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Article: Phosphatonins: From Discovery to Therapeutics.

Kritmetapak, Kittrawee / Kumar, Rajiv

Endocrine practice : official journal of the American College of Endocrinology and the American Association of Clinical Endocrinologists

2022

Abstract: Objective: Phosphate is crucial for cell signaling, energy metabolism, nucleotide synthesis, and bone mineralization. The gut-bone-parathyroid-kidney axis is influenced by parathyroid hormone, 1,25-dihydroxyvitamin D, and phosphatonins, especially ... ...

Abstract	Objective: Phosphate is crucial for cell signaling, energy metabolism, nucleotide synthesis, and bone mineralization. The gut-bone-parathyroid-kidney axis is influenced by parathyroid hormone, 1,25-dihydroxyvitamin D, and phosphatonins, especially fibroblast growth factor 23 (FGF23). These hormones facilitate maintenance of phosphate homeostasis. This review summarizes current knowledge regarding the phosphate homeostasis, phosphatonin pathophysiology, and clinical implications of FGF23-related hypophosphatemic disorders, with specific focus on burosumab treatment. Method: A focused literature search of PubMed was conducted. Results: Phosphatonins including FGF23, secreted frizzled-related protein 4, matrix extracellular phosphoglycoprotein, and fibroblast growth factor 7 play a pathogenic role in several hypophosphatemic disorders. Excess FGF23 inhibits sodium-dependent phosphate cotransporters (NaPi-2a and NaPi-2c), resulting in hyperphosphaturia and hypophosphatemia. Additionally, FGF23 suppresses 1,25-dihydroxyvitamin D synthesis in the proximal renal tubule, and thus, it indirectly inhibits intestinal phosphate absorption. Disorders of FGF23-related hypophosphatemia include X-linked hypophosphatemia (XLH), autosomal dominant hypophosphatemic rickets, autosomal recessive hypophosphatemic rickets, fibrous dysplasia/McCune-Albright syndrome, and tumor-induced osteomalacia (TIO). Complications of conventional therapy with oral phosphate and vitamin D analogs comprise gastrointestinal distress, hypercalcemia, nephrocalcinosis, and secondary/tertiary hyperparathyroidism. In both children and adults with XLH and TIO, the anti-FGF23 antibody burosumab exhibits a favorable safety profile and is associated with healing of rickets in affected children and improvement of osteomalacia in both children and adults. Conclusion: The treatment paradigm for XLH and TIO is changing based on data from recent clinical trials. Research suggest that burosumab is effective and safe for pediatric and adult patients with XLH or TIO.
Language	English
Publishing date	2022-10-07
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	1473503-9
ISSN	1530-891X
ISSN	1530-891X
DOI	10.1016/j.eprac.2022.09.007
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Article ; Online: Novel Insights into Mechanisms of Intestinal Phosphate Absorption in Patients with Chronic Kidney Disease.

Kritmetapak, Kittrawee / Kumar, Rajiv

Journal of the American Society of Nephrology : JASN

2021 Volume 32, Issue 8, Page(s) 1830–1832

MeSH term(s)	Fibroblast Growth Factor-23 ; Humans ; Intestinal Absorption ; Phosphates ; Renal Insufficiency, Chronic ; Vitamin D
Chemical Substances	FGF23 protein, human ; Phosphates ; Vitamin D (1406-16-2) ; Fibroblast Growth Factor-23 (7Q7P4S7RRE)
Language	English
Publishing date	2021-07-31
Publishing country	United States
Document type	Editorial ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Comment
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.2021050610
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Article ; Online: The Impact of New-Onset Diabetes Mellitus and Hypertension on All-Cause Mortality in an Apparently Healthy Population: A Ten-Year Follow-Up Study.

Charoensri, Suranut / Kritmetapak, Kittrawee / Tangpattanasiri, Tassanapong / Pongchaiyakul, Chatlert

Journal of diabetes research

2021 Volume 2021, Page(s) 3964013

Abstract: Introduction: The comparative effect of new-onset diabetes mellitus (DM) and hypertension (HT) on long-term mortality is a matter of debate.: Materials and methods: From 2007 to 2017, a 10-year longitudinal retrospective cohort study was conducted in ...

Abstract	Introduction: The comparative effect of new-onset diabetes mellitus (DM) and hypertension (HT) on long-term mortality is a matter of debate. Materials and methods: From 2007 to 2017, a 10-year longitudinal retrospective cohort study was conducted in Thailand's tertiary care setting. As baseline data, health check-up data from apparently healthy participants without underlying disease from 2007 were extracted. The vital status of all participants was determined in 2017, ten years after an initial examination. The impact of new-onset DM and HT at baseline on 10-year all-cause mortality was investigated using multivariable logistic regression analysis. Results: The prevalence of new-onset DM and HT was 6.4% and 28.8%, respectively, at baseline. Newly diagnosed diabetes increased the risk of all-cause mortality over 10 years (adjusted OR 4.77 and 95% CI 2.23-9.99). HT, on the other hand, did not increase the risk of death (adjusted OR 1.24 and 95% CI 0.65-2.35). Different HT and DM status combinations were compared to a nondiabetic, nonhypertensive reference. Individuals who were diabetic and hypertensive had a greater risk of death (adjusted OR 6.22 and 95% CI 2.22-17.00). Having DM without HT also increased the risk of death (adjusted OR 4.36 and 95% CI 1.35-12.87). However, having HT without DM did not result in a significant increase in 10-year mortality risk (adjusted OR 1.21 and 95% CI 0.57-2.56). Conclusion: In an apparently healthy population, new-onset DM is more strongly associated with 10-year all-cause mortality than new-onset HT. Having both DM and HT was associated with a greater risk of death when compared to having DM or HT alone.
MeSH term(s)	Adult ; Blood Glucose/analysis ; Cohort Studies ; Diabetes Mellitus/diagnosis ; Diabetes Mellitus/epidemiology ; Diabetes Mellitus/mortality ; Female ; Follow-Up Studies ; Humans ; Hypertension/diagnosis ; Hypertension/epidemiology ; Hypertension/mortality ; Longitudinal Studies ; Male ; Middle Aged ; Mortality/trends ; Retrospective Studies ; Thailand/epidemiology
Chemical Substances	Blood Glucose
Language	English
Publishing date	2021-11-05
Publishing country	England
Document type	Journal Article
ZDB-ID	2711897-6
ISSN	2314-6753 ; 2314-6753
ISSN (online)	2314-6753
ISSN	2314-6753
DOI	10.1155/2021/3964013
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Article: Parathyroid Hormone Measurement in Chronic Kidney Disease: From Basics to Clinical Implications.

Kritmetapak, Kittrawee / Pongchaiyakul, Chatlert

International journal of nephrology

2019 Volume 2019, Page(s) 5496710

Abstract: Accurate measurement of parathyroid hormone (PTH) is crucial for therapeutic decision-making in patients with chronic kidney disease-mineral and bone disorder (CKD-MBD). The second-generation PTH assays, often referred to as "intact PTH" assays, are the ... ...

Abstract	Accurate measurement of parathyroid hormone (PTH) is crucial for therapeutic decision-making in patients with chronic kidney disease-mineral and bone disorder (CKD-MBD). The second-generation PTH assays, often referred to as "intact PTH" assays, are the current standard and most available assays in clinical practice. However, intact PTH assays measure both full-length biologically active PTH and heterogeneous PTH fragments in the circulation, providing the equivocal value of PTH measurement in patients with CKD-MBD. Due to the variability of PTH assays, preanalytical sample errors, and the phenomenon of end-organ PTH hyporesponsiveness, current CKD-MBD guidelines recommend a wide range for serum PTH targets (2-9 the upper normal limit of the intact PTH assay) in dialysis patients to diminish the risk of developing adynamic bone disease. Nevertheless, a sizeable proportion of CKD patients still experience renal osteodystrophy despite having serum PTH levels within the recommended range. The primary cause of this inconsistency is the analytical interference of various PTH fragments and oxidized PTH forms that considerably accumulate in CKD patients. Therefore, a new mass spectrometry-based assay, which is capable of specifically measuring the whole spectra of PTH fragments, can potentially improve diagnostic accuracy for renal osteodystrophy. However, the effects of different PTH fragments on bone metabolism, vascular calcification, and mortality in CKD patients warrant further research.
Language	English
Publishing date	2019-09-17
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	2573904-9
ISSN	2090-2158 ; 2090-214X
ISSN (online)	2090-2158
ISSN	2090-214X
DOI	10.1155/2019/5496710
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Article ; Online: Phosphate as a Signaling Molecule.

Kritmetapak, Kittrawee / Kumar, Rajiv

Calcified tissue international

2019 Volume 108, Issue 1, Page(s) 16–31

Abstract: Phosphorus plays a vital role in diverse biological processes including intracellular signaling, membrane integrity, and skeletal biomineralization; therefore, the regulation of phosphorus homeostasis is essential to the well-being of the organism. Cells ...

Abstract	Phosphorus plays a vital role in diverse biological processes including intracellular signaling, membrane integrity, and skeletal biomineralization; therefore, the regulation of phosphorus homeostasis is essential to the well-being of the organism. Cells and whole organisms respond to changes in inorganic phosphorus (Pi) concentrations in their environment by adjusting Pi uptake and altering biochemical processes in cells (local effects) and distant organs (endocrine effects). Unicellular organisms, such as bacteria and yeast, express specific Pi-binding proteins on the plasma membrane that respond to changes in ambient Pi availability and transduce intracellular signals that regulate the expression of genes involved in cellular Pi uptake. Multicellular organisms, including humans, respond at a cellular level to adapt to changes in extracellular Pi concentrations and also have endocrine pathways which integrate signals from various organs (e.g., intestine, kidneys, parathyroid glands, bone) to regulate serum Pi concentrations and whole-body phosphorus balance. In mammals, alterations in the concentrations of extracellular Pi modulate type III sodium-phosphate cotransporter activity on the plasma membrane, and trigger changes in cellular function. In addition, elevated extracellular Pi induces activation of fibroblast growth factor receptor, Raf/mitogen-activated protein kinase/ERK kinase (MEK)/extracellular signal-regulated kinase (ERK) and Akt pathways, which modulate gene expression in various mammalian cell types. Excessive Pi exposure, especially in patients with chronic kidney disease, leads to endothelial dysfunction, accelerated vascular calcification, and impaired insulin secretion.
MeSH term(s)	Animals ; Biological Transport ; Extracellular Signal-Regulated MAP Kinases/metabolism ; Humans ; Oncogene Protein v-akt/metabolism ; Phosphates/metabolism ; Receptors, Fibroblast Growth Factor/metabolism ; Signal Transduction ; Sodium-Phosphate Cotransporter Proteins, Type III/metabolism ; raf Kinases/metabolism
Chemical Substances	Phosphates ; Receptors, Fibroblast Growth Factor ; Sodium-Phosphate Cotransporter Proteins, Type III ; Oncogene Protein v-akt (EC 2.7.11.1) ; raf Kinases (EC 2.7.11.1) ; Extracellular Signal-Regulated MAP Kinases (EC 2.7.11.24)
Language	English
Publishing date	2019-11-25
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Review
ZDB-ID	304266-2
ISSN	1432-0827 ; 0944-0747 ; 0008-0594 ; 0171-967X
ISSN (online)	1432-0827
ISSN	0944-0747 ; 0008-0594 ; 0171-967X
DOI	10.1007/s00223-019-00636-8
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Article: Elevated Serum Uric Acid is Associated with Rapid Decline in Kidney Function: A 10-Year Follow-Up Study.

Kritmetapak, Kittrawee / Charoensri, Suranut / Thaopanya, Rattrai / Pongchaiyakul, Chatlert

International journal of general medicine

2020 Volume 13, Page(s) 945–953

Abstract: Purpose: The long-term impact of changes in serum uric acid (SUA) concentration on the estimated glomerular filtration rate (eGFR) among the general population remains unclear. We investigated the longitudinal associations between changes in SUA and ... ...

Abstract	Purpose: The long-term impact of changes in serum uric acid (SUA) concentration on the estimated glomerular filtration rate (eGFR) among the general population remains unclear. We investigated the longitudinal associations between changes in SUA and eGFR over 10 years in 1222 participants with baseline eGFR ≥60 mL/min/1.73 m Methods: This was a 10-year retrospective cohort study conducted from 2007 to 2017. Rapid eGFR decline (defined as the highest quartile of change in eGFR between 2007 and 2017) and new-onset kidney disease (defined as an eGFR <60 mL/min/1.73 m Results: SUA was inversely correlated with eGFR, and the slopes of the SUA-eGFR regression lines were consistently steeper in females than males. A significant inverse correlation was also observed between 10-year changes in SUA and eGFR in both sexes. Multivariate analysis showed that every 1 mg/dL increase in SUA from baseline was associated with higher risk of rapid eGFR decline and new-onset kidney disease (OR 1.25; 95% CI 1.14-1.33 and OR 1.40; 95% CI 1.26-1.49, respectively). Furthermore, the subjects in the highest SUA quartile (>6.0 mg/dL) had a 2.45 times higher risk of rapid eGFR decline (95% CI 1.51-3.42) compared to those in the lowest SUA quartile (<3.9 mg/dL). Conclusion: Elevated baseline SUA is an independent risk factor for rapid eGFR decline and new-onset kidney disease in the general population.
Language	English
Publishing date	2020-10-23
Publishing country	New Zealand
Document type	Journal Article
ZDB-ID	2452220-X
ISSN	1178-7074
ISSN	1178-7074
DOI	10.2147/IJGM.S277957
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Article ; Online: High-Resolution Mass Spectrometry for the Measurement of PTH and PTH Fragments: Insights into PTH Physiology and Bioactivity.

Ulmer, Candice Z / Kritmetapak, Kittrawee / Singh, Ravinder J / Vesper, Hubert W / Kumar, Rajiv

Journal of the American Society of Nephrology : JASN

2022 Volume 33, Issue 8, Page(s) 1448–1458

Abstract: Full-length parathyroid hormone (PTH 1-84) is crucial for the regulation of calcium and phosphate homeostasis and bone remodeling. PTH 1-84 is metabolized into various PTH fragments, which are measured with varying levels of efficiency by PTH ... ...

Abstract	Full-length parathyroid hormone (PTH 1-84) is crucial for the regulation of calcium and phosphate homeostasis and bone remodeling. PTH 1-84 is metabolized into various PTH fragments, which are measured with varying levels of efficiency by PTH immunoassays. These PTH fragments, which increase in serum as CKD progresses, could potentially modulate the effects of PTH 1-84 and contribute to CKD-associated bone disorders. To obtain a true biologic representation of total PTH bioactivity, it is necessary to measure not only PTH 1-84 but also PTH fragments that are present in circulation. Traditional second-generation PTH immunoassays collectively measure PTH 1-84, PTH fragments, and post-translationally modified PTH 1-84, making it difficult to accurately predict the character of underlying renal osteodystrophy. This review highlights current advances in methods available for PTH measurement and the clinical relevance of PTH fragments in CKD. We emphasize the usefulness of mass spectrometry as a potential reference method for PTH measurement.
MeSH term(s)	Bone and Bones ; Chronic Kidney Disease-Mineral and Bone Disorder ; Humans ; Mass Spectrometry ; Parathyroid Hormone ; Peptide Fragments ; Renal Insufficiency, Chronic
Chemical Substances	Parathyroid Hormone ; Peptide Fragments
Language	English
Publishing date	2022-04-08
Publishing country	United States
Document type	Journal Article ; Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
ZDB-ID	1085942-1
ISSN	1533-3450 ; 1046-6673
ISSN (online)	1533-3450
ISSN	1046-6673
DOI	10.1681/ASN.2022010036
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Article: Pseudohyperphosphatemia in a patient with relapsed multiple myeloma after bone marrow transplantation: A case report.

Kritmetapak, Kittrawee / Dumrongsukit, Sophon / Jinchai, Jittirat / Wongprommek, Panibud

Clinical case reports

2019 Volume 7, Issue 7, Page(s) 1426–1429

Abstract: Pseudohyperphosphatemia is a laboratory artifact characterized by falsely elevated serum phosphate mostly due to paraprotein interference on the conventional automated analyzer. Clinician recognition of this phenomenon and pre-analytical preparation, ... ...

Abstract	Pseudohyperphosphatemia is a laboratory artifact characterized by falsely elevated serum phosphate mostly due to paraprotein interference on the conventional automated analyzer. Clinician recognition of this phenomenon and pre-analytical preparation, including dilution or protein precipitation, can obviate unnecessary therapy and potentially unveil the diagnosis of paraproteinemia especially related to multiple myeloma.
Language	English
Publishing date	2019-06-14
Publishing country	England
Document type	Case Reports
ZDB-ID	2740234-4
ISSN	2050-0904
ISSN	2050-0904
DOI	10.1002/ccr3.2264
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Article ; Online: Pseudohyperphosphatemia in a patient with relapsed multiple myeloma after bone marrow transplantation

Kittrawee Kritmetapak / Sophon Dumrongsukit / Jittirat Jinchai / Panibud Wongprommek

Clinical Case Reports, Vol 7, Iss 7, Pp 1426-

A case report

2019 Volume 1429

Abstract: Abstract Pseudohyperphosphatemia is a laboratory artifact characterized by falsely elevated serum phosphate mostly due to paraprotein interference on the conventional automated analyzer. Clinician recognition of this phenomenon and pre‐analytical ... ...

Abstract	Abstract Pseudohyperphosphatemia is a laboratory artifact characterized by falsely elevated serum phosphate mostly due to paraprotein interference on the conventional automated analyzer. Clinician recognition of this phenomenon and pre‐analytical preparation, including dilution or protein precipitation, can obviate unnecessary therapy and potentially unveil the diagnosis of paraproteinemia especially related to multiple myeloma.
Keywords	multiple myeloma ; paraprotein ; phosphate ; pseudohyperphosphatemia ; Medicine ; R ; Medicine (General) ; R5-920
Language	English
Publishing date	2019-07-01T00:00:00Z
Publisher	Wiley
Document type	Article ; Online
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Article: Bile cast nephropathy in a patient with cholangiocarcinoma - a case report.

Kritmetapak, Kittrawee / Sathidatekoonchorn, Thanatarn / Papanrueng, Weerapat

Clinical case reports

2018 Volume 6, Issue 5, Page(s) 779–783

Abstract: Bile cast nephropathy is characterized by the presence of bile casts associated with renal failure and/or proximal tubulopathy in cases of severe hyperbilirubinemia. The clinician should carefully examine the urine samples for characteristic bile-stained ...

Abstract	Bile cast nephropathy is characterized by the presence of bile casts associated with renal failure and/or proximal tubulopathy in cases of severe hyperbilirubinemia. The clinician should carefully examine the urine samples for characteristic bile-stained granular casts in suspected case.
Language	English
Publishing date	2018-03-05
Publishing country	England
Document type	Case Reports
ZDB-ID	2740234-4
ISSN	2050-0904
ISSN	2050-0904
DOI	10.1002/ccr3.1465
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