| disease | Acute Glomerulonephritis |
| alias | Acute Nephritis, Kidney Disease, Acute Glomerulonephritis |
Acute glomerulonephritis (AGN) is commonly referred to as acute nephritis. Broadly speaking, it refers to a group of glomerular diseases with diverse etiologies and pathogenic mechanisms, but clinically presenting as an acute onset characterized by hematuria, proteinuria, edema, hypertension, and a decline in glomerular filtration rate. Hence, it is often termed acute nephritic syndrome. The vast majority of cases clinically fall under acute poststreptococcal glomerulonephritis (APSGN). This condition is the most common kidney disease in children, predominantly affecting those aged 3 to 8 years, and is rare in children under 2 years old. The male-to-female ratio is approximately 2:1.
bubble_chart Etiology
Epidemiological, immunological, and clinical studies have demonstrated that this condition is an immune complex-mediated glomerulonephritis caused by infection with group A β-hemolytic streptococci. The evidence is as follows: ① The onset of nephritis is preceded by a streptococcal infection; ② There is no evidence of direct invasion of the kidneys by streptococci; ③ There is an interval between streptococcal infection and the onset of nephritis, which corresponds to the time required for antibody formation; ④ Antibodies against streptococci and their products, as well as immune complexes, can be detected in the patient's blood; ⑤ There is a decrease in complement components in the blood; ⑥ Deposits of IgG and complement components are found on the glomerular basement membrane.
Among group A β-hemolytic streptococci, type 12 is the predominant strain causing nephritis following respiratory infections, with a few cases attributed to types 1, 3, 4, 6, 26, and 49, and an attack rate of approximately 5%. For nephritis resulting from skin infections, type 49 is the predominant strain, with a few cases caused by types 2, 55, 57, and 60, and an attack rate as high as 25%.
bubble_chart PathogenesisRegarding the mechanism of post-infection-induced nephritis, it is generally believed that the body produces antibodies against certain antigenic components of streptococci (such as the M protein in the cell wall or some antigenic components in the cytoplasm), forming circulating immune complexes that travel through the bloodstream to the kidneys. These complexes deposit on the glomerular basement membrane, subsequently activating complement and causing localized glomerular immunopathological injury, leading to disease. However, other mechanisms have been proposed in recent years. Some suggest that certain cationic antigens from streptococci first implant in the glomerular basement membrane, causing disease through in-situ immune complex formation. Others propose that infection alters the body's normal IgG via enzymatic action, rendering it antigenic and triggering the production of anti-IgG antibodies, indicating that autoimmune mechanisms also contribute to the disease. Additionally, some believe that streptococcal antigens share cross-reactivity with glomerular basement membrane glycoproteins, meaning that a minority of cases may fall under the category of anti-glomerular basement membrane antibody-mediated nephritis.
bubble_chart Pathological Changes
The immune-mediated inflammation of glomerular capillaries narrows or even occludes the capillary lumen and damages the glomerular filtration membrane, leading to manifestations such as hematuria, proteinuria, and cylindruria. It also reduces the glomerular filtration rate, thereby decreasing the excretion of water and various solutes (including nitrogenous metabolites and inorganic salts), resulting in water and sodium retention. This subsequently increases extracellular fluid volume, clinically presenting as edema, oliguria, and systemic circulatory congestion such as dyspnea, hepatomegaly, and elevated venous pressure. The hypertension observed in this condition is currently believed to be caused by increased blood volume. Whether it is related to enhanced activity of the "renin-angiotensin-aldosterone system" remains inconclusive.
The clinical manifestations of this condition vary widely in severity. Mild cases may be "subclinical," meaning there are no specific clinical symptoms apart from abnormal laboratory findings. Severe cases may be complicated by hypertensive encephalopathy, severe circulatory congestion, and acute renal failure.
1. **Preceding Infection and Latent Period** The preceding illness is often an upper respiratory infection caused by streptococci, such as acute purulent tonsillitis, pharyngitis, lymphadenitis, or scarlet fever, or a skin infection, including impetigo or furunculosis. There is an asymptomatic latent period between the preceding infection and the onset of symptoms. For respiratory infections, this period is about 10 days (6–14 days), while for skin infections, it is 20 days (14–28 days).
2. **Clinical Manifestations of Typical Cases** After a preceding streptococcal infection, there is an asymptomatic latent period of 1–3 weeks before acute onset, presenting with **edema**, **hematuria**, **hypertension**, and varying degrees of renal dysfunction.
**Edema** is the most common symptom, caused by reduced glomerular filtration rate and sodium-water retention. Generally, the edema is not very severe, initially affecting only the **eyelids** and face, and is more pronounced in the morning. In severe cases, it may spread throughout the body, with a few patients experiencing pleural or peritoneal effusions. Mild cases may only show weight gain and a sense of limb fullness. Unlike the markedly pitting edema seen in nephrotic syndrome, the edema in acute nephritis is non-pitting.
Half of the children have **gross hematuria**, while microscopic hematuria is seen in almost all cases. Gross hematuria may present as tea-colored, smoky gray, brownish-red, or bright red urine, depending on the urine's pH. Acidic urine appears smoky gray or brownish-red, while neutral or alkaline urine appears bright red or tea-colored. Severe gross hematuria may be accompanied by dysuria or even urinary difficulty. Typically, gross hematuria resolves within 1–2 weeks, turning into microscopic hematuria, though a few cases may persist for 3–4 weeks. It may also recur temporarily due to infection or exertion. Microscopic hematuria usually lasts 1–3 months, with a few cases extending to half a year or longer, but most patients recover completely. Hematuria is often accompanied by varying degrees of **proteinuria**, generally mild to **grade II**, though a few may reach nephrotic levels. Reduced urine output is not uncommon, but true oliguria or anuria is rare.
Along with the above symptoms, children often experience **lack of strength**, **nausea**, **vomiting**, dizziness, and older children may complain of dull lower back pain, while younger ones report **abdominal pain**.
3. **Atypical Clinical Presentations** Several variants exist:
(1) **Asymptomatic subclinical cases** may show no edema, hypertension, or gross hematuria. Only during streptococcal infection outbreaks or routine urine tests in close contacts of acute nephritis patients might microscopic hematuria be detected. Some may even have normal urine tests but show decreased serum complement C3 levels, which recover in 6–8 weeks.
(2) **Extranephritic symptomatic nephritis** presents with edema, hypertension, or even severe circulatory congestion and hypertensive encephalopathy, while urinary abnormalities are minimal or normal on routine tests. These cases show the typical pattern of acute-phase C3 complement reduction, recovering in 6–8 weeks, which aids diagnosis.
(3) Some cases exhibit **severe proteinuria** and **edema**, resembling nephrotic syndrome, with some children even showing **hypoproteinemia** and **hyperlipidemia**, making differentiation from nephrotic syndrome difficult.
bubble_chart Auxiliary Examination
1. Urinalysis Hematuria is an important finding in acute nephritis, either gross hematuria or microscopic hematuria. The red blood cells in the urine are mostly severely deformed red blood cells, but when loop diuretics are used, they may temporarily appear as non-renal deformed red blood cells. Additionally, red blood cell casts may be observed, indicating glomerular hemorrhagic exudative inflammation, which is a key feature of acute nephritis. The urine sediment often shows renal tubular epithelial cells, white blood cells, and a large number of hyaline and granular casts. Urinary protein is usually (+) to (++), mostly non-selective, with increased fibrin degradation products (FDP) in the urine. Routine urinalysis typically returns to normal within 4 to 8 weeks. Residual microscopic hematuria (or abnormal Addis count) or mild proteinuria (which may present as orthostatic proteinuria) can persist for six months or longer.
2. Blood Routine The red blood cell count and hemoglobin may be slightly low due to blood volume expansion and hemodilution. The white blood cell count may be normal or elevated, depending on whether the primary infection site persists. The erythrocyte sedimentation rate (ESR) increases and returns to normal within 2 to 3 months.
3. Blood Chemistry and Renal Function Tests The glomerular filtration rate (GFR) decreases to varying degrees, but renal plasma flow may remain normal, leading to a reduced filtration fraction. Compared to glomerular function impairment, tubular function is relatively preserved, and renal concentrating ability is often maintained. Clinically, transient azotemia is common, with elevated blood urea nitrogen and creatinine. In children without fluid restriction, grade I dilutional hyponatremia may occur. Additionally, patients may have hyperkalemia and metabolic acidosis. Plasma proteins may show grade I decline due to hemodilution, and in cases where proteinuria reaches nephrotic levels, serum albumin decreases significantly, possibly accompanied by a certain degree of hyperlipidemia.
4. Cytological and Serological Tests After the onset of acute nephritis, the positive rate of β-hemolytic streptococcus culture from the throat or skin infection sites is about 30%. Those who receive early penicillin treatment are less likely to test positive. Streptococcal infection can produce corresponding antibodies, which are often used to confirm prior streptococcal infection. For example, anti-streptolysin O antibody (ASO) has a positive rate of 50–80%, usually appearing 2–3 weeks after streptococcal infection, peaking at 3–5 weeks, and returning to normal within six months in 50% of patients. When assessing its clinical significance, it should be noted that elevated titers only indicate recent streptococcal infection and are not directly correlated with the severity of acute nephritis. The positive rate decreases with effective antibiotic treatment and is also lower in patients with skin infections. Other tests include anti-deoxyribonuclease B (anti-DNAse B) and anti-hyaluronidase (anti-HAse). Follow-up tests after 2–3 weeks are recommended; if titers rise, the diagnostic value increases.
5. Blood Complement Measurement Except in rare cases, total blood complement and C3 levels are significantly decreased in the early stages of nephritis and return to normal after 6–8 weeks. This pattern is a typical feature of the condition. The degree of complement reduction does not correlate with the severity of acute nephritis, but if hypocomplementemia persists for more than 8 weeks, other types of nephritis should be considered, such as membranoproliferative nephritis, cryoglobulinemia, or lupus nephritis.
6. Other Tests Some cases may show circulating immune complexes and cryoglobulins during the acute phase. Typically, renal biopsy is unnecessary for classic cases, but it may be required if differentiation from rapidly progressive nephritis is difficult, or if hypertension, persistent hypocomplementemia, or renal dysfunction persists beyond three months.
Typical acute nephritis is not difficult to diagnose. After streptococcal infection, following a 1 to 3-week asymptomatic interval, the appearance of edema, hypertension, hematuria (which may be accompanied by varying degrees of proteinuria), along with dynamic changes in blood complement C3 can confirm the diagnosis.
bubble_chart Treatment Measures
Currently, there is no specific treatment by scientists directly targeting the glomerular immune pestilence process. The main approach is to correct the pathophysiological process (such as water and sodium retention, excessive blood volume) through symptomatic treatment, prevent and manage acute-phase complications, and protect renal function to facilitate natural recovery.
1. Bed rest during the acute phase: Usually, 2–3 weeks are required until gross hematuria disappears, blood pressure normalizes, and edema subsides, after which indoor activity can be gradually increased. For residual grade I proteinuria and hematuria, close follow-up observation is necessary without extending bed rest, but if urinary abnormalities worsen, bed rest should be resumed. Strenuous physical activity should be avoided within 3 months. Activity levels can be gradually increased after stopping bed rest. If no clinical symptoms persist and urine tests are essentially normal after 2 months, half-day schooling can begin, gradually transitioning to full-day attendance.
2. Diet and fluid intake: To prevent further water and sodium retention and severe complications from circulatory overload, the burden on the kidneys must be reduced. During the acute phase, salt, water, and protein intake should be restricted. A salt-free or low-salt diet is recommended for those with edema and high blood pressure. Water intake should be limited for those with severe edema and oliguria. Protein intake should be restricted for those with azotemia. For children, high-quality protein can be used short-term, calculated at 0.5g/kg. Ensure adequate caloric intake through carbohydrates, etc.
3. Treatment of infection sites: For those with persistent throat or skin infections, penicillin or other sensitive antibiotics should be administered for 7–10 days.
4. Use of diuretics: The main pathophysiological changes in acute nephritis are water retention and expanded extracellular fluid volume, so diuretics not only help with diuresis and reducing edema but also aid in preventing complications. Diuretics should be given to those with oliguria, edema, and high blood pressure despite water and salt restriction. If thiazides are ineffective, potent loop diuretics such as furosemide and ethacrynic acid can be used. Mercury diuretics are generally contraindicated.
5. Use of Antihypertensive Drugs For patients whose blood pressure remains high after rest, water and salt restriction, and diuretics, antihypertensive drugs should be administered. In pediatrics, reserpine is still commonly used. The initial dose can be 0.07 mg/kg (maximum 2 mg per dose) orally or intramuscularly, and may be repeated after 12 hours if necessary. After the initial dose, oral administration is generally continued at 0.02–0.03 mg/kg per day, divided into 2–3 doses. Side effects include nasal congestion, fatigue, conjunctival congestion, facial flushing, and bradycardia. Repeated large injections or concurrent use with chlorpromazine should be avoided, as it may occasionally induce Parkinson-like symptoms, such as slurred speech, involuntary tremors, and increased muscle tone. If reserpine is unsatisfactory, hydralazine may be added at 0.1 mg/kg intramuscularly or 0.5 mg/(kg·d) orally in divided doses. Main side effects include headache, tachycardia, and gastrointestinal irritation. For significantly elevated blood pressure requiring rapid reduction, calcium channel blockers such as nifedipine (oral or sublingual) are often used in recent years. Blood pressure begins to drop within 20 minutes, peaks at 1–2 hours, and lasts for 6–8 hours. Alternatively, angiotensin-converting enzyme inhibitors like captopril may be used. For hypertensive encephalopathy requiring emergency blood pressure reduction, the following intravenous drugs may be selected: - **Sodium nitroprusside**: Particularly suitable for patients with pulmonary edema. It acts rapidly, with effects seen within tens of seconds after infusion, but the duration is short. Effects disappear 3–5 minutes after discontinuation, requiring continuous infusion. For children, 5–20 mg may be dissolved in 100 ml of glucose solution, starting at 1 μg/(kg·min), with the infusion rate adjusted based on blood pressure. Note: The infusion rate must be monitored, the solution must be freshly prepared, and the infusion bottle should be wrapped in black paper to avoid light. - **Diazoxide (Hyperstat)**: A rapid-acting vasodilator, administered intravenously at 3–5 mg/kg. If the effect is unsatisfactory, it may be repeated after 30–60 minutes. Maximum antihypertensive effect occurs within 5 minutes and lasts for 8 hours. Side effects include occasional nausea, headache, palpitations, and transient ventricular arrhythmias. Magnesium sulfate, once a commonly used antihypertensive, is now rarely used due to the availability of other effective drugs and the risk of magnesium toxicity in patients with renal insufficiency or oliguria.
6. Treatment of Acute Complications
(1) Treatment of Acute Circulatory Congestion: This condition is primarily caused by water-sodium retention and expanded blood volume. Therefore, the focus of treatment should be on correcting typical edema and sodium retention, restoring blood volume, rather than using cardiotonic drugs like Digitalis. In addition to diuretics, phentolamine or sodium nitroprusside may be added if necessary to reduce cardiac preload and afterload. If the above treatments fail to control the condition, peritoneal dialysis can be performed to promptly and rapidly relieve circulatory overload.
(2) Treatment of Hypertensive Encephalopathy: In addition to controlling blood pressure with potent antihypertensive drugs, symptomatic treatment should be emphasized. For persistent spasm, diazepam 0.3mg/(kg·dose), with a total dose not exceeding 20mg, can be administered intravenously, or other antispasmodic drugs may be used. Diuretics can assist in lowering blood pressure. This condition is often accompanied by cerebral edema, so fast-acting and potent diuretics are recommended.
(3) Acute Renal Failure: Refer to the relevant chapter.
7. Other Treatments Generally, adrenal corticosteroids are not used. For severe oliguria or anuria unresponsive to medical treatment, severe circulatory congestion, or uncontrolled hypertension, dialysis therapy may be employed.
8. Traditional Chinese Medicine Treatment Traditional Chinese Medicine believes that acute nephritis is caused by invasion of wind pathogens, dampness-heat, and sores, affecting the qi transformation functions of the lung, spleen, and kidney meridians. Therefore, the acute phase focuses on expelling pathogens, with treatments aimed at clearing and draining dampness. A possible prescription includes Ephedra 9g, Forsythia 9g, Rice Bean 30g, Tuckahoe Peel 15g, Alisma 10g, Chinese Waxgourd Peel 15–30g, and Lalang Grass Rhizome 15g. Modifications based on symptoms: ① For severe exterior pathogens, add Saposhnikovia Root 10g and Schizonepeta 6g; ② For severe toxic heat, add Honeysuckle Flower 10g and Dandelion 10g; ③ For edema and oliguria, add Plantain Seed 15g; ④ For severe hematuria, add Small Thistle 10g and Unprocessed Rehmannia Root 10g; ⑤ For high blood pressure, add Raw Abalone Shell 15–30g, Skullcap Root 10g, and Chrysanthemum Flower 10g. During the convalescence stage, when only mild urinary abnormalities remain, treatment focuses on regulating the spleen, tonifying the kidney, and clearing residual pathogens. Commonly used prescriptions include modified Jianpi Tang. Example prescription: Poria 10g, Chinese Yam 10g, Glossy Privet Fruit 10g, Platycladus 10g, Eclipta 10g, and Ricepaperplant Pith 3g.
The prognosis of acute nephritis in children is generally favorable. In the 1950s, the reported mortality rate among hospitalized children could be as high as 5% (due to pulmonary edema, hypertensive encephalopathy, acute renal failure, and infections). In recent years, with advancements in diagnosis and treatment, the mortality rate among hospitalized children has decreased to below 0.5%–2.0%, and some cities have eliminated deaths during the acute phase, with renal failure being the primary cause of death. In the vast majority of cases, gross hematuria resolves within 2–4 weeks, diuresis and edema subside, blood pressure gradually normalizes, and residual mild proteinuria and microscopic hematuria typically disappear within 6 months. A small number of cases may persist for 1–3 years, but most of these still recover eventually.
The fundamental prevention is to control streptococcal infections. Daily exercise and attention to skin hygiene should be strengthened to reduce respiratory and skin infections. If an infection occurs, prompt and thorough treatment is necessary. After infection, a urine routine test should be conducted within 2–3 days to promptly detect any abnormalities.
The main complications during the acute phase The severe complications during the acute phase primarily include severe circulatory congestion, hypertensive encephalopathy, and acute renal failure. With the strengthening of prevention and treatment efforts in recent years, their incidence and mortality rates have significantly decreased.
1. Circulatory congestion: Caused by water and sodium retention, leading to increased blood volume and eventually pulmonary edema. The reported incidence varies, depending on the severity of the condition and treatment. In China during the 1950s and 1960s, this complication was observed in 24–27% of hospitalized children with acute nephritis, but recent reports show a decline to 2.4%. It mostly occurs within 1–2 weeks after the onset of acute nephritis. Clinical manifestations include dyspnea, inability to lie flat, chest tightness, cough, moist rales at the lung bases, hepatomegaly with tenderness, and gallop rhythm—symptoms of left and right heart failure due to expanded blood volume, distinct from true myocardial pump failure. In such cases, cardiac output is often increased rather than decreased, circulation time remains normal, the arteriovenous oxygen difference does not widen, and digitalis-based cardiotonics are ineffective, while diuretics often provide relief. A very small number of severe cases may progress to true heart failure, rapidly developing pulmonary edema within hours to 1–2 days, which can be life-threatening.
2. Hypertensive encephalopathy: Refers to a sharp rise in blood pressure (especially diastolic pressure) accompanied by central nervous system symptoms. It is generally more common in children than in adults. This condition is typically attributed to cerebral hypoxia and edema caused by spasms of small resistance vessels in the brain against a backdrop of systemic hypertension. However, some argue that it results from the failure of the brain's inherent autoregulatory mechanisms during acute blood pressure spikes, leading to severe cerebral congestion and edema. Additionally, water and sodium retention in acute nephritis also play a role in its pathogenesis. It often occurs early in the course of acute nephritis, with a sudden onset marked by severe headache, frequent nausea and vomiting, followed by visual disturbances such as blurred vision, diplopia, or transient amaurosis, along with drowsiness or dysphoria. Without timely treatment, convulsions, unconsciousness, or even transient hemiplegia and aphasia may occur, with severe cases leading to brain herniation. Neurological examinations often reveal no focal signs, though superficial and tendon reflexes may weaken or disappear, ankle clonus may be positive, and pathological reflexes may appear. Severe cases may exhibit signs of brain herniation. Funduscopic examination often shows retinal arteriolar spasms and sometimes optic disc edema. Cerebrospinal fluid is clear, with normal or slightly elevated pressure and protein levels. A diagnosis can be made if blood pressure exceeds 18.7/12.0 kPa (140/90 mmHg) and is accompanied by at least one of the following: visual disturbances, convulsions, or unconsciousness.
3. Acute renal failure: A significant proportion of children with acute nephritis experience varying degrees of azotemia during the acute phase, but only a very small number progress to acute renal failure. Effective preventive measures for this complication are lacking, making it a leading cause of death in acute nephritis. Clinical manifestations include oliguria or anuria, elevated blood urea nitrogen and serum creatinine, hyperkalemia, and metabolic acidosis. Oliguria or anuria may persist for 3–5 days or longer, after which urine output increases, symptoms resolve, and renal function gradually recovers (for details, see the chapter on "Acute Renal Failure").
Due to varying severity of symptoms and the fact that multiple disease causes of kidney disorders can manifest as acute nephritis syndrome, differentiation from the following conditions is sometimes necessary:
1. Glomerulonephritis after infection with other pathogens It is known that infections caused by various pathogens can also lead to nephritis, presenting as acute nephritis syndrome. Pathogens that can cause proliferative nephritis include bacteria (e.g., staphylococci, pneumococci), viruses (e.g., influenza virus, EB virus, chickenpox virus, coxsackievirus, mumps virus, ECHO virus, cytomegalovirus, and hepatitis B virus), Mycoplasma pneumoniae, and protozoa. Differentiation can generally be made based on medical history, the primary infection site, and various clinical features.
2. Other primary glomerular diseases
(1) Membranoproliferative glomerulonephritis: The onset resembles acute nephritis, but it is often accompanied by significant proteinuria and persistently low serum complement C3 levels. The chronic course of the disease aids in differentiation, and renal biopsy may be necessary during seasonal epidemics.
(2) Rapidly progressive glomerulonephritis: The onset is similar to acute nephritis, but the condition worsens progressively within three months, with persistent hematuria, hypertension, acute renal failure accompanied by oliguria or anuria, and a high mortality rate.
(3) IgA nephropathy: Typically presents with hematuria within 1–2 days after an upper respiratory tract infection, usually without edema or hypertension. Complement levels are generally normal, and a history of recurrent hematuria episodes may be present. Renal biopsy is required if differentiation is difficult.
(4) Primary nephrotic syndrome with nephritis type: Occasionally, severe proteinuria reaching nephrotic levels may occur during the acute phase of nephritis, making it easily confused with nephritic nephrotic syndrome. Differentiation can be achieved by analyzing medical history, complement testing, or even follow-up observation. Renal biopsy may be necessary in difficult cases.
3. Systemic diseases or certain hereditary disorders Conditions such as lupus, Henoch-Schönlein purpura, hemolytic uremic syndrome, polyarteritis nodosa, Goodpasture syndrome, and Alport syndrome can be differentiated based on their other clinical manifestations.
4. Acute urinary tract infection or pyelonephritis In children, these conditions may also present with hematuria, but they are often accompanied by fever, urinary irritation symptoms, a predominance of white blood cells in the urine, and positive urine bacterial cultures, aiding in differentiation.
5. Acute exacerbation of chronic nephritis This can easily be mistaken for "acute nephritis," but the two have different prognoses, necessitating differentiation. Such cases often involve a prior history of kidney disease, with episodes triggered within 1–2 days of infection, lack of an intermittent period, and frequently include severe anemia, persistent hypertension, renal dysfunction, and sometimes cardiac or fundus changes. B-ultrasound may reveal smaller kidney size.
