How is chronic glomerulonephritis treated?

Treatment goals for chronic glomerulonephritis

Therapeutic tactics for chronic glomerulonephritis in children include pathogenetic treatment using glucocorticosteroids and, if indicated, immunosuppressants, as well as symptomatic therapy using diuretics, antihypertensive agents, and correction of complications of the disease.

In children with congenital or infantile nephrotic syndrome, a nephrobiopsy is required before glucocorticoid and immunosuppressive therapy. Early detection of the causes of congenital and infantile nephrotic syndrome helps avoid unjustified administration of immunosuppressive therapy. If a genetic disease is suspected in a child with congenital and infantile nephrotic syndrome, a molecular genetic study is indicated to identify possible mutations in genes involved in the formation of urinary system organs, including those encoding slit diaphragm proteins.

Indications for hospitalization

In chronic glomerulonephritis in children, hospitalization is advisable in the following cases.

• In case of CRNS or steroid-dependent nephrotic syndrome, for the prescription of immunosuppressive therapy in order to discontinue prednisolone and correct toxic complications.
• In case of SRNS, for the purpose of performing a nephrobiopsy to establish the morphological variant of chronic glomerulonephritis, as well as for pathogenetic immunosuppressive therapy with individual selection of the drug dose.
• In case of uncontrolled arterial hypertension, requiring daily monitoring of blood pressure with individual selection of combined antihypertensive therapy.
• In case of decreased functional state of the kidneys for differential diagnosis with various variants of chronic glomerulonephritis, and nephroprotective therapy.
• To monitor the activity of chronic glomerulonephritis and the functional state of the kidneys when using immunosuppressive therapy in order to assess the effectiveness and safety of treatment.

Non-drug treatment of chronic glomerulonephritis

In the presence of nephritic or nephrotic syndrome, patients with chronic glomerulonephritis should observe bed rest until blood pressure is normalized, edema syndrome disappears or significantly decreases. With improvement in well-being, a decrease in blood pressure, and disappearance of edema, the regime is gradually expanded.

During the same period of time, the diet restricts liquid and table salt in order to reduce edema syndrome and arterial hypertension. Liquid is prescribed according to the diuresis of the previous day, taking into account extrarenal losses (approximately 500 ml for school-age children). With the normalization of blood pressure and the disappearance of edema syndrome, salt intake is gradually increased, starting with 1.0 g / day. In patients with signs of acute renal failure, the intake of animal protein is also limited for a period of no more than 2-4 weeks to reduce azotemia, proteinuria and hyperfiltration.

In the case of low-symptom chronic glomerulonephritis and in children with the hematuric form of chronic glomerulonephritis, there is usually no need to limit the regimen and diet. A liver table is used (diet No. 5 according to Pevzner).

A gluten-free diet with the exclusion of products rich in the cereal protein gluten (all types of bread, pasta, semolina, oatmeal, millet, wheat groats, sweets made from wheat and rye flour) can be used in patients with IgA nephropathy only in the presence of antibodies to antigens of gliadin-containing (densely containing) products. However, a pronounced positive effect on the functional state of the kidneys has not been proven.

Drug treatment of chronic glomerulonephritis

Therapy for chronic glomerulonephritis depends on the characteristics of the clinical course, sensitivity to glucocorticosteroids in the presence of nephrotic syndrome, the morphological variant of the pathology and the degree of renal dysfunction.

In children with various morphological variants of chronic glomerulonephritis, especially with SRNS, it is necessary to conduct syndrome-based therapy; this is due to the frequent development of edema syndrome and arterial hypertension. To correct edema syndrome, furosemide is used orally, intramuscularly, intravenously at a dose of 1-2 mg / kg 1-2 times a day, if necessary, the dose is increased to 3-5 mg / kg. In case of edema refractory to furosemide in children with nephrotic syndrome, a 20% albumin solution is prescribed intravenously by drip at the rate of 0.5-1 g / kg per administration for 30-60 minutes. Spironolactone (Veroshpiron) is also used orally at 1-3 mg / kg (up to 10 mg / kg) 2 times a day in the afternoon (from 4 to 6 p.m.). The diuretic effect occurs no earlier than the 5th-7th day of treatment.

As an antihypertensive therapy in children with arterial hypertension caused by chronic glomerulonephritis, ACE inhibitors are prescribed, mainly prolonged action (enalapril orally 5-10 mg per day in 2 doses, etc.). Slow calcium channel blockers are widely used (nifedipine orally 5 mg 3 times a day, in adolescents the dose can be increased to 20 mg 3 times a day; amlodipine orally up to 5 mg 1 time per day). As antihypertensive agents in adolescents with chronic glomerulonephritis, it is possible to use angiotensin II receptor blockers: cozaar (losartan) - 25-50 mg 1 time per day, diovan (valsartan) - 40-80 mg 1 time per day. Much less frequently, cardioselective beta-blockers (atenolol orally up to 12.5-50 mg once a day) are used in children with chronic glomerulonephritis.

Anticoagulants and antiplatelet agents are indicated for the prevention of thrombosis in children with chronic glomerulonephritis with severe NS with hypoalbuminemia less than 20-15 g/l, elevated platelet levels (>400x10 ⁹ /l) and fibrinogen (>6 g/l) in the blood. As an antiplatelet agent, dipyridamole is usually used orally at a dose of 5-7 mg/kg per day in 3 doses for 2-3 months. Heparin is prescribed under the skin of the abdominal wall at the rate of 200-250 U/kg per day, divided into 4 injections, the course is 4-6 weeks. Low molecular weight heparins are also used: fraxiparin (subcutaneously once a day at 171 IU/kg or 0.1 ml/10 kg, course - 3-4 weeks) or fragmin (subcutaneously once a day at 150-200 IU/kg, a single dose should not exceed 18,000 IU, course - 3-4 weeks).

In case of manifestation of nephrotic syndrome [excluding congenital (infantile nephrotic syndrome) and nephrotic syndrome associated with hereditary pathology or genetic syndrome] prescribe prednisolone orally at 2 mg/kg per day or 60 mg/m2 ⁽ <80 mg/day) daily in 3-4 doses (2/3 of the dose in the morning) for 8 weeks; then switch to an alternating course of glucocorticosteroids at the rate of 1.5 mg/kg every other day for 6 weeks; then - gradual reduction of the dose until complete withdrawal within 1-2 months. With a decrease in the duration of treatment with glucocorticosteroids, most children with manifestation of SNNS experience relapses of the disease in the next 6 months after the withdrawal of glucocorticosteroids, which indicates a high probability of developing SNNS in the next 3 years.

Treatment of rarely recurring SSNS consists of prescribing prednisolone orally at a dose of 2 mg/kg per day or 60 mg/m2 ⁽ <80 mg/day), daily in 3-4 doses (2/3 of the dose in the morning) until proteinuria disappears in 3 consecutive urine tests, then switching to an alternating course of prednisolone at a rate of 1.5 mg/kg every other day for 4 weeks, followed by a gradual reduction in the dose until complete withdrawal within 2-4 weeks.

Patients with CRNS and SNS, who in most cases have pronounced steroid-toxic complications, upon achieving remission using glucocorticosteroids against the background of an alternating course of prednisolone, are prescribed immunosuppressive drugs that help prolong remission of the disease. Subsequently, the dose of prednisolone is gradually reduced until complete withdrawal within 2-4 weeks. It is recommended to strictly regulate the course dose of drugs, which should not exceed the maximum permissible (for chlorbutin - 10-11 mg / kg, for cyclophosphamide - 200 mg / kg). With an increase in these doses, the potential risk of developing remote complications, especially gonadotoxic ones, increases sharply.

• Chlorbutin is used orally at a rate of 0.15-0.2 mg/kg per day for 8-10 weeks under the control of a clinical blood test to exclude a cytopenic effect.
• Cyclophosphamide is administered orally at a dose of 2.5-3 mg/kg per day for 8-10 weeks under the control of the concentration of red blood cells.
• Cyclosporine A is used orally at a rate of 5 mg/kg per day in 2 doses under control of the drug concentration in the blood (target level - 80-160 ng/ml) when switching to alternating prednisolone for 3 months. Then the dose of cyclosporine A is gradually reduced to 2.5 mg/kg per day and therapy is continued for up to 9 months (sometimes longer). The drug is discontinued gradually, reducing the dose of the drug by 0.1 mg/kg per week.
• Mycophenolate mofetil is used orally at a rate of 1-2 g per day in 2 doses for 6 months; if effective, treatment is continued for up to 12 months. Compared with other immunosuppressants, the spectrum of side toxic effects of mycophenolate mofetil is the smallest.
• Levamisole at a dose of 2.5 mg/kg every other day for 6-12 months is used as a drug of choice in children with CHRNS and SZNS, in whom exacerbations of nephrotic syndrome are provoked by ARVI. The use of this drug allows to reduce the frequency of relapses and to cancel glucocorticosteroids in about half of the patients. When taking levamisole, control blood tests are carried out weekly. If leukopenia is detected (< 2500 in ml), the dose of the drug is halved or the drug is temporarily canceled until the leukocyte content in the blood is restored. In case of relapses of nephrotic syndrome against the background of taking levamisole, prednisolone is prescribed according to the usual scheme, levamisole is temporarily canceled and prescribed again when switching to an alternating course of prednisolone.

The choice of immunosuppressive therapy in patients with SRNS depends on both the functional state of the kidneys and the morphological variant of glomerulonephritis, the severity of tubulointerstitial and fibroplastic components in the renal tissue. Most randomized controlled trials of the effectiveness of various immunosuppressive drugs in SRNS in children were conducted in MI and FSGS.

All immunosuppressive drugs used in SRNS are usually prescribed against the background of an alternating course of prednisolone orally at a dose of 1 mg/kg every other day (<60 mg over 48 hours) for 6-12 months with a gradual reduction in the dose until complete withdrawal.

Below are the frequently used regimens of pathogenetic therapy for SRNS.

• Cyclophosphamide is administered intravenously by drip or jet slowly at 10-12 mg/kg once every 2 weeks (repeat twice), then 15 mg/kg once every 3-4 weeks for 6-12 months (total course dose - up to 200 mg/kg).
• Cyclophosphamide is administered orally at 2-2.5 mg/kg per day for 12 weeks.
• Cyclosporine A is used orally at 5 mg/kg per day in 2 doses under the control of the concentration of the drug in the blood (target level at point C ₀ - 80-160 ng/ml) for 3 months against the background of alternating administration of prednisolone, then at 2.5 mg/kg per day for 9 months or more with a gradual reduction in the dose of the drug by 0.1 mg/kg per week until complete withdrawal or a dose of 2.5 mg/kg per day is used for a long time.
• Mycophenolate mofetil is prescribed orally at 1-2 g per day in 2 doses against the background of alternating administration of prednisolone for at least 6 months; if effective, treatment is continued for 12-18 months. In order to control possible toxic manifestations, the starting dose of mycophenolate mofetil in the first 1-2 weeks of therapy should be 2/3 of the full therapeutic dose.

Calculation of starting and therapeutic doses of mycophenolate mofetil for the treatment of chronic glomerulonephritis in children

Patient's body weight, kg	Starting dose, mg		Full dose, mg		Full dose,
	Morning	Evening	Morning	Evening	Mg/kg per day
25-30	250	250	500	250	25-30
30-40	250	250	500	500	25-33
40-45	500	250	750	500	28-31
45-50	500	500	750	750	30-33
50-55	500	500	1000	750	32-35
£55	500	500	1000	1000	<36

• Tacrolimus (Prograf) is administered orally at a dose of 0.1 mg/kg per day against the background of alternating administration of prednisolone with subsequent possible increase in the dose under the control of the drug concentration in the blood (the target concentration is 5-10 ng/ml). In SRNS and FSGS, according to the recommendations of evidence-based medicine, it is optimal to prescribe cyclosporine A both as monotherapy and in combination with an alternating course of oral prednisolone or in combination with pulse therapy with methylprednisolone. Methylprednisolone is administered intravenously by drip in a 5% glucose solution for 20-40 minutes (the maximum dose per administration should not exceed 1 g/1.73 m2 ⁾.

Pulse therapy with methylprednisolone according to the Waldo FB regimen (1998)

Week	Methylprednisolone, 30 mg/kg IV	Prednisolone	Cyclosporine A
1-2	3 times a week	-	-
3-8	1 time per sneaker	2 mg/kg every other day	6 mg/kg per day
9-29	-	1 mg/kg every other day	3 mg/kg per day
30-54	-	0.5 mg/kg every other day	3 mg/kg per day

In SRNS, a combination of methylprednisolone pulse therapy and oral prednisolone and cyclophosphamide may also be used.

Pulse therapy with methylprednisolone according to the scheme of Mendoza SA (1990)

Week	Methylprednisolone 30 mg/kg IV	Number of injections	Prednisolone 2 mg/kg every other day	Cyclophosphamide 2-2.5 mg/kg per day per os
1-2	Every other day (3 times a week)	6	They don't prescribe	-
3-10	1 time per week	8	+	-
11-18	1 time in 2 weeks	4	+	+
19-50	1 raevmes	8	Slow decline	-
51-82	1 time in 2 months	4	Slow decline	-

In membranous nephropathy with isolated proteinuria (<3 g per day) without signs of nephrotic syndrome and impaired renal function, a wait-and-see approach to prescribing immunosuppressive drugs is advisable due to the high incidence of spontaneous remission of the disease. During this period, only ACE inhibitors are prescribed.

In membranous nephropathy with nephrotic syndrome or with isolated proteinuria with impaired renal function, combined use of methylprednisolone pulse therapy with oral prednisolone and chlorambucil is possible according to the following scheme by Ponticelli (1992): methylprednisolone intravenously 30 mg/kg once a day for 3 days, then prednisolone orally 0.4 mg/kg per day for 27 days, then chlorambucil orally 0.2 mg/kg per day for the next month. The course of therapy is 6 months with alternation: a month of glucocorticosteroids (methylprednisolone intravenously and prednisolone per os) and a month of chlorambucil - a total of 3 cycles are carried out.

If immunosuppressive therapy is ineffective in patients with SRNS, ACE inhibitors are prescribed for a long time as monotherapy or in combination with angiotensin II receptor blockers (in older children and adolescents) for nephroprotective purposes.

• Captopril orally 0.5-1.0 mg/kg per day in 2-3 doses.
• Enalapril orally 5-10 mg per day in 1-2 doses.
• Valsartan (Diovan) 40-80 mg per day per dose.
• Losartan (Cozaar) orally 25-50 mg per day per dose.

These drugs help reduce the severity of arterial hypertension and proteinuria even in normotensive patients, reducing the rate of disease progression.

In the case of rapidly progressive chronic glomerulonephritis, plasmapheresis is used and combined pulse therapy with methylprednisolone and cyclophosphamide is prescribed against the background of oral administration of prednisolone at a dose of 1 mg/kg per day for 4-6 weeks, then 1 mg/kg every other day for 6-12 months, followed by a gradual reduction in the dose until complete discontinuation.

In children with the hematuric form of chronic glomerulonephritis (usually this is MsPGN and IgA nephropathy), occurring with proteinuria less than 1 g per day or with isolated hematuria and preserved renal function, treatment consists of long-term (years) use of ACE inhibitors as nephroprotectors.

Patients with IgA nephropathy with severe proteinuria over 3 g per day or nephrotic syndrome and preserved renal function are given glucocorticosteroids (prednisolone orally at 1-2 mg/kg per day, maximum 60 mg per day, for 6-8 weeks, then 1.5 mg/kg every other day with a gradual reduction in dose, total course - 6 months) in combination with immunosuppressants (cyclophosphamide, mycophenolate mofetil), as well as taking ACE inhibitors and/or angiotensin II receptor blockers.

In IgA nephropathy, occurring with pronounced proteinuria of more than 3 g per day and with a decrease in renal function (SCF <70 ml/min), renoprotective therapy is carried out with ACE inhibitors and polyunsaturated fatty acids - omega-3 orally, 1 capsule 2-3 times a day; the course is at least 3 months. Polyunsaturated fatty acids can help slow the decrease in SCF by reducing the synthesis of mediators of glomerular damage and platelet aggregation in patients with chronic renal failure, without affecting proteinuria.

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Surgical treatment of chronic glomerulonephritis

Tonsillectomy is necessary only if there is a clear connection between exacerbations of chronic tonsillitis or sore throats and the activation of chronic glomerulonephritis, the appearance of macrohematuria, an increase in the ASLO titer in the blood during the course of the disease, and the presence of pathogenic microflora in a throat smear.

Tonsillectomy can lead to a decrease in the frequency of macrohematuria episodes, a decrease in the severity of hematuria without a significant effect on the functional state of the kidneys.

Indications for consultation with other specialists

In case of persistent arterial hypertension, it is advisable to consult an ophthalmologist to examine the fundus of the eye in order to exclude retinal vascular angiopathy. In case of association of congenital or infantile nephrotic syndrome, SRNS with a number of developmental anomalies of other organs (eyes, reproductive system, etc.), a consultation with a geneticist is necessary to exclude hereditary pathology or genetic syndrome. Consultation with an ENT specialist is necessary if chronic tonsillitis, adenoiditis is suspected to decide on the nature of the therapy (conservative, surgical). If the child has carious teeth, a consultation with a dentist is necessary for the purpose of oral sanitation.

Forecast

In children with chronic glomerulonephritis, the prognosis depends on the clinical form of the disease, the morphological variant of the pathology, the functional state of the kidneys and the effectiveness of the pathogenetic therapy. In children with chronic glomerulonephritis occurring with isolated hematuria in the form of MsPGN, or with SRNS without renal dysfunction and without arterial hypertension, the prognosis is favorable. Chronic glomerulonephritis with SRNS is characterized by a progressive course of the disease with the development of chronic insufficiency over 5-10 years in more than half of the patients.

Factors of unfavorable prognosis of MZPGN are pronounced proteinuria, development of nephrotic syndrome and arterial hypertension.

The course of MPGN is progressive, approximately 50% of children develop chronic renal failure within 10 years, only 20% of children have normal renal function for 20 years. Relapses of the disease are observed quite often in the transplanted kidney.

The prognosis for membranous glomerulonephritis is relatively favorable; spontaneous remissions are possible (up to 30%).

In patients with FSGS, the average period from the onset of proteinuria to the development of chronic renal failure is 6-8 years. More than 50% of patients with FSGS experience a relapse of the disease within 2 years after kidney transplantation.

Slow progression of the disease is typical for IgA nephropathy: after 5 years from the onset of the disease, chronic renal failure develops in 5% of children, after 10 years - in 6%, after 15 years - in 11%. Factors indicating an unfavorable prognosis of the disease include arterial hypertension, severe proteinuria, familial nature of the disease and decreased renal function at the first manifestations of the disease. Morphological signs of an unfavorable course of IgA nephropathy include:

• tubulointerstitial fibrosis;
• glomerulosclerosis;
• hyaline arteriolosclerosis;
• cellular crescents (>30%).

After kidney transplantation, relapses of IgA nephropathy are observed in 30-60% of adult recipients, with graft loss observed in more than 15% of patients.

The prognosis of patients with RPGN is determined by the extent of the lesion and, first of all, by the number of glomeruli with crescents. If crescents are present in more than 50% of glomeruli, RPGN is rarely subject to remission and without special therapy, renal survival does not exceed 6-12 months. If less than 30% of glomeruli are affected, especially if crescents are superimposed on previously existing glomerulonephritis, for example, with IgA nephropathy, impaired renal function can be restored with timely adequate therapy. With moderate damage (30-50% of glomeruli), the loss of renal function occurs more slowly, but without therapy, terminal chronic renal failure develops.

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