1.
The Effect of Extended Release Niacin on Markers of Mineral Metabolism in CKD.
Malhotra, R, Katz, R, Hoofnagle, A, Bostom, A, Rifkin, DE, Mcbride, R, Probstfield, J, Block, G, Ix, JH
Clinical journal of the American Society of Nephrology : CJASN. 2018;(1):36-44
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Abstract
BACKGROUND AND OBJECTIVES Niacin downregulates intestinal sodium-dependent phosphate transporter 2b expression and reduces intestinal phosphate transport. Short-term studies have suggested that niacin lowers serum phosphate concentrations in patients with CKD and ESRD. However, the long-term effects of niacin on serum phosphate and other mineral markers are unknown. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS The Atherothrombosis Intervention in Metabolic Syndrome with Low HDL/High Triglycerides: Impact on Global Health Trial was a randomized, double-blind, placebo-controlled trial testing extended release niacin in persons with prevalent cardiovascular disease. We examined the effect of randomized treatment with niacin (1500 or 2000 mg) or placebo on temporal changes in markers of mineral metabolism in 352 participants with eGFR<60 ml/min per 1.73 m2 over 3 years. Changes in each marker were compared over time between the niacin and placebo arms using linear mixed effects models. RESULTS Randomization to niacin led to 0.08 mg/dl lower plasma phosphate concentrations per year of treatment compared with placebo (P<0.01) and 0.25 mg/dl lower mean phosphate 3 years after baseline (3.32 versus 3.57 mg/dl; P=0.03). In contrast, randomization to niacin was not associated with statistically significant changes in plasma intact fibroblast growth factor 23, parathyroid hormone, calcium, or vitamin D metabolites over 3 years. CONCLUSIONS The use of niacin over 3 years lowered serum phosphorous concentrations but did not affect other markers of mineral metabolism in participants with CKD.
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[GENETIC DISORDERS OF RENAL PHOSPHATE HANDLING].
Magen, D
Harefuah. 2017;(10):654-658
Abstract
Hereditary disorders of renal phosphate handling comprise a diverse group of genetic diseases, usually characterized by excessive urinary phosphate wasting and a negative phosphate balance. In the minority of cases, perturbations of renal phosphate handling are associated with excessive urinary phosphate reabsorption, leading to pathological hyperphosphatemia. Inorganic phosphate is an essential mineral in the human body, playing a crucial role in cellular metabolism and skeletal mineralization. Whole body phosphate balance is maintained by a highly controlled equilibrium between intestinal uptake, skeletal deposition and renal excretion. The human kidney plays a crucial role in phosphate homeostasis. The bulk filtered phosphate is reabsorbed in the renal proximal tubule by two specialized phosphate transporters, NaPi-IIa and NaPi-IIc. Phosphate balance is regulated by dietary phosphate intake, and by the action of the parathyroid hormone, vitamin D3 and fibroblast growth factor-23 (FGF-23). All these regulators exert their effect by modulating the activity of the proximal-tubular phosphate transporters, NaPi-IIa and NaPi-IIc. Based on the versatile molecular mechanism underlying various renal phosphate wasting disorders, these diseases can be divided into three main subgroups: (1) primary impairment of proximal tubular phosphate transporters; (2) disorders of FGF-23 metabolism; (3) generalized dysfunction of the proximal tubule, also known as renal Fanconi syndrome. The clinical similarity between various renal phosphate wasting disorders, combined with their rarity, pose a diagnostic and therapeutic challenge. Recent advancement in molecular biology has led to the identification of the genetic basis of many disorders in this group, has improved our understanding of underlying disease mechanisms, and enables accurate genetic diagnosis. Nevertheless, the current therapy of most renal phosphate wasting disorders is mainly supportive, with limited capacity to change their natural course.
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Osteomalacia-Inducing Tumors of the Brain: A Case Report, Review and a Hypothesis.
Fathalla, H, Cusimano, M, Di Ieva, A, Karamchandani, J, Fung, R, Kovacs, K
World neurosurgery. 2015;(1):189.e1-5
Abstract
BACKGROUND Osteomalacia-inducing tumors (OIT) are mesenchymal tumors that characteristically secrete fibroblast growth factor 23, resulting in a paraneoplastic syndrome of hypophosphatemic osteomalacia. These tumors are known to occur in soft tissues and bones in various sites. It is very unusual for OITs to occur intracranially, with only 10 reported intracranial cases since their discovery in 1959. The most common intracrainal OITs are phosphaturic mesenchymal tumors and hemangiopericytomas. We report a case of hypophosphatemic osteomalacia caused by a tumor in the right anterior cranial fossa. We also hypothesize, based on our review of the literature, that this entity is underdiagnosed. CASE DESCRIPTION A 49-year-old woman had a history of a nonhealing ankle fracture that required repeated surgery over 3 years. She subsequently was found to have severe hypophosphatemia and evidence of osteomalacia together with multiple occult fractures. A diagnosis of tumor-induced osteomalacia was suspected. An elevated serum fibroblast growth factor 23 level confirmed the diagnosis. An octreotide scan that was performed to locate the responsible tumor revealed an area of avid uptake in the right frontal lobe. Magnetic resonance imaging showed a large right anterior fossa extra-axial mass. The patient was referred for surgical intervention and was cured clinically after surgical removal of the tumor. Pathologic examination revealed a phosphaturic mesenchymal OIT. Her phosphate levels returned to normal 3 weeks after surgery. CONCLUSIONS The diagnosis of OIT should be considered in a case of severe hypophosphatemia and metabolic bone disease that is not explained by any other metabolic or hereditary disease. These tumors can occur intracranially and may be confused with a meningioma or a hemangiopericytoma. Taking OIT into consideration in such cases could lead to a shorter time to diagnosis and management, which in our case took 4 years.
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Serum phosphate predicts early mortality in adults starting antiretroviral therapy in Lusaka, Zambia: a prospective cohort study.
Heimburger, DC, Koethe, JR, Nyirenda, C, Bosire, C, Chiasera, JM, Blevins, M, Munoz, AJ, Shepherd, BE, Potter, D, Zulu, I, et al
PloS one. 2010;(5):e10687
Abstract
BACKGROUND Patients starting antiretroviral therapy (ART) for acquired immunodeficiency syndrome (AIDS) in sub-Saharan Africa have high rates of mortality in the initial weeks of treatment. We assessed the association of serum phosphate with early mortality among HIV-infected adults with severe malnutrition and/or advanced immunosuppression. METHODOLOGY/PRINCIPAL FINDINGS An observational cohort of 142 HIV-infected adults initiating ART in Lusaka, Zambia with body mass index (BMI) <16 kg/m(2) or CD4(+) lymphocyte count <50 cells/microL, or both, was followed prospectively during the first 12 weeks of ART. Detailed health and dietary intake history, review of systems, physical examination, serum metabolic panel including phosphate, and serum ferritin and high-sensitivity C-reactive protein (hsCRP) were monitored. The primary outcome was mortality. Baseline serum phosphate was a significant predictor of mortality; participants alive at 12 weeks had a median value of 1.30 mmol/L (interquartile range [IQR]: 1.04, 1.43), compared to 1.06 mmol/L (IQR: 0.89, 1.27) among those who died (p<0.01). Each 0.1 mmol/L increase in baseline phosphate was associated with an incremental decrease in mortality (AHR 0.83; 95% CI 0.72 to 0.95). The association was independent of other metabolic parameters and known risk factors for early ART-associated mortality in sub-Saharan Africa. While participant attrition represented a limitation, it was consistent with local program experience. CONCLUSIONS/SIGNIFICANCE Low serum phosphate at ART initiation was an independent predictor of early mortality among HIV patients starting ART with severe malnutrition or advanced immunosuppression. This may represent a physiologic phenomenon similar to refeeding syndrome, and may lead to therapeutic interventions that could reduce mortality.