Minimal changes in glomeruli (lipoid nephrosis)

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

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10]

Causes of the minimal changes in glomeruli (lipoid nephrosis)

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

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

Often, the disease "minimal glomerular changes (lipoid nephrosis)" develops after infection of the upper respiratory tract, allergic reactions (food allergy, insect bites, medications, vaccinations) and is often combined with atopic diseases, allergic disorders (asthma, eczema, milk intolerance, pollinosis) . Sometimes it is preceded by other infections. The role of streptococcus has not been proven, anti-streptococcal antibody titres are sometimes lower than in healthy individuals. Separate cases of communication with neoplastic diseases (lymphomas, intestinal cancer, lungs, etc.), but more rare than with membranous nephropathy, are described. Familiar cases are known, more often in siblings, which indicates the possibility of a genetic predisposition.

[11], [12], [13], [14]

Symptoms of the minimal changes in glomeruli (lipoid nephrosis)

Most patients note the following symptoms of minimal changes in glomeruli (lipoid nephrosis): nephrotic syndrome - with massive proteinuria, marked edema, anasarka, severe hypoalbuminemia, hapovolemia, very pronounced lipidemia; children often develop  ascites, sometimes accompanied by  pain in the abdomen. With severe hypovolemia, it is possible to develop a nephrotic crisis with abdominal pain and cutaneous erythema and cardiovascular shock with circulatory insufficiency, cold extremities.

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%. A child under 10 years old who has a nephrotic syndrome with selective proteinuria and no hematuria, hypertension, azotemia, and no lowered complement level, "minimal changes" are so likely that there is no need to do a kidney biopsy.

However, this isolated nephrotic syndrome (in its "pure" form) is not always observed: in 20-25% of patients moderate erythrocyturia is detected, 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 and women is 1: 1.4.

In rare cases, there are symptoms of minimal changes in glomeruli (lipoid nephrosis), such as retention of nitrogenous slags, or even acute renal failure, which can be based on severe hypovolemia, intra-neural occlusion with protein precipitates, marked adhesion of podocytes with closure of cracks in the basal membrane, severe edema of interstitium , hypercoagulation.

ESR is sharply accelerated. During exacerbations IgG level is usually lowered, the level of IgE or IgM, fibrinogen can be increased. The level of C3-complement is normal, and sometimes elevated.

It is with this form that the most effective corticosteroid therapy, often leading for 1 week to the disappearance of edema. Later, the disease can take a relapsing course with the development of steroid dependence, but chronic renal failure develops rarely.

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 caused more than 60% of children to die in the first 5 years of the disease. Currently, the prognosis is quite favorable, despite the possibility of relapses and complications: a 5-year survival rate of 95% or more.

Treatment of the minimal changes in glomeruli (lipoid nephrosis)

Spontaneous remission of a nephrotic syndrome with urinary infections is possible, but they develop after a long time. The risk of complications of prolonged 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.

With the first arising nephrotic syndrome recommend:

• prednisolone at a dose of 1 mg / kgg until the complete remission is reached (proteinuria <0.3 g / day) for at least 6-8 weeks;
• within 8 weeks of remission develops in 50% of patients, during 12-16 weeks - in 60-80% of patients. If there is partial remission (proteinuria <2.0-3.0 g / day, but> 0.3 g / day), treatment for minimal changes in glomeruli (lipoid nephrosis) continues for another 6 weeks or more, after which a transition to taking the drug every other day with a drop of 0.2-0.4 mg / kg every month for 48 hours. In 20-40% of patients, relapses subsequently develop;
• if there is no remission, then prednisolone is recommended to give with a constant decrease in the dose as a whole for 4-6 months, and only after that the patient is considered as resistant to corticosteroids.

In patients older than 65 who have a high risk of steroid therapy side effects and a relatively low risk of relapse, reduce the dose and abolish prednisolone more quickly. With the development of severe complications of steroid therapy should quickly cancel the drug.

In children, prednisolone is recommended [60 mg / m ²  body surface, or 2-3 mg / (kghsut), maximum 80-100 mg / day]. This dose is given until the time of remission (no proteinuria for at least 3 days) occurring in 90% of patients during the first 4 weeks of therapy, then taking prednisolone every other day.

With contraindications to high doses of corticosteroids (for example, diabetes mellitus, cardiovascular pathology, severe dyslipidemia, obliterating peripheral vascular arteriosclerosis, mental disorders, osteoporosis, etc.), treatment with minimal changes in glomeruli (lipoid nephrosis) begins with cyclophosphamide [2 mg / kgsut)] or chlorbutin [0,15 mg / (kghsut)], which with 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 the nephrotic syndrome is carried out according to the same rules as in the beginning of the disease: prednisolone is prescribed in a dose of 1 mg / kghsut) for adults and 60 mg / m ² / day for children until remission develops. Then the dose is gradually reduced and switched 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), lasting 4 more weeks.
• With frequent relapses, or steroid dependence, or pronounced side effects of glucocorticoids (hypercorticosis), cytostatics are prescribed (reducing the dose of prednisolone). Usually, alkylating cytotoxic drugs are used for 12 weeks (a period less than in other morphological variants); while about 2/3 of the steroid-dependent patients remain in remission for 2 years. Long-term treatment of minimal changes in glomeruli (lipoid nephrosis) with cytostatics increases not only the probability of development and duration of remission, but also the risk of serious side effects.
• With continued relapse, it is not recommended to reassign cytotoxic drugs, since their toxic effects are cumulative. If there is no pronounced hypercorticism, corticosteroids are again used: first in the form of pulses with methylprednisolone (10-15 mg / kg intravenously for 3 consecutive days), then prednisolone inside [0.5 mg / kghsut]] until the remission develops. This regimen reduces the risk of complications of corticosteroid therapy. If hypercortisy develops, then after the remission with glucocorticoids is prescribed, cyclosporine in the initial dose of 5 mg / kghsut). If the remission is maintained for 6 to 12 months, the dose of cyclosporine is slowly reduced (by 25% every 2 months) to determine the minimum maintenance dose [usually at least 2.5-3 mg / kghs.]]. In any case, after 2 years of treatment, cyclosporine is desirable to be canceled because of the risk of nephrotoxicity.

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

At the same time, the risk of recurrence in adults is lower than in children, which, apparently, is associated with a longer initial period of treatment. It was established that the longer the initial treatment of minimal changes in glomeruli (lipoid nephrosis) with glucocorticoids, the longer the remission.

The risk of developing kidney failure in children is minimal, but in patients older than 60 years in 14% of cases develop chronic renal failure.

With steroid resistance, which occurred at the first episode or when relapses, cytostatics (for 2-3 months) or cyclosporin A - according to the above scheme are used. It should be noted that in patients with a morphological diagnosis of MI that do not respond to a sufficiently long treatment of minimal changes in glomeruli (lipoid nephrosis) with high doses of prednisolone, the focal-segmental glomerulosclerosis, which requires a special therapeutic approach, is sooner or later revealed in repeated biopsies. Thus, in the treatment of patients with urinary symptoms, the following provisions should be borne in mind:

• The risk of complications of nephrotic syndrome in adults and especially elderly patients is higher than in children.
• A standard 6-8-week treatment with prednisolone gives remission in only half of the adult patients with MI.
• Continuation of treatment to 12-16 weeks causes remission in most patients.
• With contraindications to steroid therapy, treatment begins with cytostatics.
• With often recurring course or steroid dependence, cytostatics or cyclosporine are used.