Uric acid nephropathy (gout nephropathy) is a condition in which the concentration of uric acid in the blood increases to a state of supersaturation and uric acid crystals are deposited in the kidneys, causing lesions. The incidence of uric acid nephropathy in Europe and the United States is about 0.3%, and the European Dialysis Transplantation Association reported that end-stage renal failure caused by gout accounts for 0.6 to 1.0%. In recent years, the increased intake of protein and purine-rich foods in our diet has increased the incidence of gout. The average age of attack is 45 years old, and the occurrence of gout nephropathy is more than 10 years after the onset of hyperuricemia.
[Western medical etiology]
The disease is divided into two categories: primary and secondary. The primary ones are basically hereditary, but the mode of inheritance is not clear. Increasingly, clinical data show that primary gout is closely related to obesity, primary hypertension, dyslipidemia, diabetes mellitus, and insulin resistance.
Etiology and classification of hyperuricemia and goutDysregulation of uric acid metabolismGenetic characteristicsPrimary
1. Molecular defects of unknown cause (idiopathic)
(1) Reduced uric acid excretion (80-90% of primary)
(2) Excessive production of uric acid (10-20% of primary)
2. Enzyme and metabolic defects (1% of primary)
(1) Phosphoribosyl pyrophosphate synthase (PRS) hyperactivity
(2) Hypoxanthine-guanine phosphate ribosyltransferase (HGPRT)
Deficiency secondary to
1, enzyme and metabolic defects Myogenic hyperuricemia, Lesch-Nyhan syndrome, Von Gierke disease, adenine ribonucleic acid ribosyltransferase (APRT) deficiency
2, Excessive cell destruction Hemolysis, burn trauma, chemotherapy, radiotherapy, excessive exercise
3, cell proliferation Leukemia, lymphoma, myeloma, erythroblastosis
4, exogenous High purine diet, excessive alcohol consumption
5.Reduced renal clearance Renal failure, ketoacidosis, hypertensive syndrome of pregnancy, drugs, toxins
6, Decreased extracellular fluid volume dehydration, uremia decreased renal clearance.
[Western medical pathology]
A large number of autopsies have confirmed that 100% of gout patients have renal lesions. The characteristic histological manifestation of gout nephropathy is the appearance of urate deposits in the renal interstitium and tubules, which can be seen as birefringent needle-shaped urate crystals, and these crystals cause infiltration of individual nucleated cells around them, leading to tubular epithelial cell necrosis, tubular atrophy, tubular occlusion, interstitial fibrosis, and then renal unit destruction. The formation of microcalcifications in the collecting duct can cause dilatation of the collecting duct and predispose to secondary bacterial infections. During uric acid-induced renal damage, the role of uric acid concentration and urinary uric acid concentration in tubular fluid, especially in the renal medulla and renal papillae, is more significant than that of blood uric acid concentration.
[TCM etiology and pathogenesis]
1.Insufficient innate endowment or old age, resulting in the lack of spleen and kidney, loss of qi-transformation, lifting and lowering, and lack of separation of clear and turbid, so that metabolic waste accumulates in the body, breeding dampness, turbidity, phlegm, and stasis as a problem.
2, over-eating fat, sweet and alcoholic wine, dampness and heat, spleen and stomach damage, fluid perfusion metabolism is not normal, water and grain can not be transformed into gas and blood essence, but brewed brewed water and dampness, phlegm, blood stasis stay and not go.
3, excessive labor and weariness or indiscipline, labor injury to the kidney, depletion of liver and kidney essence and blood, kidney loss of gasification, liver loss of regulation, hyperactive phase fire, under the robbing liver and kidney Yin essence.
4. The kidney is damaged by poison or poisonous drugs, the kidney loses its function of qi-transformation, the opening and closing of the body is lost, water-dampness and phlegm turbidity are generated internally and stagnate.
[Clinical symptoms]
Polyuria and nocturia can be caused by tubular interstitial lesions; the occurrence of urinary stones can lead to hematuria, lumbar and abdominal cramps, and even sudden anuria; combined with urinary tract infections can lead to urinary frequency, urinary urgency, and urinary pain; in the late stage of severe renal damage, chronic renal failure manifestations such as dizziness and weakness, nausea and vomiting, halitosis, oliguria and swelling can occur.
[Diagnostic points]
History features and symptoms: middle-aged or middle-aged men with family history and manifestations of metabolic syndrome such as obesity, hypertension, hyperlipidemia, diabetes mellitus, etc. without history of other renal diseases but polyuria, nocturia, microscopic or carnal hematuria may be accompanied by a small amount of proteinuria, or urinary tract stones and sudden onset of joint redness, swelling and pain.
Signs: redness and swelling of the toes, ankles, knees, elbows, wrists, metacarpals and interphalangeal joints are common; in the acute stage, severe local skin pain, fever, dark redness, repeated episodes, local gout stones may be formed, joint deformities; if the skin breaks down at the gout stones, ulcers may be formed, which are difficult to heal over time, and there may be chalky or batter-like crystalline material overflowing. There may be elevated blood pressure, anemia, and edema in the late stage.
Laboratory tests: urinary routine: urine pH <6, mild proteinuria and microscopic hematuria and leukocyturia may be present, combined with stones often appear carnal hematuria; blood uric acid measurement, men >420μmmol/L (7.0mg/dl), women >350μmmol/L (6.0mg/dl), 24-hour urinary acid excretion after 5 days of purine restricted diet >3.57mmol ( 600mg); uric acid stones can be detected on abdominal ultrasound without abdominal radiographs (if uric acid stones are combined with calcium deposits, abdominal radiographs can be visualized); advanced renal damage can be severe with elevated blood creatinine and urea nitrogen, decreased endogenous creatinine clearance, metabolic acidosis, electrolyte disturbance, and ultrasound suggesting bilateral renal atrophy.
[Differential diagnosis]
1, secondary hyperuricemia due to various causes: this disease must be differentiated from other renal diseases causing renal decompensation and secondary hyperuricemia caused by reduced urinary uric acid excretion. In primary hyperuricemia, gout attacks are frequent, arthritis is obvious, and renal dysfunction appears late; while in renal disease secondary hyperuricemia, gout attacks are not obvious and renal dysfunction appears first. Because the renal tubules are severely damaged in the end stage of kidney disease, resulting in significant reduction of uric acid reabsorption by the renal tubules, the uric acid excretion may not be reduced, so the 24-hour uric acid excretion cannot be used as the basis for the diagnosis of primary or secondary hyperuricemia, and the diagnosis of uric acid nephropathy should not be made easily when the evidence is insufficient, and other kidney diseases should be carefully excluded.
2. Acute hyperuric acid nephropathy: If the patient has myeloma, lymphatic system proliferative disease, or has malignant tumor during radiotherapy or chemotherapy, blood uric acid can rise sharply in a short period of time, causing acute hyperuricemia, which can be manifested as oliguric acute renal failure, when uric uric acid excretion/urinary creatinine >1.0, while in acute renal failure caused by other etiologies, this ratio is often <1.0.
[Treatment]
I. Prevention of elevated blood uric acid and urate deposition
(1) Community physicians should examine patients and their families for early detection of hyperuricemia, especially for those who are already suffering from obesity, primary hypertension, dyslipidemia, diabetes mellitus, etc., and spread the relevant health knowledge.
(2) Reduce exogenous purine sources and avoid high purine diet, such as animal offal, seafood such as fish, shrimp, clams and crabs, meat, peas, etc.
(3) Strictly abstain from alcohol, beer and wine are not suitable for consumption because they contain purine substances, and other alcohols are not suitable for consumption because they have a competitive inhibitory effect on renal tubular excretion of uric acid after metabolism into lactic acid.
(4) Promote healthy diet structure, prevent obesity, eat more fresh vegetables, fruits and vitamin-rich foods, control protein intake to 1.0g/Kg per day, and account for 50-60% of total calories from carbohydrates.
(5) Increase uric acid excretion, drink more water, so that the daily urine volume reaches more than 2000ml, and drink enough water before going to bed at night to prevent the concentration of uric acid from increasing during sleep, the dilution of urine can slow down the growth of stones and promote the discharge of stones.
(6) Avoid overexertion and tension, moderate physical exercise, and bed rest for those with acute gouty arthritis.
Western medical treatment
(1) Treatment of primary disease: For all types of secondary hyperuricemia with clear etiology, the first step is to actively control and treat the primary disease and provide symptomatic treatment for the mechanism causing the elevated uric acid.
(2) Alkalinization of urine: It is an important measure to prevent uric acid stones. Maintaining urine pH at 6.5-6.8 is the most appropriate. Commonly used drugs sodium bicarbonate (baking soda) 3-6g/day, alkaline combination (citrate 140g, sodium citrate 98g, add water to 1000ml to make, take 20-30ml each time, 3 times/day).
(3) Promote uric acid excretion. The main mechanism of action of these drugs is to prevent the reabsorption of uric acid by the renal tubules, which is ineffective when the endogenous creatinine clearance rate is <20ml/min. It is suitable for the intermittent and chronic phases of hyperuricemia attacks, and should not be used when there are urinary stones and the 24-hour urinary acid excretion is >3.57mmol (600mg).
Commonly used drugs: ①Probenecid, the starting dose is 0.25g, 2/day, if there are no side effects such as loss of appetite, nausea and vomiting, it can be gradually increased to 1~3g/day, divided into 3~4 oral doses. ②Sulfinpyrazone (benzosulfone), stronger than propofol, 50mg, 2/day, gradually increase to 100mg, 3/day. The initial dose of 25mg/day can be increased to 50mg/day and 150mg/day, with a maintenance dose of 50mg once every other day. After the use of these drugs, because of the increase in uric acid excretion, there are side effects such as stimulation of acute attacks of gout and easy formation of uric acid crystals to block the renal tubules and aggravate renal lesions, so during the use of drugs, we must drink more water and take alkaline drugs such as sodium bicarbonate at the same time.
(4) Inhibit uric acid synthesis drugs: At present, there is only allopurinol, which blocks the conversion of xanthine into uric acid through the principle of enzyme competition inhibition, so that the blood and uric acid concentration can be rapidly reduced, and it can be used in combination with uric acid excretory drugs or alone. For the treatment of chronic hyperuricemia nephropathy, 200-400mg/day in 2-4 oral doses; for the treatment of acute hyperuricemia nephropathy, 600-800mg/day in 3-4 oral doses; for the treatment of uric acid stones, the first day dose is 300-400mg in 3-4 oral doses, and when the blood uric acid drops to the normal range, it is changed to 200mg/day maintenance dose. The side effects of the drug are gastrointestinal irritation, rash, fever, liver damage and bone marrow suppression, mostly occurring in renal insufficiency, so it is appropriate to reduce the amount of application by half for those with renal insufficiency.
(5) Adjuvant therapy: Most patients with hyperuricemia are obese, often combined with hyperlipidemia, especially hypertriglyceridemia, according to the condition of the selection of beta and niacin to lower lipids; about 1/3 of patients with hyperuricemia suffer from hypertension, control of blood pressure is important to protect the heart, brain, kidneys and other important organs, according to the specific situation of patients can choose angiotensin-converting enzyme inhibitors, such as angiotensin II receptor The use of angiotensin-converting enzyme inhibitors, angiotensin II receptor antagonists, beta-blockers, calcium channel blockers, alpha-blockers and diuretics should be avoided to avoid inhibiting uric acid excretion.
(6) For chronic renal insufficiency with severe renal damage, the treatment principle is the same as that for chronic renal failure due to other causes, and renal replacement therapy is necessary; for combined urinary tract infection, active anti-infection; for urinary tract stones such as simple uric acid stones, the stones can be gradually dissolved and removed by alkalinizing the urine and promoting uric acid excretion; for uric acid stones combined with calcium deposits, especially when the stones cause urinary tract obstruction If uric acid stones are combined with calcium deposits, especially when the stones cause urinary tract obstruction, they should be referred to urology for treatment.
(7) When acute arthritis attacks, various non-steroidal anti-inflammatory drugs, such as fenbid, diclofenac, anti-inflammatory pain, etc., should be used, but attention should be paid to the reduction of the dose after the reduction of symptoms, so as not to cause long-term use of painkiller nephropathy.
Third, Chinese medicine treatment
1, identification and treatment: the disease is always based on the original deficiency (liver, spleen, kidney qi, yin, essence, blood deficiency) evil real (water-damp, damp-heat, phlegm, blood stasis) as the key to the pathogenesis, treatment benefits to support the positive and drive away evil, according to the severity of the disease into latent symptoms, manifest evidence and the end stage to stage treatment.
(1) Latent symptoms: no obvious discomfort or only slight discomfort, elevated blood/urinary uric acid level and mild proteinuria on urinalysis.
Treatment: Regulating the spleen and kidney, relieving dampness and lowering turbidity, regulating qi and activating blood circulation.
Main formula: Radix Angelicae Sinensis and Paeoniae San (Radix Angelicae Sinensis, Paeoniae Sinensis, Chuanxiong Ligustici, Poria, Zedoary, Atractylodes Macrocephalae) plus or minus: for deficiency of both qi and yin, add Radix Astragali and Radix Astragali; for deficiency of liver and kidney, add Cianling Spleen and Huai Niu Kne; for dysuria, add Plantago lanceolata and Money Plant.
(2) Damp-heat injury to the kidneys: lumbar soreness and lumbago, yellow and red urine, stinging and embarrassment or with gravel, red tongue, yellow and greasy coating, slippery pulse.
Treatment: Clearing heat, relieving dampness and promoting lymphatic flow.
The main formula: eight positive san cut (Che Qian Cao, Bian Cao, Qu Mai, slippery stone, licorice, gardenia, rhubarb) plus or minus: hematuria, plus small thistle, white foxglove, raw ground elm; with stones, plus money grass, sea gold sand, chicken internal gold, stone reed; urinary frequency, painful urination, plus honeysuckle, dandelion, septoria; lumbago, plus Zhi Mu, Huang Cai, Du Zhong.
(3) Damp-heat obstruction of ligaments: joint pain, even like cutting, local skin redness, swelling, heat and pain, drowsiness and weakness, heavy back, unfavorable turning. The tongue is red or dark red, with yellowish greasy coating and slippery pulse.
Treatment: Clearing heat and relieving dampness, activating blood circulation and relieving pain.
Main formula: San Miao Wan and Angelica sinensis Pain Relief Soup (Huang Bai, Cang Zhu, Chuan Niu Kne, Angelica sinensis, Qiang Wu, Ge Ge Gen, Fang Feng, Zhi Mu, Ze Di, Pig Yin Ling, Yin Chen, Scutellaria baicalensis) plus and minus: for fever, add raw gypsum; for swollen joints and lower extremities, add Fu Ling, raw Coix Seed, Dioscorea, Papaya; for painful joints at night, add Chicken Blood Vine, Red Peony, Peach Nut, Red Flower; for proteinuria, add Panax notoginseng; for hematuria, add Xiaoxiao Thistle, Bai Mao Root, Sheng Di Yu For proteinuria, add Xiaoxi thistle, Bai Mao Root, Sheng Di Yu, Xian He Cao.
(4) Main evidence of phlegm-stasis retention: lumbago, peripheral joint swelling and pain, joint stones, drowsiness and weakness, swelling of limbs, dark red tongue with petechiae, white or white greasy coating, thin or slippery pulse.
Treatment: Promoting blood circulation and eliminating blood stasis, promoting circulation and relieving pain.
(5) qi and yin deficiency main evidence: fatigue, no color, waist and knee soreness, frequent nocturnal urination, dry mouth and stool, light red tongue or light dark, with tooth marks on the side, sunken or weak pulse.
Treatment: Benefit qi and nourish yin. Main formula: Tai tonic yuan decoction (Shu Di, Cornu Cervi Pantotrichum, Yam, Fructus Lycii, Eucommia, Radix Astragali, Radix Angelicae Sinensis) plus and minus: for joint pain, add Chicken Blood Vine, Chuan Niu Knee; for heat in the hands and feet, add Zhi Mu, Huang Bai, Radix et Rhizoma Polygonati, Dry Lotus Grass; for frequent nocturnal urination, add Uva Ursi, Fructus Fructus; for dry mouth and bowel movements, add Radix et Rhizoma Shengdi, Radix et Rhizoma Shou Wu.
(6) End-stage symptoms: withered or black face, cold fear, cold limbs, lack of food and drink, or even nausea and vomiting, drowning in the mouth, puffy urine, or withered body, palpitation and shortness of breath, poor bowel movement, pale and fat tongue, greasy moss, sunken or weak pulse.
Treatment: Tonifying the spleen and kidney, removing turbidity and detoxification.
Main formula: Wenzhou Tang combined with Huanglian Wenzhi Tang (Rhubarb, Xianling Spleen, Prince’s Ginseng, Huanglian, Radix Panax notoginseng, Bamboo Roo, Chen Pi) plus or minus: for poor appetite and stuffy stomach, add Huohuo Stem, Su Stem, Sharen; for nausea and vomiting, add Radix etiolatum, Ochre, Su Ye, ginger juice); for edema, add Poria, Zedoary, Plantago; for palpitation and shortness of breath, add Huangjing, Salviae Miltiorrhizae; for itching skin, add Radix etiolatum, White Moss Peel.
2, proprietary Chinese medicine treatment, waist and knee weakness, joint pain can be taken Yi kidney remission pill, 1 ~ 2 bags, 3 / day, warm yang to nourish the kidneys, through the pain; joint swelling and pain, lower limb edema, available Zhengqing wind pain Ning slow-release tablets, 1 ~ 2 tablets, 3 / day, diuresis, swelling, dispel wind and dampness, blood circulation; advanced renal insufficiency, can be taken urinary toxicity Qing, 1 ~ 2 bags, 3 / day, blood circulation, blood stasis, pass the internal organs to lower turbidity.
3, other Chinese medicine treatment: fumigation treatment Angelica sinensis 20g, Chuanxiong 60g, Niu Knee 60g, Safflower 30g, Su Mu, Chuan Jian, Dog Chi, Fang Feng, Dou Wu, Qiang Wu 100g each, Wu slightly snake 60g, chicken blood vine 150g, made frankincense, made myrrh 20g each, blood exhaust, pediatric tea 60g each, water decoction juice, mixed into the temperature of the bath water, bath, once a day, 15 to 30 days for a 15-30 days as a course of treatment.