Spurious Hyperphosphatemia in a Patient with Chronic Kidney Disease - a Rare Case of Alteplase Contamination.

Spurious hyperphosphatemia, a rare occurrence, typically arises from substances in a patient's blood interfering with the colorimetric method for serum phosphate measurement. We present a case of factitious hyperphosphatemia caused by alteplase-contaminated blood samples in an 88-year-old CKD patient on hemodialysis, leading to misleadingly high phosphorus levels. Thorough investigations ruled out other etiologies, highlighting the necessity of stringent adherence to blood collection protocols to prevent sample contamination and avert erroneous laboratory results. This unique cause of hyperphosphatemia should be considered in the differential diagnosis when encountering unexplained elevations in phosphorus levels, particularly in the context of normal blood calcium levels.

Health Economic Benefits of Introducing Sucroferric Oxyhydroxide in the Treatment of Patients with Chronic Kidney Disease under Dialysis in the Kingdom of Saudi Arabia.

Hyperphosphatemia is an electrolyte disorder highly prevalent in patients with chronic kidney disease undergoing hemodialysis (HD) that usually requires treatment with oral phosphate binders (PBs). Sucroferric oxyhydroxide (SO) is a calcium-free, iron-based PB indicated for the control of serum phosphorus. In the real-world setting, SO has shown clinical effectiveness with a lower pill burden and has also been associated with reduced hospital admission rates. This study aims to assess the potential economic benefits resulting from the introduction of SO to the health-care setting of the Kingdom of Saudi Arabia (KSA). An economic analysis using data from a retrospective real-world study that compared HD patients with uninterrupted SO prescriptions with patients who discontinued SO and switched to other PBs (oPBs). Annual drug costs for the estimated PB-eligible population in KSA were quantified. Costs per responder were estimated for all treatments. Hospital admissions' incidence rates were converted into annual inpatient cost savings and were deducted from drug costs to estimate the annual economic effect of SO versus oPBs. Sensitivity and breakeven analyses were also conducted. The eligible population for PB therapy in KSA was estimated at n = 14,748. Treating therapy-eligible populations exclusively with SO was estimated to generate annual inpatient cost-savings of SAR 107.4-119.4 million compared to treating the population with oPBs. The estimated economic effect signified overall annual savings ranging from SAR 82.8 to SAR 94.8 million when the population is treated with SO. Sensitivity analyses showed persistent cost savings. The estimated benefit-cost ratios showed that for every SAR 1 spent on SO, the expected return on investment was SAR 4.4-4.9. SO is an effective therapy that may result in substantial cost savings from reducing hospital admission costs that are attributable to hyperphosphatemia among HD patients.

Evaluation of methods to eliminate analytical interference in multiple myeloma patients with spurious hyperphosphatemia.

OBJECTIVE: The acid/molybdate assay performed on the Beckman Coulter AU5821 could be subject to paraprotein interference, which potentially results in spurious hyperphosphatemia. We attempted to find a reliable solution to eliminate paraprotein interference in laboratory test results and discuss the causes of paraprotein interference. METHODS: We observed 50 multiple myeloma patients with serum paraproteins. We used the trichloroacetic acid (TCA) deproteinizing method to confirm that paraproteins indeed interfered with phosphate detection in the serum acid/molybdate assay. Furthermore, we used the dry chemical method (Vitros 5.1 FS, Johnson) and deionized water (H2O), normal saline (NS), and healthy human serum as alternative diluents. We assessed the clinical acceptability of the 4 methods by evaluating a bias percentage (bias%) lower than 10% under the premise of TCA treatment as a serum phosphate reference method. RESULTS: In total, comparing the results of the TCA treatment on the Beckman Coulter AU5821, 3/50 (6%) multiple myeloma patients exhibited phosphate pseudo-elevation (bias% >10%). Additionally, we found pseudo-hypophosphate only in immunoglobulin (Ig)G-kappa paraprotein samples, and all were above 50 g/L. The bias% between TCA and dry chemical method for the 3 patients was below 10%. The maximum acceptable dilutions for patient 22 were 8-fold H2O, 4-fold H2O , and 2-fold serum; those for patient 45 were 16-fold H2O, 16-fold H2O, and 2-fold serum. However, the bias% of patient 40 was beyond the acceptable range in all 3 dilution groups. CONCLUSION: High concentrations of IgG kappa-type paraproteins are more likely to interfere with serum phosphorous detection. Both the TCA and dry chemical method can effectively eliminate paraprotein interference.

Transient Hyperphosphatasemia in a Child with Autism Spectrum Disorder.

INTRODUCTION: Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by deficits in social communication and the presence of restricted interests and repetitive behaviors. Transient hyperphosphatasemia of infancy and early childhood (THI) is a benign laboratory disorder characterized by transiently extremely elevated activity of serum alkaline phosphatase (S-ALP). CASE REPORT: We present a 21-month-old girl with a right leg limp, most probably due to reactive arthritis after febrile viral infection, and deterioration of psychomotor development with concomitant transient elevation of S-ALP (61.74 µkat/L; normal 2.36-7.68 µkat/L). Normal values of serum creatinine, aspartate-aminotransferase, alanin-aminotransferase, calcium, phosphate, together with normal wrist X-ray ruled out rickets or other bone or hepatic cause of high S-ALP. The S-ALP gradually decreased within 3 months, thus fulfilling the THI criteria. Screening for inborn errors of metabolism was negative and meticulous neurologic, psychologic and psychiatric assessment pointed to the diagnosis of autism spectrum disorder (ASD). There was no causal relationship between THI and ASD, as high S-ALP was an accidental and transient finding within the routine laboratory assessment. However, when THI occurs in a child with an onset of a new disorder, or with a pre-existing bone or liver disease, it might seriously concern the physician. CONCLUSION: Children with THI should be spared from extensive evaluations and unnecessary blood draws.

Use of Teriparatide in Hyperphosphatemic Familial Tumor Calcinosis: Evaluating the Interaction Between FGF23 and PTH on the Phosphaturic Effect.

Hyperphosphatemic familial tumor calcinosis (HFTC) is a rare disease characterized by hyperphosphatemia and calcium and phosphorus crystal deposition. It occurs due to the loss of function of FGF23. Herein, we report a case of a 50-year-old woman diagnosed with HFTC (homozygous variant in the GALNT3 gene, c.803_804 C insertion) with a history of ectopic calcifications in the past 30 years. Laboratory tests on admission were as follows: phosphate (P) 7.1 mg/dL (Normal range (NR) 2.5-4.5 mg/dL), FGF23 c-terminal 2050 RU/mL (NR < 150 RU/mL), and intact FGF23 (iFGF23) 18.93 pg/mL (NR 12.0-69.0 pg/mL). Treatment with acetazolamide, sevelamer, and a phosphorus-restricted diet was started, but phosphatemia remained high and calcifications continued to progress. In an attempt to further decrease P, a 36-day cycle of teriparatide (TPTD) 20 mcg twice daily was added, decreasing P from 6.2 to 5.2 mg/dL and increasing the 1.25(OH)2 vitamin D by 34.2%. As urinalysis was not feasible at the end of the 36-day cycle, a second cycle was performed for another 28 days, producing a similar decrease in P (from 6.4 to 5.5 mg/mL) and an evident decrease in the rate of tubular reabsorption of P (from 97.2 to 85.3%), however, accompanied by a worrying increase in calciuria. The use of TPTD 20 mcg twice daily in a patient with genetic resistance to FGF23 (HFTC) was associated with consistent increase in phosphaturia and reduction in phosphatemia, in addition to an increase in calcitriol. The resulting hypercalciuria precludes the therapeutic use of TPTD in HFTC and suggests an important role of FGF23, not only in phosphate homeostasis but also in avoiding any excess of calcitriol.

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.

Serum fibroblast growth factor 23 (FGF-23): associations with hyperphosphatemia and clinical staging of feline chronic kidney disease.

Fibroblast growth factor 23 (FGF-23) is an independent monitor of the progression of chronic kidney disease (CKD) in human medicine, and FGF-23 may have value as a biomarker in feline CKD. We evaluated the relationship between serum FGF-23 and CKD stages, and the effect of age on FGF-23 in normal cats. We measured FGF-23 and intact parathyroid hormone (iPTH) concentrations by ELISA, with intra- and inter-assay CVs ≤ 15%. The percentage recovery of FGF-23 and iPTH remained stable for up to 7 d in samples stored at -20°C and -80°C. We measured FGF-23 in 304 cats, among which 196 were diagnosed with CKD. The 108 clinically healthy cats were divided into 5 subgroups based on growth stage (0-2 y, 3-6 y, 7-10 y, 11-14 y, ≥ 15 y). No statistical difference was found in FGF-23 among age groups (p = 0.15) or by sex in healthy subjects. Using the International Renal Interest Society guideline, 34 cats were defined as CKD stage 1, 74 stage 2, 51 stage 3, and 37 stage 4. FGF-23 was higher in cats in all CKD stages than in controls. Higher serum phosphorus was observed in stage 3 (p = 0.04) and 4 (p < 0.01) compared to controls. iPTH increased as CKD progressed. Pearson analysis indicated a positive linear relationship between FGF-23 and iPTH (control: r = 0.70, p < 0.01; CKD: r = 0.46, p = 0.02). FGF-23 may be a useful biomarker of feline CKD and may precede hyperphosphatemia in advanced feline CKD.

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.

Association of hyperphosphatemia with an increased risk of sudden death in patients on hemodialysis: Ten-year outcomes of the Q-Cohort Study.

BACKGROUND AND AIMS: Sudden death is one of the most common causes of death among patients on hemodialysis. Although hyperphosphatemia is a well-known risk factor for cardiovascular and all-cause deaths, the studies focusing on the relationship between serum phosphate levels and the risk of sudden death are limited. This study aimed to clarify the relationship between serum phosphate levels and the risk of sudden death in patients on hemodialysis. METHODS: This is a multicenter, longitudinal, and observational study. A total of 3505 patients, registered in the Q-Cohort Study, who underwent maintenance hemodialysis, and were followed up for 10 years, were included. Patients were divided into quartiles on the basis of baseline serum phosphate levels: Q1 (n = 886), <4.2 mg/dL; Q2 (n = 837), 4.2-4.8 mg/dL; Q3 (n = 908), 4.9-5.6 mg/dL; and Q4 (n = 874), ≥5.7 mg/dL. Associations between baseline serum phosphate levels and sudden death were analyzed using the Cox proportional hazards model and the Fine-Gray regression model. RESULTS: During the follow-up period, 227 patients died from sudden death. The risk for sudden death was significantly higher in the highest quartile (Q4) than in the lowest quartile (Q1) as the reference group (multivariable-adjusted hazard ratios and 95% confidence intervals: Q1, 1.00; Q2, 1.15 [0.77-1.70], Q3, 1.31 [0.89-1.93], and Q4, 1.72 [1.14-2.59]; hazard ratio for every 1-mg/dL increase in the serum phosphate level, 1.23 [1.09-1.39]; p < 0.001). CONCLUSIONS: Hyperphosphatemia is independently associated with an elevated risk of sudden death in patients on hemodialysis.

[Pediatric reference values for alkaline phosphatase and pathophysiological variations]. / Valeurs de référence de la phosphatase alcaline en pédiatrie et variations physiopathologiques.

Alkaline phosphatase activity is a parameter included in biochemical liver test. These isoenzymes are of various cellular origin inducing physiological variations on age and sex. The alkaline phosphatase activity standardization as well as numerous international studies have made it possible to standardize the pediatric reference values. The hyperphosphatasemia etiologies are very well know but the hypophosphatasemia are hardly explored and can allow the diagnosis of pathologies including hypophosphatasia, a rare treatable disease.

Interferences in the measurement of circulating phosphate: a literature review.

Background Inorganic phosphate in blood is currently determined by the reaction with molybdate. This report aims at reviewing conditions underlying spuriously altered levels of circulating inorganic phosphate. Content A systematic search of the Excerpta Medica, the National Library Database and the Web of Science database was conducted without language restriction from the earliest publication date available through January 31, 2020. Summary For the analysis, 80 reports published in English (n = 77), French (n = 1), German (n = 1) and Spanish (n = 1) were retained. Well-documented pseudohyperphosphatemia was observed in individuals exposed to liposomal amphotericin, in patients affected by a gammopathy, in patients with hyperlipidemia and in patients with hyperbilirubinemia. An unexplained elevated inorganic phosphate level sometimes provided a clue to the diagnosis of a gammopathy. Well-documented cases of pseudohypophosphatemia were observed in patients on large amounts of intravenous mannitol. Finally, pseudohypophosphatemia was occasionally observed on treatment with liposomal amphotericin and in patients with a gammopathy. Outlook In order to avoid unnecessary testing and treatment, the phenomenon of spuriously altered inorganic phosphate should be recognized. An unexplained hyperphosphatemia may provide a clue to the diagnosis of a gammopathy or a severe hyperlipidemia.

LED&Paper-based analytical device for phosphatemia/calcemia diagnostics☆.

In this communication a prototype of paper-based analytical device designed for simultaneous determination of orthophosphate and calcium ions, which levels are significant for hyperphosphatemia diagnostics, is presented. The laboratory-on-paper structure for two analytes detection was wax-printed on the surface of filter paper. These two-analyte disposable paper strips are combined with two paired LED-based fluorescence detectors and simple voltmeter used as recorder of analytical signal, what makes the developed device miniature, extremely low-cost, portable and user-friendly. Thus the developed device allows usage outside of specialized clinical laboratory. Moreover, each paper strip is disposable and its utilization is easy and fast and, additionally, burnt strip tests ensure waste non-infectious. The presented LED&Paper-based analytical device provides low detection limits: 1.4 µmol L-1 and 7.4 µmol L-1 for orthophosphate and calcium ions, respectively. The practical utility of the developed device for calcemia/phosphatemia diagnostics is demonstrated using control serum standards and real human serum.

Moderate to severe hyperphosphataemia as an independent prognostic factor for 28-day mortality in adult patients with sepsis.

BACKGROUND: Ischaemic tissue injury caused by tissue hypoperfusion is one of the major consequences of sepsis. Phosphate concentrations are elevated in ischaemic tissue injury. This study was performed to investigate the association of phosphate concentrations with mortality in patients with sepsis. METHODS: This was a retrospective cohort study of patients with sepsis conducted at an urban, tertiary care emergency department (ED) in Korea. Patients with sepsis arriving between March 2010 and April 2017 were stratified into four groups according to the initial phosphate concentration at presentation to the ED: group I (hypophosphataemia, phosphate <2 mg/dL), group II (normophosphataemia, phosphate 2-4 mg/dL), group III (mild hyperphosphataemia, phosphate 4-6 mg/dL), group IV (moderate to severe hyperphosphataemia, phosphate ≥6 mg/dL). Multivariable Cox proportional hazard regression analyses were performed to evaluate the independent association of initial phosphate concentration with 28-day mortality. RESULTS: Of the 3034 participants in the study, the overall mortality rate was 21.9%. The 28-day mortality rates were group I (hypophosphataemia) 14.6%, group II 17.4% (normophosphataemia), group III (mild hyperphosphataemia) 29.2% and group IV (moderate to severe hyperphosphataemia) 51.4%, respectively (p<0.001). In the multivariable analyses, patients with severe hyperphosphataemia had a significantly higher risk of death than those with normal phosphate levels (HR 1.59; 95% CI 1.23 to 2.05). Mortality in the other groups was not significantly different from mortality in patients with normophosphataemia. CONCLUSIONS: Moderate to severe hyperphosphataemia was associated with 28-day mortality in patients with sepsis. Phosphate level could be used as a prognostic indicator in sepsis.