Intraperitoneal pyrophosphate treatment reduces renal calcifications in Npt2a null mice

Caballero, Daniel; Li, Yuwen; Fetene, Jonathan; Ponsetto, Julian; Chen, Alyssa; Zhu, Chuanlong; Braddock, Demetrios T.; Bergwitz, Clemens

doi:10.1371/journal.pone.0180098

Cited by 5 publications

(2 citation statements)

References 48 publications

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“…Many clinical conditions that cause increased levels of PP i in urine, intracellular mitochondrial or synovial fluids 60-66 could be traced within this detection range. For example, patients with hypophosphatasia show increased levels of PP i with concentrations between 5 µM and 17.5 µM in plasma and 45-234 µM in urine [60][61][62][63] .…”

Section: Detection Of Pp I In Biological Environmentsmentioning

confidence: 99%

Ratiometric fluorescent sensing of pyrophosphate with sp³-functionalized single-walled carbon nanotubes

Settele,

Schrage,

Jung

et al. 2024

Nat Commun

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Inorganic pyrophosphate is a key molecule in many biological processes from DNA synthesis to cell metabolism. Here we introduce sp3-functionalized (6,5) single-walled carbon nanotubes (SWNTs) with red-shifted defect emission as near-infrared luminescent probes for the optical detection and quantification of inorganic pyrophosphate. The sensing scheme is based on the immobilization of Cu2+ ions on the SWNT surface promoted by coordination to covalently attached aryl alkyne groups and a triazole complex. The presence of Cu2+ ions on the SWNT surface causes fluorescence quenching via photoinduced electron transfer, which is reversed by copper-complexing analytes such as pyrophosphate. The differences in the fluorescence response of sp3-defect to pristine nanotube emission enables reproducible ratiometric measurements in a wide concentration window. Biocompatible, phospholipid-polyethylene glycol-coated SWNTs with such sp3 defects are employed for the detection of pyrophosphate in cell lysate and for monitoring the progress of DNA synthesis in a polymerase chain reaction. This robust ratiometric and near-infrared luminescent probe for pyrophosphate may serve as a starting point for the rational design of nanotube-based biosensors.

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Section: Detection Of Pp I In Biological Environmentsmentioning

confidence: 99%

Ratiometric fluorescent sensing of pyrophosphate with sp³-functionalized single-walled carbon nanotubes

Settele,

Schrage,

Jung

et al. 2024

Nat Commun

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“…Specifically, plasma PPi level was negatively associated with vascular calcification in patients with end-stage renal disease and stage 4 chronic kidney disease [27]. Reduced plasma PPi was also found in nephrocalcinosis [33] and aortic valve calcification [34,35].…”

Section: Fig 1 Distribution Of Ppi Values By Type Of Ssc For the Us (...mentioning

confidence: 99%

Inorganic pyrophosphate is reduced in patients with systemic sclerosis

Hsu

Kozák

et al. 2021

Rheumatology

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Objective The pathogenesis of calcinosis cutis, a disabling complication of systemic sclerosis (SSc), is poorly understood and effective treatments are lacking. Inorganic pyrophosphate (PPi) is a key regulator of ectopic mineralization, and its deficiency has been implicated in ectopic mineralization disorders. We therefore sought to test the hypothesis that SSc may be associated with reduced circulating PPi, which might play a pathogenic role in calcinosis cutis. Methods Subjects with SSc and age-matched controls without SSc were recruited from the outpatient Rheumatology clinics at Rutgers and Northwestern Universities (US cohort), and from the Universities of Szeged and Debrecen (Hungarian cohort). Calcinosis cutis was confirmed by direct palpation, by imaging, or both. Plasma PPi levels were determined in platelet-free plasma using ATP sulfurylase to convert PPi into ATP in the presence of excess adenosine 5’ phosphosulfate. Results Eighty-one patients with SSc (40 diffuse cutaneous, and 41 limited cutaneous SSc) in the US cohort and 45 patients with SSc (19 diffuse cutaneous and 26 limited cutaneous SSc) in the Hungarian cohort were enrolled. Calcinosis was frequently detected (40% of US and 46% of the Hungarian cohort). Plasma PPi levels were significantly reduced in both SSc cohorts with and without calcinosis (US: p= 0.003; Hungarian: p< 0.001). Conclusions Circulating PPi are significantly reduced in SSc patients with or without calcinosis. Reduced PPi may be important in the pathophysiology of calcinosis and contribute to tissue damage with chronic SSc. Administering PPi may be a therapeutic strategy and larger clinical studies are planned to confirm our findings.

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Hereditary hypophosphatemic rickets with hypercalciuria: pathophysiology, clinical presentation, diagnosis and therapy

Bergwitz

Miyamoto

2018

Pflugers Arch - Eur J Physiol

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Hereditary hypophosphatemic rickets with hypercalciuria (HHRH; OMIM: 241530) is a rare autosomal recessive disorder with an estimated prevalence of 1:250,000 that was originally described by Tieder et al. Individuals with HHRH carry compound-heterozygous or homozygous (comp/hom) loss-of-function mutations in the sodium-phosphate co-transporter NPT2c. These mutations result in the development of urinary phosphate (Pi) wasting and hypophosphatemic rickets, bowing, and short stature, as well as appropriately elevated 1,25(OH)D levels, which sets this fibroblast growth factor 23 (FGF23)-independent disorder apart from the more common X-linked hypophosphatemia. The elevated 1,25(OH)D levels in turn result in hypercalciuria due to enhanced intestinal calcium absorption and reduced parathyroid hormone (PTH)-dependent calcium-reabsorption in the distal renal tubules, leading to the development of kidney stones and/or nephrocalcinosis in approximately half of the individuals with HHRH. Even heterozygous NPT2c mutations are frequently associated with isolated hypercalciuria (IH), which increases the risk of kidney stones or nephrocalcinosis threefold in affected individuals compared with the general population. Bone disease is generally absent in individuals with IH, in contrast to those with HHRH. Treatment of HHRH and IH consists of monotherapy with oral Pi supplements, while active vitamin D analogs are contraindicated, mainly because the endogenous 1,25(OH)D levels are already elevated but also to prevent further worsening of the hypercalciuria. Long-term studies to determine whether oral Pi supplementation alone is sufficient to prevent renal calcifications and bone loss, however, are lacking. It is also unknown how therapy should be monitored, whether secondary hyperparathyroidism can develop, and whether Pi requirements decrease with age, as observed in some FGF23-dependent hypophosphatemic disorders, or whether this can lead to osteoporosis.

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Intraperitoneal pyrophosphate treatment reduces renal calcifications in Npt2a null mice

Cited by 5 publications

References 48 publications

Ratiometric fluorescent sensing of pyrophosphate with sp³-functionalized single-walled carbon nanotubes

Ratiometric fluorescent sensing of pyrophosphate with sp³-functionalized single-walled carbon nanotubes

Inorganic pyrophosphate is reduced in patients with systemic sclerosis

Hereditary hypophosphatemic rickets with hypercalciuria: pathophysiology, clinical presentation, diagnosis and therapy

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