Diagnosis of chronic glomerulonephritis

Clinical diagnosis is based on a typical clinical picture (nephrotic syndrome, proteinuria, hematuria, arterial hypertension), laboratory data allowing to establish the activity of glomerulonephritis and assess the functional state of the kidneys. Only carrying out a histological examination of the kidney tissue allows us to establish a morphological variant of glomerulonephritis. At the same time, it is necessary to evaluate the presence of indications for a kidney biopsy, the results of which may determine the choice of further treatment tactics and the prognosis of the disease.

Indications for kidney biopsy in children with chronic glomerulonephritis

Clinical syndrome or disease		Indications for kidney biopsy
Nephrotic syndrome		SRNS NA in the first year of life Secondary National Assembly
Proteinuria		Persistent proteinuria> 1 g daily Decreased kidney function Suspicion of systemic or familial pathology
Acute nephritic syndrome		Progression of the disease after 6-8 weeks from the manifestation (the increase of proteinuria, persistent arterial hypertension, decreased kidney function)
Chronic Renal Failure		To clarify the nature of kidney damage in order to clarify the prognosis of the disease after replacement therapy (in the initial stage of chronic renal failure and in the absence of diminishing sizes of both kidneys)
BNGN		In all cases
Systemic diseases: vasculitis, lupus nephritis		To clarify the diagnosis Decreased kidney function
Hematuria		Suspicion of hereditary pathology of the kidneys Long-term glomerular hematuria Proteinuria> 1 g daily

The morphological substratum of minimal changes is a disruption of the structure and function of the podocytes, which are detected with EM nephrobiopsy, leading to a loss of charge selectivity of GBM and the emergence of proteinuria. There are no deposits of immunoglobulins in glomeruli. In some patients with NSMY, the process is transformed into FSGS.

Morphological characteristics of FSSS:

• focal changes - sclerosis of individual glomeruli;
• segmental sclerosis - multiple sclerosis sclerosis;
• global sclerosis - complete defeat of the glomerulus.

With EM nephrobioptate, a diffuse loss of "small" processes of podocytes is revealed. Immunofluorescence in 40% of cases reveals the luminescence of segmental IgM in the affected glomeruli. Currently, five morphological variants of FSGS are distinguished (depending on the topical level of glomerular damage): typical (nonspecific), vascular (in the zone of the vascular pedicle), cellular, tubular (tubular side of the glomerulus), collapsing.

A characteristic feature of membranous nephropathy is the diffuse thickening of the walls of the glomerular capillaries, associated with subepithelial deposition of immune complexes, the splitting and doubling of the GBM.

IGNA is immune glomerulopathy, which is characterized by the proliferation of mesangial cells and expansion of mesangium, thickening and splitting (two-contour) of the capillary wall due to the interposition of mesangium in them. With histological examination using EM, 3 morphological types of PGMN are isolated, although until now the interpretation of the morphological features of IGPN remains a subject of discussion.

• Type I MGNH is characterized by normal lamina densa in GBM and the predominant presence of subendothelial deposits of immune complexes.
• II type of IGOS (a disease of "dense" deposits) is represented by dense homogeneous deposits in the GBM.
• In case of III type of MPGN (when silver is colored by ultrathin sections), lamina densa ruptures in GBM are determined and the accumulation of a new membrane-like substance located in layers. More common is the mixed nature of deposits located subendothelial, subepithelial and in mesangium.

MZPGN is characterized by mesangial cell proliferation, mesangium expansion, and the deposition of immune complexes in mesangium and subendothelium. The diagnosis of IgA nephropathy is based on a clinical picture (micro- or macrohematuria, more often during or after ARI), family history and, mainly, morphological examination kidney tissue. The nature and severity of clinico-laboratory manifestations of the disease are only of relative importance for the diagnosis of IgA-nephropathy.

[1], [2], [3], [4], [5]

Laboratory research

The content of IgA in the blood does not have a high diagnostic value, as it is increased in 30-50% of adult patients and only in 8-16% of children. The titer of ASLO in the blood is increased only in a small number of patients. The concentration of C ₃ -fraction of complement in the blood is not reduced. Skin biopsy does not have high specificity and sensitivity for the diagnosis of IgA-nephropathy.

Histological examination of the renal tissue of patients with IgA-nephropathy reveals a predominant fixation of granular deposits of IgA in mesangium of glomerulus (often in combination with IgM deposits and y, often marked by the expansion of mesangium due to hyperproliferation of cells.With EM in 40-50% of children and 15- 40% of adults can detect changes in GBM in the form of subendothelial deposits, the presence of which indicates an unfavorable prognosis of the disease.

In the immunofluorescence study of renal tissue, 5 types of PTCA are distinguished:

• I - linear luminescence of immunoglobulins, no ANCA;
• II - granular luminescence of immunoglobulins, no anti-GBM and ANCA;
• III - there is no glow of immunoglobulins, ANCA +;
• IV - linear glow of anti-GBM, ANCA +;
• V - no anti-GBM and ANCA.

Differential diagnostics

Often, differential diagnosis between acute and chronic forms of glomerulonephritis is difficult. It is important to clarify the period from the onset of the infectious disease to the appearance of clinical manifestations of glomerulonephritis. In acute glomerulonephritis, this period is 2-4 weeks, and with chronic glomerulonephritis may be only a few days or more often do not note the connection with the transferred diseases. The urinary syndrome may be equally pronounced, but a persistent decrease in the relative density of urine below 1015 and a decrease in the filtration function of the kidneys are more characteristic of a chronic process. In addition, acute post-streptococcal glomerulonephritis is characterized by a low concentration of C ₃ -fraction complement in the blood at a normal C ₄ content .

Most often there is a need to conduct differential diagnosis between different morphological variants of chronic glomerulonephritis.

During MPGN in some cases may resemble symptoms IgA-nephropathy, but is usually accompanied by more severe proteinuria and hypertension, characterized by reducing the concentration of C ₃ fraction of complement in blood, often in combination with reduced concentration of C ₄. The diagnosis is confirmed only with nephrobiopsy.

Differential diagnosis with IgA-nephropathy is possible only on the basis of a study of kidney biopsy with the conduct of immunofluorescence study and the identification of predominantly granular deposition of IgA deposits in mesangium.

In addition, differential diagnosis is carried out with diseases occurring with torpid hematuria.

• Hereditary nephritis (Alport syndrome) is manifested by persistent hematuria of varying severity, often in combination with proteinuria. The family character of renal pathology, chronic renal failure in relatives is typical, and neurosensory hearing loss is often noted. The most common type of inheritance is the X-linked dominant, rarely autosomal recessive and autosomal dominant.
• Disease of thin basal membranes. Along with torpid hematuria, often of a family nature, with EM kidney tissue, diffuse uniform thinning of the GBM (<200-250 nm in more than 50% of the glomerular capillaries) is noted. There are no IgA-nephropathy deposits of IgA deposits in mesangium and an expansion of mesangial matrix.
• Nephritis in hemorrhagic vasculitis (Schönlein-Henoch disease), in contrast to IgA-nephropathy, accompanies extrarenal clinical manifestations in the form of symmetrical hemorrhagic rash, mainly on the shins, often in combination with abdominal and articular syndromes. Histopathological changes in nephrobiopsytes in the form of fixed deposits of IgA in the mesangium of the glomeruli are identical with those of IgA-nephropathy. It is often necessary to exclude kidney damage in systemic connective tissue diseases: SLE, nodular periarteritis, microscopic polyangiitis, Wegener syndrome, etc. To clarify the diagnosis, it is necessary to determine the markers of the system pathology in the blood: ANF, antibodies to DNA, ANCA (perinuclear and cytoplasmic), rheumatoid factor, concentration of complement fractions, LE cells, cryoprecipitins in the blood. Investigation of antibodies to GBM and ANCA is carried out to clarify the nature of the PGNS and the rationale for therapy.

The manifestation of lupus nephritis in the clinical picture may be similar to IgA nephropathy, but in the future, as a rule, systemic extrarenal clinical manifestations are added, an increase in antibody titer to DNA and a decrease in the concentration of components of the complement system in the blood, a lupus anticoagulant, antibodies to cardiolipins M and G, less often detect LE-cells.

[6], [7], [8], [9], [10],