Clinicopathological Features Of Primary IgA Nephropathy And The Prognosis And Treatment Analysis Of IgA Nephropathy Presenting With Mild Proteinuria

Background and objective:IgA nephropathy is the most common primary glomerulonephritis, and it is also an important cause of chronic kidney disease and ESRD. IgA nephropathy has various clinical symtoms and pahthological manifestations. It’s nessesary to investigate the correlation between the clinical features and pathological manifestations. The Oxford Classification of IgA nephropathy in 2009 improved the pathological reproducibility and the predictive value of renal outcomes. IgA nephropathy is diagosed by deposits of IgA in the renal mesangium and capillary loop.There are few studies concerning of pathological leisons of IgA nephropathy in both light microscope and immunofluorescence at present. The first part of the study is to analyze the correlations between clinical features and pathological lesions of IgA nephropathy as well as the pathological leisons in light microscope and immunofluorescence. IgA nephropathy has the potential in slowly chronic renal impaiement, while the prognosis and treatment of patients presenting with mild proteinuria is still unclear. Therefore the second and third parts of the study aim to investigate the renal outcomes and risk factors of IgAN patients with mild proteinuria and explore the therapy to the patients.Methods:(1) Data of 3035 adult patients with biopsy-proven primary IgA nephropathy between January 1995 and December 2014 in our hosipital were analyzed retrospectively. The clinical data and renal pathological leisions including Lee’s grading system, Oxford Classification, crescents, renal artery lesions and immunofluorescence were collected. And the correlation between clinical and pathological characteristcs were evaluated; (2) 510 IgAN patients who met the criteria of proteinuria< 1 g/d, eGFR>60 ml/min/1.75 m2, having no immunosuppresive therapy before biopsy and follow-up≥12 months were enrolled. The baseline clinicopathological features and follow-up data were analyzed to evaluate the renal outcomes and risk factors of IgAN patients with mild proteinuria. (3) The subjects and methods were the same as the second part of the study. Therapy to IgAN patients with mild proteinuria was analyzed and evaluated the influence to renal outcomes.Results:1.(1) Primary IgA nephropathy mainly affected young and middle-aged adults. The ratio of male was slightly more than female.45.8% of the patients were diagnosed of high blood pressure before renal biopsy. The percentage of CKD1 stage was 50.7%. The proteinuria of most IgAN patients was 1-3.5 g/d. (2) Most patients were classified as Lee’s III grade. M1 lesion accounted for 44.7% of the patients, E1 lesion accounted for 14.6% of the patients, S1 lesion accounted for 73.8% of the patients, T1 lesion accounted for 23.0% and T2 lesions accounted for 15.6% of the patients. Crescent lesions accounted for 34.1% of patients. Renal arterial lesions accounted for 65.8% of the patients and most lesions were mild.78.1% of the patients showed global glomerulosclerosis. Immunofluorescence with IgG deposition accounted for 30.4% of the patients. IgA deposition concomitant with capillary loops accounted for 8.5% of the patients. The 2+ intensity of IgA deposition was the most common pattern (71.5%). (3) The baseline proteinuria was affected more severe with the increased degree of M1 lesion, E1 leision, T1/T2 lesion and C1 lesion. While renal arterial lesion and global glomerulosclerosis were not associated with proteinuria. The decrease of baseline eGFR was associated with pathological lesions of A, T, M and global glomerulosclerosis.The increase of baseline MAP was associated with pathological lesions of T, A, C and global glomerulorsclerosis. IgG deposition was more severe with the increase of proteinuria and MAP as well as the decrease of eGFR. IgA deposition concomitant with capillary loop was more severe with the increase of proteinuria. The intensity of IgA deposition was negtively related to the proteinuria and MAP and positively related to the eGFR. (4) IgA deposition concomitant with capillary loop was positively related with Lee’s grading system, M, S and global glomerulosclerosis. IgG deposition was positively related with global glomerulosclerosis. The intensity of IgA deposition was positively related with M, S lesions and global glomerulosclerosis.2. (1) Hypertention was diagnosed in 32.7% of IgAN patients with mild proteinuria at renal biopsy. Macrohematuria was found in 32.3% of the patients. The mean value of proteinuria and eGFR was 0.6g/d and 103 ml/min/1.73m2 respectively. Lee’s III grade was classified in 73.1% of the patients. Comparing to the patients in the first part study, the Oxford Classification and the leision of crescent and renal arteria. global glomerulosclerosis were milder in the patients of this part. (2) ESRD was diagnosed in 4 patinets (0.8%). eGFR declinine≥30% of the baseline was found in 31 patients (6.1%). Renal rapid progress was found in 78 patients (15.3%). Proteinuria≥1g/d was found in 45 patients (8.8%). Complete clinical remission was found in 82 patients (16.1%). Age and proteinuria at renal biopsy were the risk factors of Proteinuria≥ 1g/d during the follow-up. TA-P was the risk factor of renal rapid progress and ESRD of IgA patients with mild proteinuria. (3) For the patients with mild proteinuria, TA-P was suggested to be controlled within 0.7g/d.3. (1) The clinicopathological features were more severe in patients with immuno-suppressive therapy and mild in patients without any therapy. The proportion of new-onset hypertention and TA-P level were the highest in patients with immunosuppressive therapy. But matching baseline informations with the patients without therapy, the therapy of ACEI/ARB and glococorticoids and (or) immunosuppresive agents had no improvements on the renal function and proteinuria of IgAN patients with mild proteinuria. (2) In our hospital, the immunosuppresive therapy to patients with mild proteinuria was related with cell/fibrocell crescent, age, blood pressure,baseline proteinuria and eGFR level. (3) The immunosuppressive therapy to patients with cell/fibrocell crescents had no improvements on the renal outcomes.Conclusion:1. Comparing with the Oxford Classification, the proportions of the lesions are different in our hospital. Clinical features were related with pathological lesions in both light microscope and immunofluorescence. IgG deposition in glomeruli, IgA deposition in capillary loop and the intensity of IgA deposition were all correlated with clinical features and pathological lesions in light microscope.2. The progonosis of IgAN patients with mild proteinuria is not favorabl. Monitor and controlling of proteinuria and blood pressure during flollow-up was very important.3. ACEI/ARB and immunosuppressive therapy may not have significant effect on renal function and proteinura.