Rapidly Progressing Glomerulonephritis

Rapidly progressing glomerulonephritis is an aggressively occurring lesion of the glomerular apparatus, accompanied by the formation of cellular half-moons in more than half of the renal glomeruli. It is manifested by the clinic of nephritic syndrome: hematuria, proteinuria, oliguria, edema, arterial hypertension. Kidney failure develops within a few days to weeks or months. It is diagnosed according to the results of blood and urine tests, ultrasound of the kidneys, histology of the biopsy. Glucocorticoids, cytostatics, plasmapheresis, hemodialysis, kidney transplantation are used for treatment.

ICD 10

N01.7 Diffuse sickle-shaped glomerulonephritis

Meaning

Rapidly progressing glomerulonephritis (RPGN, subacute, extracapillary glomerulonephritis with half–moons) is a malignant glomerulopathy that leads to a rapid decrease in kidney function. The proportion of RPGN among all forms of glomerulonephritis is 2-10%. It occurs in all age groups, more often in people 20-50 years old. The age and sex distribution correlates with the etiology. The need for timely recognition of rapidly progressing glomerulonephritis is associated with the formation of terminal renal failure and the dependence of patients on dialysis therapy.

Causes

Rapidly progressing glomerulonephritis may have an infectious, autoimmune, tumor etiology. In some cases, primary glomerulonephritis (IgA-nephropathy, mesangiocapillary GN) acquire a rapidly progressive course. Sometimes RPGN develops for no apparent reason (idiopathic variant). The main etiofactors of subacute glomerulopathy are:

1. Infection. Most often, RPGN is a consequence of acute post-streptococcal glomerulonephritis caused by nephritogenic strains of beta-hemolytic streptococcus group A. Observations have been described when rapidly progressing glomerulonephritis was preceded by viral (hepatitis C) and parasitic infections, subacute endocarditis, sepsis.
2. Systemic diseases. In most cases, RPGN manifests against the background of autoimmune pathologies: systemic lupus erythematosus, cryoglobulinemia, systemic vasculitis (hemorrhagic, microscopic polyangiitis, Wegener’s granulomatosis), Goodpasture syndrome.
3. Malignant tumors. In rare cases, rapidly progressing glomerulonephritis is associated with lymphoproliferative diseases: chronic lymphocytic leukemia, lymphoma.

Pathogenesis

The group of rapidly progressing glomerulonephritis is heterogeneous in etiological and morphological terms. A distinctive histological feature of RPGN is the presence in most glomeruli of cellular deposits – half-moons, partially or completely filling the space of the Shumlyansky-Bowman capsule.

They are formed due to damage to the walls of the renal capillaries by immune complexes, antibodies to the glomerular basement membrane (At to GBM), antibodies to the cytoplasm of neurophils (ANCA). Half-moons consist of proliferating epithelium of the parietal leaf capsule, fibrin, macrophages, monocytes. As a result, the number of functioning cells in the glomeruli decreases, glomerular necrosis develops.

Over time, the stage of diffuse edema and inflammatory infiltration is replaced by the process of fibrosis of the half-moons. It involves profibrogenic cytokines, TGF-beta, fibroblasts, fibrinogen. Fibrosis of the half-moons develops, the glomerular membrane thickens, the renal parenchyma scleroses and loses its functionality.

Classification

Based on the mechanisms of damage to the glomerular apparatus (the presence of antibodies) and detectable morphological signs (the type of glow during IF microscopy), the following types of rapidly progressive glomerulonephritis are distinguished in modern nephrology:

• RPGN 1 (anti-GBM-jade). There are At to GBM in the blood serum, the glow of linear antibodies is determined in the kidney biopsy. It is characteristic of isolated glomerulopathy, Goodpasture syndrome. It accounts for about 20% of cases of rapidly progressive glomerulonephritis.
• RPGN 2 (immunocomplex). There are no antibodies in the blood, and an accumulation of granular immune complexes is detected during immunofluorescence. It is diagnosed with post-streptococcal, lupus nephritis, Schenlein-Genoch purpura, cryoglobulinemia. In the structure of malignant glomerulonephritis, it occupies about 25%.
• RPGN 3 (weakly immune). It is distinguished by the presence of neutrophils circulating At to the cytoplasm (c-ANCA and p-ANCA), the absence or slightly pronounced glow in the sample of renal tissue. It develops with microscopic polyangiitis, granulomatous necrotizing vasculitis of Wegener. It accounts for more than half of all forms of rapidly progressive glomerulonephritis.
• RPGN 4 (mixed). It is a combination of types 1 and 3: At to GBM and ANCA are present in the serum, linear luminescence is present in the nephrobioptate.
• RPGN 5 (idiopathic). Antibodies and immune complexes are not detected either in the blood or in the biopsy, there are no collagenosis and glomerular pathologies in the anamnesis.

Symptoms of rapidly progressive glomerulonephritis

Glomerulonephritis with half-moons, as a rule, manifests with acute nephritic syndrome. A few weeks before the debut, many patients suffer from respiratory disease. Peripheral edema appears and rapidly increases – in one week, an increase in body weight can reach 5-10 kg. Ascites may develop already during the first decade, later – hydrothorax and hydropericardium.

A visible admixture of blood in the urine (macrohematuria) is detected. From the first days, the course of RPGN is accompanied by arterial hypertension (AH). In the malignant variant, the blood pressure figures reach 200/110 mm Hg and above, do not decrease when taking antihypertensive drugs. Approximately half of patients with rapidly progressing glomerulonephritis have oliguria.

Along with renal manifestations, systemic changes may occur: hemoptysis with Goodpasture syndrome, hemorrhagic skin rashes with vasculitis, maculopapular rash on the face with SLE, etc.

Complications

With rapidly progressing glomerulonephritis, generalized anasarca edema is detected early, which is fraught with the development of respiratory and cardiac disorders. RPGN associated with systemic vasculitis and SLE may be complicated by DIC syndrome.

Without treatment, 80% of patients develop the final stage of renal dysfunction (uremia) within a year after the onset of the disease, often this happens in a few weeks. Prognostically unfavorable factors are nephrotic syndrome and malignant arterial hypertension: in the first case, the median survival is 10 months, in the second – 1 year 7 months.

Diagnostics

Suspicion of a rapidly progressing form of glomerulonephritis requires immediate initiation of therapy, so the examination should be carried out as soon as possible. It is necessary to clarify the history of infectious, autoimmune diseases. According to the results of the patient’s examination by a nephrologist, the following are prescribed:

1. Ultrasound of the kidneys. According to sonography, the kidneys at the beginning of the disease are of normal size or enlarged, but as sclerotic changes develop, they shrink and decrease. With rapidly progressing glomerulonephritis, this occurs against the background of rapidly increasing renal insufficiency.
2. Blood test. The concentration of creatinine and urea in the blood serum increases rapidly. With nephrotic syndrome, hypoproteinemia, dysproteinemia, hyperlipidemia are detected. It is necessary to control the electrolyte balance, coagulogram.
3. Immunological tests. In various variants of rapidly progressing glomerulonephritis, antibodies to GBM, antistreptolysin-O, cryoglobulins, antineutrophil cytoplasmic antibodies (to myeloperoxidase, proteinase-3), CEC, hypocomplementemia C3 can be detected.
4. Urine test. Characterized by the presence of hematuria, leukocyturia, proteinuria (3.5 g/day), and cylindruria. In Zimnitsky’s sample, hypostenuria is noted, sometimes isostenuria. According to the results of the Rehberg test, a decrease in the glomerular filtration rate is detected.
5. Kidney biopsy. The main method to confirm the diagnosis of rapidly progressing glomerulonephritis is nephrobiopsy. Light microscopy reveals extracapillary half-moons in 50-100% of the glomeruli. The immunofluorescence method makes it possible to clarify the form of RPGN by the presence/absence of immune complexes or immunoglobulins and their characteristic glow.
6. Oculist’s examination. During ophthalmoscopy, changes due to arterial hypertension are detected: stenosis of arterioles, edema of the LV disc, spot hemorrhages. With malignant hypertension, retinal detachment may occur.

Differential diagnosis

In the course of complex diagnostics, it is necessary to exclude conditions that clinically resemble rapidly progressing glomerulonephritis, but have a different etiology and require different therapeutic tactics:

• acute glomerulonephritis (postinfectious, interstitial);
• exacerbation of chronic glomerulonephritis;
• acute tubular necrosis;
• hemolytic-uremic syndrome;
• secondary nephropathies (sclerodermic, antiphospholipid);
• vasorenal AH;
• cholesterol embolism of the intrarenal arteries.

Treatment

Patients with extracapillary GN are hospitalized in the nephrology department. The disease itself is regarded as an urgent clinical situation requiring early intensive therapy. Patients are prescribed a salt-free low-protein therapeutic diet No. 7a with fluid restriction, cooking boiled, steamed, baked dishes. Daily monitoring of diuresis and water balance is carried out. Treatment of rapidly progressive glomerulonephritis provides:

1. Immunosuppressive therapy. Treatment begins with pulse therapy with glucocorticoids until the condition stabilizes. In the future, they switch to taking GCS inside with a gradual decrease in dosage. At the same time, immunosuppressants from the group of alkylating agents, antimetabolites are prescribed.
2. Extracorporeal hemocorrection. In order to eliminate circulating antibodies in rapidly progressing glomerulonephritis of type 1 and 3, plasmapheresis sessions are performed daily for 2 weeks. Cryoaferesis is recommended for RPGN associated with cryoglobulinemia.
3. Antithrombotic therapy. For the prevention of DIC syndrome, transfusion of freshly frozen plasma is carried out, anticoagulants are injected subcutaneously, antiplatelet agents are prescribed.
4. Antihypertensive therapy. ACE inhibitors, calcium channel blockers, beta-blockers are used to stabilize blood pressure independently or in combination with loop diuretics.
5. Renal replacement therapy. In terminal CRF, dialysis therapy is indicated. If kidney function cannot be restored, nephrotransplantation is the method of choice. However, the risk of recurrence of rapidly progressing glomerulonephritis in the graft is quite high.

Prognosis and prevention

Rapidly progressive glomerulonephritis is one of the most severe nephrological diseases. In the absence of pathogenetic treatment, patients die within a few months. A significant part of patients become dialysis-dependent. Factors determining the prognosis are the type of glomerulonephritis, the timing of the start of treatment, creatinine concentration at the time of initiation of therapy. The best prognosis is weakly immune RPGN, the most serious is anti–GBM-glomerulonephritis.

In order to avoid the development of rapidly progressive nephritis, it is necessary to carry out individual prevention of infectious diseases, examination after infections, control and treatment of autoimmune pathologies, and undergo regular medical examinations.