Diabetic nephropathy is one of the most important microvascular complications of diabetes, and the prevalence of type 2 diabetes patients with concurrent nephropathy in China is 34.7%. With the rapid development of China’s economy and the continuous improvement of people’s living standards, the incidence of diabetes is increasing year by year, and the number of patients with diabetic nephropathy is also increasing. In developed countries, diabetic nephropathy has become the first cause of end-stage renal disease, and in China, it has become the second cause after sexual glomerular disease, and is one of the main causes of disability and death from diabetes, so effective prevention and treatment of diabetic nephropathy has become one of the major issues today. The development and staging of diabetic nephropathy Diabetic nephropathy is one of the diabetic microangiopathies and is often accompanied by diabetic retinopathy. Proteinuria is the hallmark of diabetic nephropathy progression. In the early stage of diabetic nephropathy, i.e., the stage of persistent microproteinuria, urine protein may be negative or only trace in urine routine, and urine microalbumin excretion rate (UAER) of 20-200 μg/min or 30-300 mg/24 h is detected; once the stage of clinical diabetic nephropathy is developed, i.e., urine protein (+) or more, UAER >200 μg/min or >500 mg/ 24 h, the patient’s glomerular filtration rate (GFR) is progressively decreasing and blood pressure is often elevated, and the renal pathological damage will enter an irreversible stage and eventually develop into the stage of renal failure. Diabetic nephropathy is divided into 5 stages, but stage 1 and 2 are more difficult to diagnose clinically, and the clinical diagnosis is often confirmed only when there is persistent microalbuminuria, i.e. stage 3 diabetic nephropathy. At this time, after active and effective antihypertensive and hypoglycemic treatment, some patients have reduced or turned negative urinary albumin excretion and reversed or delayed the development of nephropathy. However, if we fail to regularly check the urinary routine or urinary microalbumin excretion rate for patients, and consider the possibility of diabetic nephropathy only when patients have edema, hypertension, large amount of proteinuria and abnormal renal function, the disease has already developed to stage 4 of diabetic nephropathy and the lesion is irreversible. Therefore, clinical guidelines suggest that patients with diabetes mellitus should be monitored regularly (once/3-6 months) for urinary routine and urine microalbumin testing for early diagnosis and treatment. The occurrence and development of diabetic nephropathy follow the pattern of two cross curves: one is the proteinuria curve, which gradually increases from negative, trace to large amount of urine protein, and the other is the glomerular filtration rate curve, which gradually decreases from above normal, normal to gradually decreasing, and the two curves are mostly crossed in stage 4 of diabetic nephropathy. In addition, we should pay attention to the differentiation, for patients with diabetes and proteinuria, they should not be diagnosed as diabetic nephropathy. For patients with less than 5 years of history of diabetes and sudden appearance of large amount of proteinuria and normal renal function, if they do not have diabetic retinopathy, the possibility of diabetic nephropathy can be basically ruled out, and it is better to refer them to the nephrology department of higher hospitals for pathological diagnosis of renal aspiration biopsy, in order to give the correct treatment plan. If we treat diabetic nephropathy as it is, we will miss the disease. The etiology of diabetic nephropathy is very complex and not yet well understood, but there are some main risk factors: genetics, hypertension, hyperglycemia and obesity, dyslipidemia and hyperuric acid. Among them, hypertension and hyperglycemia are important risk factors for the occurrence and development of diabetic nephropathy. Previous studies have recognized cardiovascular disease as the most common comorbidity and direct cause of death in diabetes, and hypertension and hyperglycemia can significantly increase the incidence of cardiovascular and cerebrovascular lesions. Relationship between hypertension and diabetic nephropathy Hypertension is transmitted through systemic blood pressure to the glomerular capillary bed, which increases intraglomerular pressure and filtration pressure, thus leading to and exacerbating glomerulosclerosis. Hypertension and diabetic nephropathy can contribute to each other. Hypertension can cause a progressive increase in urinary albumin in type 2 diabetic patients with normal urinary albumin levels and a progressive deterioration in renal function in patients with clinical diabetic nephropathy. The onset and progression of both of these processes can be halted or delayed by antihypertensive therapy. The level of blood pressure control has been shown to be an independent risk factor for the prognosis of diabetes. The decrease in glomerular filtration rate (GFR) is related to the level of blood pressure. According to the 2007 edition of the Chinese Diabetes Prevention and Control Guidelines, patients with proteinuria <1 g/24 h should have blood pressure control below 130/80 mm Hg [including the 2007 American Diabetes Association (ADA) guidelines and the European Society of Cardiovascular Diseases/European Society of Hypertension (ESC/ESH) guidelines also set blood pressure control below 130/80 mm Hg as the target value for lowering blood pressure in patients with proteinuria <1 g/d The main basis for this is the MDRD (The Modification of Diet in Renal Disease Study) clinical evidence-based medical study. The MDRD study, led by the National Institutes of Health (NIH) in 15 kidney disease centers, compared the effects of different blood pressure targets on slowing the progression of kidney damage in patients with chronic kidney disease, and concluded that for patients with proteinuria >1 g/d, strict control of mean arterial pressure (MAP) to 92 mm Hg was necessary to effectively slow the progression of kidney damage. Moreover, at the same MAP level, lowering systolic and pulse pressure was more important than lowering diastolic blood pressure. Therefore, this study recommends controlling blood pressure below 125/75 mm Hg as the target value for lowering blood pressure in patients with proteinuria >1 g/d. As for the level of blood pressure control in CKD patients with proteinuria <1 g/d, the MDRD study was inconclusive. Selection and application of antihypertensive drugs Which antihypertensive drug do we choose to benefit more in delaying the onset and progression of diabetic nephropathy? The preferred antihypertensive drugs are angiotensin-converting enzyme inhibitors (ACEI), angiotensin II receptor antagonists (ARB), and the newly released renin inhibitors, which have been shown to improve the prognosis of early diabetic nephropathy in basic and clinical studies. cytokine production and secretion, inhibit the activation and proliferation of thylakoid cells, fibroblasts and macrophages, improve filtration membrane permeability, and reduce urinary protein excretion, and so on. Therefore, clinically, ACEI or ARB should be given when patients develop microproteinuria, regardless of the presence of hypertension. It is recommended to start with a small dose and increase the dose every 1 to 2 weeks to the maximum dose that the patient can tolerate, i.e. without symptomatic hypotension, drug-related elevation of serum creatinine and hyperkalemia. For patients with trace or small amounts of proteinuria, 1 drug is usually applied at 1 to 2 times the dose, and most patients can reach the urinary protein standard after several months when other interfering factors have been excluded. For patients with large amounts of proteinuria, the 24-hour urine protein quantification should be checked first, and then the individual drug dose should be gradually increased or ACEI combined with ARB, and the drug dose should be increased or decreased according to the monthly urine protein quantification and the patient's tolerance status of the drug (there is no more and better evidence-based medical evidence to prove that the combination of drugs is more effective than monotherapy). If blood pressure is not achieved with ACEI or ARB, a calcium antagonist can be combined. If edema is present, a diuretic can be combined. Beta-blockers are not preferred, but can be applied in young and middle-aged patients with a rapid heart rate and a history of ischemic heart disease. In addition to lowering blood pressure, lifestyle modification therapy such as limiting sodium intake, increasing exercise and quitting smoking are also needed. Relationship between hyperglycemia and diabetic nephropathy Hyperglycemia can cause a series of pathophysiological changes in the kidney, including: increased non-enzymatic glycation end products, increased sorbitol production, enhanced oxidative stress, enhanced protein kinase C and transforming growth factor (TGF) β activity, which leads to increased glomerular extracellular matrix, cell damage and increased proteinuria. In addition, long-term hyperglycemia puts the glomerulus in a hyperfiltration state, leading to hyperperfusion and intra-glomerular hypertension, which results in glomerular hypertrophy, basement membrane thickening, increased capillary permeability, proteinuria formation, and eventually glomerulosclerosis. In those who already have cardiovascular disease or are at high risk, the glucose target value should be relaxed a bit to avoid the occurrence of hypoglycemia and the increased risk of death. The choice of glucose-lowering drugs is preferred to sulfonylurea oral drugs and insulin. Biguanides can be applied when renal function is normal, and α-glucosidase inhibitors have fewer side effects and can be taken regardless of renal function. For insulin sensitizers are currently more controversial and have been taken off the market in the United States, so they are not recommended.