Diabetic nephropathy is the first cause of end-stage renal failure in western developed countries and temporarily ranks second in China. It is believed that with social automation and excessive diet, diabetic nephropathy will soon replace glomerulonephritis and become the number one killer of kidney health. However, there are various treatments for diabetic nephropathy, and the effect is not obvious. Now we will make a comparison and summary of some treatments in recent years.
First, the goal of blood sugar control
Glycemic control is the core of diabetic nephropathy treatment. In the past, emphasis was placed on intensive glucose lowering, requiring glycemic control in the normal range, which did have some effect on some young patients, but had the opposite effect on the elderly and frail patients. Many studies found that the mortality rate of diabetic nephropathy was U-shaped curve, that is, glycemic control was too low or too high would increase the mortality rate, so the target of glycemic control should be appropriately determined. The fasting blood glucose should be kept at about 6.5 mmol/L and glycosylated hemoglobin at about 6.5% for young people and those who are in good physical condition, and should be relaxed to 7.0 mmol/L and glycosylated hemoglobin at about 7% for the elderly and the frail.
Second, the choice of glucose-lowering drugs
The choice of insulin should be the most ideal drug for both type I and type II diabetic nephropathy, but because of the need for long-term injections to bring a lot of inconvenience to the patient’s treatment, for a significant portion of patients with type II diabetic nephropathy is a waste, so a reasonable choice of oral hypoglycemic drugs is very necessary. In the early stage of diabetic nephropathy most glucose-lowering drugs can be chosen, with the aggravation of renal function damage, it is necessary to choose glucose-lowering drugs that have no effect on renal function or have less effect.
In people with decompensated renal function, try to avoid biguanide hypoglycemic drugs such as metformin; sulfonylurea hypoglycemic drugs such as glibenclamide and gliclazide are mainly excreted through the kidneys, so they should not be taken, glimepiride can be excreted through the biliary tract and can be taken in mild to moderate renal insufficiency, gliptone is basically not excreted from the kidneys and can be used in patients with renal insufficiency, in order to avoid adverse reactions such as hypoglycemia, it is generally recommended that creatinine Clearance rate of less than 30ml/minute when discontinued; Lenexa class such as Miglinide, Repaglinide rarely excreted through the kidneys, in renal insufficiency can still be used, but should not be too large a dose; increase insulin sensitivity drugs such as rosiglitazone and pioglitazone, can be applied to renal insufficiency, because of the role of increasing weight and liver toxicity, the past application of less, but in recent years the use rate has increased trend; lower postprandial blood sugar The drugs glucosidase inhibitors acarbose and voglibose have no adverse effects on liver and kidney function, but increase the risk of hypoglycemia when blood creatinine exceeds 180umol/l, and should be discontinued; DPP-4 inhibitors can inhibit β-cell apoptosis, promote β-cell neogenesis, and increase the number of β-cells in type 2 diabetic patients, representing the drugs selegiline, ligliptin and saxagliptin, with safety Significantly improved, and ligliptin can be taken in all stages of renal insufficiency, but care needs to be taken to reduce the dose.
Sodium-dependent glucose carrier inhibitors, with excellent hypoglycemic effect, without the adverse effects of other drugs, representative drugs are dagliflozin, kagliflozin and igliflozin, but recently it was found that the chance of infection is significantly increased in patients who are combined with Kai Tong (alfa keto acid).
Third, the control of proteinuria drugs
The central part of the treatment of diabetic nephropathy to control proteinuria, there is a wide range of treatment methods, but the lack of satisfactory methods.
The drugs are classified into the following categories according to their different protein-lowering effects.
1, angiotensin-converting enzyme inhibitors and angiotensin receptor blockers
These two classes of drugs are currently effective drugs for hypertension and heart disease, and also have a fairly strong effect on proteinuria in various chronic kidney diseases. These two types of drugs can be used in diabetic nephropathy to achieve a double effect. The representative drugs with good effect of angiotensin converting enzyme inhibitors are benazepril, perindopril and enalapril, and the representative drugs with good effect of angiotensin receptor blockers are valsartan, irbesartan and temisartan. These drugs can control microproteinuria well, and also have considerable effect on large amount of proteinuria.
2.Aldosterone receptor blockers
The classic drug is spironolactone, which has a strong inhibitory effect on proteinuria in various chronic kidney diseases, and at the same time can delay the progress of chronic kidney diseases, and can significantly reduce proteinuria in diabetic nephropathy. The application of eplerenone has increased in recent years, with stronger binding to aldosterone receptors, and it is believed that with the promotion of this drug, the treatment of diabetic nephropathy will achieve better results.
3.Glomerular basement membrane repair drugs
The important cause of proteinuria is the destruction of the negative charge barrier of glomerular basement membrane. Heparin has a negative charge and has a good repair effect on the basement membrane, which can be used to treat proteinuria caused by various reasons. However, heparin needs to be absorbed by subcutaneous injection or intravenous injection, and diabetic nephropathy requires a longer period of medication, so it brings a lot of inconvenience to patients. Sulodexide is a highly purified mucopolysaccharide compound for oral administration, consisting of 80% heparin sulfate and 20% dermatan sulfate, with a chemical structure similar to heparin, which can have the effect of controlling proteinuria by reducing the breakdown of endogenous heparin in the body. Due to its high price, it is mainly used for the treatment of diabetic nephropathy, and good results have been achieved. Sulodexide seems to have no significant effect on advanced diabetic nephropathy, and early use of the drug is recommended.
4.Vitamin D receptor activators
These drugs can reduce proteinuria and kidney damage by inhibiting thylakoid cell proliferation and reducing the increase of extracellular matrix. They can control proteinuria that is not treated with angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in diabetic nephropathy.
5.Endothelin antagonists
A drug that has a direct inhibitory effect on endothelin, atrasentan, has been used in the treatment of proteinuria and has made its debut in diabetic nephropathy, with the major disadvantages of increasing body weight and inducing heart failure.
6.Direct renin inhibitors
Aliskiren aliskiren is a non-peptide renin blocking drug, can block the renin angiotensin system in the first link, reduce renin activity, reduce the production of angiotensin II and aldosterone, does not affect the metabolism of bradykinin and prostaglandin, play a role in the treatment of hypertension and treatment of cardiovascular disease, has a significant protective effect on the kidney. In diabetic nephropathy also achieved significant results.
7.Anti-fibrotic drugs
Mephenylpyridone can counteract connective tissue growth factor and has been shown to be effective in the treatment of focal glomerulosclerosis and idiopathic pulmonary fibrosis. Preliminary observations show that small doses of mephenylpyridone can improve glomerular filtration rate, but there is no protective effect on urinary albumin-creatinine ratio.
8.Protein kinase C inhibitor
Ruboxistaurin methanesulfonate hydrate is a drug for the treatment of diabetic retinopathy, the average reduction in proteinuria in the treatment of diabetic nephropathy is about 28%, recommended for patients with poor results of other drugs or combined retinopathy.
9.Anti-inflammatory drugs
The representative drug hexaconitine is a methylxanthine derivative, which has significant anti-inflammatory, anti-proliferative and anti-fibrotic effects and is reported to have the effect of reducing proteinuria, but the author applied hundreds of cases and did not see any obvious effect.
IV. Other therapies
Islet cell transplantation has been proved to have good glycemic control and reversal effect on the damage of diabetes; vitamin E and vitamin B6 have certain effect on proteinuria in diabetic nephropathy; autologous stem cell transplantation, theoretically, has better effect, but the technology is immature and there is no good information to support it.