Diagnosis of chronic glomerulonephritis

The clinical diagnosis is based on the typical clinical picture (nephrotic syndrome, proteinuria, hematuria, arterial hypertension), laboratory test data that allow to establish the activity of glomerulonephritis and assess the functional state of the kidneys. Only a histological examination of the renal tissue allows to establish the morphological variant of glomerulonephritis. In this case, it is necessary to assess 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 renal biopsy in children with chronic glomerulonephritis

Clinical syndrome or disease		Indications for kidney biopsy
Nephrotic syndrome		SRNS NS in the first year of life Secondary NS
Proteinuria		Persistent proteinuria >1 g per day Decrease in kidney function Suspected systemic or familial pathology
Acute nephritic syndrome		Progression of the disease 6-8 weeks after manifestation (increasing proteinuria, persistent arterial hypertension, decreased renal 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 a decrease in the size of both kidneys)
BPGN		In all cases
Systemic diseases: vasculitis, lupus nephritis		To clarify the diagnosis Decrease in kidney function
Hematuria		Suspected hereditary kidney disease Prolonged glomerular hematuria Proteinuria >1 g per day

The morphological substrate of minimal changes is the disturbance of the structure and function of podocytes, revealed by EM of the nephrobiopsy, leading to the loss of charge selectivity of the GBM and the development of proteinuria. There are no immunoglobulin deposits in the glomeruli. In some patients with NSMI, the process is transformed into FSGS.

Morphological characteristics of FSGS:

• focal changes - sclerosis of individual glomeruli;
• segmental sclerosis - sclerosis of several lobes of the glomerulus;
• global sclerosis - complete damage to the glomerulus.

EM of nephrobiopsy reveals diffuse loss of "small" podocyte processes. Immunofluorescence reveals segmental IgM luminescence in the affected glomeruli in 40% of cases. Currently, there are 5 morphological variants of FSGS (depending on the topical level of glomerular damage): typical (non-specific), vascular (in the vascular pedicle area), cellular, tubular (tubular side of the glomerulus), collapsing.

A characteristic feature of membranous nephropathy is a diffuse thickening of the walls of glomerular capillaries, revealed during a morphological examination of a nephrobiopsy specimen, associated with subepithelial deposition of immune complexes, splitting and doubling of the GBM.

MPGN is an immune glomerulopathy characterized by mesangial cell proliferation and mesangial expansion, thickening and splitting (double-contour) of the capillary wall due to mesangial interposition. Histological examination using EM identifies 3 morphological types of MPGN, although the interpretation of the morphological features of MPGN remains a subject of debate to date.

• Type I MPGN is characterized by normal lamina densa in the GBM and the predominant presence of subendothelial deposits of immune complexes.
• Type II MPGN (disease of “dense” deposits) is represented by dense homogeneous deposits in the GB.
• In type III MPGN (with silver staining of ultra-thin sections), ruptures of the lamina densa in the GBM and accumulation of a new membrane-like substance located in layers are determined. Mixed deposits located subendothelially, subepithelially and in the mesangium are more common.

MsPGN is characterized by proliferation of mesangial cells, expansion of the mesangium, deposition of immune complexes in the mesangium and subendothelium. The diagnosis of IgA nephropathy is based on the clinical picture (micro- or macrohematuria, more often during or after acute respiratory viral infection), family history data and, mainly, morphological examination of renal tissue. The nature and severity of clinical and laboratory manifestations of the disease are of only relative importance for the diagnosis of IgA nephropathy.

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Laboratory research

The IgA content in the blood does not have a high diagnostic value, since it is elevated in 30-50% of adult patients and only in 8-16% of children. The ASLO titer in the blood is elevated only in a small number of patients. The concentration of the C3 _complement fraction in the blood is not reduced. Skin biopsy does not have high specificity and sensitivity for the diagnosis of IgA nephropathy.

Histological examination of renal tissue of patients with IgA nephropathy reveals predominant fixation of granular IgA deposits in the glomerular mesangium (often in combination with IgM and (y) deposits, mesangium expansion is often noted due to cell hyperproliferation. With EM, changes in the GBM in the form of subendothelial deposits can be detected in 40-50% of children and 15-40% of adults, the presence of which indicates an unfavorable prognosis for the disease.

In immunofluorescence examination of renal tissue, 5 types of RPGN are distinguished:

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

Differential diagnostics

Differential diagnostics between acute and chronic forms of glomerulonephritis is often 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 in chronic glomerulonephritis it can be only a few days or more often there is no connection with previous diseases. Urinary syndrome can 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 the chronic process. In addition, acute poststreptococcal glomerulonephritis is characterized by a low concentration of the C3 _fraction of complement in the blood with a normal content of _C4.

Most often, there is a need to conduct differential diagnostics between various morphological variants of chronic glomerulonephritis.

The course of MPGN in some cases may resemble the manifestations of IgA nephropathy, but is usually accompanied by more pronounced proteinuria and arterial hypertension, a decrease in the concentration of the C3 complement fraction in the blood is characteristic _, often in combination with a decrease in the concentration of C4 _. The diagnosis is confirmed only by nephrobiopsy.

Differential diagnosis with IgA nephropathy is possible only on the basis of studying kidney biopsies with immunofluorescence testing and identifying predominantly granular deposits of IgA in the mesangium.

In addition, differential diagnostics are carried out with diseases that occur with torpid hematuria.

• Hereditary nephritis (Alport syndrome) is manifested by persistent hematuria of varying severity, often in combination with proteinuria. Kidney pathology is characterized by a familial nature, chronic renal failure in relatives, and sensorineural hearing loss is often noted. The most common type of inheritance is X-linked dominant, autosomal recessive and autosomal dominant are rare.
• Thin basement membrane disease. Along with torpid hematuria, often familial, EM of renal tissue shows diffuse uniform thinning of the GBM (<200-250 nm in more than 50% of glomerular capillaries). There are no deposits of IgA in the mesangium and expansion of the mesangial matrix characteristic of IgA nephropathy.
• Nephritis in hemorrhagic vasculitis (Schonlein-Henoch disease), unlike IgA nephropathy, is accompanied by 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 nephrobiopsy specimens in the form of fixed IgA deposits in the glomerular mesangium are identical to those in IgA nephropathy. It is often necessary to exclude kidney damage in systemic connective tissue diseases: SLE, nodular periarteritis, microscopic polyangiitis, Wegener's syndrome, etc. To clarify the diagnosis, it is necessary to determine markers of systemic pathology in the blood: ANF, antibodies to DNA, ANCA (perinuclear and cytoplasmic), rheumatoid factor, concentration of complement fractions, LE cells, cryoprecipitins in the blood. The study of antibodies to GBM and ANCA is carried out to clarify the nature of RPGN and justify therapy.

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

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