I. Basic countermeasures to delay the progression of chronic renal failure (CRF): At present, the purpose of CRF drug therapy mainly includes alleviating CRF symptoms and delaying the progression of CRF disease. The basic countermeasures are: 1, adhere to the etiology of treatment: especially for hypertension, diabetes, primary or secondary glomerulonephritis, whether to adhere to long-term reasonable treatment and regular follow-up is a very important factor affecting the development of these diseases to CRF and the rate of CRF progression. 2.Block or inhibit the various pathways of progressive development of renal unit damage, control or slow down the rate of progression of glomerulosclerosis and tubulointerstitial fibrosis, and protect the surviving renal units. 3. Avoid or eliminate certain risk factors for the deterioration of CRF, such as hypovolemia, severe hypertension, nephrotoxic drugs, severe infections, urinary tract obstruction, and high viscosity status. In order to prevent and delay the progression of CRF, it is necessary not only to actively control certain factors affecting progressive progression, but also to avoid the above-mentioned risk factors that lead to rapid exacerbation, or to control or eliminate them in time when they occur. In order to control certain factors affecting the progressive progression of chronic renal failure, in addition to active treatment of the cause, anti-hypertensive drugs, antioxidant drugs, anti-acidic drugs (sodium bicarbonate), phosphorus binding agents, lipid-lowering drugs, and combined Chinese and Western medicine measures can be applied appropriately according to the condition; and a low-protein diet should be reasonably applied, with the addition of essential amino acids or alpha-keto acid preparations if necessary. Angiotensin-converting enzyme inhibitors (ACEI, ARB) and new calcium antagonists may have the effect of delaying the progression of the disease. Non-dialysis treatment measures for CRF (a) Nutritional therapy: High quality low protein, low phosphorus, high calorie, high vitamin diet has a definite clinical significance in relieving the symptoms of CRF and delaying its progression. 1.Low protein diet (LPD) High protein diet can increase blood BUN due to the formation of large amounts of urea and other nitrogenous metabolites after amino acid metabolism, and uremic syndrome can occur in combination with other factors; reducing protein intake can make BUN decrease, reduce uremic symptoms and delay the rate of deterioration of renal function. It is generally believed that a daily protein intake of 0.6g/kg can maintain the patient’s nitrogen balance, of which at least 60% is high bioeffective protein rich in essential amino acids, such as poultry eggs, lean meat and milk, called high-quality protein, and allocated to be given in three meals. To limit the proportion of vegetable protein intake, starchy meals are the main staple food. Also pay attention to supplementing calcium and limiting phosphorus intake, and appropriately supplementing vitamins B and C and folic acid, etc. 2. Ensure adequate caloric intake Ensuring adequate caloric intake is particularly important for LPD patients. Only when the calorie intake is sufficient, it will not cause protein decomposition in the body and maintain positive nitrogen balance. Caloric intake should be 30-40cal/kg/d. 3. LPD plus essential amino acid (EAA) therapy CRF patients have decreased EAA levels. Although histidine and tyrosine are non-essential amino acids (NEAA), they are also deficient in CRF patients, and other NEAA levels are increased. It is possible to reduce the accumulation of protein metabolic end products in the body by promoting the synthesis of NEAA. In non-dialysis treatment of CRF, in order to improve the efficacy of LPD, protein can be limited to a lower level, e.g., 0.4 g/kg/d. LPD plus EAA makes it possible to strictly limit protein, because on the one hand, LPD reduces the glomerular hyperfiltration load and delays the rate of renal unit damage and sclerosis; on the other hand, the addition of EAA does not lead to malnutrition due to insufficient protein supply On the other hand, the addition of EAA does not lead to malnutrition due to insufficient protein supply, while the phosphorus level of extracellular fluid decreases due to increased protein synthesis in the body. In addition, EAA can also improve the lipid generation disorder in CRF patients. The application of EAA: on the basis of LPD, adequate calories are given, and then EAA is added, when the protein source in the patient’s diet can be appropriately relaxed, and it is not necessary to monotonically focus on high biovalent protein. This is because there is no amino acid pool in human body, so the fast drip rate is not conducive to absorption in the body, and it can also cause dizziness, facial redness and other discomforts. 4.LPD plus α-keto acid therapy α-keto acid (α-KA) is an amino acid precursor, and through the effect of transamino or amination, α-KA can be transformed into the corresponding amino acid in the body. (1) Keto acid itself does not contain nitrogen, so even if a slightly higher amount is given, it will not cause an increase in nitrogen metabolites in the body. At the same time, α-KA generates EAA with NH3, which facilitates the reuse of urea. Therefore, the nitrogen saving effect is obvious, the rate of urea ammonia production and BUN decrease more significantly, and the rate of protein synthesis is high; (2) reduce blood phosphorus, alkaline phosphatase and PTH levels; (3) due to the reduction of phosphorus and sulfur-containing amino acid intake, protein metabolite production is reduced, and metabolic acidosis is improved; (4) animal experiments show that α-KA does not have the phenomenon of elevated GFR and increased albumin excretion caused by EAA; ( (5) delaying the process of CRF. It has been reported that LPD plus α-KA for early CRF can stop the progression of the disease for at least 2 years. The α-KA preparation (Kai Tong) currently used at home and abroad contains leucine, isoleucine, valine, phenylalanine, methionine (Danine) and other 5 EAAs corresponding to α-KA and 5 EAAs. the general dosage is 4-8 tablets taken orally 3 times a day. Because the drug contains calcium salts, it is contraindicated in hypercalcemia, and no other side effects have been found. The disadvantage is that the price is too high, making it difficult for many patients to afford long-term application. LPD+α-KA therapy is more effective than LPD alone in promoting protein synthesis, correcting plasma EAA levels, and improving renal function and nitrogen balance. However, the effect of nutritional therapy in delaying the progression of CRF varies in patients with CRF of different etiologies and stages. (B) Control of hypertension: Hypertension is the main factor leading to progressive deterioration of renal function in chronic kidney disease; therefore, timely and reasonable control of blood pressure and enhanced follow-up are the two main factors in delaying the progression of CRF. In recent years, a number of scholars have emphasized the important role of 24-hour continuous and effective control of hypertension in protecting target organs, and recommended that blood pressure in CRF patients should be controlled at around 120/85 mmHg. The specific therapeutic measures and drugs include: 1. low-salt diet and diuretic The limitation of sodium should be based on the presence or absence of edema and the degree of hypertension and 24-hour urine output, etc. Generally, 2-3g/d of refined salt is given, which can be increased to 3-4g/d for sodium-losing nephropathy. some patients have difficulty tolerating this therapy and can be treated with diuretics instead. Commonly used diuretic drugs include thiazides and furosemide. The above measures mainly lower blood pressure by lowering blood volume, so attention should be paid to maintaining water and electrolyte balance during the use of drugs. 2, calcium ion antagonists have the effect of inhibiting calcium inward flow, can directly relax vascular smooth muscle, dilate small peripheral arteries, reduce peripheral vascular resistance, to achieve the purpose of lowering blood pressure. It has been reported that although calcium channel blockers do not affect glomerular capillary pressure and glomerular filtration rate, they also have the effect of preventing glomerulosclerosis, so they are ideal drugs for the treatment of CRF hypertension. 3, angiotensin-converting enzyme inhibitor (ACEI) ACEI in addition to lowering blood pressure; still has its unique effect of reducing hyperfiltration, mainly through the expansion of the small arteries to achieve; and has the effect of reducing proteinuria, may also have antioxidant, reduce glomerular basement membrane damage and other effects. In addition, the results of relevant experimental studies in recent years suggest that angiotensin II receptor I antagonist has a significant role in inhibiting glomerulosclerosis and delaying the progress of CRF. (C) Correction of water and electrolyte disorders and acid-base imbalance: The daily water intake of CRF patients should be supplemented with the previous day’s urinary excretion and increased by about 500 ml of non-significant water loss, which can be adjusted at any time according to the situation of suffocation and sweating. If there is water and sodium retention, diuretics can be used to increase urinary output and reduce edema. However, it should be noted that when GFR <30ml/min, thiazide diuretics are ineffective and should be replaced by tachyphylaxis and other tab diuretics; if there is no water and sodium retention, water and salt should not be restricted, and potassium salt may not be restricted in non-oliguric patients. The common types of water and electrolyte disorders and acid-base imbalance in CRF and their management measures are: 1. Hyperkalemia should be actively treated. When the blood potassium is >5.5 mmol/L, in addition to reducing the intake of potassium and avoiding the input of stock blood, oral potassium-lowering resins can be administered, among which calcium-based resins are better. When blood potassium >7 mmol/L, 10% calcium gluconate 10ml can be given intravenously to antagonize the myocardial toxicity of K+; or 5-10% glucose with common trypsin can be given intravenously to promote the entry of K+ into the cells and temporarily reduce blood potassium, and if necessary, dialysis treatment with potassium-free dialysis solution can be used. 2. High blood phosphorus and low blood calcium In case of high blood phosphorus, a low phosphorus diet should be given, limiting the phosphorus intake to about 600-800mg/d. LPD can bring the phosphorus intake down to this range. Phosphorus binding agents such as calcium bicarbonate and aluminum hydroxide can also be applied, all of which can increase phosphorus excretion, lower blood phosphorus, protect residual renal units and slow down the progression of CRF. When CRF < 40 ml > 2.63 mmol/L, calcium supplementation should be stopped. In addition, low blood calcium and high blood phosphorus can be secondary to hyperparathyroidism and renal osteodystrophy, both of which are related to 1,25(OH)2D3 deficiency and are treated well with 1,25(OH)2D3. Currently, the commonly used drugs are rocalciferol and alpha-D3. 3.Correction of acidosis Most CRF patients have metabolic acidosis, so they should take sodium bicarbonate orally, usually 3-10g/d, in three doses. If the acidosis is severe, it must be given intravenously, and the dose should be adjusted according to the results of CO2-CP and blood gas analysis. Dialysis treatment is performed if necessary. Experimentally, it is proved that metabolic acidosis can damage the renal tubular interstitium by a mechanism related to the increased tubular production of NH4, and sodium bicarbonate treatment can reduce this renal damage effect, thus protecting renal function. (iv) Correction of lipid metabolism disorders: As mentioned earlier, lipid metabolism disorders have an important role in the progression of CRF, and CRF may accelerate its progression due to secondary lipid metabolism disorders. Recent research studies have confirmed that statin lipid-lowering drugs not only reduce the high blood lipids in combination with various renal diseases, but also have the effect of reducing proteinuria and delaying the progression of renal insufficiency. Commonly used drugs such as sulforaphane. (E) intestinal clearance therapy: CRF, the intestine due to various reasons, such as enteritis, bleeding, bacterial infection, intestinal excretion of potassium, etc., so that the intestine formed metabolites and “toxins” accumulation site, part of the back absorption into the body circulation, aggravating the disease, therefore, through some measures to increase the intestinal clearance of these substances, can Therefore, by increasing the clearance of these substances from the intestine, we can alleviate the symptoms of CRF. 1.Oral adsorbent Activated carbon can adsorb phenols and medium-molecule substances in the intestine, which has certain effects, but its ability to bind “toxins” is limited because it binds to lipids in the intestine. Oxystarch can bind urea and be excreted from the intestine, and Esit can bind creatinine and uric acid and be excreted from the intestine to reduce blood urea nitrogen and creatinine. In recent years, there are still studies on oral adsorbents abroad, such as AST-120, which is porous carbon particles of 0.2-0.4mm in diameter, insoluble in water, not decomposed by intestinal bacteria, with high adsorption power for small and medium molecular weight substances, combined with low protein diet, and has a delaying effect on the progress of CRF. 2, mannitol induced diarrhea According to research, oral administration of large amounts of mannitol saline, 200ml every 5 minutes, a total of 7000ml in 3 hours, 3 times a week. Each liter of mannitol saline contains 180mmol of mannitol, 60mmol of sodium, 4mmol of potassium, 46mmol of chlorine and 20mmol of sodium bicarbonate. After taking it, diarrhea is frequent and increases the excretion of BUN, Cr and phosphorus, the disadvantage is that it is not easily tolerated by patients. According to research, the intestine contains 70g of urea, 2.5g of creatinine, 2.5g of uric acid and 2g of phosphorus per day, which is significantly more than the daily excretion in urine. The use of Chinese herbal decoction enema is safe and effective for excreting the above “toxins” contained in the intestine, and it is practical. Since 1978, Peking Union Medical College Hospital has been using the decoction of rhubarb, gong ying and calcined oyster to enemas, and has achieved good results. In addition, animal experiments also confirmed that BUN decreased, Scr was stable or slightly decreased, blood phosphorus level decreased, and the progress and deterioration of CRF was delayed after rhubarb enema treatment. (f) Combination of Chinese and Western medicine: There are two common ways to treat CRF, one is to use effective single herbal medicine or a simple formula based on single herbal medicine with Western medicine; the other is to use Chinese medicine to discriminate and legislate prescriptions for the condition. Regarding the treatment of CRF with single herbs, there have been many studies in China and Japan in recent years, and rhubarb is one of the most notable ones. In addition, the role of Cordyceps sinensis has also been studied in China. Chinese medicine is commonly used to treat CRF by warming the kidneys and strengthening the spleen, harmonizing the stomach and lowering the rebellion, activating blood circulation and removing heat and toxins, etc. However, because the condition of CRF is different, and the condition is more complicated if it is combined with comorbidities, Chinese medicine has the characteristic of differing from person to person in terms of evidence-based treatment. In recent years, the commonly used combination of traditional Chinese and Western medicine for the treatment of CRF are: 1, LPD plus rhubarb preparations as the basis of treatment Research has shown that rhubarb has the effect of inhibiting the proliferation of glomerular thylakoid cells, correcting lipid metabolism disorders, reducing CH and TG levels in the blood, and delaying the onset of glomerulosclerosis. It can also reduce the hypermetabolic state of the remnant kidney, inhibit the compensatory hypertrophy of the remnant kidney tissue, reduce proteinuria, improve azotemia and delay the progression of CRF. In addition to its effect on systemic nitrogen metabolism, rhubarb has an inhibitory effect on renal thylakoid cells and can inhibit the hypermetabolic state of renal tubular cells, so it has a preventive and curative effect on the early stage of CRF, which is receiving increasing attention. 2, LPD plus Chuanxiongzin as the basic treatment Research has confirmed that Chuanxiongzin can antiplatelet aggregation, antispasmodic, increase arterial blood flow in experimental animals, and protect the integrity of renal tissue structure in ARF experimental rabbits. In addition, it has an antibacterial effect on a variety of Gram-negative intestinal bacilli, which can reduce toxins produced by bacterial decomposition in the intestine, thus reducing urea nitrogen and alleviating clinical symptoms. 3.LPD plus Cordyceps preparation Cordyceps is a valuable traditional Chinese herbal medicine in China, which has been documented to have the effect of “protecting lung and benefiting kidney” and “secreting essence and benefiting qi”. Since its application in 1981 for the treatment of CRF, it has achieved satisfactory clinical results. Lai Leishi reported that Cordyceps sinensis had the effects of reducing urinary lysosomal enzyme excretion, maintaining the sodium retention function of renal tubules, reducing azotemia after poisoning, protecting renal function, and reducing histological changes, especially protecting lysosomal enzymes, in animal models. Another study claimed that Cordyceps can improve the cellular immune function of CRF patients and make the disease stabilize or slow down the progress of CRF. 4, Chinese medicine diagnosis and treatment plus Western medicine symptomatic treatment is generally based on the use of Western medicine anti-infection, diuretic and swelling, correction of water and electricity disorders and acid-base imbalance, based on the diagnosis and typing of internal Chinese medicine, or the use of fixed Chinese medicine formula plus reduction of internal consumption. Jin Peijian et al. divided CRF into four types: spleen and kidney yang deficiency, kidney yang weakening, both spleen and kidney deficiency, and qi stagnation and blood stagnation, and achieved certain results by differentiating the treatment separately. It is also believed that detoxification and draining of turbid evil in the three jiao, harmonizing the stomach and lowering rebelliousness, and facilitating urination are the basic principles of treating CRF, and the treatment of CRF with the addition of Huanglian Wenchu Tang has also been effective. Although the combined treatment of CRF with Chinese and Western medicine has made promising progress in recent years, providing a theoretical basis for the non-dialysis treatment of CRF and showing a broad prospect, there are still some problems that need to be solved, especially the specific mechanism of action of traditional Chinese medicine, the method of observation of efficacy and the measurement indexes, which need further in-depth research and discussion. (VII) Treatment of anemia: The main cause of anemia in CRF is the decrease in erythropoietin or activity, followed by insufficient intake of hematopoietic substances such as iron and folic acid, and the chronic blood loss due to bleeding tendency caused by CRF is also a cause. In recent years, recombinant erythropoietin (rEpo) has been applied to treat renal anemia with good results and is an ideal drug for treating CRF anemia. It can elevate and maintain red blood cell levels, bring red blood cell pressure (Hct) and Hb to ideal levels, relieve anemia symptoms and improve quality of life. However, it cannot be used as an emergency measure to improve anemia because Hb elevation does not start until two weeks after rEpo injection. The common dose and usage are (1) starting dose: 50-100u/kg, 3 times a week, injected intravenously or subcutaneously; (2) reducing dose: when Hct rises to 30-33% or rises more than 4 percentage points in 2 weeks, reduce the dose by 25u/kg; (3) increasing dose: when Hct rises less than 5-6 percentage points in 8 weeks of treatment and is below 30%, increase the dose by 25u/kg; (4) maintenance dose: when Hct rises less than 5-6 percentage points and is below 30%, increase the dose by 25u/kg. The side effects of rEpo are mainly elevated blood pressure, seizures and thrombosis. Blood pressure should be controlled within a safe range (150/90mmHg or less). Contraindicated in patients with uncontrolled hypertension and those with known hypersensitivity to mammalian cell derivatives or known hypersensitivity to human albumin. (H) Other measures: including avoiding the application of nephrotoxic drugs as far as possible; adjusting the type and dose of medication for CRF patients according to renal function at any time, and performing clinical blood concentration monitoring if available. In conclusion, CRF is a complex process that develops from decompensated renal function to ESRD with multiple pathological mechanisms, and it is important to address the main problems at different stages and pay attention to early and mid-term prevention and treatment. However, non-dialysis treatment cannot replace hemodialysis and renal transplantation. Regarding when to stop non-dialysis treatment, it is generally believed that when GFR 5-10 ml/min and Scr>707umol/L, it should be changed to dialysis treatment. At this time, non-dialysis therapy can be used as an adjunctive measure.