When kidney damage occurs in gout, it is called gouty nephropathy. Gout often has obvious clinical symptoms of arthritis, while renal changes are often insidious. Generally speaking, gouty arthritis recurs for many years before kidney damage occurs. However, there are exceptions, and even renal damage occurs before arthritis. Gout kidney damage are chronic gouty nephropathy, urinary tract uric acid stones and acute obstructive nephropathy are introduced separately.
I. Chronic gouty nephropathy
The average uric acid pool in normal human body is 1200mg, and 750mg is produced every day, about 2/3 is cleared by kidney and 1/3 is excreted from the intestine. Most of uric acid is excreted by the kidneys in the form of free uric acid sodium salt, and the kidneys excrete uric acid mainly through 4 processes.
1.Glomerular filtration;
2.Proximal tubular reabsorption;
3.Secretion by the distal tubule;
4, renal tubular secretion after reabsorption. The amount of uric acid excreted in urine is about 500mg per day in normal people, if the amount excreted in urine exceeds 700mg per day, it is called hyperuricuria.
Factors that affect the excretion of uric acid by the kidneys are
1, urine pH;
2, the flow rate of fluid in the renal tubules;
3, renal blood flow.
The first two are related to the decrease of uric acid or the deposition of urate in the collecting duct and urethra, while the renal blood flow is one of the main factors affecting uric acid excretion. A small amount of uric acid can be destroyed, mainly the uric acid secreted into the intestine is broken down by bacteria into allantoin and carbon dioxide. Decreased uric acid catabolism is not found in patients with gout; in fact, in hyperuricemia, especially after the onset of renal failure, uric acid entering the intestinal lumen for catabolism only increases and becomes an important second-line defense of the organism; therefore, increased purine anabolism and/or decreased uric acid excretion is an important mechanism for increased serum uric acid values in patients with gout.
Uric acid is 2,6,8-trioxopurine, and the hydrogen ion attached to its 9th position can ionize into urate, which makes the solution slightly acidic. Uric acid has a pH of 5.75, which is alkaline in body fluids, and therefore exists mainly as sodium or potassium salts in the blood and synovial membranes. Since the main cation in the extracellular fluid is sodium ion, uric acid salt in the body is mainly sodium urate. The sodium ion concentration in the papilla of the renal cone is 2 to 3 times higher than that in the plasma and the urine in the medullary region of the kidney is acidic, with urine pH <5.5.
These two points make the urate content in the renal medullary area 6 times higher than that in the renal cortex, which becomes the main site of sodium urate deposition. Therefore, the main damage sites of gouty nephropathy are renal tubules and renal interstitium, and the lesions are most serious in the renal medullary area. The deposited sodium urate comes from blood uric acid or urine uric acid, which can enter the interstitium directly through the epithelial cells of renal tubules. Macrophages phagocytose sodium urate, activate lysosomal enzymes and stimulate local inflammatory reaction in the interstitium, and lymphocytes, monocytes and plasma cells infiltration can be seen in the interstitial area of the kidney.
In addition, uric acid crystals deposited in the renal tubules can block the tubular lumen, eventually leading to tubular occlusion, destruction and irreversible tubular dysfunction. Light microscopy reveals needle-like, birefringent radiolucent uric acid crystals deposited in the tubular interstitium, which is a characteristic change of gout nephropathy. In the late stage of interstitial fibrosis, the kidney atrophy, fibrous tissue compression of blood vessels caused renal ischemia, small renal artery sclerosis and glomerulosclerosis, the above are two important causes of renal failure.
Chronic gouty nephropathy is the most common kidney damage, produced by the following three main mechanisms
The kidneys are the main organ for excreting uric acid. Excessive excretion of uric acid by the kidneys can easily cause urate crystals to be deposited in the kidney tissue, mainly in the interstitial kidney tissue, leading to interstitial nephritis, which can also block the renal collecting duct. Although only 1/3 of patients with gout clinically show kidney damage, it is much more serious than arthritis. And the degree of kidney damage and arthritis do not necessarily parallel each other.
2.High uric acid Increased uric acid concentration in renal tubular lumen and urine can cause obvious damage to the kidney, and the degree of damage is even more serious than that caused by increased blood uric acid concentration.
Most of the so-called “gouty nephropathy” is not caused by simple hyperuricemia, but by the combination of obesity, hypertension, hyperlipidemia, diabetes, arteriosclerosis, coronary heart disease, cerebrovascular disease, kidney stones and urinary tract infection. These combined diseases or complications can aggravate kidney damage and complicate the condition. For example, gout patients with hypertension are more than twice as likely as controls, but it is sometimes difficult to ascertain whether hypertension is an early manifestation of kidney damage or whether hypertension causes kidney damage.
Clinical features: About 85% of patients start to notice kidney lesions after the age of 30. Mild unilateral or bilateral low back pain is present in the early stages. A small amount of proteinuria, usually no more than ++, may appear intermittently in about 20% to 40% of patients in the early stages. As the disease progresses, persistent proteinuria may appear, and microscopic hematuria may also be present. The urine is acidic, and there may be mild swelling and moderate benign hypertension. There is almost always a decrease in renal tubular concentration, and the impaired tubular concentration precedes the impaired glomerular function.
There may be increased nocturia, polyuria, decreased urine specific gravity, and isotonic urine. Subsequently, glomerular filtration rate decreases and urea nitrogen increases. The disease often progresses slowly, and in the late stages, interstitial nephritis or kidney stones lead to life-threatening renal insufficiency, requiring hemodialysis treatment. 17-25% of patients die of renal failure. Chronic renal failure due to gouty nephropathy accounts for about 1% of the causes of uremia.