How To Identify 7 Types Of Membranous Proliferative Glomerulonephritis Through Pathological Clues?

Membranoproliferative glomerulonephritis (MPGN) is a primary glomerular disease (PG), and its proliferation may be caused by mitosis of resident cells in the glomerulus or by inflammatory cell infiltration. Although the etiology and pathogenesis are still unclear, most of them are caused by the antigen-antibody reaction of the immune mechanism (caused by immune complexes, complement system, abnormal proteins, or metabolic abnormalities), usually not related to mechanical force and cytokine stimulation.

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For kidney disease, most of the time, the initial diagnosis can be made by biochemical test indicators or composite indicators, such as urine albumin-creatinine ratio (ACR), urine protein-creatinine ratio (ACR), and even some studies have pointed out that the ratio between the two is the ratio of albumin to total protein. The ratio (APR) also has some diagnostic value (Figure 1).

In addition, preliminary judgments can also be made based on symptoms, such as hematuria and proteinuria. Hematuria can be suspected: mesangial proliferative lesions, glomerular capillary-related lesions, warfarin-related nephropathy, renal venous return disorders, etc. The proteinuria can be suspected by quantitative analysis: glomerular, tubular, overflow, or mixed nephropathy.

However, MPGN seems to lack valuable "apparent" judgment markers, and pathological diagnosis is more necessary for the diagnosis of such diseases. It can be said that PG including MPGN, secondary glomerular nephropathy, and other renal diseases can show similar symptoms, but the clinical manifestations are not all closely related to the pathological type, which suggests that doctors should pay close attention to the pathological diagnosis. Pay attention to the clues in the slices.

Diagnosis and pathological classification of MPGN

As the name suggests, the most important pathological change in MPGN is the formation of a "basement membrane-like structure", which can show a double-track sign under a light microscope, and occasionally a subepithelial deposit called "spike process" can be seen. Among them, the double-track-like change is the synthesis of a new basement membrane after long-term and chronic glomerular endothelial cell injury, and the new basement membrane and the original basement membrane coexist. In contrast, for example, in glomerulonephritis after acute infection, bi-track-like changes are absent.

There are 3 types of MPGN, all of which can be caused by primary (idiopathic) or secondary causes, of which type II MPGN has been replaced by a new definition of "dense deposition disease" (DDD).

However, even with the support of pathology, the differential diagnosis of MPGN may be difficult. Based on electron microscopy information alone, MPGN and C3 glomerulonephritis (C3GN) may be confounded by preferential electron microscopy (EM) results for MPGN and immunofluorescence (IF) results for C3GN. In general, type I MPGN and type III MPGN is immune complex-related diseases characterized by subendothelial/subepithelial manifestations after EM analysis.

Deposition sites of immune complexes in MPGN

In practice, it has been found that there are immunoglobulin-negative "type I MPGN" or "type III MPGN", which is actually a category of C3GN, while type II MPGN (now called DDD) is a type of C3GN (Figure 3a). . Therefore, MPGNs were classified as immunoglobulin-positive or negative according to IF, instead of MPGN I and MPGN III to avoid confounding the diagnosis (Fig. 3b). Globulin-negative, C3-positive MPGNs are due to dysregulation of the alternative pathway (AP) and terminal complement complex (TCC).

Diagnosis based on electron microscopy results may lead to overlapping diagnosis of MPGN and C3GN [2]

According to different pathological manifestations, MPGN is divided into the following 7 types:

• Immunoglobulin and complement deposition without clear etiology/extrarenal involvement;

• Immunoglobulin and complement deposition with clear etiology/extrarenal involvement;

• There is complement deposition, and the deposited immunoglobulins are obscured;

• Complement and monoclonal immunoglobulin deposition;

• Complement and immunoglobulin deposits, with well-defined substructures of the deposits;

• Complement deposition only, lack of immunoglobulin deposition;

• Lack of complement and immunoglobulin deposition.

The pathological patterns of type I and type II MPGN (Fig. 5) show that: the increase of mesangial cells and matrix leads to a significant increase in glomerular lobules (1) mesangial cytoplasm invades the membrane; (2) large immune cells Complex deposition; (3) The change of 2+3 makes the basement membrane thicken obviously, but in type I, it is shown as subendothelial discontinuity, and in type II, it forms continuous linear dense deposition, which is DDD.

Pathological patterns of type Ⅰ and type Ⅱ MPGN[4]

The proliferative glomerulonephritis-like lesion is a morphological description term under a light microscope. In addition to clinical manifestations, the diagnosis of MPGN also requires information from electron microscopy and immunofluorescence examination. In the immune complex deposition of MPGN, the deposition of immunoglobulins, monoclonal immunoglobulins, complement and immunoglobulins with well-defined substructure, only complement deposition and lack of immunoglobulin deposition and lack of complement and immunoglobulin deposition for subclassification.

Among them, immunoglobulin deposition can be divided into lack of clear etiology/extrarenal involvement, presence of clear etiology/extrarenal involvement, and obscured deposition of immunoglobulin, while only complement deposition and lack of immunoglobulin deposition can be further divided into C3GN, DDD, and C4 DDD. A refined pathological diagnosis can provide support for the selection of treatment strategies after the etiology and diagnosis are identified.

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