Renal osteodystrophy and clinical outcomes: data from the Brazilian Registry of Bone Biopsies - REBRABO.

INTRODUCTION: Mineral and bone disorders (MBD) are major complications of chronic kidney disease (CKD)-related adverse outcomes. The Brazilian Registry of Bone Biopsy (REBRABO) is an electronic database that includes renal osteodystrophy (RO) data. We aimed to describe the epidemiological profile of RO in a sample of CKD-MBD Brazilian patients and understand its relationship with outcomes. METHODS: Between August 2015 and March 2018, 260 CKD-MBD stage 3-5D patients who underwent bone biopsy were followed for 12 to 30 months. Clinical-demographic, laboratory, and histological data were analyzed. Bone fractures, hospitalizations, and death were considered the primary outcomes. RESULTS: Osteitis fibrosa, mixed uremic osteodystrophy, adynamic bone disease, osteomalacia, osteoporosis, and aluminum (Al) accumulation were detected in 85, 43, 27, 10, 77, and 65 patients, respectively. The logistic regression showed that dialysis vintage was an independent predictor of osteoporosis (OR: 1.005; CI: 1.001-1.010; p = 0.01). The multivariate logistic regression revealed that hemodialysis treatment (OR: 11.24; CI: 1.227-100; p = 0.03), previous parathyroidectomy (OR: 4.97; CI: 1.422-17.241; p = 0.01), and female gender (OR: 2.88; CI: 1.080-7.679; p = 0.03) were independent predictors of Al accumulation; 115 patients were followed for 21 ± 5 months. There were 56 hospitalizations, 14 deaths, and 7 fractures during follow-up. The COX regression revealed that none of the variable related to the RO/turnover, mineralization and volume (TMV) classification was an independent predictor of the outcomes. CONCLUSION: Hospitalization or death was not influenced by the type of RO, Al accumulation, or TMV classification. An elevated prevalence of osteoporosis and Al accumulation was detected.

Increased Risk of Infection-Related and All-Cause Death in Hypercalcemic Patients Receiving Hemodialysis: The Q-Cohort Study.

Although hypercalcemia is a risk factor for all-cause mortality in hemodialysis patients, it remains unknown whether hypercalcemia increases the risk of infection-related death. A total of 2869 hemodialysis patients registered in the Q-Cohort Study, a multicenter, prospective cohort study of hemodialysis patients, were analyzed. The predictor was albumin-corrected serum calcium level at baseline. The main outcome was infection-related death. Death risk were estimated by multivariable-adjusted Cox proportional hazard risk models and competing risk models. During the follow-up period of 4 years, 107 patients died of infection and 473 died of any cause. The patients were divided into four groups by the serum calcium level at baseline (G1, 5.7-8.9 mg/dL; G2, 9.0-9.4 mg/dL; G3, 9.5-9.9 mg/L; G4 10.0-16.5 mg/dL). In the multivariable-adjusted model, the incidence of infection-related death was significantly higher in the highest serum calcium group (G4) compared with the lowest serum calcium group (G1): hazard ratio [95% confidence interval], 2.34 [1.35-4.04], P = 0.002. Furthermore, higher serum calcium level was significantly associated with increased risk of all-cause death. In conclusion, our data suggest that a higher serum calcium level may be a risk factor for infection-related and all-cause death in hemodialysis patients.

Association of changes in bone mineral parameters with mortality in haemodialysis patients: insights from the ARO cohort.

BACKGROUND: There is little information in haemodialysis (HD) patients on whether temporal changes in serum calcium, phosphate or intact parathyroid hormone (iPTH) are associated with mortality. METHODS: We analysed associations of phosphate, total calcium and iPTH with all-cause and cardiovascular mortality in 8817 incident HD patients from the European second Analyzing Data, Recognizing Excellence and Optimizing Outcomes (AROii) cohort enrolled in 2007-09, which were prospectively followed for a median of 3 years, using time-dependent Cox proportional hazards models. We evaluated changes in risk over time depending on changes in phosphate, calcium or iPTH. RESULTS: The association of phosphate and iPTH with all-cause mortality was U-shaped, with the lowest risk ranges between 1.20 and 1.89 mmol/L for phosphate and between 239 and 710 ng/L for iPTH. For total calcium, the associations were J-shaped, with an increased risk for all-cause mortality at levels >2.36 mmol/L. Lowest risk ranges for cardiovascular mortality did not change markedly for all three parameters. If iPTH was below the lowest risk range at baseline (iPTH <239 ng/L), a subsequent increase in levels was associated with improved survival. For phosphate, an increase or decrease out of the lowest risk range was associated with increased mortality risk. For calcium, this was only the case when the values increased above the lowest risk range. CONCLUSION: In the AROii cohort, the ranges of bone mineral biomarkers associated with the lowest mortality ranges were largely consistent with the current Kidney Disease: Improving Global Outcomes chronic kidney disease-mineral and bone disorder guideline recommendations. Allowing a suppressed iPTH to increase was associated with a lower mortality, whereas shifts of phosphate or calcium outside the lowest risk range increased mortality.

Associations of plasma fibroblast growth factor 23 and other markers of chronic kidney disease-Mineral and bone disorder with all-cause mortality in South African patients on maintenance dialysis: A 3-year prospective cohort study.

INTRODUCTION: Few studies have linked high levels of plasma C-terminal fibroblast growth factor 23 (FGF23) with poor clinical outcomes in patients on maintenance haemodialysis (MHD), while the association between intact FGF23 and mortality in this group of patients remains inconclusive. Therefore, the aim of this study was to evaluate the association between plasma levels of intact FGF23 and mortality in dialysis patients. METHODS: A prospective multicenter study involving patients undergoing dialysis at three dialysis centers in Johannesburg was undertaken between 1st October 2014 and 31st December 2017. RESULTS: The study comprised 165 chronic dialysis patients (111 blacks, 54 whites) with a mean age of 46.6 ±14.2 years. During a three year follow up period, there were 46 deaths (1.03 per 100 person-years). The median plasma FGF 23 level was 382 pg/ml (interquartile range [IQR], 145-2977). In adjusted multivariable analyses, there was a non-statistically significant increase in the risk of mortality with higher quartiles of FGF 23 levels: the adjusted hazard ratios (HR) for the second, third and fourth quantiles were HR 3.20 (95% CI, 0.99-10.35; P = 0.052), HR 2.43(95% CI,0.65-9.09; P = 0.19), and HR 2.09 (95% CI, 0.66-7.32; P = 0.25),respectively. Corrected serum calcium 2.38-2.5 mmol/l [HR 2.98 (95% CI, 1.07-8.29; P = 0.04] and > 2.50 mmol/l [HR 5.50 (95% CI, 1.84-16.48; P = 0.002] were independently associated with increased risk of death. Likewise, patients with intact parathyroid hormone > 600 pg/ml had a 3.46-fold higher risk of death (HR 3.46, 95% CI, 1.22-9.82 P = 0.019). These findings persisted in time -dependent analyses. CONCLUSION: Higher levels of intact FGF 23 appear not to be independently associated with all-cause mortality in our dialysis patients, while hypercalcaemia and severe hyperparathyroidism were found to be independent predictors of mortality in this cohort of patients.

Fibroblast Growth Factor 23 Genotype and Cardiovascular Disease in Patients Undergoing Hemodialysis.

BACKGROUND: Elevated serum concentrations of fibroblast growth factor 23 (FGF23) are associated with cardiovascular mortality in patients with chronic kidney disease and those undergoing dialysis. OBJECTIVES: We tested the hypotheses that polymorphisms in FGF23, its co-receptor alpha-klotho (KL), and/or FGF23 receptors (FGFR) are associated with cardiovascular events and/or mortality. METHODS: We used 1,494 DNA samples collected at baseline from the Evaluation of Cinacalcet HCl Therapy to Lower Cardiovascular Events Trial, in which patients were randomized to the calcimimetic cinacalcet or placebo for the treatment of secondary hyperparathyroidism. We analyzed European and African Ancestry samples separately and then combined summary statistics to perform a meta-analysis. We evaluated single-nucleotide polymorphisms (SNPs) in FGF23, KL, and FGFR4 as the key exposures of interest in proportional hazards (Cox) regression models using adjudicated endpoints (all-cause and cardiovascular mortality, sudden cardiac death, and heart failure [HF]) as the outcomes of interest. RESULTS: rs11063112 in FGF23 was associated with cardiovascular mortality (risk allele = A, hazard ratio [HR] 1.32, meta-p value = 0.004) and HF (HR 1.40, meta-p value = 0.007). No statistically significant associations were observed between FGF23 rs13312789 and SNPs in FGFR4 or KL genes and the outcomes of interest. CONCLUSIONS: rs11063112 was associated with HF and cardiovascular mortality in patients receiving dialysis with moderate to severe secondary hyperparathyroidism.

Detecting high-risk chronic kidney disease-mineral bone disorder phenotypes among patients on dialysis: a historical cohort study.

BACKGROUND: The clinical management of chronic kidney disease-mineral bone disorder (CKD-MBD) remains extremely challenging, partially due to difficulties in defining high-risk phenotypes based on serum biomarkers. We evaluated the prevalence and outcomes of 27 mutually exclusive CKD-MBD phenotypes in a large, multi-national cohort of chronic dialysis patients over a 5-year follow-up study. METHODS: In this historical cohort study, we enrolled all haemodialysis patients registered in EuCliD® on 1 July 2011 across 28 Europe, the Middle East and Africa (EMEA) and South American countries. We created 27 mutually exclusive phenotypes based on combinations of serum parathyroid hormone (PTH), phosphorus (P) and calcium (Ca) 6-month averages (L, low; T, target; H, high). We tested the association between CKD-MBD phenotypes and 5-year mortality and hospitalization risk by outcome risk score-adjusted proportional hazard regression. RESULTS: We enrolled 35 721 eligible patients. Eastern European and South American countries generally achieved poorer CKD-MBD control when compared with Western European countries (prevalence ratio: 0.79; P < 0.001). There were 15 795 deaths [126.7 deaths/1000 person-years; 95% confidence interval (CI) 124.7-128.7]; 18 014 had at least one hospitalization (203.9 hospitalizations/1000 person-years; 95% CI 201.0-206.9); the incidence of the composite endpoint was 280.0 events/1000 person-years (95% CI 276.6-283.5). In the fully adjusted model, relative mortality risk ranged from hazard ratio (HR) = 1.07 (PTH/Ca/P: TLT) to HR = 1.59 (PTH/Ca/P: LTL), whereas the relative composite endpoint risk ranged from HR = 1.07 (PTH/Ca/P: TTH) to HR = 1.36 (PTH/Ca/P: LTL). CONCLUSION: We identified several CKD-MBD phenotypes associated with reduced hospitalization-free survival and increased mortality. Ranking of relative risk estimates or excess events concurs in informing healthcare priority setting.

Functional impairment attenuates the association between high serum phosphate and mortality in dialysis patients: a nationwide cohort study.

BACKGROUND: Both functional impairment and abnormalities in mineral and bone disorder (MBD) parameters are well-known predictors of mortality in dialysis patients. However, previous studies have not evaluated whether functional impairment modifies the association between MBD parameters and mortality. METHODS: A nationwide prospective cohort study was conducted using data from the Japanese Society for Dialysis Therapy Renal Data Registry collected at the end of 2009 and 2010. The Eastern Cooperative Oncology Group performance status (PS) was used to assess functional status. Cox proportional hazards models were used to assess the associations of baseline functional status, serum phosphate, albumin-corrected calcium and intact parathyroid hormone (PTH) with 1-year all-cause mortality. RESULTS: By 31 December 2010, 18 447 of 220 054 prevalent dialysis patients (8.4%) had died. Mortality significantly increased with worsening PS grade. PS grade modified the association of serum phosphate levels with mortality (Pinteraction = 0.001). Worsening PS grade attenuated the association of hyperphosphatemia (≥7.4 mg/dL) with mortality, and hyperphosphatemia was no longer significant on mortality among patients with the worst PS grade (hazard ratio = 1.1, 95% confidence interval 0.88-1.39), compared with the level between 3.5 and 4.7 mg/dL. In contrast, hypophosphatemia (<3.5 mg/dL) had a greater adjusted risk of mortality irrespective of PS grade. Serum-corrected calcium (Pinteraction = 0.26) and intact PTH (Pinteraction = 0.17) showed consistent associations with mortality irrespective of PS grade. Findings were robust in several sensitivity analyses. CONCLUSIONS: Functional impairment was significantly associated with 1-year mortality and attenuated the effect of hyperphosphatemia on mortality among prevalent dialysis patients.

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

BACKGROUND: 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. METHODS: 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. RESULTS: 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). CONCLUSION: 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.

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.

Impact of surgical parathyroidectomy on chronic kidney disease-mineral and bone disorder (CKD-MBD) - A systematic review and meta-analysis.

For more than 6 decades, many patients with advanced chronic kidney disease (CKD) have undergone surgical parathyroidectomy (sPTX) for severe secondary hyperparathyroidism (SHPT) mainly based historical clinical practice patterns, but not on evidence of outcome.We aimed in this meta-analysis to evaluate the benefits and harms of sPTX in patients with SHPT. We searched MEDLINE (inception to October 2016), EMBASE and Cochrane Library (through Issue 10 of 12, October 2016) and website clinicaltrials.gov (October 2016) without language restriction. Eligible studies evaluated patients reduced glomerular filtration rate (GFR), below 60 mL/min/1.73 m2 (CKD 3-5 stages) with hyperparathyroidism who underwent sPTX. Reviewers working independently and in duplicate extracted data and assessed the risk of bias. The final analysis included 15 cohort studies, comprising 24,048 participants. Compared with standard treatment, sPTX significantly decreased all-cause mortality (RR 0.74 [95% CI, 0.66 to 0.83]) in End Stage Kidney Disease (ESKD) patients with biochemical and / or clinical evidence of SHPT. sPTX was also associated with decreased cardiovascular mortality (RR 0.59 [95% CI, 0.46 to 0.76]) in 6 observational studies that included almost 10,000 patients. The available evidence, mostly observational, is at moderate risk of bias, and limited by indirect comparisons and inconsistency in reporting for some outcomes (eg. short term adverse events, including documented voice change or episodes of severe hypocalcaemia needing admission or long-term adverse events, including undetectable PTH levels, risk of fractures etc.). Taken together, the results of this meta-analysis would suggest a clinically significant beneficial effect of sPTX on all-cause and cardiovascular mortality in CKD patients with SHPT. However, given the observational nature of the included studies, the case for a properly conducted, independent randomised controlled trial comparing surgery with medical therapy and featuring many different outcomes from mortality to quality of life (QoL) is now very strong.

Association of Parameters of Mineral Bone Disorder with Mortality in Patients on Hemodialysis according to Level of Residual Kidney Function.

BACKGROUND AND OBJECTIVES: The relationship between mineral and bone disorders and survival according to residual kidney function status has not been previously studied in patients on hemodialysis. We hypothesized that residual kidney function, defined by renal urea clearance, modifies the association between mineral and bone disorder parameters and mortality. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: The associations of serum phosphorus, albumin-corrected calcium, intact parathyroid hormone, and alkaline phosphatase with all-cause mortality were examined across three strata (<1.5, 1.5 to <3.0, and ≥3.0 ml/min per 1.73 m2) of baseline residual renal urea clearance using Cox models adjusted for clinical characteristics and laboratory measurements in 35,114 incident hemodialysis patients from a large United States dialysis organization over the period of 2007-2011. RESULTS: A total of 8102 (23%) patients died during the median follow-up of 1.3 years (interquartile range, 0.6-2.3 years). There was an incremental mortality risk across higher serum phosphorus concentrations, which was pronounced among patients with higher residual renal urea clearance (Pinteraction=0.001). Lower concentrations of serum intact parathyroid hormone were associated with higher mortality among patients with low residual renal urea clearance (i.e., <1.5 ml/min per 1.73 m2), whereas higher concentrations showed a higher mortality risk among patients with greater residual renal urea clearance (i.e., ≥1.5 ml/min per 1.73 m2; Pinteraction<0.001). Higher serum corrected total calcium and higher alkaline phosphatase concentrations consistently showed higher mortality risk (Ptrend<0.001 for both) irrespective of residual renal urea clearance strata (Pinteraction=0.34 and Pinteraction=0.53, respectively). CONCLUSIONS: Residual kidney function modified the mortality risk associated with serum phosphorus and intact parathyroid hormone among incident hemodialysis patients. Future studies are needed to examine whether taking account for residual kidney function into the assessment of mortality risk associated with serum phosphorus and intact parathyroid hormone improves patient management and clinical outcomes in the hemodialysis population.

Differentially expressed miR-3680-5p is associated with parathyroid hormone regulation in peritoneal dialysis patients.

Mineral and bone disorder (MBD) is observed universally in patients with chronic kidney disease (CKD). Detrimental MBD-related skeletal changes include increased prevalence of fracture, cardiovascular disease, and mortality. MicroRNAs (miRNAs) have been identified as useful biomarkers in various diseases, and the aim of this study was to identify miRNAs associated with parathyroid hormone level in peritoneal dialysis (PD) patients. Fifty-two PD patients were enrolled and grouped by their intact parathyroid hormone (iPTH) level; 11 patients had low iPTH (<150 pg/mL) and 41 patients had high iPTH (≥150 pg/mL). Total RNA was extracted from whole blood samples. Total RNA from 15 patients (7 and 8 patients in the low and high iPTH groups, respectively) underwent miRNA microarray analysis, and three differentially upregulated (>2-fold change) miRNAs previously associated with human disease were selected for real-time quantitative PCR (qPCR) analysis. Interaction analyses between miRNAs and genes were performed by using TargetScan and the KEGG pathway database. Microarray results revealed 165 miRNAs were differentially expressed between patients with high iPTH levels and low iPTH levels. Of those miRNAs, 81 were upregulated and 84 were downregulated in patients with high iPTH levels. Expression levels of miR-1299, miR-3680-5p, and miR-548b-5p (previously associated with human disease) in 52 patients were analyzed by using qPCR. MiR-3680-5p was differentially expressed in low and high iPTH patients (P < 0.05). The predicted target genes of miR-3680-5p were USP6, USP32, USP46, and DLT, which are involved in the ubiquitin proteolysis pathway. This pathway has roles in PTH and parathyroid hormone related protein degradation and proteolysis. The mechanisms involved in the associations among low PTH, adynamic bone disease, miR-3680-5p, and the target genes should be explored further in order to elucidate their roles in CKD-MBD development.

Roles of Serum Calcium, Phosphorus, PTH and ALP on Mortality in Peritoneal Dialysis Patients: A Nationwide, Population-based Longitudinal Study Using TWRDS 2005-2012.

Biomarkers of chronic kidney disease-mineral and bone disorder (CKD-MBD) correlate with morbidity and mortality in dialysis patients. However, the comparative roles of each CKD-MBD biomarker remained undetermined on long-term peritoneal dialysis (PD) patients. This retrospective study, employing a population-based database, aimed to evaluate the performance and provide the best evidence of each biomarker of CKD-MBD as predictor of all-cause mortality. Throughout the 8-year study period, total 12,116 PD patients were included in this study. Cox proportional regression and Kaplan-Meier method were used for survival analysis. For Cox regression model, baseline measurements and time-varying covariates were used for analysis. In Cox regression model using time-dependent covariates, serum calcium level of ≧9.5 mg/dL was associated with increased mortality. For phosphorus, serum levels of either ≧6.5 mg/dL or <3.5 mg/dL were associated with increased mortality. For parathyroid hormone (PTH), higher serum levels were not associated increased mortality. For alkaline phosphatase (ALP), mortality increased at levels ≧100 IU/L. Our findings suggested that the detrimental effect of ALP on survival was more consistent, while serum calcium, phosphorus and PTH may have a less prominent effect on mortality. This study provided additional information for manipulating CKD-MBD biomarkers in PD patients.

Association between the Achievement of Target Range CKD-MBD Markers and Mortality in Prevalent Hemodialysis Patients in Taiwan by Using the Kidney Disease: Improving Global Outcomes Clinical Guidelines.

Background. This study evaluated the association between achieving target chronic kidney disease-mineral and bone disorder (CKD-MBD) marker levels and mortality in Taiwanese hemodialysis (HD) patients. Target levels were based on the Kidney Disease: Improving Global Outcomes (KDIGO) guidelines. Methods. We performed a retrospective medical record review of 1126 HD patients between 2009 and 2013. A logistic regression model was used to evaluate the relationship between achieving target marker levels and the risk for all-cause and cardiovascular (CV) mortality. Reference target ranges were 7.9 ≤ calcium (Ca) ≤ 9.9 mg/dL, 2.4 ≤ phosphate (P) ≤ 4.7 mg/dL, and 144 ≤ intact parathyroid hormone (iPTH) ≤ 648 pg/mL. Results. Achievement of target P levels was associated with a lower risk for all-cause mortality compared to achievement of either target Ca or iPTH levels. Achieving target P + iPTH levels (OR 1.32) was associated with a lower odds ratio for all-cause mortality compared to achieving target Ca + P (OR 1.66) and Ca + iPTH (OR 1.43) levels. Similar trends were observed for CV mortality risk. Conclusions. The present study demonstrated that achieving serum P levels within the KDIGO target range is the most important factor for lowering mortality in HD patients.

Facility-level CKD-MBD composite score and risk of adverse clinical outcomes among patients on hemodialysis.

BACKGROUND: Patients receiving hemodialysis with values outside of target levels for parathyroid hormone (PTH: 150-600 pg/mL), calcium (Ca: 8.4-10.2 mg/dL), and phosphate (P: 3.5-5.5 mg/dL) are at elevated morbidity and mortality risk. We examined whether patients receiving care in dialysis facilities where greater proportions of patients have at least two values out of target have a higher risk of adverse clinical outcomes. METHODS: The study cohort consisted of 39,085 prevalent hemodialysis patients in 1298 DaVita dialysis facilities as of September 1, 2009, followed from January 1, 2010, until an outcome, a censoring event, or December 31, 2010. We determined the quintile of the distribution across facilities of the proportion of patients with at least two of three parameters out of, or above, target over a 4-month baseline period. The primary composite outcome was cardiovascular hospitalization or death. Secondary outcomes included death, cardiovascular hospitalization, and parathyroidectomy. Poisson regression models were used to estimate the association of facility quintile with outcomes. RESULTS: Facility quintile was associated with a 7 % increased risk of cardiovascular hospitalization or death (quintile 5 versus 1, RR 1.07, 95 % CI 1.01-1.13) using the out-of-target measure of exposure and a 12 % increased risk (RR 1.12, 95 % CI 1.06-1.19) using the above-target measure. No association was seen for death using either measure. Patients in facility quintiles 3-5 (versus 1) were at increased parathyroidectomy risk (RR ranged from 2.05, 95 % CI 1.10-3.82, for quintile 3 to 2.73, 95 % CI 1.50-4.98, for quintile 5). CONCLUSIONS: Facility level analysis of a large prevalent sample of US patients on hemodialysis demonstrates that patients in facilities with the least control of PTH, Ca, and P had the greatest risk of parathyroidectomy or the combination of cardiovascular hospitalization or death.

The Relation Between Variability of Intact Parathyroid Hormone, Calcium, and Cardiac Mortality in Hemodialysis Patients.

Chronic kidney disease-mineral and bone disorder (CKD-BMD) is a condition known to be associated with cardiovascular disease and mortality in hemodialysis (HD) patients. The relation between calcium (Ca), phosphorus (P), and intact parathyroid hormone (iPTH) variability in HD patients and cardiac mortality is unknown. The purpose of this study was to assess the relation between variability in these parameters and cardiac mortality. Baseline demographic and biochemical parameters of 218 HD patients together with Ca values corrected with albumin and P values measured on a monthly basis and iPTH levels measured at 3-monthly intervals were recorded over 2 years. Standard deviation (SD) and smoothness index (SI) for each parameter were calculated to assess Ca, P, and iPTH variability. The relations between all parameters and cardiac mortality were then analyzed. Cardiac mortality was observed in 38 patients in the 2-year study period. Nonsurviving patients' ages, systolic and diastolic blood pressure (DBP), high sensitivity C-reactive protein (HsCRP) levels, mean iPTH, and SD iPTH were significantly higher than those of surviving patients, while albumin levels, SI iPTH and SI Ca were significantly lower. Age, low albumin, high DBP, SI iPTH, and SI Ca were identified as independent predictors of cardiac mortality at multivariate analysis. Our study shows that Ca and iPTH variability affect cardiac mortality independently of mean and baseline values. When supported by further studies, the relation between Ca and iPTH variability and cardiac mortality in HD patients can lead to a new perspective in terms of prognosis and treatment planning.

Changes in Markers of Mineral and Bone Disorders and Mortality in Incident Hemodialysis Patients.

BACKGROUND: Abnormalities in mineral and bone disorder (MBD) markers are common in patients with chronic kidney disease. However, previous studies have not accounted for their changes over time, and it is unclear whether these changes are associated with survival. METHODS: We examined the association of change in MBD markers (serum phosphorus (Phos), albumin-corrected calcium (Ca(Alb)), intact parathyroid hormone (iPTH) and alkaline phosphatase (ALP)) during the first 6 months of hemodialysis (HD) with all-cause mortality across baseline MBD strata using survival models adjusted for clinical characteristics and laboratory measurements in 102,754 incident HD patients treated in a large dialysis organization between 2007 and 2011. RESULTS: Across all MBD markers (Phos, Ca(Alb), iPTH and ALP), among patients whose baseline MBD levels were higher than the reference range, increase in MBD levels was associated with higher mortality (reference group: MBD level within reference range at baseline and no change at 6 months follow-up). Conversely, decrease in Phos and iPTH, among baseline Phos and iPTH levels lower than the reference range, respectively, were associated with higher mortality. An increase in ALP was associated with higher mortality across baseline strata of ALP ≥80 U/l. However, patients with baseline ALP <80 U/l trended towards a lower risk of mortality irrespective of the direction of change at 6 months follow-up. CONCLUSIONS: There is a differential association between changes in MBD markers with mortality across varying baseline levels in HD patients. Further study is needed to determine if consideration of both baseline and longitudinal changes in the management of MBD derangements improves outcomes in this population.

A Review of Pediatric Chronic Kidney Disease.

Chronic kidney disease is complex in both adults and children, but the disease is far from the same between these populations. Here we review the marked differences in etiology, comorbidities, impact of disease on growth and quality of life, issues unique to adolescents and transitions to adult care, and special considerations of congenital kidney and urinary tract anomalies for transplantation.

Mineral and bone disorders in kidney transplant recipients: reversible, irreversible, and de novo abnormalities.

Given the advances in medical technologies related to kidney transplantation, the post-transplant graft survival rate and quality of life have improved dramatically. Nevertheless, post-transplant mortality rate still remains high as compared to the general population due to the development of cardiovascular events. It has recently been widely recognized that chronic kidney disease-mineral and bone disorders (CKD-MBD) significantly contribute to such poor prognosis at least in part. In the majority of kidney recipients, abnormal serum parameters for mineral and bone disorder (MBD), such as phosphorus, calcium, 1,25-dihydroxyvitamin D, parathyroid hormone and fibroblast growth factor 23, gradually return toward acceptable levels following the re-establishment of kidney function after transplantation; however, some irreversible abnormalities, developed as the result of long-term dialysis, persist, require treatment, or even progress after kidney transplantation. Thus, better management of CKD-MBD during pre-dialysis and dialysis period as well as after kidney transplantation is highly appreciated.