: 1 urine total sialic acid (UTSA), UPSA, ULSA in the microalbuminuria group compared with the control group and no urinary albumin increase There was a significant increase in the diabetic group; 2 patients had damage to the basement membrane before the abnormal urine protein, resulting in an increase in urinary sialic acid; 3 There was a positive correlation between the three companies, UPSA, ULSA and VISA, and the first two were complicated and expensive. UTSA Given relatively simple and inexpensive, suitable for routine screening, at the same time, as the disease progresses UTSA increased, indicating a certain extent, UTSA may reflect the degree of damage to the kidneys.
4. Exercise stimulation test
Some diabetic patients can not detect the increase of urinary protein excretion in quiet state or general activities, but the urinary protein excretion increases after strenuous exercise, which is roughly equivalent to DNII period. Christensen found that the exercise amount is 400-500Kpm/min for normal people. Does not affect the amount of urinary protein excretion, but for some patients with diabetes can increase their urinary protein output, domestic Wang Xiaonan and other reports using the domestic bicycle heart function machine for exercise stimulation test to observe the early diagnostic value of DN, pre-exercise urine protein There was no significant difference with the healthy control group. The amount of urinary protein increased significantly after exercise, and the course of diabetes was found to affect the outcome. After exercise for >2 years, the amount of urinary protein increased significantly compared with that before exercise; and the patient with disease duration <2 years, urine The amount of protein was not significantly increased compared with that before exercise.
5. Changes in early hemodynamic parameters of glomeruli
Some of the above early diagnostic indicators are mainly located in stage III, and some can reach stage II, that is, structural damage of the glomerulus. After exercise, the protein output in the urine increases. Before this, the high-filtered GFR increased in the first stage.DN(GFR)Sampson65DNGFR GFRIDDM10GFR>150ml/minGFRGFRDNDNIDDM1990131I-OIHGFR(ERPF)(FF)NIDDMGFRERPFGFRERPFDN 99mTc-DTPAGFRGFR>140ml/minDN
6.
NAG(N--BD)DN
(1)NAGNAGNAG(130000140000)DNNAGNAG/NAGMocan(1994)NAGNIDDM331010NAG2-NAG36IDDMNAG9DN2NAGNAGDN
(2)(RBP)21000RBP100µg/24hRBPRBPRBP
RBP2-MG2-MGpHRBPpHpH(5.75.8)2-MGRBPRBP2-MGIDDMRBPUAERRBPBRPRBPBRPDN
(3)Tamm-HorsfallTorffvit56IDDMTamm-Horsfall;GFRTamm-HorsfallUAERTamm-Horsfall
7.G4(IgG4)
IgG4G4IgG4DNIgG4
8.
DNDNDNDN
ACEI/DDNMarre(0.06)(0.24)Doria4Na /Li+(SLC)DNGarrIDDMSLCSLC(KS-PG)NAT2HS-PGNAT21(AR)DN
XB
Diagnosis
Diagnostic criteria
(5>10)
;(>90%)
<150mg/24h<30mg/24h(20µg/ml)<300mg/24h(<200µg/ml) >200µg/ml(>300mg/24h)()
16324h220200µg/min(30300µg/24h)324hUAER>0.5g/24hDNDN
1%2%20%
<10
B
Differential diagnosis
1.DN
2.
3.DN
4.
5.DN
