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Serum carnitine is decreased in hemodialysis patients, which induces muscle atrophy. Thus, we examined the different effects of l‐carnitine and exercise on exercise activity and muscle status in hemodialysis patients. Twenty patients were divided into l‐carnitine and cycle ergometer groups and were followed for 3 months. Muscle and fat mass, physical activities, and muscle status were evaluated by an impedance, physical function test, and magnetic resonance imaging, respectively. The l‐carnitine significantly increased muscle mass (P =.023) and thigh circumference (P =.027), decreased fat mass (P =.007), and shortened chair stand‐up time (P =.002) and 10‐m walk test (P =.037). The fat fraction was improved by the l‐carnitine (P =.047). Compared with the exercise group, l‐carnitine improved the changes in 10‐m walk test (P =.026), chair stand‐up time (P =.014), and thigh circumference (P =.022). Baseline fibroblast growth factor‐21 and myostatin levels predicted the l‐carnitine‐associated changes in exercise activities. l‐carnitine, rather than exercise, improved physical activity and muscle status in hemodialysis patients. [ABSTRACT FROM AUTHOR]

Mitochondrial diseases (MDs) are occasionally difficult to diagnose. Growth differentiation factor 15 (GDF15) has been reported as a biomarker useful for not only diagnosing MDs, but also evaluating disease severity and therapeutic efficacy. To enable the measurement of serum GDF15 concentrations at medical institutions, we developed a new latex‐enhanced turbidimetric immunoassay (LTIA) as an automated diagnostic indication test for MDs. We also examined the equivalency of specificity and sensitivity in measuring serum GDF15 concentrations between a commercially available enzyme‐linked immunosorbent assay (ELISA) kit and a novel LTIA device in patients with MDs, disease controls, and healthy controls. A clinical performance study used a newly developed LTIA device and an existing ELISA kit to measure the concentrations of GDF15 in 35 MD patients, 111 disease controls, and 86 healthy controls. The median (first quartile‐third quartile) of serum GDF15 concentrations measured with the LTIA device was significantly higher (P <.001) in MD patients (1389.0 U/mL [869.5‐1776.0 U/mL]) than in healthy controls (380.5 U/mL [330.2‐471.8 U/mL]); the interquartile ranges did not overlap between MD patients and healthy controls. The areas under the curve in disease and healthy controls were 0.812 (95% confidence interval [CI]: 0.734‐0.886) and 0.951 (95% CI: 0.910‐0.992), respectively. The automated, high‐throughput technology‐based LTIA device has definite advantages over the ELISA kit in shorter processing time and lower estimated cost per sample measurement. The LTIA device of GDF15 may be a sufficiently reliable, frontline, diagnostic indicator of individuals with suspected MDs in the general population. [ABSTRACT FROM AUTHOR]

Leukocyte apheresis (LCAP) is a safe and effective treatment for active ulcerative colitis (UC) in Japan. Nevertheless, a limitation of LCAP is its requirement for two puncture sites (double‐needle [DN] apheresis), sometimes leading to problems with needle puncture. Single‐needle (SN) apheresis is useful in hemodialysis and reduces needle puncture pain. If SN apheresis were found to be useful in LCAP for UC, it may reduce patient burden. The aim of this study was to compare the safety and efficacy of SN apheresis with that of DN apheresis. Twenty‐four patients with active UC were retrospectively enrolled. They underwent either SN apheresis (n = 12) or conventional double‐needle (DN) apheresis (n = 12) at the Kurume University Hospital from February 2014 to March 2018. At each session, we recorded access problems defined by the time required to initiate apheresis and the frequency of puncture‐related problems, as well as blood circuit clotting, defined as clotting necessitating interruption of apheresis and changing of the circuit. Efficacy was assessed using partial Mayo scores. The number of apheresis sessions was comparable between SN and DN apheresis (9.0 ± 2.0 times vs 9.6 ± 1.4 times, mean ± SEM). SN significantly reduced the time required to start apheresis (10.0 ± 5.4 minutes vs 19.4 ± 11.9 minutes, P <.05) as well as needle puncture troubles (0.9% vs 11.5%, P <.05). SN had comparable frequency of blood clotting episodes (5.6% vs 8.7%). SN apheresis had similar clinical efficacy (P <.001 in SN and P <.01 in DN). The improvement and remission rates were comparable between groups. SN apheresis may be safe and effective and may reduce patient burden during UC treatment. Nevertheless, further comparative studies are needed. [ABSTRACT FROM AUTHOR]

Peritoneal protein loss due to high peritoneal permeability may contribute to hypoalbuminemia and early withdrawal from peritoneal dialysis ( PD) therapy in end stage renal disease ( ESRD) patients. We have found that pigment epithelium-derived factor ( PEDF) has anti-vasopermeability properties both in cell culture and animal models by counteracting the biological actions of vascular endothelial growth factor ( VEGF). However, it remains unknown which clinical variables, including dialysate VEGF and PEDF, are associated with decreased serum albumin levels and could predict early withdrawal from the PD in ESRD patients. We address these issues. Twenty-seven ESRD patients undergoing PD were enrolled. Clinical variables were measured at 6 months after commencing PD. We examined the independent correlates of serum albumin in PD patients and then prospectively investigated the predictors of withdrawal from the PD therapy over 4 years. Dialysate VEGF was associated with peritoneal solute transport rate ( P = 0.002), serum albumin (inversely, P < 0.001) and dialysate PEDF levels ( P < 0.001). In multiple stepwise regression analysis, age ( P = 0.002) and dialysate VEGF levels ( P < 0.001) were independent determinants of serum albumin levels. High VEGF (>27 pg/mL), low serum albumin (≤3.31 g/dL) and low hemoglobin (≤11.2 g/dL) were correlated with withdrawal from the PD therapy during the 4 years. The odds ratio of dialysate VEGF for early withdrawal from the PD was 6.310 ( P = 0.035). The present study demonstrated that increased dialysate VEGF was associated with decreased serum albumin and early withdrawal from the PD therapy. Inhibition of peritoneal VEGF production may be a therapeutic target in PD patients. [ABSTRACT FROM AUTHOR]

Phosphate binders are useful for the treatment of hyperphosphatemia in hemodialysis ( HD) patients. This study was performed to examine the effects of switching from calcium carbonate ( CC) to lanthanum carbonate ( LC) on bone mineral metabolism and inflammatory markers in HD patients. We conducted 29 stable HD patients receiving CC, which was replaced by LC and followed-up for 12 weeks. Patients underwent determinants of blood chemistries such as serum calcium ( Ca), phosphorus, parathyroid hormone ( PTH) and vitamin D status, and interleukin-6 ( IL-6) mRNA levels in whole blood cells were evaluated by real-time PCR just before and after the treatment with LC. Corrected levels were significantly reduced, but serum phosphorus levels ( P levels) were unchanged after LC treatment. Switching to LC increased whole- PTH, osteocalcin, 1,25 (OH)2D3 levels and 1,25 (OH)2D3/25 (OH)D3 ratio. 1,25 (OH)2D3/25 (OH)D3 ratio was negatively correlated with HD duration. Furthermore, whole blood cell IL-6 mRNA levels were significantly reduced by LC treatment. We provided that the switching from CC to LC improved Ca overload and ameliorated vitamin D and inflammatory status in HD patients. These observations suggest that LC may play a protective role for the progression of atherosclerosis and vascular calcification in these patients. [ABSTRACT FROM AUTHOR]

ABSTRACT: Aim: There is accumulating evidence that advanced glycation end products (AGE) play a role in cardiovascular disease (CVD) in patients with haemodialysis (HD). Carnitine deficiency is frequently observed in HD patients, which may also contribute to CVD. In this study, we examined whether carnitine deficiency was independently associated with increased tissue accumulation levels of AGE in HD patients. Methods: One hundred and twenty-nine HD patients underwent determinations of blood chemistries including serum level of carnitine. Tissue AGE levels were evaluated by measuring skin autofluorescence with an AGE-reader. Results: Serum carnitine levels were significantly lower, while skin AGE levels were significantly higher in HD patients compared with healthy controls ( P < 0.001). In univariate analysis, β2-microglobulin (β2-MG) and carnitine (inversely) were correlated with skin AGE levels. Multiple stepwise regression analysis revealed that carnitine levels were one of the independent determinants of skin AGE levels ( P = 0.024). When β2-MG-adjusted skin AGE levels were stratified by serum carnitine levels, a statistical significance and dose-response relationship were observed ( P = 0.043). Furthermore, skin AGE levels were one of the independent determinants of serum carnitine levels as well ( P = 0.012). Conclusion: The present study demonstrated that decreased carnitine levels were independently associated with increased skin AGE levels in HD patients. Since carnitine is reported to inhibit the formation of AGE in vitro, our study suggests that supplementation of carnitine may be a therapeutic target for preventing the accumulation of tissue AGE and subsequently reducing the risk of CVD in HD patients. [ABSTRACT FROM AUTHOR]

C-reactive protein (CRP) level predicts future cardiovascular events in patients on haemodialysis (HD). Advanced glycation end products (AGE) play a role in cardiovascular disease (CVD) in HD patients. However, which variables including tissue AGE levels are independently associated with CRP remains unknown. Therefore, whether tissue AGE and CRP levels were correlated with atherosclerosis in HD patients was examined. Fifty-four HD patients underwent determinations of blood chemistries and tissue AGE. Tissue AGE levels were evaluated by measuring skin autofluorescence. Pulsatility index (PI) in the carotid artery was measured using a Doppler ultrasonography. Univariate analyses showed that age, white blood cells, serum albumin (inversely), alkaline phosphatase (inversely), tartrate-resistant acid phosphatase 5b (TRAP5b) (inversely) and skin AGE levels were significantly correlated with high-sensitivity CRP (hsCRP). Multiple stepwise regression analysis revealed that serum albumin, TRAP5b and skin AGE levels were independent determinants of hsCRP. Further, PI was highest among HD patients with high skin AGE and high hsCRP levels. The present study suggests that tissue AGE level is one of the independent determinants of hsCRP in HD patients. Tissue AGE and hsCRP levels may be correlated with each other, which could in concert contribute to the progression of atherosclerosis in these subjects. This study demonstrates the association between tissue advanced glycation end products (AGE) level and high-sensitivity C-reactive protein (hsCRP) in haemodialysis patients. In addition, tissue AGE and hsCRP levels could in concert contribute to the progression of atherosclerosis in these subjects. [ABSTRACT FROM AUTHOR]

1. Regulatory T cells (Treg) and cytotoxic T cells (CTL) are involved in various immune diseases. However, the prognostic impact of Treg and CTL in patients with myeroperoxidase anti-neutrophil cytoplasmic antibody-associated glomerulonephritis (MPO-ANCA-GN) is not well known. Therefore, in the present study, we examined the relationship between expression of forkhead box P3 (Foxp3) and T cell intracytoplasmic antigen (TIA)-1, Treg and CTL markers and renal survival in patients with MPO-ANCA-GN. 2. Forty patients with MPO-ANCA-GN and 10 patients with minimal change nephrotic syndrome (MCNS) underwent physical examination, determination of blood chemistry and renal biopsy. Immunohistochemical staining for Foxp3 and TIA-1 was performed on paraffin-embedded renal sections. 3. Although almost all patients received standard immunosuppressive treatment for 6 months, seven MPO-ANCA-GN patients needed maintenance haemodialysis (HD), whereas 33 patients did not (non-HD). Both Foxp3- and TIA-1-positive cells were detected in the interstitium and glomeruli of MPO-ANCA-GN patients, whereas they were rarely detected in patients with MCNS. The total crescent rate was significantly higher in the HD group than in the non-HD group (35.9 ± 3.5 vs 65.8 ± 7.4, respectively). In the interstitium, the age-adjusted Foxp3/TIA-1 ratio was significantly higher in the non-HD group than in the HD group (0.016 ± 0.016 vs 0.004 ± 0.008, respectively; P < 0.05). The Foxp3/TIA-1 ratio, but not the Foxp3/CD3 ratio, remained significantly higher in the non-HD group than in the HD group even after adjustment for crescent rate. Age- and total crescent rate-adjusted renal survival rates were higher in patients with a Foxp3/TIA-1 ratio ≥ 0.06 than in patients with a Foxp3/TIA-1 ratio < 0.06 ( P = 0.02). 4. The results of the present study suggest that Treg could play a protective role against MPO-ANCA-GN and that a decreased Foxp3/TIA-1 ratio in interstitial areas may predict future renal failure in patients with MPO-ANCA-GN. [ABSTRACT FROM AUTHOR]

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