[Low flux dialysate daily home hemodialysis: A result for the 62 first French and Belgian patients]. / Hémodialyse quotidienne à bas débit de dialysat à domicile : résultats cliniques et biologiques des 62 premiers patients traités en France et en Belgique.

Since 2011, a new device is available for low flux dialysate quotidian home hemodialysis in France and Belgium. This study aims to evaluate the characteristics and dialysis prescriptions for Nx Stage System One™ users. We retrospectively included patients trained between 2011 and 2013 in France and Belgium. We collected data concerning their clinical features, their dialysis prescriptions, their laboratory parameters until 6 months of dialysis and, reason for dropping in case of cessation. Sixty-two patients from 31 centers, aged 48±18 years old, with a sex ratio 46/16 (M/F) are included with a median Charlson comorbidity index of 1 [0-3]. Of these patients, 71% are anuric and have been on dialysis for a mean time of 136.6±125 months. Previously, most of them had been taken care of in satellite units of dialysis (45%) and 14% are incident patients. In total, A total of 60% have an arterio-veinous fistula (AVF), with 18 patients using the Buttonhole system and 2 patients have a tunneled catheter. Median time for training was 26.5 days (17-45). Among the patients, 69% are dialyzed 6 days a week, during a mean time of 142.5±20 minutes with a volume of 20.9±3 liters of dialysate and without anticoagulant (63%). Predialytic levels of hemoglobin, creatinin, urea, phosphorus and ß2microglobulin remain stable. On the contrary, there is a significant improvement of albumin and bicarbonate levels. Technique survival was 75% at 1 year, and major reason for cessation was kidney transplant. It seems that this device fits for young patients, with few comorbidities and a long past in renal chronic failure. These results suggest that dialysis adequacy is acceptable despite low dialysate volumes but need confirmation with a longer follow up and a larger cohort.

Impact of simultaneous pancreas and kidney transplantation on progression of coronary atherosclerosis in patients with end-stage renal failure due to type 1 diabetes.

OBJECTIVE: Mortality in type 1 diabetic patients with end-stage renal failure is high and dominated by coronary atherosclerotic events. With regard to prognosis, simultaneous transplantation of pancreas and kidney (SPK) may be superior to kidney transplantation alone (KTA) in type 1 diabetic patients, because normalization of blood glucose levels may reduce progression of coronary atherosclerosis and because it is well known that progression of coronary atherosclerosis is one of the major factors that determines clinical prognosis. However, no data are available on progression of coronary atherosclerosis after SPK. RESEARCH DESIGN AND METHODS: We performed an observational angiographic study comparing progression of coronary atherosclerosis, analyzed with quantitative coronary angiography, in patients with (n = 26) and those without (n = 6) a functioning pancreas graft after SPK, to test the hypothesis that normalization of blood glucose levels by SPK may indeed reduce progression of coronary atherosclerosis in type 1 diabetic patients and thereby improve prognosis. RESULTS: Mean follow-up was 3.9 years. Average glucose control was significantly worse for the patients without a pancreas graft than for patients with a functioning pancreas graft: 11.3 (SD 3.5) vs. 5.9 mmol/l (SD 1.1) (P = 0.03). Mean segment diameter loss (progression of diffuse coronary atherosclerosis) was 0.024 mm/year (SD 0.067) in patients with a functioning pancreas graft, compared with 0.044 mm/year (SD 0.038) in patients in whom the pancreas graft was lost. Minimum obstruction diameter loss (progression of focal coronary atherosclerosis) was 0.037 mm/year (SD 0.086) in patients with a functioning pancreas graft compared with 0.061 mm/year (SD 0.038) in patients in whom the pancreas graft was lost. Regression of atherosclerosis occurred in 38% of patients with a functioning pancreas graft compared with 0% of patients of whom the pancreas graft was lost (P = 0.035). CONCLUSIONS: Our study provides, for the first time, evidence that in patients who have undergone SPK, progression of coronary atherosclerosis in patients with a functioning pancreas graft is reduced compared with patients with pancreas graft failure. Our observation is an important part of the explanation for the observed improved mortality rates reported in type 1 diabetic patients with end-stage renal failure after SPK compared with KTA. In light of these findings described above, SPK must to be carefully considered for all diabetic transplant candidates.

Glucose-induced fibronectin and collagen type III expression in renal fibroblasts can occur independent of TGF-beta1.

BACKGROUND: Various renal cell types have been shown to contribute to the excessive matrix deposition observed in diabetic nephropathy. The present study examined the effect of high ambient glucose and transforming growth factor-beta1 (TGF-beta1) on matrix production by human renal fibroblasts. METHODS: Human renal fibroblasts (TK173) were used to examine the effects of high glucose and TGF-beta1 on fibronectin and collagen type III expression. Stable transfectants were generated of TK173 cells expressing a dominant negative TGF-beta type II receptor. Matrix components were measured in enzyme-linked immunosorbent assay (ELISA) and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Fibronectin secretion by renal fibroblasts was increased upon exposure to high glucose, but with delayed kinetics compared to TGF-beta1-induced fibronectin. Exposure to high glucose resulted in an increased secretion of latent TGF-beta1. However, treatment with neutralizing pan-specific anti-TGF-beta antibodies could not attenuate the effects of glucose. Furthermore, collagen type III was up-regulated by high glucose, but not by TGF-beta1. Importantly, fibroblasts expressing a dominant negative TGF-beta type II receptor were defective in TGF-beta1-induced fibronectin production, whereas glucose-induced fibronectin and collagen type III were unaffected. CONCLUSIONS: These data show that in renal fibroblasts exposure to high glucose can increase matrix production independent of endogenous TGF-beta1. Although glucose activation is accompanied by an increased production of latent TGF-beta1, which can have an important role in vivo, the data suggest involvement of alternative growth factors in the mechanism by which hyperglycemic conditions can modulate matrix accumulation in diabetic nephropathy.

Deposition of nucleosomal antigens (histones and DNA) in the epidermal basement membrane in human lupus nephritis.

OBJECTIVE: Antinuclear autoantibodies complexed to nucleosomes can bind to heparan sulfate (HS) in the glomerular basement membrane. This binding is due to the binding of the positively charged histones to the strongly anionic HS. Nucleosomes and histones have been identified in glomerular deposits in human lupus nephritis. We investigated whether nucleosomes are present in the basement membrane of nonlesional skin of lupus patients. METHODS: Skin biopsy samples from patients with systemic lupus erythematosus (SLE) (30 with active lupus nephritis and 15 with inactive disease) and controls (with parapemphigus or diabetes) were stained for IgG, histones, DNA, and nucleosomes. RESULTS: IgG deposits were found in 87% of the patients with lupus nephritis, in 33% of the patients with inactive disease, and in 71% of the parapemphigus patients. Using polyclonal antihistone antibodies, histones were detected in 87% of lupus nephritis patients, but in none of the other SLE patients or the diabetes controls (P < 0.0001). Among the parapemphigus controls, 14% of samples stained positive in one of the polyclonal antihistone stainings (P < 0.0001). Using monoclonal antibodies, histones and DNA were identified in 21% of the lupus nephritis patients. Although none of the other groups showed positive staining for nucleosomes, 7% of the lupus nephritis biopsy samples were positive using antinucleosome monoclonal antibodies. Colocalization of nucleosomal antigens and IgG was confirmed using confocal laser microscopy. CONCLUSION: These findings suggest that nucleosome-mediated binding of autoantibodies to basement membranes may also occur at sites in the body other than in the glomerulus.