Diabetic nephropathy (DN) is one of the most common chronic complications in patients with diabetes and an important cause of death in diabetes. The cumulative incidence of DN in diabetic patients ranges from 20-40% (1). In developed countries, the first cause of end-stage renal failure is DN; in China, according to the Shanghai Dialysis Transplantation Registry, diabetic nephropathy has accounted for 15% of the total number of patients on dialysis, and the rate is increasing at a very high rate every year, according to this trend, DN will also become the primary cause of end-stage renal failure in China. Therefore, how to prevent and treat diabetic nephropathy has become a more urgent issue for medical workers in China. It is believed that the occurrence and development of DN is the result of multiple mechanisms, including the role of long-term hyperglycemia, altered glomerular hemodynamics, the role of multiple growth factors/cytokines, genetic susceptibility, etc. However, due to the complexity of DN pathogenesis, although many aspects of its pathogenesis have been studied, it is far from being systematically and comprehensively understood. In terms of preventive and curative measures for DN, it has been demonstrated that glycemic control, application of angiotensin-converting enzyme inhibitors (ACEI) or angiotensin II receptor antagonists (ARB), and low-protein diet can reduce the occurrence and delay the progression of DN. However, once diabetic patients enter the clinical stage of diabetic nephropathy, they will inevitably progress to end-stage renal failure, so further and more in-depth research on the mechanisms of DN development is needed to improve the prevention and treatment of DN. TCM emphasizes holistic regulation and macroscopic diagnosis and treatment, and Chinese medicine may be able to prevent and treat DN by intervening in multiple aspects of disease development, and the combination of Chinese and Western medicine may be a way to improve DN prevention and treatment. In this paper, we discuss the advantages of combining Chinese and Western medicine in the prevention and treatment of diabetic nephropathy, based on the main measures of DN prevention and treatment in Western medicine, the current research status of DN prevention and treatment in Chinese medicine, and our experience in DN research and clinical treatment. The main clinical measures for the prevention and treatment of diabetic nephropathy in Western medicine are to control blood glucose at a level close to normal, which is the most important therapeutic measure to prevent the occurrence and delay the development of DN. The results of the Diabetes Control and Comorbidity Trial (DCCT) in the United States showed that intensive insulin therapy to control blood glucose at near-normal levels for a long time can reduce the incidence and delay the development of DN in patients with type 1 diabetes (2). The “UK Prospective Diabetes Study” (UKPDS trial) showed that long-term tight glycemic control similarly reduced the incidence of diabetic nephropathy in patients with type 2 diabetes (3). Thus, glycemic control is the basis for preventing and controlling the occurrence and development of diabetes. A large number of studies have demonstrated that the application of ACEI or ARB to strictly control hypertension can reduce the occurrence and development of DN in diabetic patients.ACEI or ARB can reduce urinary protein excretion in DN patients through various mechanisms, they can significantly dilate the small glomerular efferent arteries and reduce glomerular intra-glomerular pressure; they can inhibit various cytokines/growth factors locally in the kidney, thus inhibiting the hypertrophy of renal cells, the inhibit the accumulation of extracellular matrix. In patients with type 1 and type 2 diabetes with normal blood pressure, ACEI may also reduce the development of diabetic nephropathy and reduce proteinuria.ACEI or ARB have renoprotective effects in addition to the antihypertensive effect in patients with DN. In terms of delaying the progression of DN, large clinical trials have failed to confirm that dihydropyridine calcium channel blockers (DCCB, such as nifedipine and amlodipine) have renoprotective effects beyond the antihypertensive effect, and thus DCCB is not the first choice for antihypertensive treatment of DN in the diabetes treatment criteria published by the American Diabetes Association (ADA) in 2006 (1). Some clinical studies have found that non-dihydropyridine calcium channel blockers, such as thiodiazepines, nicardipine, and nisoldipine, can reduce urinary protein excretion and delay the decline in renal function, with the same renoprotective effects as ACEIs. For DN patients with hypertension, if they cannot tolerate ACEI and ARB, non-dihydropyridine calcium channel blockers, β-blockers or diuretics should be considered for blood pressure control. However, it should be noted that diabetic patients, especially elderly type 2 diabetic patients, have a higher incidence of vascular complications and may have renal artery stenosis. For patients with renal artery stenosis, taking ACEI may induce acute renal failure; for patients with advanced diabetic nephropathy, taking ACEI may cause hyperkalemia, and thus should be monitored after starting ACEI Patients’ renal function and blood electrolytes should be monitored after starting ACEI. Many clinical studies have shown that the lower the blood pressure control in patients with diabetic nephropathy, the slower the rate of decline in GFR, and thus the goal of controlling hypertension in patients with diabetic nephropathy is lower than in non-diabetic hypertensive patients, and many scholars recommend that the goal of blood pressure control in patients with diabetic nephropathy should be below 120/80 mmHg. Both clinical and experimental studies have observed that a high-protein diet increases glomerular perfusion, elevates glomerular internal pressure, and exacerbates the renal hemodynamic changes caused by diabetes mellitus. A low-protein diet can reduce urinary protein excretion and slow the rate of glomerular filtration rate decline in patients with diabetic nephropathy. For patients with early diabetic nephropathy, protein intake should be controlled at the normal low limit (0.8g~1.0g/kg/d); for DN patients with overt proteinuria, protein intake should be limited to 0.8g/kg/d, and when the glomerular filtration rate (GFR) decreases, protein intake should be controlled at about 0.6g/kg/d, and can be supplemented with compounded α-keto acid preparation at the same time Alpha-keto acid is used to produce essential amino acids with NH3 in the body, which is beneficial to the reuse of urea nitrogen. alpha-keto acid preparations contain calcium salts, which are beneficial to the correction of calcium and phosphorus metabolism disorders caused by renal insufficiency and secondary hyperparathyroidism. During the low protein diet, to avoid the occurrence of malnutrition in patients, adequate caloric intake should be ensured. Since the intake of protein and fat is restricted in DN patients, insufficient calories need to be supplied with carbohydrates, and blood glucose should be controlled with insulin at the same time. A low-salt diet is also important for DN patients with hypertension and edema. Once DN patients develop renal insufficiency, the rate of progression is often faster than that due to non-diabetic nephropathy, and is often accompanied by chronic complications of diabetes such as cardiovascular disease. Patients with DN in the uremic phase should start replacement therapy earlier than non-diabetic patients and can choose hemodialysis, peritoneal dialysis or renal transplantation according to their specific conditions. For DN, it is still a progressive and refractory disease. In the early stage of DN (microalbuminuria phase), DN can be reversed with aggressive treatment, from microalbuminuria to normal urinary albumin excretion, however, once DN enters the clinical phase, the lesion is irreversible. Although there have been numerous studies on the mechanism of progressive DN, most of the current studies are limited to single biological pathogenic factors of vertical type, such as abnormal glucose metabolism, protein non-enzymatic glycosylation, renin-angiotensin system, cytokines (transfer growth factor β1, platelet-derived growth factor, etc.), endothelin, etc. These factors are all related to the progression of DN, but none of them can explain the whole picture. Because of this, there has been no fundamental progress in the clinical prevention and treatment of DN in recent years. It is a challenge to integrate classical biological vertical studies with systemic biological horizontal studies and to integrate various pathogenic mechanisms of DN at the systemic level to arrive at a more holistic understanding of the developmental mechanisms of DN (4). Diabetic nephropathy is one of the part-time diseases of thirst in Chinese medicine. The ancient physicians have long found that edema can occur with prolonged thirst disease, such as the Sui dynasty Chao Yuanfang in the “Treatise on the Origin of Diseases” said: “thirst disease for a long time, or carbuncles and gangrene, or become water disease”, “Shengji General Record”: “thirst disease for a long time, kidney gas injury, the kidney is the main water, kidney gas deficiency, abnormal gasification, opening and closing adverse, can be edema. It can be edema”. With the development of medicine, DN can be diagnosed at an early stage, so the current DN is not limited to the time when edema occurs in Chinese medicine. In recent years, Chinese medicine treatment of DN has been under continuous exploration in China. 2.1 Identification and treatment At present, the clinical treatment of DN in Chinese medicine mainly adopts identification and treatment, but the identification and classification of DN are not yet identical, and there is no unified classification and diagnostic criteria for DN. The basic pathogenesis of DN is characterized by “deficiency of the root and the symptoms of the symptoms”, and as the disease progresses, Yin deficiency, Qi deficiency, Yang deficiency, and deficiency of the five organs may appear. In the deficiency of qi, blood, yin and yang, most of the medical practitioners of all generations believe that the deficiency of both qi and yin is the main pathogenesis of the disease. Among the deficiencies of the internal organs, kidney deficiency is the key, which runs through the whole process of thirst disorders. In terms of symptoms, blood stasis is the most common. Yin deficiency and fire in patients with thirst disorders, which torments the fluid, inevitably causes blood stagnation and stasis, which is called “Yin deficiency and blood stagnation”. Qi is the marshal of blood, blood is the mother of qi, qi carries blood, blood carries qi. Yin and blood deficiency, qi has no attachment, resulting in qi deficiency. The deficiency of qi and blood causes stasis, which is called “qi deficiency and turbidity”. In addition, diabetes mellitus is difficult to heal, and prolonged illness can also cause loss of blood vessels. Treatment should be based on the identification of the symptoms, and the main focus should be on treating the root cause, but the method of activating the blood and removing stasis should be used throughout the treatment. Even if the symptoms of blood stasis are not obvious, it should be prevented before it happens and “dredge its qi and blood, so that it can be organized”. Of course, DN is a chronic and prolonged disease, and there are various symptoms that can occur at different stages of the disease during the long course of the disease. In the early stage of the disease, there is a deficiency of both qi and yin, insufficient kidney qi and internal blood stasis, with the kidney as the center of the disease, which can also manifest as liver and kidney disease, spleen and kidney disease. Subsequently, yin and yang can be lost, resulting in deficiency of both yin and yang, weakening of kidney qi and loss of spleen health, which can lead to edema. In the late stage, qi, blood, yin and yang are all weakened, the five organs are all diseased, blood vessels are stagnant, and toxins are retained, which may manifest as complicated five organ symptoms with poor prognosis. Based on the basic TCM pathogenesis of DN, i.e., deficiency of both qi and yin (yin loss and yang in the late stage), deficiency of spleen and kidney, stagnant blood, water-dampness, and turbid toxins, in the long-term process of DN development, various combinations of symptoms can be formed to produce different types of evidence due to different major contradictions in each period. In recent years, most scholars have agreed that the Chinese medical evidence of DN is closely related to the western medical stage of DN, and advocate for evidence-based treatment according to the western medical stage of DN. Although the classification of evidence types for DN staging differs, for example, Dongzhimen Hospital of Beijing University of Traditional Chinese Medicine (6) classifies early DN into 3 main and 6 concurrent evidence types, and middle and late DN into 3 main and 4 concurrent evidence types, the classification of evidence types for each stage of DN is based on the basic pathogenesis and the determination of the severity of organ deficiency and the priority of blood stasis, water and dampness, and the actual evil of turbidity and toxicity. We believe that patients with early DN (microproteinuria stage) do not yet have edema and other symptoms of clinical kidney disease, but have been suffering from thirst for a long time and have symptoms such as weakness, spontaneous sweating, dry mouth, constipation, lumbago and knee weakness, or numbness of the limbs, or chest tightness and chest pain, etc. At this stage, Qi and Yin deficiency, kidney deficiency and blood stasis are common, and treatment is mainly based on benefiting Qi and nourishing Yin, tonifying the kidney and activating Blood. In clinical stage DN, edema is often obvious, accompanied by weakness, dullness, lumbar soreness and knee weakness, or cold extremities, the evidence of spleen and kidney deficiency, internal obstruction of blood stasis is common. In late stage DN (uremic phase), patients often have severe edema, nausea and vomiting, abdominal distension and poor circulation. Although the function of the internal organs is decayed and the yin and yang are deficient in qi and blood at this stage, the evil of turbidity and toxicity, blood stasis and water-dampness is often the most urgent problem. As DN is a chronic disease, its prevention and treatment is a long-term process, and it is often difficult to adhere to the treatment of patients with DN using Chinese herbal tonics. In recent years, some domestic scholars have conducted a large number of basic or clinical studies on the effects of some Chinese medicine specific prescriptions, single Chinese medicines or their extracts on the prevention and treatment of diabetic nephropathy. These studies suggest that certain Chinese medicine specific prescriptions may have the effect of reducing the pathological changes of DN and improving certain biochemical indicators. Some studies suggest that single herbal medicines or herbal extracts may have preventive and curative effects on DN, including rhubarb, astragalus, quercetin, baicalin, astragaloside, chuanxiongzin, geranoside, Cordyceps preparations, etc. Some studies suggest that herbal formulas may have preventive and curative effects on DN, including “Liu Wei Di Huang Wan”, ” The herbal formulas that have been suggested to have possible preventive and curative effects on DN include “Liou Wei Di Huang Wan”, “Jisheng Ren Qi Wan”, “Stopping and eliminating Tong Yin”, “Sugar Micro Kang Capsules”, “Yi Qi Yang Yin Oral Liquid” and so on. We have conducted an experimental study on the preventive and curative effects of “Cuscuta and Arrow Combination”, which consists of Cuscuta, Gizo and Han Fangji, on DN and its mechanism, and found that “Cuscuta and Arrow Combination” can significantly reduce the 24-hour urinary protein excretion in single nephrectomized streptozotocin-induced diabetic rats. The effect of Dodder and Arrow combination was found to reduce the accumulation of extracellular matrix in the glomeruli of diabetic rats and inhibit the abnormal phenotypic transformation of glomerular thylakoid cells in diabetic nephropathy (7). Our study also found that cuscuta and arrow combination could inhibit the activation of protein kinase C in the renal cortical cells of diabetic rats (8). 3.Strengthen the research of combined Chinese and Western medicine treatment of diabetic nephropathy to improve the prevention and treatment of diabetic nephropathy DN is still an intractable disease, especially when it enters the clinical stage DN, which mostly develops progressively and eventually progresses to uremia. Due to the complexity of DN pathogenesis, the mechanism of its development has not been systematically and comprehensively elucidated, and there is a lack of measures to interrupt its progression. Many scholars believe that the development of DN is the result of multiple mechanisms acting together, with the involvement of multiple other factors in addition to metabolic factors such as long-term blood glucose. Treatment may require some other comprehensive measures in addition to blood glucose control and blood pressure control to achieve a more satisfactory prevention and treatment effect. Chinese medicine may improve the prevention and treatment of DN based on blood glucose and blood pressure control through multi-linked interventions. The results of many small clinical observations and experimental studies have suggested that TCM has a role in the prevention and treatment of DN. However, the current research on the mechanisms of DN prevention and treatment in Chinese medicine is still relatively shallow and requires more in-depth studies. More importantly, the current clinical studies on the prevention and treatment of DN in Chinese medicine have a short clinical observation time, and the main indicators observed are mostly laboratory indicators. There is a lack of multicenter, long-course, prospective large-scale clinical trials to prove that a certain Chinese medicine can reduce the occurrence of DN and delay the progression of DN. This status quo has limited the promotion and application of TCM in preventing and treating the development of DN. It is believed that with the deepening of basic research on the treatment of DN in TCM, with the increase of national investment in TCM, and with the development of large multicenter clinical trials, TCM can play its positive role in the prevention and treatment of DN.