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Background: Living kidney donors (LKD) experience an abrupt decline in glomerular filtration rate (GFR) resulting in abnormalities of mineral and bone metabolism (MBD), and this may have implications for skeletal health. We prospectively studied acute and long term MBD adaptation of LKD from two kidney transplant centers (São Paulo, Brazil and Miami, USA)., Methods: Renal function and MBD parameters longitudinally after kidney donation (baseline - D0, day 1, 14, 180 and 360 post-operatively) were measured in 74 patients (40 y, 73% female, 54% Brazilian). A subset of 20 donors from Brazil were reassessed after 10 years of nephrectomy., Results: At baseline, Brazilian donors presented lower intact FGF23 (20.8 vs. 80.1 pg/mL, P < 0.01) and higher PTH (47.4 vs. 40.1, P = 0.04) than their US counterparts. GFR decreased to 63% of its baseline levels just after donation but improved 10% during the first year. PTH levels increased on D1, returning to baseline levels on D14, while FGF23 remained higher than baseline over the first year. LKD had a significant reduction of serum phosphate on D1, which returned to baseline levels on D180. A higher fractional excretion of phosphate (FEP) was noted since D14. After 10 years of donation, 20 LKD presented a sustained reduction in GFR (74.8 ± 14mL/min). There was a return to baseline in serum FGF23 [21.8 (18-30) pg/mL] and FEP, accompanied by an increase in serum calcium. PTH remained elevated (57.9 ± 18 pg/mL), whereas serum calcitriol and Klotho were lower than before the donation., Conclusions: The abrupt decline in kidney mass is associated with an increase in PTH and FGF23 that is not explained by phosphate retention. In a long-term evaluation, LKD showed a sustained drop in GFR, with lower serum calcitriol and Klotho, and higher PTH. The effects of these changes should be investigated in further studies., (© 2024. The Author(s).)

Introduction Primary aldosteronism is characterized by the autonomous excretion of aldosterone, which may induce bone mineral disorders. Methods A total of 96 patients with primary aldosteronism were analyzed to identify differences in the regulation of serum calcium/phosphate balance between patients with unilateral and bilateral aldosterone hypersecretion and to determine whether or not adrenalectomy or mineralocorticoid receptor blockers affected such differences. Results Serum phosphate concentrations were significantly lower in patients with unilateral aldosterone hypersecretion than in patients with bilateral aldosterone hypersecretion (2.96±0.45 vs. 3.36±0.55 mg/dL, p<0.05), and recovered after adrenalectomy (2.96±0.45 vs. 3.49±0.32 mg/dL, p<0.01). In patients with bilateral aldosterone hypersecretion, the baseline serum phosphate levels were significantly lower in responders to mineralocorticoid receptor blocker treatment, defined as post-treatment plasma renin activity ≥1 ng/mL/h, than in non-responders. In responders, these levels tended to recover after treatment. A weak negative correlation between the plasma aldosterone concentration (PAC) and serum phosphate was observed, but there were no associations between the PAC and serum calcium concentration or between the aldosterone renin ratio and serum calcium and phosphate concentrations. Conclusion The effects on calcium/phosphate homeostasis may differ according to the primary aldosteronism subtype.

Introduction: Hypophosphatemia is common in critically ill patients. We have described the epidemiology of hypophosphatemia in patients admitted to the Intensive Care Units., Methods: A multicentre, retrospective cohort study of 12 ICUs in Queensland, Australia from January 1st, 2015, to December 31st, 2021. Exclusions included readmissions, renal replacement therapy, end-stage renal disease, and palliative intent admissions and transfers from other ICUs. Patients were classified into four groups based on the severity of the first episode of low serum phosphate (PO 4 ): "None" (PO4: ≥0.81 mmol/L, "Mild" (PO4: ≥0.50 & <0.81 mmol/L) "Moderate" (PO4: ≥0.30 & <0.50 mmol/L) and "Severe" (PO4: <0.30 mmol/L). A mixed-effect logistic regression model, including hospital as a random effect, was developed to examine factors associated with 90-day case fatality., Results: Of the 89,776 patients admitted, 68,699 patients were included in this study, with 23,485 (34.2%) having hypophosphatemia with onset mostly on Day 2 of ICU admission and correcting to normal 3 days after hypophosphatemia was identified. There was substantial variation among participating ICUs in phosphate replacement; the threshold, and the route by which it was replaced. Day-90 case fatality increased with severity of hypophosphatemia (None: 3974 (8.8%), Mild: 2306 (11%), Moderate: 377 (14%); Severe: 108 (21%) (p < 0.001)). Multivariable regression analysis showed that compared to those without hypophosphatemia, patients with moderate (odds ratio (OR) 1.24; 95% confidence intervals (CI) 1.07-1.44; p = 0.004) or severe (OR 1.49; 95% CI 1.13-1.97; p = 0.005) hypophosphatemia had increased risk of 90-day case fatality., Conclusion: Hypophosphatemia was common, and mostly occurred on day 2 with early correction of serum phosphate. Phosphate replacement practices were variable among ICUs. Moderate and severe hypophosphatemia was associated with increased 90-day case fatality., (Copyright © 2024. Published by Elsevier Masson SAS.)

Infantile hypercalcemia (IH) is a rare genetic disorder characterized by hypercalcemia, hypercalciuria, low parathyroid hormone, and nephrocalcinosis during the first months of life. Biallelic variants in the genes CYP24A1 and SCL34A1 cause IH1 and 2, respectively. We present the case of a newborn with an antenatal diagnosis of IH2 due to the identification of echogenic, yet normal-sized kidneys at 23 weeks gestation. Trio whole-exome sequencing initially identified only a heterozygous pathogenic variant in SLC34A1. Re-analysis of the exome data because of the clinical suspicion of IH2 revealed a 21-basepair deletion in trans that had initially been filtered out because of its high allele frequency. The diagnosis of IH2 enabled postnatal screening for hypercalcemia, present already at week 1, resulting in early treatment with phosphate supplementation and vitamin D avoidance. In the subsequent course, biochemical parameters were normalized, and the patient showed no obvious clinical complications of IH2, apart from the nephrocalcinosis., (© 2024. The Author(s), under exclusive licence to International Pediatric Nephrology Association.)

Background: Aberrations in blood phosphate (Pi) levels, whether presenting as hypo- or hyperphosphatemia, appear to be associated with clinical complications and adverse outcomes in patients admitted to an intensive care unit (ICU). However, the prevalence of Pi disorders and the association with subsequent factors and organ failures leading to death in ICU patients are poorly described. Despite endeavors to understand the etiology and treatment of low Pi levels from systematic reviews and meta-analyses, the literature lacks comprehensive guidance for managing hypophosphatemia. Hyperphosphatemia, on the other hand, appears to be associated with higher mortality among critically ill patients, yet its prevalence among ICU patients, particularly following phosphate repletion, remains unknown. The present study aims to investigate the prevalence of Pi abnormalities upon ICU admission and their incidence during the first week of ICU stay, the factors associated with Pi alterations, and the effect of phosphate repletion on the normalization of Pi levels, and its associations with clinical outcomes., Methods: This multicentre, prospective, non-interventional cohort study will include at least 1000 consecutive adult ICU patients (≥18 years) as part B of the GUTPHOS study. Sites are eligible if an anticipated minimal inclusion of 50 eligible patients during eight weeks from January 2024 until June 2024 and daily phosphate measurements during the first seven days of ICU stay are expected. All consecutive adult patients admitted to a participating ICU during the recruitment period, lasting up to eight weeks, or up to 120 patients if enrollment reaches that limit earlier, will be included. Study parameters include study site characteristics, patient demographics, daily assessment of Pi levels, Pi-related treatment, feeding details, renal replacement therapy details, the incidence of refeeding-associated hypophosphatemia and administered medication (during the first seven calendar days of ICU stay). There will be a follow-up period of a maximum of 90 days to document 28- and 90-day all-cause mortality as the primary outcome. Multiple logistic regression will be used to assess independent associations with mortality in addition to Receiver Operating Characteristics curves to identify cut-off Pi values associated with mortality and overcorrection. Linear mixed models will be conducted to assess Pi treatment effects. Subgroup analyses will be performed based on Pi abnormalities observed during ICU admission, categorized as normo-, hypo-, hyper-, or mixed, along with its severity (mild, moderate, or severe)., Discussion: The GUTPHOS study will be the first multicentre, prospective observational cohort study to investigate the prevalence, management practices, and consequent outcomes associated with Pi abnormalities during the first week of ICU admission. Its results may bridge the current evidence gap in repletion protocols while establishing the groundwork for a subsequent randomized controlled trial., Clinical Trial Registry: NCT05909722., Competing Interests: Declaration of competing interest IWKK received a Veni Fellowship (2024–2028) through the Dutch Research Council (NWO Talent Program). SJS received grants and non-financial support from Reactive Robotics GmbH (Munich, Germany), ASP GmbH (Attendorn, Germany), STIMIT AG (Biel, Switzerland), ESICM (Geneva, Switzerland), grants, personal fees, and non-financial support from Fresenius Kabi Deutschland GmbH (Bad Homburg, Germany), grants from the Innovationsfond of The Federal Joint Committee (G-BA), personal fees from Springer Verlag GmbH (Vienna, Austria) for educational purposes and Advanz Pharma GmbH (Bielefeld, Germany), non-financial support from national and international societies (and their congress organizers) in the field of anesthesiology and intensive care medicine, outside the submitted work. SJS holds stocks in small amounts from Alphabet Inc., Bayer AG, and Siemens AG; these holdings have not affected any decisions regarding his research or this study. ARHvZ reported receiving honoraria for advisory board meetings, lectures, research, and travel expenses from Abbott, AOP Pharma, Baxter, Cardinal Health, Danone-Nutricia, Fresenius Kabi, GE Healthcare, Medcaptain, Nestlé, PAION, and Rousselot. ARB received speaker or consulting fees from Nutricia and VIPUN Medical and is holding a grant from Estonian Research Council (PRG1255). MPC has obtained research funding by grants from Research Foundation Flanders, KU Leuven and Department for Innovation of the Flanders Government, and reported receiving consulting fees from Baxter and VIPUN. MLNGM reported receiving honoraria for advisory board meetings, lectures, research, and travel expenses from Getinge, Serenno Medical, Potrero Medical, Sentinel Medical, Baxter, BBraun, Becton Dickinson, ConvaTec, Spiegelberg, Medtronic, MedCaptain, and Holtech Medical, and PeerVoice. He holds stock options for Sentinel, Serenno and Potrero. JG is granted a senior clinical investigator fellowship by Research Foundation – Flanders (1842724N), and has obtained research funding by grants from KU Leuven (STG/23/032) and the European Society of Intensive Care Medicine (Fundamental Research Award 2022). The other authors declare no competing interests., (Copyright © 2024 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Background: Existing studies investigating the impact of serum calcium (Ca), phosphate (P), 25 hydroxyvitamin D (25[OH]D), and parathyroid hormone (PTH) levels on kidney function have produced inconsistent results. Further research is needed to establish the direct causal relationship between these factors and kidney function., Methods: The study used genome-wide association study datasets for exposure and outcome, mainly derived from the UK Biobank and CKDGen Consortium, with sample sizes ranging from 3,310 to 480,699 individuals of European ancestry. Heritability and genetic correlations among these phenotypes were assessed using linkage disequilibrium score regression (LDSC) and phenotypes with a heritability z-score <4 were excluded from further analyses. Pleiotropic analyses were performed to identify potential horizontal pleiotropic variants at gene and LD-independent locus levels. Mendelian randomization (MR) analysis, using instrumental variables (IVs) based on two distinct selection criteria, was conducted to investigate the potential causal relationships between serum Ca, P, 25(OH)D, PTH, and kidney function., Results: PTH was excluded from further analysis due to a heritability z-score < 4. Genetic correlations were observed between serum Ca and urine albumin-to-creatinine ratio (UACR) (rg = 0.202, P-value = 5.0E-04), between serum 25(OH)D and estimated glomerular filtration rate using serum creatinine (eGFRcrea) (rg = -0.094; P-value = 1.4E-05), and between serum 25(OH)D and blood urea nitrogen (BUN) (rg = 0.127; P-value = 1.7E-06). In univariable MR analysis using IVs based on two different selection criteria, it consistently demonstrated that genetically predicted serum Ca consistently showed an increase in UACR (beta 0.11, P- value 2.0E-03; beta 0.13, P- value 2.0E-04). Similarly, serum P was associated with a decrease in eGFRcrea (beta -0.01, P- value 2.0E-04; beta -0.005, P- value 2.0E-03) and an increase in BUN (beta 0.02, P- value 3.0E-03; beta 0.02, P- value 7.5E-07). The influence of serum P on kidney function was further supported in multivariable MR analysis. However, genetically predicted 25(OH)D did not have a significant impact on kidney function., Conclusions: Elevated serum Ca or P levels could both impair kidney function, whereas 25(OH)D has no impact on renal function., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024 Liang, Liang, Xie, Guo, Yang, Xiao, Zhuang, Xu, Wang, Wang, Zhang, Chen, Chen and Cai.)

Background and Aims: Refeeding syndrome (RFS) is defined by the presence of acute electrolyte disturbances, including hypophosphatemia. Underlying disease(s), malnutrition and hospitalisation are known risk factors for RFS. It can occur in patients with inflammatory bowel disease (IBD). We aimed to determine the frequency of hypophosphatemia and the relationship between hypophosphatemia, disease severity and nutritional status in hospitalized patients with IBD., Methods: This study was performed prospectively in hospitalized adult patients for the treatment of IBD in a tertiary-care hospital. Disease severity was assessed using Truelove and Witts score for ulcerative colitis (UC) and Crohn's Disease Activity Index for Crohn's disease (CD). Nutritional status was determined using Subjective Global Assessment (SGA). Serum phosphate concentration was recorded for first 7 days after hospitalization, and less than 0.65 mmol/l was defined as hypophosphatemia., Results: Fifty participants (33 with UC and 17 with CD) were included in the study. The mean age of the study sample was 43.4±14.9 years, of which 64% were male. A total of 8.8% of patients with UC and 37.5% of patients with CD had severe (>moderate) disease upon study admission. Seventeen patients (34%) were malnourished. During the 7 study days, 23 participants (46%) had at least one episode of hypophosphatemia. Serum phosphate concentration was significantly and moderately correlated with serum potassium concentration in both the patients and the hypophosphatemia group on study day 3 (p<0.05). Multivariate logistic regression analysis showed that the presence of malnutrition [odds ratio (OR) = 3.64, 95% confidence interval (CI): 1.52-5.58, p=0.008), the administration of parenteral nutrition (OR=2.91, 95%Cl: 1.37-4.63, p=0.015), and severe IBD (OR=1.74, 95%CI: 1.03-3.42, p=0.020) were associated with hypophosphatemia., Conclusions: Approximately half of the participants exhibited at least one instance of hypophosphatemia during the study period. Hypophosphatemia was found to be associated with malnutrition, parenteral nutrition, and severe disease in patients with IBD requiring hospitalization.

Background: VS-505 (AP301), an acacia and ferric oxyhydroxide polymer, is a novel fiber-iron-based phosphate binder. This two-part Phase 2 study evaluated the tolerability, safety and efficacy of oral VS-505 administered three times daily with meals in treating hyperphosphatemia in chronic kidney disease (CKD) patients receiving maintenance hemodialysis (MHD)., Methods: In Part 1, patients received dose-escalated treatment with VS-505 2.25, 4.50 and 9.00 g/day for 2 weeks each, guided by serum phosphorus levels. In Part 2, patients received randomized, open-label, fixed-dosage treatment with VS-505 (1.50, 2.25, 4.50 or 6.75 g/day) or sevelamer carbonate 4.80 g/day for 6 weeks. The primary efficacy endpoint was the change in serum phosphorus., Results: The study enrolled 158 patients (Part 1: 25; Part 2: 133), with 130 exposed to VS-505 in total. VS-505 was well tolerated. The most common adverse events were gastrointestinal disorders, mainly feces discolored (56%) and diarrhea (15%; generally during Weeks 1-2 of treatment). Most gastrointestinal disorders resolved without intervention, and none was serious. In Part 1, serum phosphorus significantly improved (mean change -2.0 mg/dL; 95% confidence interval -2.7, -1.4) after VS-505 dose escalation. In Part 2, serum phosphorus significantly and dose-dependently improved in all VS-505 arms, with clinically meaningful reductions with VS-505 4.50 and 6.75 g/day, and sevelamer carbonate 4.80 g/day [mean change -1.6 (-2.2, -1.0), -1.8 (-2.4, -1.2) and -1.4 (-2.2, -0.5) mg/dL, respectively]. In both parts, serum phosphorus reductions occurred within 1 week of VS-505 initiation, returning to baseline within 2 weeks of VS-505 discontinuation., Conclusion: VS-505, a novel phosphate binder, was well tolerated with a manageable safety profile, and effectively and dose-dependently reduced serum phosphorus in CKD patients with hyperphosphatemia receiving MHD., Clinical Trial Registration Number: NCT04551300 ., (© The Author(s) 2024. Published by Oxford University Press on behalf of the ERA.)

Phosphate has a fundamental role in bone mineralization, and its chronic deficiency has multiple negative consequences in the body, including defects in bone mineralization that will manifest in children as rickets and osteomalacia. Here we present a young boy known to have Wiedemann-Steiner syndrome with multiple co-morbidities that necessitated gastric tube feeding. The child at 22 months was found to have hypophosphatemia and a high alkaline phosphatase level associated with rachitic skeletal manifestations that were attributed to low phosphate intake and/or gastrointestinal absorption, as there was no evidence of excessive phosphate wasting based on appropriate tubular renal re-absorption of phosphate. The primary nutritional source was an elemental amino acid-based milk formula (Neocate ® ) from 12 months of age. After switching from Neocate ® to another elemental amino-acid based milk formula, all biochemical and radiological abnormalities returned to normal, indicating that the Neocate ® formula was the possible cause of the patient’s low phosphate intake. However, in the literature, this formula-associated effect was only described in a limited number of patients. Whether or not some patient-related factors, such as the very rare syndrome described in our patient, could influence this effect warrants further exploration., Competing Interests: Conflict of interest: None declared., (©Copyright 2024 by Turkish Society for Pediatric Endocrinology and Diabetes / The Journal of Clinical Research in Pediatric Endocrinology published by Galenos Publishing House.)

Background: Hemolysis is a common reason for nonreporting results in biochemistry and is measured using the hemolysis index (HI), with nonreporting limits set for analytes by manufacturers., Objective: To verify the nonreporting HI limit for potassium, phosphate, magnesium, aspartate aminotransferase (AST), lactate dehydrogenase (LDH), iron, CA19-9, and vitamin D on the Beckman Coulter AU5800/DxI800 analyzers., Method: Hemolysate was created from EDTA-lined tubes of whole blood using an osmotic shock procedure. The hemolysate underwent serial dilutions with saline and was spiked in paired serum. The delta changes in HI and analyte concentration were measured, assessed using regression analysis, and compared against calculated reference change values., Results: A linear relationship between increasing HI and increasing analyte concentration (R2 > 0.9) was observed for potassium (y = 0.8864x), phosphate (y = 0.1079x), magnesium (y = 0.0678x), AST (y = 29.035x), and LDH (y = 350x). Increasing HI values did not have a linear effect on iron (y = -0.2544x), CA19-9 (y = 2.7019x), or vitamin D (y = 8.036x) concentrations., Conclusion: The results from this experiment support increasing the HI nonreporting limit to 100 mg/dL for potassium; 200 mg/dL for magnesium; and 300 mg/dL for phosphate, CA19-9, and vitamin D. The iron assay is not affected by hemolysis as high as 500 mg/dL. The current HI nonreporting limit of 50 mg/dL is appropriate for LDH., (© The Author(s) 2024. Published by Oxford University Press on behalf of American Society for Clinical Pathology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

To assess the efficacy and safety of burosumab in children and adults with X-linked hypophosphatemia based on real-world evidence. MEDLINE (via PubMed) and Cochrane Library were searched until 18 October 2023 for single-arm (before-after) studies. Registries including Clinicaltrials.gov, EU Clinical Trials, WHO International Clinical Trials Registry Platform, and conference abstracts. The outcomes were a change in serum phosphorus concentrations and change in RSS, a change in serum ALP, bone-specific ALP, a change in the ratio of Tubular maximum reabsorption of Phosphate to Glomerular Filtrate rate, a change in serum 1,25(OH) 2 D and 25(OH) 2 D concentrations, change in height Z-score, McMaster Universities Osteoarthritis Index (WOMAC) and safety outcomes. An inverse variance random-effects meta-analysis was applied for data synthesis. Fifteen studies (289 participants) were included. Burosumab treatment improved serum phosphate concentrations [mean difference 0.88 mg/dl, 95% confidence interval 0.70 to 1.07, I 2  = 92%), Rickets Severity score (mean difference - 1.86, 95% confidence interval - 2.5 to - 1.21, I 2  = 71%), serum alkaline phosphate concentrations (mean difference - 1.86, 95% confidence interval - 2.5 to - 1.21, I 2  = 71%), serum 1,25(OH) 2 D concentrations (mean difference 18.91 pg/ml, 95% confidence interval 6.39 to 31.43, I 2  = 96%) and renal phosphate reabsorption (mean difference 1.22 mg/dl, 95% confidence interval 0.70 to 1.74, I 2 93%). Burosumab treatment improved overall clinical and laboratory findings in patients with X-linked hypophosphatemia., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Purpose: This aim of this study was to assess the possible association between diurnal oscillations and biochemical markers associated with calcium homeostasis. This included the markers parathyroid hormone (PTH), total calcium, total alkaline phosphatase, phosphate, and 25-hydroxyvitamin D (25-OH-D). By examining the influence of circadian rhythms on these parameters, the study aimed to deepen the understanding of calcium metabolism dynamics and its clinical implications., Patients and Methods: Blood samples from 24 Caucasian male volunteers aged 20 to 40 (mean age 26) with normal pulse, blood pressure, and BMI were analyzed for biochemical markers related to calcium homeostasis. Data was obtained from the Bispebjerg study of diurnal variations. Blood samples were collected every three hours over a 24-hour period. Patients were fasting from 22:00 to 09:00. The participants spent 24 h in the hospital ward, receiving regular meals and engaging in low-intensity activities. They experienced 15 h of daylight and 9 h of complete darkness during sleep. Diurnal oscillations were analyzed using cosinor analysis with statistical significance set at p  < 0.05., Results: Total calcium, phosphate, and PTH exhibited significant diurnal variations. Total calcium and PTH were inversely synchronized while PTH and phosphate oscillated in synchronization. The three parameters showed relatively large amplitude/reference range ratios from 25.4% to 41.5%., Conclusion: This study found notable fluctuations in total calcium, phosphate, and PTH levels over a 24-hour cycle, while 25-OH-D and total alkaline phosphatase remained consistent. It highlights the importance of considering sampling times for total calcium, PTH, and phosphate in clinical settings.

Background: Numerous studies have explored the role of kidney replacement therapy (KRT) in phosphorus (P) control among prevalent hemodialysis (HD) patients. However, whether the reduction of P achieved during KRT affects parathyroid hormone (PTH) levels is still a matter of debate., Methods: We conducted a retrospective observational study on the prevalent HD population at the Division of Nephrology, University Hospital of Verona, from January to December 2022. We Included clinically stable adult patients undergoing HD for over 6 months, with multiple recorded visits during the follow-up. Demographic, clinical, laboratory, and medication data were collected. Time-varying variables were updated at each study visit. The primary outcome of interest was PTH levels. The absolute intra-HD change in P (intra-HD ∆P), defined as the difference between pre- and post-HD P levels, served as the main exposure. Multivariable adjusted linear mixed models were used to investigate the relationship between intra-HD ∆P and PTH levels., Results: A total of 211 patients contributed to 904 study visits. A significant and positive relationship was observed between intra-HD ∆P and pre-HD P (β = 0.76, 95% CI 0.75, 0.78, p < 0.001) and urea reduction ratio (β = 0.38, 95% CI 0.35, 0.41; p < 0.001). An increase in intra-HD ∆P was significantly and independently associated with low PTH levels (β = - 0.16, 95% CI - 0.30, -0.03; p = 0.020)., Conclusions: The extent of intra-HD P reduction significantly correlates with low PTH levels. Strategies focused on optimizing or enhancing depurative efficiency in KRT can exert a substantial impact on managing positive phosphorus balance and secondary hyperparathyroidism. The assessment of intra-HD P reduction may play a pivotal role in the management and follow-up of secondary hyperparathyroidism in HD patients., (© 2024. The Author(s) under exclusive licence to Italian Society of Nephrology.)

The mitochondrial phosphate carrier is critical for adenosine triphosphate synthesis by serving as the primary means for mitochondrial phosphate import across the inner membrane. Variants in the SLC25A3 gene coding mitochondrial phosphate carrier lead to failure in inorganic phosphate transport across mitochondria. The critical dependence on mitochondria as an energy source is especially evident in tissues with high-energy demands such as the heart, muscle; defects in the mitochondrial energy production machinery underlie a wide range of primary mitochondrial disorders that present with cardiac and muscle diseases. The characteristic clinical picture of a prominent early-onset hypertrophic cardiomyopathy and lactic acidosis may be an indication for analysis of the SLC25A3 gene. Here, described a patient with suspicion of infantile Pompe disease due to involvement of heart and muscle and high-level of plasma creatinine kinase but finally diagnosed mitochondrial phosphate-carrier deficiency., (© 2024 Wiley Periodicals LLC.)

Objective: Hyperphosphatemia is a common complication in patients with kidney failure, despite the use of phosphate binders. Vitamin B3, either in the form of niacin or niacinamide (NAM), shows potential as "add-on" treatment to reduce serum phosphate concentrations in this population. NAM seems to lack many of the side effects that are observed with niacin. The aim of this study was to investigate whether NAM is an effective and acceptable treatment in reducing serum phosphate concentrations in patients with kidney failure., Methods: DiaNia was a double-blind placebo-controlled randomized crossover trial, comparing NAM (250-500 mg/day) to placebo as "add-on" treatment to an individual treatment with approved phosphate binders for 12 weeks in patients receiving hemodialysis. The primary outcome was serum phosphate concentrations, and the secondary outcomes were platelet counts as well as drop-outs due to side effects. Data were analyzed using both per-protocol and intention-to-treat analyses., Results: Mean age of the per-protocol population (n = 26) was 63.6 ± 17.2 years and 53.8% were men. NAM treatment significantly reduced serum phosphate with 0.59 mg/dL (p = .03). Linear mixed-effects models demonstrated superiority of 12 weeks NAM over 12 weeks placebo with a between-treatment difference of 0.77 mg/dL (95% CI 0.010, 1.43; P = .03). Similar results, although not significant, were found in the intention-to-treat population. We found no between-treatment differences in platelet counts and during the NAM treatment we observed 3 drop-outs due to side effects (8.6%)., Conclusion: NAM is effective in reducing serum phosphate concentrations in patients with kidney failure receiving hemodialysis. In addition, NAM is well-tolerated and seems not to increase the risk of thrombocytopenia. Thus, NAM can be valuable as "add-on" treatment to combat hyperphosphatemia in patients with kidney failure. However, more research in larger populations is needed to confirm this., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

This systematic review was performed to understand better the myriad presentations, various therapeutic options, response to therapy, and its clinical outcomes in hyperphosphatemic tumoral calcinosis (HTC). Full texts were selected according to strict inclusion criteria. All case reports of HTC wherein baseline phosphate was measured, treatment offered was mentioned, and information on follow-up and response to therapy that were available were included. A total of 43 of 188 eligible studies (N = 63 patients) met the inclusion criteria. A list of desired data was extracted and graded for methodological quality. A total of 63 individuals (Males = 33) were included from the 43 eligible case studies. The median age of the patients was 18 (IQR 8-32) years. The most frequently involved sites were the hip/gluteal region (34/63; 53.9%) followed by the elbow/forearm (26/63; 41.2%), and the shoulder (18/63; 28.5%). Three patients had conjunctival calcific deposits. The mean (SD) phosphate was 6.9 (1.1) mg/dL. Among the subjects, 36/63 (57.1%) underwent surgical excision with some form of medical therapy. Two patients underwent only surgical excision (2.1%). One patient was maintained on follow-up (1.6%) and 24/63 (38.1%) patients were treated with medical measures. The median (IQR) follow-up duration was 3 (1-9) years. Regression or reduction in lesion size was reported in 19/63 (30.2%) subjects; 20/63 (31.7%) showed progression, 24/63 (38.1%) had features of stable disease, and mortality was reported in 3 patients (4.7%). We report for the first time a detailed description of the clinical and therapeutic response of HTC. A combination of medical measures aimed at lowering serum phosphate appears to be the cornerstone of treatment, although clinical responses may vary., (© 2024. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Chronic kidney disease (CKD) is associated with various pathologic changes, including elevations in serum phosphate levels (hyperphosphatemia), vascular calcification, and skeletal muscle atrophy. Elevated phosphate can damage vascular smooth muscle cells and cause vascular calcification. Here, we determined whether high phosphate can also affect skeletal muscle cells and whether hyperphosphatemia, in the context of CKD or by itself, is associated with skeletal muscle atrophy. As models of hyperphosphatemia with CKD, we studied mice receiving an adenine-rich diet for 14 weeks and mice with deletion of Collagen 4a3 ( Col4a3 -/- ). As models of hyperphosphatemia without CKD, we analyzed mice receiving a high-phosphate diet for three and six months as well as a genetic model for klotho deficiency ( kl / kl ). We found that adenine, Col4a3 -/- , and kl / kl mice have reduced skeletal muscle mass and function and develop atrophy. Mice on a high-phosphate diet for six months also had lower skeletal muscle mass and function but no significant signs of atrophy, indicating less severe damage compared with the other three models. To determine the potential direct actions of phosphate on skeletal muscle, we cultured primary mouse myotubes in high phosphate concentrations, and we detected the induction of atrophy. We conclude that in experimental mouse models, hyperphosphatemia is sufficient to induce skeletal muscle atrophy and that, among various other factors, elevated phosphate levels might contribute to skeletal muscle injury in CKD.

Background: Tenofovir disoproxil fumarate (TDF) is often used in treating pregnant women living with HIV. Third-trimester TDF exposure is associated with a 12% reduction in bone mineral content in HIV-exposed uninfected (HEU) neonates. The potential mechanisms underlying this observation are unknown., Methods: The TDF study enrolled newborns of gestational age ≥36 weeks from the Surveillance Monitoring for Antiretroviral Therapy and Toxicities study based on in utero TDF exposure (TDF use ≥8 weeks in the third trimester vs none). Blood and urine samples were collected cross-sectionally within 30 days of birth to assess renal function (serum creatinine, serum phosphate, eGFR, percent tubular reabsorption of phosphate [PTRP]), and bone turnover (serum parathyroid hormone, 25-OH vitamin D [25(OH)D], and urinary cross-linked N-telopeptide of type 1 collagen). For each biomarker, a LOESS plot was fit using values at age at specimen collection; regression lines over age were fit among samples collected from 4 to 30 days, to compare slopes by TDF exposure., Results: Among 141 neonates, 77 were TDF-exposed and 64 TDF-unexposed. Between age 4 and 30 days, PTRP decreased more rapidly in the TDF-exposed compared to the unexposed group with slopes of -0.58 vs -0.08/day (difference -0.50/day [95% CI -0.88, -0.11]). Slopes for 25(OH)D were similar in both groups, but serum levels were lower in TDF-exposed neonates (median [IQR]: 22 [19, 29] vs 26 [22, 37] ng/mL). No differences were observed for other biomarkers., Conclusions: Third-trimester in utero exposure to TDF is associated with increased urinary loss of phosphate and lower serum concentrations of 25(OH)D in HEU neonates., (© The Author(s) 2024. Published by Oxford University Press on behalf of The Journal of the Pediatric Infectious Diseases Society. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

Target values for 25-hydroxy vitamin D and 1,25(OH) 2 D or 1,25-dihydroxy vitamin D remain a topic of debate among clinicians. We analysed data collected from December 2012 to April 2020 from two cohorts. Cohort A, comprising 455,062 subjects, was used to investigate the relationship between inflammatory indicators (white blood cell [WBC] count and C-reactive protein [CRP]) and 25(OH)D/1,25(OH) 2 D. Cohort B, including 47,778 subjects, was used to investigate the connection between 25(OH)D/1,25(OH) 2 D and mineral metabolism markers (phosphate, calcium, and intact parathyroid hormone [iPTH]). Quadratic models fit best for all tested correlations, revealing U-shaped relationships between inflammatory indicators and 25(OH)D and 1,25(OH) 2 D. Minimal CRP and WBC counts were observed at 1,25(OH) 2 D levels of 60 pg/mL and at 25(OH)D levels of 32 ng/mL, as well as of 42 ng/mL, respectively. iPTH correlated inversely with both 1,25(OH) 2 D and 25(OH)D, while phosphate as well as calcium levels positively correlated with both vitamin D forms. Calcium-phosphate product increased sharply when 25(OH)D was more than 50 ng/mL, indicating a possible risk for vascular calcification. Multiple regression analyses confirmed that these correlations were independent of confounders. This study suggests target values for 25(OH)D between 30-50 ng/mL and for 1,25(OH) 2 D between 50-70 pg/mL, based particularly on their associations with inflammation but also with mineral metabolism markers. These findings contribute to the ongoing discussion around ideal levels of vitamin D but require support from independent studies with data on clinical endpoints.

Objective: To describe serum fibroblast growth factor 23 (FGF-23) concentrations in young adult cats with remnant kidney model-induced chronic kidney disease (CKD) and to evaluate the effects of orally administered aluminum hydroxide (ALOH) on serum phosphate and FGF-23 concentrations in these cats., Animals: 17 adult, purpose-bred cats with induced CKD and 13 healthy, age-matched cats., Methods: A prospective, randomized study. Cats with induced CKD fed a wet renal diet received treatment with ALOH (90 mg/kg/d, PO) on days 0 to 42 and no treatment on days 43 to 84 (treatment group, n = 9) or no treatment on days 0 to 84 (control group, n = 8). Standard serum and urine biochemical analyses and several parameters reflective of calcium-phosphate balance, including serum parathyroid hormone and FGF-23 concentrations, were evaluated at baseline and various time points, including days 42 and 84. Age-matched, healthy, community-owned cats underwent similar evaluations at a single time point. Baseline data from CKD cats were compared to those of healthy cats. Longitudinal data from CKD cats were compared over time., Results: Serum phosphate, total and ionized calcium, and FGF-23 concentrations were significantly higher in CKD cats at baseline relative to healthy cats (all P ≤ .009). Serum phosphate concentration did not change significantly over time in either CKD group; however, FGF-23 concentrations significantly increased over time in the control group (P < .02) but not the treatment group (P = .059)., Clinical Relevance: Aluminum hydroxide did not reduce serum phosphate or FGF-23 concentrations in this small study of cats with induced CKD chronically eating a phosphate-restricted diet.

This study aimed to evaluate the incidence and risk factors associated with refeeding syndrome (RFS) in preterm infants (≤32 weeks gestational age) during their first week of life. Infants (gestational age ≤ 32 weeks; birth weight < 1500 g) who were admitted to the neonatal intensive care unit (NICU), level III, and received parenteral nutrition between January 2015 and April 2024 were retrospectively evaluated. Modified log-Poisson regression with generalized linear models and a robust variance estimator was applied to adjust the relative risk of risk factors. Of the 760 infants identified, 289 (38%) developed RFS. In the multivariable regression analysis, male, intraventricular hemorrhage (IVH), and sodium phosphate significantly affected RFS. Male infants had significantly increased RFS risk (aRR1.31; 95% CI 1.08-1.59). The RFS risk was significantly higher in infants with IVH (aRR 1.71; 95% CI 1.27-2.13). However, infants who received higher sodium phosphate in their first week of life had significantly lower RFS risk (aRR 0.67; 95% 0.47-0.98). This study revealed a notable incidence of RFS among preterm infants aged ≤32 gestational weeks, with sex, IVH, and low sodium phosphate as significant risk factors. Refined RFS diagnostic criteria and targeted interventions are needed for optimal management.

Introduction: Several calcimimetics, other than cinacalcet, are commercially available; however, their effects on calcium and phosphate levels have not yet been fully studied. We conducted a systematic review and meta-analysis of randomized controlled trials to evaluate the impact of calcimimetics on the management of serum calcium and phosphate levels in patients with secondary hyperparathyroidism undergoing dialysis., Methods: A systematic literature search through October 2023 and a meta-analysis were conducted on the effects of upacicalcet, etelcalcetide, evocalcet, and cinacalcet on serum calcium and phosphate levels in patients with secondary hyperparathyroidism undergoing dialysis; we searched PubMed, Ovid MEDLINE, and the Cochrane Central Register of Controlled Trials, and 21 studies comprising 6371 patients undergoing dialysis were included., Results: Participants treated with calcimimetics had lower serum calcium and phosphate levels than placebo., Conclusion: Calcimimetics significantly reduced serum calcium and phosphate levels compared to placebo in patients with secondary hyperparathyroidism undergoing dialysis, independent of therapeutic strategy or concomitant vitamin D treatment., (© 2024 International Society for Apheresis and Japanese Society for Apheresis.)

Purpose: Frailty is common in older patients with chronic kidney disease (CKD) and has been considered an independent risk factor for adverse clinical outcomes in this population. CKD-associated mineral and bone metabolism (CKD-MBD) increases energy expenditure and causes malnutrition and inflammation leading to frailty. We investigated whether CKD-MBD markers and energy metabolism are associated with frailty in patients with advanced CKD on conservative management., Methods: In this cross-sectional study, we investigated factors associated with frailty in a sample of 75 patients ≥ 65 years, with stage 4 or 5 CKD. Collected data included age, sex, body mass index, physical activity status, educational level, Charlson Comorbidity Index, and laboratory markers. Frailty was evaluated according to Fried's classification., Results: Frailty was observed in 51.3% and pre-frailty in 47.3%. The frail population was significantly older, with a high proportion of females, more inactive, had lower educational levels, spent a long time sitting throughout the day, and had higher phosphate and fibroblast growth factor 21 (FGF-21). In the multivariate logistic analysis age (odds ratio 1.13, p = 0.026) and phosphate (odds ratio 3.38, p = 0.021) remained independently associated with frailty., Conclusion: Serum phosphate seems to be a toxin associated with the frailty phenotype in older patients with CKD. Whether strategies to decrease serum phosphate would reduce the risk of frailty in this population deserves further evaluation., (© 2024. The Author(s), under exclusive licence to Springer Nature B.V.)

Background and Objective: X-linked hypophosphatemic rickets (XLH) is due to loss-of-function mutations in the phosphate-regulating endopeptidase homologue on the X chromosome (PHEX) that lead to increased fibroblast growth factor 23 (FGF23) production. FGF23 excess causes renal phosphate wasting and insufficient 1,25-dihydroxyvitamin D (1,25(OH) 2 D) synthesis with reduced intestinal phosphate absorption, ultimately resulting in chronic hypophosphatemia. Children with XLH show typical skeletal lesions of rickets, deformities of the lower limbs, stunted growth with disproportionate short stature, bone pain, and physical dysfunctions. Burosumab, a fully human IgG1 monoclonal antibody that binds to FGF23 to inhibit its activity, is more effective to improve the biochemical and clinical signs of XLH than conventional treatment with phosphate supplements and vitamin D active metabolites. Data on adolescents with XLH during the transition period to young adulthood are few. In this prospective case series, we aimed to assess safety and efficacy of burosumab in adolescents with XLH who discontinued long-term conventional therapy., Methods: Five Caucasian adolescents (4 males, 1 female; mean age 15.4 ± 1.5 years) with XLH were recruited and switched from conventional treatment to burosumab (0.8-1.2 mg/kg, s. c. QW2). Burosumab was continued for 12-48 months and, once discontinued, patients were followed-up for 6-12 months. In all patients, serum calcium, phosphate, alkaline phosphatase (ALP), parathyroid hormone (PTH), and 1,25(OH) 2 D levels, and renal tubular reabsorption of phosphate (TmP/GFR) values were assessed at entry and during burosumab. Intact FGF23 plasma levels were measured at entry. Patient-reported outcomes (PROs) were assessed at entry and every 3-6 months to evaluate the impact of low extremity pain, stiffness, and difficulties performing daily activities., Results: At entry, all patients showed hypophosphatemia, increased intact FGF23 levels, reduced TmP/GFR, insufficient 1,25(OH) 2 D levels, and in four out of five increased ALP levels. Two patients had radiological signs of rickets. During burosumab, all patients showed a significant increase in serum phosphate and 1,25(OH) 2 D levels, and in TmP/GFR values (P < 0.05 - P < 0.0001). Serum ALP levels significantly declined (P < 0.05) to normal values. No changes of serum calcium and PTH levels (PNS) were found during burosumab. PROs significantly improved (P < 0.02 - P < 0.0001) in all patients. Four patients discontinued burosumab when they turned 18 or 19, whereas one continued the treatment since he was still younger than 18 during the study period. Four patients who suspended burosumab showed a rapid decline in serum phosphate and 1,25(OH) 2 D levels and in TmP/GFR values; serum ALP levels increased, and PROs progressively worsened with a significant reduction in quality of life. These consequences were not observed in the patient who continued burosumab treatment., Discussion: Our data showed that conventional treatment improved only in part the signs and symptoms of XLH. Burosumab was well tolerated and was effective in improving phosphate metabolism, bone health, and PROs. All the benefits of burosumab were lost after its discontinuation. These results suggested that continuing burosumab is required to achieve and maintain the clinical benefits of the treatment during the transition to young adulthood in patients with XLH., Competing Interests: Declaration of competing interest The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2024. Published by Elsevier Masson SAS.)

Purpose of Review: Fibroblast growth factor 23 (FGF23) is a hormone to reduce blood phosphate concentration. Excessive actions of FGF23 induce FGF23-related hypophosphatemic disorders, such as X-linked hypophosphatemic rickets (XLH) and tumor-induced osteomalacia (TIO). We will summarize recent advances in the diagnosis and treatment of FGF23-related hypophosphatemic disorders., Recent Findings: The measurement of blood FGF23 is useful to make a diagnosis of FGF23-related hypophosphatemic disorders. It was reported that many patients with FGF23-related hypophosphatemic disorders, especially TIO, were misdiagnosed, therefore, it is necessary to enhance the awareness of these diseases. A novel method to inhibit excessive actions of FGF23 by a human monoclonal antibody for FGF23, burosumab, has been approved in several countries. In more long-term observation than clinical trials, burosumab has also been shown to improve biochemical abnormalities and symptoms of rickets/osteomalacia. Following these advances, several registries and consensus recommendations on FGF23-related hypophosphatemic disorders, especially XLH, have been established in each country or region., Summary: Further long-term effects of burosumab and the precise mechanism of FGF23 overproduction in patients with FGF23-related hypophosphatemic disorders need to be clarified in the future studies., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Objectives: Acute pancreatitis (AP) is a complex disease representing a significant portion of gastrointestinal-related hospitalizations in the U.S. Understanding risk factors of AP might provide attractive therapeutic targets. We evaluated hypophosphatemia a prognostic marker in AP., Methods: We performed a retrospective review of electronic health records of patients with AP from 01/ 01/2012-12/31/2021 at Cedars-Sinai Medical Center with serum phosphate measured within 48 hours of admission. Multivariable logistic regression modeling was used to evaluate associations with ICU admission and AP severity. Multivariable log-linear modeling was employed to examine associations with length of stay (LOS)., Results: Of 1526 patients admitted for AP, 33% (499) had a serum phosphate level measured within 48 hours. Patients with hypophosphatemia were more likely to have ICU admission (adjusted odds ratio (AOR) = 4.57; 95% confidence interval (CI): 2.75-7.62; P < 0.001), have a longer hospital stay (log-LOS = 0.34; SE; 0.09; 95% CI: 0.17-0.52; P < 0.001), and have moderate or severe AP (AOR = 1.80; 95% CI: 1.16-2.80; P < 0.001) compared with those without hypophosphatemia., Conclusion: Serum phosphate is infrequently measured in patients with AP and shows promise as an early prognostic marker for outcomes of AP., Competing Interests: The content is solely the responsibility of the authors and does not necessarily represent the official views of the Department of Defense. The authors declare no conflict of interest., (Copyright © 2024 Wolters Kluwer Health, Inc. All rights reserved.)

Background: Hyperphosphatemia occurs universally in end-stage renal disease(ESRD), and the attainment of target serum phosphate levels remains suboptimal with currently available phosphate binders. This meta-analysis aimed to evaluate the efficacy and safety of tenapanor in end-stage renal disease patients with hyperphosphatemia., Methods: Data sources included PubMed, Embase, Web of Science, and Cochrane Library. This meta-analysis included randomized controlled trials evaluating both the efficacy of tenapanor in reducing serum phosphate levels and its safety profile. The risk of bias was assessed using the Cochrane risk of bias tool for RCTs. The GRADE system was used to assess the overall certainty of evidence. A meta-analysis was carried out by using fixed effects ( I 2 values < 50%) or random effects ( I 2 values ≥ 50%) models to calculate MD with 95% CI for continuous outcome variables and RR with 95% CI for dichotomous variables. Publication bias was evaluated using funnel plots., Results: A total of seven RCTs involving 877 individuals were included. The pooling analysis demonstrates that the reduction in mean serum phosphorus levels in the tenapanor group was significantly greater than that in the placebo group [MD= -1.06 mg/dl, 95% CI (-1.59, -0.53); I 2  = 83%, p  < 0.0001]. The proportion of patients achieving a serum phosphorus level of < 5.5 mg/dL, along with the incidence of any adverse events (AEs) and gastrointestinal disorders, was higher in the tenapanor group compared to the placebo group., Conclusion: Tenapanor has the potential to significantly reduce serum phosphorus levels and enhance the rate of achieving target levels compared to placebo, all while maintaining an acceptable safety and tolerability profile., Registration: PROSPERO registration number CRD42024544531.

Introduction: Excess growth hormone (GH) secretion in acromegaly has a major impact on mineral balance and serum phosphate levels. However, the clinical utilization of serum phosphate levels as a marker for long-term disease outcomes in acromegaly has not been evaluated., Methods: This is a retrospective study of patients with acromegaly who were followed in a tertiary center. Data were retrieved on patient characteristics, endocrine and biochemical evaluation, and tumor parameters. Comparisons were performed by measuring baseline phosphate levels and conducting correlation analysis and multivariable logistic regression., Results: Sixty-one patients were followed for 4.5 years (range 1-21). Patients with hyperphosphatemia (> 4.5 mg/dl) at baseline had larger adenomas (15.0 mm [8.0, 47.0] vs. 10.0 mm [3.0, 24.0], p = 0.001), a rate chance of invasive adenoma (16 [80.0%] vs. 14 [46.7%], p = 0.02), and lower serum cortisol levels (226.0 nmol/l [27.6, 516.0] vs. 294.0 nmol/l [32.0, 610.0], p = 0.02). Baseline serum phosphate levels positively correlated with IGF-1 levels (r = 0.43, p = 0.003) and negatively correlated with morning plasma cortisol levels (r = -0.46, p = 0.002). Regarding long-term impact, baseline phosphate levels correlated with the number of pituitary axes involved 6 months after diagnosis (r-0.34, p = 0.01). In multivariable analysis, baseline plasma phosphate levels were independently associated with risk for disease progression/recurrence (odds ratio [OR] 9.66, 95% confidence interval [CI] 1.5, 105.9, p = 0.03) and for invasive adenoma (OR 6.21, 95% CI 1.6, 28.7, p = 0.01)., Conclusion: Elevated pretreatment serum phosphate levels are associated with a greater risk of disease persistence and recurrence and with altered pituitary function in patients with acromegaly., (© 2024. The Author(s), under exclusive licence to Hellenic Endocrine Society.)

Burosumab is indicated for treatment of a rare bone disease, X-linked hypophosphatemia (XLH). The aim of this analysis was to evaluate the relationship between a treatment response biomarker and patient-reported outcomes (PROs). Longitudinal data for PROs were obtained from adults with XLH from a phase III study. Individual rich time profiles of the biomarker, serum phosphate were simulated using a prior population pharmacokinetic-pharmacodynamic model to calculate serum phosphate exposure metrics for each 28-day treatment cycle, which were then merged with PROs data. Item response theory parameters were first estimated to map a latent variable, ψ, that is, disability score, relative to baseline. Next, the relationships between serum phosphate exposures and ψ were modeled using a nonlinear mixed-effect (NLME) modeling approach. A combined item response theory-NLME model with average serum phosphate as a predictor of ψ described PROs data well. The model estimates suggested 28%, 31%, and 25% reduction in Western Ontario and McMaster Universities Osteoarthritis Index, brief pain inventory, and brief fatigue inventory scores, respectively, with every unit increase in average serum phosphate from the lower limit of normal (2.5 mg/dL). Additionally, a time effect of ~ 0.08% improvements each week was estimated. The analysis suggested that burosumab treatment-induced improvements in serum phosphate levels are associated with improvements in PROs in adults with X-linked hypophosphatemia. The analyses confirmed the importance of prolonged serum phosphate level correction in adult patients with XLH. These results can be useful to guide the design of further studies and to design treatment optimization strategies., (© 2024 The Author(s). Clinical Pharmacology & Therapeutics published by Wiley Periodicals LLC on behalf of American Society for Clinical Pharmacology and Therapeutics.)

Objective: Compare the efficacy and safety of daily versus fortnightly oral vitamin D 3 in treating symptomatic vitamin D deficiency in children aged 1-10 years., Design: Open labelled randomized controlled trial., Patients: Eighty children with symptomatic vitamin D deficiency were randomized into group daily (D) and group bolus (B) [40 in each group] to receive oral vitamin D 3 , 4000 IU daily or 60,000 IU fortnightly for 12 weeks respectively. Both groups received daily oral calcium of 500 mg/day., Measurements: Serum calcium (Ca), phosphate (P), alkaline phosphatase (ALP), 25-hydroxy cholecalciferol (25(OH)D), parathyroid hormone (PTH) levels, urine calcium: creatinine ratio and radiological score were assessed at baseline, 4 weeks and 12 weeks. At the end of 12 weeks, 74 children were available for evaluation of the efficacy and safety of both regimens., Results: Both regimens led to a significant increase in Ca and P levels and a fall in ALP and PTH levels from baseline to 4 and 12 weeks of therapy, with no intergroup difference. At 4- and 12-week assessments, all children in both treatment arms achieved 25(OH)D level in sufficiency range, with no significant difference in their geometric mean. Both regimens were associated with asymptomatic transient hypercalcemia [group D-51.4% vs. group B-34.3%; p -0.14] and hypercalciuria (5.7%) in group D that resolved spontaneously on follow-up., Conclusions: Daily and fortnightly oral vitamin D 3 in similar cumulative doses are efficacious for treating symptomatic vitamin D deficiency in children (1-10 years). Treated children should be monitored for serum 25(OH)D, Ca and urinary calcium creatinine ratio., (© 2024 John Wiley & Sons Ltd.)

Aims: Bariatric surgery induces several micronutrient deficiencies that require supplementation. For iron, parenteral infusions are usually preferred over oral supplementation. Ferric carboxymaltose infusion has been associated with hypophosphataemia, mostly transient and asymptomatic. However, in some cases, ferric carboxymaltose-induced hypophosphataemia may persist for weeks to months and may induce muscle weakness, osteomalacia and bone fractures. The aim of this study was to identify possible predictors of a clinically relevant decrease in serum phosphate after ferric carboxymaltose infusion in patients with previous Roux-en-Y gastric bypass., Methods: Patients with previous Roux-en-Y gastric bypass who received ferric carboxymaltose infusions between January 2018 and September 2019 and had recorded phosphataemia before and after ferric carboxymaltose infusion at the Lausanne University Hospital, Lausanne, Switzerland, were studied retrospectively. A multiple linear regression model was built with delta phosphataemia as the outcome to investigate the factors related to magnitude of serum phosphate lowering., Results: Seventy-seven patients (70 females and 7 males) with previous Roux-en-Y gastric bypass were studied. Mean age (SD) was 43.2 (10.7) years and median BMI was 30.9 kg/m2 (IQR 27.9-36.4). Sixty-eight patients (88.3%) received an infusion of 500 mg ferric carboxymaltose and 9 patients (11.7%) received 250 mg ferric carboxymaltose. Forty-nine patients (63.6%) developed hypophosphataemia (<0.8 mmol/l) after ferric carboxymaltose infusion. Median plasma phosphate significantly decreased by 0.33 mmol/l (IQR 0.14-0.49) (p<0.0001). Multiple linear regression identified the ferric carboxymaltose dose as the only risk factor significantly associated with the magnitude of serum phosphate lowering, with an additional mean loss of 0.26 mmol/l with a 500 mg infusion compared to a 250 mg infusion (p = 0.020)., Conclusion: Ferric carboxymaltose infusions substantially decreased plasma phosphate levels in patients with previous Roux-en-Y gastric bypass. Compared to a dose of 250 mg, infusion of a dose of 500 mg ferric carboxymaltose decreased the plasma phosphate further in this population.

Background: Data is limited on the prevalence of hypophosphatemia in general hospitalized patients, and its association with length of hospital stay (LOS) and mortality remained unclear. We aimed to investigate the prevalence of admission phosphate abnormality and the association between serum phosphate level and length of hospital stay and all-cause mortality in adult patients., Methods: This was a multi-center retrospective study based on real-world data. Participants were classified into five groups according to serum phosphate level (inorganic phosphorus, iP) within 48 h after admission: G1, iP < 0.64 mmol/L; G2, iP 0.64-0.8 mmol/L; G3, iP 0.8-1.16 mmol/L; G4, iP 1.16-1.45 mmol/L; and G5, iP ≥ 1.45 mmol/L, respectively. Both LOS and in-hospital mortality were considered as outcomes. Clinical information, including age, sex, primary diagnosis, co-morbidity, and phosphate-metabolism related parameters, were also abstracted from medical records., Results: A total number of 23,479 adult patients (14,073 males and 9,406 females, aged 57.7 ± 16.8 y) were included in the study. The prevalence of hypophosphatemia was 4.74%. An "L-shaped" non-linear association was determined between serum phosphate level and LOS and the inflection point was 1.16 mmol/L in serum phosphate level. Compared with patients in G4, patients in G1, G2 or G3 were significantly associated with longer LOS after full adjustment of covariates. Each 0.1 mmol/L decrease in serum phosphate level to the left side of the inflection point led to 0.64 days increase in LOS [95% confidence interval (CI): 0.46, 0.81; p for trend < 0.001]. But there was no association between serum phosphate and LOS where serum levels of phosphate ≥ 1.16 mmol/L. Multivariable logistic regression analysis showed that adjusted all-cause in-hospital mortality was 3.08-fold greater in patients in G1 than those in G4 (95% CI: 1.52, 6.25; p for trend = 0.001). Similarly, no significant association with either LOS or mortality were found in patients in G5, comparing with G4., Conclusions: Hypophosphatemia, but not hyperphosphatemia, was associated with LOS and all-cause mortality in adult inpatients. It is meaningful to monitor serum levels of phosphate to facilitate early diagnosis and intervention., (© 2024. The Author(s).)

Purpose: COPD patients frequently have abnormal serum phosphorus levels. The objective of this study was to examine the correlation between serum phosphorus levels with hospital and 90-day mortality in critically ill patients with COPD., Patients and Methods: The MIMIC IV database was used for this retrospective cohort analysis. We extracted demographics, vital signs, laboratory tests, comorbidity, antibiotic usage, ventilation and scoring systems within the first 24 hours of ICU admission. Restricted cubic splines and multivariate cox regression analysis models were used to evaluate the connection between serum phosphorus with hospital and 90-day mortality. We assessed and classified various factors including gender, age, renal disease, severe liver disease, the utilization of antibiotics and congestive heart failure., Results: We included a total of 3611 patients with COPD, with a median age of 70.7 years. After adjusting for all other factors, we observed a significant positive association between serum phosphate levels with both hospital mortality (HR 1.19, 95% CI: 1.07-1.31, p<0.001) and 90-day mortality (HR 1.15, 95% CI: 1.06-1.24, p<0.001). Compared to the medium group (Q2 ≥3.15, <4.0), the adjusted hazard ratios for hospital mortality were 1.47 (95% CI: 1.08-2, p=0.013), and 1.31 (95% CI: 1.06-1.61, p=0.013) for 90-day mortality in the high group (Q3≥4.0). Hospital mortality decreased at serum phosphate levels below 3.8 mg/dl (HR 0.664, 95% CI: 0.468-0.943, p=0.022), but increased for both hospital (HR 1.312, 95% CI: 1.141-1.509, p<0.001) and 90-day mortality (HR 1.236, 95% CI: 1.102-1.386, p<0.001) when levels were above 3.8 mg/dl. Subgroup and sensitivity analyses yielded consistent results., Conclusion: In critical ill COPD patients, this study demonstrated a non-linear association between serum phosphate levels and both hospital and 90-day mortality. Notably, there was an inflection point at 3.8 mg/dl, indicating a significant shift in outcomes. Future prospective research is necessary to validate this correlation., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2024 Du et al.)

Objectives: To study the diagnosis, treatment, and complications of hypophosphatemic rickets (HR) in children, explore effectiveness evaluation indicators for the disease, and understand the pattern in height growth among these patients., Methods: A retrospective analysis of the initial clinical data and five-year follow-up data of 85 children with HR treated at Children's Hospital of Nanjing Medical University from January 2008 to December 2022., Results: Among the 85 children with HR, there were 46 males (54%) and 39 females (46%). The age at initial diagnosis ranged from 6 months to 13 years and 9 months, with a median age of 2.75 years. The average height standard deviation score was -2.0±1.1. At initial diagnosis, children exhibited reduced blood phosphate levels and elevated alkaline phosphatase (ALP), with 99% (84/85) presenting with lower limb deformities. The positive rate for PHEX gene mutations was 93% (55/59). One year post-treatment, there was a significant reduction in ALP levels and the gap between the lower limbs ( P <0.05). The fastest height growth occurred in the first year after treatment, at 8.23 cm/year, with a peak height velocity (PHV) phase lasting about two years during puberty. The height increased by 9-20 cm in male children during the PHV stage and 10-15 cm in female children. Major complications included nephrocalcinosis and hyperparathyroidism. The incidence rate of nephrocalcinosis in the first year after treatment was 55% (22/40), which increased with the duration of the disease ( P <0.001); an increased urinary phosphate/creatinine ratio was positively associated with a higher risk of nephrocalcinosis ( OR =1.740, P <0.001). The incidence of hyperparathyroidism in the first year after treatment was 64% (27/42)., Conclusions: For children presenting with lower limb deformities, short stature, and slow growth, early testing for blood levels of phosphate, calcium, and ALP, along with imaging examinations of the lower limbs, can aid in the early diagnosis of HR. Genetic testing may be utilized for definitive confirmation when necessary. ALP combined with improvements in skeletal deformities and annual height growth can serve as indicators of therapeutic effectiveness for HR. Compared to normal children, children with HR demonstrate a lower height increase during the PHV phase, necessitating close follow-up and timely adjustment of treatment plans Citation:Chinese Journal of Contemporary Pediatrics, 2024, 26(7): 677-682 .

Background: Adequate levels of calcium, phosphate and Vitamin D are essential for bone physiology and growth, as well as preventing some common childhood illnesses. This study aimed to determine the prevalence of the deficiencies of these nutrients and factors affecting their serum levels in Nigerian children., Methods: This was a cross-sectional study that involved 220 apparently healthy children aged 6-24 months in Ikenne Local Government Area of Ogun State, Nigeria. Serum calcium and phosphate were assayed using the calorimetric method, while Vitamin D (25-OH Vitamin D) was assayed with ELISA., Results: The mean (±standard deviation [SD]) serum Vitamin D level was 55.07 ± 16.53 ng/ml, while the mean (±SD) serum calcium and phosphate were 2.27 ± 0.13 mmol/l and 1.28 ± 0.18 mmol/l, respectively. Eleven (5%) of the children had hypovitaminosis D, 23 (10.5%) had hypocalcaemia and 12 (5.5%) had hypophosphataemia. Factors found to be significantly associated with hypovitaminosis D included low consumption of milk and the use of a hijab veil, while malnutrition (both undernutrition and overnutrition) was significantly associated with hypocalcaemia., Conclusion: The prevalence levels of hypovitaminosis D and hypophosphataemia were low, while hypocalcaemia was more common. Low milk consumption and use of a hijab veil were risk factors for hypovitaminosis D, while malnutrition was a risk factor for hypocalcaemia. Malnourished children, especially overnourished ones, should be routinely screened for hypocalcaemia because of its high prevalence among them., (Copyright © 2024 Copyright: © 2024 Nigerian Postgraduate Medical Journal.)

Introduction: Previous research has demonstrated the impact of postoperative phosphate levels on liver regeneration and outcomes after liver resection surgeries, a potential predictor for regenerative success and liver failure. However, little is known about the association between low preoperative serum phosphate levels and outcomes in liver resections., Methods: We performed a retrospective analysis of liver resections performed at our institution. Patients were categorized based on preoperative phosphate levels (low versus normal). Our primary outcome measure was posthepatectomy liver failure., Results: A total of 265 cases met the study criteria. 71 patients (26.7%) had low preoperative phosphate levels. The incidence of posthepatectomy liver failure was higher in the low preoperative phosphate group (19.2% versus 12.4%). However, after propensity score matching, rates of posthepatectomy liver failure were similar between low and normal preoperative phosphate cohorts (13% versus 14%, P = 0.83)., Conclusions: Low preoperative phosphate levels were not associated with worse postoperative outcomes in this study. Further studies are warranted to investigate this association and its relevance as a clinical prognostic factor for postoperative liver failure., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objectives: Aortic valve sclerosis has been proposed to signify greater cardiovascular risk; the correlation between serum trace elements and aortic valve sclerosis has been reported. Therefore, an in-depth exploration of the risk factors for aortic valve sclerosis and early intervention may reduce the risk of cardiovascular disease., Methods: In this study, Patients with aortic valve sclerosis and non-aortic valve sclerosis who underwent echocardiographic diagnosis in the People's Hospital of Xinjiang Uygur Autonomous Region during the period from 2019 to 2021 were selected for this study. The correlation between aortic valve sclerosis and serum phosphorus, calcium, and magnesium levels was explored using the propensity score matching technique by pairing the two groups of patients 1:1., Results: A total of 1,533 non-aortic valve sclerosis and 1,533 aortic valve sclerosis patients were included. Logistic regression analysis showed that serum magnesium [OR: 0.346; 95%CI: 0.227, 0.528] and serum calcium [OR: 7.022; 95%CI: 4.755, 10.369] were influential factors. Patients with low, intermediate, and high serum magnesium levels had a significantly lower risk of aortic valve sclerosis compared to patients with very low micronutrient levels ( p  < 0.05). Comparatively, patients with low or high serum calcium levels had an elevated risk of aortic valve sclerosis ( p  < 0.05)., Conclusion: Serum magnesium may have a protective role against aortic valve sclerosis, while both low and high levels of serum calcium could be risk factor for the condition. These serum micronutrients may be indications of cardiovascular disease risk prediction or prevention, and more research is required.

Background: Plasma total magnesium concentration (tMg) is a prognostic indicator in cats with chronic kidney disease (CKD), shorter survival time being associated with hypomagnesemia. Whether this risk factor is modifiable with dietary magnesium supplementation remains unexplored., Objectives: Evaluate effects of a magnesium-enriched phosphate-restricted diet (PRD) on CKD-mineral bone disorder (CKD-MBD) variables., Animals: Sixty euthyroid client-owned cats with azotemic CKD, with 27 and 33 allocated to magnesium-enriched PRD or control PRD, respectively., Methods: Prospective double-blind, parallel-group randomized trial. Cats with CKD, stabilized on a PRD, without hypermagnesemia (tMg >2.43 mg/dL) or hypercalcemia (plasma ionized calcium concentration, (iCa) >6 mg/dL), were recruited. Both intention-to-treat and per-protocol (eating ≥50% of study diet) analyses were performed; effects of dietary magnesium supplementation on clinicopathological variables were evaluated using linear mixed effects models., Results: In the per-protocol analysis, tMg increased in cats consuming a magnesium-enriched PRD (β, 0.25 ± .07 mg/dL/month; P < .001). Five magnesium supplemented cats had tMg >2.92 mg/dL, but none experienced adverse effects. Rate of change in iCa differed between groups (P = .01), with decreasing and increasing trends observed in cats fed magnesium-enriched PRD and control PRD, respectively. Four control cats developed ionized hypercalcemia versus none in the magnesium supplemented group. Log-transformed plasma fibroblast growth factor-23 concentration (FGF23) increased significantly in controls (β, 0.14 ± .05 pg/mL/month; P = .01), but remained stable in the magnesium supplemented group (β, 0.05±.06 pg/mL/month; P =.37)., Conclusions and Clinical Importance: Magnesium-enriched PRD is a novel therapeutic strategy for managing feline CKD-MBD in cats, further stabilizing plasma FGF23 and preventing hypercalcemia., (© 2024 The Author(s). Journal of Veterinary Internal Medicine published by Wiley Periodicals LLC on behalf of American College of Veterinary Internal Medicine.)

Objectives: Hypophosphatemia occurs frequently. Enteral, rather than IV, phosphate replacement may reduce fluid replacement, cost, and waste., Design: Prospective, randomized, parallel group, noninferiority clinical trial., Setting: Single center, 42-bed state trauma, medical and surgical ICUs, from April 20, 2022, to July 1, 2022., Patients: Patients with serum phosphate concentration between 0.3 and 0.75 mmol/L., Interventions: We randomized patients to either enteral or IV phosphate replacement using electronic medical record-embedded program., Measurement and Main Results: Our primary outcome was serum phosphate at 24 hours with a noninferiority margin of 0.2 mmol/L. Secondary outcomes included cost savings and environmental waste reduction and additional IV fluid administered. The modified intention-to-treat cohort comprised 131 patients. Baseline phosphate concentrations were similar between the two groups. At 24 hours, mean ( sd ) serum phosphate concentration were enteral 0.89 mmol/L (0.24 mmol/L) and IV 0.82 mmol/L (0.28 mmol/L). This difference was noninferior at the margin of 0.2 mmol/L (difference, 0.07 mmol/L; 95% CI, -0.02 to 0.17 mmol/L). When assigned IV replacement, patients received 408 mL (372 mL) of solvent IV fluid. Compared with IV replacement, the mean cost per patient was ten-fold less with enteral replacement ($3.7 [$4.0] vs. IV: $37.7 [$31.4]; difference = $34.0 [95% CI, $26.3-$41.7]) and weight of waste was less (7.7 g [8.3 g] vs. 217 g [169 g]; difference = 209 g [95% CI, 168-250 g]). C O2 emissions were 60-fold less for comparable phosphate replacement (enteral: 2 g producing 14.2 g and 20 mmol of potassium dihydrogen phosphate producing 843 g of C O2 equivalents)., Conclusions: Enteral phosphate replacement in ICU is noninferior to IV replacement at a margin of 0.2 mmol/L but leads to a substantial reduction in cost and waste., Competing Interests: Drs. Nguyen’s, Panganiban’s, and Ali Abdelhamid’s institutions received funding from the Clive and Vera Ramaciotti Foundations. Dr. Nguyen’s institution received funding from the Fox Family Foundation. Dr. Ali Abdelhamid’s institution received funding from the Intensive Care Foundation of Australia and New Zealand and the Victorian Medical Research Acceleration Fund. The remaining authors have disclosed that they do not have any potential conflicts of interest., (Copyright © 2024 by the Society of Critical Care Medicine and Wolters Kluwer Health, Inc. All Rights Reserved.)

Background: Clinical laboratory tests are being evaluated with reference intervals (RI). Therefore, it is important that each laboratory determines and classifies its own reliable RI for each test to ensure an accurate and effective interpretation. The proposed method for determining RI is the "direct" approach, but it is a difficult, troublesome, time-consuming, and expensive method. An alternative approach is the "indirect" approach. In this study, we aimed to compare the RI values determined by the indirect method from the Calcium (Ca), Magnesium (Mg), Phosphate (P), 25-Hydroxy Vitamin D (25(OH)D), and Parathyroid hormone (PTH) test results with the RI provided by the manufacturer., Methods: A total of 1,520,314 Ca, Mg, P, 25(OH)D, and PTH test results, which were studied in our laboratory between January and November 2022, were included in the study. Data cleaning was done for individuals between the ages of 18 - 89, and only one record was allowed. The Tukey method was used to determine and exclude extreme values. Ca and Mg tests were divided into age groups (18 - 59 and 60 - 89 years), P, 25(OH)D, and PTH tests were divided into female - male groups. RI was calculated by using the Bhattacharya and Hoffmann methods. CLIA 19 acceptable limits were used to evaluate the compliance with the manufacturer's RI., Results: The RI results obtained by applying the Bhattacharya and Hoffmann methods were found to be significantly consistent and compatible with each other. According to the manufacturer's RI, Ca and Mg were compatible with RI in both methods, P was considered compatible with PTH and 25(OH)D upper reference limit in the Bhattacharya method, P was considered compatible with 25(OH)D lower reference limit and PTH upper reference limit in the Hoffmann method, while 25(OH)D lower reference limit was found to be different in the Bhattacharya method, and 25(OH)D upper reference limit and PTH lower reference limit were found to be different in the P male group in the Hoffmann method., Conclusions: We believe that it is of great importance for each laboratory to determine the RI specific for the population they serve and to choose the analytical method they use according to age and gender while periodically updating them to interpret the test results correctly.

Objective: Evaluate utility of postoperative phosphate and calcium/phosphate ratio (Ca/P) as surrogates for parathyroid hormone (PTH) following total thyroidectomy., Study Design: Retrospective cohort study., Setting: Tertiary care hospital., Methods: We retrospectively reviewed patients 18 years or older who underwent total thyroidectomy in a tertiary care hospital by a single surgeon from 2015 through 2021. Patients with incomplete data, pre-existing hypoparathyroidism, vitamin D deficiency, or renal failure were excluded. All patients had PTH drawn within 4 hours of surgery and serum calcium, albumin, and phosphate levels on postoperative Day 1. Corrected calcium was used to calculate a Ca/P. Receiver operating characteristic (ROC) curves were generated to compare phosphate level or Ca/P with PTH. Each possible surrogate was assessed relative to PTH cutoffs of less than 5, 10, 15, and 20 pg/mL. A good screening test was defined as having an area under the curve (AUC) greater than 0.8., Results: A total of 185 patients underwent total thyroidectomy with 1 fellowship-trained otolaryngologist. Most patients were female (62%), median age 48 years. Most surgeries were performed for cancer (68%). Six (3.2%) patients required IV calcium supplementation and 2 (1.1%) required readmission for symptomatic hypocalcemia. ROC curves comparing phosphate and Ca/P to PTH at the listed cutoffs demonstrated AUC ranging from 0.55 to 0.66 and 0.61 to 0.79, respectively. None met the threshold for a good screening test., Conclusion: Postoperative phosphate and Ca/P ratio are not surrogates for PTH levels following total thyroidectomy. More research is needed to identify cost-effective strategies for postoperative calcium monitoring in patients undergoing total thyroidectomy., Level of Evidence: Retrospective cohort study., (© 2024 American Academy of Otolaryngology–Head and Neck Surgery Foundation.)

Background: Hyperphosphataemia is a common cardiovascular risk factor in chronic kidney disease (CKD). Dietary counseling and control are key aspects in the management of CKD. Although some studies have shown the beneficial effects of dietary phosphate restriction on cardiovascular and bone health in haemodialysis patients, little is known about its effect in pre-dialysis CKD patients., Aim: To determine the effect of dietary phosphate restriction in predialysis CKD patients with hyperphosphataemia., Methods: A hospital-based interventional study involving 72 predialysis CKD patients with hyperphosphataemia randomly allocated into 2 groups. Group 1 had nutritional counseling on dietary phosphate restriction while group 2 had no form of dietary phosphate restriction. All participants were placed on a phosphate binder throughout the study period of 3 months. At the end of the third month, a repeat of baseline tests (serum phosphate, calcium, albumin, creatinine and serum lipids) and anthropometric measurements were done and compared between the 2 groups., Results: The mean age in the treatment and control groups were 54.6±14.7 years and 54.9±14.5 years, respectively. The mean serum phosphate (5.7±0.5 vs. 5.5± 0.4mg/dl), calcium (7.9±0.9 vs. 7.8± 0.7mg/dl), albumin (3.8±0.4 vs. 3.9±0.7g/dl), creatinine (3.9±1.3 vs. 3.7±1.2mg/dl) and body mass index (BMI) (25.0±3.9 vs.25.4±3.1kg/m2) were similar in both groups. Serum phosphate, potassium, fasting blood glucose (FBG), total cholesterol, triglycerides and BMI were significantly reduced while there was no significant change in serum calcium-phosphate product and haematocrit following dietary phosphate restriction in addition to use of phosphate binders. However, on comparison of the changes between the treatment and control groups preand post- intervention, there was no significant change in serum phosphate but there was significant decrease in serum potassium, triglyceride and FBG., Conclusion: The use of phosphate binders in pre-dialysis CKD significantly reduced serum phosphate while additional dietary phosphate restriction had no significant effect on serum phosphate lowering and there was no significant change in nutritional status in predialysis CKD patients with hyperphosphataemia., Competing Interests: The Authors declare that no competing interest exists, (Copyright © 2024 by West African Journal of Medicine.)

Background: Patients with autosomal dominant polycystic kidney disease (ADPKD) have disproportionately high levels of fibroblast growth factor 23 (FGF-23) for their chronic kidney disease stage, however only a subgroup develops kidney phosphate wasting. We assessed factors associated with phosphate wasting and hypothesize that it identifies patients with more severe disease and predicts disease progression., Methods: We included 604 patients with ADPKD from a multicenter prospective observational cohort (DIPAK; Developing Intervention Strategies to Halt Progression of Autosomal Dominant Polycystic Kidney Disease) in four university medical centers in the Netherlands. We measured parathyroid hormone (PTH) and total plasma FGF-23 levels, and calculated the ratio of tubular maximum reabsorption rate of phosphate to glomerular filtration rate (TmP/GFR) with <0.8 mmol/L defined as kidney phosphate wasting. We analysed the association of TmP/GFR with estimated GFR (eGFR) decline over time and the risk for a composite kidney outcome (≥30% eGFR decline, kidney failure or kidney replacement therapy)., Results: In our cohort (age 48 ± 12 years, 39% male, eGFR 63 ± 28 mL/min/1.73 m2), 59% of patients had phosphate wasting. Male sex [coefficient -0.2, 95% confidence interval (CI) -0.2; -0.1], eGFR (0.002, 95% CI 0.001; 0.004), FGF-23 (0.1, 95% CI 0.03; 0.2), PTH (-0.2, 95% CI -0.3; -0.06) and copeptin (-0.08, 95% CI -0.1; -0.08) were associated with TmP/GFR. Corrected for PTH, FGF-23 and eGFR, every 0.1 mmol/L decrease in TmP/GFR was associated with a greater eGFR decline of 0.2 mL/min/1.73 m2/year (95% CI 0.01; 0.3) and an increased hazard ratio of 1.09 (95% CI 1.01; 1.18) of the composite kidney outcome., Conclusion: Our study shows that in patients with ADPKD, phosphate wasting is prevalent and associated with more rapid disease progression. Phosphate wasting may be a consequence of early proximal tubular dysfunction and insufficient suppression of PTH., (© The Author(s) 2023. Published by Oxford University Press on behalf of the ERA.)