Phosphate Control in Peritoneal Dialysis Patients: Issues, Solutions, and Open Questions.

Hyperphosphatemia is a common complication in advanced chronic kidney disease and contributes to cardiovascular morbidity and mortality. The present narrative review focuses on the management of phosphatemia in uremic patients receiving peritoneal dialysis. These patients frequently develop hyperphosphatemia since phosphate anion behaves as a middle-size molecule despite its low molecular weight. Accordingly, patient transporter characteristics and peritoneal dialysis modalities and prescriptions remarkably influence serum phosphate control. Given that phosphate peritoneal removal is often insufficient, especially in lower transporters, patients are often prescribed phosphate binders whose use in peritoneal dialysis is primarily based on clinical trials conducted in hemodialysis because very few studies have been performed solely in peritoneal dialysis populations. A crucial role in phosphate control among peritoneal dialysis patients is played by diet, which must help in reducing phosphorous intake while preventing malnutrition. Moreover, residual renal function, which is preserved in most peritoneal dialysis patients, significantly contributes to maintaining phosphate balance. The inadequate serum phosphate control observed in many patients on peritoneal dialysis highlights the need for large and well-designed clinical trials including exclusively peritoneal dialysis patients to evaluate the effects of a multiple therapeutic approach on serum phosphate control and on hard clinical outcomes in this high-risk population.

Genetic Evidence for a Causal Role of Serum Phosphate in Coronary Artery Calcification: The Rotterdam Study.

Background Hyperphosphatemia has been associated with coronary artery calcification (CAC) mostly in chronic kidney disease, but the association between phosphate levels within the normal phosphate range and CAC is unclear. Our objectives were to evaluate associations between phosphate levels and CAC among men and women from the general population and assess causality through Mendelian randomization. Methods and Results CAC, measured by electron-beam computed tomography, and serum phosphate levels were assessed in 1889 individuals from the RS (Rotterdam Study). Phenotypic associations were tested through linear models adjusted for age, body mass index, blood pressure, smoking, prevalent cardiovascular disease and diabetes, 25-hydroxyvitamin D, total calcium, C-reactive protein, glucose, and total cholesterol : high-density lipoprotein cholesterol ratio. Mendelian randomization was implemented through an allele score including 8 phosphate-related single-nucleotide polymorphisms. In phenotypic analyses, serum phosphate (per 1 SD) was associated with CAC with evidence for sex interaction (Pinteraction=0.003) (men ß, 0.44 [95% CI, 0.30-0.59]; P=3×10-9; n=878; women ß, 0.24 [95% CI, 0.08-0.40]; P=0.003; n=1011). Exclusion of hyperphosphatemia, chronic kidney disease (estimated glomerular filtration rate <60 mL/min per 1.73 m2) and prevalent cardiovascular disease yielded similar results. In Mendelian randomization analyses, instrumented phosphate was associated with CAC (total population ß, 0.93 [95% CI: 0.07-1.79]; P=0.034; n=1693), even after exclusion of hyperphosphatemia, chronic kidney disease and prevalent cardiovascular disease (total population ß, 1.23 [95% CI, 0.17-2.28]; P=0.023; n=1224). Conclusions Serum phosphate was associated with CAC in the general population with stronger effects in men. Mendelian randomization findings support a causal relation, also for serum phosphate and CAC in subjects without hyperphosphatemia, chronic kidney disease, and cardiovascular disease. Further research into underlying mechanisms of this association and sex differences is needed.

Dietary Advice in Hemodialysis Patients: Impact of a Telehealth Approach During the COVID-19 Pandemic.

OBJECTIVE: The purpose of this study was to assess the effect of a telehealth-delivered nutritional intervention via telephone in maintenance hemodialysis (HD) patients during the coronavirus outbreak. METHODS: This was a multicenter, observational, prospective, and longitudinal study of 156 patients undergoing maintenance HD from 15 dialysis units conducted during the COVID-19 pandemic. We assigned patients to receive dietary counseling through a phone call, according to their biochemical and nutritional parameters. Dry weight, intradialytic weight gain percentage (%IDWG), body mass index, potassium, phosphorus, calcium, calcium/phosphorus product, normalized protein catabolic rate, albumin, and hemoglobin were recorded at baseline and 1 month after nutrition counseling. RESULTS: The prevalence of hyperkalemia and hyperphosphatemia decreased significantly after dietary advice. A statistically significant reduction in serum potassium and phosphorus levels was observed in patients receiving counseling for hyperkalemia and hyperphosphatemia. In addition, there was a statistically significant decrease in the prevalence of hypophosphatemia. We also observed a significant decrease in %IDWG, although no statistically significant differences were detected in patients with high %IDWG. The data demonstrated statistically significant differences in potassium and phosphorus values when the person receiving the phone contact was the patient or the caregiver. The main statistically significant differences in hypophosphatemia %IDWG were only observed when contact was made directly with the patient. No differences were observed when the contact was made through nursing homes. CONCLUSION: Our results suggest that telehealth-delivered dietary interventions can improve the clinical and nutritional parameters of HD patients. Consequently, this strategy may be effective for promoting continuous nutritional monitoring in these patients, in particular when conducting a face-to-face option is not crucial.

Dysmagnesemia Is the Most Common Disturbance of the Calcium-Magnesium-Phosphorous Balance among Older Hospitalized People in Warsaw.

The elderly are at great risk of developing life-threatening disturbances in calcium-magnesium-phosphate homeostasis because of comorbidities, long-term medication use, and dietary deficiencies, but it is still not known how often they occur in this group of patients. This study aimed to assess the prevalence of these disturbances in a group of hospitalized patients over 65 years of age according to age and sex. The study was conducted between January 2018 and September 2020 at the Central Clinical Hospital in Warsaw. A total of 66,450 calcium, magnesium, phosphate, and vitamin D concentration results were included in the analysis. Dysmagnesemia was present in 33% of the calcium results, dyscalcemia, dysphosphatemia, and dysvitaminosis D-in 23.5%, 26%, and 70% of the results, respectively. The magnesium concentration was found to be age-dependent, and older people were found to be at higher risk of developing abnormal magnesium concentrations (p < 0.001). Sex influenced the occurrence of abnormal magnesium (p < 0.001), vitamin D (p < 0.001), and calcium (p < 0.00001) concentrations, with hypercalcemia and hypervitaminosis D disorders being significantly more common in women (p < 0.0001). In conclusion, disorders of the calcium-magnesium-phosphate metabolism are common in hospitalized patients over 65 years of age, and the concentrations of these substances should be routinely monitored in this group.

Infigratinib (BGJ398) in previously treated patients with advanced or metastatic cholangiocarcinoma with FGFR2 fusions or rearrangements: mature results from a multicentre, open-label, single-arm, phase 2 study.

BACKGROUND: Treatment options are sparse for patients with advanced cholangiocarcinoma after progression on first-line gemcitabine-based therapy. FGFR2 fusions or rearrangements occur in 10-16% of patients with intrahepatic cholangiocarcinoma. Infigratinib is a selective, ATP-competitive inhibitor of fibroblast growth factor receptors. We aimed to evaluate the antitumour activity of infigratinib in patients with locally advanced or metastatic cholangiocarcinoma, FGFR2 alterations, and previous gemcitabine-based treatment. METHODS: This multicentre, open-label, single-arm, phase 2 study recruited patients from 18 academic centres and hospitals in the USA, Belgium, Spain, Germany, Singapore, Taiwan, and Thailand. Eligible participants were aged 18 years or older, had histologically or cytologically confirmed, locally advanced or metastatic cholangiocarcinoma and FGFR2 fusions or rearrangements, and were previously treated with at least one gemcitabine-containing regimen. Patients received 125 mg of oral infigratinib once daily for 21 days of 28-day cycles until disease progression, intolerance, withdrawal of consent, or death. Radiological tumour evaluation was done at baseline and every 8 weeks until disease progression via CT or MRI of the chest, abdomen, and pelvis. The primary endpoint was objective response rate, defined as the proportion of patients with a best overall response of a confirmed complete or partial response, as assessed by blinded independent central review (BICR) according to Response Evaluation Criteria in Solid Tumors, version 1.1. The primary outcome and safety were analysed in the full analysis set, which comprised all patients who received at least one dose of infigratinib. This trial is registered with ClinicalTrials.gov, NCT02150967, and is ongoing. FINDINGS: Between June 23, 2014, and March 31, 2020, 122 patients were enrolled into our study, of whom 108 with FGFR2 fusions or rearrangements received at least one dose of infigratinib and comprised the full analysis set. After a median follow-up of 10·6 months (IQR 6·2-15·6), the BICR-assessed objective response rate was 23·1% (95% CI 15·6-32·2; 25 of 108 patients), with one confirmed complete response in a patient who only had non-target lesions identified at baseline and 24 partial responses. The most common treatment-emergent adverse events of any grade were hyperphosphataemia (n=83), stomatitis (n=59), fatigue (n=43), and alopecia (n=41). The most common ocular toxicity was dry eyes (n=37). Central serous retinopathy-like and retinal pigment epithelial detachment-like events occurred in 18 (17%) patients, of which ten (9%) were grade 1, seven (6%) were grade 2, and one (1%) was grade 3. There were no treatment-related deaths. INTERPRETATION: Infigratinib has promising clinical activity and a manageable adverse event profile in previously treated patients with locally advanced or metastatic cholangiocarcinoma harbouring FGFR2 gene fusions or rearrangements, and so represents a potential new therapeutic option in this setting. FUNDING: QED Therapeutics and Novartis.

Factors associated with the absence of pharmacological treatment for common modifiable complications in children with chronic kidney disease.

BACKGROUND: Chronic kidney disease (CKD) is associated with many comorbidities requiring complex management. We described treatment patterns for common modifiable CKD complications (high blood pressure, anemia, hyperphosphatemia, and acidosis) according to severity of CKD and examined factors associated with the absence of drug therapy, among participants with a persistent comorbidity, for 1 year in children enrolled in the CKiD study. METHODS: A total of 703 CKiD participants contributed 2849 person-visits over a median 3.5 years of follow-up. Using pairs of annual visits, we examined whether participants with abnormal biomarker levels at the first (index) visit persisted in the abnormal levels 1 year later according to CKD risk stage. Multivariate analyses identified demographic and clinical factors associated with the absence of drug therapy among those with persistent comorbid conditions for 1 year. RESULTS: The overall proportions of person-visits prescribing therapy at 1-year follow-up for treating anemia, acidosis, hyperphosphatemia, and high blood pressure were 54%, 45%, 29%, and 81%, respectively. The frequency of therapy increased with advanced CKD risk stage for all comorbidities; however, 19-23% of participants with acidosis, 24-27% with anemia, and 30-39% with hyperphosphatemia at high-risk stages (E and F) were not prescribed appropriate therapy despite the persistence of abnormal levels of these biomarkers for at least 1 year. The resolution of comorbidities at advanced CKD stages without treatment was unlikely. CONCLUSIONS: Many children with CKD in the CKiD cohort did not receive pharmacological treatment for common and persistent modifiable comorbidities, even in severe CKD risk stages.

Prevalence of renal dysfunction among HIV infected patients receiving Tenofovir at Mulago: a cross-sectional study.

BACKGROUND: There is an increasing burden of non-communicable disease globally. Tenofovir disoproxil fumarate (TDF) is the most commonly prescribed antiretroviral drug globally. Studies show that patients receiving TDF are more prone to renal dysfunction at some point in time during treatment. Evaluation of kidney function is not routinely done in most HIV public clinics. Identification of renal dysfunction is key in resource constrained settings because managing patients with end stage renal disease is costly. METHOD: This was a cross-sectional study conducted at an outpatient clinic in 2018 involving patients on TDF for at least 6 months who were 18 years or older. Patients with documented kidney disease and pregnancy were excluded. Estimated glomerular filtration rate (eGFR) was calculated using the CKD-Epi formula. Renal dysfunction was defined as any of the following; either eGFR< 60 mL/min/1.73m2,or proteinuria of ≥2+ on urine dipstick, glycosuria with normal blood glucose. Electrolyte abnormalities were also documented. RESULTS: We enrolled 278 participants. One hundred sixty nine (60.8%) were females, majority 234(84.2%) were < 50 years old, 205 (73.74%) were in WHO stage 1, most participants 271(97.5%) in addition to TDF were receiving lamivudine/efavirenz. The median age was 37(IQR 29-45) years; median duration on ART was 36 (IQR 24-60) months. The prevalence of renal dysfunction was 2.52% (7/278). Most noted electrolyte abnormality was hypocalcaemia (15.44%). CONCLUSIONS: The prevalence of renal dysfunction was low though some participants had hypocalcaemia. Screening for kidney disease should be done in symptomatic HIV infected patients on TDF.

Mineral bone disorder and osteoporosis in hemodialysis patients.

BACKGROUND: Bone disease is common in patients undergoing hemodialysis. It is the result of bone turnover abnormalities and the decrease of bone mineral density (BMD). We aimed to determine the usefulness of serum bone turnover markers and BMD measurement by dual-energy x-ray absorptiometry (DXA) in hemodialysis patients. METHODS: We conducted a cross-sectional study including 90 hemodialysis for more than 12 months. Bone mineral density was assessed by DXA. Peripheral blood samples were obtained from each patient before dialysis in a fasting state within a week of the DXA. Biochemical variables of calcium and phosphate were measured. One bone formation marker (bone-specific alkaline phosphatase (bAP), one bone resorption marker (carboxy-terminal telopeptides of type 1 collagen (CTX)) were measured. Total alkaline phosphatase (TAP), intact parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF23) which is a bone-derived hormone were also measured. RESULTS: CTX values were 6.25 times higher than the normal limit of the assay. Bone alkaline phosphatase levels were less than 10 ng/mL in 28.8% of cases. 23% of patients have osteoporosis and 45% have osteopenia. Femoral BMD had negative correlations with age and PTH levels. FGF23 levels were significantly increased in patients with osteoporosis affecting the lumbar. The levels of bAP and CTX showed a positive correlation. Both circulating bAP and CTX levels showed also positive correlations with PTH levels. Fractures, observed in 12.2% of cases, were associated with low PTH values and the existence of osteoporosis. CONCLUSIONS: Our study showed that osteoporosis and fracture are common in dialysis patients. The reduced BMD was associated with advanced age and elevated levels of PTH. Markers of bone turnover and FGF23 may play a role in the diagnosis of bone disease in hemodialysis patients. DXA measurement is necessary for the monitoring for bone loss.

Anion gap predicts early mortality after starting hemodialysis in the elderly.

BACKGROUND: Serum anion gap (AG) has recently been proven to represent a biomarker for predicting prognosis in patients with end-stage renal disease (ESRD). However, whether change in AG (ΔAG) at the time of starting hemodialysis predicts mortality after starting hemodialysis in elderly patients with ESRD remains unknown. METHODS: This retrospective cohort investigated the association between ΔAG and mortality after starting hemodialysis in the elderly. The cohort comprised patients ≥ 75 years old who started hemodialysis for ESRD at National Center for Global Health and Medicine between 2010 and 2017 and at Yokosuka Kyosai Hospital between 2007 and 2011. Patients were stratified into three groups (G1-3) based on ΔAG, calculated according to the equation: ΔAG = sodium - (chloride + bicarbonate) - 12. The primary outcome was death within 1 year of starting hemodialysis. Data were analyzed using Cox proportional hazard models with adjustments for baseline characteristics. RESULTS: We enrolled 254 patients (59% male). Median ΔAG was 2.6 (G1: > 3, n = 111; G2: 0-3, n = 103; G3: < 0, n = 40). The primary outcome was observed in 43 patients. Hazard ratios (HRs) were significantly higher for G1 and G3 than for G2 (G1: HR 2.47, 95% confidence interval 1.13-5.37; G3: HR 3.86, 95% confidence interval 1.62-9.16). Adjusted HRs (aHRs) were significantly higher for G1 and G3 than for G2 (G1: aHR 3.06, 95% confidence interval 1.23-7.62; G3: aHR 3.12, 95% confidence interval 1.10-8.78). CONCLUSIONS: A J-curve phenomenon is evident between ΔAG and early mortality after starting hemodialysis in the elderly.

Interventional study to improve adherence to phosphate binder treatment in dialysis patients.

BACKGROUND: Adherence to phosphate binder treatment is important to prevent high serum phosphate level in chronic dialysis patients. We therefore wanted to investigate patient knowledge, beliefs about and adherence to phosphate binders among these patients and assess whether one-to-one pharmacist-led education and counselling enhance adherence and lead to changes in serum phosphate levels. METHODS: A descriptive, interventional, single arm, pre-post study was performed at a hospital in Norway, including chronic dialysis patients aged 18 years or more using phosphate binders. The primary end-point was change in the proportion of patients with serum phosphate below 1.80 mmol/L and the secondary end-points included change in the patient's knowledge, beliefs and adherence after the intervention measured by completion of questionnaires 'Patient Knowledge', Medication Adherence Report Scale (MARS- 5) and Beliefs about Medicines Questionnaire (BMQ). Data was collected both prior to and after one-to-one pharmacist-led education and counselling about their phosphate binders. Other medicines used by the patient was also registered. RESULTS: A total of 69 patients were enrolled in the study. After intervention, the probability of serum phosphate being below the target threshold 1.80 mmol/L (5.58 mg/dL) increased, although no significant change in mean serum phosphate levels was seen. On the other hand, the knowledge regarding phosphate binder treatment and the patients' beliefs about the necessity of the treatment increased, while the concerns decreased (BMQ). This effect did not lead to increase in self-reported adherence measured by MARS-5. However the scores were high before the intervention. CONCLUSIONS: Short term one-to-one individualized pharmacist-led education and counselling about phosphate binders increased the probability of serum phosphate concentrations being below the target threshold level 1.80 mmol/L (5.58 mg/dL), although not statistically significant. However, it did not decrease the mean serum phosphate level or increase the patients' self-reported adherence. The patients increased their knowledge about the phosphate binder and their understanding of adherence, and were less concerned about the side effects of the medication. TRIAL REGISTRATION: ISRCTN52852596 , registered 11 April 2019. The trial was registered retrospectively.

Mineral disorders in pediatric pre-emptive kidney transplantation.

BACKGROUND: Pre-emptive kidney transplantation (PEKT) is beneficial for patients, improves graft survival and minimizes the complications associated with chronic kidney disease. Reports on pediatric PEKT, however, are limited, and little is known about the parathyroid hormone (PTH) abnormalities and calcium-phosphorus disorders (CPD) in this condition. This study was the first to report on mineral disorders in pediatric PEKT patients during a 1 year period. METHODS: We conducted a comparative examination of the abnormalities in calcium, phosphorus, calcium-phosphorus products and PTH before and 1 year after living donor kidney transplantation in PEKT and non-PEKT patients. RESULTS: Thirty-one patients were included. The patients were divided into two groups: PEKT (n = 11; 5 months in CKD stage 4-5) and non-PEKT (n = 20; 31.5 months in dialysis). Mean age at transplantation was 9.4 ± 5.0 years. Hypercalcemia and hyperphosphatemia were observed before and after transplantation in the PEKT and non-PEKT groups, and >15% of patients in each group had bone disorder and ectopic calcification associated with mineral disorder. Mineral disorder was present for approximately 3 months after transplantation in both treatment groups. CONCLUSIONS: No significant differences in PTH or CPD were noted between PEKT and non-PEKT groups; moreover, normalization of abnormal values did not differ between the PEKT and non-PEKT groups. Compared with non-PEKT, PEKT did not improve the course of mineral metabolism disorders. Mineral and bone disorder treatment was likely insufficiently provided to pediatric PEKT patients. To obtain the maximum advantage of PEKT, calcium and phosphorus levels should be strictly controlled before kidney transplantation.

Phosphate supplementation for hypophosphatemia during continuous renal replacement therapy in adults.

BACKGROUND: Hypophosphatemia is common during continuous renal replacement therapy (CRRT) in critically ill patients and can cause generalized muscle weakness, prolonged respiratory failure, and myocardial dysfunction. This study aimed to investigate the efficacy and safety of adding phosphate to the dialysate and replacement solutions to treat hypophosphatemia occurring in intensive CRRT in critically ill patients. METHODS: We retrospectively analyzed 73 patients treated with intensive CRRT (effluent flow ≥35 ml/kg/hr) in the intensive care unit. The control group (group 1, n = 22) received no phosphate supplementation. The treatment groups received dialysate and replacement solution phosphate supplementation at 2.0 mmol/L (group 2, n = 26) or 3.0 mmol/L (group 3, n = 25). RESULTS: The CRRT-induced hypophosphatemia incidence was 59.0%. Correction of hypophosphatemia with phosphate supplementation changed the mean serum phosphorus levels to 1.24 ± 0.37 and 1.44 ± 0.31 mmol/L in groups 2 and 3, respectively (p = .02). The time required for correction was 1.65 ± 0.80 and 1.39 ± 1.43 days for groups 2 and 3, respectively and was significantly longer in group 2 (p = .02). After supplementation, hypophosphatemia, and hyperphosphatemia both occurred in 7% of group 2. Group 3 developed no hypophosphatemia, but 20% developed hyperphosphatemia. The serum phosphate levels in hyperphosphatemia cases returned to normal within 2.0 days (group 2) and 1.0 day (group 3) after stopping phosphate supplementation. CONCLUSION: Phosphate supplementation effectively corrected CRRT-induced hypophosphatemia in critically ill patients with an acute kidney injury. The use of 2 mmol/L phosphate is appropriate in patients with CRRT-induced hypophosphatemia, but a different concentration could be required to prevent hypophosphatemia at the start of CRRT.

Auditing the Efficacy and Safety of Alfacalcidol and Calcium Therapy in Idiopathic Hypoparathyroidism.

CONTEXT: Patients with hypoparathyroidism are treated with vitamin D and calcium. PTH is an emerging option because of its physiological action. It is important to assess the efficacy and shortcomings of conventional therapy. OBJECTIVE: We assessed the efficacy and safety of alfacalcidol in a large cohort of patients with idiopathic hypoparathyroidism (IH) and identified a subset who could be treated without oral calcium. DESIGN AND SETTING: Observational study at tertiary care center. SUBJECTS AND METHODS: We assessed 92 patients with IH who were receiving alfacalcidol and oral calcium to maintain an optimal serum total calcium level of 8.0 to 8.5 mg/dL during routine follow-up. Patients with suboptimal control were provided free medicines and followed up frequently. Oral calcium and alfacalcidol doses were titrated sequentially to determine the minimum doses for optimal calcium control. Serum phosphate level, 1,25-dihydroxyvitamin D, fractional excretion of phosphorus (FEPh), and hypercalciuria (urine calcium-to-creatinine ratio, >0.2) were assessed at each step of titration. RESULTS: Only 38% of patients had optimal calcium control during routine follow-up. With good compliance, all achieved optimal serum calcium and 1,25-dihydroxyvitamin D levels and 43% of patients could stop taking oral calcium. Hyperphosphatemia, hypercalciuria, and low FEPh persisted at all stages of therapy. Serum phosphorus levels normalized when the serum calcium level increased to 9.9 mg/dL, but this level of serum total calcium was associated with hypercalciuria in 90% of patients. CONCLUSION: Alfacalcidol is effective in achieving calcemic control in IH. Calcemic control without oral calcium was achieved in 43% of patients receiving alfacalcidol. However, optimal calcium control was associated with hyperphosphatemia and hypercalciuria in most patients.

Lack of Awareness of Dietary Sources of Phosphorus Is a Clinical Concern.

Hyperphosphatemia is a serious complication in patients with chronic kidney disease (CKD), and is associated with more rapid progression as well as higher risk of mortality, and higher rate of cardiovascular disease accidents. CKD patients are usually advised to adopt a low phosphate diet in addition to phosphate-lowering medications, if necessary. However, there is a lack of awareness of the dietary sources of phosphate, especially hidden phosphate intake from phosphate additives in processed foods and carbonated beverages. Appropriate nutritional education could be an effective solution in reducing phosphate toxicity without introducing an additional pill burden or malnutrition.

Adequacy of Plant-Based Proteins in Chronic Kidney Disease.

Concerns regarding protein and amino acid deficiencies with plant-based proteins have precluded their use in chronic kidney disease (CKD) patients. Many of these concerns were debunked years ago, but recommendations persist regarding the use of "high-biological value" (animal-based) proteins in CKD patients, which may contribute to worsening of other parameters such as blood pressure, metabolic acidosis, and hyperphosphatemia. Plant-based proteins are sufficient in meeting both quantity and quality requirements. Those eating primarily plant-based diets have been observed to consume approximately 1.0 g/kg/day of protein, or more. CKD patients have been seen to consume 0.7-0.9 g/kg/day of mostly plant-based protein without any negative effects. Furthermore, those substituting animal-based proteins for plant-based proteins have shown reductions in severity of hypertension, hyperphosphatemia, and metabolic acidosis. Plant-based proteins, when consumed in a varied diet, are not only nutritionally adequate but have pleiotropic effects which may favor their use in CKD patients.

Cost-Effectiveness of First-Line Sevelamer and Lanthanum versus Calcium-Based Binders for Hyperphosphatemia of Chronic Kidney Disease.

BACKGROUND: Phosphate binders are used to treat hyperphosphatemia among patients with chronic kidney disease (CKD). OBJECTIVES: To conduct an economic evaluation comparing calcium-free binders sevelamer and lanthanum with calcium-based binders for patients with CKD. METHODS: Effectiveness data were obtained from a recent meta-analysis of randomized trials. Effectiveness was measured as life-years gained and translated to quality-adjusted life-years (QALYs) using utility weights from the literature. A Markov model consisting of non-dialysis-dependent (NDD)-CKD, dialysis-dependent (DD)-CKD, and death was developed to estimate the incremental costs and effects of sevelamer and lanthanum versus those of calcium-based binders. A lifetime horizon was used and both costs and effects were discounted at 1.5%. All costs are presented in 2015 Canadian dollars from the Canadian public payer perspective. Results of probabilistic sensitivity analysis were presented using cost-effectiveness acceptability curves. Sensitivity analyses were conducted for risk pooling methods, omission of dialysis costs, and persistence of drug effects on mortality. RESULTS: Sevelamer resulted in an incremental cost-effectiveness ratio of $106,522/QALY for NDD-CKD and $133,847/QALY for DD-CKD cohorts. Excluding dialysis costs, sevelamer was cost-effective in the NDD-CKD cohort ($5,847/QALY) and the DD-CKD cohort ($11,178/QALY). Lanthanum was dominated regardless of whether dialysis costs were included. CONCLUSIONS: Existing evidence does not clearly support the cost-effectiveness of non-calcium-containing phosphate binders (sevelamer and lanthanum) relative to calcium-containing phosphate binders in DD-CKD patients. Our study suggests that sevelamer may be cost-effective before dialysis onset. Because of the remaining uncertainty in several clinically relevant outcomes over time in DD-CKD and NDD-CKD patients, further research is encouraged.

Prevention and treatment of hyperphosphatemia in chronic kidney disease.

Hyperphosphatemia has consistently been shown to be associated with dismal outcome in a wide variety of populations, particularly in chronic kidney disease (CKD). Compelling evidence from basic and animal studies elucidated a range of mechanisms by which phosphate may exert its pathological effects and motivated interventions to treat hyperphosphatemia. These interventions consisted of dietary modifications and phosphate binders. However, the beneficial effects of these treatment methods on hard clinical outcomes have not been convincingly demonstrated in prospective clinical trials. In addition, exposure to high amounts of dietary phosphate may exert untoward actions even in the absence of overt hyperphosphatemia. Based on this concept, it has been proposed that the same interventions used in CKD patients with normal phosphate concentrations be used in the presence of hyperphosphatemia to prevent rise of phosphate concentration and as an early intervention for cardiovascular risk. This review describes conceptual models of phosphate toxicity, summarizes the evidence base for treatment and prevention of hyperphosphatemia, and identifies important knowledge gaps in the field.

Secondary hyperparathyroidism among Nigerians with chronic kidney disease.

BACKROUND: Secondary hyperparathyroidism (SHPT) is a manifestation of chronic kidney disease mineral bone disorder (CKD-MBD). SHPT is common in patients with chronic kidney disease (CKD) and is associated with significant morbidity and mortality. METHODS: A cross- sectional descriptive study involving 230 patients with CKD. RESULTS: The mean age of the study population was 44.17±15.24 years. The median intact parathyroid hormone and alkaline phosphatase levels were 96pg/ml (range 4-953pg/ml) and 88 iu/l (range 10-800 iu/l) respectively. The mean (with standard deviation) calcium, serum phosphate, calcium phosphate product and haemoglobin levels were 2.22±0.29mmol/l, 1.8±0.62mmol/l, 3.94±1.42mmol2/l2 and 9.90±1.87g/dl respectively. Majority of patients had advanced CKD with 70.3% of patients in stage G5. The prevalence rates of SHPT, hypocalcaemia, hyperphosphataemia, elevated alkaline phosphatase and elevated calcium phosphate product were 55.2%, 34.8%, 66.1%, 42.2% and 25.2% respectively.Univariate analysis revealed that SHPT was associated with hypocalcaemia, hyperphosphataemia, elevated alkaline phosphatase, proteinuria, anaemia, hypertension, left ventricular hypertrophy and stage of kidney disease; being worse with advancing kidney disease. Independently associated with SHPT were hypocalcaemia (OR=4.84), hyperphosphataemia (OR=3.06), and elevated alkaline phosphatase (OR=2.04). CONCLUSION: The prevalence of SHPT in CKD is high, occurs early and is independently associated with hypocalcaemia, hyperphosphataemia and elevated alkaline phosphatase. The prevalence of SHPT also increases with worsening renal function.

Sleep quality and risk factors of atherosclerosis in predialysis chronic kidney disease.

INTRODUCTION: Chronic kidney disease (CKD) patients have more frequent sleep disorders and cardiovascular disease than normals. Since arterial stiffness as a risk factor of atherosclerosis can be evaluated with pulse wave velocity (PWV), we aimed to investigate the prevalance of sleep quality (SQ) and the relationship between SQ and risk factors of atherosclerosis and whether there is a relationship between SQ and PWV (the indicator of arterial stiffness) in predialysis CKD patients. METHODS: This cross-sectional study was carried out in CKD patients followed at the Nephrology Department in Konya, Turkey, between November 2014 and March 2015. A total of 484 CKD patients were screened. Of the 484 patients, 285 patients were excluded. The remaining 199 CKD patients without cardiovascular disease at stage 3, 4, and 5 (predialysis) were included in the final study. The SQ of the patients was evaluated by the Pittsburgh Sleep Quality Index (PSQI). PWV was measured by using a single-cuff arteriography device (Mobil-O-Graph PWA, a model pulse wave analysis device; IEM). RESULTS: A total of 199 predialysis CKD patients were included in the study, 73 of whom (36.7 %) were 'poor sleepers' (global PSQI >5). Patients with poor SQ were older than those with good SQ (p = 0.077). SQ was worse in female patients compered to male patients (p = 0.001). SQ was worse in obese patients. As laboratory parameters, serum phosphorus, LDL cholesterol, and triglycerides levels correlated positively with SQ (respectively; r = 0.245, p&0.001; r = 0.142, p = 0.049; r = 0.142, p = 0.048). The indicator of arterial stiffness, PWV, was higher in patients with poor SQ (p = 0.033). Hyperphosphatemia and female gender are determined as risk factors for poor SQ in multivariate analysis (p = 0.049, ExpB = 1.477; p = 0.009, ExpB = 0,429, respectively). CONCLUSIONS: Our study showed for the first time that there is a relationship between SQ and risk factors of atherosclerosis in predialysis CKD patients.

Survival of Patients on Hemodialysis and Predictors of Mortality: a Single-Centre Analysis of Time-Dependent Factors.

INTRODUCTION: This study aimed to evaluate the outcome and predictors of survival in hemodialysis patients of Hasheminejad Kidney Center where a comprehensive dialysis care program has been placed since 2004. MATERIALS AND METHODS: Data of 560 hemodialysis patients were used to evaluate 9-year survival rates and predictors of mortality. Cox regression models included comorbidities as well as averaged and 6-month-averaged time-dependent values of laboratory findings as independent factors. RESULTS: Survival rates were 91.9%, 66.0%, 46.3%, and 28.5%,  at 1, 3, 5, and 9 years, respectively, in all patients and 90.8%, 61.6%, 42.1%, and 28.0% in 395 incident patients starting hemodialysis after 2004. Adjusted survival models demonstrated age, male sex, diabetes mellitus, cardiovascular disease, and high-risk vascular access as baseline predictors of mortality, as well as averaged low hemoglobin level (hazard ratio [HR], 1.98; 95% confidence interval [CI], 1.36 to 2.90) and a single-pool KT/V < 1.2 (HR, 2.28; 95% CI, 1.60 to 3.26). The averaged high-density lipoprotein cholesterol (HR, 0.67; 95% CI, 0.55 to 0.81) and serum creatinine (HR, 0.71; 95% CI, 0.64 to 0.79) levels demonstrated protective effects. The adjusted time-dependent model further revealed the significant association of hypocalcemia (HR, 1.63; 95% CI, 1.13 to 2.34), hypercalcemia (HR, 1.50; 95% CI, 1.02 to 2.21), and hyperphosphatemia (HR, 1.68; 95% CI, 1.20 to 2.37) with death. CONCLUSIONS: Our patients have relatively comparable survival rates with high-profile dialysis centers. Aiming to better achieve the recommended targets, especially hemoglobin and nutritional and bone metabolism factors, should be considered for optimal dialysis outcomes.