Rapidly progressive glomerulonephritis

Epidemiology and disease forms

Primary RPGN in children is extremely rare (about 1–2% of cases) and is mostly diagnosed in adolescence. The secondary variant is significantly more common, developing against the background of severe infections, systemic autoimmune, or oncological diseases. In addition, rapidly progressive nephritis often becomes the final stage of Goodpasture syndrome or acute poststreptococcal glomerulonephritis.

The classification is based on an immunopathogenetic principle. According to immunofluorescence, three types are distinguished:

• Anti-GBM type (anti-glomerular basement membrane). Autoantibodies attack type IV collagen of the glomerular basement membrane. A characteristic linear staining pattern is observed in the biopsy specimen. This form is associated with idiopathic RPGN and Goodpasture syndrome.
• Immune complex variant. Occurs due to the deposition of preformed immune complexes in the mesangium and capillary walls (granular staining). Blood levels and activity of the C3 complement component decrease. It accompanies lupus, IgA nephropathy, and Henoch-Schönlein purpura.
• Pauci-immune variant (pauci-immune). Immune deposits are absent, but antineutrophil cytoplasmic antibodies (ANCA) are detected in the serum. This variant is typical for systemic vasculitis.

Pathogenesis and morphology

A common pathomorphological feature of all severe forms is extracapillary proliferation—the proliferation of cells of the parietal layer of Bowman's capsule. Histologically, this appears as the formation of arcuate clusters called "crescents".

The process of their formation takes place in several stages:

1. Any of the three immune mechanisms causes severe glomerular damage.
2. Capillary walls rupture.
3. Plasma proteins and inflammatory cells enter the Bowman's capsule space.
4. A cell-protein infiltrate composed of epithelial cells, macrophages, and fibrin strands is formed.

The cellular "crescent" compresses the capillaries from the outside, leading to their collapse. Macrophages gradually destroy the glomerular capsule, paving the way for fibroblasts from the interstitium. They penetrate inside and begin to actively synthesize extracellular matrix (type I and III collagens). As a result, cellular structures are replaced by fibrous tissues, and the glomerulus undergoes irreversible sclerosis.

Clinical presentation and syndromes

The disease debuts as a classic nephritic syndrome resembling a post-infectious process, but it is distinguished by rapidly progressive renal failure.

Main clinical manifestations:

• Arterial hypertension: usually reaches high values, is persistent, and is extremely difficult to correct with medications.
• Urinary syndrome: non-selective proteinuria, which most often remains at a subnephrotic level but can progress to full-blown nephrotic syndrome.
• Early uremia: manifests as early as the 2nd–3rd week. Pronounced weakness (asthenia), aversion to food, nausea, and vomiting develop. Blood tests record a critical drop in the glomerular filtration rate (GFR), an increase in azotemia, hyperkalemia, and metabolic acidosis. Anemia and secondary hyperparathyroidism join in.

Therapeutic principles and prognosis

Treatment tactics are based on the principle of urgency: it is necessary to start immediately, without waiting for biopsy or immunology data. Delay threatens the irreversible loss of renal parenchyma.

The treatment regimen includes:

1. Initial pulse therapy: intravenous infusion of methylprednisolone (20 mg/kg/day, maximum 1000 mg) for 3 consecutive days, then switching to oral maintenance doses. Pulse therapy is repeated every 3–4 weeks.
2. Addition of cytotoxic drugs: after verifying the diagnosis, cyclophosphamide is added. A pulse regimen (intravenously 15 mg/kg/day) or daily tablet intake (2 mg/kg/day) is used until stable improvement is achieved.
3. Features of the anti-GBM variant: if anti-GBM antibodies are detected, intensive plasmapheresis is strictly included in the treatment complex.

In the terminal stage, patients are transferred to regular hemodialysis and then prepared for kidney transplantation. In general, the prognosis of the disease is severe. A biopsy is always required for an accurate outcome assessment. The most favorable prognosis is for RPGN that developed after acute poststreptococcal nephritis—in this case, there is a chance of achieving remission.

Class and exam questions

What else to study on this topic

• Acute poststreptococcal glomerulonephritis in children
• Goodpasture syndrome and anti-GBM antibodies
• Systemic vasculitis: microscopic polyangiitis and Granulomatosis with polyangiitis
• Methods of renal replacement therapy in pediatrics

Other topics in "Chapter 8. Kidney and Urinary Tract Diseases"

Prepared by WhiteCoat Pro faculty in accordance with the medical school curriculum. For educational purposes only.