Hospital-acquired serum phosphate derangements and their associated in-hospital mortality.

BACKGROUND: We aimed to report the incidence of hospital-acquired hypophosphataemia and hyperphosphataemia along with their associated in-hospital mortality. METHODS: We included 15 869 adult patients hospitalised at a tertiary medical referral centre from January 2009 to December 2013, who had normal serum phosphate levels at admission and at least two serum phosphate measurements during their hospitalisation. The normal range of serum phosphate was defined as 2.5-4.2 mg/dL. In-hospital serum phosphate levels were categorised based on the occurrence of hospital-acquired hypophosphataemia and hyperphosphataemia. We analysed the association of hospital-acquired hypophosphataemia and hyperphosphataemia with in-hospital mortality using multivariable logistic regression. RESULTS: Fifty-three per cent (n=8464) of the patients developed new serum phosphate derangements during their hospitalisation. The incidence of hospital-acquired hypophosphataemia and hyperphosphataemia was 35% and 27%, respectively. Hospital-acquired hypophosphataemia and hyperphosphataemia were associated with odds ratio (OR) of 1.56 and 2.60 for in-hospital mortality, respectively (p value<0.001 for both). Compared with patients with persistently normal in-hospital phosphate levels, patients with hospital-acquired hypophosphataemia only (OR 1.64), hospital-acquired hyperphosphataemia only (OR 2.74) and both hospital-acquired hypophosphataemia and hyperphosphataemia (ie, phosphate fluctuations; OR 4.00) were significantly associated with increased in-hospital mortality (all p values <0.001). CONCLUSION: Hospital-acquired serum phosphate derangements affect approximately half of the hospitalised patients and are associated with increased in-hospital mortality rate.

Serum phosphate and mortality in incident dialysis patients in Australia and New Zealand.

AIM: Hyperphosphataemia is associated with increased adverse outcomes, including mortality. Re-examining this association using up-to-date data reflecting current and real-world practices, across different global regions and in both haemodialysis and peritoneal dialysis patients, is important. METHODS: We describe the association between serum phosphate and all-cause and cardiovascular mortality in incident dialysis patients between 2008 and 2018 using the Australia and New Zealand Dialysis and Transplant (ANZDATA) Registry. Time-dependent Cox proportionate hazards models were used. Models were adjusted for available covariates and fitted for the overall cohort, and also each dialysis modality. RESULTS: 31 989 patients were followed over 97 122 person-years at risk (mean age at first dialysis 61 years, 38% female, 67% haemodialysis). We observed a U-shaped association between serum phosphate and all-cause mortality. In the fully adjusted model, categories of serum phosphate above and below 1.25-1.99 mmol/L were associated with progressively higher risk, reaching a hazard ratio of 2.13 (95% CI 1.93-2.36, p < .001) for serum phosphate ≥2.75 mmol/L, and 1.56 (95% CI 1.44-1.69, p < .001) for serum phosphate <1.00 mmol/L. Low and high levels of serum phosphate were also associated with increased risk of cardiovascular mortality, however the association with high serum phosphate was more pronounced ("J-shaped relationship"). The associations were consistent across sub-analyses of patients receiving haemodialysis and peritoneal dialysis treatment. CONCLUSION: In this large contemporary dialysis cohort, both high and low levels of serum phosphate were independently associated with increased risk of mortality. Future studies are required to determine whether treatment of abnormal serum phosphate levels improves mortality.

Association between phosphate disturbances and mortality among critically ill patients with sepsis or septic shock.

OBJECTIVE: The aim of this study is to examine the association of hypophosphatemia and hyperphosphatemia on the first day of ICU admission with mortality in septic critically ill patients. METHODS: In this retrospective cohort study, all adult patients who were admitted to the medical-surgical ICUs between 2014 and 2017 with sepsis or septic shock were categorized as having hypophosphatemia, normophosphatemia and hyperphosphatemia based on day 1 serum phosphate values. We compared the clinical characteristics and outcomes between the three groups. We used multivariate analysis to examine the association of hypophosphatemia and hyperphosphatemia with these outcomes. RESULTS: Of the 1422 patients enrolled in the study, 188 (13%) had hypophosphatemia, 865 (61%) normophosphatemia and 369 (26%) had hyperphosphatemia. The patients in the hyperphosphatemia group had significantly lower GCS, higher APACHE II scores, higher serum creatinine, increased use of vasopressors, and required more mechanical ventilation with lower PaO2/FiO2 ratio compared with the other two groups. In addition, the hyperphosphatemia group showed significantly higher ICU and hospital mortality in comparison with the other two groups. CONCLUSION: Hyperphosphatemia and not hypophosphatemia on the first ICU admission day was associated with an increase in the ICU and hospital mortality in septic critically ill patients.

Predictors of Survival in Chronic Hemodialysis Patients: A 10-Year Longitudinal Follow-Up Analysis.

BACKGROUND: Risk factors of mortality in chronic hemodialysis patients have not yet been sufficiently evaluated. In particular, chronological transits and interactions of the impact of risk factors have rarely been described. METHODS: This study is a post hoc analysis of the participants in the Olme-sartan Clinical Trial in Okinawan Patients under OKIDS (OCTOPUS) study conducted between June 2006 and June 2011. We additionally followed up on the prognosis of the participants until July 31, 2018. Standardized univariable and multivariable Cox regression analyses were used to evaluate the influences of the participants' baseline characteristics on all-cause mortality. We also evaluated chronological changes in the impacts of risk factors, interactions among predictors, and the influence of missing values using sensitivity analyses. RESULTS: Of the 469 original trial participants, 461 participants were evaluated. The median time of follow-up was 10.2 years. A total of 211 (45.8%) participants were deceased. The leading causes of death were infection (n = 72, 34.1%) and cardiovascular disease (n = 66, 31.3%). Univariate and multivariate Cox regression analyses revealed that the impact of diabetes mellitus, history of coronary intervention, and hypoalbuminemia were significant risk factors for mortality during the whole follow-up period. During the early follow-up period (≤3 years), standardized univariate Cox regression analyses revealed that history of amputation (hazard ratio [HR] = 4.61, p < 0.001), lower dry weight, higher cardiothoracic ratio, and lower potassium levels were statistically significant risks. In those who survived for longer than 3 years, a history of stroke (HR = 1.73, p = 0.006), higher systolic blood pressure, lower serum sodium levels, and higher levels of hemoglobin, and serum phosphate were significant risks. We also observed a stable interaction between the impacts of serum phosphate and albumin on all-cause mortality. CONCLUSION: In chronic hemodialysis patients, targets to improve the short-term prognosis and long-term prognosis are not equivalent. Hyperphosphatemia was a significant risk factor for the all-cause mortality among patients with normal serum albumin levels but not among patients with compromised albumin levels.

Hyperphosphatemia rather than hypophosphatemia indicates a poor prognosis in patients with sepsis.

BACKGROUND: Sepsis is the leading cause of hospitalization and death in the intensive care unit. It is vital to identify high-risk patients with poor prognosis in the early stages of sepsis. We aimed to investigate the prognostic value of serum phosphorus levels for sepsis. METHODS: The data of 4767 patients with sepsis were collected from the Multiparameter Intelligent Monitoring in Intensive Care III database. The Locally Weighted Scatterplot Smoothing technique and Kaplan-Meier analysis were used to test the crude relationship between serum phosphorus levels and mortality or overall survival. The multivariable logistic regression was used to further analyze the relationship between serum phosphorus levels and in-hospital mortality. The subgroup analysis was performed according to renal failure, use of vasopressin and the Sequential Organ Failure Assessment (SOFA) score. RESULTS: Only hyperphosphatemia significantly correlated with in-hospital mortality [odds ratio (OR) 1.48; 95% confidence interval (CI) 1.19-1.85], while the correlation between hypophosphatemia and in-hospital mortality was not significant (OR 0.91; 95% CI 0.70-1.19). The interactions between serum phosphorus and renal failure, use of vasopressin or the SOFA score were not significant. CONCLUSIONS: Hyperphosphatemia rather than hypophosphatemia indicates a poor prognosis in patients with sepsis.

Normal-range emergency department serum phosphorus levels and all-cause mortality.

PURPOSE OF THE STUDY: Hypophosphataemia and hyperphosphataemia are frequently encountered in hospitalised patients and are associated with significant clinical consequences. However, the prognostic value of normal-range phosphorus levels on all-cause mortality and hospitalisations is not well established. Therefore, we examined the association between normal-range phosphorus levels, all-cause mortality and hospitalisations in patients presenting to the emergency department of a tertiary medical centre in Israel. STUDY DESIGN: A retrospective analysis of patients presenting to the Chaim Sheba Medical Center emergency department between 2012 and 2018. The cohort was divided into quartiles based on emergency department phosphorus levels: 'very-low-normal' (p ≥ 2 mg/dL and p ≤ 2.49 mg/dL), 'low-normal' (p ≥ 2.5 mg/dL and p ≤ 2.99 mg/dL), 'high-normal' (p≥  3 mg/dL and p≤3.49 mg/dL) and 'very-high-normal' (p ≥  3.5 mg/dL and p ≤ 4 mg/dL). We analysed the association between emergency department phosphorus levels, hospitalisation rate and 30-day and 90-day all-cause mortality. RESULTS: Our final analysis included 223 854 patients with normal-range phosphorus levels. Patients with 'very-low-normal' phosphorus levels had the highest mortality rate. Compared with patients with 'high-normal' phosphorus levels, patients with 'very-low-normal' levels had increased 30-day all-cause mortality (OR 1.3, 95% CI 1.1 to 1.4, p<0.001), and increased 90-day all-cause mortality (OR 1.2, 95% CI 1.1 to 1.3, p<0.001). Lower serum phosphorus levels were also associated with a higher hospitalisation rate, both for the internal medicine and general surgery wards (p<0.001). CONCLUSIONS: Lower phosphorus levels, within the normal range, are associated with higher 30-day and 90-day all-cause mortality and hospitalisation rate.

Impact of Serum Phosphate in Mechanically Ventilated Patients With Severe Sepsis and Septic Shock.

BACKGROUND: Hypo- and hyperphosphatemia are common in severe sepsis and septic shock. Published outcome data in patients with phosphate derangements primarily focus on hypophosphatemia and the general critically ill population. This study aimed to determine the impact of serum phosphate on clinical outcomes in patients with severe sepsis and septic shock. METHODS: A retrospective cohort analysis of adult mechanically ventilated patients with severe sepsis or septic shock was performed. Patients were randomly selected from an internal intensive care unit (ICU) database at an academic medical center in the United States and screened for inclusion and exclusion criteria. Time-weighted phosphate was calculated using all phosphate measurements obtained during ICU admission. The associations between time-weighted phosphate and duration of mechanical ventilation, 28-day mortality, and ICU and hospital length of stay were evaluated using linear or logistic regression as appropriate. RESULTS: One-hundred ninety-seven patients were evaluated: 33 were categorized as hypophosphatemia, 123 as normophosphatemia, and 41 as hyperphosphatemia. Patients with time-weighted hyperphosphatemia had a higher Simplified Acute Physiology Score III score and incidence of septic shock. Significantly higher rates of 28-day mortality were observed among those with time-weighted phosphate levels above 3.5 mg/dL. However, both time-weighted hypo- and hyperphosphatemia were associated with decreased duration of mechanical ventilation. For every 0.5 mg/dL increase in time-weighted phosphate referent values from 4.0 to 6.0, the duration of mechanical ventilation decreased by 8% to 26%. For every 0.5 mg/dL decrease in time-weighted phosphate referent values from 3.0 to 1.0, significant decreases in duration of mechanical ventilation ranged from 14% to 41%. CONCLUSION: Time-weighted hyperphosphatemia may be associated with increased mortality in mechanically ventilated patients with severe sepsis or septic shock. However, time-weighted hypo- and hyperphosphatemia were associated with decreased duration of mechanical ventilation. Future studies should further describe the impact of hypo- and hyperphosphatemia on clinical outcomes among critically ill patients with severe sepsis or septic shock.

Non-adherence to Haemodialysis, Interdialytic weight gain and cardiovascular mortality: a cohort study.

BACKGROUND: Patients with chronic kidney diseases (CKD) on haemodialysis (HD) have high morbidity and mortality rates, which are also due to the inherent risks associated with nephropathy. Non-adherence (NA) to the different demands of the treatment can have consequences for the outcome of patients undergoing HD; nevertheless, there are still doubts about such repercussions. This study was conducted to evaluate the association between NA to conventional HD and all-cause mortality and cardiovascular mortality. METHODS: We prospectively evaluated mortality in a 6-year period in a cohort of 255 patients on HD in northeast Brazil. The evaluated parameters of NA to HD were interdialytic weight gain (IDWG) ≥ 4% of dry weight (DW), hyperphosphatemia and regular attendance at treatment, assessed as the correlation between the periods on HD completed and those prescribed. We used the Cox multivariate regression model to analyse survival and the predictors of all-cause mortality and cardiovascular mortality. RESULTS: With a median follow-up period of 1493 days and a mortality rate of 9.1 per 100 people-years, there were 87 deaths, of which 54% were cardiovascular deaths. IDWG ≥4% of DW was associated with a risk of all-cause mortality however presenting a borderline outcome for cardiovascular mortality, with hazard ratios of 2.02 (CI 95% 1.17-3.49, p = 0.012) and 2.09 (CI 95% 1.01-4.35, p = 0.047), respectively. No significant association was found between other parameters of NA and mortality. Subgroup analysis showed that for patients with IDWG ≥4% of DW, malnutrition, age and diagnosis of cardiovascular and cerebrovascular diseases were associated with higher all-cause mortality. CONCLUSIONS: IDWG ≥4% of DW was identified as an independent predictor of all-cause mortality and demonstrated a borderline outcome for cardiovascular mortality in patients on conventional HD. The occurrence of excessive IDWG in the presence of malnutrition represented a significant increase in the risk of death, indicating a subgroup of patients with a worse prognosis.

Are We Aware that Hyperphosphatemia Affects Mortality and Morbidity as much as Hypophosphatemia in Pediatric Intensive Care Patients?

OBJECTIVE: Hypophosphatemia was previously shown to affect the duration of admission, mechanical ventilator requirements, mortality and morbidity during pediatric intensive care. Different from previous studies, our study was planned with the aim of showing whether hyperphosphatemia affects morbidity and mortality in pediatric intensive care patients as much as hypophosphatemia. METHOD: Patients' ages, genders, reason for admission, underlying diseases, phosphorus levels examined on admission and on the 1-4th and 5-10th-days, duration on mechanical ventilation, duration of admission, final status and PRISM and PELOD scores calculated in the first 24 hours of admission were recorded. RESULTS: Mortality was distinctly higher for those who were hypophosphatemic and hyperphosphatemic compared to those who were normophosphatemic. The highest mortality was identified in those who were hyperphosphatemic on the 5-10th-days. PELOD scores were only significantly different according to admission phosphorus levels (p:0.04). CONCLUSION: In our study, we identified that hyperphosphatemia is a serious problem as hypophosphatemia for patients who admitted to the PICU. Patients identified to be hyperphosphatemic on admission had a significantly higher PELOD score. The significant difference of hyperphosphatemia in terms of PELOD score is one of the important points shown in our study. It should not be forgotten that like hypophosphatemia, hyperphosphatemia may cause serious problems in pediatric intensive care patients.

Hyperphosphatemia and risks of acute kidney injury, end-stage renal disease, and mortality in hospitalized patients.

BACKGROUND: Hyperphosphatemia is associated with vascular calcification and bone mineral disorders and is a major concern among patients with chronic kidney disease (CKD). However, the relationship between hyperphosphatemia and renal outcome in non-CKD patients has not been studied. Furthermore, the clinical implications of hyperphosphatemia in relation to the risks of acute kidney injury (AKI), end-stage renal disease (ESRD), and mortality after hospitalization remain unresolved. METHODS: A total of 20,686 patients (aged ≥18 years) admitted to Seoul National University Bundang Hospital from January 2013 to December 2013 were retrospectively reviewed. Patients were divided into quartiles according to serum phosphorus level at the time of admission. The odds ratios (ORs) for AKI and hazard ratios (HRs) for ESRD and all-cause mortality were calculated after adjustment of multiple covariates. RESULTS: AKI developed in 2319 patients (11.2%), with higher ORs for patients in the third and fourth quartiles (1.4 [1.24-1.68] and 2.8 [2.44-3.22], respectively) compared with the first quartile group. During a median follow-up period of 4.0 years, 183 patients (0.88%) developed ESRD and 3675 patients (17.8%) died. Patients in the fourth quartile had higher risks of ESRD and mortality than patients in the first quartile (HRs, 2.3 [1.46-3.75] and 1.4 [1.22-1.49], respectively). These trends remained consistent in patients with an estimated glomerular filtration rate > 60 ml/min/1.73 m2. CONCLUSIONS: Hyperphosphatemia is related to the risks of AKI, ESRD, and mortality, and it may therefore be necessary to monitor serum phosphorus level in hospitalized patients, irrespective of kidney function.

Admission serum phosphate levels predict hospital mortality.

BACKGROUND: The aim of this study was to assess the relationship between admission serum phosphate levels and in-hospital mortality in all hospitalized patients. METHODS: All adult hospitalized patients who had admission serum phosphate available between years 2009 and 2013 were enrolled. Admission serum phosphate was categorized based on its distribution into six groups (<2.5, 2.5-3.0, 3.1-3.6, 3.7-4.2, 4.3-4.8 and ≥4.9 mg/dL). The odds ratio (OR) of in-hospital mortality by admission serum phosphate, using the phosphate category of 3.1-3.6 mg/dL as the reference group, was obtained by logistic regression analysis. RESULTS: 42,336 patients were studied. The lowest incidence of in-hospital mortality was associated with a serum phosphate within 3.1-4.2 mg/dL. A U-shaped curve emerged demonstrating higher in-hospital mortality associated with both serum phosphate <3.1 and >4.2 mg/dL. After adjusting for potential confounders, both serum phosphate <2.5 and >4.2 mg/dL were associated with in-hospital mortality with ORs of 1.60 (95%CI 1.25-2.05), 1.60 (95%CI 1.29-1.97), and 3.89 (95%CI 3.20-4.74) when serum phosphate were <2.5, 4.3-4.8 and ≥4.9 mg/dL, respectively. Among subgroups of patients with chronic kidney disease (CKD) and cardiovascular disease (CVD), the highest mortality was associated with a serum phosphate ≥4.9 mg/dL with ORs of 4.11 (95%CI 3.16-5.39) in CKD patients and 5.11 (95%CI 3.33-7.95) in CVD patients. CONCLUSION: Hospitalized patients with admission serum phosphate <2.5 and >4.2 mg/dL are associated with an increased risk of in-hospital mortality. The highest mortality risk is associated with CKD and CVD patients with admission hyperphosphatemia.

Effect of Lanthanum Carbonate on All-Cause Mortality in Patients Receiving Maintenance Hemodialysis: a Meta-Analysis of Randomized Controlled Trials.

BACKGROUND/AIMS: Hyperphosphatemia is common in patients on hemodialysis. The efficacy of lanthanum carbonate (LC) in the treatment of hyperphosphatemia in these patients remains controversial. The objective of this meta-analysis was to evaluate the effect of LC on all-cause mortality in patients on maintenance hemodialysis. METHODS: We electronically searched the PubMed, EMBASE, and Cochrane Library databases for all randomized controlled trials (RCTs) comparing LC with other phosphate binders used in adult hemodialysis patients, including calcium carbonate, calcium acetate, and sevelamer. RESULTS: Nine RCTs involving 2813 patients were suitable for inclusion. Our results showed that all-cause mortality was significantly lower in patients who received LC than in those who received standard therapy (odds ratio [OR]: 0.45, 95% confidence interval [CI]: 0.32-0.63, P<0.00001). Compared with the controls, patients who received LC had significantly lower serum calcium and higher serum intact parathyroid hormone levels. However, there was no significant difference between the groups in the cardiovascular event rate (OR: 0.58, 95% CI: 0.31-1.06, P=0.07) or in serum phosphorus levels. CONCLUSION: Compared with standard therapy, LC reduced all-cause mortality in patients on hemodialysis but did not decrease the risk of cardiovascular events. The decrease in serum phosphorus level was similar between LC and the other phosphate binders, but the risk of hypercalcemia was lower in patients who received LC.

Initiation of Sevelamer and Mortality among Hemodialysis Patients Treated with Calcium-Based Phosphate Binders.

BACKGROUND AND OBJECTIVES: Prior studies have shown that sevelamer attenuates progression of arterial calcification and may reduce the risk of death compared with calcium-based phosphate binders. In clinical practice, however, sevelamer is used not only as an alternative but also as an add-on therapy in patients already being treated with calcium-based phosphate binders. We analyzed the Dialysis Outcomes and Practice Patterns Study (DOPPS) data to test the hypothesis that the initiation of sevelamer is associated with improved survival in patients on hemodialysis treated with calcium-based phosphate binders. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We included 12,564 patients from DOPPS phase 3 and phase 4 (2005-2011) who were prescribed calcium-based phosphate binders at baseline or before sevelamer treatment. Mortality risk was assessed using a sequential stratification method to identify as-yet-untreated patients who were appropriately matched to the newly treated patients on the basis of their risk of death. RESULTS: Of 12,564 patients, 2606 were subsequently treated with sevelamer hydrochloride or sevelamer carbonate. After beginning sevelamer therapy, mean serum phosphorus levels decreased by 0.3 mg/dl in the first 4 months and gradually decreased thereafter. We matched 2501 treated patients with at least one as-yet-untreated patient. Patients treated with sevelamer had a 14% lower risk for mortality compared with as-yet-untreated patients (hazard ratio, 0.86; 95% confidence interval, 0.76 to 0.97). Similar results were observed in the sensitivity analyses when changing the matching calipers or the treated and as-yet-untreated ratios, and by using propensity score matching. CONCLUSIONS: The use of sevelamer as an add-on or alternative therapy to calcium-based phosphate binders is associated with improved survival in patients on maintenance hemodialysis.

Analysis of Hypo- and Hyperphosphatemia in an Intensive Care Unit Cohort.

BACKGROUND: Blood phosphate levels are vulnerable to fluctuations and changes in phosphate levels are often neglected. The aim of this study was to evaluate whether deviations in phosphate levels correlate to higher 180-day overall mortality or morbidity. METHODS: Four thousand six hundred fifty-six patients with 19,467 phosphate values treated at the adult intensive care unit at Skåne University Hospital, Lund, Sweden during 2006-2014 were retrospectively divided into a control group and 3 study groups: hypophosphatemia, hyperphosphatemia, and a mixed group showing both hypo/hyperphosphatemia. Sex, age, disease severity represented by maximal organ system Sequential Organ Failure Assessment score, renal Sequential Organ Failure Assessment score, lowest ionized calcium value, and diagnoses classes were included in a Cox hazard model to adjust for confounding factors, with time to death in the first 180 days from the intensive care unit (ICU) admission as outcome. RESULTS: When compared to normophosphatemic controls, the hyperphosphatemic study group was associated with higher risk of death with a hazard ratio of 1.2 (98.3% confidence interval 1.0-1.5, P = .0089). Mortality in the hypophosphatemic or mixed study group did not differ from controls. The mixed group showed markedly longer ventilator times and ICU stays compared to all other groups. CONCLUSIONS: Phosphate alterations in ICU patients are common and associated with worse morbidity and mortality. Many underlying pathophysiologic mechanisms may play a role. A rapidly changing phosphate level or isolated hypo or hyperphosphatemia should be urgently corrected.

Use of Phosphorus Binders among Non-Dialysis Chronic Kidney Disease Patients and Mortality Outcomes.

BACKGROUND: Whether the benefits of phosphorus binders extend to those without end stage renal disease is uncertain. Among a large diverse non-dialysis chronic kidney disease (CKD) population with hyperphosphatemia, we sought to evaluate phosphorus binder use and compare mortality risk between patients prescribed and not prescribed binders. METHODS: A retrospective cohort study within an integrated health system (January 1, 1998 - December 31, 2012) among CKD patients (age ≥18) was performed. Non-dialysis CKD patients with 2 separate estimated glomerular filtrate rate (eGFR) <30 mL/min/1.73 m2 and serum phosphorus ≥5.0 mg/dL within 180 days of eGFR were included. Multivariable cox proportional hazards and inverse probability of treatment-weighted models were used to estimate mortality hazard ratios (HRs) for patients who received phosphorus binders compared to no binders. RESULTS: Among 10,165 study patients, 2,733 subjects (27%) received phosphorus binders. Compared to the no-phosphorus-binder group, the binder group had mortality HRs (95% CI) of 0.86 (0.79-0.94) and 0.86 (0.80-0.93) using traditional multivariable and inverse probability of treatment-weighted models respectively. Sensitivity analyses removing patients who were prescribed binders >180 days after index date revealed no difference in mortality between those with binders and with no binders. CONCLUSION: Our findings from a real-world clinical environment revealed that 27% of hyperphosphatemic non-dialysis CKD patients were prescribed binders. They also had lower risk of mortality compared to those not prescribed phosphorus binders. However, the lower mortality risk was not observed when we accounted for immortal time bias. Whether phosphorus binder use in CKD improves survival remains to be determined.

Hypophosphatemia: nutritional status, body composition, and mortality in hemodialysis patients.

PURPOSE: The aim of the present study was to investigate the relationship between serum phosphate levels, clinical parameters, body composition, and mortality. METHODS: Multicenter longitudinal observational study of a cohort of 3552 patients in hemodialysis (HD) from 34 Nephrocare dialysis units in Portugal with 24 months of follow-up. Patients were divided into three groups depending on their serum phosphorus (<3.5; 3.5-5.5; >5.5 mg/dL). Statistical tests were performed with SPSS, version 20.0. A p < 0.05 was considered significant. RESULTS: On the one hand, hypophosphatemia was significantly associated with better dialysis adequacy, higher age and overhydration. On the other hand, it was associated with lower albumin, protein intake, creatinine, hemoglobin, calcium, potassium, magnesium, body mass index (BMI), body cell mass index, fat tissue index and lean tissue index. These patients had lower survival rates compared with those with normo- and hyperphosphatemia. Hypophosphatemia was a predictor of death when adjusted for age, diabetes, HD vintage, gender, and Kt/V. Comparing the mortality predictors in hypo- and hyperphosphatemia, we found that low albumin, BMI, and high overhydration increased the mortality risk in the hypophosphatemic group, whereas in hyperphosphatemic patients data were not statistically significant. CONCLUSION: Currently, a high prevalence of hypophosphatemia exists in Portuguese HD patients. This condition is associated with worst nutritional and body composition parameters. In the context of additional indices of malnutrition (low albumin, low BMI or severe overhydration), hypophosphatemic patients presented higher mortality risk.

Association of Serum Phosphorus Concentration with Mortality and Graft Failure among Kidney Transplant Recipients.

BACKGROUND AND OBJECTIVES: Hyperphosphatemia in kidney transplant recipients has been shown to predict poorer graft and patient survival. However, studies examining hypophosphatemia are scarce. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: To evaluate the association of serum phosphorus level with patient and graft survival, we performed a retrospective multicenter cohort study. Between January of 1997 and August of 2012, 2786 kidney transplant recipients (41.7±11.4 years; 59.3% men; 73.5% living donors; 26.1% with diabetes; 3.8% with prior history of cardiovascular disease) were classified into seven groups according to serum phosphorus levels 1 year after transplantation, with intervals of 0.5 mg/dl (lowest group, <2.5 mg/dl; highest group, ≥5.0 mg/dl; reference group, 3.5-3.99 mg/dl). Survival analysis was performed by defining baseline time point as 1 year after transplantation. RESULTS: During median follow-up of 78.5 months, 60 patient deaths and 194 cases of graft loss occurred. In multivariate analysis, both lowest and highest serum phosphorus groups were associated with higher mortality, compared with the reference group (hazard ratio [HR], 4.82; 95% confidence interval [95% CI], 1.36 to 17.02; P=0.01; and HR, 4.24; 95% CI, 1.07 to 16.84; P=0.04, respectively). Higher death-censored graft loss was observed in the lowest and highest groups (HR, 3.32; 95% CI, 1.42 to 7.79; P=0.01; and HR, 2.93; 95% CI, 1.32 to 6.49; P=0.01, respectively), despite eGFR exhibiting no difference between the lowest group and reference group (65.4±19.3 versus 61.9±16.7 ml/min per 1.73 m2; P=0.33). Moreover, serum phosphorus showed a U-shape association with patient mortality and graft failure in restricted cubic spline curve analysis. CONCLUSIONS: Serum phosphorus level 1 year after transplantation exhibits a U-shape association with death-censored graft failure and patient mortality in kidney transplant patients characterized by relatively high rate of living donor transplant and low incidence of diabetes and prior cardiovascular disease compared with Western countries.

Design and baseline characteristics of the LANDMARK study.

BACKGROUND: Calcium (Ca)-based phosphate (P) binders, compared to non-Ca-based P binders, contribute to vascular calcification, which is associated with cardiovascular events. METHODS: The LANDMARK study is a multicenter, randomized, open-label, parallel comparative study of lanthanum carbonate (LC) and calcium carbonate (CC) in hemodialysis patients. Stable hemodialysis patients with intact parathyroid hormone ≤240 pg/mL meeting ≥1 of the following criteria (age >65 years, postmenopause, diabetes mellitus) were randomized into the LC and CC groups. LC group patients initially received LC 750 mg/day or the previously used dose and were titrated up to a maximum 2250 mg/day to achieve serum P levels of 3.5-6.0 mg/dL. CC group patients received CC 3 g/day or the previously used dose and were titrated to achieve the same P range. If the target serum P level was not achieved, non-Ca-based P binders (other than LC) could also be added. The primary endpoint is survival time free of cardiovascular events, including cardiovascular death, non-fatal myocardial infarction or stroke, and unstable angina. RESULTS: Overall, 2309 patients were allocated to the LC (N = 1154) or CC group (N = 1155). At baseline, the mean age was 68.4 years, 40.4 % were women, 55.9 % had diabetes, 18.3 % had a history of ischemic heart disease, and 13.9 % had cerebrovascular disease. A total of 184 patients (8.4 %) had undergone coronary intervention procedures. Baseline characteristics were well balanced between groups. CONCLUSIONS: The LANDMARK study will determine whether LC, a non-Ca-based P binder, reduces cardiovascular mortality and morbidity in chronic hemodialysis patients.