Pediatric glomerulonephritis

　　1. Etiology

　　This disease has various etiologies. Generally, those with extrarenal manifestations or those with clear primary diseases are called secondary rapidly progressive nephritis, such as secondary to allergic purpura, systemic lupus erythematosus, etc. Occasionally, it may be secondary to certain primary glomerular diseases, such as mesangiocapillary glomerulonephritis and membranous nephropathy. Those with unknown etiology are called primary rapidly progressive nephritis, and this type of disease is the focus of this description.

　　Approximately more than half of the patients with primary rapidly progressive nephritis have a history of upper respiratory tract prodromal infection, among whom a few present with typical streptococcal infection, and other patients present with viral respiratory tract infection. The patients with this disease have serological evidence of Coxsackievirus B5 infection, but the serum titer of influenza and other common respiratory viruses does not show significant increase, so the relationship between this disease and viral infection is still waiting for further observation.

　　In addition, a few patients with rapidly progressive nephritis have a history of tubercle bacillus antigen sensitization (tuberculosis infection history), and this disease occurs during the treatment with rifampicin. Some individual intestinal inflammatory diseases may also be associated with this disease. The classification of various etiologies is as follows:

　　1. Secondary to certain primary glomerular diseases:

　　Such as post-streptococcal nephritis, IgA nephropathy, membranoproliferative glomerulonephritis (especially types I and II), and membranous nephropathy, etc.

　　2. Secondary to multisystem diseases:

　　Such as systemic lupus erythematosus, Goodpasture disease, allergic purpura, necrotizing vasculitis, cryoglobulinemia (type B, type C hepatitis virus-associated cryoglobulinemia), tumor, recurrent polychondritis, Behcet disease (Behcet disease), rheumatoid arthritis, and others.

　　3. Secondary to certain drugs or toxins:

　　Allopurinol, D-penicillamine, rifampicin, hydralazine, and others.

　　4. Idiopathic crescentic glomerulonephritis (this disease):

　　(1) Type I: Anti-glomerular basement membrane antibody type (without pulmonary hemorrhage).

　　(2) Type II: Immune complex type.

　　(3) Type III: Minimal immunoglobulin deposition type (70% to 80% of which are small vessel vasculitis nephritis or ANCA-positive nephritis).

　　5. Membranoproliferative glomerulonephritis:

　　(1) Membranous nephropathy.

　　(2) IgA nephropathy.

　　(3) Secondary glomerular diseases.

　　6. Goodpasture syndrome (pulmonary hemorrhage-nephritis syndrome);

　　7. Post-infectious nephritis:

　　(1) Post-streptococcal nephritis.

　　(2) Post-endocarditis nephritis.

　　(3) Post-sepsis and other infectious nephritis.

　　8. Secondary to other systemic diseases:

　　(1) Purpura nephritis.

　　(2) Lupus nephritis.

　　(3) Polyarteritis nodosa.

　　(4) Wegener's granulomatosis.

　　(5) Scleroderma.

　　(6) Cryoglobulinemia.

　　(7) Other: Certain chemical toxins may also be the cause of rapidly progressive glomerulonephritis (anti-basement membrane antibody type), and may be related to the activation of polyclonal B cells leading to the formation of autoantibodies. There have also been reports of cases induced by antihypertensive drugs such as hydralazine. Immune genetic susceptibility may be related to the disease, with HLA-DR2 found in more than 85% of type I patients; while type II DR2, MT3, and BfF frequencies are increased.

　　Second, pathogenesis

　　Pathology is unknown.

　　1. Circulatory congestion state:Due to water and sodium retention, blood volume exhaustion, and even pulmonary edema. The incidence is reported differently by different studies, and is related to the severity of the disease and the treatment. In China, in the 1950s and 1960s, it was reported that such complications were seen in 24% to 27% of hospitalized children with acute glomerulonephritis. In recent years, the reported incidence has decreased to 2.4%. It usually occurs within 1-2 weeks after the onset of acute glomerulonephritis. Clinical manifestations include shortness of breath, inability to lie flat, chest tightness, cough, moist rales at the base of the lung, liver enlargement with tenderness, galloping rhythm, and symptoms of left and right heart failure. These are caused by expansion of blood volume, and are different from true myocardial pump failure. At this time, the cardiac output is often increased rather than decreased, the circulatory time is normal, the difference in oxygen partial pressure between arteries and veins has not increased, and the efficacy of digitalis-type cardiotonic agents is poor, while the application of diuretics often relieves the symptoms. A very few severe cases may develop into true heart failure, and pulmonary edema may occur rapidly within a few hours to 1-2 days, posing a threat to life.

　　2. Hypertensive encephalopathy:Refers to a sudden and sharp increase in blood pressure (especially diastolic pressure), accompanied by central nervous system symptoms. It is more common in children than in adults. It is generally believed that this condition occurs on the basis of systemic hypertension, caused by spasm of small resistance arteries in the brain, leading to cerebral anoxia and edema; but some people believe that it is due to the loss of control of the automatic contraction and relaxation regulation function of cerebral blood vessels during the sudden increase in blood pressure, leading to severe congestion of cerebral blood vessels and edema. In addition, water and sodium retention during acute glomerulonephritis also plays a certain role in the onset.

　　3. Renal failure:A pathological condition in which partial or complete loss of renal function occurs in the late stage of renal failure. Renal failure can be divided into acute renal failure and chronic renal failure. Acute renal failure has a rapid progression of the disease, and it is usually caused by insufficient renal blood supply (such as trauma or burn), renal dysfunction due to obstruction caused by certain factors, or injury from toxins, leading to the occurrence of acute renal failure. Chronic renal failure is mainly caused by long-term renal lesions, with the gradual decline of renal function over time and the progression of the disease, leading to the occurrence of renal failure.

　　First, primary glomerular disease

　　1. Glomerulonephritis:

　　(1) Acute glomerulonephritis (AGN): It is an acute onset, mostly with previous infection, characterized by hematuria, with varying degrees of proteinuria. There may be edema, hypertension, or renal insufficiency, and the course of the disease is usually within one year. It can be divided into:

　　①Acute post-streptococcal glomerulonephritis (APSGN): There is serological evidence of streptococcal infection, and blood complement levels are low within 6-8 weeks of onset.

　　②Post-streptococcal glomerulonephritis.

　　(2) Acute proliferative glomerulonephritis (RPGN): Onset is acute, with changes in urine (hematuria, proteinuria, cast urine), hypertension, edema, and often persistent anuria or oliguria, progressive renal function decline. If there is a lack of active and effective treatment measures, the prognosis is serious.

　　(3) Persistent glomerulonephritis: Refers to patients with a clear history of acute glomerulonephritis, hematuria and/or proteinuria persisting for more than one year, or without a clear history of acute glomerulonephritis, but hematuria and proteinuria exceeding half a year, without renal insufficiency or hypertension.

　　(4) Chronic glomerulonephritis: Glomerulonephritis with a course of more than one year or with concealed onset, with varying degrees of renal insufficiency or renal hypertension.

　　2. Nephrotic syndrome (NS):

　　(1) It is divided into two types based on clinical manifestations: simple nephrotic syndrome (simple type NS) and nephritic nephrotic syndrome (nephritic type NS).

　　(2) It is divided into:

　　Hormone-sensitive nephritis (steroid-responsive NS): Patients with negative urine protein within 8 weeks of prednisone treatment at full dose.

　　Hormone-resistant nephritis (steroid-resistant NS): Patients with positive urine protein after 8 weeks of prednisone treatment at full dose.

　　Hormone-dependent nephritis (steroid-dependent NS): Sensitive to hormones, but recurrence within 1 month after reduction or discontinuation of medication, and recurrence more than twice.

　　3. Isolated hematuria or proteinuria:

　　(1) Isolated hematuria: Refers to glomerular source hematuria, which is divided into persistent and recurrent.

　　(2) Isolated proteinuria: It is divided into postural and non-postural.

　　Secondary glomerular disease

　　1. Purpura nephritis;

　　2. Lupus nephritis;

　　3. Hepatitis B virus-associated nephritis;

　　4. Other: Toxins, drug poisoning, or other systemic diseases causing nephritis and related nephritis.

　　Three, hereditary glomerular disease

　　1. Congenital nephrotic syndrome:

　　Refers to the onset of the disease within three months of birth, the clinical manifestations are consistent with nephrotic syndrome, and secondary causes can be excluded, (such as TORCH or congenital syphilis infection, etc.). It is divided into:

　　(1) Hereditary: Finnish type, French type (diffuse mesangial sclerosis, DMS).

　　(2) Primary: Refers to primary nephrotic syndrome that occurs in the early stage of life.

　　2. Hereditary progressive nephritis:

　　That is, Alport syndrome.

　　3Family recurrent hematuria.

　　4. Other:

　　Such as alpha-knee syndrome.

　　1. Combine work and rest in daily work. Whether it is physical or mental labor, patients with nephritis should not overwork and should strengthen rest. Otherwise, it will increase abnormal metabolism and increase the burden on kidney function, and even damage the kidneys.

　　2. Pay attention to emotional regulation. Patients with chronic nephritis must establish the confidence to fight against the disease, because the condition of chronic nephritis is slow and prolonged, so it is necessary to maintain the determination and confidence in treatment; temper, worry, and anxiety will cause liver damage, affect the secretion system disorder, and directly damage kidney function.

　　3. Pay attention to diet. Unreasonable diet is more likely to increase the renal burden of patients with chronic nephritis, causing further damage to renal function, leading to the continuous deterioration and progression of the disease. According to the characteristics of chronic nephritis, patients should have a reasonable renal disease diet.

　　4. Sexual life should be regular. For patients with chronic nephritis, sexual life should not be too frequent. Generally, it should not exceed twice a month. If it exceeds, it is easy to lead to recurrence and deterioration of the disease.

　　5. It is forbidden to take anti-inflammatory and analgesic drugs privately, such as cold medicine and antibiotics. It is necessary to take these drugs under the guidance of a relevant physician before taking them, because the improper use of these drugs directly injures the renal function, leading to renal dysfunction.

　　One, Urinalysis

　　In addition to varying degrees of proteinuria, urine sediment can be seen red blood cells, white blood cells, transparent casts, and granular casts, especially red blood cell casts, which are rarely seen in acute tubular necrosis and interstitial nephritis similar to the clinical symptoms of this disease.

　　Two, Blood routine

　　Commonly, there is significant anemia, hemoglobin is often below 90g/L, belonging to normochromic, normocytic anemia. In peripheral blood smears, a few schistocytes are sometimes seen, suggesting a certain degree of hemolysis. There is often mild to moderate thrombocytopenia.

　　Three, Renal function

　　Significant reduction; often low to less than 50% of normal, so blood urea nitrogen and creatinine increase. In patients with acute renal failure and oliguria, hyperkalemia may occur. If the child can continue to eat and drink, hyponatremia is often present. Acidosis is common. Due to the decrease in GFR and the increase in blood phosphorus, and the decrease in blood calcium. If the course is long and hyperparathyroidism has occurred, blood calcium can also be normal, and free calcium is generally normal. In patients with nephrotic syndrome, there are corresponding biochemical changes (i.e., plasma albumin decreases, blood lipids increase).

　　Four, Increased immunoglobulin IgG, IgM

　　Lupus, systemic vasculitis, post-infection glomerulonephritis. Elevated IgE: Churg-Strauss syndrome (CSS). Atypical immunoglobulin (usually IgM): Primary cold agglutinin disease type II.

　　Five, Anti-glomerular basement membrane antibody in blood

　　Positive mainly seen in Goodpasture syndrome, and the concentration of anti-glomerular basement membrane antibodies can also be quantitatively detected by ELISA. Generally, complement C3 is normal, and a decrease is seen in post-streptococcal glomerulonephritis, lupus nephritis, and membranous proliferative glomerulonephritis.

　　Six, Antineutrophil Cytoplasmic Antibody (ANCA)

　　Positive ANCA is seen in ANCA-positive RPGN. ANCA can be divided into C-ANCA and p-ANCA, the former positive mainly seen in Wegener's granulomatosis, and the latter positive mainly seen in microscopic polyarteritis nodosa, so-called idiopathic RPGN, which may be microscopic polyarteritis nodosa.

　　Seven, Pathology and biopsy examination of rapidly progressive glomerulonephritis

　　1, Light microscopy:

　　It is a diffuse lesion. More than 50% of glomeruli have large crescents occupying more than 50% of the glomerular capsule cavity. Initially, the composition of crescents is mainly cellular, that is, cellular crescents. At this time, if treated actively and correctly, the lesion can have a certain degree of recovery; otherwise, it will gradually transform into fibrocellular crescents with the progression of the disease, and finally into fibrous crescents that are difficult to absorb and recover. The glomerular capillary loops often have severe structural damage, and the capillary loops are皱缩于肾小球血管极一侧due to compression by crescents. Sometimes,纤维素样坏死 and microthrombosis can be seen in the capillary loops. In the early stage of the disease, the renal tubules show turbid swelling, granular degeneration, and vacuolar degeneration. There is edema and leukocyte infiltration in the renal interstitium. In the later stage, renal tubular atrophy and renal interstitial fibrosis occur.

　　2, Immunofluorescence:

　　Immunopathology is the main basis for distinguishing the three types of rapidly progressive nephritis. The fine linear deposition of IgG along the glomerular capillary basement membrane is the most characteristic manifestation of anti-GBM nephritis. Almost all glomerular IgG staining is moderate to strong positive, while other immunoglobulins are generally negative. There are reports of IgA anti-GBM nephritis, mainly manifested as linear deposition of IgA along the basement membrane. If the λ chain is also deposited in a linear manner, it suggests a heavy chain deposition disease. This type can see C3 deposited along the basement membrane in a continuous or discontinuous linear or fine granular form, but C3 is only positive in 2/3 of the patients. Sometimes, IgG deposition along the tubular basement membrane can also be seen. In diabetic nephropathy, sometimes IgG deposition along the basement membrane is linear, but the clinical manifestations and microscopic characteristics of the two are easy to distinguish. The IgG deposition in diabetic nephropathy is a non-specific deposition caused by increased vascular permeability, leading to the exudation of plasma proteins (including IgG and albumin), so the former is positive for albumin staining. The immune fluorescence of immune complex type rapidly progressive nephritis is mainly manifested as coarse granular deposition of IgG and C3.

　　Due to the fact that this type can secondary to various immune complex nephritis, the rapidly progressive nephritis secondary to immune complex nephritis also has immune fluorescence manifestations of the primary disease, such as in secondary to IgA nephritis, mainly manifested as mesangial IgA deposition; the rapidly progressive nephritis secondary to post-infection glomerulonephritis is manifested as coarse granular or clumpy deposition; in patients with membranous nephropathy, IgG can be seen along the capillaries in a fine granular form. Membranous nephropathy can be complicated with anti-GBM nephritis, at this time, IgG is deposited in a fine linear form below the fine granular deposition along the basement membrane of the capillaries. As the name implies, the renal immune fluorescence staining of non-immune complex type rapidly progressive nephritis is generally negative or weakly positive. Occasionally, scattered IgM and C3 deposition can be seen. Fibronectin staining can be positive in crescents or thrombi. Some scholars have reported that the less immunoglobulin deposition in crescent glomerulonephritis, the greater the chance of serum ANCA positivity.

　　3, Electron Microscopy:

　　The electron microscopic findings of rapidly progressive glomerulonephritis correspond to those of light microscopy and immunopathology. There is no electron-dense deposit (immunecomplex) in the electron microscopy of anti-GBM nephritis and non-immunecomplex type rapidly progressive glomerulonephritis. Capillary basement membrane and glomerular capsule basement membrane rupture can be seen, accompanied by infiltration of neutrophils and monocytes. While the electron microscopic feature of immunecomplex type rapidly progressive glomerulonephritis is the visible deposition of a large amount of electron-dense immunecomplexes, mainly in the mesangial area.

　　The site of electron-dense deposit in rapidly progressive glomerulonephritis secondary to immune complex nephritis depends on the type of primary glomerulonephritis, and it can be seen in mesangial, subepithelial, or subendothelial areas. Sometimes, there may also be gaps in the basement membrane of the capillaries and glomerular capsules, but they are less common than other subtypes of rapidly progressive glomerulonephritis.

　　8, Imaging Examinations

　　Nuclear renal scans show reduced renal perfusion and filtration; digital subtraction angiography (DSA) can detect non-functional cortical areas. Abdominal X-ray examination can show that the kidneys are enlarged or of normal size with a regular outline, but the junction between the cortex and medulla is unclear. Intravenous pyelography (IVP) shows poor results, but renal arteriography shows normal intravascular diameter, no reduction in blood flow, and even so in systemic vasculitis.

　　9, Kidney Ultrasound Examination

　　It can be found that the kidneys are enlarged or of normal size with a regular outline, but the junction between the cortex and medulla is unclear.

　　1, Energy: Sufficient energy can improve the utilization rate of protein, with a nitrogen-to-calorie ratio of 1:200 being appropriate, and energy supply should be 35kcal/(kg.d).

　　2, Protein: In cases with large protein loss, traditional nutritional therapy advocates a high-protein diet [1.5-2.0g/(kg.d)]. However, clinical practice has proven that when the energy supply is 35kcal/d and the protein supply is 0.8-1.0g/(kg.d)/(kg.d), the synthesis rate of albumin approaches normal, protein degradation decreases, hypoalbuminemia is improved, blood lipids decrease, and a positive nitrogen balance can be achieved. If the energy supply remains unchanged and the protein supply is >1.2g/(kg.d), the synthesis rate of protein decreases, the degradation of albumin increases even more, hypoalbuminemia is not corrected, and urinary protein increases instead. This is because a high-protein diet can cause glomerular hyperfiltration, promoting glomerulosclerosis. A high-protein diet can activate the renin-angiotensin system within the renal tissue, leading to increased blood pressure, increased blood lipids, and further deterioration of renal function.

　　3, Carbohydrates: Should account for 60% of total energy.

　　4, Fat: In cases with coexisting hyperlipidemia and hypoalbuminemia, the hypoalbuminemia should be corrected first; fat should account for ≤30% of total energy, and the intake of cholesterol and saturated fatty acids should be limited, while the intake of unsaturated and monounsaturated fatty acids should be increased.

　　5, Water: Patients with obvious edema should limit their water intake. Water intake = the urine output of the previous day plus 500-800ml.

　　6, Natrium: Generally controlled at 3-5g/d, the amount of water should be adjusted according to the total protein level and blood sodium level in patients with obvious edema.

　　7. Potassium: Timely supplementation of potassium preparations and potassium-rich foods according to blood potassium levels.

　　8. Choose foods rich in vitamin C and vitamin B in moderate amounts.

　　7. Potassium: Timely supplementation of potassium preparations and potassium-rich foods according to blood potassium levels.

　　First, Basic Principles

　　There is no specific drug treatment for this disease, and it is also an autoimmune disease, so basic symptomatic treatment is mainly used, necessary links include preventing water and sodium retention, controlling blood volume, so as to alleviate symptoms, prevent fatal complications (heart failure, hypertensive encephalopathy), protect renal function, and prevent various factors that may worsen the disease, promote the repair of renal pathological tissue and function.

　　Second, Specific Treatment Plan

　　1. General Treatment

　　After the acute onset, bed rest should be taken. The dietary principles are low salt, high vitamin, and high-calorie diet. Protein intake should be maintained at 40-70g/day. Salt intake should be 2-3g/day, and the intake of high-potassium foods should be limited.

　　2. Symptomatic Treatment

　　Diuretics, commonly used thiazide diuretics; antihypertensive drugs, commonly used thiazide diuretics, vasodilators, and in necessary cases, ganglion blockers can be used, or calcium channel blockers can be added; treatment of hyperkalemia, mainly limiting high potassium diet and using potassium-wasting diuretics.

　　3. Treatment of Complications

　　Control heart failure, the focus of treatment should be on correcting water and sodium retention, restoring blood volume, rather than using digitalis drugs to strengthen myocardial contraction, that is, the main measures are diuretic hypotension; hypertensive encephalopathy, can be infused with sodium nitroprusside and other drugs, convulsants can be used for intravenous injection of Valium; uremia.

　　4. Treatment of Infection Focus

　　Currently, it is advocated that antibiotics should be used actively when the focus bacteria culture is positive, and commonly used penicillin or macrolide antibiotics are used to control the focus of infection, which has the effect of preventing the spread of bacteria, for about 2 weeks or until cured. The tonsillectomy has no definite effect on the course of acute glomerulonephritis.

　　5. Anticoagulation and Thrombolysis

　　Urokinase intravenous drip, which can be supplemented with diuretics and potassium.

　　6. Dialysis Treatment

　　Dialysis treatment should be used in the following situations for acute glomerulonephritis: severe water and sodium retention; acute renal failure, oliguria for more than 2 days, with hyperkalemia, acute left heart failure, and severe acidosis.