Toxic nephropathy is damage to the glomerular apparatus and renal tubules caused by the action of exo— and endotoxins, hemodynamic and metabolic disorders in poisoning. It is manifested by lower back pain, asthenic syndrome, swelling, oligoanuria, which is subsequently replaced by polyuria, multiple organ disorders. It is diagnosed with the help of general, biochemical blood and urine tests, samples of Rehberg, Zimnitsky, ultrasound and tomography of the kidneys, ultrasound of renal vessels, chemical and toxicological studies. Treatment includes detoxification therapy, infusion correction of metabolic disorders, RRT.
Meaning
Toxic nephropathy is a collective concept that combines a number of nephrological diseases with a similar etiopathogenesis and clinical picture. The prevalence of pathology reaches 0.04%, which is up to 20% of all registered cases of acute renal failure. The increase in morbidity is associated with the increasing use of chemicals in various industries and in everyday life: according to observations, up to 10 million people are constantly in contact with nephrotoxic chemicals every year. In addition, the downside of the success of the pharmaceutical industry has been the emergence of new medicines that affect the kidneys. The urgency of timely detection of the toxic form of nephropathies is due to the high mortality rate and severe outcomes with irreversible destruction of kidney tissue.
Causes
Damage to the renal parenchyma is caused by exposure to chemicals that have a direct or indirect nephrotoxic effect. In most cases, renal dysfunction, and in severe cases, tissue destruction, is caused by exogenous industrial and household poisons, although in some patients the disease is caused by endogenous intoxication. Specialists in the field of urology and nephrology distinguish the following groups of causes that lead to the development of nephropathy:
- Reception of substances with nephrotoxic effect. When poisons of this group enter the kidneys, acute glomerulopathy or tubular necrosis occurs, caused by the reabsorption of a large amount of toxic substances. Salts of heavy metals (cadmium, lead, mercury, gold, arsenic, iodine, bismuth, chromium, etc.), ethylene glycol, oxalic and boric acids, gasoline, phenol, toluene, orellanic fungal toxins, poisons of some animals have a direct damaging effect on kidney tissue.
- Indirect toxic kidney damage. Poisoning with substances with hemolytic effect (acetic acid, arsenic hydrogen, copper sulfate, snake venom, etc.) is complicated by blockage of nephrons with hemoglobin. Similar damage is caused by massive tissue crushing and prolonged compression syndrome, in which myoglobinuria is observed. With toxic liver damage, the renal parenchyma is damaged a second time by xenobiotics and endogenous toxins.
- General clinical manifestations of poisoning. A number of chemicals do not have a direct nephrotoxic effect, however, systemic manifestations that occur when they are taken lead to severe renal dysfunction. Most often, toxic forms of nephropathy develop against the background of poisoning with the clinic of shock, uncompensated acidosis, pronounced metabolic disorders. The same situation arises under the influence of endo- and exotoxins of pathogenic and conditionally pathogenic microflora.
The constant expansion of the range of medications, primarily antibacterial and antitumor agents, has led to an increase in the number of cases of toxic drug nephropathy. According to research results, in more than 30% of patients, neoliguric renal insufficiency is associated with taking pharmaceutical drugs.
Nephrotoxic medications can directly damage the renal tubules (aminoglycosides, amphotericins, immunoglobulins, NSAIDs, etc.), cause their blockage (sulfonamides, cyclosporines, derivatives of purine nucleosides), systematically disrupt renal hemodynamics (beta-blockers, some diuretics) or have a combined effect. The development of toxic iatrogenic nephropathy is also possible during radiation therapy.
Pathogenesis
The mechanism of development of toxic nephropathy is determined by the causes that provoked renal dysfunction. The pathogenesis of disorders caused by direct-acting nephrotoxins is based on a violation of biochemical processes in the nephrons, epithelial cells of the proximal and distal tubules. After filtration by the glomeruli, the toxic substance enters the tubular system, where, due to the reabsorption of water, its level increases almost 100 times. The resulting concentration gradient promotes the entry and accumulation of xenobiotic in the tubular epithelium to a certain critical level.
Depending on the type of exotoxin in epithelial cells, the processes of destruction of cellular and mitochondrial membranes, lysosomes, cytoplasmic components, smooth endoplasmic reticulum, ribosomes, etc. occur with the development of acute tubular necrosis in the most severe cases. Some nephrotoxins, due to the initiation of hyperimmune processes, destroy the glomerular apparatus of the cortical layer. The deposition of immune complexes in the glomerular structures or the formation of complex antigens in the membranes with subsequent attack of antibodies provoke the onset of acute glomerulonephritis or interstitial nephritis without damage to the tubular epithelial cells. An important factor of direct nephrotoxicity is the ability of some substances to stimulate the formation of free radicals.
The pathogenesis of indirect damage to the kidneys during tubule blockage is based on the development of necrotic processes in their cells, violation of reabsorption ability. Intrarenal stagnation of urine is accompanied by retrograde flow of glomerular filtrate and subsequent damage to the nephrons. In nephropathies that have arisen against the background of general poisoning, the basis of pathomorphological changes is usually cell ischemia and a violation of biochemical processes due to acid-base and water-electrolyte imbalance. At the initial stage, epithelial cell dysfunction occurs, which can subsequently be complicated by toxic degeneration and necrosis of the tubular epithelium, destruction of glomerular basement membranes, interstitial edema.
Classification
The systematization of forms of toxic nephropathy is carried out taking into account the features of the etiopathogenesis of the disease and the severity of symptoms. This approach makes it possible to develop optimal patient management tactics, and in some cases to prevent the development of irreversible tissue destruction. Taking into account the etiological factor and the mechanism of kidney damage , the following forms of the disease are distinguished:
- Toxic specific nephropathy. It develops under the influence of exogenous and endogenous substances with direct and indirect nephrotoxic effect. It is characterized by the rapid development of tissue destruction, which in some patients is irreversible. More often requires early initiation of renal replacement therapy.
- Toxic nonspecific nephropathy. Complicates the course of poisoning and diseases with severe intoxication syndrome, in which hemodynamic and metabolic disorders become the leading ones. At the initial stages, the disorders are of a functional nature and only later begins the destruction of tissues.
With a mild course, nephropathy is detected in the laboratory: in the clinical analysis of urine, an increased content of protein, leukocytes, erythrocytes is determined, cylinders appear. The average degree is characterized by a decrease in the amount of urine and a violation of filtration function with an increase in the level of urea, creatinine, potassium in the blood serum. A severe course is characterized by a clinic of acute respiratory failure, up to the onset of uremic coma.
Symptoms
Within 1-3 days after poisoning, clinical symptoms manifest themselves as a feeling of heaviness, dull aching pains in the lower back, general weakness, fatigue. With significant dysfunction and destruction of the kidneys, urine staining with blood (macrohematuria) is possible. From the 2nd-4th day, the volume of diuresis decreases, characteristic “renal” edema appears on the face, which decrease or completely disappear by the end of the day. The patient is constantly thirsty, complains of headache and muscle soreness.
Nausea, vomiting, diarrhea occur. The skin and visible mucous membranes become dry, jaundiced. The increase in renal insufficiency is accompanied by an almost complete cessation of urination, increased swelling, its downward spread to other parts of the body, the appearance of petechial rash. With severe lesions, brain symptoms develop — lethargy, lethargy, deafness, auditory, visual, tactile hallucinations, convulsive syndrome. Signs of severe renal dysfunction usually persist for 7-14 days.
At the next stage of the disease development, lasting from 10-15 to 30 days, oligoanuria is replaced by a gradual increase in diuresis. The patient secretes from 1.8 to 5-8 liters or more of urine per day. Weakness, fatigue, excruciating thirst persist, body weight decreases. The duration of the convalescence period in intoxication nephropathy depends on the volume and nature of the lesion. Usually, it takes from 6 months to 2 years to restore the functional viability of the organ.
Complications
In 20-70% of cases, toxic nephropathy ends in death due to massive irreversible destruction of the renal parenchyma. A decrease in filtration function in patients with acute renal failure leads to hyperkalemia with slowing of the heart rate, fibrillation and ventricular asystole. Cardiac dysfunction in combination with hypoproteinemia increases the risk of pulmonary edema.
Prolonged uremia is accompanied by increased release of nitrogenous metabolites through the skin, serous and mucous membranes with the development of uremic pericarditis, pleurisy, gastritis, enterocolitis, laryngotracheitis, toxic damage to the liver, bone marrow. If the secretion of the components of the renin-angiotensin system is impaired, arterial hypertension may develop. Long-term consequences of toxic kidney damage are chronic tubulointerstitial nephritis, chronic renal failure, neoplasms of the urinary tract.
Diagnostics
The diagnosis of toxic nephropathy is usually not difficult in cases where the disease occurred after poisoning with a chemical substance. The diagnostic search is aimed at assessing the nature and extent of possible tissue damage, determining the severity of renal dysfunction. The following laboratory and instrumental methods of research are recommended for patients with nephropathy:
- Urinalysis. Proteinuria, leukocyturia, microhematuria, and cylindruria are determined. The relative density of urine in the oligoanuric phase exceeds 1030 g/l, in the polyuric it is below 1003 g/l. An additional Zimnitsky test in polyuria reveals a decrease in concentration function.
- Blood test. Serum levels of creatinine, uric acid, urea nitrogen, potassium, calcium, and inorganic phosphorus increase until the volume of diuresis is restored. Violation of the filtration capacity of glomeruli is also confirmed by the results of the nephrological complex and the Rehberg test.
- Ultrasound of the kidneys. With echography, toxic-type nephropathy is manifested by an increase in the size of the renal parenchyma due to interstitial and lymphostatic edema. Areas of necrosis have the form of hypoechoic cavities or hyperechoic inclusions. Ultrasound of renal vessels reveals hemodynamic disorders.
- Kidney CT. Computed tomography of the kidneys allows you to obtain a layered image of renal tissues and detect even small areas of destruction. For safety reasons, in case of toxic lesions, it is recommended to conduct the study without contrast or replace it with MRI, although in this case the information content is somewhat reduced.
To confirm the toxic nature of nephrological pathology, chemical and toxicological studies are carried out, if possible, to establish the chemical substance that caused the disorder. Contrast research methods (excretory urography, renal angiography) are used with caution due to the risk of aggravation of the clinical situation by contrast-induced destructive processes. To monitor the condition of other organs and systems, biochemical liver tests, coagulogram, ECG are carried out. Changes in the general blood test are nonspecific: anemia, moderate leukocytosis, increased ESR, thrombocytopenia may be detected.
Nephropathy of toxic origin is differentiated with secondary nephropathies of other genesis (contrast-induced, diabetic, dysmetabolic, etc.), acute glomerulonephritis, ischemic kidney necrosis, traumatic damage to the renal parenchyma, atheroembolic disease. According to the appointment of a urologist-nephrologist, the patient is advised by a toxicologist, anesthesiologist-resuscitator, neurologist, therapist, cardiologist, pulmonologist, hepatologist.
Treatment
Patients whose kidneys are damaged as a result of poisoning with exo- or endotoxins are hospitalized in the intensive care unit. The main therapeutic tasks are the speedy elimination of the chemical, correction of metabolic disorders, prevention of possible complications. Taking into account the stage of the disease , patients are shown:
- Detoxification therapy. It is carried out in the first hours and days after poisoning. For accelerated elimination of the toxin, gastric lavage, forced diuresis with the appointment of osmotic diuretics and saluretics, adsorbents, laxatives, specific antidotes are used. In complex cases, plasmapheresis, hemosorption, hemofiltration, ultrafiltration, hemodialysis, peritoneal dialysis are effective. Some patients are prescribed transfusion of blood and its components.
- Infusion correction of metabolic disorders. It begins immediately after hospitalization and continues in the oligoanuric period of acute respiratory failure. To restore the electrolyte balance and acid-base balance, potassium antagonists (usually calcium preparations), glucose infusion with insulin, alkalizing polyionic solutions are used. Further intake of enterosorbents binding toxic metabolites is possible. In case of significant renal dysfunction, it is justified to conduct RRT.
With the aggravation of the patient’s condition, complex antishock therapy is carried out, urgent conditions are stopped (uremic coma, pulmonary edema, convulsive syndrome, hypertensive crisis). In the polyuric phase, massive (up to 5-6 l / day) infusion therapy continues to maintain BCC and physiological concentration of metabolites. At the recovery stage, general restorative treatment is carried out and the tactics of further management of the patient is determined, taking into account the degree of preservation of renal functions.
Prognosis and prevention
Toxic nephropathy is a severe, prognostically unfavorable disorder with high mortality rates. Timely identification of the toxin, correct assessment of the morphological preservation and functional viability of the renal parenchyma, and adequate intensive therapy increase the chances of a favorable outcome of nephropathy. Prevention of the disease is aimed at preventing toxic substances from entering the body: limiting the time of contact with nephrotoxic poisons, using personal protective equipment (respirators, protective clothing), refusing to eat unfamiliar mushrooms.
Employees of enterprises with harmful production conditions are recommended to undergo preventive medical examinations for early detection of renal dysfunction. To reduce the number of cases of hemodynamic and metabolic damage to renal cells in systemic disorders, patients with poisoning are recommended to regularly monitor the functional viability of the kidneys and adequate relief of the acute condition. Taking into account the increasing prevalence of medicinal nephropathies when prescribing nephrotoxic drugs, a thorough examination of the patient is necessary to identify the prerequisites for toxic damage to the renal parenchyma.