28 research outputs found

    AQP1 Promoter Variant, Water Transport, and Outcomes in Peritoneal Dialysis.

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    BACKGROUND: Variability in ultrafiltration influences prescriptions and outcomes in patients with kidney failure who are treated with peritoneal dialysis. Variants in AQP1, the gene that encodes the archetypal water channel aquaporin-1, may contribute to that variability. METHODS: We gathered clinical and genetic data from 1851 patients treated with peritoneal dialysis in seven cohorts to determine whether AQP1 variants were associated with peritoneal ultrafiltration and with a risk of the composite of death or technique failure (i.e., transfer to hemodialysis). We performed studies in cells, mouse models, and samples obtained from humans to characterize an AQP1 variant and investigate mitigation strategies. RESULTS: The common AQP1 promoter variant rs2075574 was associated with peritoneal ultrafiltration. Carriers of the TT genotype at rs2075574 (10 to 16% of patients) had a lower mean (±SD) net ultrafiltration level than carriers of the CC genotype (35 to 47% of patients), both in the discovery phase (506±237 ml vs. 626±283 ml, P = 0.007) and in the validation phase (368±603 ml vs. 563±641 ml, P = 0.003). After a mean follow-up of 944 days, 139 of 898 patients (15%) had died and 280 (31%) had been transferred to hemodialysis. TT carriers had a higher risk of the composite of death or technique failure than CC carriers (adjusted hazard ratio, 1.70; 95% confidence interval [CI], 1.24 to 2.33; P = 0.001), as well as a higher risk of death from any cause (24% vs. 15%, P = 0.03). In mechanistic studies, the rs2075574 risk variant was associated with decreases in AQP1 promoter activity, aquaporin-1 expression, and glucose-driven osmotic water transport. The use of a colloid osmotic agent mitigated the effects of the risk variant. CONCLUSIONS: A common variant in AQP1 was associated with decreased ultrafiltration and an increased risk of death or technique failure among patients treated with peritoneal dialysis. (Funded by the Swiss National Science Foundation and others.)

    The Tasmanian Epilepsy Register--a community-based cohort. Background and methodology for patient recruitment from the Australian national prescription database.

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    BACKGROUND/AIMS: Centralized prescription databases may provide an efficient mechanism for recruitment of community-treated disease. METHODS: The Australian federal government agency, the Health Insurance Commission (HIC), invited patients to participate in the Tasmanian Epilepsy Register (TER). Eligible patients included those who received at least one anticonvulsant above a 'reportable' price threshold between July 1, 2001 and June 30, 2002. Patients were asked to disclose their medical indication for anticonvulsant treatment with additional demographic and prescription information obtained from the HIC. RESULTS: 7,541 were eligible for recruitment. After two mail invitations over 6 months, 3,375 (46.6%) had responded, but TER enrollment amongst those indicating treatment for epilepsy was 1,180 (78.3%). TER participants were more likely to obtain their prescriptions exclusively from their general practitioner (70.9%) or from combined sources (19.1%) rather than from pediatrician (4.2%), neurologist (1.4%) or general physician (1.0%) sources. Patients were more likely to respond with increasing age (linear trend p < 0.001), when from a higher socioeconomic area (linear trend p < 0.001), or if their prescription was obtained from a neurologist (p < 0.001). CONCLUSION: The national Australian prescription database represents community-treated epilepsy and provides an effective and efficient method for patient recruitment for clinical epidemiological research
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