Krüppel-like factor 15 is a key suppressor of podocyte fibrosis under rotational force-driven pressure.

Krüppel-like factor 15 (KLF15) is a well-known transcription factor associated with podocyte injury and fibrosis. Recently, hypertensive nephropathy was discovered to be closely related to podocyte injury and fibrosis. However, methods to stimulate hypertension in vitro are lacking. Here, we constructed an in vitro model mimicking hypertension using a rotational force device to identify the role of KLF15 in fibrosis due to mechanically induced hypertensive injury. First, we found that KLF15 expression was decreased in patients with hypertensive nephropathy. Then, an in vitro study of hypertension due to rotational force was conducted, and an increase in fibrosis markers and decrease in KLF15 levels were determined after application of 4 mmHg pressure in primary cultured human podocytes. KLF15 and tight junction protein levels increased with retinoic acid treatment. siRNA-mediated inhibition of KLF15 exacerbated pressure-induced fibrosis injury, and KLF15 expression after treatment with angiotensin II was similar to that observed after treatment with the blood pressure modeling device. Furthermore, the reduced KLF15 levels after mechanical pressure application were restored after the administration of an antihypertensive drug. KLF15 expression was also low in vivo. We confirmed the protective role of KLF15 in fibrosis using a mechanically induced in vitro model of hypertensive injury.

Hand Grip and Leg Muscle Strength in Hemodialysis Patients and Its Determinants.

BACKGROUND: Chronic kidney disease is associated with chronic inflammation and progressive loss of peripheral muscle strength and the ability to exercise, and these changes are highly pronounced in patients receiving hemodialysis (HD). We evaluated hand grip strength (HGS) and leg muscle strength (LMS) in patients receiving HD and attempted to identify factors associated with muscle strength. METHODS: We screened HGS (opposite the fistula side) and LMS (both sides) in HD patients at a single center (n = 112) by using digital hand and leg dynamometers (T.K.K. 5401 and 5710e/5715, Takei Scientific Instruments Co. Ltd., Niigata, Japan). RESULTS: The mean age of patients was 62.6 years, and 73.2% of the patients were male. Diabetes was the cause of kidney failure in 50% of the patients, and the median HD vintage was 34 months. A total of 77.7% of patients reported that they participated in regular home-based exercise, and 29.5% of patients regularly participated in hospital-based resistance exercise. HGS and LMS showed good correlation (r = 0.715, P < 0.001). HGS (25.1 vs. 17.0 kg) and LMS (30.1 vs. 20.4 kg) were greater in males (P < 0.001 and P < 0.001, respectively) than in females. Older patients (≥ 60 years) showed less LMS than younger patients in both males and females (P = 0.012 and P = 0.037, respectively), but HGS did not differ according to age. Patients performing regular home- or hospital-based exercise showed higher HGS than those who did not exercise (24.2 vs. 18.6 kg, P = 0.011), but LMS was not significantly different (29.3 vs. 23.6 kg, P = 0.185). Multiple linear regression analysis proved that male sex, younger age, and any type of exercise were factors associated with improved HGS and LMS. Groups of older age (≥ 60 years), male sex, and shorter duration of HD (< median) benefitted more from exercise. CONCLUSION: Sex, age, and exercise were the most important determinants of muscle strength in HD patients. We need to encourage patients to engage in regular home or group exercise from the beginning of dialysis and introduce new feasible forms of exercise for HD patients.

Chemokine receptor 5 blockade modulates macrophage trafficking in renal ischaemic-reperfusion injury.

Chemokine receptor 5 (CCR5) is a pivotal regulator of macrophage trafficking in the kidneys in response to an inflammatory cascade. We investigated the role of CCR5 in experimental ischaemic-reperfusion injury (IRI) pathogenesis. To establish IRI, we clamped the bilateral renal artery pedicle for 30 min and then reperfused the kidney. We performed adoptive transfer of lipopolysaccharide (LPS)-treated RAW 264.7 macrophages following macrophage depletion in mice. B6.CCR5-/- mice showed less severe IRI based on tubular epithelial cell apoptosis than did wild-type mice. CXCR3 expression in CD11b+ cells and inducible nitric oxide synthase levels were more attenuated in B6.CCR5-/- mice. B6.CCR5-/- mice showed increased arginase-1 and CD206 expression. Macrophage-depleted wild-type mice showed more injury than B6.CCR5-/- mice after M1 macrophage transfer. Adoptive transfer of LPS-treated RAW 264.7 macrophages reversed the protection against IRI in wild-type, but not B6.CCR5-/- mice. Upon knocking out CCR5 in macrophages, migration of bone marrow-derived macrophages from wild-type mice towards primary tubular epithelial cells with recombinant CCR5 increased. Phospho-CCR5 expression in renal tissues of patients with acute tubular necrosis was increased, showing a positive correlation with tubular inflammation. In conclusion, CCR5 deficiency favours M2 macrophage activation, and blocking CCR5 might aid in treating acute kidney injury.

ST2 blockade mitigates peritoneal fibrosis induced by TGF-ß and high glucose.

Peritoneal fibrosis (PF) is an intractable complication of peritoneal dialysis (PD) that leads to peritoneal membrane failure. This study investigated the role of suppression of tumorigenicity (ST)2 in PF using patient samples along with mouse and cell-based models. Baseline dialysate soluble (s)ST2 level in patients measured 1 month after PD initiation was 2063.4 ± 2457.8 pg/mL; patients who switched to haemodialysis had elevated sST2 levels in peritoneal effluent (1576.2 ± 199.9 pg/mL, P = .03), which was associated with PD failure (P = .04). Baseline sST2 showed good performance in predicting PD failure (area under the receiver operating characteristic curve = 0.780, P = .001). In mice with chlorhexidine gluconate-induced PF, ST2 was expressed in fibroblasts and mesothelial cells within submesothelial zones. In primary cultured human peritoneal mesothelial cells (HPMCs), transforming growth factor-ß treatment increased ST2, fibronectin, ß-galactosidase and Snail protein levels and decreased E-cadherin level. Anti-ST2 antibody administration reversed the up-regulation of ST2 and fibronectin expression; it also reduced fibrosis induced by high glucose (100 mmol/L) in HPMCs. Thus, high ST2 level in dialysate is a marker for fibrosis and inflammation during peritoneal injury, and blocking ST2 may be an effective therapeutic strategy for renal preservation.

Transcriptional modulation of the T helper 17/interleukin 17 axis ameliorates renal ischemia-reperfusion injury.

BACKGROUND: Signal transducer and activator of transcription 3 (STAT3) is a latent transcription factor critical for T-cell function. Although inhibition of the Janus kinase 2 (JAK2)/STAT3 pathway has been reported to be protective against ischemia-reperfusion injury (IRI), the role of T cell-associated STAT3 in the pathogenesis of renal IRI has not been specifically defined. METHODS: We induced renal IRI in both mice with T cell-specific STAT3 knockout (Lck-Cre;STAT3flox/flox) and wild-type controls (C57BL/6) and assessed renal damage and inflammation at 48 h after IRI. Human proximal tubular epithelial cells grown under hypoxia were treated with a JAK2 inhibitor, caffeic acid 3,4-dihydroxy-phenylethyl ester, to determine the effect of JAK2/STAT3 inhibition on renal epithelia. Independently, we disrupted Cln 3-requiring 9 (Ctr9) to inhibit T helper 17 (Th17) activation via RNA interference and determined if Ctr9 inhibition aggravates renal injury through upregulated Th17 activation. RESULTS: The Lck-Cre;STAT3flox/flox mice exhibited significantly reduced kidney damage compared with controls. This protective effect was associated with reduced intrarenal Th17 infiltration and proinflammatory cytokines. Human proximal tubular epithelial cells under hypoxia exhibited significant upregulation of interleukin 17 receptors, and pharmacologic inhibition of JAK2 significantly ameliorated this change. RNA interference with Ctr9 in splenocytes enhanced differentiation into Th17 cells. In vivo knockdown of Ctr9 in mice with renal IRI further aggravated Th17-associated inflammation and kidney injury. CONCLUSIONS: STAT3 in T cells contributes to renal IRI through Th17 activation. Inhibition of Ctr9 further enhances Th17 activation and aggravates kidney injury, further supporting the role of Th17 cells in renal IRI.

Higher Serum Levels of Osteoglycin Are Associated with All-Cause Mortality and Cardiovascular and Cerebrovascular Events in Patients with Advanced Chronic Kidney Disease.

Patients with chronic kidney disease (CKD) have markedly increased rates of major adverse cardiovascular and cerebrovascular events (MACCEs) and mortality. Therefore, identifying early biomarkers predicting clinical outcomes in patients with CKD is critical. We aimed to determine whether osteoglycin, a basic component of the vascular extracellular matrix, was associated with MACCEs or all-cause mortality, using data from a prospective randomized controlled study, K-STAR (Kremezin STudy Against Renal disease progression in Korea: NCT 00860431). A total of 383 patients (mean age: 56.4 years, men/women = 252/131) with CKD stage 3 to 4 from the original trial were enrolled in the present study. We measured serum osteoglycin level and examined the impact of osteoglycin on clinical outcomes. The mean value of osteoglycin levels was 13.3 ± 9.4 ng/mL (healthy control: 5.3 ± 2.1 ng/mL). In multivariable analysis, lower levels of proteinuria and hemoglobin and higher levels of C-reactive protein were significantly associated with higher osteoglycin levels. Estimated glomerular filtration rate was not related to osteoglycin level. During a mean follow-up period of 56 months, 25 deaths, 61 MACCEs, and 76 composite outcomes (all-cause mortality or MACCEs) occurred. In the non-diabetic group, each 1-ng/mL increase in serum osteoglycin was associated with all-cause mortality and composite outcome (hazard ratio [HR] = 1.058, P = 0.031; HR = 1.041, P = 0.036). However, osteoglycin levels were not associated with mortality, MACCEs, or composite outcome in the diabetic group. Our results indicate that serum osteoglycin is a potential predictor of adverse outcomes in patients with CKD.

Viral RNA in Blood as Indicator of Severe Outcome in Middle East Respiratory Syndrome Coronavirus Infection.

We evaluated the diagnostic and clinical usefulness of blood specimens to detect Middle East respiratory syndrome coronavirus infection in 21 patients from the 2015 outbreak in South Korea. Viral RNA was detected in blood from 33% of patients at initial diagnosis, and the detection preceded a worse clinical course.

A Case Report of a Middle East Respiratory Syndrome Survivor with Kidney Biopsy Results.

A 68-year old man diagnosed with Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) presented with multiple pneumonic infiltrations on his chest X-ray, and the patient was placed on a mechanical ventilator because of progressive respiratory failure. Urinary protein excretion steadily increased for a microalbumin to creatinine ratio of 538.4 mg/g Cr and a protein to creatinine ratio of 3,025.8 mg/g Cr. The isotope dilution mass spectrometry traceable serum creatinine level increased to 3.0 mg/dL. We performed a kidney biopsy 8 weeks after the onset of symptoms. Acute tubular necrosis was the main finding, and proteinaceous cast formation and acute tubulointerstitial nephritis were found. There were no electron dense deposits observed with electron microscopy. We could not verify the virus itself by in situ hybridization and confocal microscopy (MERS-CoV co-stained with dipeptidyl peptidase 4). The viremic status, urinary virus excretion, and timely kidney biopsy results should be investigated with thorough precautions to reveal the direct effects of MERS-CoV with respect to renal complications.

Renal Complications and Their Prognosis in Korean Patients with Middle East Respiratory Syndrome-Coronavirus from the Central MERS-CoV Designated Hospital.

Some cases of Middle East Respiratory Syndrome-Coronavirus (MERS-CoV) infection presented renal function impairment after the first MERS-CoV patient died of progressive respiratory and renal failure. Thus, MERS-CoV may include kidney tropism. However, reports about the natural courses of MERS-CoV infection in terms of renal complications are scarce. We examined 30 MERS-CoV patients admitted to National Medical Center, Korea. We conducted a retrospective analysis of the serum creatinine (SCr), estimated glomerular filtration rate (eGFR), urine dipstick tests, urinary protein quantitation (ACR or PCR), and other clinical parameters in all patients. Two consecutive results of more than trace (or 1+) of albumin and blood on dipstick test occurred in 18 (60%) (12 [40%]) and 22 (73.3%) (19 [63.3%]) patients, respectively. Fifteen (50.0%) patients showed a random urine ACR or PCR more than 100 mg/g Cr. Eight (26.7%) patients showed acute kidney injury (AKI), and the mean and median durations to the occurrence of AKI from symptom onset were 18 and 16 days, respectively. Old age was associated with a higher occurrence of AKI in the univariate analysis (HR [95% CI]: 1.069 [1.013-1.128], P = 0.016) and remained a significant predictor of the occurrence of AKI after adjustment for comorbidities and the application of a mechanical ventilator. Diabetes, AKI, and the application of a continuous renal replacement therapy (CRRT) were risk factors for mortality in the univariate analysis (HR [95% CI]: diabetes; 10.133 [1.692-60.697], AKI; 12.744 [1.418-114.565], CRRT; 10.254 [1.626-64.666], respectively). Here, we report renal complications and their prognosis in 30 Korean patients with MERS-CoV.

The clinical association of the blood pressure variability with the target organ damage in hypertensive patients with chronic kidney disease.

It is known that blood pressure variability (BPV) can independently affect target organ damage (TOD), even with normal blood pressure. There have been few studieson chronic kidney disease (CKD) patients. We evaluated the relationship between BPV and TOD in a cross-sectional, multicenter study on hypertensive CKD patients. We evaluated 1,173 patients using 24-hr ambulatory blood pressure monitoring. BPV was defined as the average real variability, with a mean value of the absolute differences between consecutive readings of systolic blood pressure. TOD was defined as left ventricular hypertrophy (LVH) (by the Romhilt-Estes score ≥4 in electrocardiography) and kidney injury (as determined from an estimated glomerular filtration rate [eGFR]<30 mL/min/1.73 m(2) and proteinuria).The mean BPV of the subjects was 15.9±4.63 mmHg. BPV displayed a positive relationship with LVH in a univariate analysis and after adjustment for multi-variables (odds ratio per 1 mmHg increase in BPV: 1.053, P=0.006). In contrast, BPV had no relationship with kidney injury. These data suggest that BPV may be positively associated with LVH in hypertensive CKD patients.

Pharmacologic therapeutics in sarcopenia with chronic kidney disease.

Inflammation, metabolic acidosis, renin-angiotensin system activation, insulin resistance, and impaired perfusion to skeletal muscles, among others, are possible causes of uremic sarcopenia. These conditions induce the activation of the nuclear factor-kappa B and mitogen-activated protein kinase pathways, adenosine triphosphate ubiquitin-proteasome system, and reactive oxygen species system, resulting in protein catabolism. Strategies for the prevention and treatment of sarcopenia in chronic kidney disease (CKD) are aerobic and resistance exercises along with nutritional interventions. Anabolic hormones have shown beneficial effects. Megestrol acetate increased weight, protein catabolic rate, and albumin concentration, and it increased intracellular water component and muscle mass. Vitamin D supplementation showed improvement in physical function, muscle strength, and muscle mass. Correction of metabolic acidosis showed an increase in protein intake, serum albumin levels, body weight, and mid-arm circumference. The kidney- gut-muscle axis indicates that dysbiosis and changes in gut-derived uremic toxins and short-chain fatty acids affect muscle mass, composition, strength, and functional capacity. Biotic supplements, AST-120 administration, hemodiafiltration, and preservation of residual renal function are alleged to reduce uremic toxins, including indoxyl sulfate (IS) and p-cresyl sulfate (PCS). Synbiotics reversed the microbiota change in CKD patients and decreased uremic toxins. AST-120 administration changed the overall gut microbiota composition in CKD. AST-120 prevented IS and PCS tissue accumulation, ameliorated muscle atrophy, improved exercise capacity and mitochondrial biogenesis, restored epithelial tight junction proteins, and reduced plasma endotoxin levels and markers of oxidative stress and inflammation. In a human study, the addition of AST-120 to standard treatment had modest beneficial effects on gait speed change and quality of life.

Performance evaluation of Chronic Kidney Disease Epidemiology Collaboration equations for estimated glomerular filtration rate compared to inulin clearance in Koreans.

Background: A race-free glomerular filtration rate (GFR) estimation equation has recently been developed. However, the performance of the new Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equations needs to be evaluated in Asian populations. Methods: We performed a cross-sectional study at a single center in South Korea. The measured GFR (mGFR) was determined based on systemic inulin clearance. The GFR was estimated using the five CKD-EPI equations: 2009 CKD-EPIcr, 2012 CKD-EPIcr-cys, 2012 CKD-EPIcys, 2021 CKD-EPIcr, and 2021 CKD-EPIcr-cys. The performances of five estimated GFR (eGFR) equations were assessed by bias, precision, and accuracy (percentage of estimates within 30% of mGFR). Results: The median mGFR and interquartile range (IQR) was 53.5 (32.4-80.0) mL/min/1.73 m2. The mGFR better correlated with 2009 CKD-EPIcr (ρ = 0.628) and 2021 CKD-EPIcr-cys (ρ = 0.806) than with 2021 CKD-EPIcr (ρ = 0.623) and 2012 CKD-EPIcr-cys (ρ = 0.801). The median bias of 2009 CKD-EPIcr and 2012 CKD-EPIcr-cys were lower than those of 2021 CKD-EPI equations (2009 CKD-EPIcr, 2.24 [IQR, -8.83 to 17.39] vs. 2021 CKD-EPIcr, 5.40 [IQR, -6.04 to 20.40]; 2012 CKD-EPIcr-cys, 6.74 [IQR, -2.81 to 20.80] vs. 2021 CKD-EPIcr-cys, 10.54 [IQR, 0.30-24.37]; all in mL/min/1.73 m2). The percentage of eGFR values within 30% of mGFR was higher in 2009 CKD-EPIcr and 2012 CKD-EPIcr-cys equations than 2021 CKD-EPI equations. The CKD prevalence in 2009 CKD-EPIcr, 2021 CKD-EPIcr, 2012 CKD-EPIcr-cys, and 2021 CKD-EPIcr-cys was 54.8%, 51.0%, 47.7%, and 44.8%, respectively. Conclusion: Our study demonstrated better performance of the original CKD-EPIcr and CKD-EPIcr-cys equations than the 2021 new CKD-EPI equations. We do not recommend the adoption of the new CKD-EPI equations in Korea.

Efficacy of intradialytic neuromuscular electrical stimulation and oral nutritional supplementation in hemodialysis patients: a multicenter, randomized controlled trial.

Background: Sarcopenia is common in hemodialysis patients. This study aimed to evaluate the effect of simultaneous nutritional support and intradialytic neuromuscular electrical stimulation (NMES) in hemodialysis patients. Methods: We performed a 12-week, multicenter, randomized controlled trial. The participants were randomly assigned to the control group, the protein group (25 g of protein at every dialysis session), the NMES group (intradialytic NMES to quadriceps femoris muscles), and the NMES + P group (NMES with protein supplementation). The primary outcome was the difference in hand grip strength (HGS) and leg muscle strength (LMS) among groups. Secondary outcomes included body composition, physical performance (the 10-m walk test and the timed up and go test [TUG]), and questionnaires about quality of life (QoL), physical activity, and depression. In addition, subgroup analysis was performed by dividing NMES and NMES + P groups into high- and low-intensity NMES groups. Results: Fifty-nine patients completed all the study outcomes. There was no difference in muscle strength (HGS and LMS) and muscle mass among groups. Gait speed improved in NMES and NMES + P groups. Subscale scores for QoL (kidney disease effect, role limitations due to physical or emotional problems, and overall health ratings) improved in the NMES + P group. In subgroup analysis, LMS and TUG improved only in the high-intensity NMES group. Conclusion: In this study, NMES and-/or- protein supplementation did not make a significant difference in HGS and LMS. However, NMES or NMES + P improved functional capacity and QoL. Furthermore, higher NMES was superior in improving LMS and functional capacity.

Factors associated with gait speed: results from the RolE of AST120 (Renamezin) in sarCOpenia preVEntion in pRe-dialYsis chronic kidney disease patients (RECOVERY) study.

Background: Gait speed is an important measure of functional ability. This study aimed to investigate the factors associated with gait speed in patients with chronic kidney disease. The study focused on sarcopenic components, plasma uremic or inflammatory marker levels, and quality of life effects. Methods: The RolE of AST120 (Renamezin) in sarCOpenia preVEntion in pRe-dialYsis chronic kidney disease patients is a 48-week, randomized controlled, parallel-group, open-label, multicenter trial to determine the role of Renamezin (Daewon Pharmaceutical Co., Ltd.) in patients with chronic kidney disease. The participants were classified into four groups according to gait speed: ≤0.8, 0.8-1.0, ≤1.0-1.3, and ≥1.3 m/sec. Linear regression analysis was performed to identify the factors associated with gait speed. Results: The group with a gait speed of ≤0.8 m/sec was the oldest and had the highest proportion of participants with low education level and medical aid. Participants with a gait speed of ≤0.8 m/sec showed the lowest physical and mental component scale scores. The interleukin-6 (IL-6) level tended to be the higher trend in the lowest gait speed group. In the multivariate linear regression analysis adjusted for age, sex, diabetes mellitus, and estimated glomerular filtration rate, insurance status, handgrip strength, IL-6 level, hemoglobin level, mental component scale score, and physical component scale score were significantly associated with gait speed. Conclusion: In conclusion, gait speed is associated with handgrip strength, IL-6 level, and various components of quality of life in predialysis chronic kidney disease patients.

Change in body compositions of Asian recipients after kidney transplantation.

Kidney transplantation and accompanying medical conditions may result in changes in body composition. Such changes have been evaluated in Caucasian recipients, but not in Asian recipients. Herein, we conducted a study on Asian recipients because Asians have a different body composition from Caucasians. A total of 50 Asian recipients was enrolled as a prospective cohort. Using bioelectrical impedance analysis, body composition (muscle and fat mass) was assessed after 2 weeks (baseline), and at 1, 3, 6, 9, and 12 months following kidney transplantation. To find predictors related to changes, the data were analyzed by multivariate analysis using forward selection. All of the patients had good graft function during the study period. Patients gained approximately 3 kg within 1 yr of kidney transplantation. The proportion of muscle mass significantly decreased (P(trend) = 0.001) and the proportion of fat mass significantly increased over time (P(trend) = 0.002). The multivariate results revealed that male recipients, deceased donor type, and low protein intake were associated with an increase in fat mass and a decrease in muscle mass. The results from this study may help to investigate differences in body composition changes between races, as well as the factors related to these changes.

Sulfatide-reactive natural killer T cells abrogate ischemia-reperfusion injury.

There is a significant immune response to ischemia-reperfusion injury (IRI), but the role of immunomodulatory natural killer T (NKT) cell subtypes is not well understood. Here, we compared the severity of IRI in mice deficient in type I/II NKT cells (CD1d(-/-)) or type I NKT cells (Jα18(-/-)). The absence of NKT cells, especially type II NKT cells, accentuated the severity of renal injury, whereas repletion of NKT cells attenuated injury. Adoptively transferred NKT cells trafficked into the tubulointerstitium, which is the primary area of injury. Sulfatide-induced activation of type II NKT cells protected kidneys from IRI, but inhibition of NKT cell recruitment enhanced injury. In co-culture experiments, sulfatide-induced activation of NKT cells from either mice or humans attenuated apoptosis of renal tubular cells after transient hypoxia via hypoxia-inducible factor (HIF)-1α and IL-10 pathways. Renal tissue of patients with acute tubular necrosis (ATN) frequently contained NKT cells, and the number of these cells tended to negatively correlate with ATN severity. In summary, sulfatide-reactive type II NKT cells are renoprotective in IRI, suggesting that pharmacologic modulation of NKT cells may protect against ischemic injury.

Phase angle as a marker for muscle health and quality of life in patients with chronic kidney disease.

BACKGROUND & AIMS: Sarcopenia is associated with adverse health outcomes in individuals with chronic kidney disease (CKD); hence, a convenient and reliable method for monitoring muscle health is required. This study investigated the utility of the phase angle (PhA) to estimate muscle health and health-related quality of life (HRQoL) in patients with CKD. METHODS: Data were obtained from a multicenter randomized trial that examined the effect of AST-120 on sarcopenia and HRQoL. The PhA and skeletal muscle mass index (SMI) were derived from bioelectrical impedance analyses at baseline, 24-week, and 48-week. In addition, handgrip strength (HGS), 6 m gait speed (GS), and HRQoL were obtained simultaneously. RESULTS: In total, 149 participants were included. PhA was linearly related to SMI, HGS, and GS (r = 0.616, 0.619, and 0.290, respectively; all P < 0.001). Moreover, PhA was associated with the criteria for low muscle mass and low muscle strength (both P < 0.001), and it predicted the presence of sarcopenia (P = 0.001). Substantial agreement was observed in the diagnosis of sarcopenia (κ = 0.510; P < 0.001). In addition, PhA was related to various aspects of HRQoL, including physical functioning, general health, mental health, physical component scale, mental component scale, work status, quality of social interaction, sexual function, and social support. In the longitudinal analysis, SMI increased in the increasing PhA group (a PhA slope ≥ 0.2° per year), and HGS was reduced in the decreasing PhA group (a PhA slope of < -0.2° per year) as compared to the constant PhA group (a PhA slope of -0.2 to 0.2° per year; both P = 0.054). The GS pattern did not differ among the three groups. In addition, the prevalence of sarcopenia was comparable at baseline (P = 0.220); however, its proportion rose in the decreasing PhA group and reduced in the increasing PhA group (P at 48-week = 0.058). With regards to aspects of HRQoL, role limitations due to physical health problems worsened in the decreasing PhA group. CONCLUSIONS: PhA appears to be a reliable marker for estimating muscle health and HRQoL in patients with CKD. In addition, monitoring PhA may help estimate the longitudinal patterns of muscle health and HRQoL.

Effects of AST-120 on muscle health and quality of life in chronic kidney disease patients: results of RECOVERY study.

BACKGROUND: The prevalence of sarcopenia is increased with declining renal function. Elevated serum indoxyl sulfate levels are associated with poor skeletal muscle conditions. We aimed to determine the effects of AST-120, the oral adsorbent of indoxyl sulfate, on sarcopenia and sarcopenia-associated factors in chronic kidney disease patients. METHODS: This was a 48 week, randomized controlled, parallel group, open-label, multicentre trial (n = 150). The participants were randomly assigned in a 1:1 ratio to the control (CON) and AST-120 (Renamezin®, REN) groups. Outcome measurements were performed at baseline and every 24 weeks for 48 weeks. The primary outcome was gait speed difference ≥0.1 m/s between the two groups, and secondary outcomes included hand grip strength, muscle mass, and health-related quality of life. RESULTS: A difference of gait speed ≥0.1 m/s was not observed during the study period. The mean dynamic-start gait speed in the REN group increased from baseline to 48 weeks (1.04 ± 0.31 to 1.08 ± 0.32 m/s, P = 0.019). The static-start gait speed changed by -0.024 and 0.04 m/s (P = 0.049) in the CON and REN groups over 48 weeks, respectively. Hand grip strength decreased during the first 24 weeks and did not significantly change over the next 24 weeks in either group. The proportion of low muscle mass or sarcopenia at baseline was larger in the REN group than in the CON group, but the difference attenuated over the study period [low muscle mass and sarcopenia in the CON and REN groups at baseline, 4.0% vs. 18.9% (P = 0.004) and 2.7% vs. 13.5% (P = 0.017); at 24 weeks, 2.9% vs. 13.6% (P = 0.021) and 1.4% vs. 10.5% (P = 0.029); and at 48 weeks, 7.6% vs. 12.9% (P = 0.319) and 4.5% vs. 8.1% (P = 0.482), respectively]. Bodily pain, vitality, symptoms/problems, and cognitive function in the REN group improved, while the quality of social interactions and the kidney disease effects in the CON group aggravated from baseline to 48 weeks. Interaction between time and group was evident only in symptoms/problems, cognitive function, and kidney disease effects. CONCLUSIONS: The addition of AST-120 to standard treatment in chronic kidney disease patients did not make a significant difference in gait speed, although AST-120 modestly had beneficial effects on gait speed change and quality of life and showed the potential to improve sarcopenia. (clinicaltrials.gov: NCT03788252).

Impact of volume status on sarcopenia in non-dialysis chronic kidney disease patients.

There were few data regarding the association of volume status with sarcopenia using muscle mass, strength, and physical performance in non-dialysis chronic kidney disease (ND-CKD) patients. We aimed to evaluate the association between volume status and sarcopenia in ND-CKD patients. Our retrospective study analyzed data from a previous study which included ND-CKD patients who had stable renal function. Our study used its baseline data alone. The edema index and muscle mass were measured using a multi-frequency bioimpedance analysis machine. The edema index was calculated using extracellular water/total body water ratio. The skeletal muscle index (SMI, kg/m2) was calculated using appendicular muscle mass per height squared. Handgrip strength (HGS, kg) was measured during the standing position in all patients. Dynamic gait speed (GS, m/s) was evaluated using 6-m walking speed. Patients with both low muscle mass (SMI < 7.0 kg/m2 for men and < 5.7 kg/m2 for women using bioimpedance analysis) and low HGS (< 28 kg for men and < 18 kg for women) or low GS (< 1.0 m/s) were classified as having sarcopenia. The patients (n = 147) were divided into tertiles based on the edema index level. The mean edema index in the low, middle, and high tertiles was 0.377 ± 0.006, 0.390 ± 0.003, and 0.402 ± 0.006, respectively. The edema index was significantly correlated with SMI, HGS, and GS (r = - 0.343 for SMI, - 0.492 for HGS, and - 0.331 for GS; P < 0.001 for three indicators). The SMI, HGS, and GS values were 8.1 ± 1.0 kg/m2, 33.0 ± 9.4 kg, and 1.2 ± 0.2 m/s in the low tertile,7.8 ± 1.2 kg/m2, 30.0 ± 7.5 kg, and 1.0 ± 0.3 m/s in the middle tertile, and 7.2 ± 1.4 kg/m2, 23.7 ± 7.4 kg, and 1.0 ± 0.3 m/s in the high tertile, respectively. Univariate analyses revealed that SMI was lower in patients in the high tertile than in those in the low tertile. HGS was lowest in high tertile, and GS was greatest in the low tertile. The high tertile for predicting sarcopenia had an odds ratio of 6.03 (95% CI, 1.78-20.37; P = 0.004) compared to low or middle tertiles. The results of multivariate analyses were similar to those of the univariate analyses. The subgroup analyses showed that statistical significance was greater in < 65 years and men than ≥ 65 years and women. The present study showed that the edema index is inversely associated with sarcopenia, muscle mass index, strength, and physical performance in ND-CKD patients. However, considering the limitations of our study such as its small sample size, this association was not strong. Further studies that include volume-independent measurements, data on physical activity and diet, and a larger number of patients are warranted to overcome these limitations.