Kidney amyloidosis is a manifestation of systemic amyloidosis, characterized by a violation of protein-carbohydrate metabolism with extracellular deposition of amyloid in the renal tissue – a complex protein-polysaccharide compound that leads to organ dysfunction. Pathology proceeds with the development of nephrotic syndrome (proteinuria, edema, hypo- and dysproteinemia, hypercholesterolemia) and the outcome in chronic renal failure. Diagnostics includes urine, blood and coprogram studies; kidney ultrasound and biopsy. A diet is prescribed, drug therapy and correction of primary disorders are carried out; in severe cases, hemodialysis and kidney transplantation may be required.
In practical urology, amyloidosis of the kidneys (amyloid dystrophy, amyloid nephrosis) accounts for 1-2.8% of all kidney diseases. Kidney amyloidosis is the most frequent manifestation of systemic amyloidosis, in which a special glycoprotein substance, amyloid, accumulates in the intercellular space of various organs, disrupting their functions. Along with glomerulonephritis, it is the main cause of the development of nephrotic syndrome.
Causes of kidney amyloidosis
The etiology of idiopathic amyloidosis of the kidneys in most cases remains unknown; sometimes the disease develops with multiple myeloma. In addition to the kidneys, primary amyloidosis can affect the tongue, skin, thyroid gland, liver, lungs, intestines, spleen, heart.
Secondary amyloidosis affects the kidneys, blood vessels, lymph nodes, liver, etc. organs. It is usually associated with chronic, long-term pathologies:
- infections (syphilis, tuberculosis, malaria);
- purulent-destructive processes (bronchiectatic disease, pleural empyema, osteomyelitis, prolonged septic endocarditis);
- systemic diseases (rheumatoid arthritis, psoriatic arthritis, ankylosing spondylitis);
- intestinal diseases (ulcerative colitis, Crohn’s disease);
- tumors (lymphogranulomatosis, meningioma, kidney neoplasms), etc.
The reason for the dialysis variant of the disease is a long-term hemodialysis for the patient. Familial hereditary amyloidosis occurs with periodic illness, often in the countries of the Mediterranean basin (in particular, the Portuguese version). Senile amyloidosis is considered as a sign of aging, occurring after 80 years in 80% of people. Local forms of pathology can be caused by tumors of the endocrine system, Alzheimer’s disease, type 2 diabetes mellitus, and other causes.
Among the theories of the pathogenesis of kidney amyloidosis, the immunological, mutational hypothesis and the hypothesis of local cell synthesis are considered. The disease is characterized by extracellular deposition in the renal tissue, mainly in the glomeruli, of amyloid – a special glycoprotein with a high content of insoluble fibrillar protein.
In accordance with the etiopathogenetic mechanisms, five forms of kidney amyloidosis are distinguished: idiopathic, familial, acquired, senile, local tumor-like.
- In primary (idiopathic) amyloidosis, the causes and mechanisms remain unknown.
- Family (hereditary) forms are caused by a genetic defect in the formation of fibrillar proteins in the body.
- Secondary (acquired) amyloidosis develops in immunological disorders (chronic infections, rheumatic diseases, malignant tumors, etc.).
- The basis of the senile type of pathology is an involutive change in protein metabolism.
- The nature of local tumor-like amyloidosis of the kidneys is unclear.
Idiopathic, familial, senile and local tumor-like forms are distinguished into independent nosological units. Secondary amyloidosis of the kidneys is considered as a complication of the underlying disease. Depending on the type of fibrillar protein contained in amyloid, various forms of the disease (“A”) are commonly referred to by the following abbreviations:
- AA-type (secondary, amyloid contains serum a-globulin);
- AL-type (idiopathic, in amyloid – light chains of Ig);
- ATTR-type (familial, senile; in amyloid – protein transthyretin);
- Aß2M-type (dialysis; in amyloid – β2-microglobulin), etc.
Symptoms of kidney amyloidosis
In this pathology, renal and extrarenal manifestations are combined, causing polymorphism of the disease picture. During the course of the disease, there are 4 stages (latent, proteinuric, nephrotic, azotemic) with characteristic clinical symptoms.
In the latent stage, despite the presence of amyloid, there are no clinical manifestations. During this period, the symptoms of the primary disease (infections, purulent processes, rheumatic diseases, etc.) prevail. The latent stage can last up to 3-5 years or more.
In the proteinuric (albuminuric) stage, there is an increasing loss of protein in the urine, microhematuria, leukocyturia, increased ESR. Due to sclerosis and nephron atrophy, lymphostasis and hyperemia, the kidneys increase, become dense, and acquire a matte gray-pink color.
The nephrotic (edematous) stage is characterized by sclerosis and amyloidosis of the cerebral layer of the kidney and, as a consequence, the development of nephrotic syndrome with a typical tetrad of signs – massive proteinuria, hypercholesterolemia, hypoproteinemia, edema resistant to diuretics. Arterial hypertension may occur, but more often blood pressure is normal or low. Hepatomegaly and splenomegaly are often noted.
In the azotemic (terminal, uremic) stage, the kidneys are scar-wrinkled, dense, reduced in size (amyloid kidney). The azotemic stage corresponds to the development of chronic renal failure. Unlike glomerulonephritis, persistent edema persists.
Amyloidosis of the kidneys can be complicated by renal vein thrombosis with anuria and pain syndrome. The outcome of this stage is often the death of the patient from azotemic uremia. Systemic manifestations may include dizziness, weakness, shortness of breath, arrhythmia, anemia, etc. In the case of intestinal amyloidosis, persistent diarrhea develops.
In the early preclinical period, it is extremely difficult to diagnose kidney amyloidosis. At this stage, priority is given to laboratory methods – the study of urine and blood:
- Urine analysis. In the general analysis of urine, proteinuria is noted early, which tends to steadily increase, leukocyturia (in the absence of signs of pyelonephritis), microhematuria, cylindruria.
- Blood testing. Biochemical blood parameters are characterized by hypoalbuminemia, hyperglobulinemia, hypercholesterolemia, increased activity of alkaline phosphotase, hyperbilirubinemia, electrolyte imbalance (hyponatremia and hypocalcemia), increased fibrinogen and b-lipoproteins. In the general blood test – leukocytosis, anemia, increased ESR.
- Analysis of feces. The study of the coprogram often reveals a pronounced degree of steatorrhea (“fat stool”), creatorrhea (significant content of muscle fibers in the stool), amylorrhea (the presence of a large amount of starch in the feces).
- Instrumental diagnostics. Due to pronounced metabolic disorders, arrhythmia and conduction disorders may be recorded on the ECG; with EchoCG, cardiomyopathy and diastolic dysfunction. Ultrasound of the abdominal cavity reveals an increase in the spleen and liver. Gastrointestinal radiography determines hypotension of the esophagus, weakening of gastric peristalsis, acceleration or deceleration of the passage of barium through the intestine. On ultrasound of the kidneys, their increase is visualized (large fatty kidneys).
- Biopsy. A reliable method of diagnosing amyloidosis is a kidney biopsy. Morphological examination of the biopsy after congo red staining with subsequent electron microscopy in polarized light reveals a green glow characteristic of kidney amyloidosis. Amyloid can be detected along the vessels, tubules, in the glomeruli. In some cases, a biopsy of the rectal mucosa, skin, gums, liver is performed.
Treatment of kidney amyloidosis
In the therapy of the secondary process, the success of the treatment of the underlying disease plays a significant role. In the case of a complete stable cure of the primary pathology, the symptoms of amyloidosis of the kidneys often regress. Patients need to change their diet: it is necessary to consume raw liver for a long time, for 1.5-2 years (80-120 mg / day), restriction of protein and salt (especially in renal and heart failure); increased consumption of carbohydrates; food rich in vitamins (especially vitamin C) and potassium salts.
Pathogenetic drugs are derivatives of 4-aminoquinoline, desensitizing agents, colchicine alkaloids, complexing agents, etc. Symptomatic therapy for amyloidosis of the kidneys includes the appointment of diuretics, antihypertensive drugs, plasma transfusion, albumin, etc. The expediency of using corticosteroids and cytostatics is debated. In the terminal stage, chronic renal dialysis or kidney transplantation may be required.
Prognosis and prevention
The prognosis is largely determined by the course of the underlying disease and the rate of progression of amyloidosis of the kidneys. The prognosis worsens the development of thrombosis, hemorrhages, the addition of intercurrent infections, old age. With the development of heart or kidney failure, the survival rate is less than 1 year. The conditions for recovery are timely treatment to a neurologist and early diagnosis of kidney amyloidosis, active treatment and complete elimination of the underlying disease. Prevention requires timely treatment of any chronic pathology that may cause the development of amyloid nephrosis.