IgA nephropathy, also known as Berger’s disease, is a diagnostic immunopathology term for a series of clinical symptoms and pathological changes caused by diffuse deposition of IgA-based immunoglobulin particles in the glomerular thylakoid region and capillary collaterals. Pathological changes of IgAN Heterogeneity of IgA nephropathy Clinical manifestations are diverse and vary in severity from microscopic hematuria to acute nephritis syndrome Pathological changes vary widely and include almost all pathological manifestations of primary glomerulonephritis Response to treatment varies Prognosis varies from spontaneous remission to progression to ESRD Pathological grading/score method of IgAN Lack of efficacious treatment methods, early diagnosis and prognosis are particularly important The pathological grading of IgA nephropathy is the most effective method to evaluate the prognosis. Over the past 40 years, various pathological grading/grading methods have been developed. A simple classification of kidney disease into several grades according to the severity and extent of the lesions, taking into account some histological lesions that affect the prognosis of IgAN (1982) WHO revision (1995 ) Haas M (1997) Lee HS et al. (2005) et al. Lee’s grading method 1982 Korean pathologist Lee SM, et al. established the grading method by modifying Meadow’s tissue classification Lee SM, Rao VM, Franklin WA, et al. IgA nephropathy: morphologic predictors of progressive renal disease. Hum Pathol, 1982; 13: 314C322 Lee grading Haas grading The most widely used pathological grading. And established In 2007 Haas M improved the 97 staging and adopted by WHO Haas staging (1997) IgA nephropathy (Hass type I) IgA nephropathy (Hass type I) IgA nephropathy (Hass type II) IgA nephropathy (Hass type III) IgA nephropathy (Hass type IV) IgA nephropathy (Hass type V) IgA nephropathy Haas modified typing (2007) Comparison of single classification method Single classification method Advantages Simple, easy to apply Good repeatability Suitable for clinical diagnosis and classification, suitable for large multicenter studies Disadvantages Lack of flexibility and precision in prognostic evaluation of individual patients More emphasis on glomerular lesions, unable to account for important isolated pathological changes Sometimes some independent and important prognostic indicators may be missed Semi-quantitative classification method Analyze various lesions in the glomerulus, tubules, interstitium or blood vessels that are associated with clinical findings or are linked to each other Total score is obtained to find correlations between various lesions in IgAN and with clinical prognosis Includes Pirani and Salinas-Marrigal (1968) Andreoli SP et al. (1989) Ministry of Health and Welfare of Japan (1995) Memphis integral method (1996) Katafuchi integral method (1998), etc. In 1998, some hospital pathology departments combined Lee’s method and Haas’ method and developed the Katafuchi score method to compensate for the shortcomings of a single classification. The method has more information by scoring each of acute, proliferative and chronic lesions separately. Glomerular interstitial injury score 0 to 9, vascular lesion score 0 to 6, total score 1 to 27 The classification is more precise, which facilitates the physician to choose the treatment plan and evaluate the prognosis Katafuchi score: Glomerular score Glomerular cell proliferation degree score The mean value of all glomerular scores is divided into 1 to 4: 1:1≤mean <2 2:2≤mean <3 3:3 mean <4 4. Mean value = 4 The percentage of neo-lunar, adhesions and segmental sclerosis was divided into 0-4 points: 0 points: none 1 point: <10% 2 points: 10%-25% 3 points: 25%-50% 4 points: <50% Spherical sclerosis points The percentage of spherical sclerotic glomeruli in the total number of glomeruli was divided into 0-4 points: 0 points: none 1 point: <10% 2 points: 10%-25% 3 points: 25%- 50% 4 points:<50% Katafuchi score: tubular-interstitial score Calculated as the percentage of cortical renal tissue area occupied by the lesion 0 points:none 1 point:<25% 2 points:25%-50% 3 points:<50% Interstitial inflammatory cell infiltration (0-3 points) Interstitial fibrosis (0-3 points) Tubular atrophy (0-3 points) Katafuchi score: vascular score Vascular wall Vessel wall thickening (0-3 points) Vessel wall thickening: I.D./O.D. ≤ 0.5 in cross-section Calculated as percentage of diseased vessels 0 points: none 1 point: <10% 2 points: 10%-25% 3 points: <25% Hyaline degeneration (0-3 points) 0 points: none 1 point: <25% 2 points: 25%-50% 3 points: <50% Shortcomings of the Katafuchi score Large amount of information, complex application Reproducibility: Reproducibility of scores of the same subject by the same pathologist at different times is moderate Reproducibility of scores between different pathologists is poor It is recommended that the same pathologist apply the semi-quantitative grading method at his or her center Advantages Provides more information Suitable for comparison of multiple kidney biopsies of the same patient Disadvantages Relatively complex and time-consuming Survey of the Renal Pathology Association 2006 Shortcomings of existing grading methods There is no internationally accepted classification method to date Unclear definitions and vague terminology Lack of evidence-based basis Partially suggests prognosis, but does not guide treatment Shortcomings of existing grading methods Overemphasis on chronic lesions and their role in prognosis, while neglecting the positive role of active lesions in treatment The newly modified Lee's grading method is based on the range of sclerosis and crescent, ignoring active lesions Katafuchi's method involves active and chronic lesions, but is too cumbersome and partly unclear, and does not provide clear guidance for treatment in clinical application. The judgement of the severity of the changes is highly subjective Only simple qualitative or semi-quantitative, which makes the possible correlation in the study lost Tateno et al. performed repeat renal biopsies in 22 patients and found no lesion progression using semi-quantitative analysis, but using quantitative analysis found improvement in some patients and lesion progression in some cases, and there was a significant difference in prognosis between the two groups Danilewicz et al. used Danilewicz et al. used quantitative analysis to find a correlation between the size of deposits in the mesenteric region of IgA nephropathy and the degree of monocyte/macrophage infiltration, whereas Afima et al. used semi-quantitative analysis but did not find a correlation between the two. The Oxford Classification was proposed by the International IgA Nephropathy Collaborative Group and the Renal Pathology Association in 2004 to establish a unified clinical-pathological classification of IgA nephropathy. To find valid clinical information on the prognosis of IgA nephropathy To assess the value of pathological changes in combination with clinical data on the prognosis of IgA nephropathy (including age, geography, ethnicity) To suggest a prognosis of at least 5 years of renal survival or renal failure by clinical-pathological typing Study population and renal biopsies Retrospective observational study Follow-up 5 years 265 adults and children (~30%) IgAN patients From 8 countries on 4 continents (5 in Asia, 6 in Europe, 2 in US, 1 in South America) and 2 multicenter networks (Canada-US) Renal puncture specimens averaged 18 (8-24) glomeruli. Thylakoid cell proliferation score Percentage of glomeruli with segmental sclerosis or adhesions Percentage of glomeruli with intracapillary hyperplasia Percentage of glomeruli with cellular or cytofibrotic crescentic glomeruli Percentage of tubular atrophy/interstitial fibrosis Arterial score Clear definition of IgAN-related pathology Glomeruli: diffuse, focal, global, segmental, intracapillary hyperplasia, nuclear fragmentation, necrosis, basement membrane double track, thylakoid stromal hyperplasia,, sclerosis, adhesions, segmental sclerosis, global sclerosis, crinkled/ischemic glomeruli Extra-capillary lesions: extra-capillary hyperplasia: cellular crescent, cellular fibrous or fibrous crescent Thylakoid hyperplasia: normal (<4 thylakoid cells/thylakoid zone), mild (4-5) , moderate (6-7) , severe (≥8) Tubulointerstitial: tubular atrophy, interstitial fibrosis, interstitial inflammation, other tubular injury , acute tubular injury Vascular: arterial injury, arterial hyaline change Pathological parameters in the IgAN classification used to collect pathological information * The score for thylakoid hyperplasia should be assessed in PAS-stained sections. If more than half of the glomeruli contain more than 3 cells in the tegmental area, they are classified as M1. therefore, not all scores for tegmental hyperplasia require a formal tegmental cell count Examples of tegmental cell scores Examples of glomerular hyperplasia and sclerosis Impact of pathological variables on prognosis Impact of pathological variables on prognosis Recommended IgAN renal biopsy report form Features of the Oxford classification Clear definitions Selected pathological parameters all have Prognostic value independent of clinical parameters Easy to understand and apply for both individual and prognostic purposes Simple to apply in routine clinical practice Reproducible Shortcomings of the Oxford classification Retrospective observational studies The study population was not collected uniformly and the design itself involved multiple countries and centers with different experimental methods of testing renal function To ensure consistency among pathologists, scoring was limited to PAS staining Nevertheless, specific pathological features verified by rigorous statistical methods can independently suggest prognosis Prognosis of IgA nephropathy About 1/3 of IgAN patients enter ESRD in 10-20 years and IgAN becomes one of the main causes of ESRD Pathological changes are dynamic and reversible and irreversible are relative Many factors influence nephropathy, besides clinical and pathological indicators, there are The prognosis of IgA nephropathy requires comprehensive consideration The regression of IgA nephropathy Spontaneous remission of IgA nephropathy < 5% Persistent, benign course ~ 50% Slow progression of the disease 30-40% Rapid progression of the disease < 10% Conclusion The establishment of a pathological grading method for IgA nephropathy to guide treatment and determine prognosis has been the pursuit of clinic-pathologists in nephrology. The newly published Oxford grading method for IgA nephropathy has the advantages of simplicity and reproducibility, but still requires larger specimens and longer follow-up.