Dysmetabolic nephropathy – a group of diseases that are characterized by kidney damage due to metabolic disorders.
Depending on the cause of development, primary and secondary dysmetabolic nephropathies are distinguished.
Primary diseases are hereditary, characterized by a progressive course, early development urolithiasis chronic renal failure.
Secondary dysmetabolic nephropathies can be associated with an increased intake of certain substances in the body, impaired metabolism due to damage to other organs and systems ( for example , the gastrointestinal tract), drug therapy, etc.
The overwhelming majority of dysmetabolic nephropathies are associated with impaired calcium metabolism (from 70 to 90%), about 85–90% of them with an excess of salts of oxalic acid, oxalates (in the form of calcium oxalate), the rest with an excess of phosphates (calcium phosphates – 3–10 %) or are mixed – oxalate / phosphate- urate.
Primary dismetabolic nephropathy is rare.
It is most common in children. Its occurrence may be associated with a violation of both calcium and oxalate metabolism (oxalate salts).
Oxalates enter the body with food or are synthesized by the body itself.
Reasons for the formation of oxalates:
- Increased oxalate intake with food
- Bowel disease – Crohn’s disease, ulcerative colitis , intestinal anastomoses
- Increased production of oxalates by the body.
This is a multifactorial disease. According to various authors, the proportion of heredity in the development of oxalate nephropathy is up to 70–75%. In addition to genetic, external factors play a major role: nutrition, stress, environmental stress, etc.
The first manifestations of the disease can develop at any age, even in the neonatal period.
Most often they are detected at 5–7 years of age in the form of the detection of oxalate crystals, with a low content of protein, leukocytes and erythrocytes in the general urine analysis. Characteristic increase urine specific gravity .
The overall development of children with oxalate nephropathy, as a rule, does not suffer; but they are characteristic allergies, obesity , vegetative-vascular dystonia with a tendency to lower blood pressure ( hypotension ), headaches.
The disease is exacerbated during puberty at the age of 10–14 years, which, apparently, is connected with hormonal changes.
The progression of oxalate nephropathy can lead to the formation of urolithiasis, the development of inflammation of the kidneys during the layering of a bacterial infection.
Phosphate nephropathy occurs in diseases involving a violation of phosphorus and calcium metabolism. The main cause of phosphaturia is chronic urinary tract infection.
Often phosphate-calcium nephropathy accompanies oxalate -calcium , but it is less pronounced.
Uric acid metabolism disorders ( urate nephropathy)
During the day, 570–1000 mg of uric acid is formed in the body, one third of the amount of which is secreted into the intestine and destroyed there by bacteria.
The remaining two thirds are filtered in the kidneys, most are sucked back, and only 6–12% of the filtered amount is excreted in the urine.
Primary urate nephropathy due to hereditary disorders of uric acid metabolism.
Secondary occur as complications of other diseases (erythremia, multiple myeloma, chronic hemolytic anemia and al.), it is a consequence of the use of certain drugs (thiazides, cytostatic agents, salicylates, cyclosporin A et al.) or dysfunction of kidney tubules and physico-chemical properties of the urine (in kidney inflammation, for example).
Urate crystals are deposited in the kidney tissue – this leads to the development of inflammation and a decrease in renal functions.
The first signs of the disease can be detected at an early age, although in most cases there is a long latent course of the process.
And in the general analysis of urine urates are detected, small amount of protein and red blood cells. In the presence of a large number of urates, urine acquires brick color.
Violations of cystine metabolism
Cystine is a metabolic product of the methionine amino acid. Two main reasons for an increase in the concentration of cystine in the urine can be identified :
- excessive accumulation of cystine in the kidney cells
- impaired cystine reabsorption in the renal tubules.
Cystine accumulation in cells is the result of a genetic defect tsistinreduktazy enzyme. This metabolic disorder is systemic and is called cystinosis.
Intracellular and extracellular accumulation of cystine crystals is detected not only in the tubules and interstitium of the kidney, but also in the liver, spleen, lymph nodes, bone marrow, peripheral blood cells, nervous and muscle tissue, and other organs.
Violation of cystine reabsorption in the tubules of the kidney is observed due to a genetically determined defect of transport through the cell wall for amino acids – cystine , arginine, lysine and ornithine.
As the disease progresses, signs of urolithiasis are determined, and when the infection is added, kidney inflammation occurs.
Laboratory and instrumental diagnosis of dysmetabolic nephropathy is based on
- identifying salt crystals in urinalysis,
- increasing the concentration of certain salts in the biochemical study of urine,
- study of the crystal- forming ability of urine (АКОСМ),
- conducting tests for calciphylaxis and peroxides in the urine,
- Ultrasound of the kidneys.
Detection of salt crystals only in general urine tests is not a basis for making a diagnosis of dysmetabolic nephropathy. It should be borne in mind that the release of crystals with urine in children is often transient and is not associated with metabolic disorders.
To confirm the diagnosis of dysmetabolic nephropathy in the detection of salt crystals in the general analysis of urine biochemical analysis of urine is carried out.
The calciphylaxis test allows you to identify violations of cellular calcium metabolism. The urine peroxide test reflects the activity of cell membrane peroxidation.
Changes detected by ultrasound of the kidneys, as a rule, are not very specific. Detection of micromixes or inclusions in the kidney is possible .
Treatment of any dysmetabolic nephropathy can be reduced to four basic principles:
- normalization of lifestyle;
- correct drinking regime;
- specific methods of therapy.
Receiving a large amount of liquid is a universal way to treat any dysmetabolic nephropathy, as it helps to reduce the concentration of soluble substances in the urine.
One of the goals of treatment is to increase the nightly volume of urination, which is achieved by taking fluids before bedtime. Preference should be given to plain or mineral water.
Diet can significantly reduce the salt load on the kidneys.
Specific therapy should be aimed at preventing crystal formation, excretion of salts, and normalization of metabolic processes.
Treatment of oxalate nephropathy
- When treating patients with oxalate nephropathy, a potato-cabbage diet is prescribed, which reduces the supply of oxalates from food and the load on the kidneys.
- It is necessary to exclude jelly, strong meat broth, sorrel, spinach, cranberries, beets, carrots, cocoa, chocolate.
- It is recommended to enter into the diet dried apricots, prunes, pears.
- From mineral waters such as Slavyanovskaya and Smirnovskaya are used , 3-5 ml / kg / day . in 3 doses 1 month, 2–3 times a year.
Drug therapy includes membranotropic drugs and antioxidants. Treatment should be long.
- Pyridoxine (vitamin B6) is prescribed at a dose of 1-3 mg / kg / day . within 1 month quarterly.
- Vitamin B6 has a membrane stabilizing effect due to participation in the metabolism of fats as an antioxidant and the metabolism of amino acids. It is also advisable the appointment of the drug Magne B6 at the rate of 5-10 mg / kg / day . course for 2 months 3 times a year.
- Membrane stabilizing action renders vitamin A, which normalizes the interaction of proteins and lipids of the cell membrane. The daily dose of vitamin A 1000 IU per year of life of the child, the course – 1 month quarterly.
- Tocopherol acetate (vitamin E) is a powerful antioxidant that enters the body from the outside and is produced by the body itself. It must be remembered that the excessive introduction of vitamin E with food can inhibit its internal production by the mechanism of negative feedback. Vitamin E strengthens the protein-lipid bonds of the cell membranes. It is prescribed with vitamin A in a dose of 1-1.5 mg / kg of body weight per day.
As membrane stabilizers , dimephosphone and xyphon are used .
Dimephosphone is used in a dose of 1 ml of a 15% solution for every 5 kg of weight, 3 doses per day. The course is 1 month, 3 times a year.
Ksidifon prevents the deposition of insoluble calcium salts. It is prescribed in a dose of 10 mg / kg / day . 2% solution in 3 doses. Course – 1 month, 2 times a year.
Ciston has a high efficiency , especially during crystalluria . Cystone is prescribed in a dose of 1-2 tablets 2-3 times a day, a course of 3 to 6 months.
In addition, magnesium oxide is prescribed, especially with a high oxalate content, at a dose of 0.15–0.2 g / day .
Treatment of urate nephropathy
- When treating urate nephropathy, the diet provides for the exclusion of foods rich in purine bases (liver, kidney, meat broth, peas, beans, nuts, cocoa, etc.).
- The advantage should be given to products of dairy and vegetable origin.
- An important condition for successful therapy is adequate fluid intake – from 1 to 2 liters per day. Preference should be given to slightly alkaline and low-mineralized waters, grass decoctions (horsetail, dill, birch leaf, lingonberry leaf, clover, knotweed, etc.), oats broth.
To maintain the optimum acidity of urine, citrate mixtures can be used (uralite-U, blamaren , magurite , solimok , etc.).
In urate nephropathy, it is important to reduce the concentration of uric acid. To do this, use tools that reduce the synthesis of uric acid – allopurinol , nicotinamide .
The use of allopurinol in pediatrics is limited due to possible complications of the skin, liver, and blood.
Under the strict control of allopurinol prescribed in a dose of 0.2–0.3 g / day . in 2-3 doses within 2-3 weeks, then the dose is reduced. The duration of the general course is up to 6 months.
Nicotinamide is a weaker drug than allopurinol , but is better tolerated; appointed in a dose of 0.005-0.025 g 2-3 times a day for 1-2 months with repeated courses.
Uric acid is output as orotic acid, tsiston, etamid, Cystenalum, Phytolysinum et al.
Treatment of phosphate nephropathy
Treatment in phosphate nephropathy should be directed to the acidification of urine (mineral water – narzan, arzni , dzau- suar , etc .; drugs – cystenal , ascorbic acid, methionine).
A diet with the restriction of foods rich in phosphorus (cheese, liver, caviar, chicken, legumes, chocolate, etc.) is prescribed.
Treatment of cystinosis and cystinuria includes diet, high – liquid regimen and drug therapy aimed at alkalinization of the urine and increase the solubility of cystine .
The goal of diet therapy is to prevent excessive intake of the child’s precursor of cystine , methionine and other sulfur-containing acids.
To this end, foods that are rich in methionine and sulfur-containing amino acids — cottage cheese, fish, eggs, meat, etc., are also excluded (or severely limited) from the child’s diet.
Since methionine is necessary for the child’s body to grow, prolonged use of a strict diet is impossible, therefore, after 4 weeks from the start of dietary therapy, the child’s diet expands and approaches the usual one, but is characterized by strict exclusion of fish, cottage cheese and eggs.
The amount of liquid should be at least 2 l / day . It is especially important to take the liquid before going to bed.
For alkalinization of the urine is used citrate mixture, sodium bicarbonate solutions, blemen , alkaline mineral water.
To increase the solubility of cystine and prevent crystallization, penicillamine is prescribed . It has some toxicity, therefore at the beginning of therapy low doses of the drug are prescribed – 10 mg / kg / day . in 4–5 doses, then the dose increases during the week to 30 mg / kg / day , and for cystinosis , to 50 mg / kg / day.
Penicillamine treatment should be carried out under the control of cystine in leukocytes and / or cyanide nitroprusside test (test for cystine in the urine, where the concentration of cystine should be up to 150-200 mg / l). When these indicators are achieved, thepenicillamine dose is reduced to 10–12 mg / kg / day.
Penicillamine treatment is carried out for a long time, for years. Since penicillamine inactivates pyridoxine, vitamin B6 (pyridoxine) is prescribed in parallel at a dose of 1-3 mg / kg / day. within 2-3 months with repeated courses.
To stabilize the membranes of the renal tubules, vitamin A (6,600 IU / day ) and vitamin E (tocopherol, 1 drop for 1 year of life of a 5% solution per day) are prescribed for 4–5 weeks with repeated courses.
There is evidence of a positive effect of using a less toxic analogue of it, cuprenil, in a reduced dose in combination with xidiphon and other membrane stabilizers instead of penicillamine.
Antibacterial therapy is indicated for the addition of infection.
When cystinosis successfully used kidney transplantation, which is carried out before the end-stage development of chronic renal failure. Transplantation of the kidney can significantly increase the life of patients – up to 15-19 years, but the deposition of crystals ofcystine is observed in the graft, which ultimately leads to the defeat of the transplanted kidney.
The prognosis for dysmetabolic nephropathy is generally favorable.
In most cases, with the appropriate regimen, diet and drug therapy, it is possible to achieve a stable normalization of the corresponding indicators in the urine.
In the absence of treatment or if it is ineffective, the most natural outcome of dysmetabolic nephropathy is urolithiasis and inflammation of the kidneys.
The most frequent complication of dysmetabolic nephropathy is the development of an infection of the urinary system, primarily pyelonephritis.