This disease is often called lipoid nephrosis, zero lesion, or small process disease. In this form of idiopathic nephrotic syndrome, light microscopy reveals no or only minor changes in the capillaries of the glomeruli (hence the designation minimal change), but electron microscopic studies can detect diffuse effacement. Immunofluorescence microscopy reveals either a complete absence of deposits or uneven and nonspecific deposits of immunoglobulin and components of the complement system. Minimal change disease is the most common form of idiopathic nephrotic syndrome in children, and more than 70 to 80% of cases occur in children under 8 years of age. This disease is often observed in adults, but it accounts for 15-20% of cases of idiopathic nephrotic syndrome in patients over 16 years of age. A slightly greater predisposition to developing this disease is observed in men. Typically, these patients have overt nephrotic syndrome, normal blood pressure, normal or slightly decreased GFR, and benign urine sediment. In 20% of cases, microscopic hematuria of varying degrees is detected. In children, the excretion of protein in the urine is usually very selective (for example, the urine contains mainly albumin and minimal amounts of high molecular weight proteins, such as IgG, a2-macroglobulin or C3); in adult patients, the urine may contain a variety of proteins. This pattern of protein excretion indicates a major charge-selective permeability disorder. There are no S3 and fibrin degradation products in the urine. Serum levels of complement components are within normal limits, with the exception of a slight decrease in C1q concentrations. During relapses, IgG concentrations are often significantly reduced, while IgM levels are moderately elevated during both remission and relapse. In some cases, there may be a concomitant allergic reaction (for example, to milk, pollen, etc.), a history of recent immunization or an infectious disease of the upper respiratory tract. In some patients, using special techniques, it is possible to detect immune complexes circulating in the blood. Histocompatibility for the HLA-B12 antigen is more common in cases where minimal change disease is combined with atopy, indicating a possible genetic predisposition to this disease. Thromboembolic complications sometimes occur, but renal vein thrombosis is rare.
Spontaneous remissions and relapses of severe proteinuria may occur, usually for unexplained reasons. It is interesting to note that an identical lesion occurs in those patients with lymphogranulomatosis who develop nephrotic syndrome, suggesting the involvement of lymphocytes in its pathogenesis. With the exception of those patients who develop focal and segmental sclerosing lesions (see below), there is no progressive decline in GFR. Acute renal failure rarely develops. In the pre-antibiotic era, infectious disease caused by encapsulated microorganisms (eg, streptococci) was a leading cause of death, but today the mortality rate is very low and most deaths are due to complications caused by the treatment rather than the disease itself. In rare cases, acute renal failure can develop even in the absence of severe hypovolemia. The mechanism of this phenomenon is unclear but may be related to tubular obstruction due to severe proteinuria or deep effacement occurring in glomerular epithelial cells. Kidney failure is amenable to steroids and diuretics.
Since the etiology and pathogenesis of minimal change disease are unknown, treatment is empirical and symptomatic. A large body of evidence indicates that corticosteroids markedly enhance the disease's natural tendency to go into spontaneous remission. Steroids should be taken orally daily or every other day; Both regimens appear to be equally effective, but the latter treatment option is associated with a lower incidence of complications. The initial treatment regimen for patients is as follows: daily prednisone (60 mg/m2 for children; 1-1.5 mg/kg for adults) for 4 weeks, then prednisone every other day (35-40 mg/m2 for children, 1 mg/kg adults) also for 4 weeks. In the vast majority of treatment-responsive patients, the effect of treatment occurs within 4 weeks after initiation, but sometimes it takes longer to obtain a favorable result. Failure to respond to treatment within 8 weeks usually indicates an error in diagnosis and should prompt re-examination of the biopsy specimen. In many of those patients who have achieved a positive result of treatment, steroid withdrawal often causes a relapse of the disease; this usually occurs within the first year after stopping treatment. Patients with relapses can be treated according to the initial regimen described above, but with a gradual withdrawal of prednisone, conducting maintenance therapy for 3 to 6 months with oral administration of 5 to 10 mg of the drug daily or every other day. To treat a patient who has developed dependence on steroids or a patient suffering from multiple relapses, a short course of therapy with cyclophosphamide (2 - 3 mg/kg per day) or chlorobutine (0.1 - 0.2 mg/kg per day) can be used for 8 - 10 weeks Both of these drugs, when used in combination with steroids to induce remission, reduce the likelihood of subsequent relapse. However, they have adverse side effects on the bone marrow, and cyclophosphamide also on the gonads and bladder. Therefore, when using them, it is extremely necessary to carefully monitor hematological parameters and urine composition. These drugs can also have an oncogenic effect. As for azathioprine, its use does not lead to long-term remission. The use of cytotoxic agents should be reserved for the treatment of those patients who develop serious or life-threatening complications after repeated courses of steroid therapy. The long-term prognosis after treatment for those with minimal change disease is good; A 10-year survival rate can be expected in more than 90% of patients, although some will develop renal failure, usually as a consequence of focal sclerosing lesions of the glomeruli (see. below).
Table 223-4. Idiopathic nephrotic syndrome
Characteristic features underlying primary kidney diseases
Symptomatic treatment of minimal change disease (lipoid nephrosis). In most patients, swelling is moderate and goes away with limited salt. Fluid intake is usually not restricted unless there is severe hyponatremia. Diuretics are effective but rarely needed and should be used with caution to avoid hypovolemia. IV albumin may be risky, but can be life-saving in severe hypovolemia. IV infusions of albumin with furosemide can be used (with caution) in patients with severe edema or anasarca.
On my own hypoalbuminemia- not an indication for intravenous administration of albumin, since it is rapidly eliminated and can cause heart failure or severe arterial hypotension. Arterial hypertension, even during treatment with glucocorticoids, is uncommon; in this case, antihypertensive drugs are prescribed. Once remission is achieved, they can usually be discontinued.
Training plays an important role parents. They need to be taught that minimal change disease is characterized by long-term relapses and be taught how to identify proteinuria using test strips. The results should be recorded in a special diary, which also indicates the doses of medications taken and changes in the child’s condition. It is especially important to check the urine when the child becomes ill (for example, with an acute respiratory illness, which often provokes a relapse), but even during remission, slight proteinuria may occur from time to time.
When any proteinuria Parents should immediately consult a doctor so that treatment for relapse can be started in time and thereby avoid complications. With minor transient proteinuria, careful observation is sufficient; glucocorticoids are not indicated.
Before prescribing large doses glucocorticoids the child must be examined for tuberculosis. A child who has not had chickenpox is given immunoglobulin against the varicella-zoster virus upon contact with a patient; vaccination is carried out only a few months after glucocorticoids are discontinued. The administration of pneumococcal vaccine is also recommended. In case of illness with minimal changes, it is better not to prescribe NSAIDs as antipyretics.
Glucocorticoids for minimal change disease (lipoid nephrosis)
For the first time treat nephrotic syndrome glucocorticoids began in 1956, and for many patients they became the only salvation. In minimal change disease, glucocorticoids cause remission in 90% of cases, so children in whom minimal change disease can be clinically suspected are prescribed them without a prior biopsy. Indications for a biopsy arise only in controversial cases: in children under one year of age, with a combination of proteinuria with gross hematuria and arterial hypertension, with hypocomplementemia and with renal failure not associated with hypovolemia. Although relapse may resolve without treatment, it is now common practice to treat all cases of relapse. Treatment should begin when the previous infection has already resolved.
Optimal doses, schedule and duration No treatment has been established, but there is now strong evidence that the longer the initial course of glucocorticoid treatment, the lower the incidence of subsequent relapses.
In most cases it is prescribed prednisone at a dose of 60 mg/m2/day or 2 mg/kg/day (maximum dose 60 mg/day). If remission does not occur after 8-10 weeks of treatment, then a biopsy is performed to clarify the diagnosis and treatment plan. Sometimes a biopsy reveals that the child actually has minimal change disease, which eventually responds to longer-term treatment with glucocorticoids, alkylating agents, or cyclosporine.
Unfortunately, only 10-25% of children recover fully, without subsequent relapses. There is no standard treatment regimen for relapses - glucocorticoids are usually re-prescribed, then, upon achieving remission, their dose is gradually reduced. A common reason for treatment failure during relapse is an insufficiently high dose of prednisone. Prescribing low-dose prednisone only prolongs treatment; the total dose of prednisone often becomes higher than with conventional therapy, and stable remission is often not achieved. Another possible reason for the ineffectiveness of treatment is a hidden infection (often caries or sinusitis), the manifestations of which can, in addition, be smoothed out against the background of glucocorticoids.
In almost 50% of cases relapses are multiple. If relapses occur 2 or more times within 6 months, counting from remission, or 4 or more times during the year, then they speak of nephrotic syndrome with frequent relapses; if relapses are repeated twice in a row during treatment with glucocorticoids or within 2 weeks after their discontinuation - glucocorticoid-dependent nephrotic syndrome. All such patients, upon achieving the next remission, often continue to be given prednisone - at a lower dose and every other day. In this case, the dose is gradually reduced until it reaches the minimum for a given patient, that is, it ceases to protect him from relapse. This tactic allows you to reduce the frequency of relapses, on the one hand, and reduce the total dose of prednisone, on the other.
It is necessary to monitor child growth and development and regularly examine him for. The main task in the treatment of minimal change disease in children is the ability to select the dose of glucocorticoids so that they help cope with nephrotic syndrome, but do not cause side effects: minimal change disease, even despite multiple relapses, usually goes away over time, but complications may remain .
Other immunosuppressants for minimal change disease (lipoid nephrosis)
Side effects glucocorticoids, especially growth retardation, was the reason that children with nephrotic syndrome with frequent relapses and glucocorticoid-dependent nephrotic syndrome, as well as in cases where glucocorticoid treatment does not help, began to be prescribed more powerful, but also more toxic drugs. Patients with ineffective glucocorticoids usually undergo a biopsy before prescribing cytostatics; for nephrotic syndrome with frequent relapses and glucocorticoid-dependent nephrotic syndrome, this is not done. Alkylating agents are recognized by most (though not all) specialists as second-line drugs used when glucocorticoids are ineffective.
When taken for 8-12 weeks cyclophosphamide well tolerated with minimal risk of infertility. Chlorambucil is equally effective but is used less widely, partly due to its ability to cause epileptic seizures. To prevent hemorrhagic cystitis, alkylating agents are best added to prednisone when remission has already been achieved. In a small proportion of patients, this approach does not provide visible benefits, but in 50% of cases it is possible to achieve remission for 2-3 years. Cyclosporine gives stable remission in 85-90% of patients in whom glucocorticoids are also effective. Its effect is especially pronounced in children weakened by the disease, with side effects of glucocorticoids and the ineffectiveness of cyclophosphamide. Unfortunately, after discontinuation of cyclosporine, new relapses often occur, and the nephrotoxicity of this drug forces careful monitoring of doses.
Moreover, if treatment continues for more than 18 months, kidney biopsies should be performed periodically to assess the degree of interstitial fibrosis.
Prognosis of minimal change disease (lipoid nephrosis)
Before the appearance antibiotics and glucocorticoids, the 5-year survival rate for minimal change disease was only 60%. Patients died mainly from infectious complications. Today, 95% of patients live 20-25 years from diagnosis, but deaths still occur. The cause of death is infection, sometimes thrombosis. Late-onset renal failure is very rare, but a small proportion of patients may develop acute tubular necrosis if sepsis or hypovolemia occurs during a subsequent relapse. The risk of AKI increases with NSAID use, especially during relapse. The early onset of minimal change disease, as well as several relapses during the first year from diagnosis, suggest a long course of the disease.
After 8-10 years from diagnosis, 80% children It is possible to achieve stable remission, but in some cases relapses continue in older patients. Relapses after long-term remission are very rare, but cases have been described in which a relapse occurred 20-25 years after apparent recovery. Sometimes patients in whom glucocorticoids previously had a good effect become insensitive to them. Often this indicates focal segmental glomerulosclerosis (missed at the time by biopsy or developed as a complication of minimal change disease). These patients are at high risk of end-stage renal failure.
3.1.1 Treatment of MCD.
3.1.1.1 Treatment of the onset of MCD.For the treatment of the onset of NS in MCD, monotherapy with glucocorticoids (first-line immunosuppressive therapy) is strongly recommended.
It is recommended to use prednisolone or prednisone* in a daily dose of 1 mg/kg in one dose (maximum 80 mg) or taking a dose of 2 mg/kg (maximum 120 mg) every other day (alternating regimen), also in one dose. Convincing level of recommendations is C (confidence level –2).
Comment. Prednisolone is a synthetic glucocorticoid, an active metabolite of prednisone. Prednisolone and prednisone are equivalents, used in the same doses.
In the presence of relative contraindications (diabetes mellitus, mental disorders, severe osteoporosis, peptic ulcer disease, etc.) or in case of intolerance to prednisolone, the use of second-line immunosuppressive therapy is recommended (see section 3.1,1.7).
If complete remission develops at any time from the start of therapy, the initial dose of glucocorticoids is maintained for at least 1 more week with a total duration of treatment at the initial dose of at least 4 weeks.
Recommendation strength level C (confidence level –2).
In the absence of remission within 4-8 weeks, it is recommended to extend prednisolone therapy at the initial dose up to 16 weeks, which is associated with a later response in adults to therapy compared to children.
Recommendation strength level C (confidence level –2).
It is recommended that the absence of remission within 16 weeks of therapy with prednisolone at a dose of 1 mg/kg/day should be regarded as steroid resistance of MCD, in the case when other causes of nephrotic syndrome are excluded.
Recommendation strength level C (confidence level –2).
· In case of incomplete remission (decrease in proteinuria by 50% from the initial level with an absolute level of 0.3 - 3.4 g/day and a normal blood albumin level) in response to glucocorticoid therapy, which is not typical for MCD, it is recommended to exclude other causes of proteinuria.
Recommendation strength level C (confidence level –3).
Comments. After morphological verification of MCD, the main treatment regimen for both children and adults is the administration of prednisolone in high doses. Most patients respond to steroid therapy by developing complete remission, defined as a decrease in proteinuria to< 300 мг/сутки или соотношение белок/креатинин мочи.
In adults, prednisolone is prescribed at a dose of 1 mg/kg/day, but not higher than 80 mg/day, or every other day at a dose of 2 mg/kg/day, but not higher than 120 mg. It is advisable to take the dose in the morning, after meals, between 7 and 10 am, to avoid suppression of adrenal function. The effectiveness of GCs in MCD appears to be due to both their immunosuppressive/anti-inflammatory effects and their direct effect on podocytes. In cultured human podocytes, the presence of GC receptors and components of the signaling pathways for GC receptors were detected. GCs have been shown to increase the stability of actin filaments, increase the intracellular content of polymerized actin and cause a significant increase in the activity of the intracellular enzyme RhoA-guanine triphosphatase (RhoA-GTPasa).
The duration of the initial dose of prednisolone should be at least 4 weeks, despite the fact that proteinuria may decrease significantly, even completely disappearing, during the first 1-2 weeks of treatment. If a response to therapy develops after 4 weeks, with a stable disappearance of proteinuria within one to two weeks, the dose of prednisolone is reduced to 0.8 mg/kg/day. Simultaneously with the dose reduction, it is recommended to transfer the patient to an alternating dosage regimen, when the patient receives a double daily dose of prednisolone every other day, which will be 1.6 mg/kg/48 hours. The alternating dosage regimen has no advantages in achieving remission and preventing relapses, but it can reduce the negative effects of long-term corticosteroid therapy. The indicated dose is left for one month and then gradually, in order to avoid withdrawal syndrome, is reduced, with a total duration of treatment after achieving remission of at least 6 months. It should be remembered that in adults, as in children, the risk of exacerbation decreases with increasing total duration of treatment. Reducing the dose of prednisolone is possible according to the following scheme: 0.2 -0.4 mg/kg/48 hours once every 2 weeks to a dose of 60 mg/48 hours, after which it is reduced more slowly - 0.1 mg/kg/48 hours. After reaching a dose of 20 mg/48 hours, continue to gradually reduce the dose by 2.5 mg once every 2 weeks until complete withdrawal.
In patients over 65 years of age, due to the high risk of toxicity and possibly greater effectiveness of prednisolone in old age, initial therapy is started at the same dose, but after 4 weeks of treatment, regardless of the result, the dose is reduced. At the same time, it is recommended to switch to an alternating dose of 1.6 mg/kg/48h (no more than 120 mg every other day) for another 4 weeks. Due to the lower likelihood of relapse and, as mentioned, the greater risk of toxicity, in older adults, prednisolone dose reduction can occur at a more rapid pace - 0.4 mg/kg/48 hours every 2 weeks to a dose of 1.2 mg/kg/ 48 In the absence of remission, this dose is left for another 4 weeks and then the reduction continues according to the general scheme to the minimum maintenance level (5-10 mg/day) with a total treatment duration of up to 6 months.
If there is no effect, treatment at the maximum dose of prednisolone is recommended to be continued for up to 16 weeks. Lack of effect for at least 16 weeks of treatment is generally regarded as steroid resistance. A more gentle prednisolone regimen is also possible, when, if treatment is ineffective within 8 weeks, the patient, in the absence of contraindications and side effects, is transferred to prednisolone at a dose of 1.6 mg/kg/48h for up to another 8 weeks. If there is no effect within 16 weeks of treatment, the dose of prednisolone is gradually, according to the above scheme, reduced to maintenance (0.2-0.3 mg/kg/day) and immunosuppressive therapy is added. The drug of choice in the treatment of podocytopathies is cyclosporine A, given that this drug has not only an immunosuppressive effect, but a direct effect at the level of the podocyte cytoskeleton.
3,1,1,2 Treatment of the onset of MCD during the period of prednisolone withdrawal.
After achieving complete remission, a gradual reduction in the dose of glucocorticoids is recommended (on average 0.04 mg/kg/week), with a total withdrawal period of up to 6 months.
If proteinuria increases to more than 300 mg/day during the period of prednisolone withdrawal, after a previously achieved remission, it is recommended to increase its dose again to the level preceding the development of an exacerbation. After proteinuria disappears again, leave the same dose for another 1-2 weeks, and then start stopping prednisolone again, but at a slower pace (on average 0.02 mg/kg/week).
Recommendation strength level C (confidence level –1).
If a relapse of nephrotic syndrome develops during the period of prednisolone withdrawal, it is recommended to increase the dose of prednisolone again to the original level (1 mg/kg/day). After achieving repeated remission, reduce the dose as usual, but when approaching the level of the previous relapse, slow down the rate of reduction (average dose 0.02 mg/kg/week).
Recommendation strength level C (confidence level –1).
3,1,1,3 Treatment of MCD for steroid addiction.
With the development of two or more relapses of stable proteinuria more than 300 mg/day or nephrotic syndrome that occurs during a reduction in the dose of prednisolone or within two weeks after its discontinuation (steroid dependence), it is recommended to add second-line immunosuppressive therapy to prednisolone therapy or prescribe it as monotherapy (see section 3,1,1,7).
Recommendation strength level C (confidence level –2).
3,1,1,4 Treatment of MCD for relapses of MCD.
Relapse in MCD is the development of nephrotic syndrome or isolated proteinuria more than 300 mg/day. After a previously achieved complete remission.
3,1,1,4,1 Treatment of MCD with rare relapses.
Rare are relapses that occur once or repeatedly, but not more than once every 12 months after remission lasting at least 1 month.
For rare relapses of nephrotic syndrome, it is recommended to prescribe glucocorticoids as in the onset of MCD (see section 3.1.1.1).
Recommendation strength level C (confidence level –2).
For rare relapses of MCD, manifested by isolated proteinuria of a non-nephrotic level, it is recommended to prescribe nephroprotective therapy (angiotensin converting enzyme inhibitors, angiotensin receptor blockers) without the use of glucocorticoids.
The strength of the recommendation is D (confidence level –2).
Comments. After the onset of remission, subsequently, patients with MCD may develop a relapse, which is defined as the return of proteinuria more than 3.5 g/day with a previously achieved remission. The risk of relapse in adults is less than in children, although according to various sources it ranges from 30 to 80% [40, 44]. Exacerbations can be spontaneous, but are more often provoked by an infectious process. In the latter case, relief of the inflammatory/infectious process can lead to spontaneous remission of MCD. With rare exacerbations, as a rule, the same sensitivity to prednisolone remains as at the onset. Therefore, for rare exacerbations, prednisolone is prescribed according to the same regimen as at the onset of the disease.
3,1,1,4,2 Treatment of MCD with frequent recurrences.
Frequent relapse is the development of 2 or more exacerbations within 6 months or 3 or more exacerbations within 12 months after a previously achieved remission.
With frequent recurrence of NS in MCD, it is recommended to use second-line immunosuppressive therapy (see) as monotherapy or in combination with low doses of glucocorticoids (20-40 mg/day) (see section 3.1,1.7).
Recommendation strength level C (confidence level –2).
Comments. With frequent exacerbations, as with steroid dependence, as a rule, sensitivity to prednisolone remains, but frequent long-term administration in large doses leads to the development of serious side effects, including iatrogenic Cushing's syndrome, steroid diabetes, fluid retention, arterial hypertension, infections, myopathy , osteoporosis with pathological fractures, steroid gastric ulcers, cataracts, skin changes, mental disorders, etc. In cases of steroid dependence, frequent exacerbations, development of steroid toxicity, as well as in the presence of relative contraindications for prescribing prednisolone (severe obesity, decompensated diabetes mellitus, severe osteoporosis, mental disorders) and in case of steroid resistance, MCD therapy is carried out using immunosuppressive therapy (cytostatics and /or biological drugs).
3,1,1,5. Treatment of MCD with steroid resistance.
Steroid resistance in MCD is defined as the absence of remission of nephrotic syndrome when treated with prednisolone at a dose of 1 mg/kg/day for 16 weeks.
In case of true steroid resistance of MCD, the use of second-line immunosuppressive therapy is recommended (see Treatment of MCD with steroid dependence) as monotherapy or in combination with low doses of glucocorticoids (20-40 mg/day) (see section 3.1,1.7).
Recommendation strength level C (confidence level –2).
Comments. Steroid resistance is not typical for MCD; on average, it occurs in 8-20% of cases. In the presence of steroid resistance, it is necessary to re-examine the differential diagnosis of MCD and exclude other causes of nephrotic syndrome, including FSGS.
3,1,1,6 Treatment of MCD with the development of complications of glucocorticoid therapy.
If serious complications of prednisolone therapy develop (severe Cushing's syndrome, steroid diabetes, mental disorders, steroid osteoporosis, steroid ulcer, etc.) until remission of nephrotic syndrome is achieved, it is recommended to gradually reduce the dose of prednisolone to maintenance or until complete withdrawal, with the simultaneous addition of second-line immunosuppressive therapy (see section 3,1,1,7).
Recommendation strength level C (confidence level –2).
3,1,1,7. Second-line immunosuppressive therapy for MCD.
Second-line immunosuppressive therapy for MCD includes calcineurin inhibitors and cyclophosphamide. Second-line immunosuppressive drugs can be prescribed as monotherapy or in combination with low doses of glucocorticoids.
In case of steroid dependence, frequent relapse, steroid resistance, the presence of relative contraindications to prednisolone or the development of steroid toxicity, it is recommended to use calcineurin inhibitors (cyclosporine at an initial dose of 2-2.5 mg/kg/day, not more than 3-5 mg/kg/day , or tacrolimus 0.05 mg/kg/day, divided into two doses) for 1-2 years.
Recommendation strength level C (confidence level –2).
It is recommended to select the dose of calcineurin inhibitors based on monitoring their concentration in the blood. The optimal concentration for cyclosporine in MCD is considered to be at the zero point C0 (12 hours after taking the drug) - 80-125 (150) ng/ml, for tacrolimus - 5 - 10 ng/ml.
Recommendation strength level B (confidence level –1).
It is recommended to monitor the concentration of calcineurin inhibitors in the blood in the first month of treatment once a week, in the 2nd month of treatment - once every 2 weeks, 3 - 6 months - once a month and then once every 2 months.
Recommendation strength level C (confidence level –1).
Comments. The therapeutic concentration of calcineurin inhibitors in the blood is maintained for 1 year, then the previously selected dose is gradually reduced by half over 2-3 months, maintained for another 5-6 months and then again gradually, in order to avoid the development of relapse of the disease, reduced to full cancellations with a total duration of the reduction period of at least a year.
It is recommended to prescribe cyclophosphamide as an alternative to calcineurin inhibitors. Cyclophosphamide is prescribed orally at a dose of 2-2.5 mg/kg/day for 8 weeks.
Recommendation strength level C (confidence level –2).
Repeated administration of cyclophosphamide during relapses is not recommended due to its toxicity.
Recommendation strength level C (confidence level –4).
If there is intolerance/contraindications to corticosteroids, calcineurin inhibitors and cyclophosphamide, it is recommended to consider prescribing mycophenolate mofetil 500–1000 mg twice daily (or equivalent doses of enteric mycophenolate sodium) for 1-2 years.
Comments. Immunosuppressive therapy can be prescribed as a stand-alone treatment or in combination with low doses of prednisolone (10-20 mg/day). Cyclosporine A occupies a special place in the treatment of MCD. According to classical concepts, CsA is a calcineurin inhibitor and reversibly inhibits the proliferation of lymphocytes, primarily T cells. The main target of cyclosporine is CD4+T cells (T helper cells), in which it blocks the synthesis of interleukin-2 (IL-2), necessary for the generation and proliferation of T-cytoxic cells from their precursors. But the effects of CsA are not limited to immunosuppression. CsA acts directly at the level of the podocyte, exerting a direct antiproteinuric effect by stabilizing its actin cytoskeleton through blockade of synaptopodin dephosphorylation. Thus, CsA, in addition to affecting the immune (T- and B-lymphocytes) link in the pathogenesis of primary and secondary glomerulopathies, has unique properties to restore the structure and function of podocytes, which determines its pronounced antiproteinuric effect in NS. CsA has been successfully used in the treatment of podocytopathies, and, in particular, MCD. CsA (in the form of a microemulsion) is prescribed at a dose of 3-5 mg/kg/day in 2 divided doses. The initial dose may be 2-3 mg/kg/day with dose increases every 2 weeks until remission, maximum dose, or toxicity is achieved. CsA has greater interindividual bioavailability when taken orally. However, it is a drug with a low therapeutic index, which means a narrow range between therapeutic and toxic concentrations. This requires individualization and constant dose monitoring based on determining the concentration of the drug in the blood to ensure a therapeutic effect and prevent toxic reactions. The best method for determining the drug profile in the blood is a 12-hour serial assessment of the drug concentration in the blood by constructing a concentration-time curve and assessing the area under the curve (AUC0-12). Traditionally, the zero point C0 (minimum level) is used, which determines the level of CsA in the blood 12 hours after taking the drug. The optimal value at the zero point (C0) can be considered a level of 100-200 ng/ml. When using CsA as a basic therapy for exacerbations, it is prescribed in the above doses in combination with prednisolone at a dose of 0.6 mg/kg/day for a month, preferably in an alternating regimen. Next, the dose of prednisolone is gradually reduced to 0.15 mg/kg/day (no more than 15 mg/day) and maintained for up to 12 months. After the first 12 months, the dose of prednisolone is further reduced to a maintenance dose of 0.10 mg/kg with a total treatment duration of up to 24 months. To maintain remission, it is possible to use CsA alone. However, it seems pathogenetically appropriate to combine CsA with low doses of prednisolone until the end of CsA treatment with a total treatment duration of up to 24 months. In case of relapse of non-nephrotic proteinuria, the dose of CsA can be temporarily increased for 1-2 months. And then gradually reduced again.
Side effects when using CsA are dose-dependent and, at the doses used in nephrological practice, they are usually moderate and reversible. The most common include arterial hypertension, nephrotoxicity, hirsutism, gingival hyperplasia, tremor, hyperlipidemia, hyperglycemia, hyperuricemia, in addition, frequent, but usually mild and transient gastrointestinal disorders, such as anorexia, nausea, vomiting, diarrhea, abdominal discomfort, as well as hyperkalemia and, as with any immunosuppression, infection.
When treated with CSA, remission is usually achieved within 12 weeks of treatment. Due to the high risk of relapse with abrupt withdrawal of CsA, the general rule in the treatment of CA is long-term treatment and gradual dose reduction. There are two possible approaches. At the first, after 3 months of stable remission, the dose is gradually very slowly reduced to the minimum that maintains remission (usually less than 1-2 mg/kg/day) with a total treatment duration of 12-24 months. In the second approach, despite achieving remission, the initial dose of CsA is prescribed for 12 months, then it is gradually (0.5 mg/kg/day at 4-8 week intervals) reduced to the minimum maintenance dose (no more than 2 mg/kg/day) and maintain it until the total duration of the course of therapy is up to 24 months. This duration of treatment, with gradual withdrawal of CsA, increases the likelihood of sustained remission.
To prevent the development of nephrotoxicity when using CsA, it is necessary to monitor blood creatinine levels every 2 weeks for the first 2 months, then once a month for 6 months and then at least once every 2 months. When the concentration of creatinine in the blood increases by more than 30% compared to its basal level (even within the normal range), a reduction in the dose of CsA is required - usually by 1 mg / kg / day. If the dose is reduced by 1 mg/kg/day and after 1-2 weeks the creatinine level remains 30% of the initial level, CsA is temporarily discontinued. When creatinine decreases to a level not exceeding the initial level by 15%, CsA can be resumed at lower doses. Despite the potential nephrotoxicity of CsA, observations of patients treated with CsA for up to 4-7 years indicate that long-term use of the drug in low doses may be safe. However, with a duration of treatment of up to 2 years or more, a repeat nephrobiopsy may be discussed to identify morphological signs of cyclosporine toxicity.
If DSA is ineffective within 6 months in MCD, treatment should be discontinued and the diagnosis reconsidered, possibly with a repeat nephrobiopsy. Widespread use of CsA may be limited due to its high cost. To reduce the dose, and therefore the cost of the drug (up to 37-80%), it is possible to use it together with inhibitors of CYP3A4, the enzyme that metabolizes CsA, in particular, with the antifungal drug ketoconazole. . This tactic has found application in transplantation nephrology. However, it is rarely used in the treatment of glomerulopathies.
Another drug belonging to the group of calcineurin inhibitors is Tacrolimus (TAC), which is a macrolide. The complex of tacrolimus, intracellular binding protein FKBP-12, calcium, calmodulin and calcineurin inhibits the phosphatase activity of calcineurin and suppresses the transcription of interleukin-2 (IL-2) and interferon-β, as well as IL-3, IL-4, IL-5, granulocytes -macrophage colony stimulating factor (GM-CSF), and tumor necrosis factor–? (TNF-?). All this leads to suppression of the early stages of T-lymphocyte activation [194]. Compared to CsA, TAC produces more potent cytokine suppression, and its side effect profile is somewhat different from CsA. However, the most common dose-related side effects include nephrotoxicity, hypertension, hyperkalemia, hyperuricemia, hyperglycemia, tremor, gastrointestinal disorders, and alopecia. TAC, compared to CsA, does not cause hypertrichosis and gingival hyperplasia, is characterized by less nephrotoxicity, but hyperglycemia occurs more often. When taking TAC, constant monitoring of renal function and monitoring of other side effects is necessary; it is advisable to determine the level of the drug in the blood, which significantly increases the cost of treatment. Tacrolimus is prescribed at a dose of 0.1 - 0.2 mcg/kg/day, with a gradual reduction in the dose to a maintenance dose when a clinical effect is obtained. Good results are known from the use of TAC for steroid-dependent and steroid-resistant nephrotic syndrome in children and adults. However, information on the use of TAS in MCD is currently limited.
Another drug widely used for MCD with steroid resistance, steroid dependence, with frequent relapses, as well as with contraindications to prednisolone and still, despite high toxicity, considered the standard in these situations, is cyclophosphamide (CP), which is a cytostatic alkylating action. However, despite the low price, the use of CF is undesirable due to its toxicity, including myelotoxicity, the development of severe and opportunistic infections, hemorrhagic cystitis, the risk of malignant neoplasms, gonadotoxicity, as well as gastrointestinal disorders, and baldness. In addition, when CP is prescribed, its effectiveness against frequent exacerbations and steroid dependence is much higher than with steroid resistance. And those patients who, with steroid resistance, are sensitive to CP, as a rule, are also sensitive to CsA. CP can be administered orally at a dose of 2-2.5 mg/kg/day for 8-12 weeks or intravenously at 500-750 mg/m2/month. Within 6 months. CF, for steroid dependence and for frequent exacerbations, is usually prescribed in combination with small doses of prednisolone, but it is believed that for frequent exacerbations it is highly effective when prescribed independently. The total dose of CP should not exceed 200 mg/kg. In addition, due to the cumulative nature of toxic effects, repeated courses of CP therapy should not be prescribed.
Mycophenolic acid (MPA) preparations (mycophenolate mofetil - MMF, enteric mycophenolate sodium - KR-MN) are also used for MCD. MPA is an inhibitor of the key enzyme in the de novo synthesis of guanosine nucleotides - inosine 5-monophosphate DG, predominantly type II isoform, resulting in selective inhibition of activated T- and B-lymphocytes that do not have other pathways for nucleotide synthesis. MPA does not have a significant effect on other tissues with high proliferative activity (neutrophils, skin, intestines, bone marrow), which have a spare pathway for nucleotide resynthesis. This explains the lower toxicity of MPA compared to CP. Side effects of MPA include gastrointestinal disorders, infections, leukopenia, lymphopenia, hepatotoxicity; with long-term use, the risk of developing malignant neoplasms increases. There is evidence of the effect of MPA drugs in MCD with steroid sensitivity, with frequent exacerbations and with steroid dependence in children and adults, as well as with the ineffectiveness of CP. However, data on the use of MPA drugs in MCD have not been confirmed by large controlled studies. There is an opinion that MPA has a better effect in proliferative forms of glomerulonephritis. It is likely that MPA drugs can be prescribed to patients with MCD with frequent exacerbations and complications of steroid therapy in the presence of possible contraindications for CsA. The initial dose for adults may be 2 g/day for MMF (1440 mg for CR-MN), which is prescribed until complete remission develops, followed by a dose reduction to 1.5 g/day (1080 for CR-MN) for 2 months, and then up to 1 g/day (720 mg for CR-MN). At this dose, if well tolerated, treatment can be continued for up to 2 years. However, when the drug is discontinued after treatment, relapses are described in 68% of cases within 1-2 years.
Rituximab (RTX) is a mouse/human chimeric monoclonal antibody that specifically binds to the CD20 transmembrane antigen located on pre-B lymphocytes and mature B lymphocytes and causes lysis of these cells through complement-dependent and complement-independent mechanisms. When widely used in clinical practice, RTX is safe and well tolerated in most patients. However, infusion reactions (fever, chills, rash, bronchospasm, hypotension) and severe infections due to leukopenia and hypogammaglobulinemia may occur. The areas of application of RTX in immune renal pathology are currently rapidly expanding, in particular, since 2013, ANCA-associated vasculitis has been included in the indications for its use. There are reports of successful single and repeated prescriptions of this drug for MCD with steroid dependence and steroid resistance. There are no uniform regimens for prescribing RTX for MCD. Doses administered ranged between 375 mg/m2 once a week for 4-6 weeks and a single dose of the same dose. The duration of remission, as a rule, corresponded to the duration of B-cell suppression; relapses may develop. It is proposed to use the drug as a steroid-sparing drug for steroid resistance and steroid dependence.
As a theoretical basis for the effect of RTX in MCD, possible mechanisms of influence of B lymphocytes on the activation and regulation of T lymphocytes are discussed, both through the secretion of cytokines (IL-10, TGF-beta, IL-6), and through their direct contact due to expression on the cell surface of molecules that provide costimulatory signals (CD80/86, MHCH, CD40, OX40). One interesting theory suggests that the effect of PTX is not only due to B cell depletion, but also due, at least in part, to the induction of T regulatory cells. In addition, Fornoni et al showed that rituximab, in addition to its effect on B lymphocytes, has a direct effect on podocytes, stabilizing their cytoskeleton, and prevents their apoptosis by interacting with the protein SMPDL-3b (acid sphingomyelinase-like phosphodiesterase 3b) produced by podocytes and regulating acid sphingomyelinase (ASMase) activity). To make an informed decision about prescribing RTX, information obtained from multicenter randomized clinical trials is needed.
Azathioprine (AZA), a derivative of mercaptopurine-6, when involved in metabolic reactions, disrupts the synthesis of nucleic acids, inhibiting the proliferation of cells, especially lymphocytes. In high doses (10 mg/kg) it inhibits bone marrow function, suppresses granulocyte proliferation, and causes leukopenia. Experience with AZA in MCD is small and uncertain, but there is evidence of the effectiveness of AZA in MCD that is resistant to corticosteroids.
3,1,1,8 Treatment of secondary forms of MCD.
With the development of secondary forms of MCD, elimination of the primary cause (drug withdrawal, treatment of the primary disease) can lead to remission of nephrotic syndrome. When treating secondary forms of MCD, treatment regimens for the primary form of MCD can be used.
3,1,1,7 Treatment of edema in MCD.
Treatment of patients with MCD and nephrotic syndrome is recommended to begin from the moment of diagnosis of the latter, even before the morphology of the disease is clarified, and should be aimed at eliminating edema, as well as treating and preventing other manifestations and complications of NS.
Strength of recommendation: C (level of evidence: 2).
Comments. Edema with NS frequencies is resistant to treatment and requires an integrated approach to treatment. It is recommended to limit sodium from food in case of NS to 6-7.5 g of NaCl per day, fluids - up to 1.5 liters per day, with refractory edema and with a decrease in diuresis - a sharp restriction, with the volume of fluid consumed determined by the volume of diuresis, taking into account extrarenal losses , which are about 500 ml/day. In case of NS, the use of loop diuretics with targeted weight loss is recommended. In the absence of emergency indications, no more than 1 kg/day. To avoid the development of hemodynamic disorders. For NS, intravenous administration of diuretics is recommended:
Since the formation of nephrotic edema is, one way or another, associated with sodium retention, their treatment requires, first of all, limiting sodium from food. Sodium must be limited even when using diuretics, as their effect is inversely related to salt intake. Typical sodium intake is about 4-6 g/day. Consumption of Na+ from food in case of NS should be limited to 2.5 - 3 g/day, which corresponds to 6-7.5 g of NaCl per day [Smirnov AV, Kucher AG, Kayukov IG, Yesayan AM. Guide to therapeutic nutrition for patients with chronic kidney disease. SPb. Tver: Triada Publishing House LLC, 2009, 240 p.]. It is recommended to limit liquid to 1.5 liters per day. Sharp fluid restriction is necessary only for refractory edema and decreased diuresis. In this case, the volume of fluid consumed should be determined by the volume of diuresis, taking into account extrarenal losses, which are about 500 ml/day.
For the treatment of generalized nephrotic edema in MCD, loop diuretics (furosemide, bumetanide, torsemide), which inhibit the reabsorption of NaCl in the thick ascending limb of the loop of Henle, are traditionally used. In the absence of emergency indications, the target weight loss when prescribing diuretics should not be more than 1 kg/day. To avoid the development of hemodynamic disturbances due to electrolyte disorders and hypovolemia, and related complications. However, in NS, varying degrees of resistance to diuretics may be observed, since their pharmacodynamics and pharmacokinetics are often altered and, despite high doses of loop diuretics, it is not possible to achieve a negative sodium balance and reduce edema.
In case of NS, intravenous administration of diuretics is preferable. When taken orally, the bioavailability of diuretics, both between different classes and within the same class, as well as for the same drug, can vary significantly. For example, when administered enterally, the absorption of furosemide varies from 10 to 90%, while the absorption of bumetamide and torsemide is much more stable and higher and amounts to 80-100%. In addition, swelling of intestinal tissue during NS may slow down the absorption of the diuretic.
An important factor in reducing the effectiveness of diuretics in NS are hypoalbuminemia and high proteinuria. Due to the low content of albumin in the blood, the binding of furosemide to plasma proteins, which is necessary for its delivery to the peritubular capillaries, decreases; as a result, the metabolic clearance of furosemide in the liver increases and the secretion of its active form into the lumen of the proximal tubule, where it should exert its effect, decreases. In the lumen of the tubule, due to the high protein content in NS, partial inactivation of the diuretic by albumin occurs, the degree of which in NS can reach 1/2 - 2/3 of the diuretic concentration in the lumen of the tubule.
To correct the reduced effectiveness of furosemide in NS, the dose of the drug can be increased. Recommendations for diuretic doses used are empirical in nature and vary depending on the existing degree of diuretic resistance. With normal values of GFR (75 ml/min), a single dose of furosemide for NS when taken orally should not exceed 240 mg, daily - 480 mg, and the maximum bolus dose for intravenous (IV) administration is considered to be 80-120 mg for furosemide or equivalent to this dose for other loop diuretics (2–3 mg bumetanide and 20–50 mg torsemide). To reduce the risk of toxicity, maximum bolus doses of diuretics are usually administered over 20 to 30 minutes. Higher doses have no additional effect, and the likelihood of side effects, which include ototoxicity, electrolyte disturbances and autonomic disturbances - weakness, dizziness, nausea and vomiting, increases significantly.
Loop diuretics have a very short half-life (? 1.5 - 4 hours), which means that with a single administration of the drug over a long period of time, after the end of its action, the diuretic has no effect, and the decrease in circulating volume caused by it during the period of action fluid causes active compensatory reabsorption of sodium in the distal tubule. This so-called “adaptive response of the distal nephron” during periods of inactivity of the diuretic can lead to neutralization of its effect and even to the development of a positive sodium balance. In this regard, to overcome the reabsorption of sodium in the distal tubule in the period after the end of action of loop diuretics, they can be prescribed more than once a day. A daily dose divided into two or three doses, provided that each dose exceeds the therapeutic threshold, gives a better effect than a single daily dose. As a rule, the interval between bolus administrations of adequate doses should correspond to 1-2 half-lives of the diuretic. For furosemide, the half-life is 1.5 hours, for bumetanide - 1 hour, for torasemide - 3-4. In case of renal dysfunction, it can increase to 2.6 hours, 1.6 hours and 4-5 hours, respectively.
Another effective method of combating diuretic resistance is their continuous infusion, which avoids peaks and troughs in concentration and post-diuretic sodium retention, and also allows for the creation of a long-term effective concentration of the diuretic at the site of its action, which leads to an increase in total sodium excretion. In addition, with this method of administration, side effects of large doses of diuretics are less common. After the initial bolus dose of a diuretic (furosemide - 40 mg, bumetanide - 0.5 mg, torsemide 5 mg), it is recommended that if GFR is preserved (75 ml/min), the infusion is started with a dose of 10 mg/h for furosemide, 0.5 mg/h for bumetanide, 5 mg/h for torsemide. In the absence of adequate diuresis, the infusion rate can be increased by first reintroducing a bolus dose of the diuretic. When GFR decreases to 25 - 75 ml/min, the recommended infusion rate is 10-20, 0.5-1 and 5-10 mg/h for furosemide, bumetanide and torsemide, respectively. With GFR< 25 мл/мин – 20-40, 1-2 и 10-20 мг/ч соответственно. При сохранной СКФ (75 мл/мин) рекомендуется в/в введение начальной болюсной дозы фуросемида - 40 мг (буметанида – 1 мг, торасемид 20 мг), затем инфузия фуросемида 10-20 мг/ч (буметанида и торасемида - 1-2 мг/ч и 10-20 мг/ч соответственно). При постоянной инфузии без введения болюсной дозы требуется длительный период, соответствующий четырем периодам полувыведения данного диуретика для достижения его стабильной концентрации .
Another way to overcome the “adaptive response of the distal nephron” is the combined administration of loop diuretics and diuretics acting in the distal tubule, in particular thiazide (hypothiazide - 25-100 mg / day or metolazone 100 mg / day). Thiazide diuretics have a longer half-life and prevent or reduce sodium retention after the loop diuretic wears off, increasing natriuresis during these periods. With long-term use of loop diuretics, sodium not reabsorbed in the loop of Henle in large quantities reaches the distal nephron and over time causes hypertrophy of the cells of the distal tubule and increased sodium reabsorption in this segment. When a loop and thiazide diuretic are combined, the thiazide diuretic is prescribed 1 hour before the loop diuretic to completely block the distal tubule by the onset of action of the loop diuretic.
Another reason for resistance to diuretics may be the use of NSAIDs, which, by reducing the synthesis of prostaglandins, cause vasoconstriction and lead to a decrease in renal perfusion and, diuretic-induced natriuresis and diuresis. In addition, NSAIDs may competitively inhibit the secretion of diuretics in the proximal tubule and, thus, the diuretic concentration in the tubule does not reach the threshold required for its effect.
In severe resistant NS, with a serum albumin level of less than 20 g/l, to temporarily increase intravascular volume and increase the binding of diuretics to albumin, it is possible to administer 20% salt-free albumin (25-50 mg) intravenously, necessarily in combination with maximum doses of furosemide (120 mg). Furosemide can be given as a bolus in the middle or at the end of an albumin infusion, but for best effect with this combination, it is recommended that both drugs be mixed before intravenous administration. The infusion rate of a 20% albumin solution should not exceed 2-3 ml/min. . However, the effect of albumin will only be temporary due to its rapid elimination, and in addition, the administration of 20% albumin in patients with no reduction in intravascular volume can provoke the development of hypertension and pulmonary edema. Because of the risk of these complications and the unproven effectiveness of the method, its routine administration for the treatment of nephrotic syndrome is not recommended and should be reserved only for extremely severe cases of NS complicated by severe hypovolemia due to severe hypoalbuminemia.
The prescription of drugs from the groups of angiotensin-converting enzyme inhibitors (ACE inhibitors) and angiotensin receptor blockers (ARBs) in MCD is recommended only in the presence of prednisone-resistant NS, since in patients with MCD, due to reduced intravascular volume, the combined administration of diuretics and ACE inhibitors may easily lead to the development of clinically significant hypotension and/or azotemia.
If diuretics are ineffective, slow (low-flow) prolonged venovenous ultrafiltration using highly permeable membranes, or hemofiltration, is indicated. These methods are much more effective and safe compared to continuing to increase the dose of the diuretic. In the absence of these methods in the therapeutic arsenal of the nephrology department, it is possible to use intermittent hemodialysis in the dry ultrafiltration mode.
3.2 Surgical treatment.
Not applicable.3.3 Other therapy.
In the case of development of acute kidney injury during MCD, if there are indications for renal replacement therapy, it is recommended that it be carried out in combination with corticosteroids according to the regimen used at the onset of MCD.The strength of the recommendation is D (confidence level –1).
DISEASE OF MINIMUM CHANGE honey.
Minimal change disease is a disease of unknown etiology in children and adolescents that develops when the permeability of the glomerular filtration barrier to protein increases; the only morphological change in the renal corpuscles is the smoothing and fusion of podocyte feet, in the tubular epithelium - lipid vacuoles; manifested by edema, albuminuria, hypercholesterolemia; Kidney function is not actually affected.
Frequency
77% of cases of idiopathic nephrotic syndrome in children (23% of cases in adults).Pathomorphology. Electron microscopy reveals fusion of podocyte foot processes, but this lesion is characteristic of all proteinuric conditions.
Clinical picture
and diagnosticsNephrotic syndrome is typical for patients of all age groups
Hypertension in 10% of children and 35% of adults
Hematuria (rare)
Azotemia develops in 23% of children and 34% of adults.
Treatment
GlucocorticoidsPrednisolone orally 1-1.5 mg/kg/day for 4-6 weeks (children 2 mg/kg/day or 60 mg/m2 for 4 months) or 2-3 mg/kg every other day for 4 weeks followed by a dose reduction over 4 months until complete withdrawal. In case of relapse of the disease, glucocorticoids are re-prescribed.
Cytostatics (with resistance to glucocorticoids and with frequent relapses). It is necessary to take into account the possibility of damage to the gonads (chromosomal abnormalities)
Cyclophosphan 2-3 mg/kg/day for 8 weeks or chlorambucil 0.2 mg/kg/day for 12 weeks in combination with prednisolone (every other day)
If cyclophosphamide is ineffective - cyclosporine 5 mg/kg/day in 2 doses orally.
Forecast
Mortality is low; in 10% of cases, death is due to renal failure.Synonyms
Lipoid nephrosisNephrotic syndrome with damage to the small podocyte feet
See also, , Rapidly progressive nephritic syndrome, Acute nephritic syndrome
ICD
N00.0 Acute nephritic syndrome, minor glomerular disordersDirectory of diseases. 2012 .
See what “MINIMUM CHANGE DISEASE” is in other dictionaries:
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Honey. Diet table No. 7 according to Pevzner Limiting table salt to 4-6 g/day, liquid (the sum of all losses is 300 ml), protein to 0.5-1.0 g/kg/day Excluding spicy, canned, fried foods, strong meats, fish and vegetable broths, alcohol... Directory of diseases
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Spontaneous remissions of nephrotic syndrome due to 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 new-onset nephrotic syndrome, it is recommended:
- prednisolone at a dose of 1 mg/(kg/day) until complete remission is achieved (proteinuria
- within 8 weeks, remission develops in 50% of patients, within 12-16 weeks - in 60-80% of patients. If partial remission occurs (proteinuria 0.3 g/day), treatment of minimal changes in the glomeruli (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 of 0.2-0 every month .4 mg/kg for 48 hours. 20-40% of patients subsequently develop relapses;
- if remission does not occur, then prednisolone is recommended to be given with a constant dose reduction overall for 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, reduce the dose and discontinue prednisolone more quickly. If severe complications of steroid therapy develop, the drug should be promptly discontinued.
Prednisolone is recommended for children. 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.
If there are contraindications to high doses of corticosteroids (for example, diabetes mellitus, cardiovascular pathology, severe dyslipidemia, obliterating atherosclerosis of peripheral vessels, mental disorders, osteoporosis, etc.), treatment of minimal changes in the glomeruli (lipoid nephrosis) begins with cyclophosphamide or chlorobutine, which for 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 beginning of the disease: prednisolone is prescribed at a dose of 1 mg/kg/day) for adults and 60 mg/m2/day for children until remission develops. Then the dose is gradually reduced and switched to taking prednisolone every other day (40 mg/m2 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 severe side effects of glucocorticoids (hypercortisolism), cytostatics are prescribed (reducing the dose of prednisolone). Typically, alkylating cytostatics are used for 12 weeks (shorter period than with other morphological options); Moreover, 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 ongoing relapses, it is not recommended to re-prescribe cytostatics, since their toxic effects accumulate. If there is no pronounced hypercortisolism, corticosteroids are used again: first in the form of pulses with methylprednisolone (10-15 mg/kg intravenously for 3 days in a row), then prednisolone orally until remission develops. This regimen reduces the risk of complications of corticosteroid therapy. If hypercortisolism develops, then after achieving remission with glucocorticoids, cyclosporine is prescribed at an initial dose of 5 mg/kg/day). If remission persists for 6-12 months, the dose of cyclosporine begins to be slowly reduced (by 25% every 2 months) to determine the minimum maintenance dose [usually at least 2.5-3 mg/kg/day]]. In any case, after 2 years of treatment, it is advisable to discontinue cyclosporine due to the risk of nephrotoxicity.
Compared to children, adults respond to glucocorticoids more slowly and in a lower 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 per 1 kg of body weight) doses of glucocorticoids in children.
At the same time, the risk of relapse in adults is lower than in children, which is apparently due to a longer initial treatment period. 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 occurs during the first episode or during relapses, cytostatics are used (for 2-3 months) or cyclosporine A - according to the above scheme. It should be noted that in patients with a morphological diagnosis of MI who do not respond to sufficiently long-term treatment of minimal changes in the glomeruli (lipoid nephrosis) with high doses of prednisolone, focal segmental glomerulosclerosis is sooner or later revealed in repeated biopsies, which requires a special therapeutic approach. Thus, when treating patients with urinary tract problems, the following points 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.
- Continuation of treatment for up to 12-16 weeks causes remission in most patients.
- If there are contraindications to steroid therapy, treatment begins with cytostatics.
- In case of frequently relapsing course or steroid dependence, cytostatics or cyclosporine are used.
