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OBJECTIVE: To study the clinical and pathological characteristics of patients with microscopic polyangiitis (MPA) with medium artery involvement. METHODS: Hospitalized patients with MPA in recent two years were retrospectively studied. Their clinical and pathological features were compared between patients with and without renal medium artery involvement. RESULTS: Thirty-nine patients had renal pathology confirmed MPA. Nine cases were with medium artery involvement. For the 30 patients without medium artery involvement, 24/30 had crescentic glomerulonephritis and 11/30 also had focal segmental glomerular fibrinoid necrosis; clinically, 21/30 patients were pANCA/MPO-ANCA positive, 26/30 had acute renal failure with an average duration of 14 weeks before MPA was diagnosed, eight cases achieved complete remission after intensive immunosuppressive therapy. Nine MPA patients had medium artery involvement, manifested as segmental fibrinoid necrosis of major branch of arcuate artery, glomerulus ischemia was predominant, but crescentic lesions were mild, none of them reached crescentic glomerulonephritis. Five of the nine were pANCA/MPO-ANCA positive, eight out of the nine patients had acute renal failure with an average duration of eight weeks before diagnosed, seven of the nine achieved complete remission after intensive immunosuppressive therapy. In comparison, MPA with medium artery involvement had a shorter duration (p < 0.05), less crescentic glomerulonephritis in patients with acute renal failure (p<0.01) and more patients achieved complete remission after treatment (p<0.05). CONCLUSION: In present study, about 23% MPA patients had medium artery involvement and their impaired renal function is mainly due to extensive glomerular ischemia. These patients progressed to acute renal failure quicker and responded to therapy better. [ABSTRACT FROM AUTHOR]

Aim To investigate the changing of idiopathic membranous nephropathy ( iMN) in China. Methods This study retrospectively analyzed renal disease spectrum of 6049 patients who underwent renal biopsy at Peking University First Hospital from January 2003 to December 2012. The patients were grouped into two periods at a 5-year interval: 2003-2007 (period 1) and 2008-2012 (period 2). Results Among 6049 renal biopsied patients, 3831 (63.3%) patients were diagnosed as primary glomerular disease ( PGD). The proportion of nephrotic syndrome ( NS) in PGD was significantly higher in period 2 than that in period 1 (1016/2214 [55.0%] vs 682/1617 [42.2%], P = 0.022). The proportion of iMN in PGD increased from 16.8% (217/1617) in period 1 to 29.35% (646/2214) in period 2 in all groups of age ( P < 0.001). There was no significant difference of clinical characteristics including age, gender, hypertension, serum cholesterol and proteinuria between the two periods ( P > 0.05). However, in young patients with iMN (14-44 years old), the percentage of renal histopathology stage I and stage II of iMN in PGDs was significantly higher in period 2 than that in period 1 (101/1240 [8.15%] vs 210/1340 [15.7%], P < 0.001). Conclusion Our study suggests that the frequency of iMN in PGD in our referral diagnostic centre has doubled over the past 10 years. The increase of adult iMN is mainly due to the increase of early stages of iMN in young patients. [ABSTRACT FROM AUTHOR]

Background. Aristolochic acid nephropathy (AAN) is a worldwide problem and one of the common causes of chronic kidney disease (CKD) in China. Methods. Three hundred patients diagnosed as AAN from 1997 to 2006 were enrolled. Medical histories of Chinese herb ingestion, clinical–pathological features and risk factors for renal failure were recorded. Patients were followed up for 2–156 months. Factors involved in the prognosis of AAN were investigated. Results. The 300 patients with AAN manifested three clinical subtypes, including acute kidney injury (acute AAN) in 13 patients, abrupt tubular dysfunction with normal serum creatinine (Scr) levels in seven cases and chronic tubulointerstitial nephropathy with decreased estimated glomerular filtration rate (eGFR) (chronic AAN) in 280 cases. The acute AAN cases had the highest aristolochic acid (AA)-I intake per day and developed progressive kidney failure during 1–7 years follow-up. The tubular dysfunction AAN patients had the lowest cumulative AA-I intake and were able to keep normal Scr levels during 2–8 years follow-up. The chronic AAN patients took the lowest AA-I dose per day but with the longest period and the highest cumulative dosage and exhibited a very large range of eGFR changing rate (from −21.6 to 5.2, median −3.5 mL/min/year). The cumulative AA-I intake (r = 0.330, P = 0.045) and the time course from the termination of AA medication to the start of follow-up (r = −0.430, P = 0.009) were found to be independent factors correlated with the decrease rate of eGFR in the chronic AAN patients. AA and the metabolites could be detected in a high frequency in patients who had stopped herbal medication for 1 year, which indicates a rather long washout time for these chemicals. Conclusions. AAN has variant phenotypes with distinct prognosis, which is determined by the variable AA medications. With better understanding of toxic and environmental causes for kidney injury, there would be a better chance to uncover the causal factors of cases of ‘CKD without known causes’ which is crucial for improving the disease outcomes. [ABSTRACT FROM PUBLISHER]

Background. Massive proteinuria is often associated with hypoalbuminaemia in glomerulopathy. However, patients may have normal levels of serum albumin despite heavy proteinuria in many circumstances. This study analysed factors affecting serum levels of albumin in primary glomerulopathy patients with nephrotic-range proteinuria.Methods. The renal histopathological data of 780 consecutive adult patients (age ≥ 18 years old) with primary glomerulopathy and nephrotic-range proteinuria, who received native renal biopsies in Peking University First Hospital from 1998 to 2007, were retrospectively analysed.Results. Compared with patients with hypoalbuminaemia (serum albumin < 30 g/L), patients without hypoalbuminaemia were significantly younger (P < 0.001) and had significantly lower levels of proteinuria (P < 0.001). Patients without hypoalbuminaemia had a significantly higher proportion of IgA nephropathy (66.0% vs. 17.2%, P < 0.001). The independent predictors of hypoalbuminaemia in nephrotic-range proteinuria patients included age, gender, interval between onset of the disease and renal biopsy, proteinuria level, and pathological type of glomerulopathy. A serum level of albumin ≥ 35 g/L could predict IgA nephropathy with a specificity of 95.8%, and specificity increased with age.Conclusions. Among patients with primary glomerulopathy and nephrotic-range proteinuria, normoalbuminaemia is associated with IgA nephropathy. [ABSTRACT FROM AUTHOR]

Abstract: Aberrant glycosylation of serum IgA1 was considered as an initial event and involvement in the pathogenesis of IgAN. We previously demonstrated that aberrant glycosylation of serum IgA1 was associated with pathologic phenotype of IgAN. The present study is to investigate if abnormal sialylation of IgA1 affects renal survival of IgAN. 127 patients with biopsy-proven IgAN were enrolled and followed up to 8 years. Seventy-nine healthy and 75 patients with non-IgAN renal diseases were selected as controls. Alpha 2, 6 sialic acid (SA) of serum IgA1 was measured by sandwich-ELISA. Renal survival rate was estimated by Kaplan–Meier method. Alpha 2, 6 SA level in patients with IgAN was lower than that in healthy controls (0.92±0.14 vs. 0.98±0.12, P =0.001) and non-IgAN glomerulonephritis (0.92±0.14 vs. 1.00±0.18, n =53, P =0.001). Patients with IgAN in Low SA Group were no significant differences compared with patients in Normal SA Group in age, gender, hypertension, serum creatinine, and excretion of proteinuria. Renal cumulative survival rate was 53.3% in patients in Low SA Group and 83.5% in Normal SA Group (P =0.0008). The lower the alpha 2, 6 SA level of serum IgA1 in patients with IgAN was, the worse their renal survival rate was. Although patients in Low SA Group had worse renal function evaluated by eGFR, there was no significant difference in various CKD stages in non-IgAN renal function controls (n =42, P =0.352). Alpha 2, 6 SA level of serum IgA1 was associated with the prognosis of patients with IgAN and could serve as a predictor of poor prognosis in IgAN. [Copyright &y& Elsevier]

Abstract: Anti-GBM disease is a rare autoimmune condition characterized by autoantibodies targeting the α3 chain non-collagen 1 domain of type IV collagen (α3(IV)NC1). Recently, we isolated IgG reacting with α3(IV)NC1 from normal healthy human sera. The current study examined the antigen and epitope specificity of these natural autoantibodies (NAA) using recombinant human α1, 3, 5(IV)NC1 and three constructs expressing, previously defined epitope regions designated EA, EB and S2, in the α1(IV)NC1 background. The NAA preparations reacted with recombinant human α3(IV)NC1 to the same extent as with purified bovine α(IV)NC1, but not with recombinant human α1 and α5(IV)NC1. NAA preparations recognized the three chimeric proteins (EA, EB and S2) yielding similar absorbance values. We conclude that anti-GBM NAA recognize the same major epitopes as anti-GBM antibodies from patients with Goodpasture''s disease. [Copyright &y& Elsevier]

Abstract: Background: Chronic kidney disease (CKD) was epidemic worldwide. The prevalence of CKD indicators, including proteinuria, hematuria/uninfectious leukocyturia and reduced GFR, was investigated in the middle and old-aged population of Beijing Shijingshan district. Methods: Subjects of 2310 aged ≥40 y were enrolled. Their health conditions were taken by questionnaires and physical check-ups. Spot urine albumin to creatinine ratio, spot urine dipstick and microscopy for urine red cell and leukocyte, and serum creatinine was determined. Using simplified Modification of Diet in Renal Disease Study equation estimated GFR assessed renal function. The associations between age, gender, diabetes mellitus, and hypertension, and indicators of kidney damage were examined. Results: Through the questionnaires, the history of diabetes mellitus, hypertension and CKD were found in 28%, 47.1% and 3.6% of subjects, respectively. Albuminuria was detected in 8.4% of subjects, hematuria and uninfectious leukocyturia in 0.7%, and reduced GFR in 4.9%. Approximately 12.9% had at least 1 indicator of CKD. The known rate of CKD in the studied population was 7.1%. Age, diabetes mellitus, hyper fasting blood glucose and hypertension were independently associated with albuminuria; age, gender, hyper uric acid and albuminuria with reduced GFR. When proteinuria and reduced GFR were determined using spot urine dipstick protein ≥25 mg/dl and serum creatinine ≥133 μmol/l, the prevalence of proteinuria and reduced GFR were 4.7% and 0.8%, respectively. Conclusion: The prevalence of CKD is common in middle and old-aged population of Beijing, especially in the elderly, but the known rate was relatively low. These findings highlight the clinical and public health importance of CKD. [Copyright &y& Elsevier]

Mesangial proliferation and deposition of immunoglobulins and complement components within glomerular mesangium was one of the important pathological features of lupus nephritis. Autoantibodies against human mesangial cells could be detected in the sera of patients with IgA nephropathy (IgAN) and Henoch-Schöenlein nephritis. We speculated that autoantibodies against human glomerular mesangial cells might play a role in the development of lupus nephritis. Objective. To screen autoantibodies against human glomerular mesangial cells in sera from patients with lupus nephritis and to identify their target antigens. Methods. Sera were collected from 96 patients with lupus nephritis as well as 25 patients with IgAN and 20 patients with idiopathic membranous nephropathy (IMN). Cell lysates of in vitro cultured human glomerular mesangial cells were used as antigens in Western-blot analysis to detect autoantibodies against human mesangial cells in sera from patients with lupus nephritis as well as IgAN and IMN. The clinical and pathological significance of the autoantibodies were further investigated. Results. Autoantibodies against human mesangial cells could be detected in 94/96 (97.9%) of the sera from patients with lupus nephritis in Western-blot analysis. Twelve protein bands could be blotted by the sera from patients with lupus nephritis. The prevalence of autoantibodies against human mesangial cells in IgAN was 14/25 (56.0%) and only seven protein bands could be blotted. Five autoantibodies (anti-18, 24, 36, 46, and 91 kD) could be detected only in sera from patients with lupus nephritis. In patients with lupus nephritis, some autoantibodies might have some relationship with gender, hematuria, ANA, anti-dsDNA or anti-ENA antibodies. Conclusions. There are autoantibodies directly against heterogeneous antigens of human glomerular mesangial cells in sera from patients with lupus nephritis, and some of them might be associated with different clinical manifestations. [ABSTRACT FROM AUTHOR]

Background. Although the clinical importance of demonstrating the presence of anti-glomerular basement membrane (anti-GBM) antibodies is well established, less is known concerning the clinical utility of measuring the levels of autoantibodies. Two conformational epitopes of anti-GBM antibodies have been defined at residues 17–31 and 127–141 of the α3(IV)NC1 domain of type IV collagen [α3(IV)NC1], which were named as EA and EB, respectively. In order to elucidate the importance of such antibodies, we studied the levels and the epitope specificities of anti-GBM antibodies in a large cohort of Chinese patients with anti-GBM disease. Methods. All patients, with anti-GBM disease and available clinical data, diagnosed at Peking University First Hospital from 1996 to 2005 were included in the present study. Recombinant chimeric proteins containing previously defined epitope regions designated as EA and EB were used to detect anti-GBM antibodies by ELISA. Results were compared and correlated with clinical data collected at the time of diagnosis, biopsy findings and outcome after 1 year of follow-up. Results. A retrospective diagnosis of anti-GBM disease was made in 147 patients. Haemoptysis was recorded for 47% of these cases while 53.5% cases had oliguria or anuria at the time of diagnosis. Among these patients, the levels of anti-GBM antibodies correlated with serum creatinine at diagnosis (P < 0.05 for anti EA, EB and α3(IV)NC1). Oliguric patients had higher levels of autoantibodies than non-oliguric patients, however, the difference being statistically significant only for EB (P < 0.05). Renal biopsies were performed in 66 patients, and it was found that 50 (75.8%) had cresent formation in >85% of the glomeruli. There was a correlation between the percentage of crescents and levels of antibodies, but it was significant only for anti-EA antibodies (P < 0.05). Clinical data regarding the follow-up were available for 102 patients; at the end of 1 year, 88 (86.3%) were either dead or dialysis dependent. The absorbance values of anti-GBM antibodies against both EA and EB were also associated with the subsequent development, death or terminal renal insufficiency (P < 0.05). Conclusion. In this study, patients with high levels of circulating antibodies against the specific epitopes EA and EB had a more severe renal disease at diagnosis as well as a worse prognosis. [ABSTRACT FROM AUTHOR]