IgA nephropathy gene, pathogenesis and treatment of the new progress

IgA nephropathy gene, pathogenesis and treatment of the new progress

IgA nephropathy mainly affects young adults, but also in children and the elderly occurred. The clinical spectrum of the disease spectrum is very broad, from asymptomatic microscopic hematuria to persistent proteinuria with severe deterioration of renal function characterized by severe performance can occur. The diagnosis of IgA nephropathy requires a renal biopsy. The disease is defined as the deposition of large amounts of immunoglobulin A (IgA) in the glomeruli on immunohistology. According to a recent consensus, IgA is at least 1+ in intensity, and in most cases, 2+ or more, and is diffuse in the glomeruli. Typical manifestations of glomerular IgA staining is associated with a weak IgG and \ or IgM. The composition of the sediments was predominantly IgA1 subtypes of poly-IgA. Studies from 2249 patients in a series of 13 published renal biopsies have shown that 100% of cases are IgA positive, 43% are IgG positive, and 54% are IgM-positive. In most cases, we observed that the intensity of lambda light chains was higher than that of kappa light chains, reflecting the predominance of IgA1-lambda in blood circulation.
IgA nephropathy showed a diversity of histological features can be seen in most immune complex-mediated proliferative glomerulonephritis. This included microscopic or mild abnormal lesions, mesangial cell proliferation (defined as 4 or more cells per mesangial area under a 3-micron-thick histological section), focal capillaries Intravascular proliferation (less than 50% of glomerular involvement), diffuse intravascular proliferation (more than 50% of glomerular involvement), necrotic and crescentic lesions, and more rare, proliferative lesions of the membrane type. Erythrocyte tube may be associated with acute renal tubular injury. In the chronic phase of the disease, pathological changes from the focal or diffuse segment progression to glomerular sclerosis, accompanied by renal tubular atrophy and renal interstitial fibrosis.
Electron microscopic examination can be found, IgA nephropathy in the glomerular electron dense material is mainly located in the mesangial area, sometimes in the subcutaneous and in more severe cases, subepithelial deposition is rare. Sediments in the mesangial area tend to cluster on the glomerular basement membrane. Glomerular basement membrane can be expressed as local thinning, fracture and reconstruction, these changes may be the source of hematuria.
Henoch-Schonlein purpura nephritis is actually associated with renal manifestations of systemic manifestations of IgA vasculitis, mainly in the young people there. A typical manifestation of this disease is a tetrameric form of palpable purpura, joint pain, abdominal pain and kidney disease. Although Henoch-Schonlein purpura nephritis is often self-limiting in children, persistent proteinuria and chronic or progressive renal failure are often seen in adult cases. Kidney disease is similar to IgA nephropathy in histological presentation but is more likely to occur in severe lesions such as glomerular necrosis and crescents. Corresponding to the situation, allergic purpura nephritis IgA nephropathy compared to glomerular fibrin staining positive rate is higher.
Exploratory grading systems for prior IgA nephropathy include Lee's and Haas's grades, which are based on the type and severity of proliferation and sclerosis, similar to that of lupus nephritis in the World Health Organization. The Oxford IgA Nephropathy Grading System, developed by a team of more than 40 representatives of the International IgA Nephropathy Collaboration and the Kidney Pathology Society's nephrologist, is the first unique rating scale with evidence-based features. It attempts to determine the reproducible histological features that can predict known disease progression in a large cohort of disease cohorts, so it represents a scoring system rather than a comprehensive grading system. The cohort of patients used to develop this scoring system came from 265 cases of IgA nephropathy in Europe, North America and Asia, of which 78% were adults. As this study excluded patients with proteinuria less than 0.5 g per day and an initial glomerular filtration rate (eGFR) of less than 30 ml / min / 1.73 m2, renal biopsy progressed to end-stage renal disease within 12 months of completion ) Of patients, so the disease is extremely minor cases, rapid glomerulonephritis and severe chronic kidney disease patients can not use this scoring system. There were three well-characterized histologic features that were independently associated with the rate of decline in renal function and the end point of renal survival (defined as a decrease in eGFR greater than 50% or ESRD). These features are known as diffuse mesangial cell proliferation (M), segmental glomerulosclerosis (S) and tubular atrophy / interstitial fibrosis with cumulative cortical area over 25% (T). Tubular atrophy / interstitial fibrosis Cumulative cortical area of ​​more than 50% indicates a more serious prognosis. Capillary intracellular proliferation (E) suggests that immunosuppressive therapy is effective. S, Segmental Glomerulosclerosis / Adhesion; T, Renal Tubular Atrophy / Renal Interstitial Fibrosis) scoring system was performed using the following nomenclature record: MEST (M, Mesangial Cell Proliferation; E, Intracellular Cell Proliferation; Method, M0 and M1 that mesangial cell accumulation is less than or equal to 50% and greater than 50%, E0 and E1 that no intracellular proliferation of capillaries and at least one glomerular capillary cell proliferation occurred, S0 and S1 that there is no Segmental glomerulosclerosis / adhesions and at least one glomerular segmental glomerulosclerosis / adhesions, T0, T1 and T2, said renal tubular atrophy / renal interstitial fibrosis cumulative cortical area were less than or equal to 25%, 26-50% and greater than 50%. The drawback of the Oxford scoring system is that it can not completely treat crescentic effects and specific immunofluorescent characteristics, such as simultaneous deposition of IgA and IgG in the surrounding capillary walls.
A number of studies have attempted to validate the predictive value of the MEST lesion scoring system, each of which is independently derived from North America, Europe and Asia, including a subset of pediatric cases. These studies used univariate and multivariate analyzes to validate the predictive value of the different components in general, but there were some differences between the studies. A meta-analysis of 16 retrospective cohort studies based on 3893 patients with IgA nephropathy demonstrated the predictive value of M, S and T lesions but failed to confirm the predictive value of E-disease. Although the E-score was associated with the weakest disease progression and showed the most significant heterogeneity, the T-score was consistently considered as a predictor of poor kidney prognosis in all study cohorts. In addition, five of the 16 studies (four in Asia and one in 1487 in Europe) examined the relationship between crescent and clinical outcomes, and meta-analysis of these studies showed a C score (defined as the presence of Crescent) and progression of renal failure are closely related. The recently published VALIGA study (European IgA Nephropathy Oxford Typing Assay Trial) included 1147 patients from 13 European countries. This study again confirms the predictive value of M, S, and T lesions in different manifestations of renal disease. While the E-score was again confirmed with the prognosis of no correlation. However, the relationship between these variables, such as the E-score and clinical outcome, can be complicated and confusing because of acceptance of immunosuppressive therapy because all published confirmatory studies are based on retrospective observational study data.
In summary, the Oxford Scoring System represents a significant advance in prognostic evaluation and standardized diagnosis, but it is also necessary to refine the scoring system to enhance its usefulness in assessing prognosis. More definitive scoring system assessment requires a relatively large sample size of randomized controlled trials to make treatment decisions not based on pathology. The TESTING study may be the only current study to validate and refine this scoring system after removing the effects of internal treatment bias.