I. Overview
Diabetic nephropathy (DN), also known as diabetic glomerulosclerosis, is a renal complication specific to diabetes mellitus. Modern medicine believes that the occurrence of this disease is related to chronic hyperglycemia-induced glomerular hyperfiltration, protein non-enzymatic glycosylation, polyol pathway activation, protein kinase C activation, extracellular matrix accumulation, and cytokine involvement, and its basic pathological manifestations are glomerular thylakoid stromal hyperplasia and glomerular capillary basement membrane thickening. The prevalence of diabetic nephropathy is 40-50% in type 1 diabetic patients and 20-30% in type 2 diabetic patients. In the early stage of diabetic nephropathy, the progression of the disease can be effectively stopped by strict control of blood glucose and blood pressure. Once the clinical nephropathy occurs, the kidney function will continue to decline until the end stage of renal failure. To date, there are no effective measures to stop its occurrence and deterioration. Currently, diabetic nephropathy has become the primary factor leading to chronic renal failure. Although Chinese medicine does not have the name of diabetic nephropathy, there are records of edema, urinary turbidity, vomiting, kidney dissipation, and guan-ge, etc., which are complications of prolonged achalasia, and through reading ancient and modern literature and research on the evidence of diabetic nephropathy, it is found that the location of diabetic nephropathy never leaves the kidney, from the appearance of trace protein in the urine to end-stage renal failure, and a series of manifestations such as urinary turbidity, edema, and guan-ge, etc., which appear during such a long course of the disease, belong to the category of nephropathy, and This nephropathy is secondary to achalasia, so it is reasonable to name it “achalasia nephropathy” in Chinese medicine.
Etiology and pathogenesis
1. Causes
1.1 Insufficient endowment and deficiency of kidney energy Insufficient endowment or deficiency of kidney energy after birth, deficiency of kidney energy, lack of consolidation of kidney qi, loss of qi-transformation, abnormal water metabolism, edema and turbidity of urine, which leads to the kidney disease of achalasia.
1.2 Phlegm and stagnation of the kidney ligaments. Excessive consumption of fatty and sweet foods damages the spleen and stomach, impairs the metabolism of water and fluids, and the fat does not transform into phlegm; thirst is prolonged, qi and yin are injured, stasis of blood and phlegm obstructs the kidney ligaments.
1.3 Deficiency of liver and kidney, hyperactivity of liver yang. Emotional and mental disorders, liver depression and fire, burning kidney yin, deficiency of liver and kidney, hyperactivity of liver yang, aggravate the nephropathy of achlorhydria.
1.4 Prolonged disease into the complex, turbid toxin injury kidney Thirst disease for a long time, sugar poisoning lipid poisoning, damage to the kidney complex, damage to the kidney body, the kidney use of the disorder, turbid toxin internal stagnation.
2. Pathogenesis and evolution pattern
2.1 At the beginning of the disease, the disease is in the liver and kidney, with deficiency of both qi and yin and stagnation of the kidney ligaments
The kidney is the master of water, the division of opening and closing, thirst disease for a long time, the loss of kidney yin, yin loss of Qi, resulting in deficiency of kidney qi, stagnation of kidney ligaments, lack of power to consolidate, loss of opening and closing, frequent urination, cloudy and sweet urine, liver and kidney are of the same origin, the essence and blood interchange, liver and kidney yin deficiency, essence and blood can not be carried up to the eyes, resulting in dryness of the eyes; yin deficiency and fire, burning the blood ligaments of the eyes, bleeding from the eyes, blurred vision, liver and kidney yin deficiency, yin deficiency and hyperactivity, dizziness, tinnitus, high blood pressure. Liver and kidney yin deficiency, stagnation of ligaments and veins, loss of nourishment of tendons and veins, then numbness and pain in the limbs.
2.2 Prolonged disease, yin loss and yang, deficiency of spleen and kidney, stagnation of kidney ligaments
Spleen and kidney yang deficiency, kidney ligament stasis, water and dampness retention, overflowing skin, then face and feet edema, and even chest water and ascites, yang deficiency can not warm the four ends, then fear cold limbs cold. The waist is the house of the kidney, and deficiency of kidney qi causes soreness and weakness of the waist and knees; the spleen is not healthy, so there is dullness, abdominal distension and loose stools.
2.3 Late stage of the disease, stagnation of the kidney ligaments, exhaustion of the kidney body, loss of kidney function, internal stagnation of toxins, damage to the five organs, and decay of qi, blood, yin and yang
Stagnation of the kidney ligaments, exhaustion of the kidney body, malfunction of the kidney function, flooding of water and dampness, and internal stagnation of turbid toxins, resulting in the emergence of the evidence. If the spleen and kidneys fail, the turbid toxin stops inside, and there is no source of blood production, then the face will look yellowish, the lips, nails and tongue will be light, and the blood will be deficient; if the water-damp turbid toxin attacks the heart and the lungs, then the heart will palpitate and the breath will be short, and the chest will be stuffy and wheezing and cannot lie down; if the kidneys fail, the turbid evil will congest the three jiao, and the kidneys will not open, then there will be little or no urine, and the disease will develop into the final stage of Guange disease.
3.Location and nature of the disease
The disease is characterized by deficiency of the liver and kidney, deficiency of qi and yin of the spleen and kidney, deficiency of qi, blood, yin and yang of the five viscera, and deficiency of qi stagnation, blood stasis, phlegm, turbidity and toxicity, dampness and heat.
Diagnosis
1.Clinical manifestations
The clinical manifestations of early diabetic nephropathy are not obvious, and there is no obvious difference with diabetes; patients with clinical nephropathy may have edema, elevated blood pressure, and may be accompanied by symptoms such as lumbago, weakness, dizziness and tinnitus; patients with nephrotic syndrome may have typical large amount of proteinuria, hypoproteinemia, high edema, and even thoracic fluid and ascites; patients with renal insufficiency and azotemia may have anemia, and may be accompanied by poor circulation, or even Patients with renal insufficiency azotemia may have anemia, may be accompanied by nausea and vomiting, hand and foot convulsions, combined with heart failure may appear chest tightness, breath-holding, or even wheezing can not lie down. In addition, patients with diabetic nephropathy may have clinical manifestations of diabetic retinopathy, diabetic peripheral neuropathy and diabetic vegetative neuropathy.
2.Physical and chemical examination
2.1 Urinary microalbumin: early stage nephropathy patients show an increase in urinary microalbumin, >20μg/min.
2.2 Urine protein quantification: early diabetic nephropathy urine protein quantification 0.5g/24h.
2.3 Renal function: diabetic nephropathy renal insufficiency presents with elevated blood creatinine and urea nitrogen.
2.4 Blood routine: diabetic nephropathy renal insufficiency may appear with decreased hemoglobin.
3.Diagnostic staging criteria
3.1 Diagnostic criteria
The diagnosis of diabetic nephropathy should be made by integrating clinical manifestations, pathological examination, diabetic complications, renal function, etc.
(1) Diagnostic criteria for early diabetic nephropathy: increased albumin excretion rate, 2 consecutive urine tests within 6 months with UAE of 20-200μg/min (30-300mg/24h), and exclusion of other possible causes of increased UAE: such as urinary tract infection, exercise, primary hypertension, heart failure, ketoacidosis, etc.
(2) Clinical diabetic nephropathy diagnostic criteria: persistent proteinuria urine protein > 0.5g/24h, more than two consecutive times, and exclude other possible causes of increased urine protein (as above); progressive decline in renal function; may be accompanied by diabetic retinopathy, edema, hypertension.
(3) Typical nodular glomerulosclerosis and homogeneous hypertrophy of glomerular capillary basement membrane seen by electron microscopy on histological examination of the kidney.
3.2 Staging criteria
Danish scholar Mogensen divided DN patients into 5 stages according to their renal function and pathological changes and clinical manifestations.
Stage I: characterized by glomerular hyperfiltration and increased renal volume. increased GFR (about 150 ml/min), normal urinary albumin excretion rate (UAE) and normal blood pressure. Renal pathology: glomerular hypertrophy. normal GBM and thylakoid. Insulin therapy can restore, but not necessarily to full normal.
Stage II: i.e. normal albuminuria stage. GFR is increased or normal in this stage. UAE is normal (<20μg/min or <30mg/24h) UAE is increased after exercise but can be recovered after rest. blood pressure can be normal or mildly elevated. Renal pathology: GBM thickening and increased thylakoid matrix.
Stage III: Also called early diabetic nephropathy (incipientDN). At this stage, GFR is approximately normal, UAE 20-200μg/min, and at the early stage of UAE 20-70μg/min, GFR starts to decrease to near normal (130ml/min), blood pressure is mildly elevated, lowering blood pressure can partially reduce urinary microalbumin excretion, renal pathology: GBM thickening and marked increase of thylakoid matrix, glomerular nodular and diffuse lesions and Glomerular nodular and diffuse lesions and small arterial vitreous lesions are present, and glomerular wasting has begun to occur.
Stage IV: Also known as clinical diabetic nephropathy or overt diabetic nephropathy (overt DN). At this stage, GFR starts to decrease (130-70ml/min in early stage, 70-30ml/min in late stage), with an average decrease of about 1ml/min per month, UAE >200μg/min, or urine protein >0.5g/24h, non-selective proteinuria, increased blood pressure, marked thickening of GBM, widening of thylakoid matrix, glomerular wasting (36%), and about 30% of DN Nephrotic syndrome may develop. About 30% of DN may develop nephrotic syndrome, i.e., massive proteinuria, high edema, hyperlipidemia and hypoproteinemia.
Stage V: end-stage renal failure, uremia, GFR <10ml/min, urine protein amount may be reduced by glomerular wasting, severe hypertension. Blood creatinine (Scr) and urea nitrogen (BUN) are elevated, hypoproteinemia, edema, and extensive glomerular sclerosis and desiccation. Patients at this stage commonly have loss of appetite, nausea and vomiting and anemia, and can be followed by severe hyperkalemia, metabolic acidosis and hypocalcemic convulsions, as well as secondary uremic neuropathy and cardiomyopathy.
4.Differential diagnosis
Diabetic nephropathy must be diagnosed before other nephropathic diseases are excluded, and if necessary, renal puncture pathology examination is required. For patients with diabetic nephropathy syndrome without retinopathy and the duration of the disease is shorter than 10 years, renal biopsy should be considered to exclude other causes of glomerular disease.
IV. Treatment
1.Basic treatment
1.1 Diet: Patients with diabetic nephropathy should be given a high-quality, low-protein diet rich in vitamins, and vegetable proteins such as legumes should be restricted. For diabetic nephropathy patients with normal renal function, protein intake is generally 0.6-0.8g/kg/d. For patients with renal insufficiency and creatinine clearance rate <30ml/min, protein intake <0.6g/kg/d is better, and α-keto acid should be taken at the same time. Edema and hypertension should limit sodium intake, and sodium chloride should be <5g/24h.
1.2 Exercise: moderate activity, do not overwork: diabetic nephropathy with renal failure should be bed rest, the amount of activity should not be too much, should not do strenuous activities.
1.3 Mental health: pay attention to mental health, maintain a relaxed mood, and build up confidence to overcome the disease.
2. Identification and treatment
The early stage of the disease is characterized by the deficiency of liver and kidney Qi and Yin, and stagnation of kidney ligaments; the middle stage is characterized by the deficiency of spleen and kidney, and stagnation of kidney ligaments; the late stage is characterized by the deficiency of both Qi and Blood, Yin and Yang, and stagnation of kidney ligaments, and internal stagnation of turbid toxins; the early stage is treated by nourishing the liver and kidney, benefiting Qi and nourishing Yin, and resolving stagnation and clearing ligaments.
2.1 Liver and kidney deficiency of both Qi and Yin, stagnation of kidney ligaments
Symptoms: soreness and weakness of the waist and knees, fatigue, dizziness, fear of heat, dry stool, dry eyes, blurred vision, fat tongue, dark tongue, or petechiae and stasis, white fur. Pulse: Stringiness and thinness.
Treatment: Nourishing the liver and kidney, benefiting qi and nourishing yin, resolving blood stasis and clearing the channels.
Radix et Rhizoma Ginseng, Radix Astragali, Radix Rehmanniae, Cornu Cervi Pantotrichum, Fructus Lycii, Radix et Rhizoma Shou Wu, Radix Salviae Miltiorrhizae, Rhizoma Chuanxiong, Radix Guggul.
Addition and reduction: Dry heat: dry mouth and thirst, frequent urination, red tongue with little fluid, slippery pulse. Add gypsum, Zhi Mu, Pueraria Mirifica, and pollen to this formula. Liver stagnation: bitter mouth and dry throat, bitter fullness in the chest, depression, dark tongue with yellow fur and sunken string pulse. Add Chai Hu, Citrus aurantium, Radix Paeoniae Alba, Fructus Foetida, Xiang Yuan, etc. to this formula.
2.2 Deficiency of both spleen and kidney, stagnation of kidney ligaments
Soreness of the waist and knees, fatigue, abdominal distension, edema of the face and feet, cold in the extremities, and excessive nocturia. The tongue is fat with tooth marks, light and dark or with petechiae and stasis, with white fur. The fur is white.
Treatment: Warming the kidneys and strengthening the spleen, invigorating Qi and invigorating Blood.
Radix: Xianmao, Xianling Spleen, Atractylodes Macrocephala, Poria Cocos, Gorgonian, Primrose, Radix Astragali, Radix Angelicae Sinensis, Rhizoma Ligustici Chuanxiong, Radix Salviae Miltiorrhizae, Rhizoma Polygonati.
Add and subtract: External heat toxicity: fever and chills, swelling and pain in the throat, floating pulse, add and subtract Yin Qiao San; Damp-heat in the bladder: frequent and hot painful urination, abdominal cramps, yellow and greasy tongue coating, add Shi Wei, Sheng Di Yu, Tu Fu Ling, Plantago; Hyperactivity of Liver-Yang: dizziness and headache, bitter mouth and dizziness, strong pulse, add Tian Ma, Hooked Vine, Du Zhong and Niubizi to the main formula.
2.3 Deficiency of Qi, Blood, Yin and Yang, stasis in the kidney ligaments, internal stagnation of turbid toxins
Soreness of the waist and knees, fatigue, yellowish complexion, pale lips and nails, palpitations and panting, edema, dullness and vomiting, constipation. The tongue is fat, dull and unpleasant, with thick and greasy coating. Pulse: sunken and weak.
Treatment: Benefit Qi and nourish Blood, resolve blood stasis and disperse knots, and clear turbidity from the internal organs.
Prescription: Astragalus membranaceus, Radix Angelicae Sinensis, Radix Rehmanniae Sinensis, Curcuma longa, Psidium guajava, Rhubarb.
Addition and reduction: Damp-heat obstruction in the abdomen: distension in the chest and epigastrium, unpleasant food and drink, occasional nausea, yellow or white greasy tongue coating. Add Huo Pei each, Atractylodes, Chen Pi, Radix Panaxiae, Zhu Ru, Huang Lian to the main formula; Constipation from the internal organs: dry stools, not working for several days, dark tongue, yellow dry coating. Add rhubarb, melon atrophy, citrus aurantium, raw earth; turbid toxin injures blood: see epistaxis, epistaxis, epistaxis, etc. Add rhinoceros horn powder (punch), panax quinquefolium powder (punch), raw dioscorea; blood deficiency generates wind: see tremor, tendon rotation, limb pain, add astragalus, angelica, white peony, licorice, coix seeds, papaya.
3, other therapies (focus on writing the characteristic, effective, otherwise do not write)
3.1 Chinese medicine: liver and kidney qi and yin deficiency, kidney complex stasis evidence can take Qiju Dihuang Wan, Liu Wei Dihuang Wan, Bao Ren Kang; spleen and kidney deficiency, kidney complex stasis evidence can take Jin Kui Kidney Qi Wan, Bao Ren Kang; qi, blood, yin and yang deficiency, kidney complex stasis, turbidity and toxicity within the stop evidence can take Angelica Blood Tonic Cream, Bai Ling capsule, Xin Qing Ning tablets.
3.2 Chinese medicine reserved enema: raw rhubarb, dandelion, oyster, 200ml of concentrated decoction, reserved enema, once a day.
4.Western medicine treatment principles
4.1 High quality low protein diet: For patients with diabetic nephropathy with normal renal function, protein intake is generally 0.6-0.8g/kg/d. For patients with renal insufficiency and creatinine clearance <30ml/min, protein intake <0.6g/kg/d is good, and α-keto acid should be taken at the same time. Those with edema and hypertension should limit sodium intake, and sodium chloride should be <5g/24h.
4.2 Control of blood glucose: The following issues should be noted in the control of blood glucose in diabetic nephropathy: (1) Biguanides are prone to induce lactic acidosis and are not recommended; (2) Sulfonylurea hypoglycemic agents are preferred to glycoprotein. Euglycemia is easy to cause hypoglycemia, and is not recommended. (3) α-glucosidase inhibitors and gliadin-type hypoglycemic drugs can be used as appropriate. (4) If the Ccr is less than 30ml/min, oral hypoglycemic drugs should be stopped and insulin should be used to control blood glucose; (5) The initial dose of insulin should be small in order to avoid hypoglycemia.
4.3 Blood pressure control: If the blood pressure of diabetic patients is >18.6/12Kpa (140/90mmHg), antihypertensive treatment should be used. (1) Non-pharmacological treatment: sodium restriction, smoking ban, alcohol restriction, weight reduction, appropriate exercise, emotional stability. (2) Drug therapy: ①ACEI or ARB with diuretics; ②CCB with β-blockers; ③ACEI with CCB; ④ diuretics with β-blockers. Blood pressure should be controlled up to 17.3/10.7/Kpa (130/80mmHg) in patients without renal impairment and urine protein <1.0g/day, and up to 16.7/10Kpa (125/75mmHg) in patients with urine protein >1.0g/day.
4.4 Adjustment of lipids: control lipids to the standard: total cholesterol <4.5 mmol/L, LDL-cholesterol <2.6 mmol/L, HDL-cholesterol >1.1 mmol/L, triglycerides <1.5 mmol/L. It is particularly important to lower total cholesterol and LDL-cholesterol to protect target organs.
4.5 Management of nephrotic syndrome: Intravenous colloid drip is required for volume expansion, and intravenous collagen diuretics are required for effectiveness. (1) Low molecular dextran (molecular weight 2.0-4.0 million daltons) is preferred, and colloidal substances of this molecular weight can both expand and osmotically diuretic. ②Colloid fluid containing glucose but not sodium chloride should be used to avoid aggravating water and sodium retention, although an appropriate amount of insulin must be added to control blood glucose at this time. ③If the urine volume is less than 400ml/d, the above colloid fluid should be used with caution or not. ④If edema and body cavity fluid are extremely heavy and the above treatment is ineffective, ultrafiltration for dehydration can also be used with blood purification techniques.
4.6 Dialysis treatment: Dialysis treatment for diabetic nephropathy currently has two main modalities, namely long-term hemodialysis and ambulatory continuous peritoneal dialysis (CAPD). timing of DN dialysis: SCr>530μmol/l (6mg/dl), CCr