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Objective: The aim of this study was to investigate the association of the maximum lifetime body mass index (max BMI) with hemodialysis initiation and comorbidities in Japanese hemodialysis patients. Methods: In a retrospective cross-sectional study on 724 hemodialysis patients, max BMI, age at hemodialysis initiation, and comorbidities including sleep apnea syndrome, cerebro-cardiovascular diseases, and proliferative diabetic retinopathy (PDR) were analyzed. Early hemodialysis initiation was defined as age Result: Diabetes patients showed a higher max BMI and prevalence of atherosclerotic diseases than nondiabetes patients, despite almost the same age at hemodialysis initiation. Patients with early hemodialysis initiation showed higher male ratio, prevalence of PDR, and max BMI than those with later initiation, despite almost equal prevalence of diabetes. Receiver-operating characteristic curve analysis determined a max BMI of 28.4 kg/m2 as a reliable cutoff value for predicting early hemodialysis initiation, and this parameter was identified as an independent predictor of early hemodialysis initiation using bivariate logistic regression analysis. Vitrectomy for PDR also tended to contribute independently to early hemodialysis initiation. Conclusion: A high max BMI contributed to early hemodialysis initiation independent of diabetes. Furthermore, PDR was associated with a high max BMI and early hemodialysis initiation. These results suggest that weight reduction in young chronic kidney disease patients with obesity may prevent hemodialysis and blindness.

Diabetic nephropathy is a common complication in diabetes mellitus (DM). Thiazolidinedione (TZD) is thought to ameliorate diabetic nephropathy, however, the mechanism has not been elucidated. We hypothesized that VEGF participates in the pathogenesis of diabetic nephropathy and that TZD may be beneficial for the treatment of diabetic nephropathy through its effect on VEGF. Increased VEGF expression was demonstrated in the glomeruli of DM rats and rat mesangial cells (RMC) incubated with high medium glucose. It was also demonstrated that VEGF promoted mesangial cell proliferation, which was inhibited by TZD. It was shown that a rapid fall and rise of ambient glucose concentration induces more VEGF production and cell proliferation in RMC than in cells with continuously high glucose medium, which was also inhibited by TZD. Prostaglandin J2 and protein C kinase inhibitors significantly inhibited [3H]thymidine incorporation in RMC incubated with VEGF, which was inhibited by TZD. These findings indicate that a rapid change of glucose concentration promotes RMC proliferation by the increased production of VEGF. TZD has an inhibitory action through, at least in part, PPAR-gamma.

Glomerular hypertension aggravates glomerular sclerosis by inducing growth factors, e.g., transforming growth factor-β (TGF-β) to mesangial matrix expansion. Smads are intracellular proteins that transmit signals from TGF-β to nucleus, and Smads are also negatively regulated by inhibitory Smads (I-Smads), Smad6 and Smad7. However, little is known about the role of I-Smads in glomerular hypertension. We studied I-Smad expression in cultured mesangial cells subjected to mechanical stretch as an in vitro model of glomerular hypertension.Rat mesangial cells were cultured under cyclic mechanical stretch conditions using the Flexercell Strain Unit. Phosphorylated Smad1 and Smad2 were determined by Western blots. The expression of Smad6 and Smad7 mRNAs was determined by Northern blots. Stretch-mediated I-Smad mRNAs of cells pre-treated with MAPK-ERK kinase inhibitor, U0126, were also determined. Localization of phospho-Smad1, Smad6 and Smad7 proteins in the glomerulus of Dahl salt-sensitive rats was determined by immunohistochemistry.Stretch stress increased phospho-Smad1 levels, and significantly decreased Smad6 mRNA to 32 % of control, and increased Smad7 mRNA to 136 % of control. U0126 significantly attenuated stretch-mediated decreases in Smad6 mRNA, but had no effect on stretch-mediated increases in Smad7 mRNA. Phospho-Smad1, Smad6 and Smad7 proteins were localized in podocytes and mesangial cells of Dahl rats.Mechanical stretch increases phospho-Smad1 levels and down-regulates Smad6 mRNA expression in mesangial cells. Stretch-mediated down-regulation of Smad6 is partially involved in ERK1/2 activation. These results indicate that glomerular hypertension might augment Smad1 signaling with concomitant attenuation of Smad6-mediated negative feedback.

脳卒中片麻痺25例における足関節機能再建術の効果を装具効果との対比において,加速度計および床反力連続測定装置を用い経時的に定量的解析を行った.手術適応範囲を下肢装具による歩行パターンの矯正の程度より4つに区分したところ,各区分とも再建術の効果がみられた.特に区分3のプラスチック装具歩行レベルでは,歩行スピード,歩調,歩幅,対称性,安定性において装具歩行と近似した値を示し,さらに床反力データから得られた患側の移行性,支持性,接地性に関する指標は経時的にも安定した改善を認めた.本再建術の効果は装具の効果を大きく上回るものではないが,ほぼ全例が術前の予測値に到達し,その有効性が客観的に明らかになった.

A 42-year-old man previously diagnosed with congenital diabetes insipidus (DI) developed polydipsia and polyuria (water intake and urine excretion, above 20 l per day). On admission, a serum sodium level of 124 mEq/l, a serum chloride level of 87 mEq/l, and plasma osmolality of 254 mOsm/kg H2O were found, although urine osmolality was always less than 100 mOsm/kg H2O, with daily urine excretion of more than 15 l. Creatinine clearance was 153 l/day. Initially, he had free access to water and his daily water intake was 20–27 l. Restriction of water intake (10 l/day) normalized his serum sodium levels and alleviated his general fatigue. Hyponatremia is a rare fluid electrolyte disturbance in DI. We found no reports of hyponatremia associated with congenital nephrogenic DI, presumably because the osmosensing mechanism is intact in such patients. The use of thiazides for the treatment of polyuria, in combination with potassium-sparing diuretics and salt restriction, may accelerate the genesis of hyponatremia caused by psychogenic polydipsia in nephrogenic DI.

To determine whether plasma vascular endothelial growth factor (VEGF) level is elevated in Type 2 diabetic patients with an early stage of diabetic nephropathy.We studied 71 Japanese Type 2 diabetic patients with normal serum creatinine level (100 micromol/l) (age 63.0 [60.3-65.6] years old, diabetes duration 15.6 [14.0-17.3] years, HbA1c 7.36% [7.06-7.66%], mean [95% confidence interval, CI]): normoalbuminuric patients (n=36); microalbuminuric patients (n=21); and proteinuric patients (n=14). Plasma VEGF concentration was measured by a quantitative sandwich enzyme immunoassay technique.Plasma VEGF concentration was not related to the degree of albuminuria: normoalbuminuric patients (25 [13-95] ng/l, median [25th-75th percentile]); microalbuminuric patients (33 [15-120] ng/l); and proteinuric patients (54 [17-107] ng/l). Plasma VEGF level in patients with retinopathy (25 [15-95] ng/l, n=30) was not elevated as compared to those without retinopathy (53 [14-126] ng/l, n=34). Plasma VEGF tended to correlated negatively with diabetes duration (R's=-.217, P=.0690) and HbA1c (R's=-.221, P=.0647), whereas there was no correlation between plasma VEGF level and age, serum creatinine or urinary albumin to creatinine ratio (ACR) of the patients, respectively. Plasma VEGF level in the group of patients with HbA1c equal to or below the median (7.2%) was significantly higher than that in the group of patients with HbA1c above the median (7.2%) (P.05).The results suggested that Type 2 diabetic patients with microalbuminuria and those with retinopathy are not necessarily associated with an elevation of circulating plasma VEGF concentration. Plausible association between plasma VEGF level and glycemic control remains to be seen.