CKD-MBD Research Articles

Musculoskeletal manifestations in end-stage renal disease patients on hemodialysis and relation to parathyroid dysfunction

End-stage renal disease (ESRD) is associated with chronic kidney disease-mineral and bone disorder (CKD-MBD); including renal osteodystrophy, and biochemical changes reflecting mineral and hormonal abnormalities. CKD-MBD can lead to serious musculoskeletal manifestations with an impact on the functional status of patients. The objective is to find the frequency of the musculoskeletal manifestations in dialysis patients, to determine the impact on the functional ability of patients, and to detect the relation between parathyroid hormone (PTH) level and musculoskeletal manifestations. The sample size included 53 adult patients on hemodialysis (HD), three times weekly, divided into two groups as follows; (Group A) included 15 patients (10 males and 5 females) on HD for a year or <1 year and (Group B) included 38 patients (24 males and 14 females) on HD for >1 year. All patients were subjected to a full history and physical examination plus a comprehensive assessment of patient's disability was done with a health assessment questionnaire (HAQ)-disability index. The most common neurological manifestations are uremic polyneuropathy (43.4%) and carpal tunnel syndrome. Arthralgia is the most common musculoskeletal manifestation (83%).The most common radiological signs of SHPT is the subperiosteal resorption of the terminal phalanges (67.9%). The most common MSUS abnormalities are Achilles tendinopathy (67.9%). Osteoporosis is detected in 24.5% of patient. There are highly positive significant correlations between HAQ score and age, HD duration, serum PTH, T-score, and X-ray findings. Musculoskeletal system involvement remains a common problem which decreases the physical function of patients with ESRD.

7. CKD-MBD

7. CKD-MBD

Effect of Ronghuang Granule on serum FGF23, FGFRs and Klotho in non-dialysis patients with CKD-MBD and kidney deficiency and damp-heat syndrome

To observe the effect of Ronghuang granule on serum fibroblast growth factor 23 (FGF23), fibroblast growth factor receptor (FGFRs) and Klotho protein levels in non-dialysis patients with chronic kidney disease-mineral and bone disorder (CKD-MBD) and kidney deficiency and damp heat syndrome. Seventy non-dialysis CKD-MBD patients with kidney deficiency and dampness-heat syndrome were randomized into control group (n=35) and treatment group (n=35). All the patients were given routine treatment combined with traditional Chinese medicine retention enema, and the patients in the treatment group received additional Ronghuang granule treatment (3 times a day). After the 12-week treatments, the patients were examined for changes of TCM syndromes. Serum levels of Ca, P, parathyroid hormone (iPTH), FGF23, FGFRs and Klotho proteins were detected before and after treatment. These parameters were also examined in 20 healthy volunteers. Sixty-five patients completed the study, including 33 in the control group and 32 in the treatment group. The patients in the treatment group showed significantly better treatment responses than those in the control group (P &lt; 0.05 or 0.01). At 4, 8, and 12 weeks of treatment, the patients in the treatment group had significantly lowered scores of TCM syndromes compared with the score before treatment (P &lt; 0.05 or 0.01), while in the control group, significant reduction of the scores occurred only at 12 weeks (P &lt; 0.05); at each of the time points, the treatment group had significantly greater reductions in the score than the control group (P &lt; 0.01). Significant improvements in serum Ca, P and iPTH levels were observed at 4, 8, and 12 weeks in the treatment group (P &lt; 0.05) but only at 12 weeks in the control group (P &lt; 0.05). The patients in the control and treatment groups all showed elevated serum levels of FGF23, FGFRs and Klotho protein compared with the normal subjects (P &lt; 0.01); FGF23, FGFRs and Klotho levels were significantly reduced in the treatment group (P &lt; 0.05) but remained unchanged in the control group (P&gt;0.05), showing significant differences between the two groups. Ronghuang granule improves the clinical symptoms of non-dialysis CKD-MBD patients with kidney deficiency and dampness heat syndrome by reducing serum levels of FGF23, FGFRs and Klotho, improving calcium and phosphorus metabolism disorder, and inhibiting secondary hyperparathyroidism.

Routine Laboratory Testing Every 4 Versus Every 6 Weeks for Patients on Maintenance Hemodialysis: A Quality Improvement Project

Few data exist revealing how the frequency of routine blood work for patients on maintenance hemodialysis therapy affects patient outcomes and the costs of care. Our objective was to determine the effect of changing the frequency of blood work from 4- to 6-week intervals on the achievement of anemia and chronic kidney disease-mineral and bone disorder (CKD-MBD) targets. Retrospective interrupted time series from June 1, 2012, to December 31,2015. Tertiary hospital in Ontario, Canada, that provides maintenance hemodialysis therapy to 350 to 400 adult patients. Institution-wide switch of the interval for routine blood work from 4 to 6 weeks on March 24,2014. Achievement of recommended hemoglobin and phosphate level targets. Cost savings attributable to a change in frequency of blood work for hemoglobin, ferritin, iron saturation, calcium, and phosphate comparing 252-day periods under each testing frequency condition. Statistical process control to analyze variation in the clinical outcomes. The proportion of patients who achieved hemoglobin (10-12g/dL) and phosphate (2.5-4.6mg/dL) targets remained stable (average of 60% and 46%, respectively), with no measurements beyond 3 standard deviations from the mean. The hemodialysis unit mortality rate also remained stable (average of 2% per month). Reducing blood work frequency to every 6 weeks was associated with a saving of $85 per patient-year, corresponding to a program-wide savings of $35,000. No case-mix adjustment due to useof aggregate hemodialysis unit data, andabsence of data for hospitalizations and transfusions limiting assessment of the full cost of patient care. After switching the frequency of routine blood work from 4- to 6-week intervals, performance on anemia and CKD-MBD targets did not change and the reduction in blood work was associated with laboratory cost savings. Reducing the frequency of blood work may represent an opportunity for hemodialysis providers to devote greater efforts toward other care elements that better improve patient outcomes.

Factors Affecting Bone Mineral Density in Hemodialysis Patients

Objective: Disorders of mineral metabolism and bone density are common complications in chronic kidney disease and are an important cause of morbidity. Recently used definition is chronic kidney disease-mineral and bone disorder (CKD-MBD). The aim of our study was to evaluate the correlation between bone mineral density and influencing factors in patients with end-stage renal failure undergoing hemodialysis.Material and Methods: In our study, cases were evaluated by being divided into 3 groups depending on bone mineral density (BMD). Our study included 124 cases and was designed as a cross-sectional observational study. The demographic data of the cases were recorded separately for each case. Routine biochemical analyses were studied. Results: The median vit D value of the patients with osteoporosis participated in the study was 14.44 mg/dl in the osteopenic group and the median value of the patients without osteoporosis was 20.14 mg/dl. The lowest and highest vit D values of the patients with osteoporosis were 3 mg/dl and 34.77 mg/dl, respectively. There was a statistically significant difference between all 3 groups for the age variable (p=0.002). There was a statistically significant difference between all 3 groups for the BMI variable (p=0.011). For 3 groups divided according to BMD measurements, statistically significant results were found in the PTH, Ferritin, Hgb, CRP, ALP, Albumin, e-GFR, hip and lumbar BMD values, respectively (p&amp;lt;0.001, p=0.001, p=0.004, p=0.001, p=0.003,p=0.005, p=0.001, p&amp;lt;0.001, p&amp;lt;0.001). Conclusion: In conclusion, our study revealed that the most important risk factor associated with osteoporosis in patients undergoing hemodialysis was PTH elevation and low vitamin D levels. For this purpose, BMD measurements and biochemical parameters of CKD patients undergoing hemodialysis should be studied in appropriate periods by adhering to the guidelines. Vit D replacement should not be neglected in order to avoid osteoporosis and to treat the detected cases.

Parathyroid Hormone Fragments: New Targets for the Diagnosis and Treatment of Chronic Kidney Disease-Mineral and Bone Disorder.

As a common disorder, chronic kidney disease (CKD) poses a great threat to human health. Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a complication of CKD characterized by disturbances in the levels of calcium, phosphorus, parathyroid hormone (PTH), and vitamin D; abnormal bone formation affecting the mineralization and linear growth of bone; and vascular and soft tissue calcification. PTH reflects the function of the parathyroid gland and also takes part in the metabolism of minerals. The accurate measurement of PTH plays a vital role in the clinical diagnosis, treatment, and prognosis of patients with secondary hyperparathyroidism (SHPT). Previous studies have shown that there are different fragments of PTH in the body's circulation, causing antagonistic effects on bone and the kidney. Here we review the metabolism of PTH fragments; the progress being made in PTH measurement assays; the effects of PTH fragments on bone, kidney, and the cardiovascular system in CKD; and the predictive value of PTH measurement in assessing the effectiveness of parathyroidectomy (PTX). We hope that this review will help to clarify the value of accurate PTH measurements in CKD-MBD and promote the further development of multidisciplinary diagnosis and treatment.

Early diagnosis, prevention and treatment for calcific uremic arteriolopathy

Calcific uremic arteriopathy (CUA), termed calciphylaxis, is a rare but highly fatal clinical syndrome. There is no clearly laboratory diagnostic criteria for CUA. The medium and small arterial calcification and microthrombosis discovered by skin biopsy, radiologic imaging，bone scan and the evidence of activation of the bone morphogenetic protein signal (BMPs) transduction pathway are useful for early diagnosis of this disease. The common therapies (including intravenous sodium thiosulfate (STS) and bisphosphonates, hyperbaric oxygen therapy and other symptomatic supports) are used for the management of wounds, pain, nutrition, dialysis and so on. Controlling the chronic kidney disease-mineral and bone disorder (CKD-MBD) and some complications of dialysis and drugs (such as warfarin, active vitamin D) can prevent CUA. However, CUA patients still have poor prognosis and high mortality. Since some patients progress rapidly, it is of great importance to make early diagnosis and provide effective treatments with multidisciplinary management.

Non-mercaptalbumin, Oxidized Form of Serum Albumin, Significantly Associated with Renal Function and Anemia in Chronic Kidney Disease Patients

Oxidative stress plays a major role in development of cardiovascular disease in patients with chronic kidney disease (CKD). Human mercaptalbumin (HMA), a reduced form of serum albumin, and non-mercaptalbumin (HNA), an oxidized form of serum albumin, are known as indicators for evaluating oxidative stress in systemic circulation, including end-stage renal disease cases. We investigated factors associated with fraction of HNA [f(HNA)] in 112 pre-dialysis CKD patients (63.6 ± 14.0 years old; 59 males, 53 females) using a newly established anion-exchange column packed with hydrophilic polyvinyl alcohol gel as well as high performance liquid chromatography. Mean f(HNA) in our CKD patients was 30.0 ± 6.1%, higher than that previously reported for healthy subjects. In multiple regression analysis, age (β = 0.200, p = 0.014), eGFR (β = −0.238, p = 0.009), hemoglobin (β = −0.346, p < 0.001), and ferritin (β = 0.200, p = 0.019) were significantly and independently associated with f(HNA) (R2 = 0.356, p < 0.001). In addition, factors related to CKD-mineral and bone disorder (CKD-MBD), including intact-PTH (β = 0.218, p = 0.049) and 1,25-dihydroxyvitamin D (1,25(OH)2D) (β = −0.178, p = 0.040), were significantly and independently associated with serum f(HNA) (R2 = 0.339, p < 0.001), whereas fibroblast growth factor-23 was not. These findings indicate the importance of management of hemoglobin and ferritin levels, as well as appropriate control of CKD-MBD factors for a better redox state of serum albumin in CKD patients.

Rethinking Bone Disease in Kidney Disease.

ABSTRACTRenal osteodystrophy (ROD) is the bone component of chronic kidney disease mineral and bone disorder (CKD‐MBD). ROD affects bone quality and strength through the numerous hormonal and metabolic disturbances that occur in patients with kidney disease. Collectively these disorders in bone quality increase fracture risk in CKD patients compared with the general population. Fractures are a serious complication of kidney disease and are associated with higher morbidity and mortality compared with the general population. Furthermore, at a population level, fractures are at historically high levels in patients with end‐stage kidney disease (ESKD), whereas in contrast the general population has experienced a steady decline in fracture incidence rates. Based on these findings, it is clear that a paradigm shift is needed in our approach to diagnosing and managing ROD. In clinical practice, our ability to diagnose ROD and initiate antifracture treatments is impeded by the lack of accurate noninvasive methods that identify ROD type. The past decade has seen advances in the noninvasive measurement of bone quality and strength that have been studied in kidney disease patients. Below we review the current literature pertaining to the epidemiology, pathology, diagnosis, and management of ROD. We aim to highlight the pressing need for a greater awareness of this condition and the need for the implementation of strategies that prevent fractures in kidney disease patients. Research is needed for more accurate noninvasive assessment of ROD type, clinical studies of existing osteoporosis therapies in patients across the spectrum of kidney disease, and the development of CKD‐specific treatments. © 2018 The Authors. JBMR Plus published by Wiley Periodicals, Inc. on behalf of the American Society for Bone and Mineral Research.

How does calcium compare with alternative phosphate binders for adults with chronic kidney disease-mineral and bone disorder (CKD-MBD)?

How does calcium compare with alternative phosphate binders for adults with chronic kidney disease-mineral and bone disorder (CKD-MBD)?

Dialysate Calcium Concentration below 3.0 mEq/L Is Not Associated with Improved Outcomes in the Japanese Dialysis Outcomes and Practice Patterns Study

Background: Abnormal chronic kidney disease-mineral and bone disorder (CKD-MBD) markers have been associated with adverse outcomes in hemodialysis (HD) patients. Dialysate calcium concentration (D-Ca) likely influences serum calcium and phosphorus levels. Optimal D-Ca level remains unclear. We hypothesized that higher D-Ca is associated with cardiovascular events and mortality among Japanese HD patients. Methods: Enrollment data of chronic HD patients in the prospective observational study JDOPPS, phases 1–5 (1999–2015), provided exposures and covariates. All-cause mortality, non-arrhythmic cardiovascular events (NonAR-CVE), or their composites were analyzed by D-Ca, and divided into 2.5, 2.75, and 3.0 mEq/L. To minimize confounding by indication, analyses were restricted to facilities in which at least 90% of patients received the same D-Ca prescription. Association of D-Ca level with outcomes was evaluated in Cox models stratified by phase and accounting for facility clustering. Covariates describing patient demographics, comorbidities, laboratory values, CKD-MBD therapy, and facility attributes provided adjustment. Results: Of 9,201 patients included, 25.0% had D-Ca of 2.5 mEq/L; 6.8% D-Ca 2.75; and 68.2% D-Ca 3.0. Median follow-up time was 2.03 years. D-Ca was not associated with all-cause mortality, with hazards ratios for 2.5 vs. 3.0 mEq/L of 0.90 and 95% CI (0.73–1.11), nor with other outcomes. One effect modification occurred, protective for lower D-Ca on NonAR-CVE in the absence of cardiovascular comorbidities (p = 0.032), although corresponding D-Ca effects were not significant after multiple comparisons adjustment (p = 0.261 [D-Ca 2.5] and 0.125 [D-Ca 2.75]). Conclusion: Lowering D-Ca level below 3.0 mEq/L seems not to have a meaningful effect on patient outcomes.

Moving from the second to the third generation Roche PTH assays: what are the consequences for clinical practice?

Background The determination of parathyroid hormone (PTH) is essential for exploring phosphocalcic disorders especially in patients with renal failure. At present, second or third generation PTH assays are available on the market from Roche Diagnostics as well as from others companies but the lack of standardization has complicated the interpretation. Methods We wanted to assess the clinical impact by measuring the PTH levels with the two generations concomitantly on different groups of populations including 46 healthy, 103 pre-dialyzed and 73 hemodialyzed (HD) patients. Results In healthy subjects, the PTH concentrations were not different whatever the generation used, whereas beyond 200 pg/mL, we reported an overestimation of the second generation PTH. In patients with chronic kidney disease (CKD) stage 3-5 the observed differences between the two generations increase with increasing PTH levels and decreasing glomerular filtration rate (GFR). Classification according to the kidney disease: improving global outcomes (KDIGO) revealed a high percentage of discordant results between the two generations (κ coefficient <0.20). These discrepancies are clinically relevant as PTH levels remain the cornerstone for diagnosis and treatment of the CKD-mineral and bone disorder (CKD-MBD). Conclusions The introduction of a new PTH assay generation in clinical practice should be carried out with caution.

Role of the Wnt/b-Catenin Pathway Inhibitor Sclerostin in Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)

Role of the Wnt/b-Catenin Pathway Inhibitor Sclerostin in Chronic Kidney Disease-Mineral and Bone Disorder (CKD-MBD)

Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD).

Phosphate binders for preventing and treating chronic kidney disease-mineral and bone disorder (CKD-MBD).

Uremic Cardiomyopathy: A New Piece in the Chronic Kidney Disease-Mineral and Bone Disorder Puzzle.

Cardiovascular diseases are the main cause of death in chronic kidney disease (CKD) patients. In dialysis patients, sudden cardiac death accounts for 40% of all deaths. In these patients, sudden cardiac death is usually secondary to an underlying cardiomyopathy, which is clinically identified by the high prevalence of left ventricular hypertrophy and the resultant mechanical and electrical dysfunction. CKD-related cardiomyopathy has a multifactorial pathophysiology. Recent evidence has highlighted the central pathophysiological role of chronic kidney disease-mineral and bone disorder (CKD-MBD) with hyperphosphatemia and high fibroblast growth factor 23 (FGF23) levels in these patients. Further, since CKD is known to be an αKlotho deficiency state, experimental studies have demonstrated that the deleterious effects of FGF23 can be minimized by reestablishing adequate soluble Klotho levels. Herein, we present a review that addresses not only the development of the understanding of CKD-related cardiomyopathy pathophysiology, but also explores the recent data that identify the triad of hyperphosphatemia, high FGF23 levels and αKlotho deficiency as playing a central role on it. Taken together, the data suggest that the uremic cardiomyopathy can be considered a new piece in the CKD-DMO puzzle.

Is serum sclerostin a marker of atherosclerosis in patients with chronic kidney disease-mineral and bone disorder?

The complexity of chronic kidney disease-mineral and bone disorder (CKD-MBD) led to many preclinical and clinical trials. The role of sclerostin in renal pathophysiology remained unresolved, and question whether sclerostin is related to cardiovascular (CV) outcome in patients with CKD is still open. Our aim was to evaluate the possible association between serum sclerostin levels and carotid intima-media thickness (CIMT) in CV pathophysiology through various CKD stages. Eighty-eight patients in various CKD stages were involved in this analysis. CKD-EPI (Chronic kidney disease Epidemiology Collaboration Equation) was used to estimate glomerular filtration rate (eGFR). CKD-MBD parameters were determined in patients' serum after an overnight fasting. Early atherosclerosis was assessed by ultrasound measurement of CIMT. In order to assess the association between serum sclerostin with other CKD-MBD parameters and CIMT, correlation and regression analyses were performed. Mean age was 62.84 ± 11.37years and 56% were female. Mean values of serum sclerostin were 1.67 ± 0.44ng/ml. Negative correlation was noticed with serum calcium and phosphate product (CaxP), alkaline phosphatase (ALP), intact parathyroid hormone (iPTH), serum creatinine, and HbA1c level. There was no association with FGF23, CIMT, and carotid atherosclerotic plaque occurence. Serum levels of sclerostin were significantly higher in female patients compared to males (p < 0.001). Advanced CKD showed a trend of declining sclerostin levels and significantly higher CIMT levels. Serum sclerostin was not associated with CIMT. More studies are needed in order to reveal the exact role of sclerostin in the complexity of CKD-MBD pathophysiological mechanism.

Relationship of coronary artery calcification with renal function decline and mortality in predialysis chronic kidney disease patients.

Patients with chronic kidney disease (CKD) have higher levels of coronary artery calcification (CAC) compared with the general population. The role of CAC in renal function decline is not well understood. In this prospective cohort study of Stages 3-5 CKD patients with CAC scores kidney function decline, development of end-stage kidney disease (ESKD) and all-cause mortality were determined at 5 and 10 years. Baseline variables included markers of CKD and chronic kidney disease mineral and bone disorder (CKD-MBD), demographics and comorbidities. Multivariable analyses identified predictors of outcomes, and survival curves demonstrated the association of CAC score with ESKD and mortality. One hundred and seventy-eight patients were enrolled between 2005 and 2007. Independent predictors of ESKD at 5 years were estimated glomerular filtration rate (eGFR) and urine albumin-creatinine ratio (UACR); at 10 years, eGFR was no longer a predictor, but CAC was now significant. Those who developed ESKD at the fastest rate either had the highest CAC score (≥400 AU) or were youngest and had the lowest calcidiol, and highest serum phosphate, UACR and percentage change in CAC per year. Predictors of eGFR decline over 5 years were UACR, parathyroid hormone and CAC score. Predictors of mortality at 5 years were age, diabetes and eGFR and at 10 years also included CAC score. In Stages 3-5 CKD patients, CAC is an independent predictor of both ESKD and mortality at 10 years. Those who developed ESKD at the fastest rate either had the highest CAC score or the worst CKD-MBD derangements.

The intervention effect of zuogui pill on chronic kidney disease-mineral and bone disorder regulatory factor

Chronic kidney disease-mineral and bone disorder (CKD-MBD) play a critical role in the pathogenesis of cardiovascular complications in patients with chronic kidney disease (CKD). Zuogui pill as a traditional Chinese herbal drug has been used for nourish kidney essence improve bone malnutrition of renal bone disease by regulating the metabolism of calcium and phosphorus and participating in osteoblast metabolism. In the present study, 5/6 nephrectomy rat model was used to reveal the mechanism of zuogui pill in treatment of CKD-MBD. Compared with sham rats, the levels of serum phosphorus, PTH, iPTH and creatinine were significantly decreased, while the serum calcium level was significantly increased, and the Cbfa1 protein level was significantly decreased and FGF23 protein level was significantly increased by Zuogui pill treatment. Compared with model rats, the BMD of rat was significantly increased by Zuogui pill treatment. Histological analysis revealed that the kidney injury of rats with CKD was significantly reduced by zuogui pill treatment. Compared with model rats, the CYP27B1 mRNA level was significantly increased, and the PTH mRNA level and NaPiIIa protein level were significantly decreased in the kidney by zuogui pill treatment. We inferred that zuogui pill exhibited potential therapeutic effects on CKD-MBD in the rats by regulating bone metabolism and nourish kidney.

Augmented Fibroblast Growth Factor-23 Secretion in Bone Locally Contributes to Impaired Bone Mineralization in Chronic Kidney Disease in Mice.

Chronic kidney disease-mineral and bone disorder (CKD-MBD) is a systemic disorder of mineral and bone metabolism caused by CKD. Impaired bone mineralization together with increased bony secretion of fibroblast growth factor-23 (FGF23) are hallmarks of CKD-MBD. We recently showed that FGF23 suppresses the expression of tissue nonspecific alkaline phosphatase (TNAP) in bone cells by a Klotho-independent, FGF receptor-3-mediated signaling axis, leading to the accumulation of the mineralization inhibitor pyrophosphate. Therefore, we hypothesized that excessive FGF23 secretion may locally impair bone mineralization in CKD-MBD. To test this hypothesis, we induced CKD by 5/6 nephrectomy in 3-month-old wild-type (WT) mice and Fgf23−/−/VDRΔ/Δ (Fgf23/VDR) compound mutant mice maintained on a diet enriched with calcium, phosphate, and lactose. Eight weeks postsurgery, WT CKD mice were characterized by reduced bone mineral density at the axial and appendicular skeleton, hyperphosphatemia, secondary hyperparathyroidism, increased serum intact Fgf23, and impaired bone mineralization as evidenced by bone histomorphometry. Laser capture microdissection in bone cryosections showed that both osteoblasts and osteocytes contributed to the CKD-induced increase in Fgf23 mRNA abundance. In line with our hypothesis, osteoblastic and osteocytic activity of alkaline phosphatase was reduced, and bone pyrophosphate concentration was ~2.5-fold higher in CKD mice, relative to Sham controls. In Fgf23/VDR compound mice lacking Fgf23, 5/6-Nx induced secondary hyperparathyroidism and bone loss. However, 5/6-Nx failed to suppress TNAP activity, and bone pyrophosphate concentrations remained unchanged in Fgf23/VDR CKD mice. Collectively, our data suggest that elevated Fgf23 production in bone contributes to the mineralization defect in CKD-MBD by auto-/paracrine suppression of TNAP and subsequent accumulation of pyrophosphate in bone. Hence, our study has identified a novel mechanism involved in the pathogenesis of CKD-MBD.

Serum phosphate optimal timing and range associated with patients survival in haemodialysis: the COSMOS study.

Serum phosphate is a key parameter in the management of chronic kidney disease-mineral and bone disorder (CKD-MBD). The timing of phosphate measurement is not standardized in the current guidelines. Since the optimal range of these biomarkers may vary depending on the duration of the interdialytic interval, in this analysis of the Current management of secondary hyperparathyroidism: a multicentre observational study (COSMOS), we assessed the influence of a 2- (midweek) or 3-day (post-weekend) dialysis interval for blood withdrawal on serum levels of CKD-MBD biomarkers and their association with mortality risk. The COSMOS cohort (6797 patients, CKD Stage 5D) was divided into two groups depending upon midweek or post-weekend blood collection. Univariate and multivariate Cox's models adjusted hazard ratios (HRs) by demographics and comorbidities, treatments and biochemical parameters from a patient/centre database collected at baseline and every 6 months for 3 years. There were no differences in serum calcium or parathyroid hormone levels between midweek and post-weekend patients. However, in post-weekend patients, the mean serum phosphate levels were higher compared with midweek patients (5.5 ± 1.4 versus 5.2 ± 1.4 mg/dL, P < 0.001). Also, the range of serum phosphate with the lowest mortality risk [HR ≤ 1.1; midweek: 3.5-4.9 mg/dL (95% confidence interval, CI: 2.9-5.2 mg/dL); post-weekend: 3.8-5.7 mg/dL (95% CI: 3.0-6.4 mg/dL)] showed significant differences in the upper limit (P = 0.021). Midweek and post-weekend serum phosphate levels and their target ranges associated with the lowest mortality risk differ. Thus, clinical guidelines should consider the timing of blood withdrawal when recommending optimal target ranges for serum phosphate and therapeutic strategies for phosphate control.