Exchange nephropathy (hyperuricemia): causes, symptoms, diagnosis, treatment

Dysmetabolic nephropathy with purine metabolism disorder or metabolic nephropathy is a group of rare hereditary diseases that are characterized by metabolic disorders in the kidneys and, as a result, the development of renal disorders. These diseases are usually genetic in nature and can manifest at different ages, including childhood and adulthood.

Metabolic nephropathy usually requires long-term medical care and management, including diet and treatments to control symptoms and slow the progression of the disease. Treatment and management of these conditions are best done under the guidance of a nephrologist, a kidney disease specialist. Genetic counseling to assess inherited risk and genetic testing may also be needed.

Over the past decades, the prevalence of uricosuria and uricosemia has increased in both children and adults. Kidney pathology caused by purine metabolism disorders can be diagnosed in 2.4% of the child population. According to screening studies, increased uricosuria occurs in 19.2% of adults. Such an increase in purine base metabolism disorders is explained by environmental factors: the products of gasoline engines that saturate the air of large cities significantly affect purine metabolism. The term "econephropathy" has emerged. It is practically important to take into account that maternal hyperuricemia is dangerous for the fetus due to its teratogenic effect and the possibility of developing congenital nephropathies - anatomical and histological. Uric acid and its salts have a direct nephrotoxic effect.

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Causes metabolic nephropathy (hyperuricemia)

Metabolic nephropathy is a group of rare inherited diseases caused by genetic mutations that affect the metabolism of the kidneys. Metabolic nephropathy is caused by these genetic mutations. Here are some of the most common forms of metabolic nephropathy and their genetic causes:

1. Cystinosis: This disease is associated with mutations in the CTNS gene, which codes for a protein involved in the transport of cystine across the lysosome membrane. Mutations in this gene lead to the accumulation of cystine in the kidneys and other tissues.
2. Fankoni syndrome: Fankoni syndrome can be caused by genetic mutations affecting different genes responsible for transporting different substances in the kidneys. For example, Fankoni syndrome, associated with mutations in the SLC34A3 gene, causes impaired phosphate reabsorption.
3. Aminoaciduria: This condition can be caused by mutations in the genes responsible for transporting amino acids in the kidneys.
4. Renal glycogen storage diseases: These rare diseases are associated with mutations in genes involved in glycogen metabolism in the kidneys.
5. Lipurias: Mutations in genes responsible for lipid processing can cause lipurias.

The genetic mutations responsible for metabolic nephropathy can be inherited from one or both parents. These mutations result in a deficiency or dysfunction of certain proteins, which in turn affects kidney function and metabolism.

Pathogenesis

In the pathogenesis of hyperuricemia, it is important to determine its type: metabolic, renal or mixed. The metabolic type involves increased synthesis of uric acid, a high level of uricosuria with normal or increased clearance of uric acid. The renal type is diagnosed with impaired excretion of uric acid and, accordingly, with a decrease in these parameters. The combination of metabolic and renal, or mixed type, is a condition in which uraturia does not exceed the norm or is reduced, and the clearance of uric acid is unchanged.

Since purine metabolism disorders are hereditarily determined, the main markers of hereditary nephropathy can be found in most patients with this pathology: the presence of people with kidney diseases in the family tree; frequently recurring abdominal syndrome; a large number of small stigmas of dysembryogenesis; a tendency to arterial hypo- or hypertension. The range of diseases in the family tree of a proband with dysmetabolic nephropathy by the type of purine metabolism disorders is wide: pathology of the digestive tract, joints, endocrine disorders. Staging is observed in the development of uric acid metabolism pathology. Metabolic disorders without clinical manifestations have a toxic effect on the tubulointerstitial structures of the kidneys, as a result of which interstitial nephritis of dysmetabolic genesis develops. When a bacterial infection is added, secondary pyelonephritis occurs. When lithogenesis mechanisms are triggered, urolithiasis may develop. Participation of uric acid and its salts in the immunological restructuring of the body is allowed. Children with purine metabolism disorders are often diagnosed with a hypoimmune condition. The development of glomerulonephritis is not excluded.

Symptoms metabolic nephropathy (hyperuricemia)

Intestinal manifestations of the uncomplicated form of purine metabolism disorder are non-specific. In younger children (1-8 years old), the most common symptoms are abdominal pain, constipation, dysuria, myalgia and arthralgia, increased sweating, nocturnal enuresis, tics, and logoneurosis. The most common manifestations in older children and adolescents are excess body weight, itching in the urethra, biliary dyskinesia, and lower back pain. Moderate signs of intoxication and asthenia are possible. Children with purine metabolism disorders usually have a large number of external stigmas of dysembryogenesis (up to 12) and anomalies in the structure of internal organs (minor heart defects, i.e. valve prolapses, additional chords; anomalies in the structure of the kidneys and gallbladder). Chronic pathology of the digestive tract is diagnosed in 90% of cases. Signs of myocardial metabolic disorders are almost as common - 80-82%. More than half of such children have arterial hypotension, 1/4 of patients have a tendency to arterial hypertension, which increases with the child's age. Most children drink little and have low diuresis ("opsiuria"). Urinary syndrome is typical of tubulointerstitial disorders: crystalluria, hematuria, less often - leukocyturia (mainly lymphocyturia) and cylindruria, inconstant proteinuria. Obviously, there is a close relationship between purine metabolism and oxalate metabolism. Crystalluria can be of mixed composition. In 80% of cases, circadian rhythm disorders of urination can be detected - predominance of night diuresis over daytime. With the progression of interstitial nephritis, the daily excretion of ammonium ions decreases.

Diagnostics metabolic nephropathy (hyperuricemia)

Diagnosis of metabolic nephropathy includes a number of clinical, laboratory and instrumental methods that help determine the type and degree of metabolic disorder in the kidneys. Here are the main steps in diagnosing metabolic nephropathy:

1. Clinical examination and medical history: The physician performs a general clinical examination and collects the patient's medical history, including family history and the presence of symptoms associated with kidney disorders.
2. Laboratory tests:
   • Urinalysis: Urinalysis may reveal abnormalities such as protein in the urine (proteinuria), blood in the urine (hematuria), or the presence of amino acids.
   • Blood tests: Measuring the level of uric acid in the blood (uroxanthinuremia) may be useful in diagnosing some forms of metabolic nephropathy.
   • Electrolyte and acid-base tests: Measuring electrolyte and acid-base levels in the blood can help identify deficiencies associated with metabolic nephropathy.
3. Kidney ultrasound: A kidney ultrasound can be used to visualize the structure of the kidneys and look for abnormalities such as cysts or enlarged kidneys.
4. Kidney biopsy: In some cases, it may be necessary to take a sample of kidney tissue for more detailed analysis. A kidney biopsy can reveal specific changes associated with metabolic nephropathy.
5. Genetic testing: If your doctor suspects you have an inherited form of metabolic nephropathy, genetic testing may be done to look for a specific mutation.

Treatment metabolic nephropathy (hyperuricemia)

Treatment of patients with purine metabolism disorders is based on dietary restrictions of products rich in purine bases or provoking their increased synthesis (strong tea, coffee, fatty fish, dishes containing gelatin), and increased fluid intake. Alkaline mineral waters (Borjomi) are recommended, a citrate mixture is prescribed in courses of 10-14 days or Magurlit.

In case of metabolic type of purine metabolism disorder, uricosis-depressant agents are indicated: allopurinol at a dose of 150 mg/day for children under 6 years old, 300 mg/day for those aged 6 to 10 years and up to 600 mg/day for older schoolchildren. The drug is prescribed in full dose for 2-3 weeks after meals with transition to half maintenance dose for a long course of up to 6 months. Additionally, orotic acid is prescribed (potassium orotate at a dose of 10-20 mg/kg per day in 2-3 doses).

For the renal type, uricosuric drugs are prescribed - aspirin, etamide, urodan, anturan - which inhibit the reabsorption of uric acid by the renal tubules.

In the case of a mixed type, a combination of uricosis depressants with uricosuric drugs is applicable. Both drugs are prescribed in half doses each. It is necessary to monitor the urine reaction with mandatory alkalization.

For long-term use in outpatient settings, the drug allomaron is recommended, containing 50 mg allopurinol and 20 mg benzobromarone. Senior schoolchildren and adults are prescribed 1 tablet per day.

Forecast

Prognosis of dysmetabolic nephropathy with purine metabolism disorder. In rare cases, extreme situations are possible when hyperuricemia leads to acute occlusion of the tubular system of the kidneys and urinary tract with the development of acute renal failure ("acute uric acid crisis"). Glomerulonephritis against the background of purine metabolism disorders usually proceeds according to the hematuric variant with episodes of reversible decrease in kidney function with the prospect of developing chronic renal failure within 5-15 years. Secondary pyelonephritis, as a rule, proceeds latently. The doctor's task is to diagnose purine metabolism disorders at the preclinical stage, that is, to identify patients at risk and give recommendations regarding lifestyle and nutrition, which will help slow down the development of pathology and prevent complications.