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Physiological Reports Dec 2023In-depth understanding of intra- and postdialytic phosphate kinetics is important to adjust treatment regimens in hemodialysis. We aimed to modify and validate a...
In-depth understanding of intra- and postdialytic phosphate kinetics is important to adjust treatment regimens in hemodialysis. We aimed to modify and validate a three-compartment phosphate kinetic model to individual patient data and assess the temporal robustness. Intradialytic phosphate samples were collected from the plasma and dialysate of 12 patients during two treatments (HD1 and HD2). 2-h postdialytic plasma samples were collected in four of the patients. First, the model was fitted to HD1 samples from each patient to estimate the mass transfer coefficients. Second, the best fitted model in each patient case was validated on HD2 samples. The best model fits were determined from the coefficient of determination (R ) values. When fitted to intradialytic samples only, the median (interquartile range) R values were 0.985 (0.959-0.997) and 0.992 (0.984-0.994) for HD1 and HD2, respectively. When fitted to both intra- and postdialytic samples, the results were 0.882 (0.838-0.929) and 0.963 (0.951-0.976) for HD1 and HD2, respectively. Eight patients demonstrated a higher R value for HD2 than for HD1. The model seems promising to predict individual plasma phosphate in hemodialysis patients. The results also show good temporal robustness of the model. Further modifications and validation on a larger sample are needed.
Topics: Humans; Phosphates; Renal Dialysis; Kinetics
PubMed: 38129113
DOI: 10.14814/phy2.15899 -
Frontiers in Endocrinology 2023The serum calcium (Ca)-to-phosphorus (P) ratio has been proposed to identify patients with primary hyperparathyroidism and chronic hypoparathyroidism (HPT), but it has... (Observational Study)
Observational Study
OBJECTIVE
The serum calcium (Ca)-to-phosphorus (P) ratio has been proposed to identify patients with primary hyperparathyroidism and chronic hypoparathyroidism (HPT), but it has never been tested in pseudohypoparathyroidism (PHP). The aim of this study was to test the performance of Ca/P ratio in PHP diagnosis compared with that in healthy subjects and patients with HPT for differential diagnosis.
DESIGN
A retrospective, cross-sectional, and observational study was carried out.
METHODS
Serum Ca, P, creatinine, parathyroid hormone (PTH), and albumin were collected. Ca and P were expressed in mmol/L. Ca/P diagnostic performance was evaluated by receiver operating characteristic curve, sensitivity, specificity, and accuracy.
RESULTS
A total of 60 patients with PHP, 60 patients with HPT, and 120 controls were enrolled. The Ca/P ratio was lower in patients with PHP and HPT than that in controls (p < 0.0001). The cutoff of 1.78 (2.32 if Ca and P measured in mg/dL) for Ca/P ratio could identify patients with PHP and HPT among the entire cohort (sensitivity and specificity of 76%). No valid cutoff of Ca/P was found to distinguish patients with PHP from patients with HPT; in this case, PTH above 53.0 ng/dL identified patients with PHP (sensitivity and specificity of 100%). The index (Ca/P × PTH) above 116 ng/L recognized patients with PHP from controls (sensitivity of 84.7% and specificity of 87.4%), whereas (Ca/P × PTH) below 34 ng/L recognized patients with HPT from controls (sensitivity of 88.9% and specificity of 90.8%).
CONCLUSIONS
The Ca/P ratio below 1.78 (2.32 CU) is highly accurate to identify patients with PHP and HPT, although it is not reliable to differentiate these two conditions. The index (Ca/P × PTH) is excellent to specifically recognize PHP or HPT from healthy subjects.
Topics: Humans; Calcium; Retrospective Studies; Cross-Sectional Studies; Pseudohypoparathyroidism; Parathyroid Hormone; Hypoparathyroidism; Phosphorus
PubMed: 37854194
DOI: 10.3389/fendo.2023.1268704 -
Experimental and Therapeutic Medicine Oct 2023Acromegaly is a rare disease, usually caused by a pituitary tumor. It typically exhibits slow evolution and can result in numerous complications. In the present case...
Acromegaly is a rare disease, usually caused by a pituitary tumor. It typically exhibits slow evolution and can result in numerous complications. In the present case report, the patient presented with hyperthyroidism associated with ophthalmopathy and right nodular goiter. The laboratory tests revealed persistent high levels of phosphorus without an apparent cause. After ruling out common pathologies associated with this finding, a focus was placed on the clinical aspects associated with acromegaly, a rare cause of hyperphosphatemia. Laboratory tests and MRI confirmed the diagnosis. The patient underwent transsphenoidal surgery, but the disease remained active, thus medical treatment was initiated, to a poor initial response. Associated with acromegaly, two distinct thyroid pathologies were diagnosed: Toxic adenoma and Graves' disease. This case highlights the challenges in diagnosing and managing a rare endocrine pathology.
PubMed: 37664685
DOI: 10.3892/etm.2023.12176 -
Scientific Reports Sep 2023Phosphate binders are the main treatment for hyperphosphatemia in patients with chronic kidney disease, and iron-based phosphate binders have been used with increasing...
Phosphate binders are the main treatment for hyperphosphatemia in patients with chronic kidney disease, and iron-based phosphate binders have been used with increasing frequency in recent years. This study examined the association of the use of iron-based, rather than non-iron-based, phosphate binders with the incidence of cardiovascular events, in a real-world setting. We used data from a cohort comprising representative adult patients on maintenance hemodialysis in Japan. The exposure of interest was the time-varying use of phosphate binders, classified into "iron-based", "only non-iron-based", and "no use". The primary outcome was a composite of cardiovascular events and all-cause deaths. A marginal structural Cox regression model was used to deal with possible time-dependent confounding. Of the 2247 patients from 58 hemodialysis facilities, iron-based and only non-iron-based phosphate binders were used in 328 (15%) and 1360 (61%), respectively, at baseline. Hazard ratios (95% confidence intervals) for iron-based and non-iron-based phosphate binders versus no use of phosphate binders were 0.35 (0.24, 0.52) and 0.44 (0.33, 0.58), respectively. The hazard ratio for iron-based relative to non-iron-based phosphate binders was 0.81 (0.58, 1.13), which was not statistically significant. Further studies are warranted to elucidate whether the use of iron-based phosphate binders reduces the event rate.
Topics: Adult; Humans; Iron; Renal Dialysis; Hyperphosphatemia; Cardiovascular Diseases; Phosphates
PubMed: 37749304
DOI: 10.1038/s41598-023-43177-9 -
Journal of Pediatric Genetics Dec 2023Hyperphosphatemic familial tumoral calcinosis (HFTC) presents with varied neurological manifestations that have been reported in the literature like facial palsy, vision...
Hyperphosphatemic familial tumoral calcinosis (HFTC) presents with varied neurological manifestations that have been reported in the literature like facial palsy, vision and hearing impairment, stroke, and headache. In this article, we reported a 12-year-old girl child patient with recurrent facial weakness with bilateral hearing impairment and multiple ulcerative lesions on lower limbs and elbows. On examination, she had lower motor neuron (LMN) facial palsy with conductive hearing loss. The investigations showed hyperphosphatemia (9.3 mg/dL) with normal serum calcium (10.4 mg/dL), alkaline phosphatase (147.9 U/L), parathyroid hormone (23.12 pg/mL), and renal function tests. Elevated serum calcium and phosphorus product (96.72 mg /mL ) and elevated renal tubular reabsorption of phosphate (TMPxGFR) value (9.16) were noted. Skeletal survey showed hyperostosis in the long bone diaphysis, vertebrae, ribs, pelvic bone, skull, and facial bones with narrowing of cranial ostium, characteristically without any peri-articular soft tissue calcifications. An angiogram showed multiple intravascular calcifications. She was managed with a low-phosphate diet, sevelamer, niacinamide, acetazolamide, sucroferric oxyhydroxide to lower serum phosphate level, and topical sodium thiosulfate ectopic cutaneous calcification. Exome sequencing showed novel homozygous inframe deletion of ACG in gene exon 3 at c.374_376 delins position (p. Asp125del) in the proband and a mutation in the heterozygous state in the mother and elder sibling, thus confirming a molecular diagnosis of HFTC. Our case had a unique neurological presentation of recurrent bilateral lower motor nerve facial palsy, hearing loss, multiple ectopic cutaneous calcifications without peri-articular deposits, multiple intravascular, intracranial, and vertebral endplate calcification, which has not been reported earlier. The proband showed a novel pathogenic variant suggesting an expanding phenotype of HFTC.
PubMed: 38162162
DOI: 10.1055/s-0041-1741522 -
International Urology and Nephrology Dec 2023Endothelial dysfunction is the primary step for the development of CKD-related cardiovascular disease. Early prediction and management can influence patient survival....
BACKGROUND
Endothelial dysfunction is the primary step for the development of CKD-related cardiovascular disease. Early prediction and management can influence patient survival. Serum testing of FGF 23 hormone and urinary phosphate excretion were studied as predictors of all-cause cardiovascular morbidity in CKD patients; however, their relation to endothelial dysfunction is controversial. A combination of both in one index is hypothesized to increase their sensitivity in detecting endothelial dysfunction, especially in the early stages of CKD before the dominance of hyperphosphatemia, the original risk.
METHODS
A cross-sectional comparative analysis between thirty CKD stage 3 patients and sixty stage 4-5 CKD patients was conducted. All patients were tested for markers of mineral bone disorders including serum FGF 23 and 24-h urinary phosphate excretion. A combination of both in one index (nephron index) is calculated and hypothesized to correlate with nephron number. Endothelial dysfunction was assessed by measuring the post-occlusion brachial flow-mediated dilatation (FMD).
RESULTS
In univariate and multivariate regression analyses, the nephron index was the only predictor of endothelial dysfunction in individuals with stage 3 CKD (r = 0.74, P 0.01). This was not applied to stage 4-5 CKD patients where serum phosphorus (r = - 0.53, P 0.001), intact PTH (r = - 0.53, P 0.001), uric acid (r = - 0.5, P 0.001), and measured GFR (r = 0.59, P 0.001) were the highest correlates to FMD; the Nephron index had the weakest correlation (r = 0.28, P = 0.02) and is not predictive of endothelial dysfunction.
CONCLUSION
Nephron index calculation showed better correlation with endothelial dysfunction than using any of its determinants alone in early stages of CKD when FGF 23 levels are just beginning to rise. In advanced CKD patients, hyperphosphatemia, hyperparathyroidism, hyperuricemia, and measured GFR are more reliable than nephron index.
Topics: Humans; Cross-Sectional Studies; Fibroblast Growth Factors; Hyperphosphatemia; Phosphates; Renal Insufficiency, Chronic
PubMed: 37043155
DOI: 10.1007/s11255-023-03589-y -
PloS One 2024Hyperphosphatemia and hyperparathyroidism are common in end-stage kidney disease and are associated with poor outcomes. In addition to adequate dialysis, medications are...
The impact of accessibility to non-calcium-based phosphate binders and calcimimetics on mineral outcomes in patients receiving maintenance hemodialysis: A 10-year retrospective analysis of real-world data.
INTRODUCTION
Hyperphosphatemia and hyperparathyroidism are common in end-stage kidney disease and are associated with poor outcomes. In addition to adequate dialysis, medications are usually required for optimum control of serum phosphate and parathyroid hormone (PTH) levels. The use of calcium-based phosphate binders (CBPBs) and active vitamin D is associated with an increase in serum calcium and worsening vascular calcification. To overcome these limitations, non-calcium-based phosphate binders (NCBPBs) and calcimimetics have been developed. However, the coverage for these new medications remains limited in several parts of the world due to the lack of patient-level outcome data and cost. The present study examined the differences in mineral outcomes between two main categories of healthcare programs that provided different coverage for medications used to control mineral and bone disorders (MBD). The Social Security/Universal Coverage (SS/UC) program covered only CBPBs and active vitamin D, whereas the Civil Servant/State Enterprise (CS/SE) program provided coverage of CBPBs, active vitamin D, NCBPBs, and calcimimetics.
METHODS
This 10-year retrospective cohort study examined the differences in mineral outcomes between two healthcare programs in maintenance hemodialysis patients. The differences in serum calcium, phosphate, and PTH levels, as well as the aortic arch calcification score, were analyzed according to dialysis vintage by linear mixed-effects regression analyses. The difference in the composite outcome of severe hyperparathyroidism and parathyroidectomy was analyzed by the Cox-proportional hazard regression model.
RESULTS
714 patients were included in the analyses (full cohort). Of these patients, 563 required at least one type of medication to control MBD (MBD medication subgroup). Serum calcium, phosphate, and the proportions of patients with hypercalcemia and hyperphosphatemia were substantially higher in the SS/UC group compared with the CS/SE group after appropriate adjustments for confounders in both the full cohort and the MBD medication subgroup. These findings were confirmed in propensity-score matched analyses. Higher parathyroid hormone levels and a higher rate of the composite endpoint of severe hyperparathyroidism and parathyroidectomy were also observed in the SS/UC group. A more rapid progression of aortic arch calcification was suggested in the SS/UC group, but between-group changes were not significant.
CONCLUSION
Patients under the healthcare program that did not cover the use of NCBPBs and calcimimetics showed higher serum calcium and phosphate levels and a more rapid progression of hyperparathyroidism. The difference in the progression of vascular calcification could not be confirmed in the present study.
Topics: Humans; Renal Dialysis; Male; Female; Retrospective Studies; Middle Aged; Calcimimetic Agents; Hyperphosphatemia; Calcium; Aged; Phosphates; Kidney Failure, Chronic; Parathyroid Hormone; Vitamin D; Chelating Agents
PubMed: 38820324
DOI: 10.1371/journal.pone.0304649 -
Case Reports in Oncology 2023Tumor lysis syndrome (TLS) is an oncologic emergency characterized by several metabolic derangements, such as hyperuricemia, hyperkalemia, hyperphosphatemia, and...
INTRODUCTION
Tumor lysis syndrome (TLS) is an oncologic emergency characterized by several metabolic derangements, such as hyperuricemia, hyperkalemia, hyperphosphatemia, and hypocalcemia. TLS is typically observed in hematologic malignancies, especially after starting the first administration of antineoplastic therapies. TLS in a solid malignancy is very unusual, and exceedingly rare when occurring spontaneously, in the absence of chemotherapy.
CASE PRESENTATION
We report a case of a 76-year-old man with lung adenocarcinoma, which started as a cancer with indolent behavior and small tumor burden but relapsed in 5 months with rapidly proliferating metastatic disease. Spontaneous TLS was the presenting clinical manifestation of the tumor relapse, and it led to the patient's death.
CONCLUSION
To our knowledge, this is the first case of spontaneous TLS in a relapsed adenocarcinoma of the lung reported in the medical literature. The development of the metabolic derangements of TLS should prompt the consideration of tumor relapse during the follow-up of patients with solid malignancies.
PubMed: 37942403
DOI: 10.1159/000534398 -
ESMO Open Jun 2024Fibroblast growth factor receptor 2 (FGFR2) fusions and rearrangements are clinically actionable genomic alterations in cholangiocarcinoma (CCA). Pemigatinib is a...
BACKGROUND
Fibroblast growth factor receptor 2 (FGFR2) fusions and rearrangements are clinically actionable genomic alterations in cholangiocarcinoma (CCA). Pemigatinib is a selective, potent, oral inhibitor of FGFR1-3 and demonstrated efficacy in patients with previously treated, advanced/metastatic CCA with FGFR2 alterations in FIGHT-202 (NCT02924376). We report final outcomes from the extended follow-up period.
PATIENTS AND METHODS
The multicenter, open-label, single-arm, phase II FIGHT-202 study enrolled patients ≥18 years old with previously treated advanced/metastatic CCA with FGFR2 fusions or rearrangements (cohort A), other FGF/FGFR alterations (cohort B), or no FGF/FGFR alterations (cohort C). Patients received once-daily oral pemigatinib 13.5 mg in 21-day cycles (2 weeks on, 1 week off) until disease progression or unacceptable toxicity. The primary endpoint was objective response rate (ORR) in cohort A assessed as per RECIST v1.1 by an independent review committee; secondary endpoints included duration of response (DOR), progression-free survival (PFS), overall survival (OS), and safety.
RESULTS
FIGHT-202 enrolled 147 patients (cohort A, 108; cohort B, 20; cohort C, 17; unconfirmed FGF/FGFR alterations, 2). By final analysis, 145 (98.6%) had discontinued treatment due to progressive disease (71.4%), withdrawal by patient (8.2%), or adverse events (AEs; 6.8%). Median follow-up was 45.4 months. The ORR in cohort A was 37.0% (95% confidence interval 27.9% to 46.9%); complete and partial responses were observed in 3 and 37 patients, respectively. Median DOR was 9.1 (6.0-14.5) months; median PFS and OS were 7.0 (6.1-10.5) months and 17.5 (14.4-22.9) months, respectively. The most common treatment-emergent AEs (TEAEs) were hyperphosphatemia (58.5%), alopecia (49.7%), and diarrhea (47.6%). Overall, 15 (10.2%) patients experienced TEAEs leading to pemigatinib discontinuation; intestinal obstruction and acute kidney injury (n = 2 each) occurred most frequently.
CONCLUSIONS
Pemigatinib demonstrated durable response and prolonged OS with manageable AEs in patients with previously treated, advanced/metastatic CCA with FGFR2 alterations in the extended follow-up period of FIGHT-202.
Topics: Humans; Cholangiocarcinoma; Male; Female; Middle Aged; Aged; Adult; Bile Duct Neoplasms; Pyrimidines; Receptor, Fibroblast Growth Factor, Type 2; Aged, 80 and over; Morpholines; Pyrroles
PubMed: 38838500
DOI: 10.1016/j.esmoop.2024.103488 -
Endocrinology, Diabetes & Metabolism... Oct 2023A 73-year-old woman with type 2 diabetes mellitus was referred to our department for glycaemic control. Physical examination revealed two subcutaneous hard masses around...
SUMMARY
A 73-year-old woman with type 2 diabetes mellitus was referred to our department for glycaemic control. Physical examination revealed two subcutaneous hard masses around the left shoulder and the right hip joint. The patient could not fully extend her fingers because of skin sclerosis in both hands. Laboratory studies showed hyperphosphataemia and a high ratio of renal tubular maximum reabsorption of phosphate to glomerular filtration rate. There were no abnormalities in serum calcium, creatinine, alkaline phosphatase, and intact parathyroid hormone levels, whereas serum fibroblast growth factor 23 was low. Hyperphosphataemic familial tumoural calcinosis/hyperostosis-hyperphosphataemia syndrome (HFTC/HHS) was diagnosed using whole genome sequencing that revealed a novel frameshift beyond the 584th threonine located in the lectin domain of UDP-N-acetyl-alpha-D-galactosamine:polypeptide N-acetylgalactosaminyltransferase 3 associated with a duplication of the 1748th thymine in the coding region of the corresponding gene. Furthermore, anti-nuclear, anti-centromere, and anti-cardiolipin antibodies were positive, implying that comorbid limited type scleroderma might play a role in tumoural calcinosis (TC) development. A low phosphate diet was prescribed with phosphate-lowering medications, including aluminium hydroxide, acetazolamide, and sevelamer hydrochloride. The patient displayed a decrease in serum phosphate levels from 6.5 to 5.5 mg/dL 10 months after the initiation of treatment, but her TC had not improved during treatment for more than 1 year. This case was interesting because the patient with HFTC/HHS exhibited TC despite being over her 60s, and subsequent scleroderma might contribute to the specific clinical course. When HFTC/HHS presents with elderly-onset TC, the involvement of comorbidities in exacerbating TC should be considered.
LEARNING POINTS
HFTC/HHS occurs on an autosomal recessive basis, but its clinical course and manifestations differ significantly throughout the cases. HFTC/HHS may be undiagnosed until later in life because of its rarity, unfamiliarity, and phenotype diversity; therefore, HFTC/HHS should be included in the differential diagnosis of elderly patients with unexplained hyperphosphataemia or ectopic calcinosis. Comorbidities, including rheumatologic disorders, may contribute to developing HFTC/HHS-associated calcinosis.
PubMed: 37787752
DOI: 10.1530/EDM-23-0071