What causes interstitial nephritis?

The causes of tubulointerstitial nephritis are varied. Acute tubulointerstitial nephritis can develop with various infections, as a result of the use of certain medications, poisoning, burns, injuries, acute hemolysis, acute circulatory disorders (shock, collapse), as a complication of vaccination, etc.

Chronic tubulointerstitial nephritis is also a heterogeneous polyetiological group of diseases in which, in addition to the above factors, hereditary predisposition and renal dysembryogenesis, metabolic disorders, chronic infection and intoxication, immunological diseases, unfavorable environmental factors (heavy metal salts, radionuclides), etc. are of great importance. Chronic tubulointerstitial nephritis can develop as a continuation of acute nephritis.

Tubulointerstitial nephritis was first described by W. T. Councilman in 1898 after examining 42 cases of acute nephritis following scarlet fever and diphtheria. Later, other bacterial, viral and parasitic agents were identified that lead to the development of tubulointerstitial nephritis. Among bacteria, in addition to streptococcus and diphtheria bacilli, they can include pneumococcus, meningococcus, chlamydia, pathogens of syphilis, typhoid, etc. These bacterial agents cause damage to the renal interstitium by toxic effects, while leptospira and mycobacterium tuberculosis are capable of directly invading kidney tissue. Among viruses, the toxic effect on tubulointerstitium can be exerted by the causative agent of mononucleosis, hepatitis viruses, measles virus, etc., as well as herpes viruses, Coxsackie, Epstein-Barr, AIDS, cytomegalovirus, etc. that persist in the renal tissue. The possibility of tubulointerstitial nephritis formation as a result of long-term persistence of respiratory viruses - influenza viruses, parainfluenza, adenoviruses, which lead to activation of endogenous coxsackievirus infection persistent in the urinary system, has been shown. According to various authors, postviral tubulointerstitial nephritis accounts for up to 50% of all interstitial nephritis.

Among parasites, toxoplasma, mycoplasma, and the causative agent of leishmaniasis can lead to the development of tubulointerstitial nephritis.

Of particular importance in the development of tubulointerstitial nephritis is given to drugs, especially (beta-lactam antibiotics, sulfonamides, non-steroidal anti-inflammatory drugs, diuretics. In this case, it is not so much the dose that is important, but the duration of taking the drug and individual sensitivity to it. A high risk of developing tubulointerstitial nephritis occurs after 10 days of taking the drug.

Various chemical agents, especially heavy metal salts (cadmium, lead, chromium, mercury, gold, silver, arsenic, strontium), can have a toxic effect on the tubulointerstitium.

Among endogenous factors, a special role in the development of tubulointerstitial nephritis is played by dysmetabolic nephropathy and instability of cytomembranes; vesicoureteral reflux, polycystic disease and other developmental anomalies accompanied by impaired differentiation of tubules and tubular dysfunction. The development of tubulointerstitial nephritis is possible against the background of congenital disorders of hemodynamics and urodynamics, accompanied by circulatory hypoxia, impaired lymph flow.

Drugs that can cause tubulointerstitial nephritis

Beta-lactam antibiotics	Other antibiotics and antiviral drugs	Anti-inflammatory drugs	Diuretics	Other medicines
Methicillin Penicillin Ampicillin Oxacillin Nafcillin Carbenicillin Amoxicillin Cephalotin Cephalexin Cephradine Cefotaxime Cefoxitin Cefotetan	Sulfonamides Co-trimoxazole Rifampicin Polymyxin Ethambutol Tetracycline Vancomycin Erythromycin Kanamycin Gentamicin Colistin Interferon Acyclovir Ciprofloxacin	Indomethacin Phenylbutazone Fenoprofen Naproxen Ibuprofen Phenazone Metafenamic acid Tolmetin Diflunisal Aspirin Phenacetin Paracetamol	Thiazides Furosemide Chlorthalidone Triamterene	Phenindion Glafenin Diphenyl hydantoin Cimetidine Sulfinpyrazone Allopurinol Carbamazepine Clofibrate Azathioprine Phenylpropanolamine Aldomet Phenobarbital Diazepam D-penicillamine Antipyrine Carbimazole Cyclosporine Captopril Lithium

Some of the most common nephrotoxic agents

Heavy metals	Inorganic mercury (chloride), organomercuric compounds (methyl-, ethyl-, phenylmercury, sodium ethylmercurithiosalicylate, mercury diuretics), inorganic lead, organic lead (tetraethyl lead), cadmium, uranium, gold (especially sodium aurothiomalate), copper, arsenic, arsine (arsenic hydrogen), iron, chromium (especially trioxide), thallium, selenium, vanadium, bismuth
Solvents	Methanol, amyl alcohol, ethylene glycol, diethylene glycol, cellosol, carbon tetrachloride, trichloroethylene, various hydrocarbons
Substances that cause oxalosis	Oxalic acid, methoxyflurane, ethylene glycol, ascorbic acid, anti-corrosion agents
Antitumor drugs	Cyclosporine, cisplatin, cyclophosphamide, streptozocin, methotrexate, nitrosourea derivatives (CCNU, BCNU, methyl-CCNU), doxorubicin, daunorubicin
Diagnostic agents	Sodium iodide, all organic iodine contrast agents
Herbicides and pesticides	Paraquat, cyanides, dioxin, cyphenyl, cyclohexamides and organochlorine insecticides: endrin, aldrin, endosulfan, dieldrin, lindane, hexachlorobenzene, dichlorodiphenyltrichloroethane (DDT), heptachlor, chlordecone, polychlorinated terpenes, chlordane, dicofol (keltan), chlorobenzilate, mirex, methoxychlor
Biological factors	Mushrooms (eg, Amanito phalloides causes severe muscarine poisoning), snake and spider venoms, insect bites, aflatoxins
Immune complex inducers	Penicillamine, captopril, levamisole, gold salts

Allergic reactions and immunodeficiency states also play an important role in the development of tubulointerstitial nephritis.