Shorter dialysis session length was not associated with lower mental health and physical functioning in elderly hemodialysis patients: Results from the Japan Dialysis Outcome and Practice Patterns Study (J-DOPPS)

<div><p>Background</p><p>Health-related quality of life (HRQOL) is often prioritized over long-term survival in elderly patients. Although a longer dialysis session length (DSL) has been shown to reduce mortality, its effects on improving the HRQOL are unknown.</p><p>Methods</p><p>Using data from the Japan Dialysis Outcomes and Practice Patterns Study (J-DOPPS), patients aged ≥ 65 years on maintenance hemodialysis were enrolled. DSL was categorized as short (<210 minutes), medium (210–240 minutes), or long (>240 minutes). The primary outcomes were changes in mental health (ΔMH) and physical functioning (ΔPF) scores assessed using the Japanese version of SF-12, in one year. The differences in the ΔMH and ΔPF among the three groups were assessed via regression (beta) coefficients derived using a linear regression model.</p><p>Results</p><p>Of 1,187 patients at baseline, 319 (26.9%) had a short length, 686 (57.8%) a medium length, and 182 (15.3%) a long length. We assessed the ΔMH data from 793 patients and the ΔPF data from 738. No significant differences in the ΔMH were noted for the short or long groups compared with the medium group (score difference: 0.26, 95% confidence interval [CI]: -4.17 to 4.69 for short; score difference: -1.15, 95% CI: -6.17 to 3.86 for long). Similarly, no significant differences were noted for these groups versus the medium group in ΔPF either (score difference: -1.43, 95% CI: -6.73 to 3.87 for short; score difference: -1.71, 95% CI: -7.63 to 4.22 for long).</p><p>Conclusions</p><p>A shorter DSL might have no adverse effects on MH or PF for elderly patients.</p></div

Multiple imputation using predictive mean matching (pmm) for censoring during study follow-up.

<p>Multiple imputation using predictive mean matching (pmm) for censoring during study follow-up.</p

Association between dialysis session length and change in mental health or physical functioning at one year after study initiation.

<p>Association between dialysis session length and change in mental health or physical functioning at one year after study initiation.</p

Baseline characteristics of patients, categorized by dialysis session length.

<p>Baseline characteristics of patients, categorized by dialysis session length.</p

Participant flow diagram and the study selection process.

<p>Participant flow diagram and the study selection process.</p

Characteristics of non-diabetic and diabetic wild-type and VASH2-deficient mice at the end of study.

<p>Characteristics of non-diabetic and diabetic wild-type and VASH2-deficient mice at the end of study.</p

The role of VASH2 knockdown in extracellular matrix production in cultured mesangial cells.

<p>Human mesangial cells (HMCs) were cultured under normal glucose (NG, 5.5 mM), NG plus mannitol (MN; NG plus mannitol, 19.5 mM) or high glucose (HG, 25 mM) condition for 24 hours in the presence of negative control siRNA (siCont, 10 nM) or VASH2 siRNA (siVASH2, 10 nM). (A) The expression of VASH2 mRNA relative to 18S rRNA was elevated in HG but not in MN condition. (B, C) Immunoblots for VASH2 and β-actin are shown (B). Each lane was loaded with 20 μg of protein obtained from cultured HMCs. Each band was scanned and subjected to a densitometric analysis (C). Transfection of siVASH2 reduced the level of VASH2 by approximately 80%. (D, E) The amount of type IV collagen α3 (D) and connective tissue growth factor (CTGF; E) relative to 18S rRNA is shown. Increase in these mRNA level caused by HG condition was significantly prevented by transfection of siVASH2. n = 4 for each group. ^§<i>P</i><0.05 versus NG or MN, *<i>P</i><0.05 versus NG with siCont or NG with siVASH2, ^#<i>P</i><0.05 versus HG with siCont. Each column shows the mean ± SE.</p

Localization of endogenous VASH2 in glomeruli.

<p>(A) The mRNA level of VASH2 in the kidney cortex from wild-type mice was assessed by real-time PCR. VASH2 expression was increased in diabetic condition compared with non-diabetic mice kidney. n = 6 for each group. *<i>P</i><0.05 versus wild-type mice. (B) VASH2 expression is detected with immunofluorescence for β-galactosidase. No immunoreactivity in glomeruli is seen in wild-type mice (left panel), whereas glomeruli from non-diabetic and diabetic VAHS2 knockout (VASH2^{<i>LacZ/LacZ</i>}) mice (middle and right panel, respectively) show a β-galactosidase-positive area (original magnification, ×400). (C) Double immunofluorescence for β-galactosidase and markers for glomerular component cells in VASH2 knockout mice show that the localization of β-galactosidase-positive area are consistent with platelet-derived growth factor receptor-β (PDGFRβ)-positive mesangial cells, but not CD31-positive endothelial cells and zonula occludens-1 (ZO-1)-positive podocytes.</p

Alterations of glomerular endothelial area and VEGF-A expression in diabetic VASH2 knockout mice.

<p>(A) The distribution of CD31, a marker for endothelial cells, was determined by immunofluorescence in non-diabetic wild-type, non-diabetic VASH2 knockout, diabetic wild-type, and diabetic VASH2 knockout mice (original magnification, ×400). (B) In quantitative analysis, CD31-positive glomerular endothelial area was expanded in diabetic wild-type mice, but it was significantly prevented in diabetic VASH2 knockout mice. No difference was found in endothelial area between non-diabetic wild-type and non-diabetic VASH2 knockout mice. (C, D) Immunoblot for vascular endothelial growth factor-A (VEGF-A; C) and VEGF receptor-2 (VEGFR2; D). Each lane was loaded with 40 μg of protein obtained from the renal cortex. Each band was scanned and subjected to a densitometric analysis. Increased VEGF-A level induced by diabetes showed no difference between wild-type and VASH2 knockout mice, whereas increased VEGFR2 expression seen in diabetic wild-type mice was significantly suppressed in diabetic VASH2 knockout mice. n = 6 for each group. *<i>P</i><0.05 versus non-diabetic WT or VASH2 knockout mice, ^#<i>P</i><0.05 versus diabetic WT mice. Each column shows the mean ± SE.</p

Urine albumin excretion, renal hypertrophy and creatinine clearance in non-diabetic and diabetic wild-type and VASH2 knockout mice.

<p>(A) Six weeks after the induction of hyperglycemia, albuminuria in diabetic wild-type (WT) mice (solid circles) was significantly exacerbated compared with that in non-diabetic WT mice (open circles). Although no difference was found in albuminuria between non-diabetic WT and non-diabetic VASH2 knockout mice (open squares), increased albuminuria induced by hyperglycemia was markedly prevented in diabetic VASH2 knockout mice (solid squares). (B, C) The increase in kidney weight-to-body weight ratio (B) and urine volume (C) induced by hyperglycemia did not significantly differ between WT and VASH2 knockout mice. (D) The increase in creatinine clearance (Ccr) level induced by hyperglycemia was significantly prevented in VASH2 knockout mice compared with WT mice. n = 6 for non-diabetic WT, 6 for non-diabetic VASH2 knockout, 10 for diabetic WT, and 8 for diabetic VASH2 knockout mice. *<i>P</i><0.05 versus non-diabetic WT or VASH2 knockout mice, **<i>P</i><0.01 versus non-diabetic WT or VASH2 knockout mice, ^#<i>P</i><0.05 versus diabetic WT mice, ^##<i>P</i><0.01 versus diabetic WT mice. Each column shows the mean ± SE.</p