Pediatric Diabetic Nephropathy

Introduction to Pediatric Diabetic Nephropathy DN refers to glomerular sclerosis caused by microvascular disease caused by diabetes, and is one of the complications and major causes of death of diabetes (DM). Diabetes is a common disease that not only shows elevated blood sugar, but also is associated with fat, protein, water and electrolyte metabolism disorders. Because the eye, heart, kidney and nervous system symptoms are mostly late complications of diabetes, they are rarely seen in the pediatric stage. basic knowledge The proportion of illness: 0.001% Susceptible people: children Mode of infection: non-infectious Complications: nephrotic syndrome edema hypertension uremia

Pediatric diabetic nephropathy

(1) Causes of the disease

In recent years, a large number of studies have been carried out on the etiology of DN, and great achievements have been made. It is believed that genetic susceptibility and hyperglycemia (environmental factors) are the triggering factors (ie, etiology) of DN, and the interaction between them leads to the occurrence of DN. With development, of course, environmental factors as well as high blood lipids, high blood pressure and other factors, but high blood sugar is much more important than them.

1. Genetic susceptibility: Recent studies have found that DN has a family aggregation phenomenon. In 2-DM, there are more reports in the literature, whether in 1-DM or 2-DM patients, if the proband case is complicated by DN, his brothers and sisters The incidence of DN is significantly increased after DM, even if the blood sugar control is very poor, only 35% of 1-DM patients eventually develop into terminal DN, even if strict control of blood glucose is close to normal (including DCCT studies) has been shown to be significantly improved or Prevention of DN, but can not completely prevent the occurrence and development of DN, so there are already clues suggesting that DN has genetic susceptibility.

(1) Susceptibility mode: At present, there are three types of susceptibility patterns for DN.

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 occurrence of DN due to the interaction between several gene polymorphisms (or mutations) and poor glycemic control. These disease alleles act independently and appear Addition, as for the overall effect of the action of these alleles, 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 The frequency of occurrence is higher, this allele produces major gene effects, while several other alleles produce microgene effects.

3 polygenic effects or minor gene effects: refers to the occurrence of DN due to the interaction between many gene polymorphisms (or mutations) and poor glycemic control. Each allele is inherited against DN. Susceptibility only plays a minor role.

(2) Susceptible genes: Many authors have been searching for susceptibility genes of DN, and several possible candidate genes have been discovered, but no consistent conclusions have been drawn. Looking for DN susceptibility genes in 1-DM studies Most studies have shown that the frequency of gene polymorphisms (or mutations) of angiotensin II type 1 receptor (AT1R) is significantly higher in patients with DN than in patients without DN, suggesting that it may play a major gene. Effect, as for the relationship between angiotensinogen (AGT) gene and angiotensin-converting enzyme (ACE) gene polymorphism (or mutation) and DN has not been consistent, the main genes are studied. In terms of effects and microgene effects, the transmission disequilibrium test (TDT) is highly specific to case-control studies. Some people use the TDT method to study the relationship between AGT and ACE gene polymorphisms (or mutations) and DN. They were found to be related to DN and thought that they might play a minor genetic effect. In 2-DM, a large Pima Indian family study found that the AT1R gene polymorphism (or mutation) frequency Patients with DN were significantly higher than those without DN, and thought it might play a major genetic effect; however, no consistent results were found in other population studies. In addition, AGT, ACE, kinin and atrial natriuretic peptide aldose reductase The study of the relationship between the frequency of isogenic polymorphisms (or mutations) and DN has not reached a consistent conclusion. Because many parents of 2-DM complicated DN patients are no longer alive, it is difficult to use TDT for family research, so it cannot Determine if these genes are playing a minor genetic effect.

2. Hyperglycemia: The occurrence of DN, in addition to genetics, hyperglycemia also plays a very important role, a large number of studies have shown that strict control of blood glucose can significantly reduce the risk of DN, how high blood sugar leads to DN, This has not been fully elucidated, but many studies have shown that hyperglycemia can activate many local endocrine hormones (or cytokines) in the kidney. Current studies have found that these substances are closely related to the development of DN. Of course, the mechanism of DN also includes blood flow. Abnormalities in learning, erythrocyte aerobic dysfunction, sorbitol bypass hyperactivity, etc., but these factors are more or less related to local endocrine hormones (or cytokines).

(1) Renin angiotensin system (RAS): The level of angiotensin II (ATII) in DM rats was significantly increased, and the expression of AT1R in renal tissues was also significantly increased, and both clinical and experimental studies proved. The use of ACE inhibitors can effectively prevent the occurrence and development of DN.

(2) Renal local growth factor: It has been found that a variety of renal local 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- (TGF-). ), etc., they can stimulate mesangial cell proliferation, extracellular matrix deposition increased, TGF-1 research is more, some studies have shown that DM rat kidney tissue TGF-1 expression increased significantly, it is important to apply ACE inhibition After the agent can be significantly reduced, it is believed that it may play a key role in the pathogenesis of DN.

(3) Endothelin (ET): ET has a strong contractile vasculature, of which ET1 has the strongest effect. It is known to stimulate the proliferation of mesangial cells. Experimental studies have found that ET1 in DM rat kidney tissue Receptor expression was significantly increased, and ET1 receptor antagonists could be used to prevent and treat DN. In addition, in vitro studies showed that TGF-1 increased ET1 expression in renal tubular cells.

(4) Nitric oxide (NO): NO has a strong vasodilating effect. It is synthesized by L-arginine as a donor under the action of NO synthase (NOS). There are 2 kinds of NOS. , Structural NOS and inducible NOS (iN-OS), increased iNOS expression and NO content in early renal tissues of DM rats, thought to be related to early renal blood flow increase, renal tissue in the late stage of DM rats There was no significant increase in iNOS expression, and the expression of NOS and NO were significantly decreased. L-arginine treatment of DM rats could prevent the occurrence of DN, while long-term use of NOS inhibitors could accelerate the small kidney of DM rats. Ball lesions suggest that NO can prevent the occurrence and development of DN. The above studies suggest that NO can protect glomerular lesions in the late stage of DM rats, and many studies have shown that renal tissue NO and ATII and TGF-1 can be mutually regulated.

(two) pathogenesis

Diabetic nephropathy is a damage caused by many factors. So far, it has not been fully elucidated. In addition to high blood sugar, hormone imbalance, renal hemodynamic disorder and other factors, renal microvascular disease causes glomerular basement membrane structure changes and glomerular damage. Increased permeability leads to the main cause of proteinuria. In addition, high-risk factors including genetic defects, ethnic influence, presence of hypertension and glycemic control, and protein intake in the diet are all related to the occurrence and progression of diabetic nephropathy. In the role of glomerular damage, there is still no strong evidence, the disease has the following pathological changes:

1. Glomerulosclerosis: There are two types of nodular sclerosis and diffuse sclerosis. The former is a typical Kimmelstiel-Wilson (KW) lesion, which is found in about half of patients. This lesion occurs in the peripheral part of the glomerulus. It is specific for the diagnosis of diabetic nephropathy, the latter is more common, but unique to non-diabetic nephropathy.

2. Vascular damage: manifested as arteriosclerosis, glassy degeneration in the wall of the ball and the small artery of the ball, which is different from those of non-diabetic hypertensive patients.

3. Renal tubule-interstitial damage: including degeneration of renal tubular epithelial cells, tubule atrophy, interstitial edema, fibrosis and cell infiltration.

Pediatric diabetic nephropathy prevention

Early control of blood sugar in diabetic patients can prevent diabetic nephropathy.

Active prevention and treatment of childhood diabetes is a fundamental measure to prevent this disease.

Predictive indicator

The prevention of type 1 diabetes began in the 1970s. The method of measuring ICA was calibrated with JDF units. In 1989, the Swedish reported 405 newly diagnosed type 1 diabetes patients with age- and sex-matched 32-l normal blood test ICA. The positive rate of patients was 96% (389/405), the control was 2.8% (9/321), and the follow-up was 2 years. Two of the 9 patients in the control group developed diabetes, and the other 7 patients had ICA <40JDF units. Negative, Joslin-Sacramento began testing ICA and/or IAA in 8,000 first-degree relatives of type 1 diabetic patients from 1983, and relatives were 16/1723 (0.9%) positive. Two years of follow-up occurred in two years. ICA and/or IAA-positive people undergo a standardized intravenous glucose tolerance test (IVGTT), measuring insulin 1 min and 3 min after glucose injection. If the insulin value is less than 5% of the normal value, it is predicted that diabetes will occur within 3 years. In recent years, the measurement of GAD has become an indicator of prediction.

2. Preventive treatment

ICA and/or GAD-positive people in high-risk populations (first-degree relatives) have begun large-scale use of niacinamide or insulin for preventive treatment research in Europe and the United States. Germany has an international trial using tobacco. Amide prevention The prevention study for type 1 diabetes in children <12 years old said that the DENIS program is underway. Since animal experiments have found that insulin can delay the onset of diabetes, the United States has conducted a study called DPI-I to identify the high risk of type 1 diabetes. After humans, they were divided into two groups, respectively, with oral or insulin injection for prevention. The results still need to wait. In short, due to the progress in the research on the pathogenesis of type 1 diabetes, the method of predicting and preventing type 1 diabetes may be There is more progress and I hope to achieve good results.

Pediatric diabetic nephropathy complications Complications nephrotic syndrome edema hypertensive uremia

Diabetes complicated with nephrotic syndrome, can cause hypoproteinemia due to a large number of proteinuria, causing significant edema, hypercholesterolemia, low body resistance, often complicated infection, high blood pressure, renal dysfunction, late kidney Insufficient function, eventually developed to uremia.

Pediatric diabetic nephropathy symptoms common symptoms hypertension edema urinary protein ketoacidosis proteinuria diabetes glomerular filtration rate decreased

1. Main clinical manifestations

(1) Proteinuria: It is the first clinical manifestation of diabetic nephropathy. It is initially intermittent and then converted to persistence. The determination of albumin or microalbumin in urine by radioimmunoassay can diagnose proteinuria earlier and control the disease. Good.

(2) edema: edema caused by diabetic nephropathy is caused by a large amount of proteinuria. This stage indicates that it has progressed to the later stage of diabetic nephropathy, and is accompanied by clinical manifestations of renal dysfunction such as decreased GFR, suggesting a poor prognosis.

(3) Hypertension: Late appearance, blood pressure increased at the stage of diabetic nephropathy, which may be closely related to the changes in the structure and function of diabetic renal resistance vessels. In addition, sodium retention is also one of the factors of hypertension. Blood pressure can aggravate the development of kidney disease and the deterioration of renal function, so controlling hypertension is essential.

2. Five stages from diabetes to kidney disease can generally be divided into five stages:

(1) Functional change period: early kidney hypertrophy and high filtration, high perfusion rate, the focus of this period is to control blood sugar.

(2) Structural change period: When the disease is 2 to 5 years old, the kidney begins to undergo structural changes, and proteinuria occurs during strenuous exercise.

(3) Early kidney disease: When the course of disease is 5 to 15 years, 30% to 40% progress to this stage, proteinuria is aggravated, and renal function begins to decrease.

(4) Diabetic nephropathy: A large amount of proteinuria occurs in 10 to 30 years of illness, accompanied by edema and hypertension, and renal function is also deteriorated.

(5) Uremia period: the end stage renal stage (ESRD), which requires dialysis or kidney transplantation to maintain life.

Pediatric diabetic nephropathy

In order to make an early diagnosis of DN, creatinine clearance and microalbuminuria must be measured for each DM patient, and renal biopsy pathology should be performed if necessary.

1. Urine microalbumin determination: Also known as urinary albumin excretion (UAE), radioimmunoassay and enzyme-linked immunosorbent assay are used. In a quiet resting state, normal people should be <20g/min (30mg/ d), at 20 ~ 200g / min called microalbuminuria, can be considered DNIII phase, the standard for the diagnosis of early diabetic nephropathy is three times within 6 months, each interval of more than 1 month, of which 2 times urine white The protein excretion rate is 20 ~ 200g / min, some people think that taking morning urine for microalbumin determination, based on gram of creatinine per gram, 30 ~ 300mg / g is the phase III DN, in addition, the author believes that urinary 2-microglobulin In the early stage of DN (before urinary protein routine positive) has been significantly increased, can also be used as one of the auxiliary diagnostic methods, but most scholars believe that its correctness is not as good as UAE.

2. Urine transferrin: the molecular weight of transferrin and albumin are similar, and the mechanical barrier of glomerular filtration membrane has no effect on them. In the early stage of diabetic nephropathy, urine white may appear due to defects in the electrostatic barrier of the filtered membrane. Protein excretion increases, but the negative charge of urinary transferrin is significantly less than albumin, so it is easier to pass the negatively charged glomerular filtration membrane. Therefore, some scholars believe that urinary transferrin can be used as a diagnosis of early diabetic nephropathy. Standard and superior to urinary albumin.

3. Retinol-binding protein: It is a low-molecular protein (molecular weight 21,000). The free retinol-binding protein is quickly filtered by the glomerulus and is reabsorbed and decomposed in the renal proximal convoluted tubule. Normal human urine It is considered to be a sensitive indicator of renal tubular damage and can reflect the damage of early renal tubules. Some scholars have observed that in patients with diabetes, when urinary albumin excretion rate is normal, urinary retinol-binding protein is excreted. It is more common than normal people, and can be used as a diagnostic index for early diabetic nephropathy. B-ultrasound, electrocardiogram, X-ray examination and fundus examination are routinely performed. DM retinopathy and nephropathy are both microvascular lesions, often occurring at the same time. Therefore, the patient has DM. Retinopathy must take into account DN.

Diagnosis and diagnosis of diabetic nephropathy in children

diagnosis

1. Clinical Diabetic Nephropathy: Urine protein is the main basis for clinical diagnosis of diabetic nephropathy. It has a long history of diabetes. The urine routine examination finds protein positive, and excludes other causes such as urinary tract infection, glomerulonephritis, ketoacidosis. Heart failure, etc., can basically be diagnosed as diabetic nephropathy; if combined with diabetic retinopathy, diagnosis can be established. Diabetic nephropathy diagnosed according to this standard is clinical stage diabetic nephropathy. In the development of diabetic nephropathy, this is a comparison. In the advanced stage, at this stage, the glomerular filtration rate decreases at a relatively constant rate and will develop into renal insufficiency in a short period of time, and this process is often irreversible, so it is emphasized again here. Diagnosis and treatment of early diabetic nephropathy.

2. Early diabetic nephropathy: Urinary albumin excretion rate has been accepted by most people as a standard for the diagnosis of early diabetic nephropathy. When the conventional urine protein test is normal, the urinary albumin excretion rate of early diabetic nephropathy is increased, and patients with early diabetic nephropathy About 80% of the disease can develop into clinical stage diabetic nephropathy in 10 years. Therefore, many scholars are still looking for more sensitive indicators of urinary albumin excretion rate, in order to diagnose earlier diabetic nephropathy, increased urinary transferrin and retinol binding. Protein, which is considered to be a sensitive indicator of renal tubular damage, can reflect early tubular damage. Some scholars have observed that in patients with diabetes, when urinary albumin excretion rate is normal, urinary transferrin and urinary retinol binding protein are excreted. It is more common than normal people and can be used as a diagnostic indicator for early diabetic nephropathy.

The diagnosis of diabetic nephropathy is mainly based on the patient's history of diabetes and the increase of urinary protein. Therefore, the diagnosis should first exclude proteinuria caused by other causes, such as urinary tract infection, glomerulonephritis, ketoacidosis, heart failure, etc. For patients without diabetes history, other criteria for diabetes should be sought for identification, such as diabetic retinopathy, neuropathy, etc. For diabetic patients with short course and no diabetic retinopathy, such as nephrotic syndrome, renal biopsy should be considered. Exclude glomerular diseases caused by other causes, to avoid delay in treatment, because diabetes patients are generally older, should be carefully engaged in renal biopsy and other examinations, such as intravenous pyelography and angiography, to avoid complications .

Differential diagnosis

1, primary glomerular disease, the main symptoms of the disease are varying degrees of edema, proteinuria, hematuria and so on. Renal function is normal or decreased, but no history of diabetes, blood sugar is normal.

2, essential hypertension.

3, urinary tract infections.

4, cardiac insufficiency and so on.

5, when the hematuria is obvious, it should be differentiated from external renal papillary necrosis, kidney tumor, calculus, pyelonephritis, cystitis or nephritis.

6, secondary glomerular disease.

7, renal glucosuria, the disease caused by the reduction of glucose reabsorption function, less common, its clinical features are often persistent diabetes, often family history. However, the fasting blood glucose and glucose tolerance tests were normal.

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