Membranous nephropathy

Morphological pattern and substrate of changes

The key, fundamental sign of membranous nephropathy that determines its name is diffuse thickening of the glomerular basement membrane (GBM). Histological examination of a renal biopsy reveals no extracapillary proliferation (crescent formation), mesangial cell proliferation, or focal segmental glomerulosclerosis. The primary target and arena of the pathological process is the basement membrane itself.

This structural rearrangement of the membrane does not occur on its own. The substrate for such pronounced changes is the local accumulation of massive immune deposits. Regarding the topography of these deposits, the complexes are located in two main zones of the renal filter:

• Subepithelially — deposits are localized directly beneath the podocyte foot processes, disrupting their normal connection with the membrane.
• Intramembranously — immune complexes become embedded and trapped within the thickness of the glomerular basement membrane itself, causing its reactive thickening.

Pathogenesis of the primary form

From a pathophysiology perspective, the development of this disease is based on an immune-complex mechanism of injury. This is not a cell-mediated, hemodynamic, or isolated complement-dependent process.

In the primary (idiopathic) variant of the pathology, an autoimmune reaction is triggered. The target for the autoantibodies produced is a native, intrinsic glomerular antigen. It has been proven that this specific antigen is phospholipase receptor (transmembrane receptor). This receptor is normally expressed on the surface of podocytes. The binding of circulating antibodies to this receptor in situ leads to the formation of those very subepithelial immune complexes that disrupt the filtration barrier.

Clinical manifestations and specific risks

Disruption of the integrity of the renal filter inevitably leads to urinary protein loss. Therefore, the leading clinical syndrome in membranous nephropathy is the development of nephrotic syndrome (NS). In some cases, the disease may not reach such proportions and may be limited to subnephrotic-range proteinuria.

In addition to protein loss, the clinical picture may include additional symptoms such as microhematuria (hidden blood in the urine) and arterial hypertension.

Special attention should be paid to a specific and extremely dangerous complication of this pathology. Among all known nephropathies, the membranous form is distinguished by the highest risk of thrombosis against the background of ongoing nephrotic syndrome. This requires heightened vigilance from the physician and careful monitoring of the patient's blood coagulation system.

Features of the clinical course in pediatric practice

The clinical course of membranous nephropathy has pronounced age-specific characteristics. Unlike adult patients, the disease in children proceeds much more favorably. Often, a child does not even exhibit the full clinical picture of classical nephrotic syndrome, and renal function remains within normal limits for a long time.

The management tactics for young patients also have their own features. Children are characterized by a high tendency toward complete spontaneous remission. In many clinical cases, this unique feature allows pediatricians and nephrologists to adopt a watchful waiting approach and avoid early prescription of heavy immunosuppressive therapy.

However, the physician must always evaluate predictors of a poor outcome. The risk of disease progression increases if the patient exhibits:

1. Nephrotic syndrome accompanied by massive (heavy) proteinuria;
2. Persistent arterial hypertension;
3. Laboratory-confirmed decline in renal functional capacity.

Important addition: differential diagnosis (test minimum)

For successfully passing test controls and understanding the structure of nephrological morbidity, it is important to remember the context. Although membranous nephropathy occurs in children, it is not the leading cause in this age group.

The most common cause of nephrotic syndrome in pediatric practice is minimal change disease (MCD), rather than membranous nephropathy, focal segmental glomerulosclerosis, or IgA nephropathy.

As initial therapy for relieving the first episode of nephrotic syndrome in minimal change disease, the standard is the administration of glucocorticosteroids. Prednisolone is usually used at a calculated dose of 60 mg/m² of body surface area per day.

Class and exam questions

What else to study on this topic

• Mechanisms of thrombosis in nephrotic syndrome
• Minimal change disease: etiology and pathogenesis
• Structure and functions of renal glomerular podocytes
• Indications for starting immunosuppressive therapy in nephropathies

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.