Drug nephropathy is an acute or chronic lesion of the renal glomeruli, tubules, interstitium caused by taking medications. It is manifested by polyuria, oligoanuria, nocturia, hematuria, lower back pain, asthenic, edematous and hypertensive syndromes. It is diagnosed on the basis of general and biochemical blood, urine, ultrasound, CT, MRI of the kidneys, urography, nephroscintigraphy, renal tissue biopsy. Treatment includes detoxification therapy, corticosteroids, drug infusions, anticoagulants, antiplatelet agents, antihypertensive agents, RRT. With persistent chronic dysfunction, kidney transplantation is required.
ICD 10
N14.0 N14.1 N14.2
Meaning
According to the observations of American urologists, in recent years the frequency of medicinal kidney lesions has been increasing, manifested by various variants of acute and chronic nephropathies. First of all, this is due to the expansion of the arsenal of medications used in the treatment of various diseases, and the potential nephrotoxicity of most drugs. In 10-11% of patients with kidney diseases requiring replacement therapy, nephrological pathology is associated with taking medications.
The high-risk group includes patients of the older age group who receive long-term supportive combined treatment for chronic somatic diseases and undergo diagnostic procedures with the use of nephrotoxic drugs. Their share in the number of nephrological patients reaches 66%.
Causes
Drug nephropathy with the use of pharmaceutical and paramedical drugs with nephrotoxic effects. Usually, the prerequisites for the development of kidney damage are uncontrolled medication without taking into account contraindications (self-medication), side effects with unjustified prescription or improper combination of medications, hereditary predisposition, the presence of concomitant pathology (diabetes mellitus, hypertension, nephrological diseases, etc.). Damage to the renal tissue can cause:
- Official medicines. Renal dysfunction occurs when taking antibacterial drugs (penicillins, cephalosporins, aminoglycosides, tetracyclines, fluoroquinolones, sulfonamides, anti-tuberculosis drugs), analgesics, NSAIDs, diuretics, barbiturates, cytostatics, H2-histamine receptor blockers, ACE inhibitors, phenothiazines, etc. When using X-ray contrast, contrast-induced nephropathy may develop.
- Vaccines and serums. Up to 23% of cases of medicinal nephrological pathology are caused by the introduction of tetanus, anticorrhea, antistaphylococcal sera, ADS, ADS-M, DPT, gonovaccine. The risk of post-vaccination or serum nephropathies increases with immunization or administration of ready-made antibodies to patients with a burdened allergic history, hypersensitivity to the components of the immunopreparation.
- Paramedical drugs. According to observations, up to 80% of the population uses alternative medicine. At the same time, vasoconstrictor, cytopathic, crystalluric, and dysmetabolic effects of medicinal plants are often underestimated. According to the FDA, up to 32% of Ayurvedic drugs contain mercury, arsenic, lead, aristolochiic acid, recognized as one of the probable causes of Balkan endemic nephropathy, and other nephrotoxic ingredients.
Pathogenesis
The basis for the development of drug nephropathy is a combination of several pathogenetic mechanisms. Some medications have a direct damaging effect, leading to primary damage to the cells of the proximal tubules that reabsorb the nephrotoxic chemical compound. The tubular epithelium can also be destroyed by crystal precipitation against the background of the use of sulfonamide preparations, obstruction by myoglobin in rhabdomyolysis due to taking statins, monoamine oxidase inhibitors, phenothiazine derivatives, and some anesthetics.
The resulting tubular dysfunction provokes a secondary violation of filtration capacity. Ischemic tissue changes caused by anaphylactic shock, thrombotic microangiopathy, inhibition of prostaglandins and the renin-angiotensin system with subsequent vascular spasm become an independent or aggravating factor of destruction.
A separate link in pathogenesis is damage to glomerular and tubular basement membranes by immune complexes, which include the drug being taken or its metabolites as an antigen. Glomerulopathy and tubulopathy can develop both with the deposition of immune complexes circulating in the blood, and with the reaction of antibodies to chemicals bound to structural renal elements.
With the immune mechanism of nephropathy, the leading hyperergic reaction with impaired renal microcirculation, the release of histamine and other inflammatory mediators. Prolonged tissue ischemia in combination with the alteration of cellular elements potentiates collagenogenesis and tissue sclerosis with the replacement of functional elements by connective tissue fibers.
Classification
In american urology, the systematization of clinical forms of medicinal nephropathies based on pathomorphological changes in renal tissues has been adopted, taking into account the dynamics of the development of the disease and etiopathogenetic factors. This approach provides the most accurate prediction of possible complications and outcome, allows you to choose the optimal patient management scheme. There are seven main clinical variants of drug – induced nephropathy:
- Acute necrosis of the tubules. It is represented by symptoms of acute renal failure. It is associated with damage to the tubular epithelium, violation of reabsorption, secondary deterioration of filtration. It is detected in 5-20% of patients taking aminoglycoside drugs. It is possible with the appointment of cephalosporins, quinine, ampicillin, the introduction of X-ray contrast.
- Acute cortical necrosis. Accompanied by the clinic of the ARF. Is a secondary state. It develops against the background of systemic changes that occurred when taking medications. Most often it is the result of anaphylactic shock caused by immunization in the presence of contraindications or individual hypersensitivity to pharmaceuticals.
- Acute interstitial nephritis. In severe cases, the symptoms of acute renal failure are characteristic, indicating secondary damage to the glomeruli, with erased, the clinic of tubulopathy with polyuria prevails. Up to 72% of acute forms of interstitial nephritis have a medicinal genesis, complicate the intake of antibiotics, sulfonamides, proton pump inhibitors, NSAIDs.
- Chronic interstitial nephritis. It is asymptomatic for a long time, half of the patients are diagnosed at the stage of CRF. The proliferation of interstitial tissue, papillary necrosis, atrophy of the tubule epithelium prevails. It is provoked by taking analgesics (analgesic nephropathy), calcineurin inhibitors, lithium preparations, herbal remedies with aristocholic acid.
- Acute medicinal glomerulonephritis. It is manifested by nephritic syndrome. Morphologically, glomerulonephritis is dominated by damage to the basement membranes of the glomeruli by circulating immune complexes (membranous glomerulonephritis). It occurs due to a dose-independent allergic reaction to taking NSAIDs, gold preparations, antibiotics, diuretics, antiviral agents.
- Chronic glomerulonephritis. It is characterized by a pronounced nephrotic syndrome, rarely isolated urinary syndrome due to progressive autoimmune destruction of the glomerular apparatus, renal parenchyma sclerosis, CRF. Chronic glomerulonephritis is often the outcome of acute forms of medicinal nephritis. Develops during therapy with mercury salts, anesthetics.
- Electrolyte–hemodynamic disorders. Extrarenal disorders prevail (increased blood pressure, water-electrolyte imbalance). With short-term intake of medications, nephropathy is usually reversible. As a rule, its formation is caused by changes in renal hemodynamics due to inhibition of prostaglandin synthesis during indomethacin treatment.
More rare forms of drug-induced nephropathies are disorders caused by the loss of certain renal functions. The diseases of this group are mainly represented by dysmetabolic disorders due to tubulopathies — acquired variants of Fanconi syndrome, diabetes insipidus, and kalipenic kidney.
Symptoms
The clinical picture is polymorphic and depends on the features of the pathogenesis of the disease. Acute forms usually develop within 1-3 weeks after the start of taking NSAIDs, antibiotics, sulfonamides, diuretics, and other nephrotoxic drugs. Acute nephropathies are characterized by intense pain in the lower back, an increase or sharp restriction of the daily amount of urine up to a complete delay. Some patients note the presence of blood in the urine. There may be common symptoms caused by intoxication of the body with nitrogenous compounds: fever, headaches, weakness, drowsiness, pallor of the skin and mucous membranes, tachycardia, thirst, dry mouth, itching.
In the clinical picture of chronic nephropathies, the picture of increasing renal insufficiency prevails. Morning swelling of the face is characteristic, which subsequently spreads to other parts of the body. Polyuria and the predominance of nocturnal diuresis are often noted. Some patients develop persistent, therapeutically resistant hypertension. When concomitant anemia occurs, patients complain of fatigue, weakness, dizziness. The skin and visible mucous membranes become pale. It is possible to combine renal symptoms with signs of medicinal lesions of other organs: dyspepsia, musculoskeletal pain, recurrent stomatitis, menstrual dysfunction.
Complications
The acute toxic effect of medications on the cells of the glomeruli and renal tubules leads to a sharp decrease in filtration with the development of the ARF clinic, which in 50-70% of cases becomes the cause of death. With the progression of drug nephropathy, the death of most nephrons occurs, as a result of which, without treatment, the patient develops chronic renal failure after 3-4 years of the disease. Pathological fluctuations in the parameters of water-electrolyte metabolism, which occur with a decrease in the processes of filtration and reabsorption of urine, can provoke the appearance or aggravation of cardiac pathology (arrhythmia, coronary heart disease), a violation of calcium metabolism with subsequent osteoporosis.
Diagnostics
In the event of acute renal dysfunction associated with the administration of potentially nephrotoxic drugs, the diagnosis of drug-induced nephropathy is usually not difficult. A more thorough diagnostic search is required with a gradual increase in renal symptoms in a patient who has been taking a certain pharmaceutical drug for a long time. For the diagnosis of medicinal nephropathies, laboratory and instrumental methods are recommended to assess the morphological structure and functional ability of the kidneys:
- Urine analysis. With different variants of the pathological condition in the material, a decrease or a significant increase in relative density, erythrocytes, leukocytes, cylinders, salt crystals can be determined. To assess the reabsorption function of the tubules, the study is often supplemented by a Zimnitsky breakdown.
- Blood test. The decrease in filtration function is indicated by an increase in the levels of creatinine, uric acid, urea, a change in the content of potassium, calcium, sodium, phosphorus. An imbalance of ions is possible with a violation of their reabsorption. With proteinuria, hypo- and dysproteinemia occurs.
- Nephrological complex. The determination of the organ’s operability is based on data on the content of creatinine, urea, uric acid, macronutrients. The appearance of protein, glucose, and microalbumin in the urine is indicative. As an additional method, the Rehberg hemorenal test, the Sulkovich test, is recommended.
- Sonography. Ultrasound of the kidneys reveals an increase or decrease in the size of the organ, diffuse and focal changes in the parenchyma and brain matter. Ultrasound scanning is supplemented by ultrasound, which allows to assess renal blood flow, if necessary, by tomography (MRI, CT).
- Intravenous urography. According to the data on the removal of the contrast agent, the features of the blood supply to the kidneys and their functional activity are evaluated. Intravenous urography can be supplemented with nephroscintigraphy. Due to the possible aggravation of symptoms, the examination of patients with acute renal failure is limited.
- Puncture biopsy of the kidneys. Histological examination of the biomaterial makes it possible to most accurately assess the condition of glomeruli, tubules, interstitial tissue, capillaries, arterioles. The results of kidney biopsy are particularly valuable for the choice of medical tactics in patients with chronic drug-induced nephropathies.
In the general blood test, a moderate acceleration of ESR, an increase in the level of eosinophils, a decrease in the content of erythrocytes and hemoglobin is possible. Differential diagnosis is performed with acute and malignant glomerulonephritis, nephropathy with gout, lupus, autoimmune vasculitis, urolithiasis, kidney tuberculosis, idiopathic interstitial nephritis. In addition to a urologist or nephrologist, an anesthesiologist-resuscitator, toxicologist, rheumatologist, immunologist, phthisiologist, infectious disease specialist, oncologist may be involved in consulting the patient.
Treatment
The medical tactics of managing patients with drug-induced nephrological pathology takes into account the clinical and morphological form and features of the pathogenesis of the disease. In any case, treatment begins with the withdrawal of the drug that caused nephropathy. In acute processes, methods aimed at eliminating the damaging compound are justified — taking antidotes (if available), gastric lavage, hemosorption, plasmapheresis, acceleration of excretion (appointment of sorbents, laxatives). Therapy is carried out taking into account the filtering and reabsorption functions. Depending on the clinical situation , they can be used:
- Corticosteroids. Glucocorticoid therapy with medium and high doses is justified in the immune pathogenesis of nephropathy, is carried out for the rapid relief of autoimmune and allergic reactions. The immunosuppressive effect includes reduction of interstitial edema, suppression of macrophage functions, restriction of leukocyte migration in inflamed tissues, inhibition of the synthesis of inflammatory mediators and antibodies. Glucocorticosteroids effectively stabilize cellular and lysosomal membranes.
- Symptomatic remedies. Renal dysfunction is accompanied by the occurrence of organ and systemic disorders that require emergency correction. To restore the water-electrolyte balance, hemodynamics, microcirculation, tissue perfusion, infusion therapy is used with the introduction of colloidal, crystalloid solutions, antiplatelet agents, anticoagulants. In case of violation of renin-angiotensin regulation, antihypertensive drugs are usually required.
- Renal replacement therapy. Extrarenal blood purification is prescribed to prevent severe uremic complications with severe functional insufficiency. Hemodialysis, peritoneal dialysis, hemofiltration, hemodiafiltration can be carried out in an intermittent mode until renal functions are restored or permanently with severe CRF. In the chronic course of drug-induced nephropathy, kidney transplantation may be required.
Prognosis and prevention
The outcome of the disease depends on the timeliness of treatment and the degree of damage to the renal parenchyma. If there are no irreversible changes in the anatomical structure of the organ in acute nephropathy, the prognosis is favorable. The occurrence of massive destruction and acute renal failure in the absence of adequate therapy significantly increases the risk of death. In patients with chronic nephrological diseases and burdened with a premorbid background, there is often a persistent decrease in the filtration capacity of the kidneys, which can be somewhat slowed down by the appointment of drug therapy.
To prevent drug nephropathy, it is necessary to adjust the doses of drugs that are metabolized in the kidneys, in accordance with the values of creatinine clearance, refusal to use nephrotoxic drugs in the presence of risk factors (elderly age, female gender, intercurrent diseases, decreased BCC), exclusion of polypragmasia.
