Wan-zhong Zou

Tubulointerstitial lesions of patients with lupus nephritis classified by the 2003 International Society of Nephrology and Renal Pathology Society system

The 2003 International Society of Nephrology/Renal Pathology Society (ISN/RPS) system for classifying patients with lupus nephritis was based on glomerular lesions exclusively, despite the fact that lupus nephritis affects all compartments of the kidney. Hence, we analyzed the tubulointerstitial lesions in patients with lupus nephritis within the different classes and subclasses of the 2003 ISN/RPS system. Among 313 patients from five centers in northern China with lupus nephritis, interstitial inflammatory cell infiltration, tubular atrophy, and interstitial fibrosis were severe in 170 patients with class IV, moderate in 55 with class III, and mild in 19 with class II and in 69 with class V disease, each with significance. The severity of tubulointerstitial lesions in classes IV-segmental and III was similar, whereas the score of interstitial inflammatory cell infiltration in patients with subclass IV-global was significantly higher than that in those with subclass IV-segmental. Interstitial fibrosis and tubular atrophy were each significantly more prominent in patients with both active and chronic lesions than in those with active lesions alone. The correlation coefficient ranged from 0.222 to 0.811 comparing glomerular and tubulointerstitial indices. In multivariate Cox hazard analysis of tubulointerstitial lesions, indices of interstitial infiltration, tubular atrophy, and interstitial fibrosis were confirmed as significant independent risk factors for renal outcome. Thus, we found that the 2003 ISN/RPS classification system of lupus nephritis, based on glomerular lesions, could also reflect related tubulointerstitial lesions. Hence, we suggest that the extent of tubulointerstitial lesions may be helpful in predicting renal outcome in patients with lupus nephritis.

The changing spectrum of primary glomerular diseases within 15 years: A survey of 3331 patients in a single Chinese centre

BACKGROUND Primary glomerular disease (PGD) is the leading cause of end-stage renal disease (ESRD) in China. With the development of socioeconomic status of Chinese people in the last two decades, PGD in ESRD is intent to decrease. However, whether this affects the spectrum of PGD is not clear. The aim of the current study is to investigate the changing spectrum of PGD in China. METHODS The records of 5398 consecutive native renal biopsies performed in adults (>or=14 years of age) in our centre between 1993 and 2007 were retrospectively analysed. The criteria for renal biopsy and pathologic diagnosis were kept unchanged. The patients were grouped according to a 5-year interval, 1993-97 (period 1), 1998-2002 (period 2) and 2003-07 (period 3). Then they were divided into four groups according to age for stratified analysis: 14-24 years, 25-44 years, 45-59 years and the elderly (>or=60 years). RESULTS Three thousand, three hundred and thirty-one patients were diagnosed with PGD. PGD remained the most common renal disease, accounting for 65.9%, 57.7% and 63.2% in period 1, 2 and 3, respectively, without any significant difference. The proportion of elder patients increased significantly from 0% in 1993 to 9.1% in 2007 (P < 0.001). Within 1993-97, the leading PGD was IgA nephropathy (50.7%), followed by non-IgA MsPGN (19.9%), membranous nephropathy (MN) (13.3%) and minimal change disease (MCD) (6.3%), while within 2003-07, the most common PGD was still IgAN (58.2%), but followed by MN (14.3%), MCD (13.4%) and non-IgA MsPGN (7.0%). The age-adjusted frequency of IgAN and MCD increased significantly from period 1 to period 3 (P < 0.01 and P < 0.001, respectively), while that of non-IgA MsPGN, EnPGN and MPGN decreased significantly (P < 0.001, P < 0.01 and P < 0.05, respectively). There was no significant change in the age-adjusted frequency of FSGS, MN and CreGN during the study period. However, when patients were stratified by age, a sixfold increase in frequency of FSGS was identified in the 14- to 24-year group (P < 0.01). CONCLUSIONS The spectrum of primary glomerulonephritis has changed within the last 15 years. The relative frequency of non-IgA MsPGN, EnPGN and MPGN decreased significantly, while that of MCD and IgA nephropathy increased significantly. The relative frequency of FSGS increased significantly in younger patients.

Clinicopathological characteristics and outcomes of patients with crescentic lupus nephritis

There are few clinicopathologic and outcome data on patients with crescentic lupus nephritis, therefore, we determined factors of the disease by retrospectively reviewing the records of 327 patients diagnosed with lupus nephritis. Of these, 152 cases were regrouped as class IV-G, including 33 patients with crescentic glomerulonephritis. Significantly, all patients with crescentic glomerulonephritis had acute kidney injury as compared with only about a quarter of the patients without the disease. On pathological evaluation, activity scores, chronicity indexes, relapse rates, and the frequency of positive serum anti-neutrophil cytoplasmic antibody (ANCA) were each significantly higher, whereas complete remission rates and renal outcomes, over a mean follow-up of 4 years, were significantly poorer in patients with crescentic glomerulonephritis. Our study shows that crescentic glomerulonephritis was not rare in patients with lupus nephritis and that their long-term outcome was poor. The precise role of ANCA in the pathologic course of crescentic lupus nephritis remains to be determined.

Natural history of immunoglobulin A nephropathy and predictive factors of prognosis: A long-term follow up of 204 cases in China

Aim:  Immunoglobulin A nephropathy (IgAN) is the most common primary glomerulonephritis worldwide. However, its natural history and risk factors are not well understood. Our aim was to identify the clinical and pathological factors that could predict disease prognosis in Chinese patients.

Urinary kidney injury molecule-1 in patients with IgA nephropathy is closely associated with disease severity

BACKGROUND The pathological characteristics of IgA nephropathy (IgAN) are highly variable. Urinary kidney injury molecule-1 (KIM-1) is a sensitive biomarker for proximal tubule injury. The aim of the study is to investigate the value of KIM-1 as a biomarker for assessing the renal injury in IgAN. METHODS The levels of urinary KIM-1 in 202 patients with IgAN, 46 patients with other renal diseases as disease controls and 60 healthy blood donors as normal controls were measured. Correlations with clinical and histopathological features of patients with IgAN were evaluated. RESULTS The levels of urinary KIM-1 were significantly higher in patients with IgAN than in normal controls (P < 0.001) and in patients with non-IgAN (P = 0.011). Urinary levels of KIM-1 in IgAN positively correlated with levels of serum creatinine and proteinuria and negatively with creatinine clearance. The more severe the tubulointerstitial injury was, the higher the levels of urinary KIM-1. Patients with severe mesangial proliferation, crescents formation or endocapillary proliferation had higher levels of urinary KIM-1 than those without. The levels of tubular KIM-1 expression in immunohistochemistry closely correlated with the levels of urinary KIM-1 (r = 0.553, P = 0.032). Renal survival was significantly worse in patients with elevated urinary KIM-1 (P = 0.020). CONCLUSION Urinary KIM-1 may be a useful biomarker to evaluate kidney injury in IgAN.

Detection of the hepatitis C virus antigen in kidney tissue from infected patients with various glomerulonephritis

BACKGROUND Several studies have postulated a causal link between hepatitis C virus (HCV) infection and renal diseases through the induction of cryoglobulinaemia. However, the detection of viral antigens within kidneys of HCV-infected patients has proved to be difficult. We studied a cohort of Chinese HCV-infected patients with various glomerulonephritis (GN) in an attempt to detect HCV antigens within their kidneys. METHODS Twenty-one patients with various GN were found to be serum HCV-antibody positive (seven serum HCV-RNA positive simultaneously), at the time of renal biopsy, from January 2005 to April 2008 in our hospital. A murine monoclonal antibody against the HCV-NS3 protein was employed to detect the HCV antigen using immunohistochemistry and immunogold labelling. Their clinical and pathological data were collected and further analysed. RESULTS The HCV-NS3 antigen was detected in six (6/21, 28.6%) HCV-antibody-positive patients by immunohistochemistry and four out of the six were serum HCV-RNA positive (4/7 in HCV-RNA positive, 57.1%). The HCV antigen mainly displayed a linear or granular deposition along glomerular capillary walls and/or mesangial region. Immunoelectron microscopy showed that the labelling of HCV-NS3 was localized mainly in electronic dense deposits. In the HCV-NS3 detectable patients, three patients were with membranoproliferative glomerulonephritis (MPGN), one with membranous nephropathy, one with IgA nephropathy and one with amyloid nephropathy. The age and urinary protein were significantly greater in HCV-NS3-positive patients than those in HCV-NS3 negative, while serum C3 level was significantly lower in the former group. No significant difference was found in serum ALT, albumin and creatinine level between the two groups. CONCLUSION HCV-NS3 antigens could be detected in kidney tissue of HCV-infected patients with various GN, but mainly in those with MPGN and HCV-RNA positive. HCV itself might be involved directly in the pathogenesis of HCV-associated GN.

The renal histopathological spectrum of patients with nephrotic syndrome: an analysis of 1523 patients in a single Chinese centre

BACKGROUND Nephrotic syndrome is caused by a variety of glomerulopathy. The current study investigated the renal histopathological spectrum of patients with nephrotic syndrome who received a renal biopsy in our department within the last 15 years. METHODS One thousand five hundred and twenty-three consecutive patients (≥14 years old at renal biopsy) with nephrotic syndrome were recruited. Patients were divided into four groups according to age at the time of renal biopsy. The renal histopathological spectrum was also compared between nephrotic-range proteinuria patients with and without hypoalbuminaemia. RESULTS Among the 1523 patients, the most common cause of nephrotic syndrome was idiopathic membranous nephropathy (IMN) (20.7%), followed by minimal change disease (MCD) (20.4%). Among the patients aged 14-24, 25-44, 45-59 and ≥60 years, the most common cause of nephrotic syndrome was MCD (33.0%), lupus nephritis (LN) (23.0%), IMN (37.9%) and IMN (42.3%), respectively. Among the female patients aged 14-24 and 25-44 years, LN was the leading cause of nephrotic syndrome (35.8 and 36.2%, respectively). The proportion of patients with renal amyloidosis increased in parallel with patient age. The comparison between nephrotic patients with and without hypoalbuminaemia suggests that patients with MCD, LN or renal amyloidosis were more likely to develop hypoalbuminaemia. CONCLUSIONS The renal histopathological spectrum of nephrotic syndrome differs between ages. MCD, LN and IMN were the main cause of nephrotic syndrome among younger patients, and IMN was the main cause of nephrotic syndrome among older patients. The proportion of patients with renal amyloidosis increased in parallel with patient age.

Concise semiquantitative histological scoring system for immunoglobulin A nephropathy.

Aim:  Immunoglobulin A nephropathy (IgAN) is a common and progressive glomerulonephritis. Histological lesions of IgAN are variable and considered as a risk factor for renal outcome. Establishing a relatively concise histological semiquantitative scoring system would be valuable in clinical practice.

Elevation of serum von Willebrand factor and anti-endothelial cell antibodies in patients with immunoglobulin A nephropathy are associated with intrarenal arterial lesions

Aim:  Recent studies suggest that intrarenal arterial lesions are frequently observed in patients with immunoglobulin A nephropathy (IgAN). However, the mechanisms of the injury have not been elucidated. The level of serum von Willebrand factor (vWF) and the prevalence of anti‐endothelial cell antibodies (AECA) were investigated in patients with IgAN with different intrarenal arterial lesions.

A clinicopathological analysis in a large cohort of Chinese patients with renal amyloid light-chain amyloidosis

BACKGROUND The aim of the study is to investigate the association between clinical and pathological features in a large cohort of Chinese patients with renal immunoglobulin light-chain amyloidosis (AL). METHODS A series of 186 patients with renal AL amyloidosis diagnosed between 1990 and 2011 were retrospectively reviewed. The extent of amyloid deposition in glomeruli, blood vessels and tubulointerstitium were evaluated semiquantitatively. The renal amyloid load was defined by the sum of glomerular, vascular and interstitial deposits. The associations between the clinical manifestations and pathological features were analyzed. RESULTS The extent of glomerular amyloid deposition was positively correlated with the level of proteinuria. Patients with codeposition of amyloid and immune complexes (ICs) in glomeruli had higher levels of proteinuria than those without ICs. Advanced glomerular amyloid deposition was an independent pathological factor associated with renal insufficiency at diagnosis. The degree of vascular amyloid (VA) deposition was positively correlated with cardiac involvement and hepatic involvement. Patients with AL-κ showed a higher prevalence of hepatic involvement and more severe VA deposition than patients with AL-λ. High renal amyloid load independently predicted the increased risk for overall death after adjusting for recognized confounders. CONCLUSIONS The degree and localization of amyloid deposits in the kidney of AL patients were associated with the degree of proteinuria and renal insufficiency, as well as extrarenal organs involvement. There were some differences between AL-κ and AL -λ in clinical and pathological characteristics. The renal amyloid load was an independent predictor for overall mortality.