What causes chronic tubulointerstitial nephritis?

The main causes of chronic tubulointerstitial nephritis:

• Medications:
  • NSAIDs and non-narcotic analgesics;
  • 5-aminosalicylic acid;
  • lithium preparations;
  • immunosuppressants (cyclosporine, tacrolimus);
  • cytostatics (cisplatin);
  • diuretics (furosemide, ethacrynic acid, thiazides);
  • traditional medicine (Chinese herbs).
• Environmental factors:
  • lithium;
  • lead;
  • cadmium.
• Exchange violations:
  • impaired uric acid metabolism;
  • hypercalcemia;
  • hypokalemia;
  • hyperoxaluria.
• Systemic diseases:
  • sarcoidosis;
  • disease and Sjogren's syndrome.
• Others:
  • Balkan endemic nephropathy.

Chronic tubulointerstitial nephritis (drug variant), unlike many other variants of chronic nephropathies, is potentially preventable. Most of his cases are associated with long-term intake of NSAIDs and non-narcotic analgesics; to refer to them use the term analgesic nephropathy.

The development of analgesic nephropathy is due to the chronic blockade of the synthesis of renal prostaglandins under the action of NSAIDs and non-narcotic analgesics, accompanied by a significant deterioration of renal hemodynamics with ischemia of mainly tubulointerstitial structures. Progressing tubulo-interstitial inflammation and fibrosis lead to irreversible impairment of kidney function. In addition, a characteristic feature of analgesic nephropathy is the calcification of the renal papillae. The pronounced carcinogenic effect is attributed to N-hydroxylated metabolites of phenacetin.

The risk of analgesic nephropathy is increased with long-term use of drugs in large doses. Most NSAIDs and non-narcotic analgesics are dispensed without a prescription, which predisposes them to uncontrolled admission of patients. The combination of NSAIDs and non-narcotic analgesics with caffeine and codeine causes the development of mental dependence. In addition, patients with chronic pain syndromes (osteoarthritis, low back pain syndrome, migraine) often take drugs for prophylactic purposes, which leads to a significant increase in their dosages.

The episode worsening kidney function when taking antibiotics penicillin series in the anamnesis is a relative contraindication to the appointment of cephalosporins due to a certain generality of their antigenic structure. In patients who have suffered acute tubulointerstitial nephritis due to NSAIDs, the appointment of these drugs is possible in the future, but the dose and duration of their administration should be carefully monitored.

Prolonged uncontrolled intake of thiazide-like and loop diuretics, especially in large doses (for example, by women to reduce body weight) leads to the development of hyperkalemia accompanied by potassium-deficient nephropathy. For chronic potassium-sparing tubulointerstitial nephritis, a decrease in renal blood flow and GFR is characteristic, with a prolonged course of cyst formation.

The development of chronic drug tubulointerstitial nephritis is also possible with the appointment of aminosalicylic acid and its derivatives used to treat chronic inflammatory bowel diseases, including Crohn's disease. Men are more often ill.

Chronic drug tubulointerstitial nephritis occurs when taking cytotoxic drugs (platinum preparations), cyclosporine and tacrolimus.

With the use of some Chinese herbs, tubulointerstitia lesions develop. Excreted in the urine protein pool consists of both albumin and low-molecular proteins, normally reabsorbed by the epithelial cells of the tubules; developing glucosuria. Aristochloric acid, contained in these herbs, predisposes to the development of malignant tumors of the urinary tract.

Chronic tubulointerstitial nephritis due to environmental factors

Environmental factors, including heavy metals, cause the development of chronic tubulointerstitial nephritis; the most common are lithium and lead nephropathies.

[1], [2], [3], [4], [5], [6]

Lithium Nephropathy

The development of lithium intoxication occurs with the accumulation of salts of this substance in the environment, but most cases of kidney damage are associated with long-term use of lithium-containing drugs in the treatment of manic-depressive psychosis.

More than 50% of patients taking lithium-containing drugs develop distal renal tubular acidosis due to impaired secretion of protons in the distal tubules under the influence of lithium. Lithium directly reduces the formation of cyclic AMP in the epitheliocytes of the distal tubules, which leads to a significant decrease in the susceptibility of these cells to stimulation by an antidiuretic hormone. Lithium has a direct toxic effect on tubule cells, contributing to their dehydration. An additional factor contributing to the damage of tubulointerstitia in patients taking lithium preparations is hypercalcemia.

Lead nephropathy

The development of tubulointerstitial nephropathy is characteristic of chronic intoxication with lead. At present, domestic sources of lead are dangerous (see "Lifestyle and chronic kidney diseases"). The defeat of renal tubulointerstition is due to exposure to both lead and urate. The risk of lead intoxication is increased in the presence of predisposing factors, mainly metabolic:

• hypophosphatemia;
• iron deficiency states;
• excess vitamin D;
• insolation.

Cadmium nephropathy

The intake of excess cadmium into the body leads to the development of chronic tubulointerstitial nephritis. An increase in the frequency of cadmium damage to the kidneys is observed when an excessive amount of this element enters the environment: the largest outbreaks were observed in Belgium and Japan. Currently, cases of chronic tubulointerstitial nephritis, associated with cadmium intoxication, are rare.

[7], [8], [9]

Radiation nephropathy

Ionizing radiation at doses exceeding 2000 rad causes the development of radiation tubulointerstitial nephritis. It is observed in patients suffering from malignant tumors and receiving radiation therapy, as well as in bone marrow transplant recipients. In the latter, the nephrotoxic effects of ionizing radiation develop at lower doses (1000-1400 rad).

Ionizing radiation affects predominantly endothelial cells of renal glomeruli. Death of endotheliocytes in combination with intracapillary thrombosis leads to severe ischemia of the structures of renal tubulointerstitium, accompanied by their atrophy. Inflammatory infiltrates are often absent, therefore, to denote radiation damage, tubulointerstitia of the kidneys are recommended to use the term "nephropathy", rather than "nephritis." As a rule, tubulointerstitial fibrosis develops.

To the development of radiation nephropathy predisposes the combination of the effect of ionizing radiation with other factors that can cause damage to the kidney tissue (some cytostatics, secondary hyperuricemia in patients with malignant tumors). Reducing the duration of radiotherapy sessions and increasing the duration of breaks between them reduce the risk of kidney damage.

Chronic tubulonterstitial nephritis in systemic diseases

Chronic tubulointerstitial nephritis often develops in systemic diseases (especially in sarcoidosis). An additional factor predisposing to the development of renal tubulointerstitial lesion in sarcoidosis is the pathology of calcium metabolism caused by a violation of the transformation of vitamin D into the active form due to the fact that macrophages of sarcoid granules contain the enzyme la-hydroxylase, rather than 24-hydroxylase. As a result, hypercalciuria and hypercalcemia develop.

[10],