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.

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.

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.

BACKGROUND: Hyperuricemia is associated with the development and progression of chronic kidney disease (CKD) as well as cardiovascular diseases. However, there is no consistent recommendation regarding the treatment of asymptomatic hyperuricemia (AHU) in CKD patients. Here, we surveyed Korean physicians’ perceptions regarding the diagnosis and management of AHU in CKD patients. METHODS: Questionnaires on the management of AHU in CKD patients were emailed to regular members registered with the Korean Society of Nephrology. RESULTS: A total of 158 members answered the questionnaire. Among the respondents, 49.4%/41.1% were considered hyperuricemic in male CKD patients whereas 36.7%/20.9% were considered hyperuricemic in female CKD patients when defined by serum uric acid level over 7.0/8.0 mg/dL, respectively. A total of 80.4% reported treating AHU in CKD patients. The most important reasons to treat AHU in CKD patients were renal function preservation followed by cerebro-cardiac protection. Majority of respondents (59.5%) thought that uric acid-lowering agents (ULAs) were the most effective method for controlling serum uric acid levels. Approximately 80% chose febuxostat as the preferred medication. A total of 32.3% and 31.0%, respectively, initiated ULA treatment if the serum uric acid level was more than 8.0 or 9.0 mg/dL, respectively. In addition, 39.2% and 30.4% answered that target serum uric acid levels of less than 6.0 or 7.0 mg/dL, respectively, were appropriate. The two major hurdles to prescribing ULAs were concerns of adverse reactions and the existing lack of evidence (i.e., the absence of Korean guidelines). CONCLUSION: Most Korean physicians treat AHU in CKD patients to prevent CKD progression and cerebro-cardiovascular complications.
Cardiovascular Diseases ; Diagnosis ; Electronic Mail ; Febuxostat ; Female ; Humans ; Hyperuricemia ; Male ; Methods ; Nephrology ; Renal Insufficiency, Chronic ; Surveys and Questionnaires ; Uric Acid

No abstract available.
Humans

BACKGROUND/AIMS: Patients with chronic kidney disease (CKD) have been found to show markedly increased rates of end-stage renal disease, major adverse cardiovascular and cerebrovascular events (MACCEs), and mortality. Therefore, new biomarkers are required for the early detection of such clinical outcomes in patients with CKD. We aimed to determine whether the level of circulating renalase was associated with CKD progression, MACCEs, and all-cause mortality, using data from a prospective randomized controlled study, Kremezin STudy Against Renal disease progression in Korea (K-STAR; NCT 00860431). METHODS: A retrospective analysis of the K-STAR data was performed including 383 patients with CKD (mean age, 56.4 years; male/female, 252/131). We measured circulating renalase levels and examined the effects of these levels on clinical outcomes. RESULTS: The mean level of serum renalase was 75.8 ± 34.8 μg/mL. In the multivariable analysis, lower hemoglobin levels, higher serum creatinine levels, and diabetes mellitus were significantly associated with a higher renalase levels. Over the course of a mean follow-up period of 56 months, 25 deaths and 61 MACCEs occurred. Among 322 patients in whom these outcomes were assessed, 137 adverse renal outcomes occurred after a mean follow-up period of 27.8 months. Each 10-μg/mL increase in serum renalase was associated with significantly greater hazards of all-cause mortality and adverse renal outcomes (hazard ratio [HR] = 1.112, p = 0.049; HR = 1.052, p = 0.045). However, serum renalase level was not associated with the rate of MACCEs in patients with CKD. CONCLUSIONS Our results indicated that circulating renalase might be a predictor of mortality and adverse renal outcomes in patients with CKD.

BACKGROUND: The 24-hour mean blood pressure (mBP) is the best predictor of organ damage; however, it is not easily applicable in clinical practice. The APrODiTe study suggested that systolic blood pressure (SBP) values at 7:00 AM and 9:30 PM were associated with the 24-hour mSBP in patients with chronic kidney disease (CKD). We investigated the association of the SBP values at these time-points with the renal outcomes in patients with diabetic CKD during 1-year follow-up. METHODS: Ninety-six patients with diabetic CKD were included at 1-year follow-up. The renal outcomes were an increase in the random urine protein/creatinine ratio or estimated glomerular filtration rate (eGFR) deterioration, which means a decrease in eGFR ≥5 mL/min/1.73 m² compared to the baseline values. RESULTS: The baseline SBP values at 7:00 AM, and 9:30 PM, and the 24-hour mSBP were 135.6±24.9 mmHg, 141.7±25.6 mmHg, and 136.4±20.7 mmHg, respectively. The SBP values measured at the same time-points after 1 year were similar to those at baseline. The SBP at 7:00 AM was significantly associated with eGFR deterioration in the univariate and multivariate analyses (odds ratio [OR]: 1.032; 95% confidence interval [CI]: 1.006–1.059; p=0.016). The SBP at 7:00AM and 24-hour mSBP did not show a concordant association with sustained proteinuria in the linear and logistic analyses. In the subgroup analysis, the association between the SBP at 7:00 AM and eGFR deterioration persisted in patients with CKD stage 3–5 (OR: 1.041; 95% CI: 1.010–1.073; p=0.010). CONCLUSION The SBP at 7:00 AM, in addition to the 24-hour mSBP, is also associated with eGFR deterioration in patients with diabetic CKD, particularly in those with CKD stage 3–5.

The values of y axis in Fig. 3 should be corrected. The authors would like to apologize for any inconvenience this has caused.

OBJECTIVE: To identify the associations between polymorphisms of the 3′-untranslated region (UTR) of methylenetetrahydrofolate reductase (MTHFR) gene, which codes for an important regulatory enzyme primarily involved in folate metabolism, and idiopathic recurrent pregnancy loss (RPL) in Korean women. METHODS: The study population comprised 369 RPL patients and 228 controls. MTHFR 2572C>A, 4869C>G, 5488C>T, and 6685T>C 3′-UTR polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism analysis or by TaqMan allelic discrimination assays. Natural killer cell proportions were determined by flow cytometry. RESULTS: The MTHFR 2572-5488-6685 (A-C-T) haplotype had an adjusted odds ratio of 0.420 (95% confidence interval, 0.178–0.994; p=0.048) for RPL. Analysis of variance revealed that MTHFR 4869C>G was associated with altered CD56⁺ natural killer cell percentages (CC, 17.91%±8.04%; CG, 12.67%±4.64%; p=0.024) and folate levels (CC, 12.01±7.18 mg/mL; CG, 22.15±26.25 mg/mL; p=0.006). CONCLUSION: Variants in the 3′-UTR of MTHFR are potential biomarkers for RPL. However, these results should be validated in additional studies of ethnically diverse groups of patients.
Biomarkers ; Discrimination (Psychology) ; Female ; Flow Cytometry ; Folic Acid ; Haplotypes ; Humans ; Killer Cells, Natural* ; Metabolism ; Methylenetetrahydrofolate Reductase (NADPH2) ; Odds Ratio ; Pregnancy*

BACKGROUND: We investigated the long-term effect of AST-120, which has been proposed as a therapeutic option against renal disease progression, in patients with advanced chronic kidney disease (CKD). METHODS: We performed post-hoc analysis with a per-protocol group of the K-STAR study (Kremezin study against renal disease progression in Korea) that randomized participants into an AST-120 and a control arm. Patients in the AST-120 arm were given 6 g of AST-120 in three divided doses, and those in both arms received standard conventional treatment. RESULTS: The two arms did not differ significantly in the occurrence of composite primary outcomes (log-rank P = 0.41). For AST-120 patients with higher compliance, there were fewer composite primary outcomes: intermediate tertile hazard ratio (HR) 0.62, 95% confidence interval (CI) 0.38 to 1.01, P = 0.05; highest tertile HR 0.436, 95% CI 0.25 to 0.76, P = 0.003. The estimated glomerular filtration rate level was more stable in the AST-120 arm, especially in diabetic patients. At one year, the AST-120-induced decrease in the serum indoxyl sulfate concentration inversely correlated with the occurrence of composite primary outcomes: second tertile HR 1.59, 95% CI 0.82 to 3.07, P = 0.17; third tertile HR 2.11, 95% CI 1.07 to 4.17, P = 0.031. Furthermore, AST-120 showed a protective effect against the major cardiovascular adverse events (HR 0.51, 95% CI 0.26 to 0.99, P = 0.046). CONCLUSION: Long-term use of AST-120 has potential for renal protection, especially in diabetic patients, as well as cardiovascular benefits. Reduction of the serum indoxyl sulfate level may be used to identify patients who would benefit from AST-120 administration.
Arm ; Compliance ; Disease Progression* ; Glomerular Filtration Rate ; Humans ; Indican ; Korea* ; Renal Insufficiency, Chronic