Renal damage in metabolic diseases

Causes of the kidney damage in metabolic diseases

[1], [2], [3], [4]

Causes of hypercalcemia

Class	Most Common Causes
Idiopathic	Idiopathic hypercalcemia of childhood (Williams syndrome)
Due to increased calcium reabsorption in the intestine	Intoxication with vitamin D and calcium-containing drugs Sarcoidosis
Due to increased resorption of calcium from bone tissue	Hyperparathyroidism Metastases and primary bone tumors Multiple myeloma

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

Factors predisposing to the development of nephrocalcinosis:

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

[5]

Kidney damage in hyperoxaluria

Hyperoxaluria is one of the most common causes of nephrolithiasis. Allocate the primary and secondary hyperoxaluria.

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

Variants of primary hyperoxaluria

Option	Cause	Flow	Treatment
Type I	Insufficiency of peroxisomal alanine-glycolate aminotransferase (AGT)	Intensive nephrolithiasis Debut in the age of 20 years Possible development of severe renal failure	Pyridoxine Abundant fluid intake (3-6 l / day) Phosphates Sodium Citrate
Type II	Insufficiency of hepatic glycerate dehydrogenase	Debut in the age of 20 years 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	Most Common Causes
Due to drugs and toxins	Ethylene glycol Xylitol Methoxyflurane
Due to increased absorption of oxalates in the intestine	Condition after resection of the small intestine (in Including surgical treatment of obesity) Malabsorption syndrome Cirrhosis of the liver The use of animal protein in large quantities

Kidney damage in cases of impaired uric acid metabolism

Disorders of uric acid metabolism are widespread in the population. Most of them are classified as primary, genetically determined (for example, a 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 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.

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

Secondary hyperuricemia

Class	Most Common Causes
Diseases of the blood system	True (Vakez-Osler disease) and secondary (adaptation to high altitude, chronic respiratory failure), polycythemia Plasma cell dyscrasia (multiple myeloma, Waldenstrom macroglobulinemia) Lymphomas Chronic hemolytic anemia Hemoglobinopathies
Systemic diseases	Sarcoidosis Psoriasis
Dysfunction of the endocrine glands	Hypothyroidism Adrenal insufficiency
Intoxication	Chronic alcohol intoxication Intoxication with lead
Medications	Loop and thiazide-like diuretics Antituberculous drugs (ethambutol) NSAIDs (large doses that cause analgesic nephropathy)

There are several variants of urate nephropathy.

• Acute uric acid nephropathy with oliguric acute renal failure is usually due to simultaneous massive crystallization of urates in the lumen of the tubules. This variant of kidney damage is observed in patients with hemoblastosis, decaying malignant tumors, less often - primary disturbances of uric acid metabolism, in which urate crystallization in tubulointerstitutions is provoked by the use of a large amount of alcohol and meat products and, in particular, pronounced hypohydration (including after visiting the sauna, intensive physical activity).
• Chronic urate tubulointerstitial nephritis: characterized by early development of arterial hypertension. Increase in blood pressure, as a rule, is recorded even in the stage of hyperuricosuria, when hyperuricemia is stable, arterial hypertension assumes a permanent character. Chronic urate tubulointerstitial nephritis is the cause of terminal renal failure.
• Urinary nephrolithiasis, as a rule, is combined with chronic urate tubulointerstitial nephritis.
• Immunocomplex glomerulonephritis is not observed often, and confirmation of the role of uric acid as an etiologic factor in these cases is usually difficult.

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

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

Pathogenesis

Renal damage in hypercalcemia

With a persistent increase in serum calcium concentration, it is deposited in the kidney tissue. The main target of calcium is the structure of the medulla of the kidneys. In tubulointerstitutions, atrophic changes, fibrosis and focal infiltrates, consisting mainly of mononuclear cells, are observed. Hypercalcemia is caused by various causes.

[6], [7], [8], [9], [10], [11]

Diagnostics of the kidney damage in metabolic diseases

In chronic urate tubulointerstitial nephritis, a slight erythrocyturia is found; characteristic decrease in the relative density of urine in the sampling Zimnitsky.

[12], [13], [14], [15], [16]

Treatment of the kidney damage in metabolic diseases

Treatment of hyperoxaluria consists in the appointment of pyridoxine and orthophosphate, as well as sodium citrate. You need a lot of fluid (at least 3 liters / day).

The basis for the treatment of urate nephropathy is correction of uric acid metabolism disorders due to non-drug (low-purine diet) and drug (allopurinol administration) measures. Patients taking allopurinol, it is advisable to recommend a plentiful alkaline drink. Drugs with uricosuric action are not currently used. Patients with impaired uric acid metabolism also undergo antihypertensive therapy (diuretics are undesirable), treat associated metabolic disorders (dyslipoproteinemia, insulin resistance / type 2 diabetes mellitus).