Protein C and protein S deficiencies may be related to survival among hemodialysis patients.

BACKGROUND: Thrombophilia due to protein C (PC) and protein S (PS) deficiencies is highly prevalent among patients with stage 5 chronic kidney disease and is reported to arise due to extracorporeal circulation during hemodialysis (HD). This study aimed to evaluate the relationship between HD treatment and thrombophilia. METHODS: A total of 114 Japanese patients on maintenance HD (62 men, 52 women) were followed during 2008-2011. Their survival rates were compared against the duration of HD. Prior to each HD, coagulation/fibrinolysis parameters and PC and PS activities were measured using standard techniques. The patients were divided into two groups: Group 1, with PC and/or PS deficiencies (n = 32), and Group 2, without PC and PS deficiencies (n = 82). The influence of such deficiencies and duration of dialysis on survival was examined. Time-to-event analysis was applied using Kaplan-Meier estimates, and the log-rank test was proposed to test the equivalence of relative survival data. Hazard ratios and 95% confidence intervals (CI) were calculated. RESULTS: Of the 114 patients, 37 died (Group 1, 22; Group 2, 15). The hazard ratio (95% CI) was higher (p = 0.004) in Group 1 than Group 2. Gene analyses of PC and PS were performed in 14 patients from Group 1. No mutations in either protein were observed. We analyzed the causes of death in both groups; however, the estimated thrombophilia-related incidence of death could not be determined due to small sample size of HD patients. CONCLUSIONS: Our results suggest that PC and PS deficiencies may be related to survival in HD patients. However, this finding warrants additional research.

Current international status of home hemodialysis.

Three times weekly home hemodialysis (HHD) was introduced shortly after the initiation of chronic hemodialysis (HD) treatment in 1960. HHD eliminates the need of transportation to and from the dialysis unit and by allowing patients to set their own dialysis schedule, decreases the burden of treatment on their personal and professional lives. HHD has been found more economical and more highly associated with better patient survival than in-center dialysis. Nevertheless, the global prevalence of HHD decreased between 1980 and 2000 due to the increased availability of dialysis units and continuous ambulatory peritoneal dialysis, advances in cadaveric kidney transplantation, and several other factors. However, the availability of HHD at a frequency of more than 3 times/week, the typical frequency of conventional HD (CHD), in such forms as brief HD sessions of 2-3 h 5-6 days/week and nocturnal HD (NHD) has led to reversals in this trend. Frequent HHD, such as short daily HD (SDHD) and NHD instead of 3 times/week CHD, has been found to significantly improve hypertension, left ventricular mass, renal anemia, quality of life and mortality. On the other hand, NHD has been found to significantly improve hypertension, left ventricular mass, renal anemia, quality of life, malnutrition, mortality and phosphate clearance. Many observational clinical studies and one randomized controlled trial of SDHD and/or NHD have been conducted, and compact and convenient dialysis machines have been developed and used for HHD. The most recent data reported in the national and local registries of selected countries indicate that the prevalence of HHD among all dialysis patients from 2008 to 2010 varied from 0 to 3.3% except in New Zealand and Australia, where it was 16.3 and 9.3%, respectively. As HHD appears to be a more effective and economical dialysis modality than in-center CHD, its prevalence is likely to increase in the future.

Role of nitric oxide synthase activity in experimental ischemic acute renal failure in rats.

To determine the role of nitric oxide (NO) in acute renal failure (ARF), we have studied the time course change activities to activity of nitric oxide synthase (NOS) isoform activities, both calcium dependent and independent NOS, in experimental ischemic ARF. We have also analyzed change activities to activity of the NOS activities in both renal cortex and medulla. Male SD rats (n = 5) were inducted to ARF by ischemia-reperfusion injury and divided into the following groups; Control group (sham operation), Day 0 group, (measurement performed on that day of operation), Day 1 group, (measurement performed one day after induction of ARF), Day 3 group and Day 7 group. Measurement of NOS activity was based on the following principles; NO is synthesized from arginine by nitric oxide synthase (NOS) and NO is converted to NO2(-)/NO3(-)(NOx) by oxidation. Detection of the final metabolite of NO, NOx was done using flow injection method (Griess reaction). The results were, (1) calcium dependent NOS activity in the cortex and medulla decreased, however it increased in the recovery period in the renal cortex (Cortex; Control, 0.941 +/- 0.765, D0, 0.382 +/- 0.271, D1, 0.118 +/- 0.353, D3, 2.030 +/- 0.235, D7, 3.588 +/- 2.706, Medulla; Control, 1.469 +/- 0.531, D0, 0.766 +/- 0.156, D1, 0.828 +/- 0.187, D3, 2.078 +/- 0.094, D7, 1.289 +/- 0.313 micromol NOx produced/mg protein/30 min). (2) On the other hand, iNOS activity increased in the early phase of ARF, both in the cortex and medulla, but returned to control values during the recovery phase in cortex and was maintained at higher levels in the medulla (Cortex; Control, 0.333 +/- 0.250, D0, 0.583 +/- 0.428, D1, 1.167 +/- 0.262, D3, 0.250 +/- 0.077, D7, 0.452 +/- 0.292, Medulla; Control, 0.139 +/- 0.169, D0, 0.279 +/- 0.070, D1, 1.140 +/- 0.226, D3, 0.452 +/- 0.048, D7, 0.625 +/- 0.048 micromol NOx produced/mg protein/30 min). These findings suggest that the role of NOS in ARF are different for the different NOS isoforms and have anatomic heterogeneity.