Objective    To investigate the features of malignancy in end-stage aristolochic acid nephropathy (AAN) patients undergoing renal replacement therapy in the First Affiliated Hospital of Wenhou Medical University.    Methods    One hundred and two patients diagnosed as end-stage AAN during 2004 to 2013 were enrolled in the study, and separately udergoing hemodialysis, peritoneal dialysis and renal transplantation, to study the features of the malignancy and its risk factors.    Results (1) There were totally 42 AAN patients suffering from malignancy, and 39 of them had urinary cancer. Eight cases of urinary cancer had metastasis, and 11 cases of bladder cancer had repeated recurrences. Patients suffering from malignancy had an increased mortality compared to patients without malignancy(13/42 vs 7/60, P=0.022). (2) Thirteen malignacy cases were diagnosed before the end-stage of AAN, the rest cases appeared in 1-13 years[(4.62±3.31) years] after renal replacement. (3) A further logistic regression analysis of the 29 maligancy patients after renal replacement showed that, the dose of aristolochic acid (counted by Mutong) was the only risk factor of malignancy (P=0.091), compared with the dose of Mutong less than 60 g, the patients with an accumulated dose of Mutong more than 200 g had a 4.26 folds（95%CI 1.02, 17.83）higher risk of malignancy. There was no statistic difference of the malignancy risk among different renal replacement therapies, which however might influence the pathogenic sites of the urinary cancer. The simple bladder cancer was the most common malignancy among the hemodialysis patients (72.72%), and the upper urinary tract cancer among the peritoneal dialysis patients (66.67%), while the complex of both were dominant among the renal transplantation patients(40.00%).    Conclusions    Among the end-stage of AAN patients undergoing renal replacement therapy in Wenzhou area, the incidence of urinary cancer is high, with a character of complex, multiple and repeated recurrences. The occurence of malignancy seems to be separated from the renal function, but turns out obviously dose-dependent. There was no statistical difference of cancer risk among hemodialysis, peritoneal dialysis, and renal transplantation, which may induce different pathogenic sites of the urinary cancer.

Objective    To explore the clinico-pathological features and outcomes of primary focal segmental glomerular sclerosis with IgM deposition.    Methods    One hundred and two patients with primary focal segmental glomerular sclerosis (pFSGS) in Hangzhou hospital of traditional Chinese medicine between 1996 and 2012 were retrospectively studied. The patients were divided into IgM deposition group (n=66) with IgM deposition in glomeruli and none-IgM deposition group (n=36)without IgM deposition. Baseline and clinical characteristics of all FSGS patients were assessed and outcomes were reviewed. The survival rates of the patients were analyzed using the Kaplan-Meier method.    Results    (1) There were not difference in age, sex ratio, incidence of microscopic hematuria, hypertension, renal insufficiency, eGFR, Ccr and Scr between two groups. However, proteinuria, incidence of nephrotic syndrome, urine microalbumin, urine NAG, serum cholesterol, serum high-density lipoprotein, and serum IgM in IgM deposition group were significantly higher than those in none-IgM deposition group (P＜0.05), serum albumin and serum IgA in IgM deposition group were significantly lower than those in none-IgM deposition group (P＜0.05). (2) The IgM deposition group had a significantly higher incidence of glomerular deposition of IgA, IgG, C3, C1q and fibrinogen than none-IgM deposition group (P＜0.05). The score of mesangial matrix proliferation in the IgM deposition group was lower than that in none-IgM deposition group (P＜0.05). (3) fifty-four patients (35 patients in IgM deposition group and 19 patients in none-IgM deposition group） were followed-up for a median of 64.6 (22.8, 103.8) months. Progression to renal failure was observed in 5 patients of IgM deposition group and none in none-IgM deposition group. Compared with the none-IgM deposition, the survival rates in the IgM deposition group were statistically lower (P＜0.05).    Conclusions    PFSGS patients with IgM deposition were severer in proteinuria, higher incidence of IgA, IgG, C3, C1q and fibrinogen deposition in glomeruli and worse outcome than those without IgM deposition.

Objective    To retrospectively analyze the changes of cardiovascular disorder and explore the risk factors in non-dialysis patients with chronic renal failure(CRF).    Methods    A total of 106 patients with CRF were enrolled in the cross-sectional study. The patients were divided into four groups by estimated glomerular filtration rate (eGFR): ≥45, 30-44, 15-29, ＜15 ml·min-1·(1.73 m2)-1. Clinical data and biochemical indicators were collected. Cardiac ultrasound measurement of cardiac lumen diameter parameters and function were assessed by echocardiography. The associations of different stages of eGFR with changes of cardiac structure and function were analyzed.    Results    A negative linear correlation was observed by liner regression between eGFR(MDRD) and left ventricular mass index (r=-0.345, P＜0.01). Logistic regressive analysis revealed that categories of eGFR(MDRD) [β=0.940, OR=2.561, 95%CI (1.380, 4.755), P＜0.01], the history of cardiovascular diseases[β=2.156, OR=8.639, 95%CI(1.991, 37.476), P＜0.01], urinary protein/creatinine ratio[β=0.001, OR=1.001，95%CI(1.000, 1.001), P＜0.01] correlated with left ventricular hypertrophy in the chronic renal failure without renal replacement therapy. The prevalence of concentric hypertrophy in eGFR(MDRD)≥45 ml·min-1·(1.73 m2)-1 was 3/3, while in eGFR(MDRD)=15-29 ml·min-1·(1.73 m2)-1 the prevalence was 3/12. The difference between two groups was significant(P＜0.01). There were no significant difference among the four groups in left ventricular diastolic function and systolic function. Left ventricular mass index had a linear correlation with eGFR measured by creatinine and Cystatin C(r=-0.378, P＜0.01).    Conclusions    Reduced kidney function is associated with increased left ventricular mass index. The type of left ventricular hypertrophy is mainly concentric hypertrophy at early stage of chronic renal failure. Categories of eGFR (MDRD), the history of cardiovascular diease, urinary protein /creatinine ratio may be important risk factors of left ventricular hypertrophy in the patients with chronic renal failure without renal replacement therapy.

Objective    To describe the presentation, pathology, and outcome of biopsy proved renal disease in HIV infected patients.    Methods    This retrospective study included all HIV infected patients who underwent renal biopsy during the course of their clinical care at PUMC hospital from 2002 to 2012. The pathology and clinical information were abstracted from each patient’s clinical record.    Results    Eight HIV infected patients had biopsy confirmed renal disease. The commonest presentation was proteinuria in eight patients, and microscopic hematuria in six patients. Two patients had serum creatinine levels abnormal. Renal pathologies included IgA nephropathy in four patients, and lupus-like nephropathy, non-specific focal segmental glomerulosclerosis, membranous nephropathy and Henoch-Schonlein purpura nephritis in one patient each. All 8 patients received highly active antiretroviral treatment (HAART). Urinary protein was decreased significantly in one of them. Another was relieved with ACEI/ARB in addition to HAART. Corticosteroid was given to the other 6 patients. Among them, two got remission. one presented no reaction and was given cyclosporine. One, whose urinary protein didn't decrease with ACEI/ARB, received corticosteroid and needed further observation. One had continued aggravation of the renal disease. One case died of AIDS. One case companied with IgA nephropathy whose proteinuria recurrence was considered having association with tenofovir renal toxicity relieved after adjustment of HAART.    Conclusions    Classical HIVAN is uncommon in Chinese HIV infected population, a variety of other pathologies were seen in HIV infected patients, renal biopsy can help confirm the diagnosis. In HIV infected patients with evidence of nephropathy should be treated with HAART at diagnosis. Addition of prednisone should be considered if HAART alone does not result in improvement of renal disease. 

Objective        To investigate the role of activated cylic AMP(cAMP) signaling in chemical-induced podocyte injury.    Methods    Eight-weeks-old male BalB/C mice were randomly divided into three groups: control group, Adriamycin (ADR) group and Forskolin+ADR group. ADR nephropathy models were established by tail intravenous injection，and part of them were injected Forskolin, an agonist of adenylate cyclase, intraperitoneally. Phosphorylation of cAMP response element binding protein (CREB) was detected by laser confocal microscopy，morphology of foot processes were determined with transmission electron microscope, and WT-1 expression in glomeruli were detected by immunohistochemistry. Conditionally immortalized podocytes were treated with puromycin aminonucleoside (PAN), Exchange protein directly activated by cAMP (Epac) agonist 8-pCPT-2-O-Me-cAMP (2Me), protein kinase A (PKA) antagonist H89 and its agonist pCPT-cAMP(pCPT). Western blot was used to detect the expression levels of Epac, caspase3 and cleaved caspase3. PKA activity was assayed using cAMP-dependent protein kinase detection system. Cell viability was determined by a cell count kit and podocyte apoptosis was estimated by TUNEL staining. Mitochondrial membrane potential was evaluated by JC-1 staining.     Results    （1）Compared with ADR group, the urine albumin decreased significantly (P＜0.05) among Forskolin+ADR group and the WT-1 positive cells per glomerulus increased obviously (P＜0.05). （2）PAN decreased podocyte number in a time-dependent manner (P＜0.05), pre-treatment with pCPT obviously inhibited PAN induced podocyte decrease (P＜0.05), but H89 prevented the effect of pCPT in a dose-dependent manner (P＜0.05). （3）JC-1 staining showed that the percentage of podocyte with green fluorescence for control, PAN and pCPT+PAN group were (12.67±2.15)%, (31.35±4.60)% and (16.96 ± 2.51)% respectively (P＜0.05), and pretreatment with H89 inhibited the effect of pCPT (P＜0.05). （4）PAN promoted podocyte apoptosis and cleaved caspase3 expression (P＜0.05), and pretreatment with pCPT significantly prevented PAN-induced podocyte apoptosis and cleaved caspase3 expression (P＜0.05).    Conclusions    cAMP signaling activation ameliorated podocyte injury in ADR mice and PAN-induced podocyte apoptosis, and cAMP/PKA pathway may mediate these processes.