Minimal changes in the tubules (lipoid nephrosis)

Minimal changes in the glomeruli (lipoid nephrosis) are not detected by light microscopy and immunofluorescence studies. Only electron microscopy reveals the fusion of the pedunculated processes of epithelial cells (podocytes), which is considered the main cause of proteinuria in this form of glomerulonephritis.

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Causes minimal changes in the tubules (lipoid nephrosis)

According to one hypothesis of pathogenesis, minimal changes in the glomeruli (lipoid nephrosis) develop as a result of a factor that increases glomerular vascular permeability, produced by T-lymphocytes.

This morphological form is observed more often in children, and in boys 2 times more often than in girls, but it is also found in adults, including the elderly. Thus, in the observations of A. Davison (1996) among 317 patients with nephrotic syndrome over 60 years old, 11% had minimal changes in the glomeruli.

Often the disease "minimal glomerular changes (lipoid nephrosis)" develops after an upper respiratory tract infection, allergic reactions (food allergy, insect bites, drugs, vaccination) and is often combined with atopic diseases, allergic disorders (asthma, eczema, milk intolerance, hay fever). Sometimes it is preceded by other infections. The role of streptococcus has not been proven, titers of antistreptococcal antibodies are sometimes lower than in healthy individuals. Isolated cases of association with neoplastic diseases (lymphoma, intestinal cancer, lung cancer, etc.) have been described, but they are rarer than with membranous nephropathy. Familial cases are known, more often in siblings, which suggests the possibility of a genetic predisposition.

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Symptoms minimal changes in the tubules (lipoid nephrosis)

Most patients report the following symptoms of minimal glomerular changes (lipoid nephrosis): nephrotic syndrome - with massive proteinuria, severe edema, anasarca, severe hypoalbuminemia, hypovolemia, very severe lipidemia; ascites often develops in children, sometimes accompanied by abdominal pain. With severe hypovolemia, nephrotic crisis with abdominal pain and skin erythema and cardiovascular shock with circulatory failure, cold extremities may develop.

In young children, "minimal changes" are observed in 80-90% of all cases of nephrotic syndrome, in adolescents - in 50%, in adults - in 10-20%. In a child under 10 years of age who has nephrotic syndrome with selective proteinuria and no hematuria, hypertension, azotemia, and no decreased complement levels, "minimal changes" are so likely that there is no need to do a kidney biopsy.

However, such isolated nephrotic syndrome (in its "pure" form) is not always observed: 20-25% of patients have moderate erythrocyturia, 10% of children and 30-35% of adults have diastolic hypertension. 47% of adults with minimal glomerular changes have arterial hypertension, 33% have transient microhematuria, 96% have hypertriglyceridemia, 41% have transient hyperuricemia; the ratio of men to women is 1:1.4.

In rare cases, symptoms of minimal glomerular changes (lipoid nephrosis) such as retention of nitrogenous waste or even acute renal failure are observed, which may be based on severe hypovolemia, intranephron blockage with protein precipitates, pronounced adhesion of podocytes with closure of gaps in the basement membrane, severe interstitial edema, hypercoagulation.

ESR is sharply accelerated. During exacerbations, the IgG level is usually reduced, the IgE or IgM level, fibrinogen may be increased. The C3 complement level is normal, and sometimes increased.

It is in this form that corticosteroid therapy is most effective, often leading to the disappearance of edema within 1 week. Subsequently, the disease may take a recurrent course with the development of steroid dependence, but chronic renal failure rarely develops.

Among the complications, the most severe are hypovolemic shock, nephrotic crises, thromboses, severe infections. In the past - before the use of antibiotics and glucocorticoids - these complications led to death in the first 5 years of the disease in more than 60% of children. At present, the prognosis is quite favorable, despite the possibility of relapses and complications: 5-year survival is 95% and higher.

Treatment minimal changes in the tubules (lipoid nephrosis)

Spontaneous remissions of nephrotic syndrome in urinary infections are possible, but they develop after a long time. The risk of complications of long-term nephrotic syndrome, especially cardiovascular (early atherosclerosis) and thrombosis, increases in adults and elderly patients. Since these complications are dangerous, immunosuppressive therapy (corticosteroids, cytostatics, cyclosporine) is generally accepted.

For newly diagnosed nephrotic syndrome, it is recommended:

• prednisolone at a dose of 1 mg/(kg x day) until complete remission is achieved (proteinuria <0.3 g/day) for at least 6-8 weeks;
• within 8 weeks, remission develops in 50% of patients, within 12-16 weeks - in 60-80% of patients. If partial remission occurs (proteinuria <2.0-3.0 g/day, but >0.3 g/day), treatment of minimal glomerular changes (lipoid nephrosis) is continued for another 6 weeks or more, after which it is possible to switch to taking the drug every other day with a decrease every month by 0.2-0.4 mg/kg for 48 hours. Relapses subsequently develop in 20-40% of patients;
• If remission does not occur, then prednisolone is recommended to be given with a constant reduction in dose over a total of 4-6 months, and only after this the patient is considered resistant to corticosteroids.

In patients over 65 years of age who have a high risk of side effects from steroid therapy and a fairly low risk of relapse, the dose is reduced and prednisolone is discontinued more quickly. If severe complications from steroid therapy develop, the drug should be discontinued quickly.

In children, prednisolone is recommended [60 mg/m2 ^of body surface, or 2-3 mg/(kg x day), maximum 80-100 mg/day]. This dose is given until remission develops (absence of proteinuria for at least 3 days), which occurs in 90% of patients during the first 4 weeks of therapy, then prednisolone is taken every other day.

In cases of contraindications to high doses of corticosteroids (e.g. diabetes mellitus, cardiovascular pathology, severe dyslipidemia, obliterating atherosclerosis of peripheral vessels, mental disorders, osteoporosis, etc.), treatment of minimal glomerular changes (lipoid nephrosis) begins with cyclophosphamide [2 mg/kg x day)] or chlorbutin [0.15 mg/(kg x day)], which in urinary infections can lead to remission within 8-12 weeks. The effectiveness of this approach has been confirmed in both adults and elderly patients.

Treatment of relapses

• Treatment of the first relapse of nephrotic syndrome is carried out according to the same rules as at the onset of the disease: prednisolone is prescribed at a dose of 1 mg / kg x day) for adults and 60 mg / m ² / day for children until remission develops. Then the dose is gradually reduced and they switch to taking prednisolone every other day (40 mg / m ² for 48 hours for children and 0.75 mg / kg for 48 hours for adults), continuing for another 4 weeks.
• In case of frequent relapses, or steroid dependence, or pronounced side effects of glucocorticoids (hypercorticism), cytostatics are prescribed (reducing the dose of prednisolone). Usually, alkylating cytostatics are used for 12 weeks (a shorter period than in other morphological variants); in this case, about 2/3 of steroid-dependent patients remain in remission for 2 years. Long-term treatment of minimal glomerular changes (lipoid nephrosis) with cytostatics increases not only the likelihood of development and duration of remission, but also the risk of severe side effects.
• In case of continuing relapses, repeated administration of cytostatics is not recommended, since their toxic effects are cumulative. If there is no pronounced hypercorticism, corticosteroids are used again: first in the form of methylprednisolone pulses (10-15 mg/kg intravenously for 3 days in a row), then prednisolone orally [0.5 mg/kg x day] until remission develops. This regimen reduces the risk of complications of corticosteroid therapy. If hypercorticism develops, then after achieving remission with glucocorticoids, cyclosporine is prescribed at an initial dose of 5 mg/kg x day). If remission is maintained for 6-12 months, the cyclosporine dose is slowly reduced (by 25% every 2 months) to determine the minimum maintenance dose [usually not less than 2.5-3 mg/kg x day)]. In any case, after 2 years of treatment, cyclosporine should be discontinued due to the risk of nephrotoxicity.

Compared with children, adults respond to glucocorticoids more slowly and in a smaller percentage of cases. Complete remissions of nephrotic syndrome in 90% of children occur within the first 4 weeks of treatment, while in adults only 50-60% within 8 weeks and 80% within 16 weeks of treatment. This is explained by differences in treatment regimens for children and adults, in particular, higher (2-3 times higher per 1 kg of body weight) doses of glucocorticoids in children.

At the same time, the risk of relapses in adults is lower than in children, which is probably due to a longer initial period of treatment. It has been established that the longer the initial treatment of minimal glomerular changes (lipoid nephrosis) with glucocorticoids, the longer the remission.

The risk of developing renal failure in children is minimal, but in patients over 60 years of age, chronic renal failure develops in 14% of cases.

In case of steroid resistance that arose during the first episode or during relapses, cytostatics (for 2-3 months) or cyclosporine A are used - according to the above scheme. It should be noted that in patients with a morphological diagnosis of MI, who do not respond to a sufficiently long-term treatment of minimal changes in the glomeruli (lipoid nephrosis) with high doses of prednisolone, focal segmental glomerulosclerosis is sooner or later detected in repeated biopsies, which requires a special therapeutic approach. Thus, when treating patients with urinary tract infections, the following provisions should be kept in mind:

• The risk of complications of nephrotic syndrome in adults and especially elderly patients is higher than in children.
• Standard 6-8-week treatment with prednisolone produces remission in only half of adult patients with MI.
• Continuing treatment for 12-16 weeks causes remission in most patients.
• If there are contraindications to steroid therapy, treatment begins with cytostatics.
• In case of frequently recurring course or steroid dependence, cytostatics or cyclosporine are used.