Evaluation of metabolic risk marker in obesity-related glomerulopathy.

OBJECTIVE: Insulin resistance is a common metabolic abnormality, which increases the risk of renal events in obesity. The present study is aimed to examine the relation between metabolic factors and obesity-related glomerulopathy (ORG), and then compare the risk markers of insulin resistance for clinical prediction. METHODS: A total of 112 cases with proven renal ORG and 135 age- and gender-matched lean controls were included. The degree of proteinuria, endogenous creatinine clearance rate, body mass index, amylin, fasting glucose, insulin, lipid and lipoprotein concentrations were measured during the steady state. RESULTS: The patients with ORG were clinically characterized by increased body mass index and proteinuria, with higher levels of amylin, homeostasis model assessment of insulin resistance (HOMA-IR), insulin, glucose, and lipid proteins when compared with the lean controls. Multiple logistic regression analysis revealed that amylin and HOMA-IR were significantly associated with the prevalence of ORG. In patients with ORG, proteinuria level correlated with amylin, total cholesterol, fasting insulin, and HOMA-IR. Moreover, proteinuria correlated positively with HOMA-IR and amylin in a multiple regression analysis. In addition, the endogenous creatinine clearance rate did not correlate with any metabolic marker. CONCLUSION: This study suggested that screening for HOMA-IR might have predictive value for renal damage in obese patients. In addition to insulin resistance, amylin also showed positive effects on evaluation of such renal impairment.

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. METHODS: A prospective observation was performed on 130 patients with type 2 diabetes and 150 patients not undergoing renal biopsy. The complications were monitored at 4 h, 8 h, 24 h, 48 h and 72 h sequentially after biopsy. RESULTS: Haematoma was observed in 34 (26.15%) patients with diabetes and 50 (33.33%) in controls (P=0.19). The timing of large haematoma peaked at 4 h. Gross haematuria occurred in 12 (9.23%) diabetic patients and eight (5.33%) controls (P=0.207). It happened mainly within 8 h. Renal pathological diagnosis showed 96 (73.85%) cases with diabetic nephropathy and 34 (26.15%) cases with non-diabetic renal disease. CONCLUSION: Renal biopsy in patients with type 2 diabetes is safe. The frequency of complications after renal biopsy in diabetes is no higher than those without diabetes. The complications mostly happened within 8 h, especially within 4 h. Biopsy is also very necessary to rule out other chronic renal diseases in diabetes.

Obesity-related glomerulopathy: body mass index and proteinuria.

BACKGROUND AND OBJECTIVES: Obesity-related glomerulopathy (ORG) is an increasing cause of end-stage renal disease, but evidence concerning the effects of treatments is rather limited. This study was aimed at exploring the renoprotective effects of weight loss on patients with ORG. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: A total of 63 patients with renal biopsy-proven ORG had food and exercise intervention in the physician-supervised weight loss program and were divided into three groups on the basis of the percentage of weight change from baseline to follow-up: significant weight loss (>3% reduction in body mass index [BMI]), stable weight, or significant weight gain (>3% increase). Metabolic parameters and renal lesions were evaluated regularly for 2 years. RESULTS: After 6 months, 27 patients lost weight by 8.29 +/- 4.00%, with a mean decrease in proteinuria of 35.3%, whereas 24 months later, 27 patients achieved a 9.20 +/- 3.78% reduction in BMI and a 51.33% reduction in urine protein secretion. The levels of serum triglyceride, serum uric acid, and BP were also decreased. Contrarily, in patients with increased BMI, urine protein was increased by 28.78%. Correlation analysis showed proteinuria was associated with BMI, serum triglyceride, and uric acid, and multivariate regression analysis indicated the changes in BMI were the only predictor of proteinuria (P < 0.01). CONCLUSIONS: Weight loss intervention benefited remission of proteinuria in patients with ORG, whose function could not be replaced by conventional pharmacotherapy.

Triptolide reduces proteinuria in experimental membranous nephropathy and protects against C5b-9-induced podocyte injury in vitro.

Membranous nephropathy is a major cause of nephrotic syndrome in adults where podocyte injuries were found to mediate the development of proteinuria. Triptolide, a major active component of Tripterygium wilfordii Hook F, has potent immunosuppressive, anti-inflammatory and antiproteinuric effects. To study its antiproteinuric properties, we established an experimental rat model of passive Heymann nephritis and a C5b-9 injury model of podocytes in vitro. Treatment or pretreatment with triptolide markedly reduced established proteinuria as well as the titer of circulating rat anti-rabbit IgG antibodies in these nephritic rats, accompanied by a reduction in glomerular C5b-9 deposits. Expression of desmin, a marker of podocyte injury, diminished after triptolide treatment, whereas quantitative analysis of mean foot process width showed that effacement of foot processes was substantially reversed. In in vitro studies we found that triptolide deactivated NADPH oxidase, suppressed reactive oxygen species generation and p38 mitogen-activated protein kinase, and restored RhoA signaling activity. Triptolide did not interfere with the formation of C5b-9 on the membrane of podocytes. Thus, triptolide reduces established heavy proteinuria and podocyte injuries in rats with passive Heymann nephritis, and protects podocytes from C5b-9-mediated injury.

Crush syndrome after the Wenchuan earthquake: new experience with regional citrate anticoagulation continuous veno-venous hemofiltration.

PURPOSE: Acute renal failure (ARF) related to crush syndrome is usually treated with hemodialysis. Continuous veno-venous hemofiltration (CVVH) has seldom been adopted in this situation due to the main drawback of continuous anticoagulation. The purpose of this study was to evaluate the effectiveness and safety of regional citrate anticoagulation (RCA)-CVVH in two crush syndrome patients following the Wenchaun earthquake. METHODS: Two victims from the Wenchuan earthquake in Southwest China were admitted to our hospital on May 23, 2008, 11 days after their injury. The total entrapment time under the rubble was 5.5 and 22.5 hrs respectively. They remained oliguric on admission, in spite of vigorous treatment in the local hospital including aggressive fluid infusion, fasciotomy and intermittent hemodialysis. On admission, their serum myoglobin levels were 765 and 829 ng/mL, respectively. Further debridement and drainage were performed. RCA-CVVH was conducted; the citrate containing substitution fluid was infused in a pre-dilution manner at a rate of 4 l/h; calcium was infused through a separate access to the venous inlet of the double lumen catheter. The infusion rate was adjusted according to the serum ionized calcium and whole blood activated clotting time (WBACT). A low dose of low molecular weight heparin (LMWH) was infused at the rate of 150 approximately 300 U/h simultaneously for anticoagulation after anemia had been corrected and their wounds were stable. RCA-CVVH was substituted by conventional CVVH and LMWH anticoagulation when case 2 complicated with hypoxia. RESULTS: RCA-CVVH was well tolerated, hemodynamic status was stable, and no complications related with RCA-CVVH were noted. The body temperature and WBC decreased to normal range, while anemia and hypoalbuminia were corrected. The levels of serum myoglobin and creatine phosphokinase were also decreased to normal range. Their urine volume increased after 20 and 22 days of oliguria and the tubular function of the patients recovered well. Although the second case encountered acute cholecystitis and acute lung injury in the hospital, both the patients recuperated and neither of them underwent amputation. CONCLUSIONS: The present two crush patients have been successfully treated, but due to the limits of the small sample, it is difficult to generalize whether RCA-CVVH is safe enough for crush syndrome with a high risk of bleeding diathesis. Additional investigation with a larger number of patients is required. Fluid equilibrium, nutritional support, prevention of bleeding and infection are fundamental in this situation.

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.

Rhein improves renal lesion and ameliorates dyslipidemia in db/db mice with diabetic nephropathy.

Rhein (4,5-dihydroxyanthraquinone-2-carboxylic acid) is purified from rhubarb (Rheum officinale), a widely used traditional Chinese herb. In our previous studies, rhein was shown to be effective in ameliorating diabetic renal pathological changes and attenuating hyperlipidemia. Statins have also been proven to ameliorate renal pathological changes associated with diabetic nephropathy (DN) through lipid-dependent and -independent mechanisms. We here study the protective and regulatory effects of rhein on renal injury and dyslipidemia in db/db mice with DN, using simvastatin as the control, and provide information on the mechanisms by which rhein protects against renal damage from DN. The results indicated that urinary albumin excretion (UAE) was reduced after 8 weeks of treatment in the rhein group, and 12 weeks in the simvastatin group. The morphometric analysis revealed that levels of extracellular matrix (ECM) significantly decreased in the rhein group after the full treatment course, but not in the simvastatin group. The more powerful effects of rhein on decreasing transforming growth factor-beta1 (TGF-beta1) and fibronectin immunohistochemistry expression in renal tissue were also observed. And the plasma levels of cholesterol (Chol), triglyceride (TG), low-density lipoprotein cholesterol (LDL-C) and ApoE all decreased in both the rhein and the simvastatin groups. Together, our data suggested that both rhein and simvastatin regulate dyslipidemia. The powerful effect of rhein in renal protection is due to its widespread effects. Rhein is a new drug that can decrease lipid levels and protect against DN progression in a different fashion with simvastatin.

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.

Ultrastructural changes in the glomerular filtration barrier and occurrence of proteinuria in Chinese patients with type 2 diabetic nephropathy.

AIM: Diabetic nephropathy (DN) is one of the most important causes of end stage renal disease in the world. Its hallmark is proteinuria. Therefore, we set out to clarify the structural changes that occur in the glomerular filtration barrier in Chinese patients with true type 2 diabetic nephropathy, and to examine the relationship between these structural changes and proteinuria. METHODS: 42 Chinese patients with true T2DN were divided into three groups according to urinary protein excretion. Glomerular volume, endothelial cell density, endothelial cell number, glomerular basement membrane (GBM) width, podocyte density, podocyte number and foot process width were evaluated using light and electron microscopic morphometry. RESULT: Glomerular volume and endothelial cell number were increased in diabetic patients, but there was no difference between patients with respect to the degree of proteinuria. As proteinuria progressed, endothelial cell density remained unchanged, while the glomerular basement membrane (GBM) and podocyte foot process width increased, podocyte density and number decreased. CONCLUSIONS: Podocyte and GBM change more obviously during the development of proteinuria. Besides, proteinuria was inversely related to podocyte density, and directly related to GBM and glomerular volume.

The Oxford classification of IgA nephropathy: pathology definitions, correlations, and reproducibility.

Pathological classifications in current use for the assessment of glomerular disease have been typically opinion-based and built on the expert assumptions of renal pathologists about lesions historically thought to be relevant to prognosis. Here we develop a unique approach for the pathological classification of a glomerular disease, IgA nephropathy, in which renal pathologists first undertook extensive iterative work to define pathologic variables with acceptable inter-observer reproducibility. Where groups of such features closely correlated, variables were further selected on the basis of least susceptibility to sampling error and ease of scoring in routine practice. This process identified six pathologic variables that could then be used to interrogate prognostic significance independent of the clinical data in IgA nephropathy (described in the accompanying article). These variables were (1) mesangial cellularity score; percentage of glomeruli showing (2) segmental sclerosis, (3) endocapillary hypercellularity, or (4) cellular/fibrocellular crescents; (5) percentage of interstitial fibrosis/tubular atrophy; and finally (6) arteriosclerosis score. Results for interobserver reproducibility of individual pathological features are likely applicable to other glomerulonephritides, but it is not known if the correlations between variables depend on the specific type of glomerular pathobiology. Variables identified in this study withstood rigorous pathology review and statistical testing and we recommend that they become a necessary part of pathology reports for IgA nephropathy. Our methodology, translating a strong evidence-based dataset into a working format, is a model for developing classifications of other types of renal disease.

The Oxford classification of IgA nephropathy: rationale, clinicopathological correlations, and classification.

IgA nephropathy is the most common glomerular disease worldwide, yet there is no international consensus for its pathological or clinical classification. Here a new classification for IgA nephropathy is presented by an international consensus working group. The goal of this new system was to identify specific pathological features that more accurately predict risk of progression of renal disease in IgA nephropathy, thus enabling both clinicians and pathologists to improve individual patient prognostication. In a retrospective analysis, sequential clinical data were obtained on 265 adults and children with IgA nephropathy who were followed for a median of 5 years. Renal biopsies from all patients were scored by pathologists blinded to the clinical data for pathological variables identified as reproducible by an iterative process. Four of these variables: (1) the mesangial hypercellularity score, (2) segmental glomerulosclerosis, (3) endocapillary hypercellularity, and (4) tubular atrophy/interstitial fibrosis were subsequently shown to have independent value in predicting renal outcome. These specific pathological features withstood rigorous statistical analysis even after taking into account all clinical indicators available at the time of biopsy as well as during follow-up. The features have prognostic significance and we recommended they be taken into account for predicting outcome independent of the clinical features both at the time of presentation and during follow-up. The value of crescents was not addressed due to their low prevalence in the enrolled cohort.

Clinical features and renal outcome in lupus patients with diffuse crescentic glomerulonephritis.

The objectives of the study are to investigate the clinical features and renal outcomes in lupus patients with diffuse crescentic glomerulonephritis (DCGN). Ninety-four DCGN lupus patients were enrolled. Their clinical features and renal outcomes were investigated. There were 84 females and 10 males, with a mean age of 27.9 ± 10.7 years old. They represented: hypertension in 73 cases (77.7%), rapidly progressive glomerulonephritis in 62 cases (66.0%), 46 cases (48.9%) with nephritic syndrome, 35 (37.2%) gross hematuria, and 14 cases (14.9%) with uremic syndrome needed dialysis therapy. There were 25 cases received repeated renal biopsy. Their histological examination showed the decreasing of active lesions and the increasing chronic lesions. All patients were more than 6 months follow-up, and 79 patients (84.0%) were more than 12 months follow-up. At the first time of follow-up (3 months), the renal function, proteinuria, and anemia were improved significantly in all of cases received intensive immunosuppressive therapy. At the last time of follow-up (56.1 ± 18.8 months), only four patients eventually developed to the end-stage renal failure and five died with normal renal function. The lupus patients with DCGN presented more severe clinical syndromes, which were similar to those patients of type II of DCGN. The relative good renal outcomes were observed in those lupus patients, to which may be contribute to the effective induction therapy.

Mycophenolate mofetil versus cyclophosphamide for induction treatment of lupus nephritis.

Recent studies have suggested that mycophenolate mofetil (MMF) may offer advantages over intravenous cyclophosphamide (IVC) for the treatment of lupus nephritis, but these therapies have not been compared in an international randomized, controlled trial. Here, we report the comparison of MMF and IVC as induction treatment for active lupus nephritis in a multinational, two-phase (induction and maintenance) study. We randomly assigned 370 patients with classes III through V lupus nephritis to open-label MMF (target dosage 3 g/d) or IVC (0.5 to 1.0 g/m(2) in monthly pulses) in a 24-wk induction study. Both groups received prednisone, tapered from a maximum starting dosage of 60 mg/d. The primary end point was a prespecified decrease in urine protein/creatinine ratio and stabilization or improvement in serum creatinine. Secondary end points included complete renal remission, systemic disease activity and damage, and safety. Overall, we did not detect a significantly different response rate between the two groups: 104 (56.2%) of 185 patients responded to MMF compared with 98 (53.0%) of 185 to IVC. Secondary end points were also similar between treatment groups. There were nine deaths in the MMF group and five in the IVC group. We did not detect significant differences between the MMF and IVC groups with regard to rates of adverse events, serious adverse events, or infections. Although most patients in both treatment groups experienced clinical improvement, the study did not meet its primary objective of showing that MMF was superior to IVC as induction treatment for lupus nephritis.

Diagnosis, pathogenesis, treatment, and prognosis of hereditary fibrinogen A alpha-chain amyloidosis.

Mutations in the fibrinogen A alpha-chain gene are the most common cause of hereditary renal amyloidosis in the United Kingdom. Previous reports of fibrinogen A alpha-chain amyloidosis have been in isolated kindreds, usually in the context of a novel amyloidogenic mutation. Here, we describe 71 patients with fibrinogen amyloidosis, who were prospectively studied at the UK National Amyloidosis Centre. Median age at presentation was 58 yr, and renal involvement led to diagnosis in all cases. Even after a median follow-up of 4 yr, clinically significant extra-renal disease was rare. Renal histology was characteristic: striking glomerular enlargement with almost complete obliteration of the normal architecture by amyloid deposition and little or no vascular or interstitial amyloid. We discovered four amyloidogenic mutations in fibrinogen (P552H, E540V, T538K, and T525fs). A family history of renal disease was frequently absent. Median time from presentation to ESRD was 4.6 yr, and the estimated median patient survival from presentation was 15.2 yr. Among 44 patients who reached ESRD, median survival was 9.3 yr. Twelve renal transplants survived for a median of 6.0 (0-12.2) yr. Seven grafts had failed after median follow up from transplantation of 5.8 yr, including three from recurrent amyloid after 5.8, 6.0, and 7.4 yr; three grafts failed immediately for surgical reasons and one failed from transplant glomerulopathy after 5.8 yr with no histological evidence of amyloid. At censor, the longest surviving graft was 12.2 yr. In summary, fibrinogen amyloidosis is predominantly a renal disease characterized by variable penetrance, distinctive histological appearance, proteinuria, and progressive renal impairment. Survival is markedly better than observed with systemic AL amyloidosis, and outcomes with renal replacement therapy are comparable to those for age-matched individuals with nondiabetic renal disease.

Etiology and clinical characteristics of membranous nephropathy in Chinese patients.

BACKGROUND: Membranous nephropathy (MN) is a common cause of proteinuria and can be subdivided into idiopathic and secondary classifications. Most patients with MN present with associated systemic diseases that need to be identified before appropriately diagnosing idiopathic MN. However, the cause and clinical characteristics of MN in Chinese patients have not been investigated. STUDY DESIGN: Case series. SETTING & PARTICIPANTS: Patients with biopsy-proven MN at the Research Institute of Nephrology, Jinling Hospital, Nanjing University School of Medicine, Nanjing, China. OUTCOME: The diagnosis of idiopathic and secondary MN was based on clinical, initial laboratory, and histological findings. RESULTS: 390 patients with MN were identified from 1985 to 2005. Of 390 patients with MN, 124 (31.8%) had idiopathic MN and 266 had secondary MN (68.2%). Of patients with idiopathic MN, 75 (60.5%) were men and 49 (39.5%) were women. Mean age was 43.9 +/- 13.2 years (range, 14 to 78 years). Common presentations of idiopathic MN were 60.5% with proteinuria (39.5% of whom presented with nephrotic syndrome), 29.8% with hypertension, 17.7% with hematuria, and 0.8% with decreased kidney function. In patients with secondary MN, causes were autoimmune diseases (73.3%), infections (17.7%), tumors (4.5%), and drugs or toxins (4.5%). Systemic lupus erythematosus was the most common autoimmune disease (predominately in younger women). Hepatitis B predominated in younger men. Greater levels of proteinuria were found in patients who presented with drugs or toxins compared with patients with other secondary MNs (P < 0.05). LIMITATIONS: Not all patients underwent all tests, particularly serum tumor markers, hepatitis C virus antibody, and hepatitis C virus RNA tests. CONCLUSION: Proteinuria was a common presentation in patients with idiopathic MN, which was predominately found in middle-aged to elderly men. Secondary MN was more common than idiopathic MN, and most secondary MN diagnoses were secondary to systemic lupus erythematosus and hepatitis B infection.

Successful treatment of class V+IV lupus nephritis with multitarget therapy.

Treatment of class V+IV lupus nephritis remains unsatisfactory despite the progress made in the treatment of diffuse proliferative lupus nephritis. In this prospective study, 40 patients with class V+IV lupus nephritis were randomly assigned to induction therapy with mycophenolate mofetil, tacrolimus, and steroids (multitarget therapy) or intravenous cyclophosphamide (IVCY). Patients were treated for 6 mo unless complete remission was not achieved, in which case treatment was extended to 9 mo. An intention-to-treat analysis revealed a higher rate of complete remission with multitarget therapy at both 6 and 9 mo (50 and 65%, respectively) than with IVCY (5 and 15%, respectively). At 6 mo, eight (40%) patients in each group experienced partial remission, and at 9 mo, six (30%) patients receiving multitarget therapy and eight (40%) patients receiving IVCY experienced partial remission. There were no deaths during this study. Most adverse events were less frequent in the multitarget therapy group. Calcineurin inhibitor nephrotoxicity was not observed, but three patients developed new-onset hypertension with multitarget therapy. In conclusion, multitarget therapy is superior to IVCY for inducing complete remission of class V+IV lupus nephritis and is well tolerated.

Recurrent or de novo IgA nephropathy with crescent formation after renal transplantation.

IgA nephropathy is the most common glomerular disease in China, accounting for 38.8% of primary glomerular disease. It has been reported that 20.8% patients of IgA nephropathy had a different degree of crescent formation. From January 1995 to December 2004, 1000 patients had undergone cadaveric renal transplantation, and 1742 allograft renal biopsies were reviewed in the Department of Nephrology at Jinling Hospital, Nanjing University. Among them, 18 cases were found with crescent formation, in which 10 patients were diagnosed as recurrent or de novo IgA nephropathy because their immunofluorescence showed strong IgA deposition in mesangial area and capillary. The initial treatment protocol was CsA+Azp+Pred, except in two cases of CsA+MMF+Pred. There were 8 males and 2 females, with ages from 25 to 69 (mean of 37.1) years old. All of them showed progressive renal dysfunction with increasing level of serum creatinine ranged from 1.48 to 6.25 mg/dL. Seven cases presented edema with an increasing level of proteinuria (1.36 to 3.58 g/24hr), and nine cases presented with hematuria ranging from 50 to 1250 x 10(4)/mL (one showed gross hematuria). In pathological examinations, they showed mesangial proliferation and matrix expansion with 10% to 66.7% crescents (mean of 37.5%) in their allograft renal biopsy's samples. All patients changed their immunosuppressive regimens; however, nine of them eventually advanced to ESRD and returned to hemodialysis after 6 to 36 months. Two cases received second renal transplantation after six months to five years, and one kept stable renal function with 2.5 mg/dL of serum creatinine after three years of follow-up. IgA nephropathy with crescentic formation was not rare in renal allografts or native glomerulonephritis in Chinese patients. These patients showed rapidly progressive renal dysfunction, and most of them lost graft function and needed hemodialysis therapy.

Triptolide protects podocytes from puromycin aminonucleoside induced injury in vivo and in vitro.

Extracts of Tripterygium wilfordii Hook F have been used to treat glomerulonephritis for more than 30 years in China with dramatic antiproteinuric effects. Triptolide, a diterpene triepoxide, is one of the major active components of these extracts. To clarify its antiproteinuric effects we induced podocyte injury by puromycin aminonucleoside. Triptolide effectively reduced the proteinuria induced by puromycin in nephrotic rats without reducing the glomerular filtration rate. The antiproteinuric effect was associated with improvement in the foot process effacement, a decrease in the podocyte injury marker desmin as well as the restoration of nephrin and podocin expression and distribution. In cultured mouse podocytes triptolide pretreatment prevented the puromycin-induced disruption of the actin cytoskeleton and microfilament-associated synaptopodin while protecting nephrin and podocin expression. Triptolide suppressed reactive oxygen species generation and p38 mitogen-activated protein kinase activation while restoring RhoA signaling activity. These results show that triptolide ameliorates puromycin aminonucleoside-mediated podocyte injury in vivo and in vitro.

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.

Clinicopathological and genetic characteristics in Chinese patients with lipoprotein glomerulopathy.

OBJECTIVE: In this study, we report on 16 Chinese patients with biopsy-proven lipoprotein glomerulopathy (LPG) investigated for clinical manifestations, pathological characteristics and apolipoprotein E (apoE) genetic analysis. METHODS: A retrospective analysis of the clinical and pathological features was made in 16 patients with LPG. Plasma concentrations and genetic analysis of apoE were completed. Glomerular depositions of apoA, apoB and apoE were detected using monoclonal antibodies on cryostatic sections in all patients. RESULTS: All 16 patients presented with edema; 14 presented with nephrotic syndrome. Anemia, microhematuria, hypertension and abnormal levels of serum creatinine were detected in 12 patients (75%), 11 patients (69%), 8 patients (50%) and 6 patients (37.5%), respectively. All the patients showed hypertriglyceridemia, while only 7 showed slight hypercholesterolemia. The characteristic features of hyperlipidemia in these patients were approximately in accord with those of type IV hyperlipoproteinemia. Concentrations of apoB correlated with urine protein, triglycerides and cholesterol (r=0.558, p=0.038; r=0.6, p=0.023; r=0.65, p=0.012; respectively). No correlation was found between serum level of apoE and clinicopathological features in patients with LPG. The genotype of apoE-epsilon3/epsilon4 is the predominant one in Chinese patients with LPG. No mutated forms of apoE were found, compared with previous reports. CONCLUSION: Unique clinicopathological and genetic features were found in this group of Chinese patients with LPG compared with the general population, including lower serum levels of apoE and cholesterol, as well as anemia and microhematuria. Multiple factors other than apoE were involved in the pathogenesis of LPG.