Understanding renal phosphate handling: unfinished business

Lederer, Eleanor

doi:10.1097/mnh.0000000000000889

Cited by 3 publications

(2 citation statements)

References 38 publications

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“…Intravenous calcium phase taking a few days is continued with oral calcium phase, which might take a few months. The central piece of the related biochemistry panel is calcium, but serum magnesium and phosphorus might play an important role, especially considering the longstanding kidney disease and the phosphate-associated challenging issues [114,115].…”

Section: Post-operatory Findings In Rhpt: Focus On Hbsmentioning

confidence: 99%

Forestalling Hungry Bone Syndrome after Parathyroidectomy in Patients with Primary and Renal Hyperparathyroidism

Cârșote

Nistor

2023

Diagnostics

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Hungry bone syndrome (HBS), severe hypocalcemia following parathyroidectomy (PTX) due to rapid drop of PTH (parathormone) after a previous long term elevated concentration in primary (PHPT) or renal hyperparathyroidism (RHPT), impairs the outcome of underlying parathyroid disease. Objective: overview HBS following PTx according to a dual perspective: pre- and post-operative outcome in PHPT and RHPT. This is a case- and study-based narrative review. Inclusion criteria: key research words “hungry bone syndrome” and “parathyroidectomy”; PubMed access; in extenso articles; publication timeline from Inception to April 2023. Exclusion criteria: non-PTx-related HBS; hypoparathyroidism following PTx. We identified 120 original studies covering different levels of statistical evidence. We are not aware of a larger analysis on published cases concerning HBS (N = 14,349). PHPT: 14 studies (N = 1545 patients, maximum 425 participants per study), and 36 case reports (N = 37), a total of 1582 adults, aged between 20 and 72. Pediatric PHPT: 3 studies (N = 232, maximum of 182 participants per study), and 15 case reports (N = 19), a total of 251 patients, aged between 6 and 18. RHPT: 27 studies (N = 12,468 individuals, the largest cohort of 7171) and 25 case reports/series (N = 48), a total of 12,516 persons, aged between 23 and 74. HBS involves an early post-operatory (emergency) phase (EP) followed by a recovery phase (RP). EP is due to severe hypocalcemia with various clinical elements (<8.4 mg/dL) with non-low PTH (to be differentiated from hypoparathyroidism), starting with day 3 (1 to 7) with a 3-day duration (up to 30) requiring prompt intravenous calcium (Ca) intervention and vitamin D (VD) (mostly calcitriol) replacement. Hypophosphatemia and hypomagnesiemia may be found. RP: mildly/asymptomatic hypocalcemia controlled under oral Ca+VD for maximum 12 months (protracted HBS is up to 42 months). RHPT associates a higher risk of developing HBS as compared to PHPT. HBS prevalence varied from 15% to 25% up to 75–92% in RHPT, while in PHPT, mostly one out of five adults, respectively, one out of three children and teenagers might be affected (if any, depending on study). In PHPT, there were four clusters of HBS indicators. The first (mostly important) is represented by pre-operatory biochemistry and hormonal panel, especially, increased PTH and alkaline phosphatase (additional indicators were elevated blood urea nitrogen, and a high serum calcium). The second category is the clinical presentation: an older age for adults (yet, not all authors agree); particular skeleton involvement (level of case reports) such as brown tumors and osteitis fibrosa cystica; insufficient evidence for the patients with osteoporosis or those admitted for a parathyroid crisis. The third category involves parathyroid tumor features (increased weight and diameter; giant, atypical, carcinomas, some ectopic adenomas). The fourth category relates to the intra-operatory and early post-surgery management, meaning an associated thyroid surgery and, maybe, a prolonged PTx time (but this is still an open issue) increases the risk, as opposite to prompt recognition of HBS based on calcium (and PTH) assays and rapid intervention (specific interventional protocols are rather used in RHPT than in PHPT). Two important aspects are not clarified yet: the use of pre-operatory bisphosphonates and the role of 25-hydroxyitamin D assay as pointer of HBS. In RHPT, we mentioned three types of evidence. Firstly, risk factors for HBS with a solid level of statistical evidence: younger age at PTx, pre-operatory elevated bone alkaline phosphatase, and PTH, respectively, normal/low serum calcium. The second group includes active interventional (hospital-based) protocols that either reduce the rate or improve the severity of HBS, in addition to an adequate use of dialysis following PTx. The third category involves data with inconsistent evidence that might be the objective of future studies to a better understanding; for instance, longer pre-surgery dialysis duration, obesity, an elevated pre-operatory calcitonin, prior use of cinalcet, the co-presence of brown tumors, and osteitis fibrosa cystica as seen in PHPT. HBS remains a rare complication following PTx, yet extremely severe and with a certain level of predictability; thus, the importance of being adequately identified and managed. The pre-operatory spectrum of assessments is based on biochemistry and hormonal panel in addition to a specific (mostly severe) clinical presentation while the parathyroid tumor itself might provide useful insights as potential risk factors. Particularly in RHPT, prompt interventional protocols of electrolytes surveillance and replacement, despite not being yet a matter of a unified, HBS-specific guideline, prevent symptomatic hypocalcemia, reduce the hospitalization stay, and the re-admission rates.

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Section: Post-operatory Findings In Rhpt: Focus On Hbsmentioning

confidence: 99%

Forestalling Hungry Bone Syndrome after Parathyroidectomy in Patients with Primary and Renal Hyperparathyroidism

Cârșote

Nistor

2023

Diagnostics

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“…Bones store much of total body Pi which can be mobilized in states of low Pi and Ca 2+ levels, crucially regulated by parathyroid hormone (PTH) and—indirectly—by 1,25(OH) 2 vitamin D 3 . Endocrine signalling also affects transcellular Pi absorption in the intestine and controls renal excretion to maintain body Pi homeostasis [ 16 , 17 ]. In the kidney, Pi is freely filtered in the glomerulus followed by transcellular re-uptake from the primary urine in the proximal tubule.…”

Section: Introductionmentioning

confidence: 99%

XPR1: a regulator of cellular phosphate homeostasis rather than a Pi exporter

Burns,

Berlinguer-Palmini,

Werner

2024

Pflugers Arch - Eur J Physiol

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Phosphate (Pi) is an essential nutrient, and its plasma levels are under tight hormonal control. Uphill transport of Pi into cells is mediated by the two Na-dependent Pi transporter families SLC34 and SLC20. The molecular identity of a potential Pi export pathway is controversial, though XPR1 has recently been suggested by Giovannini and coworkers to mediate Pi export. We expressed XPR1 in Xenopus oocytes to determine its functional characteristics. Xenopus isoforms of proteins were used to avoid species incompatibility. Protein tagging confirmed the localization of XPR1 at the plasma membrane. Efflux experiments, however, failed to detect translocation of Pi attributable to XPR1. We tested various counter ions and export medium compositions (pH, plasma) as well as potential protein co-factors that could stimulate the activity of XPR1, though without success. Expression of truncated XPR1 constructs and individual domains of XPR1 (SPX, transmembrane core, C-terminus) demonstrated downregulation of the uptake of Pi mediated by the C-terminal domain of XPR1. Tethering the C-terminus to the transmembrane core changed the kinetics of the inhibition and the presence of the SPX domain blunted the inhibitory effect. Our observations suggest a regulatory role of XPR1 in cellular Pi handling rather than a function as Pi exporter. Accordingly, XPR1 senses intracellular Pi levels via its SPX domain and downregulates cellular Pi uptake via the C-terminal domain. The molecular identity of a potential Pi export protein remains therefore elusive.

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Understanding the Regulatory Mechanisms of Phosphorus Metabolism

Segawa

2023

JJSNFS

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Understanding renal phosphate handling: unfinished business

Cited by 3 publications

References 38 publications

Forestalling Hungry Bone Syndrome after Parathyroidectomy in Patients with Primary and Renal Hyperparathyroidism

Forestalling Hungry Bone Syndrome after Parathyroidectomy in Patients with Primary and Renal Hyperparathyroidism

XPR1: a regulator of cellular phosphate homeostasis rather than a Pi exporter

Understanding the Regulatory Mechanisms of Phosphorus Metabolism

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