Search

BACKGROUND The objective of this study was to evaluate the interaction between the length polymorphism of the guanosine thymidine repeat [(GT)n] in the heme oxygenase-1 (HO-1) gene and far-infrared (FIR) therapy on access flow (Qa) and arteriovenous fistula (AVF) patency in hemodialysis (HD) patients. METHODS A total of 280 HD patients were randomized into a control group (n = 141) and the FIR group (n = 139) who received 40 min of FIR therapy three times weekly for a year during the study period from May 2005 to December 2007. Access flow was measured during HD. The [(GT)n] was determined with the definition of long (L) allele as [(GT)n] ≥ 30 and short (S) allele as [(GT)n] < 30. RESULTS The Qa decreased from S/S to S/L and further to the L/L group but increased by FIR therapy with the highest Qa increase in the S/S group. The incidence of AVF malfunction decreased both from the L/L, S/L to S/S group (32.4 versus 17.2 versus 10.9%, P = 0.007) and from the control group to FIR group (27.5 versus 12.6%, P = 0.004). Significant associations were found between AVF malfunction and the following factors (hazard ratio, P-value): a past history of AVF malfunction (2.45, P = 0.044), FIR therapy (0.369, P = 0.03) and L/L genotypes of HO-1 (2.531 versus S/S + S/L genotypes). The 1-year unassisted patency decreased from 91.9 and 77.6% in S/S and S/L subgroups with and without FIR therapy to 75.8 and 60% for L/L subgroup with and without FIR therapy, respectively (P < 0.001). CONCLUSIONS FIR therapy improves Qa and patency of AVF in HD patients, with the best protective effect in those with S/S genotype of HO-1.

Background. Glomerular filtration rate (GFR) and comorbidity at dialysis initiation in relation to mortality in end-stage renal disease is still controversial. We studied factors potentially related to the mortality in incident haemodialysis (HD) patients. Methods. A national database included 23 551 incident HD patients from July 2001 to December 2004. Kaplan–Meier and Cox regression analyses were performed to assess the association between GFR estimated by the four-variable Modified Diet in Renal Disease equation and all-cause mortality. Analyses were performed from Day 91 after the start of dialysis. Patients were classified into five groups (quintiles) based on estimated glomerular filtration rate (eGFR) at the start of dialysis. Results. The median eGFR at dialysis initiation was low (4.7 mL/min/1.73 m 2 ), as was the mortality in the first year of dialysis [13.2/100 patient-year, 95% confidence interval (95% CI)=12.8–13.7]. There was an inverse association between lower eGFR and higher survival rate. The Cox regression model revealed an increase in mortality risk in Q5 (hazard ratio [HR]=2.44, 95% CI=2.11–2.81), Q4 (HR= 1.66, 95% CI=1.43–1.93), Q3 (HR=1.21, 95% CI=1.04– 1.41) and Q2 (HR=1.18, 95% CI=1.01–1.37) compared with the reference group of Q1 after adjusting for year of application, primary diseases (chronic glomerulonephritis, diabetic nephropathy, hypertension, chronic tubulointerstitial nephritis and others), demographics (age, sex), presence of co-morbidity (diabetes mellitus, hypertension, congestive heart failure, ischaemic heart diseases, cerebrovascular diseases, malignancies, liver cirrhosis, tuberculosis, other diseases and free of reported of comorbidities) and haematocrit. Propensity score analysis also showed a higher eGFR to be associated with increased mortality risks. Adjustment for all covariates explained a high percentage of excess risk of mortality in the groups with low eGFR, but less risk in the groups with higher eGFR. Conclusions. Lower eGFR at dialysis initiation is associated with lower mortality. Conditions at dialysis initiation explained excess 1-year mortality risk differently in patients who began dialysis at different levels of eGFR. Other factors likely contribute to the mortality of patients initiating dialysis at higher eGFR levels, and further study is needed.

Keywords: angiomyolipoma; computed tomography;focal segmental glomerulosclerosis; kidney cancer;liposarcoma; proteinuriaA 63-year-old man with type 2 diabetes mellitus andhypertension presented with increasing abdominalgirth and foamy urine for the previous 2 years.Impaired renal function (BUN 33mg/dl, serum crea-tinine 2.3mg/dl), hypoalbuminaemia (2.3g/dl), overtproteinuria (11.2g/day), microscopic haematuria(RBC 21-35/HPF) and bilateral perinephric tumourwere noted at a local hospital. Non-contrast enhancedcomputed tomography of the abdomen confirmedgiant bilateral perinephric tumour with fat component(Figure 1). The differential diagnosis included retro-peritoneal liposarcomas or bilateral angiomyolipomaarising from renal capsule. After referral, physicalexamination revealed distended abdomen withoutpalpable mass. Magnetic resonance imaging(T1-weighted) demonstrated a lipomatous tumour ofabout 10cm in size, in the bilateral perinephric space(Figure 2). There was absence of radiological featuresof angiomyolipoma, including linear or branchingappearance of intra-tumoural vessels with evidentcontrast enhancement, aneurysmal dilatation of intra-tumoural vessels, haemorrhage within and outside thetumour, and the bridging vessel or beak signs [1].Hence, bilateral perinephric liposarcoma was favoured.However, a sonography-guided needle biopsy of theleft tumour showed only fibroadipose tissue, withoutidentification of malignant cells. The simultaneousneedle biopsy of left kidney revealed focal segmentalglomerulosclerosis (FSGS). Considering the invasiveclinical course of the tumours, bilateral radicalnephrectomy, with excision of the retroperitonealtumours, was performed. The pathology disclosedwell-differentiated liposarcomas with encasement ofbilateral kidney and involvement of the renal sinus,and further confirmed FSGS. The patient thereafterunderwent regular uneventful haemodialysis. TheFSGS and liposarcomas may just be coincidental inthis patient. However, the probability of bilateralperinephric liposarcoma with secondary FSGS stillcannot be completely excluded.Around 12–40% of liposarcomas occur in theretroperitoneum [2,3], and of these, 35% originate inthe perirenal fat [2]. Although liposarcoma is the mostcommon retroperitoneal soft tissues sarcoma, retro-peritoneal liposarcoma comprises only about 0.1% ofall cancers [2,3]. Liposarcomas tend to grow slowly in

Background Fas-mediated apoptosis is important in the regulation of immune response. Human peritoneal mesothelial cells (HPMCs) are able to regulate peritoneal inflammation, but the role of Fas in HPMCs is not clear. This study addresses the mechanisms of Fas-mediated apoptosis in HPMCs. Methods Tumour necrosis factor-alpha (TNF-alpha) primed HPMCs were stimulated with agonistic anti-Fas antibody. The expression of Fas was evaluated by real-time reverse transcription polymerase chain reaction (TaqMan quantitative polymerase chain reaction) and flow cytometry. Apoptosis was assessed by nuclear morphology, TUNEL assay, fractional DNA content and cytokeratin 18 cleavage. Caspase activation and bcl-2 expression were analysed by western blotting. The phagocytosis of apoptotic HPMCs was demonstrated by immunofluorescence and transmission electron microscopy. Results Cultured HPMCs constitutively expressed Fas, and the Fas expression was upregulated by TNF-alpha. TNF-alpha primed HPMCs underwent apoptosis after anti-Fas antibody treatment, and the apoptotic HPMCs could be phagocytosed by macrophages. TNF-alpha was able to downregulate bcl-2 expression. Activation of caspase-3 and caspase-8 was noted during the apoptotic process. The inhibitors of either caspase-3 or caspase-8 could prevent the Fas-induced apoptosis in HPMCs. We also detected increased HPMC apoptosis in dialysate effluent during the recovery phase of peritonitis in peritoneal dialysis patients. Conclusions TNF-alpha directs HPMCs to commit apoptosis via the Fas/Fas ligand pathway through a modulation of Fas and bcl-2. Our study shows that HPMCs undergo apoptosis during peritonitis and suggests that the apoptosis of HPMCs may be related to the resolution of peritoneal inflammation.