Kidney damage in metabolic diseases

Causes kidney damage from metabolic diseases

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Causes of hypercalcemia

Class	The most common reasons
Idiopathic	Idiopathic hypercalcemia of childhood (Williams syndrome)
Caused by increased calcium reabsorption in the intestine	Vitamin D and calcium-containing drug intoxication Sarcoidosis
Caused by increased resorption of calcium from bone tissue	Hyperparathyroidism Metastases and primary tumors of bone tissue Multiple myeloma

Nephrocalcinosis of varying severity is observed in many chronic progressive kidney diseases, especially in analgesic nephropathy.

Factors predisposing to the development of nephrocalcinosis:

• hypercalcemia;
• increased calcium reabsorption in the intestine (hyperparathyroidism, vitamin D intoxication);
• hypercalciuria caused by impaired calcium reabsorption in the tubules;
• deficiency in urine of factors that maintain calcium salts in soluble form (citrate).

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Kidney damage in hyperoxaluria

Hyperoxaluria is one of the most common causes of nephrolithiasis. Primary and secondary hyperoxaluria are distinguished.

Oxalate deposition occurs mainly in the renal tubulointerstitium. In severe hyperoxaluria (especially in type I primary), terminal renal failure sometimes develops.

Variants of primary hyperoxaluria

Option	Cause	Flow	Treatment
Type I	Peroxisomal alanine-glycolate aminotransferase (AGT) deficiency	Intensive nephrolithiasis Debut at the age of 20 Development of severe renal failure is possible.	Pyridoxine Abundant fluid intake (3-6 l/day) Phosphates Sodium citrate
Type II	Hepatic glycerate dehydrogenase deficiency	Debut at the age of 20 Hyperoxaluria is less pronounced than in type I Nephrolithiasis is less intense than in type I	Abundant fluid intake (3-6 l/day) Orthophosphate

Variants of secondary hyperoxaluria

Class	The most common reasons
Drug and toxin induced	Ethylene glycol Xylitol Methoxyflurane
Caused by increased absorption of oxalates in the intestine	Condition after resection of sections of the small intestine (in Including in surgical treatment of obesity) Malabsorption syndrome Cirrhosis Eating animal protein in large quantities

Kidney damage due to uric acid metabolism disorders

Uric acid metabolism disorders are widespread in the population. Most of them are considered primary - genetically determined (for example, mutation of the uricase gene), but they acquire clinical significance only under the influence of exogenous factors associated with lifestyle (see "Lifestyle and chronic kidney diseases"), including the use of drugs (diuretics).

Secondary hyperuricemia is often observed in patients with myelo- and lymphoproliferative diseases, as well as in systemic diseases. The severity of secondary hyperuricemia also depends to a certain extent on hereditary predisposition.

A tendency to uric acid metabolism disorders is more often observed in patients with other signs of metabolic syndrome ( obesity, insulin resistance, type 2 diabetes mellitus, dyslipoproteinemia). Family history is burdened with metabolic and cardiovascular diseases, as well as chronic nephropathy.

Secondary hyperuricemia

Class	The most common reasons
Diseases of the blood system	True (Vaquez-Osler disease) and secondary (adaptation to high altitude, chronic respiratory failure), polycythemia Plasma cell dyscrasias (multiple myeloma, Waldenstrom's macroglobulinemia) Lymphomas Chronic hemolytic anemia Hemoglobinopathies
Systemic diseases	Sarcoidosis Psoriasis
Dysfunctions of endocrine glands	Hypothyroidism Adrenal insufficiency
Intoxication	Chronic alcohol intoxication Lead poisoning
Medicines	Loop and thiazide-like diuretics Anti-tuberculosis drugs (ethambutol) NSAIDs (high doses causing analgesic nephropathy)

There are several variants of urate nephropathy.

• Acute uric acid nephropathy with oliguric acute renal failure is usually caused by simultaneous massive crystallization of urates in the lumen of the tubules. This type of kidney damage is observed in patients with hemoblastoses, decaying malignant tumors, and less often - primary disorders of uric acid metabolism, in which the crystallization of urates in the tubulointerstitium is provoked by the consumption of large amounts of alcohol and meat products and, especially, severe hypohydration (including after visiting a sauna, intense physical activity).
• Chronic urate tubulointerstitial nephritis: early development of arterial hypertension is typical. Increased arterial pressure is usually recorded at the stage of hyperuricosuria; with the formation of persistent hyperuricemia, arterial hypertension becomes permanent. Chronic urate tubulointerstitial nephritis is the cause of terminal renal failure.
• Urate nephrolithiasis is usually associated with chronic urate tubulointerstitial nephritis.
• Immune complex glomerulonephritis is not often observed, and confirmation of the role of uric acid as an etiologic factor in these cases is usually difficult.

Damage to the renal tubulointerstitium in hyperuricosuria occurs not only due to the formation of salt crystals. No less important is the ability of uric acid to directly cause processes of tubulointerstitial inflammation and fibrosis by inducing the expression of proinflammatory chemokines and endothelin-1 by resident macrophages and activating the migration of these cells into the renal tubulointerstitium.

Uric acid directly leads to endothelial dysfunction, thereby contributing to the progression of kidney damage and the development of arterial hypertension.

Pathogenesis

Kidney damage in hypercalcemia

With a persistent increase in serum calcium concentration, it is deposited in kidney tissue. The main target of calcium is the structures of the renal medulla. Atrophic changes, fibrosis and focal infiltrates consisting mainly of mononuclear cells are observed in the tubulointerstitium. Hypercalcemia is caused by various reasons.

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Diagnostics kidney damage from metabolic diseases

In chronic urate tubulointerstitial nephritis, slight erythrocyturia is detected; a decrease in the relative density of urine is characteristic when performing the Zimnitsky test.

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Treatment kidney damage from metabolic diseases

Treatment of hyperoxaluria consists of prescribing pyridoxine and orthophosphate, as well as sodium citrate. It is necessary to drink a large amount of fluid (at least 3 l/day).

The basis of urate nephropathy treatment is correction of uric acid metabolism disorders by non-drug (low-purine diet) and drug (allopurinol) measures. It is advisable to recommend patients taking allopurinol to drink plenty of alkaline fluids. Drugs with uricosuric action are not currently used. Patients with uric acid metabolism disorders also undergo antihypertensive therapy (diuretics are undesirable), and treatment of concomitant metabolic disorders (dyslipoproteinemia, insulin resistance/type 2 diabetes mellitus) is performed.