Improvement of intradialytic hypotension in diabetic hemodialysis patients using vitamin E-bonded polysulfone membrane dialyzers.

Currently, there are no detailed reports on the effects of vitamin E-bonded polysulfone (PS) membrane dialyzers on intradialytic hypotension (IDH) in diabetic hemodialysis (HD) patients. This study was designed to evaluate changes in intradialytic systolic blood pressure (SBP) using "VPS-HA" vitamin E-bonded super high-flux PS membrane dialyzers. The subjects were 62 diabetic HD patients whose intradialytic SBP fell by more than 20%. Group A comprised patients who required vasopressors to be able to continue treatment or who had to discontinue therapy due to their lowest intradialytic SBP being observed at 210 min (28 patients). Group B comprised patients who showed no symptoms and required no vasopressors but showed a gradual reduction in blood pressure, with the lowest intradialytic SBP seen at the end of dialysis (34 patients). The primary outcome was defined as the lowest intradialytic SBP after 3 months using VPS-HA. Secondary outcomes included changes in the following: lowest intradialytic diastolic blood pressure, pulse pressure, pulse rate, plasma nitric oxide and peroxynitrite, serum albumin, and hemoglobin A1c. Group A's lowest intradialytic SBP had significantly improved at 3 months (128.0 ± 25.1 mm Hg vs. 117.1 ± 29.2 mm Hg; P = 0.017). Group B's lowest intradialytic SBP had significantly improved at 1 month (134.4 ± 13.2 mm Hg vs. 121.5 ± 25.8 mm Hg; P = 0.047) and 3 months (139.1 ± 20.9 mm Hg vs. 121.5 ± 25.8 mm Hg; P = 0.011). We conclude that VPS-HA may improve IDH in diabetic HD patients.

Two novel aquaporin-2 mutations in a sporadic Japanese patient with autosomal recessive nephrogenic diabetes insipidus.

We identified two novel mutations of the aquaporin-2 (AQP2) gene in a sporadic Japanese patient diagnosed with an autosomal recessive nephrogenic diabetes insipidus (NDI). The patient, a Japanese boy, was referred to our clinic at the age of 5 months because of unexplained recurrent fever. He was diagnosed with NDI by clinical, biochemical and endocrine findings. Molecular analysis demonstrated that he was a compound heterozygote for two mutations. One mutation consisted of a two base deletion in exon 1 (197, 198 delCA). This deletion caused a frameshift in the open reading frame, resulting in a premature stop codon 186 bases downstream in exon 1. The second mutation was a G to A transition of the terminal exon splice site (1502-1G-->A). To date, several mutations in the AQP2 gene have been described, however no splicing mutation in the AQP2 gene has been identified. The deletion mutation described in this case study was inherited patemally and the splicing site mutation was inherited maternally, indicating an autosomal recessive inheritance. In the present case study, we identified two new mutations in the AQP-2 gene. Previous studies have shown that there is no hot spot for mutations in the AQP-2 gene, and thus genetic analysis for individual patients is helpful for genetic counseling and early diagnosis.

Two novel mutations of thiazide-sensitive Na-Cl cotrans porter (TSC) gene in two sporadic Japanese patients with Gitelman syndrome.

Gitelman syndrome is a renal disorder characterized by hypokalemia, hypomagnesemia, metabolic alkalosis and hypocalciuria due to the defective tubular reabsorption of magnesium and potassium. This disease is caused by mutations of thiazide-sensitive Na-Cl cotransporter (TSC) gene. Gitelman syndrome is usually distinguished from Bartter syndrome by the presence of both hypomagnesemia and hypocalciuria. However, a phenotypic overlap is sometimes observed. We encountered two sporadic Japanese patients with Gitelman syndrome and analyzed their TSC gene. These patients were diagnosed as Gitelman syndrome by the typical clinical findings and biochemical abnormalities, such as mild muscular weakness, periodic paralysis, tetany, metabolic alkalosis, hypomagnesemia and hypocalciuria. In patient 1, a novel two base deletion (del TG at nucleotide 731 and 732) in exon 5 and a two base deletion (del TT at nucleotide 2543 and 2544) in exon 21 previously reported in a Japanese patient were identified. The patient 2 had a missense mutation (L623P), that was also identified in Japanese patients, and a novel in-frame 18 base insertion in exon 6 as a heterozygous state. Family analysis of two patients confirmed an autosomal recessive inheritance. In conclusion, we add two new mutations of the TSC gene in Japanese patients with Gitelman syndrome. Because the differential diagnosis between Bartter syndrome and Gitelman syndrome is sometimes difficult, molecular analysis would be a useful diagnostic tool, particularly in unusual cases with phenotypic overlapping.