Interstitial nephritis is an acute or chronic non—purulent inflammation of the stroma and tubules of the kidneys caused by a hyperergic immune response. It is manifested by lower back pain, impaired diuresis (oligoanuria, polyuria), intoxication syndrome. It is diagnosed with the help of general and biochemical analyses of urine, blood, ultrasound of the kidneys, determination of β2-microglobulin, histological examination of the biopsy. The treatment regimen combines detoxification for poisoning, etiopathogenetic therapy of the underlying disease with the appointment of immunosuppressants, antihistamines, anticoagulants, antiplatelet agents. In severe cases, RRT and kidney transplantation are required.
ICD 10
N10 N11
Meaning
The peculiarity of interstitial nephritis is the involvement of interstitial tissue, tubular structures, blood and lymphatic vessels in the pathological process without spreading to the cup-pelvic system and gross purulent destruction of the organ. Since the leading role in the pathogenesis of the disorder is played by tubular dysfunction, currently the disease is commonly called tubulointerstitial nephritis (TIN).
According to large-scale population studies, acute variants of interstitial inflammation account for up to 15-25% of all cases of acute kidney injury. The prevalence of chronic forms of the disease according to the results of puncture nephrobiopsy ranges from 1.8 to 12%. Pathology can develop at any age, but it is more often observed in 20-50-year-old patients.
Causes
The lesion of the renal tubular apparatus and the interstitial tissue has a polyethological basis, while the role of individual damaging factors differs depending on the nature of the process. The main causes of acute non-purulent interstitial inflammation of the kidneys, according to the observations of specialists in the field of urology and nephrology, are:
- Taking nephrotoxic drugs. More than 75% of cases of acute tubulointerstitial nephritis develop in sensitive patients after taking antibiotics, sulfonamides, NSAIDs, less often — thiazide diuretics, antiviral agents, analgesics, barbiturates, immunosuppressants.
- Vaccines and serums can cause a similar effect.
- System processes. In 10-15% of patients, pathological changes in interstitial tissue and tubules are associated with autoimmune diseases (Sjogren’s syndrome, SLE), sarcoidosis, lymphoproliferative diseases. This group of causes also includes cases of metabolic disorders (hyperuricemia, oxalatemia) and acute toxic nephropathies.
- Infectious agents. Although the inflammation is non-purulent in nature, in 5-10% of patients it occurs against or after an infectious process. Interstitial forms of nephritis can complicate the course of brucellosis, yersiniosis, cytomegalovirus infection, leptospirosis, rickettsiosis, schistomatosis, toxoplasmosis, other infections, sepsis.
- Unidentified factors. Up to 10% of cases of suddenly developed nephritis with interstitial lesions, tubules have an unspecified etiology and are considered idiopathic. In some patients, acute renal pathology is combined with the clinic of inflammation of the vascular membrane of the eyes (tubulointerstitial nephritis syndrome with uveitis).
Like acute forms of the disease, chronic tubulointerstitial nephritis can form against the background of prolonged use of nephrotoxic drugs (primarily NSAIDs, cytostatics, lithium salts), poisoning with poisons (cadmium salts, lead). Pathology often occurs in patients with metabolic disorders (gout, cystinosis, elevated levels of oxalates, calcium in the blood), allergic and autoimmune diseases.
Chronic TIN complicates the course of tuberculosis, blood diseases (sickle cell anemia, light chain deposition syndrome). In patients with autosomal dominant tubulointerstitial disease, non-purulent nephritis has a hereditary basis. With prolonged postrenal obstruction of the urinary tract (vesicoureteral reflux, prostate adenoma, uretero-vaginal fistulas, etc.), atherosclerosis of the renal artery, glomerulopathy, chronic interstitial inflammation is secondary.
Pathogenesis
The mechanism of interstitial nephritis development depends on the nature and intensity of the damaging factor. Often, inflammation has an autoimmune basis and is provoked by the deposition of immune complexes circulating in the blood (with lymphoproliferative processes, systemic lupus erythematosus, taking nonsteroidal anti-inflammatory drugs) or antibodies to the basement membrane of the tubules (with intoxication with antibiotics, transplant rejection).
During the chronization of the process, an important role is played by the pathological activation of macrophages and T-lymphocytes, which cause proteolysis of tubular basement membranes and enhance peroxidation with the formation of free radicals. Sometimes the tubular epithelium is damaged as a result of selective accumulation and direct destructive action of a nephrotoxic substance reabsorbed from primary urine.
Local release of inflammatory mediators in response to the damaging factor causes interstitial edema and vascular spasm, which is aggravated by their mechanical compression. The resulting renal tissue ischemia potentiates dystrophic changes in cells, reduces their functionality, in some cases provokes the development of papillary necrosis and massive hematuria.
Due to an increase in pressure in the tubules and a decrease in the effective plasma flow, the filtering ability of the glomerular apparatus is disrupted a second time, which leads to renal failure and an increase in serum creatinine levels. Against the background of edema of the interstitial tissue and damage to the tubular epithelium, water reabsorption decreases, urination increases.
In acute nephritis, a gradual decrease in interstitial edema is accompanied by the restoration of renal plasma flow, normalization of glomerular filtration rate and efficiency of tubular reabsorption. The prolonged presence of damaging agents in combination with persistent stroma ischemia against the background of blood flow disorders entails irreversible changes in the epithelium and replacement of functional tissue with connective tissue fibers.
Sclerotic processes are enhanced by stimulation of fibroblast proliferation and collagenogenesis by activated lymphocytes. Hereditary predisposition plays an essential role in the occurrence of hyperergic inflammatory reaction.
Classification
When systematizing the clinical forms of interstitial nephritis, factors such as the presence of previous pathology, the severity of symptoms, and the fullness of the clinical picture are taken into account. If acute interstitial inflammation develops in previously healthy patients with intact kidneys, the process is considered primary. In secondary tubulointerstitial nephritis, renal pathology complicates the course of gout, diabetes mellitus, leukemia and other chronic diseases. To predict the outcome of the disease and choose the optimal therapeutic tactics, it is important to take into account the nature of the course of the inflammatory process. Urologists and nephrologists distinguish two forms of interstitial inflammation:
- Acute jade. Occurs suddenly. It is accompanied by significant morphological changes in the stroma, tubules, often reversible. Glomeruli are usually not damaged. It proceeds violently with pronounced clinical symptoms of tubular lesion and secondary violation of glomerular filtration. There is often a rapid bilateral decrease or complete cessation of kidney function. Acute forms of interstitial nephritis cause 10-25% of acute renal failure. Despite the serious prognosis, the timely appointment of adequate therapy allows you to restore the functionality of the organ.
- Chronic nephritis. Morphological changes develop gradually, the processes of interstitial tissue fibrosis, atrophy of the tubular apparatus with its replacement by connective tissue and the outcome in nephrosclerosis prevail. Secondary glomerulopathy is possible. Symptoms increase slowly, with pronounced sclerotic processes is irreversible. In 20-40% of patients with chronic renal insufficiency, the violation of the filtering function of the kidneys is caused by tubulointerstitial nephritis. The prognosis of the disease is serious, with the occurrence of CRF, it is necessary to carry out RRT and kidney transplantation.
In acute inflammation, the allocation of several variants of the disease with different severity of symptoms is justified. The unfolded form of nephritis is characterized by a classic clinical picture. A distinctive feature of severe inflammation is acute renal failure with anuria, which requires urgent renal replacement therapy. With a favorably occurring abortive inflammation, there is no oligoanuria, polyuria prevails, concentration function is restored in 1.5-2 months. With the development of interstitial focal nephritis, the symptoms are erased, a violation of urine reabsorption prevails.
Symptoms
The signs of the disease are nonspecific, similar to the manifestations of other types of nephrological pathology. The clinic depends on the features of the development of the inflammatory process. With acute nephritis and exacerbation of chronic inflammation, disorders of the general condition are observed — headache, chills, fever up to 39-40 ° C, increasing weakness, fatigue. There may be an increase in blood pressure. Blood appears in the urine.
The patient complains of severe pain in the lower back, the amount of urine decreases sharply up to anuria, which is subsequently replaced by polyuria. With a progressive disease, the patient is concerned about dull pain in the lower back, a slight decrease in the volume of daily urine, papular rash. Sometimes there is subfebrility. A possible decrease in the filtration capacity of the organ in the chronic variant of nephritis is indicated by the appearance of symptoms of uremic intoxication — nausea, vomiting, itching, drowsiness.
Complications
In the absence of adequate therapy, acute interstitial nephritis often turns into a chronic form. Changes in the renal interstitium over time lead to a decrease in the number of functioning nephrons. The consequence of this is the development of chronic renal failure, disabling the patient and requiring replacement therapy. The inflammatory process can cause activation of the renin-angiotensin-aldosterone system, stimulate increased synthesis of vasoconstrictor substances, which is manifested by persistent arterial hypertension, refractory to drug therapy. Violation of erythropoietin synthesis in chronic interstitial nephritis causes severe anemia.
Diagnostics
Due to the non-specificity of clinical symptoms, it is important to exclude other causes of acute or chronic nephropathy when making a diagnosis of interstitial nephritis. As a rule, the final diagnosis of the disease is carried out on the basis of the results of histological examination, taking into account the likely damaging factors. The recommended methods of laboratory and instrumental examination are:
- Urinalysis. Proteinuria is characteristic — from small to moderate (daily urinary excretion of 0.5-2 g of protein) to nephrotic (more than 3.5 g of protein / day). In most patients, erythrocyturia, leukocyturia with the presence of eosinophils and lymphocytes in the urine is determined. Cylindrical shape is possible. There are no bacteria in the analysis. The density of urine depends on the shape and stage of nephritis.
- Ultrasound of the kidneys. For an acute interstitial process, normal or slightly enlarged kidney sizes, increased cortical echogenicity are typical. In chronic nephritis, organs are reduced, echogenicity is enhanced, and contour deformation is noted in some patients.
- Blood test. The results are indicative of the occurrence of renal failure. Characteristic signs of glomerular filtration disorders are an increase in serum levels of creatinine, uric acid, nitrogen. The corresponding changes are detected during the nephrological complex and are confirmed by the Rehberg breakdown.
- Beta-2-microglobulin. A specific marker of a violation of reabsorption in the tubular apparatus is an increase in the excretion of β2-microglobulin in the urine and a decrease in its level in the blood. In case of interstitial nephritis, the serum protein concentration determined by the immunochemiluminescent method does not exceed 670 ng/ml, and its content in urine is more than 300 mg/l.
- Puncture biopsy of the kidneys. In an acute process, biopsy examination allows detecting interstitial edema, its infiltration by eosinophils, plasmocytes, mononuclear infiltrates in the peritubular space, vacuolization of the tubular epithelium. Chronic nephritis is indicated by lymphocytic infiltration, tubular atrophy and stroma sclerosis.
With chronic interstitial inflammation, there is a significant decrease in the level of erythrocytes and hemoglobin in the general blood test, with acute nephritis, eosinophilia is possible. Accordingly, the severity of the violations may change the indicators of the electrolyte balance of the blood: increase or decrease the potassium content, decrease the concentration of calcium, magnesium, sodium. If a possible connection of nephritis with systemic diseases is suspected, tests are additionally prescribed to detect lupus anticoagulant, antibodies to ds-DNA, ribosomes, histones and other nuclear components. An increase in the levels of immunoglobulins — IgG, IgM, IgE is often determined.
Differential diagnosis is carried out between various pathological conditions that are complicated by interstitial inflammation. The disease is also differentiated with acute, chronic and rapidly progressing glomerulonephritis, pyelonephritis, urolithiasis, kidney tumors. In addition to a urologist and a nephrologist, patients with suspected interstitial immuno-inflammatory process may be shown consultations with a rheumatologist, an allergist-immunologist, a toxicologist, an infectious disease specialist, a phthisiologist, an oncologist, an oncohematologist.
Treatment
The patient’s management plan is determined by the clinical form and etiological factor of nephrological pathology. Patients with symptoms of acute interstitial nephritis are urgently hospitalized in the intensive care unit of the urological or intensive care unit. In case of chronic inflammation, planned hospitalization in a nephrological hospital is recommended.
The main therapeutic tasks are to stop the intake and withdrawal from the body of a chemical that provoked toxic damage or hyperergic immuno-inflammatory reaction, desensitization, detoxification, stabilization of the underlying disease in secondary forms of nephritis, correction of metabolic disorders. Taking into account the stage and course of the disease , the following are prescribed:
- Etiopathogenetic therapy of the underlying disease. Elimination of the cause that caused tubulointerstitial inflammation, in the absence of irreversible changes in the tubules and stroma, allows for faster normalization of reabsorption and filtering functions. In acute processes provoked by toxic effects, antidotes, enterosorbents, methods of extracorporeal detoxification are effective. Competent treatment of systemic processes is aimed at preventing the early development of CRF.
- Immunosuppressors. With the ineffectiveness of detoxification therapy of interstitial drug nephritis, idiopathic forms of the disease, autoimmune diseases, corticosteroids are often used in combination with antihistamines. Glucocorticosteroids reduce the swelling of the interstitial substance, weaken the activity of immune inflammation, antihistamines reduce the severity of hyperergic response. With a further increase in symptoms, cytostatics are prescribed.
- Symptomatic treatment. Since acute renal dysfunction is often accompanied by metabolic disorders, intensive infusion therapy is indicated for patients with tubulointerstitial nephritis. Colloidal, crystalloid solutions, and calcium preparations are usually administered under the control of diuresis. In autoimmune diseases, the use of anticoagulants and antiplatelet agents is recommended.
- Angiotensin receptor blockers are used to relieve possible arterial hypertension.
When renal insufficiency increases, replacement therapy (peritoneal dialysis, hemodialysis, hemofiltration, hemodiafiltration) is performed to prevent severe uremic disorders. Patients with the outcome of chronic inflammation in pronounced sclerotic changes of interstitial substance, atrophy of tubules and glomeruli require kidney transplantation.
Prognosis and prevention
With early diagnosis and the appointment of adequate etiotropic therapy, complete recovery occurs in more than 50% of patients. The prognosis for interstitial nephritis is favorable if the patient retains normal glomerular filtration rates. To prevent the development of the disease, timely treatment of infectious kidney diseases, systemic connective tissue lesions, restriction of taking nephrotoxic drugs (NSAIDs, antibiotics from the tetracycline group, loop diuretics) is necessary.
Measures of individual prevention of nephritis include the use of a sufficient amount of fluid, refusal to take medications on their own, regular medical examinations, especially when working with industrial poisons.