Rapidly progressive glomerulonephritis (RPGN) refers to a group of glomerular diseases that present similarly to acute nephritis but rapidly progress to oliguric or anuric renal failure. This condition can be caused by various diseases, and pathologically, it is characterized by the formation of crescents in most glomerular capsules. Clinically, it follows an acute course and, when secondary to systemic diseases, is often referred to as rapidly progressive nephritic syndrome. The male-to-female ratio of RPGN is 1.5–3.0:1, predominantly affecting young and middle-aged adults. Without dialysis treatment, 80–90% of patients develop irreversible renal failure within six months to one year, leading to a poor prognosis. Therefore, active prevention and treatment are essential.

bubble_chart Etiology

[Disease cause and pathogenesis of disease]

According to different disease causes, it is divided into two major categories: primary and secondary. The causes of primary sexually transmitted diseases are mostly unknown. Some patients have a history of streptococcal or viral infection within one month, while a few have a history of sensitization to subcutaneous node bacillus antigens or close contact with hydrocarbons. Secondary cases are seen in two scenarios: sudden formation of extensive crescents on the basis of certain primary glomerular diseases (such as membranous capillary nephritis, membranous nephropathy, or post-streptococcal nephritis); or secondary to other diseases such as pulmonary hemorrhage-nephritis syndrome (Goodpasture syndrome), systemic lupus erythematosus, allergic purpura nephritis, diffuse vasculitis, cryoglobulinemia, infective endocarditis, and sepsis. According to immunopathological classification, it is divided into three types. Type I, the anti-glomerular basement membrane antibody type, accounts for about 30%. Patients have detectable anti-glomerular basement membrane antibodies in their serum, and immunopathological examination shows diffuse linear deposits of IgG and C3 on the glomerular basement membrane. This type has a high incidence of crescent formation and a poor prognosis. Type II, the immune complex type nephritis, accounts for about 50%. Patients have positive immune complexes in their serum but no anti-glomerular basement membrane antibodies. Immunopathological examination reveals granular deposits of IgG, IgM, and C3 mainly in the glomerular basement membrane and mesangial regions. The prognosis is better than that of Type I. Type III is the non-humoral immune-mediated type, where immunopathological examination shows no immunoglobulin deposits in the glomeruli. The pathogenesis may be related to cellular immunity. This type accounts for about 20% and has a relatively good prognosis. In the above immune-inflammatory responses, the main manifestations are focal coagulation within the glomeruli, fibrin deposition, and fibrinolysis processes. These may be caused by neutrophils, activated complement, or activated factor XII, leading to intraglomerular capillary coagulation and abnormal deposition of fibrinogen in the glomeruli.

Both kidneys are symmetrically enlarged, appearing pale or dark, with possible petechial hemorrhages. The renal cortex is thickened on cross-section, and the medulla shows congestion. The pathological hallmark is diffuse extracapillary nephritis, with light microscopy revealing crescent formation in more than 50% of the glomerular capsules (Figure 5-2-3). In the early stage, the crescents are primarily composed of cells, with more than three layers of crescent cells occupying over 50% of the glomerular capsule surface area. In the late stage [third stage], fibrin and collagen deposits between the cells lead to crescent fibrosis, which continues to grow, compressing the capillary loops, narrowing or blocking the lumens, and causing ischemia and focal necrosis. Glomerular fibrosis or sclerosis develops within weeks. Electron microscopy shows compressed capillary loops, curled or fractured basement membranes, fibrin thrombi, and mesangial matrix proliferation. Immunopathological examination reveals corresponding features for each type. Renal tubular epithelial cells may exhibit degeneration, atrophy, or even focal necrosis. The renal interstitium shows leukocyte infiltration, edema, and fibrosis, and the interstitial vessels may exhibit vasculitic changes.

bubble_chart Clinical Manifestations

Some patients have a history of prodromal infections such as streptococcus or viruses, or exposure to hydrocarbon compounds within the past month. Most cases have an acute onset, though some may initially present with fatigue and loss of appetite. The early symptoms resemble acute nephritis, primarily manifesting as hematuria, proteinuria, and progressive oliguria. Edema gradually worsens, and body weight increases rapidly. After 1-2 weeks of persistent oliguria, patients may develop azotemia and metabolic acidosis, eventually presenting with clinical manifestations of uremia. Patients appear listless, with poor appetite, nausea, vomiting, and general lack of strength. Mild to grade II hypertension may accompany the condition, along with thrombocytopenia and mild to grade II anemia, possibly leading to subcutaneous ecchymosis. Persistent heavy proteinuria and decreased serum albumin may result in nephrotic syndrome. In cases of pulmonary hemorrhage-nephritis syndrome, additional symptoms such as cough, hemoptysis, cyanosis, and chest tightness may occur. Chest X-rays may reveal extensive but variable shadows of interstitial pulmonary inflammation.

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1. The urine changes often present as gross hematuria, with urine sediment microscopy showing a large number of red blood cells, white blood cells, and various casts. Urine protein is usually grade II, with only a few patients having massive proteinuria. The urine specific gravity generally does not decrease. Urinary FDP increases, and its degree correlates with the disease condition.
2. Renal function tests show progressive impairment, manifested by a decline in glomerular filtration rate, persistently elevated serum creatinine and hematuria nitrogen levels, and may be accompanied by impaired tubular reabsorption, secretion, and concentration functions. Metabolic acidosis correlates with the severity of the disease, and various electrolyte disturbances may occur.
3. Immunological tests reveal decreased immune complexes in the moistening and tonifying type, positive immune complexes, often accompanied by cryoglobulinemia. In the anti-membrane type, all complement components are normal, and serum anti-glomerular basement membrane antibodies are positive.
4. Ultrasound and X-ray examinations, including abdominal plain films and B-mode ultrasound, show kidneys of normal size or enlarged, with smooth contours.

bubble_chart Diagnosis

Acute onset, severe and progressive nephritic symptoms, renal failure within weeks to months, absence of prior nephritis or signs of systemic disease, clinically diagnose as rapidly progressive glomerulonephritis. Renal biopsy showing crescents in 50-70% or more of glomeruli confirms the diagnosis.

bubble_chart Treatment Measures

The choice of treatment regimen should be based on the immunological classification. Type I (anti-glomerular basement membrane type) is preferably treated with plasma exchange; Type II (immune complex type) and Type III (non-humoral immune-mediated type) are primarily treated with methylprednisolone pulse therapy.

1. Adrenal glucocorticoids and immunosuppressants inhibit the formation of antibodies and immune complexes, alleviating acute renal inflammatory reactions. Currently, hormone pulse therapy is commonly used, which involves intravenous infusion of methylprednisolone 1g/d dissolved in glucose solution for 3 consecutive days as one course, repeatable for 1–2 courses. Subsequently, oral prednisone 40–60mg/d is administered, along with intravenous cyclophosphamide 100–150mg/d, gradually tapering off after 3–6 months, with a total treatment duration of about 1 year. During medication, in addition to general side effects, special attention should be paid to hypertension and heart failure caused by water and sodium retention due to high-dose hormone therapy.
2. Quadruple therapy combines hormones, immunosuppressants, anticoagulants, and antiplatelet aggregation drugs. Besides anti-inflammatory and immunosuppressive effects, it also inhibits glomerular fibrin deposition and crescent formation, as well as glomerular capillary loop microthrombosis. Early medication can improve pathological changes and renal function. The usage of hormones and immunosuppressants is the same as above; anticoagulants commonly include heparin or warfarin. The dosage of heparin is not standardized, generally 5,000–10,000 units per day intravenously. The initial dose of warfarin is 5–10mg/d, reduced to 2.5mg/d orally after 2–3 days. The above anticoagulants should prolong prothrombin time to twice the normal level. Antiplatelet aggregation drugs include dipyridamole 400–600mg/d, orally or intravenously. The total duration of quadruple therapy varies, generally 3 months to 1 year. Care should be taken to monitor bleeding side effects caused by anticoagulants.
3. Plasma exchange therapy physically separates the patient's plasma from blood cells, removing plasma containing antibodies, immune complexes, complement, and hypercoagulable factors, and replenishing it with healthy plasma and albumin. Exchange 2–4L of plasma daily or every other day, totaling about 10 sessions. Since removal of plasma globulins leads to compensatory increased synthesis of immunoglobulins, prednisone (60mg/d) and cyclophosphamide (3mg/kg·d) should be concurrently administered for 3–6 months.
4. Dialysis therapy and renal transplantation are indicated when glomerular filtration rate drops to 5ml/min during acute renal failure with severe renal damage. Early dialysis is recommended. If renal function does not recover with the above therapies, renal transplantation may be considered after 6 months to 1 year of dialysis. Types II and III have lower recurrence rates post-transplantation compared to Type I.

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bubble_chart Differentiation

The diagnosis should be differentiated from the following diseases:

1. Renal failure caused by other primary glomerular diseases
   1. Acute exacerbation of chronic nephritis often has a long history of kidney disease and hypoalbuminemia, poor urine concentration function, frequent grade II or above anemia, and relatively slow progression of renal failure. Renal ultrasound and X-ray examinations showing symmetrical shrinkage can aid in differentiation.
   2. Diffuse endocapillary proliferative or necrotizing glomerulonephritis may show a small amount (<50%) of crescent formation in renal biopsy, mainly relying on pathological differentiation.
   3. IgA nephropathy and membranoproliferative glomerulonephritis, although without crescent formation, can also progress to renal failure. IgA nephropathy often has a history of recurrent hematuria, while membranoproliferative glomerulonephritis presents as type II nephrotic syndrome, both with a prolonged history of kidney disease. The onset of renal failure often has certain triggers and exhibits systemic manifestations of chronic renal failure such as anemia, hypertension, retinal lesions, and cardiac damage. Renal imaging often shows symmetrical shrinkage.
2. Oliguric renal failure caused by renal interstitial-tubular diseases
   1. Acute tubular necrosis often has clear triggers (renal ischemia, poisoning, incompatible blood transfusion, etc.), with prominent tubular dysfunction, urine specific gravity <1.010, increased urine sodium due to reduced tubular reabsorption (>25 mmol/L), mild hematuria and proteinuria, and the presence of tubular epithelial cells in urine can aid in differentiation.
   2. Acute allergic interstitial nephritis has a history of allergies and allergic manifestations such as fever and rash, often with increased eosinophils in blood and urine. Most cases follow a benign course with a good prognosis, and only a few progress to acute renal failure.
3. Obstructive renal failure: Commonly caused by renal pelvis or ureteral stones, blood clots, etc., leading to urinary tract obstruction. Bladder and prostate diseases can also cause it, often presenting with renal colicky pain, sudden decrease or absence of urine output. Ultrasound and pyelography can confirm the diagnosis.