How is chronic glomerulonephritis treated?

Objectives of chronic glomerulonephritis treatment

Therapeutic tactics for chronic glomerulonephritis in children include pathogenetic treatment using glucocorticosteroids and, according to indications, immunosuppressants, as well as symptomatic therapy with diuretics, hypotensive drugs, correction of complications of the disease.

In children with congenital or infantile nephrotic syndrome prior to the use of glucocorticoid and immunosuppressive therapy, nephrobiopsy is necessary. Early detection of the causes of congenital and infantile nephrotic syndrome allows to avoid unreasonable appointment of immunosuppressive therapy. If a genetic disorder is suspected in a child with a congenital and infantile nephrotic syndrome, a molecular genetic study is performed to identify possible mutations in the genes involved in the formation of the urinary system, including the coding proteins of the slit diaphragm.

Indications for hospitalization

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

• In CHRNS or a steroid-dependent nephrotic syndrome for the appointment of immunosuppressive therapy for the removal of prednisolone and correction of toxic complications.
• For SRNS in order to conduct nephrobiopsy to establish a morphological variant of chronic glomerulonephritis, as well as to conduct pathogenetic immunosuppressive therapy with individual selection of the dose of the drug.
• With the uncontrolled nature of arterial hypertension, requiring daily monitoring of blood pressure with an individual selection of combined antihypertensive therapy.
• With a decrease in the functional state of the kidneys for differential diagnosis with various options for chronic glomerulonephritis, nephroprotective therapy.
• To monitor the activity of chronic glomerulonephritis and the functional state of the kidneys using immunosuppressive therapy in order to evaluate the effectiveness and safety of treatment.

Non-drug treatment of chronic glomerulonephritis

In the presence of nephritic or nephrotic syndrome patients with chronic glomerulonephritis must comply with bed rest until normalization of blood pressure, disappearance or a significant reduction in edematous syndrome. With the improvement of well-being, lowering of arterial pressure and disappearance of edemas, the regime is gradually expanded.

For the same period of time, the diet is limited by liquid and salt in order to reduce edema and hypertension. The liquid is prescribed for diuresis of the previous day, taking into account extra-renal losses (approximately 500 ml for school-age children). With the normalization of blood pressure and the disappearance of edematous syndrome, gradually increase the intake of salt, starting at 1.0 g / day. Patients with signs of renal insufficiency of acute period are also restricted by the intake of animal protein for a period of no more than 2-4 weeks to reduce azotemia, proteinuria and hyperfiltration.

In the low-symptom flow of chronic glomerulonephritis and in children with a hematuric form of chronic glomerulonephritis, there is usually no need to restrict the regimen and diet. They use a hepatic table (diet No. 5 according to Pevzner).

An agglutinous diet with the exception of products rich in cereal protein gluten (all types of bread, pasta, semolina, oatmeal, millet, wheat cereals, sweets from wheat and rye flour) can be used in patients with IgA-nephropathy only in the presence of antibodies to gliadin-containing antigens dense products). In this case, a pronounced positive effect on the functional state of the kidneys has not been demonstrated.

Drug treatment for chronic glomerulonephritis

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

In children with different morphological variants of chronic glomerulonephritis, especially with SRNS, it is necessary to carry out a syndrome therapy; this is due to the frequent development of edematous syndrome and hypertension. To correct edematous syndrome, furosemide is administered orally, intramuscularly, intravenously at a dose of 1-2 mg / kg 1-2 times per day, if necessary, increase the dose to 3-5 mg / kg. With furosemide refractory edema in children with nephrotic syndrome, an intravenous drop of 20% albumin solution is calculated from the calculation of 0.5-1 g / kg for 30-60 minutes. Spironolactone (veroshpiron) is also administered orally at 1-3 mg / kg (up to 10 mg / kg) 2 times a day in the second half of the day (from 16 to 18 hours). Diuretic effect occurs not earlier than on the 5th-7th day of treatment.

As an antihypertensive therapy in children with arterial hypertension due to chronic glomerulonephritis, ACE inhibitors of a predominantly prolonged action (enalapril inside 5-10 mg per day in 2 doses or others) are prescribed. Widely used blockers of slow calcium channels (nifedipine orally 5 mg 3 times a day, in adolescents it is possible to increase the dose to 20 mg 3 times a day, amlodipine up to 5 mg 1 time per day). As an antihypertensive drug in adolescents with chronic glomerulonephritis, it is possible to use angiotensin II receptor blockers: a cosar (losartan) - 25-50 mg once a day, diovan (valsartan) - 40 to 80 mg once per day. Significantly less often in children with chronic glomerulonephritis, cardioselective beta-blockers are used (atenolol is administered orally up to 12.5-50 mg 1 time per day).

The use of anticoagulants and antiplatelet agents is indicated for the prophylaxis of thromboses for children with chronic glomerulonephritis with severe HC in hypoalbuminemia less than 20-15 g / L, increased platelet count (> 400x10 ⁹ / L) and fibrinogen (> 6 g / L) in the blood. As antiplatelet agents, as a rule, dipyridamole is used internally at a dose of 5-7 mg / kg per day in 3 doses for 2-3 months. Assign heparin under the skin of the abdominal wall from the calculation of 200-250 units / kg per day, divided into 4 introductions, the course - 4-6 weeks. Low molecular weight heparins are also used: fractiparin (subcutaneously once a day for 171 IU / kg or 0.1 ml / 10 kg, course - 3-4 weeks) or fragmin (subcutaneously once a day for 150-200 IU / kg, single dose should not exceed 18 000 ME, the course - 3-4 weeks).

In the manifestation of a nephrotic syndrome [excluding congenital (infantile nephrotic syndrome) and nephrotic syndrome associated with hereditary pathology or genetic syndrome], prednisolone is administered orally at 2 mg / kg per day or at 60 mg / m ² (<80 mg / day) daily in 3-4 doses (2/3 doses in the morning) for 8 weeks; then transferred to an alternating course of taking glucocorticosteroids at a rate of 1.5 mg / kg every other day - 6 weeks; after - 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 CNS manifestations experience recurrence of the disease within the next 6 months after the abolition of glucocorticosteroids, which indicates a high likelihood of development of the CRNS in the next 3 years.

Treatment of a rare recurrent CNS is the administration of prednisone intravenously at a dose of 2 mg / kg per day or 60 mg / m ² (<80 mg / day), 3-4 times daily (2/3 doses in the morning) until the disappearance of proteinuria in 3 consecutive urine tests, then transfer to an alternating course of taking prednisolone at a rate of 1.5 mg / kg every other day for 4 weeks, followed by a gradual dose reduction until complete withdrawal within 2-4 weeks.

Patients with CRNS and SZNS, who in most cases have expressed steroid-toxic complications, when achieving remission with glucocorticosteroids against the background of the alternating course of prednisolone, immunosuppressive drugs are prescribed that contribute to the prolongation of remission of the disease. Subsequently, the dose of prednisolone is gradually reduced to a complete withdrawal within 2-4 weeks. Recommend to strictly regulate the course dose of drugs, which should not exceed the maximum allowable (for chlorbutin - 10-11 mg / kg, for cyclophosphamide - 200 mg / kg). With the increase in these doses, the potential risk of developing long-term complications, especially gonadotoxic ones, sharply increases.

• Chlorbutin is used inward from the calculation of 0.15-0.2 mg / kg per day for 8-10 weeks under the control of a clinical blood test to exclude the cytopenic effect.
• Cyclophosphamide is administered internally 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.
• Cyclosporin A is used internally from the calculation of 5 mg / kg per day in 2 receptions under the control of the concentration of the drug in the blood (target level is 80-160 ng / ml) when switching to alternating reception of prednisolone for 3 months. Then the dose of cyclosporin A is gradually reduced to 2.5 mg / kg per day and I continue therapy up to 9 months (sometimes longer). Cancellation of the drug is carried out gradually, reducing the dose of the drug at 0.1 mg / kg per week.
• Mycophenolate mofetil is used internally from the calculation of 1-2 grams per day in 2 doses for 6 months, with the effectiveness of treatment continue to 12 months. In comparison with other immunosuppressants, the spectrum of toxic side effects of mycophenolate mofetil is the least.
• As a drug of choice in children with CHRNS and SZNS, in whom exacerbations of the nephrotic syndrome are provoked by ARVI, levamisole is used at a dose of 2.5 mg / kg every other day for 6-12 months. The use of this drug can reduce the frequency of relapses and eliminate glucocorticosteroids in about half of patients. When taking levamisole, weekly blood tests are performed. When detecting leukopenia (<2500 in ml), the dose of the drug is halved or the drug is temporarily canceled until the white blood cell count is restored. With relapses of the nephrotic syndrome with the use of 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 both on the functional state of the kidneys, and on the morphological variant of glomerulonephritis, the severity of the tubulo-interstitial and fibroplastic components in the renal tissue. The majority of randomized controlled trials of the effectiveness of various immunosuppressive drugs in SRNS in children were performed with MI and FSSS.

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

The following are often used regimens of pathogenetic therapy of SRNS.

• Cyclophosphane is administered intravenously drip or jet slowly 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).
• Cyclophosphane is administered internally at 2-2.5 mg / kg per day for 12 weeks.
• Cyclosporine A is used internally at 5 mg / kg per day in 2 receptions under the control of the concentration of the drug in the blood (the target level at the point C ₀ is 80-160 ng / ml) for 3 months against the background of alternating reception of prednisolone, then 2.5 mg / kg per day for 9 months or more with a gradual decrease in the dose of 0.1 mg / kg per week until complete withdrawal or a long dose of 2.5 mg / kg per day.
• Mycophenolate mofetil is prescribed internally 1-2 grams per day in 2 doses on the background of an alternating intake of prednisolone for at least 6 months, with the effectiveness of treatment continue to 12-18 months. In order to control possible toxic effects, the starting dose of mycophenolate mofetil in the first 1-2 weeks of therapy should be 2/3 of the total therapeutic dose.

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

Body weight, kg	Starting dose, mg		Total dose, mg		The total dose,
	Morning	Evening	Morning	Evening	Mg / kg daily
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 (progra) is used inside at a dose of 0.1 mg / kg per day against the background of an alternating intake of prednisolone, followed by a possible increase in the dose under control of the concentration of the drug in the blood (the target concentration is 5-10 ng / ml). In SRNS and FSSS, according to the recommendations of evidence-based medicine, the optimal administration of cyclosporin A is either in the form of monotherapy or in combination with an alternating course of oral administration of prednisolone or in combination with pulse therapy with methylprednisolone. Methylprednisolone is administered intravenously dropwise in a 5% solution of glucose for 20-40 minutes (the maximum dose for administration should not exceed 1 g / 1.73 m ² ).

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

A week	Methylpre-pozitolone, 30 mg / kg IV	Prednisolone	Cyclosporin A
1-2	3 times a week	-	-
3-8	1 time in a sneaker	2 mg / kg every other day	6 mg / kg daily
9-29	-	1 mg / kg every other day	3 mg / kg daily
30-54	-	0.5 mg / kg every other day	3 mg / kg daily

In SRNS, combined use of pulse therapy with methylprednisolone and oral administration of prednisolone and cyclophosphamide are also possible.

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

A week	Methylpre-pozitolone at 30 mg / kg IV	Number of Inputs	Prednisolone 2 mg / kg every other day	Cyclophosphamide at 2-2.5 mg / kg per day per os
1-2	In a day (3 times a week)	6th	Do not appoint	-
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	-

With membranous nephropathy with isolated proteinuria (<3 grams per day) without signs of nephrotic syndromes, the functional state of the kidneys is suitable for expectant management with regard to the appointment of immunosuppressive drugs due to the high incidence of spontaneous remission of the disease. In this period, only ACE inhibitors are prescribed.

With membranous nephropathy with nephrotic syndrome or with isolated proteinuria with impaired renal function, it is possible to combine pulse therapy with methylprednisolone with oral administration of prednisolone and chlorambucil according to the following scheme Ponticelli (1992): methylprednisolone intravenously 30 mg / kg 1 time per day 3 days, then prednisolone inside at 0.4 mg / kg per day for 27 days, then chlorambucil orally at 0.2 mg / kg per day for the next month. The course of therapy - 6 months with alternation: the month of glucocorticosteroids (methylprednisolone intravenously and prednisolone per os) and the month of chlorambucil - in total 3 cycles.

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

• Captopril orally within 0.5-1.0 mg / kg daily in 2-3 doses.
• Enalapril is administered orally 5-10 mg per day in 1-2 doses.
• Valsartan (diovan) for 40-80 mg per day for taking.
• Losartan (kozaar) inside on 25-50 mg in сут for reception.

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

With a rapidly progressive course of chronic glomerulonephritis, plasmapheresis is used and a combined pulse therapy with methylprednisolone and cyclophosphamide is given against oral administration of prednisolone at a dose of 1 mg / kg per day for 4-6 weeks, then 1 mg / kg every other day, 6-12 months with the subsequent gradual reduction of the dose until complete cancellation.

In children with a hematuric form of chronic glomerulonephritis (usually MZPGN and IgA-nephropathy), which occurs with proteinuria less than 1 g daily or with isolated hematuria and preserved kidney function, the treatment consists in the long-term use of ACE inhibitors as nephroprotectors.

Patients with IgA-nephropathy with severe proteinuria more than 3 grams per day or with nephrotic syndrome and preserved kidney function use glucocorticosteroids (prednisolone oral at 1-2 mg / kg per day, a maximum of 60 mg per day, for 6-8 weeks, then 1.5 mg / kg every other day with a gradual decrease in dose, the general course is 6 months) in combination with immunosuppressants (cyclophosphamide, mycophenolate mofetil), as well as the use of ACE inhibitors and / or angiotensin II receptor blockers.

With IgA-nephropathy, which takes place with pronounced proteinuria more than 3 grams per day and with a decrease in renal function (GFR <70 ml / min), Reno-protective therapy with ACE inhibitors and polyunsaturated fatty acids - omega-3 inside 1 capsule 2-3 times per day; course - not less than 3 months. Polyunsaturated fatty acids can help slow the decline in GFR by reducing the synthesis of mediators of glomerular damage and platelet aggregation in patients with chronic renal failure without affecting proteinuria.

[1], [2], [3], [4], [5], [6]

Surgical treatment of chronic glomerulonephritis

Tonsillectomy is necessary only if there is a clear connection between exacerbations of chronic tonsillitis or angina with activation of chronic glomerulonephritis, the appearance of macrohematuria, an increase in the level of ASO in the blood in the dynamics of the disease, the presence of pathogenic microflora in a smear from the throat.

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

Indications for consultation of other specialists

With persistent arterial hypertension, it is advisable to consult an ophthalmologist for examination of the fundus to exclude angiopathy of the retinal vessels. In the association of congenital or infantile nephrotic syndrome, SRNS with a number of anomalies in the development of other organs (eye, reproductive system, etc.), a geneticist's consultation is needed to exclude hereditary pathology or genetic syndrome. Consultation of an ENT doctor is necessary in case of suspicion of chronic tonsillitis, adenoiditis for resolving the issue of the nature of the therapy (conservative, surgical). If the child has carious teeth it is necessary to consult a dentist in order to sanitize the oral cavity.

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, which occurs with isolated hematuria in the form of MZPGN, or with SSHC without renal dysfunction and without hypertension, the prognosis is favorable. For chronic glomerulonephritis with SRNS is characterized by a progressive course of the disease with the development of chronic insufficiency for 5-10 years in more than half of the patients.

Factors of unfavorable prognosis MZPGN - pronounced proteinuria, the development of nephrotic syndrome and hypertension.

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

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

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

IgA nephropathy is characterized by a slow progression of the disease: 5 years after the onset of the disease, chronic renal failure develops in 5% of children, 10% in 6%, in 15 - in 11%. Factors that indicate an unfavorable prognosis of the disease are arterial hypertension, pronounced proteinuria, family character of the disease and decreased kidney function in the first manifestations of the disease. Morphological signs of adverse course of IgA-nephropathy include:

• tubulo-interstitial fibrosis;
• glomerulosclerosis;
• hyaline arteriosclerosis;
• cellular semilunium (> 30%).

After kidney transplantation, recurrences of IgA nephropathy occur in 30-60% of adult recipients, with graft loss occurring in more than 15% of patients.

The prognosis of patients with PTCA is determined by the prevalence of the lesion and, first of all, by the number of glomeruli with semilunium. In the presence of half-moon in more than 50% of the glomeruli, the PTCA is rarely susceptible to remission and without special therapy, renal survival does not exceed 6-12 months. If less than 30% of the glomeruli are affected, especially if semiluns are laminated to pre-existing glomerulonephritis, for example, with IgA-nephropathy, impaired kidney function can be restored with timely adequate therapy. With moderate damage (30-50% of glomeruli), the loss of renal function is slower, but without therapy, terminal chronic renal failure develops.

[7], [8], [9], [10],