Shi-Jun Li

Anti-Phospholipase A2 Receptor Antibody in Membranous Nephropathy

The M-type phospholipase A2 receptor (PLA2R) is a target autoantigen in adult idiopathic membranous nephropathy (MN), but the prevalence of autoantibodies against PLA2R is unknown among Chinese patients with MN. Here, we measured anti-PLA2R antibody in the serum of 60 patients with idiopathic MN, 20 with lupus-associated MN, 16 with hepatitis B (HBV)-associated MN, and 10 with tumor-associated MN. Among patients with idiopathic MN, 49 (82%) had detectable anti-PLA2R autoantibodies using a Western blot assay; an assay with greater sensitivity detected very low titers of anti-PLA2R in 10 of the remaining 11 patients. Using the standard assay, we detected anti-PLA2R antibody in only 1 patient with lupus, 1 with HBV, and 3 with cancer, producing an overall specificity of 89% in this cohort limited to patients with secondary MN. The enhanced assay detected low titers of anti-PLA2R in only 2 additional samples of HBV-associated MN. In summary, these results suggest that PLA2R is a major target antigen in Chinese idiopathic MN and that detection of anti-PLA2R is a sensitive test for idiopathic MN.

Obesity-Related Glomerulopathy in China: A Case Series of 90 Patients

BACKGROUND The epidemic of obesity has been paralleled by an increase in the incidence of chronic kidney disease. However, epidemiological data for obesity-related glomerulopathy (ORG) from developing countries, including China, are very limited. STUDY DESIGN Case series. ORG defined as body mass index (BMI) of 28.0 kg/m(2) or greater; urinary protein excretion of 0.4 g/24 h or greater, and glomerulomegaly (glomerular volume > 3.27 x 10(6) microm(3)) with or without focal segmental glomerulosclerosis (FSGS). SETTING & PARTICIPANTS 10,093 renal biopsy samples from patients obtained from February 2002 to November 2006 at the Research Institute of Nephrology, Nanjing University School of Medicine, China. PREDICTOR Obesity defined as a BMI of 28.0 kg/m(2) or greater. Subjects were divided into 3 groups: mild-obesity group with BMI of 28.0 to less than 30 kg/m(2), moderate-obesity group with BMI of 30 to less than 35 kg/m(2), and severe-obesity group with BMI of 35 kg/m(2) or greater. OUTCOMES & MEASUREMENTS Clinicoepidemiological and histopathologic characteristics of patients with ORG at the time of biopsy were described separately. RESULTS ORG was observed in 90 biopsy specimens (0.89%); frequency increased from 0.62% to 1.0% during the last 5 years (P = 0.02). Mean age was 37.5 +/- 9.3 (SD) years, 67% were men, mean BMI was 31.2 +/- 3.3 kg/m(2), waist circumference was 103 cm (range, 89.4 to 124 cm) in men and 96.5 cm (range, 88.5 to 113 cm) in women, waist-hip ratio was 0.95 +/- 0.07, and 100% had visceral obesity. Of the total, 49%, 37%, and 14% had mild, moderate, and severe obesity, respectively. Mean urinary protein excretion of subjects was 1.48 +/- 1.2 g/24 h; 51%, 39%, and 10% had proteinuria with protein of 0.4 to 1.0, 1.0 to 3.5, and greater than 3.5 g/d, respectively. Mean measured creatinine clearance (Ccr) was 109 +/- 32.2 mL/min/1.73 m(2), with 42%, 36%, and 22% with a Ccr greater than 120, 90 to 120, and less than 90 mL/min/1.73 m(2), respectively. Glucose dysmetabolism, insulin resistance, dyslipidemia, and hypertension were observed in 77%, 88%, 76%, and 63% of patients, respectively. FSGS was observed in 70%. Mean foot-process width was 534 +/- 176 nm. Foot-process fusion was seen in 36% of patients. Greater BMI was associated with greater proteinuria (P < 0.02), greater Ccr (P < 0.03), and greater foot-process width (P < 0.04). LIMITATIONS Inability to compute prevalence or incidence from case series. BMI was calculated at time of renal biopsy. CONCLUSIONS Most patients with ORG had mild obesity, visceral obesity, minor proteinuria, preserved Ccr, and FSGS.

Mercury-Induced Membranous Nephropathy: Clinical and Pathological Features

BACKGROUND AND OBJECTIVES Long-term contact with mercury may induce membranous nephropathy (MN); however, the clinical pathologic features and pathogenesis of mercury-induced MN have not been investigated. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The present study retrospectively evaluated 11 cases of mercury-induced MN to analyze its causes and its clinical and pathologic features. RESULTS A total of 10 women and 1 man ages 15 to 45 years were enrolled in the present study. Mercury exposure was caused by mercury-containing pills (five patients), skin lightening cream (four patients), hair-dyeing agents (one patient), and mercury vapor (one patient). The duration of contact with mercury ranged from 2 to 60 months, and the urinary mercury concentrations were 1.5 to 50 times higher than reference values. All patients presented with proteinuria and normal renal function; three had nephrotic syndrome. Light microscopy revealed thickened glomerular basement membrane and mildly proliferative mesangial cells. Acute tubulointerstitial injury occurred in three patients. The immunofluorescence findings showed granular deposits of IgG and C3 along the glomerular capillary wall, mostly accompanied by deposits of C4 and C1q. IgG1 and IgG4 (predominantly IgG1) deposits were observed along the glomerular capillary loops. Nine patients reached complete remission in follow-up after withdrawal from mercury exposure. CONCLUSIONS Deposits of IgG1 subclasses in renal tissues indicated that the pathogenesis of mercury-induced MN differs from that of idiopathic MN. It is important that clinicians are aware that mercury exposure should be considered a possible cause of membranous nephropathy.

Evaluation of podocyte lesion in patients with diabetic nephropathy: Wilms' tumor-1 protein used as a podocyte marker

INTRODUCTION The reduction of podocyte number and density per glomerulus has been linked to the development of proteinuria and the progression of disease in patients with diabetic nephropathy (DN). However, it has been recognized that measurement of podocyte number by light microscope is quite difficult because of the complexity of both podocyte and glomerular structure, which is not suitable for clinical research. In our research institute, we used WT1 as podocyte marker to evaluate the podocyte lesion. METHODS In our experiment, we selected the C-terminal antibody of WT1 to stain the nuclei and the N-terminal antibody of WT1 to stain the cytoplasma of podocytes. Forty patients were enrolled with type 2 diabetes and proven to have DN by renal biopsy analysis. DN patients were classified into three groups based on the degree of proteinuria: microalbuminuria (n=10, 30-300mg/24h), overt proteinuria (n=15, 0.5-3.5g/24h), and heavy proteinuria (n=15, >3.5g/24h). RESULTS The results demonstrated that the podocyte number was markedly decreased in patients with DN (30-51% reduction). There was a significant negative correlation between the proteinuria and both podocyte density and number. The cover area density of podocyte cytoplasma in glomerulus was also significantly decreased in all DN patients (39-80% reduction). A significant inverse correlation was observed between the cover area density and the degree of proteinuria. The correlation coefficient (r=-0.85) was much higher than that between proteinuria and podocyte density (r=-0.56) or podocyte number (r=-0.36). CONCLUSION In conclusion, podocyte damage occurred in patients with DN, even in the early stage and became more dramatic during the course of proteinuria progression. WT1 staining, using the polyclonal antibody to stain the nuclei and monoclonal antibody to stain the cytoplasma of podocytes together, is a valuable alternative technique in the study of podocyte injury.

Renal Involvement in Non-Hodgkin Lymphoma: Proven by Renal Biopsy

Aims To determine the spectrum of renal lesions in patients with kidney involvement in non-Hodgkins lymphoma (NHL) by renal biopsy. Methods The clinical features and histological findings at the time of the renal biopsy were assessed for each patient. Results We identified 20 patients with NHL and renal involvement, and the diagnosis of NHL was established following the kidney biopsy in 18 (90%) patients. The types of NHL include the following: chronic lymphocytic leukemia/small lymphocytic lymphoma (n = 8), diffuse large B-cell lymphoma (n = 4), T/NK cell lymphoma (n = 3), lymphoplasmacytic lymphoma (n = 2), cutaneous T-cell lymphoma (n = 1), mucosa-associated lymphoid tissue lymphoma (n = 1) and mantle cell lymphoma (n = 1). All presented with proteinuria, and 15 patients had impaired renal function. The pathological findings included (1) membranoproliferative glomerulonephritis-like pattern in seven patients; (2) crescent glomerulonephritis in four; (3) minimal-change disease in three, and glomeruli without specific pathological abnormalities in three; (4) intraglomerular large B-cell lymphoma in one; (5) intracapillary monoclonal IgM deposits in one; (6) primary diffuse large B-cell lymphoma of the kidneys in one; and (7) lymphoma infiltration of the kidney in eight patients. Conclusion A wide spectrum of renal lesions can be observed in patients with NHL, and NHL may be first proven by renal biopsies for evaluation of kidney injury or proteinuria. Renal biopsy is necessary to establish the underlying cause of renal involvement in NHL.

Renal biopsy in type 2 diabetes: timing of complications and evaluating of safety in Chinese patients.

Aim:  It has been recognized that renal lesions in patients with diabetes often have other causes of renal damage concomitantly. Renal biopsy is a valuable tool to provide histological evidence. However, the safety in patients with type 2 diabetes receiving renal biopsy is not well evaluated. This study was conducted to monitor the dynamic complications and to evaluate the safety of biopsy in diabetic patients.

Long-term outcome and prognostic factors of idiopathic membranous nephropathy in the Chinese population.

BACKGROUND Idiopathic membranous nephropathy (IMN) is a representative form of nephrotic syndrome in China. Although IMN is thought to run a more benign course in Asian patients than in the Caucasian population, there has been no persuasive study to determine the long-term prognosis and risk factors for IMN in the Chinese population. METHODS A retrospective chart review. All patients admitted to Nanjing Institution of Nephrology from January 1985 to December 2007 with biopsy-proven IMN were enrolled. The primary outcome was the renal survival rate and risk factors at renal biopsy. RESULT A total of 217 patients were included in the study, and the overall renal survival rates were 96.9%, 93.5%, and 86.6% at 5, 10, and 15 years after renal biopsy, respectively. When the clinical features at biopsy were evaluated, patients with hypertension (p = 0.023), decreased eGFR (p < 0.001), nephrotic-range proteinuria (p = 0.047), elevated urinary NAG (p = 0.045) and RBP (p = 0.007) had a worse prognosis. Cox multivariate analysis showed that decreased eGFR and chronic tubulointerstitial lesion were independent risk factors for ESRF (end-stage renal failure). CONCLUSION IMN is a disease with a comparatively good prognosis in the Chinese population, with a renal survival rate of more than 90% at 10 years after renal biopsy. Decreased eGFR at biopsy and chronic tubulointerstitial lesion are independent risk factors of ESRF. Partial or complete remission of proteinuria improved the prognosis.

Clinical and Morphologic Spectrum of Renal Involvement in Patients with HBV‐Associated Cryoglobulinemia

Cryoglobulinaemic glomerulonephritis related to hepatitis B virus (HBV) infection has been rarely reported. The aim of this study was to investigate the clinical features, renal biopsy findings in patients with HBV‐associated cryoglobulinaemia.