Significant Association of Diabetes With Mortality of Chronic Hemodialysis Patients, Independent of the Presence of Obesity, Sarcopenia, and Sarcopenic Obesity.

OBJECTIVES: This retrospective cohort study investigated the association of diabetes with mortality in hemodialysis patients with regard to obesity, sarcopenia, and sarcopenic obesity, along with examining the prevalence of each group and diabetes. METHODS: Muscle strength, muscle mass, and fat mass were evaluated using a hand dynamometer and dual-energy X-ray absorptiometry, respectively, in 308 chronic hemodialysis patients (age 58.0 ± 11.9 years, hemodialysis duration 6.5 ± 6.0 years, males 60.1%, diabetes 32.8%). Sarcopenia was defined according to the new criteria established by the Asian Working Group on Sarcopenia 2019. Obesity was defined by percent body fat mass (males ≥25%, females ≥35%). RESULTS: The enrolled patients were divided into the normal (38.7%), obesity (18.8%), sarcopenia (26.9%), and sarcopenic obesity (15.6%) groups. The prevalence of diabetes was significantly skewed among the 4 groups (χ2 test, P = .0057), being higher in the sarcopenic obesity group (54.2%) compared to the others (25.9-33.7%). Multivariate regression analysis revealed that diabetes was significantly and independently associated with sarcopenic obesity (odds ratio 3.495, 95% confidence interval 1.683-7.255, P = .0008) after adjustments for several cofounders, but not significantly associated with sarcopenia. During the follow-up period of 76 ± 35 months, 100 patients died. Those in the sarcopenia and sarcopenic obesity groups had significantly higher rates of all-cause mortality compared to patients in the normal and obesity groups (P = .0004, log-rank test). Furthermore, multivariate Cox proportional hazards analysis revealed that presence of diabetes was significantly associated with higher all-cause mortality in all 308 patients, after adjustments for several factors, including the presence of each group in 4 models. CONCLUSION: Sarcopenic obesity is highly prevalent in chronic hemodialysis patients. Diabetes was found to be a significant and independent contributor to the presence of sarcopenic obesity. Diabetes was shown to be a significant predictor of all-cause mortality, independent of the present normal, obesity, sarcopenia, and sarcopenic obesity groups.

Importance of Considering Malnutrition and Sarcopenia in Order to Improve the QOL of Elderly Hemodialysis Patients in Japan in the Era of 100-Year Life.

In the current aging society of Japan, malnutrition and resultant sarcopenia have been widely identified as important symptomatic indicators of ill health and can cause impairments of longevity and quality of life in older individuals. Elderly individuals are recommended to have sufficient calorie and protein intake so as to enjoy a satisfactory quality of life, including maintaining activities of daily living in order to avoid emaciation and sarcopenia. The prevalence of emaciation and sarcopenia in elderly hemodialysis (HD) patients in Japan is higher than in non-HD elderly subjects due to the presence of malnutrition and sarcopenia associated with chronic kidney disease (CKD). Furthermore, comorbidities, such as diabetes and osteoporosis, induce malnutrition and sarcopenia in HD patients. This review presents findings regarding the mechanisms of the development of these early symptomatic conditions and their significance for impaired QOL and increased mortality in elderly HD patients.

Significance of Adipose Tissue Maintenance in Patients Undergoing Hemodialysis.

In the general population, obesity is known to be associated with adverse outcomes, including mortality. In contrast, high body mass index (BMI) may provide a survival advantage for hemodialysis patients, which is known as the obesity paradox. Although BMI is the most commonly used measure for the assessment of obesity, it does not distinguish between fat and lean mass. Fat mass is considered to serve as an energy reserve against a catabolic condition, while the capacity to survive starvation is also thought to be dependent on its amount. Thus, fat mass is used as a nutritional marker. For example, improvement of nutritional status by nutritional intervention or initiation of hemodialysis is associated with an increase in fat mass. Several studies have shown that higher levels of fat mass were associated with better survival in hemodialysis patients. Based on body distribution, fat mass is classified into subcutaneous and visceral fat. Visceral fat is metabolically more active and associated with metabolic abnormalities and inflammation, and it is thus considered to be a risk factor for cardiovascular disease and mortality. On the other hand, subcutaneous fat has not been consistently linked to adverse phenomena and may reflect nutritional status as a type of energy storage. Visceral and subcutaneous adipose tissues have different metabolic and inflammatory characteristics and may have opposing influences on various outcomes, including mortality. Results showing an association between increased subcutaneous fat and better survival, along with other conditions, such as cancer or cirrhosis, in hemodialysis patients have been reported. This evidence suggests that fat mass distribution (i.e., visceral fat and subcutaneous fat) plays a more important role for these beneficial effects in hemodialysis patients.

Cinacalcet may suppress kidney enlargement in hemodialysis patients with autosomal dominant polycystic kidney disease.

A massively enlarged kidney can impact quality of life of autosomal dominant polycystic kidney disease (ADPKD) patients. A recent in vitro study demonstrated that an allosteric modulator of the calcium sensing receptor decreases adenosine-3',5'-cyclic monophosphate, an important factor for kidney enlargement in ADPKD. Therefore, the present study was performed to determine whether cinacalcet, a calcium sensing receptor agonist, suppresses kidney enlargement in hemodialysis patients with ADPKD. Alteration of total kidney volume together with clinical parameters was retrospectively examined in 12 hemodialysis patients with ADPKD treated at a single institution in Japan. In the non-cinacalcet group with longer hemodialysis duration (n = 5), total kidney volume had an annual increase of 4.19 ± 1.71% during an overall period of 877 ± 494 days. In contrast, the annual rate of increase in total kidney volume in the cinacalcet group (n = 7) was significantly suppressed after cinacalcet treatment, from 3.26 ± 2.87% during a period of 734 ± 352 days before the start of cinacalcet to - 4.71 ± 6.42% during 918 ± 524 days after initiation of treatment (p = 0.047). The present findings showed that cinacalcet could be a novel therapeutic tool for suppression of kidney enlargement in hemodialysis patients with ADPKD.

REM sleep latency as an independent risk for cardiovascular events in hemodialysis patients.

BACKGROUND: Clinical significance of objectively measured poor sleep quality (SQ) as a risk for cardiovascular disease (CVD) events is not well known in hemodialysis (HD) patients, independently of sleep-related breathing disorders (SRBDs) and sleep-related metabolic abnormality. METHODS: The present study investigated baseline levels of objective sleep architecture together with obstructive sleep apnea (OSA) and central sleep apnea (CSA) using polysomnography in 88 HD study participants (M/F, 56/32; age 68.4 ± 9.3). Then, HD study participants were monitored for the occurrence of new-onset CVD events with a median (range) follow-up period of 33 (1-64) months. RESULTS: Among various measures of SQ, log (REM sleep latency [REM-SL]) (interval between sleep-onset and the first REM period) alone correlated in negative manners with triglycerides and non-HDL-C in all study participants and with fasting plasma glucose and HbA1c in study participants with type-2 diabetes mellitus. In the Kaplan-Meier analysis, HD study participants with shorter REM-SL had a significantly higher rate of new-onset CVD events than those with longer REM-SL. Stepwise logistic regression analysis and multivariate Cox proportional hazard regression analysis identified shorter REM-SL as an independent risk factor for the development of a new-onset CVD events, independent of mean oxygen saturation, log (AHI+1), log (central AHI+1), diabetes mellitus, CVD history, systolic blood pressure, statins use, and non-HDL-C. CONCLUSIONS: The present study demonstrated that reduction of REM-SL is independently associated with a higher rate of new-onset of CVD events, independent of SRBDs (OSA and CSA) and diabetes mellitus, non-HDL-C in HD study participants, suggesting impaired SQ as a potential CVD risk factor, and thus a definite treatment target to protect against CVD specifically in HD study participants. REM-SL might be a new risk factor of CVD events in HD patients with SRBDs.

Inverse association of fat mass, but not lean mass, with glycated albumin in hemodialysis patients with or without diabetes mellitus.

Background: Glycated albumin (GA), which is independent of anemia and/or use of erythropoiesis-stimulating agents, might provide a more precise measure than glycated hemoglobin (HbA1c) in hemodialysis patients. The present study examines whether body composition is associated with GA besides glycemic control in hemodialysis patients. Methods: This study included 90 hemodialysis patients with diabetes mellitus (DM) and 86 hemodialysis patients without DM. We examined blood parameters after an overnight fast and body fat and lean mass using dual X-ray absorptiometry 21-24 h after completing the dialysis session. Results: The mean body mass index (BMI) was 22.0 kg/m2. BMI and truncal fat mass were significantly higher, and total fat mass tended to be higher in hemodialysis patients with DM than in those without DM. GA exhibited inverse correlations with BMI, total lean mass, total fat mass, and truncal fat mass in hemodialysis patients with and without DM; however, there was a lack of correlation with total lean mass in patients without DM. In multiple regression analysis including total fat mass and total lean mass simultaneously as independent variables, total fat mass (with DM: ß = -0.322, p = .006) (without DM: ß = -0.391, p < .001), but not total lean mass, in addition to log fasting plasma glucose, emerged as an independent factor associated with GA in hemodialysis patients with and without DM. When total fat mass was replaced with truncal fat mass (with DM: ß = -0.311, p = .007) (without DM: ß = -0.396, p < .001), the association remained significant and independent with GA in both patient groups. Conclusions: Higher total fat mass, particularly truncal fat mass, might be associated with lower GA levels, beside glycemic control, in hemodialysis patients with or without DM.

Impact of diabetes on sarcopenia and mortality in patients undergoing hemodialysis.

BACKGROUND: Sarcopenia has become a serious disorder in modern society. Chronic kidney disease requiring dialysis and diabetes are some of the disorders that accelerate the onset and progression of sarcopenia. We, therefore, investigated the prevalence of sarcopenia in patients undergoing hemodialysis (HD) and confirmed the impact of diabetes mellitus (DM) on this population. METHODS: This study included 308 patients whose muscle strength and mass had been evaluated using handgrip strength and dual-energy X-ray absorptiometry, respectively. Sarcopenia was defined according to the criteria established by the Asian Working Group on Sarcopenia. In addition, this cohort had been followed up for 9 years. RESULTS: The prevalence of sarcopenia was 40% (37% in males and 45% in females) with gender differences being insignificant (p = 0.237). The DM morbidity rate was significantly higher in those with sarcopenia than in those without sarcopenia (41% vs. 27%, p = 0.015). Multivariate regression analyses showed that the presence of DM was an independent contributor to sarcopenia in patients undergoing HD (odds ratio 3.11; 95% confidence interval 1.63-5.93; p <  0.001). During the follow-up of 76 ± 35 months, 100 patients died. Patients with sarcopenia demonstrated significantly higher rates of all-cause mortality than those without sarcopenia (p <  0.001 using the log-rank test). Multivariate Cox proportional hazards analyses revealed that the presence of DM was significantly associated with higher all-cause mortality (adjusted hazard ratio: 2.39; 95% confidence interval 1.51-3.81; p <  0.001). CONCLUSIONS: The prevalence of sarcopenia among this cohort of patients undergoing HD was determined to be 40%. Moreover, the presence of DM was an independent contributor to sarcopenia and an independent predictor of all-cause mortality in this population.

Effects of Long-Term Cinacalcet Administration on Parathyroid Gland in Hemodialysis Patients with Secondary Hyperparathyroidism.

BACKGROUND/AIM: Cinacalcet, an allosteric modulator of the calcium (Ca) sensing receptor, reduces the level of parathyroid hormone (PTH) in serum as well as parathyroid gland volume following administration in hemodialysis patients with secondary hyperparathyroidism, though long-term results are yet to be reported. METHODS: Serum parameters (n = 23), together with total parathyroid gland volume (n = 18), were determined in Japanese hemodialysis patients given cinacalcet treatment for 8 years. RESULTS: Following initiation of cinacalcet therapy, levels of serum Ca, phosphate, and intact PTH were significantly decreased. Furthermore, the baseline total volume of the parathyroid gland was 1,272 mm3 (496-2,836 mm3), which was then decreased after 6 months to 796 mm3 (377-1,146 mm3) and then to 332 mm3 (175-570 mm3) after 8 years. There was significant positive correlation between parathyroid gland volume at the start of cinacalcet treatment and reduction in volume during the 8 years cinacalcet treatment. The dose of phosphate binder was significantly decreased in a time-dependent manner after 8 years of cinacalcet treatment, likely because serum phosphate showed a progressive decrease with the treatment. CONCLUSION: In the present patients, long-term treatment with cinacalcet progressively decreased the total volume of parathyroid glands, as well as levels of intact PTH and phosphate in serum in a time-dependent manner. On the contrary, cinacalcet administration did not cause secondary failure or over-suppress the transition of parathyroid gland activity to hypoparathyroid status. These results suggest that cinacalcet treatment may postpone the need for parathyroidectomy and/or reduce its use even after long-term administration for up to 8 years.

Effect of Oral Alfacalcidol on Clinical Outcomes in Patients Without Secondary Hyperparathyroidism Receiving Maintenance Hemodialysis: The J-DAVID Randomized Clinical Trial.

Importance: Patients with chronic kidney disease have impaired vitamin D activation and elevated cardiovascular risk. Observational studies in patients treated with hemodialysis showed that the use of active vitamin D sterols was associated with lower risk of all-cause mortality, regardless of parathyroid hormone levels. Objective: To determine whether vitamin D receptor activators reduce cardiovascular events and mortality in patients without secondary hyperparathyroidism undergoing hemodialysis. Design, Setting, and Participants: Randomized, open-label, blinded end point multicenter study of 1289 patients in 207 dialysis centers in Japan. The study included 976 patients receiving maintenance hemodialysis with serum intact parathyroid hormone levels less than or equal to 180 pg/mL. The first and last participants were enrolled on August 18, 2008, and January 26, 2011, respectively. The final date of follow-up was April 4, 2015. Interventions: Treatment with 0.5 µg of oral alfacalcidol per day (intervention group; n = 495) vs treatment without vitamin D receptor activators (control group; n = 481). Main Outcomes and Measures: The primary outcome was a composite measure of fatal and nonfatal cardiovascular events, including myocardial infarctions, hospitalizations for congestive heart failure, stroke, aortic dissection/rupture, amputation of lower limb due to ischemia, and cardiac sudden death; coronary revascularization; and leg artery revascularization during 48 months of follow-up. The secondary outcome was all-cause death. Results: Among 976 patients who were randomized from 108 dialysis centers, 964 patients were included in the intention-to-treat analysis (median age, 65 years; 386 women [40.0%]), and 944 (97.9%) completed the trial. During follow-up (median, 4.0 years), the primary composite outcome of cardiovascular events occurred in 103 of 488 patients (21.1%) in the intervention group and 85 of 476 patients (17.9%) in the control group (absolute difference, 3.25% [95% CI, -1.75% to 8.24%]; hazard ratio, 1.25 [95% CI, 0.94-1.67]; P = .13). There was no significant difference in the secondary outcome of all-cause mortality between the groups (18.2% vs 16.8%, respectively; hazard ratio, 1.12 [95% CI, 0.83-1.52]; P = .46). Of the 488 participants in the intervention group, 199 (40.8%) experienced serious adverse events that were classified as cardiovascular, 64 (13.1%) experienced adverse events classified as infection, and 22 (4.5%) experienced malignancy-related serious adverse events. Of 476 participants in the control group, 191 (40.1%) experienced cardiovascular-related serious adverse events, 63 (13.2%) experienced infection-related serious adverse events, and 21 (4.4%) experienced malignancy-related adverse events. Conclusions and Relevance: Among patients without secondary hyperparathyroidism undergoing maintenance hemodialysis, oral alfacalcidol compared with usual care did not reduce the risk of a composite measure of select cardiovascular events. These findings do not support the use of vitamin D receptor activators for patients such as these. Trial Registration: UMIN-CTR Identifier: UMIN000001194.

Paradoxical positive association of serum adiponectin with all-cause mortality based on body composition in Japanese haemodialysis patients.

We have previously reported a paradoxical association of serum adiponectin with aortic calcification in haemodialysis patients. Because serum adiponectin is a nutritional marker, we examined the association between serum adiponectin and all-cause mortality based on body composition in haemodialysis patients. The trunk and total body fat were determined. The patients were divided into two groups based on serum adiponectin levels. In Kaplan-Meier analysis, the higher adiponectin group showed higher mortality than the lower adiponectin group. Serum adiponectin showed an inverse correlation with the percentage of truncal fat, suggesting serum adiponectin as an inverse marker for adiposity in haemodialysis patients. However, even after adjustment for other factors, multivariate Cox proportional hazards analysis identified higher serum adiponectin as an independent factor positively associated with higher mortality in haemodialysis patients. This association held true even when the total fat mass was replaced with the percentage of truncal fat, and when total fat mass and percentage of truncal fat were simultaneously included. Thus, we found a paradoxical association of higher serum adiponectin with higher all-cause mortality in Japanese haemodialysis patients, independent of adiposity.

Association of Decreased Handgrip Strength with Reduced Cortical Thickness in Japanese Female Patients with Type 2 Diabetes Mellitus.

LD-100, a quantitative ultrasonic device, allows us to measure cortical thickness (CoTh). Patients with type 2 diabetes mellitus (T2DM) show high prevalence of sarcopenia. This study aimed to clarify the association of handgrip strength (HGS) with cortical porosis, a major risk for fracture of DM. CoTh and trabecular bone mineral density (TrBMD) at the 5.5% distal radius were assessed in T2DM female patients (n = 122) and non-DM female controls (n = 704) by LD-100. T2DM patients aged older 40 years showed significantly lower HGS and CoTh, but not TrBMD, than non-DM counterparts. Although HGS was significantly and positively correlated with CoTh and TrBMD in T2DM patients, multivariate analysis revealed HGS as an independent factor positively associated with CoTh, but not TrBMD, in T2DM patients, suggesting the preferential association of HGS with cortical, but not trabecular, bone component in T2DM female patients. In conclusion, the present study demonstrated an early decline of HGS in T2DM female patients as compared with non-DM healthy controls after the age of 40 years, which is independently associated with thinner CoTh, but not TrBMD in T2DM patients, and thus suggested that reduced muscle strength associated with DM might be a major factor for cortical porosis development in DM patients.

The association of serum adiponectin with abdominal aortic calcification in Japanese male hemodialysis patients: a cross-sectional observational study.

The negative relation of serum adiponectin to atherosclerosis becomes a positive association in patients with chronic kidney disease (CKD). We conducted a small-scale cross-sectional observational study, in 101 Japanese male hemodialysis patients, to examine the relationship of serum adiponectin and leptin to abdominal aortic calcification (AAC). The presence of AAC was evaluated from simple X-ray radiographs of the left lateral abdomen. Serum adiponectin was significantly higher in AAC-positive patients [18.8 (13.0-28.1) µg/mL] than in AAC-negative patients [15.4 (8.9-22.8) µg/mL] (p = 0.03), whereas serum leptin did not differ significantly between the two groups. Multiple logistic regression analysis showed that log adiponectin, but not log leptin, was independently and significantly associated in a positive manner with AAC (odds ratio: 16.31, 95% confidence interval: 1.70-156.41, p = 0.02), after adjustment for age, body weight, percentage body fat, hemodialysis duration, prevalence of diabetes mellitus, and other risk factors. In conclusion, we found a positive and independent association of serum adiponectin with AAC in male hemodialysis patients, indicating that the reversed association between serum adiponectin and atherosclerosis in patients with CKD dose not result from increased serum adiponectin due to the impaired urinary secretion.

High Coronary Heart Disease Risk in Hemodialysis Patients with Central Sleep Apnea: A Pilot Study.

BACKGROUND: The high prevalence of sleep apnea is reported in hemodialysis patients despite the low prevalence of obesity. The present study compared the occurrence of central sleep apnea (CSA) in hemodialysis patients with that in non-hemodialysis patients, and its association with new-onset coronary heart disease (CHD) events. METHODS: Seventy-three hemodialysis and 444 non-hemodialysis patients were examined for CSA and obstructive sleep apnea (OSA) occurrence using polysomnography. Hemodialysis patients were monitored for the occurrence of new-onset CHD events. RESULTS: Hemodialysis patients had a significantly higher central apnea-hypopnea index (AHI; 0.7, range 0.2-3.1) than age-, sex- and obstructive AHI-matched non-hemodialysis patients (0.1, range 0-1.0; p < 0.001), in contrast with an insignificant difference for obstructive AHI. Furthermore, the prevalence of CSA was significantly higher in the hemodialysis (21.9%) than in the non-hemodialysis group (9.7%; p = 0.004). A significant and negative association existed between log (central AHI + 1) and Kt/V in hemodialysis patients. In the Kaplan-Meier analysis, hemodialysis patients with CSA had a significantly higher rate of new-onset CHD events than those without CSA. Cox proportional-hazards regression analysis identified CSA prevalence as an independent risk factor for the development of a new-onset CHD event, independent of OSA. CONCLUSIONS: The present study demonstrated that hemodialysis patients had a significantly higher CSA prevalence than non-hemodialysis patients despite similar obstructive AHI, and that hemodialysis patients with CSA had a significantly higher risk for new-onset CHD events than those without CSA independent of obstructive AHI, suggesting CSA as a potential CHD risk specifically in hemodialysis patients.

Association of Erythropoietin Resistance with Fatigue in Hemodialysis Patients: A Cross-Sectional Study.

BACKGROUND/AIMS: Fatigue is a common symptom in patients receiving hemodialysis (HD) and is generally associated with anemia. However, it can be difficult to resolve, even when anemia has been treated using erythropoiesis-stimulating agents and iron replacement therapy. In the present study, we examined the associations of anemia, the erythropoietin resistance index (ERI) and iron deficiency with fatigue during HD. METHODS: In this cross-sectional study, fatigue score was calculated on the basis of questionnaire responses in HD patients. Participants were divided into 3 groups according to their hemoglobin (Hb) levels (low, normal and high). Iron deficiency was assessed as a transferrin saturation (TSAT) of <20%. RESULTS: We included 571 HD patients (men/women 368/203; mean age 62.2 ± 10.8 years). Among the 3 groups, fatigue scores increased significantly with decreasing Hb levels. HD patients with low Hb levels (<90 g/l) had significantly higher fatigue scores than those with higher Hb levels (≥120 g/l). In the multiple regression analysis, we showed that a high ERI (ß = 0.208) and a low TSAT (ß = -0.155), but not the Hb level, were significantly associated with increased fatigue score. Moreover, this was independent of age, gender and modifiable confounders linked to anemia. Even after restricting patients to those without iron deficiency (TSAT ≥20%), the ERI (ß = 0.258) retained a significant and independent association with the fatigue score. CONCLUSION: Iron deficiency and a high ERI despite iron sufficiency may cause fatigue in HD patients.

Association of Increased Serum Ferritin With Impaired Muscle Strength/Quality in Hemodialysis Patients.

OBJECTIVE: We reported previously that muscle quality and muscle strength provide clinically relevant predictors for better survival in hemodialysis patients. Iron overload might impair muscle function by its accumulation in muscle in such patients. METHODS: Serum ferritin, a marker for body iron store, was examined for its association with handgrip strength (HGS) and muscle quality which was defined as the ratio of HGS to arm lean mass measured with dual-energy X-ray absorptiometry. RESULTS: In 300 Japanese hemodialysis patients, age, hemodialysis duration, body mass index, and serum albumin were 58.0 ±12.0 (mean ± standard deviation) years, 4.2 (1.8-10.4) (median [25th-75th percentile]) years, 20.4 ± 2.8 kg/m(2), 4.0 ± 0.3 g/dL, respectively. Hemoglobin and hematocrit were 8.9 ± 1.2 g/dL, and 28.8 ± 3.9%, respectively, whereas transferrin saturation and serum ferritin were 29.8 ± 11.0% and 100 (54-172) ng/mL, respectively. Serum ferritin significantly correlated in a positive manner with the total dose of iron orally administered during the previous 6 months (r = 0.185, P = .0013). HGS and muscle quality were 23.1 ± 10.4 kg and 11.6 ± 3.8 kg/kg, respectively. In multivariate analysis to elucidate the factors associated with HGS and muscle quality in 300 hemodialysis patients, which included transferrin saturation and log serum ferritin, in addition to age, gender, hemodialysis duration, the presence/absence of diabetes, body mass index as independent variables, log serum ferritin emerged as a significant and independent factor which associated in a negative fashion with HGS (ß = -0.091, P = .0395) and tendency toward negative association with muscle quality (ß = -0.100, P = .0754). CONCLUSION: In summary, the present study demonstrated the significant association of serum ferritin with HGS and muscle quality in hemodialysis patients and thus suggested that we should be careful of iron overload to avoid its possible harmful effect on muscle in such patients.

Restoration of parathyroid function after change of phosphate binder from calcium carbonate to lanthanum carbonate in hemodialysis patients with suppressed serum parathyroid hormone.

Control of phosphate is the most critical in the treatment of chronic kidney disease with mineral and bone disorder (CKD-MBD). Because calcium-containing phosphate binder to CKD patients is known to induce adynamic bone disease with ectopic calcification by increasing calcium load, we examined the effect of lanthanum carbonate (LaC), a non-calcium containing phosphate binder, to restore bone turnover in 27 hemodialysis patients with suppressed parathyroid function (serum intact parathyroid hormone [iPTH] ≦ 150 pg/mL). At the initiation of LaC administration, the dose of calcium-containing phosphate binder calcium carbonate (CaC) was withdrawn or reduced based on serum phosphate. After initiation of LaC administration, serum calcium and phosphate decreased significantly by 4 weeks, whereas whole PTH and iPTH increased. A significant and positive correlation between decreases of serum calcium, but not phosphate, with increases of whole PTH and iPTH, suggested that the decline in serum calcium with reduction of calcium load by LaC might increase parathyroid function. Serum bone resorption markers, such as serum tartrate-resistant acid phosphatase 5b, and N-telopeptide of type I collagen increased significantly by 4 weeks after LaC administration, which was followed by increases of serum bone formation markers including serum bone alkaline phosphatase, intact procollagen N-propeptide, and osteocalcin. Therefore, it was suggested that LaC attenuated CaC-induced suppression of parathyroid function and bone turnover by decreasing calcium load. In conclusion, replacement of CaC with LaC, either partially or totally, could increase parathyroid function and resultant bone turnover in hemodialysis patients with serum iPTH ≦ 150 pg/mL.

Serum ß2-microglobulin correlates positively with left ventricular hypertrophy in long-term hemodialysis patients.

BACKGROUND/AIMS: ß2-Microglobulin (ß2-MG) is a major protein component of dialysis-related amyloidosis. In long-term hemodialysis (HD) patients, ß2-MG amyloid deposits not only in osteoarticular tissues, but also in systemic tissues, including the heart. The purpose of this study was to investigate the relationship between serum ß2-MG concentrations and echocardiographic parameters in long-term HD patients in a cross-sectional study. METHODS: Measurement of serum ß2-MG concentrations and echocardiography were performed in 251 patients who had undergone HD therapy for more than 10 years. RESULTS: The left ventricular mass index (LVMI) of the higher serum ß2-MG (≥30 mg/l) group was significantly higher than that of the lower serum ß2-MG (<30 mg/l) group (151.5 ± 45.7 vs. 137.0 ± 44.5 g/m(2), p = 0.020). In simple regression analyses, serum ß2-MG concentrations correlated significantly and positively with interventricular septum thickness (IVST) (r = 0.215, p < 0.001), posterior left ventricular wall thickness (PWT) (r = 0.249, p < 0.001), left ventricular wall thickness (LVWT) (r = 0.252, p < 0.001), relative wall thickness (RWT) (r = 0.153, p = 0.015) and LVMI (r = 0.171, p = 0.007). Multiple regression analyses revealed that serum ß2-MG concentrations correlated significantly and positively with IVST, PWT, LVWT and RWT. CONCLUSION: Serum ß2-MG concentrations correlated significantly and positively with the echocardiographic parameters of left ventricular hypertrophy (LVH) in long-term HD patients. Thus, deposition of ß2-MG amyloid in the heart may be associated with LVH progression.

Significant association between bone-specific alkaline phosphatase and vascular calcification of the hand arteries in male hemodialysis patients.

BACKGROUND/AIMS: Bone-specific alkaline phosphatase (BAP) hydrolyzes pyrophosphate, which inhibits vascular calcification. We examined association between serum BAP and vascular calcification of male hemodialysis patients. METHODS: Hand roentgenography of 167 male maintenance hemodialysis patients was conducted, and visible vascular calcification of the hand arteries was evaluated. Serum levels of 3 bone formation markers (BAP, osteocalcin, and N-terminal propeptide of type I collagen) and 2 bone resorption markers (C-terminal telopeptide of type I collagen, and cross-linked N-telopeptide of type I collagen) were measured, along with serum intact parathyroid hormone (PTH). RESULTS: Of 167 patients, visible vascular calcification was seen in 37 patients. Among the bone formation and resorption markers, serum BAP was significantly higher in patients with vascular calcification than in those without (p<0.05); although the other 5 serum bone markers were not significantly different between them. Multivariate logistic regression analyses revealed that log [BAP] was significantly associated with vascular calcification after adjustment for age, hemodialysis duration, presence of diabetes, log [intact PTH] and each of the other 5 bone markers (p<0.0001). CONCLUSIONS: Higher serum BAP, but not other bone markers, is significantly associated with the presence of vascular calcification in male hemodialysis patients.

Relationship between serum sclerostin, bone metabolism markers, and bone mineral density in maintenance hemodialysis patients.

BACKGROUND: Sclerostin, which is secreted exclusively by osteocytes, is a negative regulator of bone formation. The role of sclerostin in chronic kidney disease-mineral and bone disorder is not well known. In the present study, we examined the relationship between serum sclerostin levels, bone turnover markers, and bone mineral density (BMD) of the radius in maintenance hemodialysis patients. METHODS: This was a cross-sectional study that analyzed sclerostin, bone alkaline phosphatase (a bone formation marker), and tartrate-resistant acid phosphatase 5b (a bone resorption marker) in stored serum samples from 181 hemodialysis patients (age, 68 ± 11 y; 105 males and 76 females; hemodialysis duration, 6.9 ± 5.9 y). The BMD in the distal one-third of the radius and in the ultradistal radius, which are enriched with cortical and cancellous bone, respectively, was examined by dual-energy x-ray absorptiometry. RESULTS: Serum sclerostin was 125 ± 53 pmol/L (mean ± SD). Serum sclerostin correlated significantly and negatively with serum bone alkaline phosphatase and tartrate-resistant acid phosphatase 5b (r = -0.265, P < .001; r = -0.218, P < .01, respectively). The BMD in the distal one-third of the radius and in the ultradistal radius both correlated significantly and positively with serum sclerostin levels (r = 0.454, P < .0001; r = 0.329, P < .0001, respectively). In multiple regression analysis, serum sclerostin was associated significantly and independently with BMD of both parts of the radius (ß = 0.200, P < .001; ß = 0.218, P < .05), after adjustment for age, hemodialysis duration, and bone metabolism markers. CONCLUSION: Serum sclerostin was associated significantly, independently, and positively with BMD of both cortical and cancellous bone. Sclerostin is considered to be one of the factors associated with chronic kidney disease-mineral and bone disorder in hemodialysis patients.