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Geoffrey A Block - One of the best experts on this subject based on the ideXlab platform.

  • relationship of dietary Phosphate intake with risk of end stage renal disease and mortality in chronic kidney disease stages 3 5 the modification of diet in renal disease study
    Kidney International, 2016
    Co-Authors: Umut Selamet, Hocine Tighiouart, Mark J Sarnak, Gerald J Beck, Andrew S Levey, Geoffrey A Block
    Abstract:

    KDIGO guidelines recommend dietary Phosphate restriction to lower serum Phosphate levels in CKD stages 3–5. Recent studies suggest that dietary Phosphate intake is only weakly linked to its serum concentration, and the relationship of Phosphate intake with adverse outcomes is uncertain. To evaluate this, we used Cox proportional hazards models to assess associations of baseline 24-h urine Phosphate Excretion with risk of end-stage renal disease (ESRD), all-cause mortality, and mortality subtypes (cardiovascular disease [CVD] and non-CVD) using the Modification of Diet in Renal Disease data. Models were adjusted for demographics, CVD risk factors, iothalamate GFR, and urine protein and nitrogen Excretion. Phosphate Excretion was modestly inversely correlated with serum Phosphate concentrations. There was no association of 24-h urinary Phosphate Excretion with risk of ESRD, CVD, non-CVD, or all-cause mortality. For comparison, higher serum Phosphate concentrations were associated with all-cause mortality (hazard ratio per 0.7 mg/dl higher, 1.15 [95% CI 1.01, 1.30]). Thus, Phosphate intake is not tightly linked with serum Phosphate concentrations in CKD stages 3–5, and there was no evidence that greater Phosphate intake, assessed by 24-h Phosphate Excretion, is associated with ESRD, CVD, non-CVD, or all-cause mortality in CKD stages 3–5. Hence, factors other than dietary intake may be key determinants of serum Phosphate concentrations and require additional investigation.

  • a 12 week double blind placebo controlled trial of ferric citrate for the treatment of iron deficiency anemia and reduction of serum Phosphate in patients with ckd stages 3 5
    American Journal of Kidney Diseases, 2015
    Co-Authors: Geoffrey A Block, Myles Wolf, Steven Fishbane, Mariano Rodriguez, Gerard Smits, Shay Shemesh, Pablo E Pergola, Glenn M Chertow
    Abstract:

    Background Iron deficiency anemia and serum Phosphate levels > 4.0mg/dL are relatively common in chronic kidney disease stages 3 to 5 and are associated with higher risks of progressive loss of kidney function, cardiovascular events, and mortality. Study Design Double-blind, placebo-controlled, randomized trial. Setting & Participants 149 patients with estimated glomerular filtration rates  2 , iron deficiency anemia (hemoglobin, 9.0-12.0g/dL; transferrin saturation [TSAT]≤30%, serum ferritin ≤ 300ng/mL), and serum Phosphate levels ≥ 4.0 to 6.0mg/dL. Use of intravenous iron or erythropoiesis-stimulating agents was prohibited. Intervention Randomization to treatment for 12 weeks with ferric citrate coordination complex (ferric citrate) or placebo. Outcomes & Measurements Coprimary end points were change in TSAT and serum Phosphate level from baseline to end of study. Secondary outcomes included change from baseline to end of treatment in values for ferritin, hemoglobin, intact fibroblast growth factor 23 (FGF-23), urinary Phosphate Excretion, and estimated glomerular filtration rate. Results Ferric citrate treatment increased mean TSAT from 22% ± 7% (SD) to 32% ± 14% and reduced serum Phosphate levels from 4.5±0.6 to 3.9±0.6mg/dL, while placebo exerted no effect on TSAT (21% ± 8% to 20% ± 8%) and less effect on serum Phosphate level (4.7±0.6 to 4.4±0.8mg/dL; between-group P P P P =0.02 vs placebo). The incidence and severity of adverse effects were similar between treatment arms. Limitations The study is limited by relatively small sample size and short duration and by having biochemical rather than clinical outcomes. Conclusions Short-term use of ferric citrate repletes iron stores, increases hemoglobin levels, and reduces levels of serum Phosphate, urinary Phosphate Excretion, and FGF-23 in patients with chronic kidney disease stages 3 to 5.

  • estimation of 24 hour urine Phosphate Excretion from spot urine collection development of a predictive equation
    Journal of Renal Nutrition, 2014
    Co-Authors: Cassianne Robinsoncohen, Geoffrey A Block, Gerard Smits, Glenn M Chertow, Martha S Persky, Bryan Kestenbaum
    Abstract:

    Background The management of hyperPhosphatemia in patients with moderate to severe chronic kidney disease (CKD) includes dietary Phosphate restriction and/or prescription of Phosphate binders. Measuring Phosphate intake in CKD is important for monitoring dietary adherence and for the effectiveness of therapeutic interventions. The 24-hour urine collection is the gold standard method for determining Phosphate intake; however, timed urine collections are cumbersome and prone to error. We investigated the precision and accuracy of spot urine Phosphate measurements, compared to 24-hour urine Phosphate (24hUrP) collection. Study Design, Setting, and Participants We evaluated simultaneous spot and 24hUrP measurements, collected on multiple occasions, from 143 participants in the Phosphate Normalization Trial, a randomized trial of Phosphate binders versus placebo among persons with an estimated glomerular filtration rate between 20-45 mL/minute per 1.73 m 2 . We used residual analyses and graphical methods to model the functional relationship of spot urine Phosphate and creatinine measurements with 24hUrP. We used multiple linear regression to test whether additional covariates improved model prediction, including treatment assignment, age, sex, height, weight, urine collection time, and last meal time. We internally validated results using leave-one-out cross-validation, and externally validated in an independent replication cohort. Results A log-log relation between the spot urine Phosphate-to-creatinine ratio and 24hUrP Excretion yielded the best model fit. In addition to spot urine Phosphate and creatinine concentrations, inclusion of age, sex, and weight significantly improved prediction of 24hUrP. Compared with a spot urine Phosphate-to-creatinine ratio alone ( r 2  = 0.12, P r 2  = 0.43, P r 2  = 0.39, P Conclusion We describe a novel equation to predict 24hUrP Excretion using spot urine Phosphate and creatinine, age, sex, and weight. The equation is more accurate and precise than the urine Phosphate-to-creatinine ratio alone, and it provides a simple method for estimating 24hUrP Excretion in patients with nondialysis-requiring CKD.

Harald Juppner - One of the best experts on this subject based on the ideXlab platform.

  • selective pharmacological inhibition of the sodium dependent Phosphate cotransporter npt2a promotes Phosphate Excretion
    Journal of Clinical Investigation, 2020
    Co-Authors: Valerie Clerin, Kevin J Filipski, Hiroshi Saito, An Hai Nguyen, Jeonifer Garren, Janka Kisucka, Monica Reyes, Harald Juppner
    Abstract:

    The sodium-Phosphate cotransporter NPT2a plays a key role in the reabsorption of filtered Phosphate in proximal renal tubules, thereby critically contributing to Phosphate homeostasis. Inadequate urinary Phosphate Excretion can lead to severe hyperPhosphatemia as in tumoral calcinosis and chronic kidney disease (CKD). Pharmacological inhibition of NPT2a may therefore represent an attractive approach for treating hyperPhosphatemic conditions. The NPT2a-selective small-molecule inhibitor PF-06869206 was previously shown to reduce Phosphate uptake in human proximal tubular cells in vitro. Here, we investigated the acute and chronic effects of the inhibitor in rodents and report that administration of PF-06869206 was well tolerated and elicited a dose-dependent increase in fractional Phosphate Excretion. This phosphaturic effect lowered plasma Phosphate levels in WT mice and in rats with CKD due to subtotal nephrectomy. PF-06869206 had no effect on Npt2a-null mice, but promoted Phosphate Excretion and reduced Phosphate levels in normophophatemic mice lacking Npt2c and in hyperPhosphatemic mice lacking Fgf23 or Galnt3. In CKD rats, once-daily administration of PF-06869206 for 8 weeks induced an unabated acute phosphaturic and hypoPhosphatemic effect, but had no statistically significant effect on FGF23 or PTH levels. Selective pharmacological inhibition of NPT2a thus holds promise as a therapeutic option for genetic and acquired hyperPhosphatemic disorders.

  • oncogenic osteomalacia due to fgf23 expressing colon adenocarcinoma
    The Journal of Clinical Endocrinology and Metabolism, 2013
    Co-Authors: David E. Leaf, Hasan Bazari, Renata C Pereira, Harald Juppner
    Abstract:

    Context: Oncogenic osteomalacia, a paraneoplastic syndrome associated with hypoPhosphatemia due to increased urinary Phosphate Excretion, is caused by excessive synthesis and secretion of fibroblast growth factor 23 (FGF23), a phosphaturic hormone that is normally produced by osteocytes. Most cases of oncogenic osteomalacia have been associated with benign tumors of bone or soft tissue; however, whether malignant neoplasms can also produce and secrete FGF23 is currently unknown. Objective: The aim was to determine whether a malignant neoplasm could cause oncogenic osteomalacia through excessive production and secretion of FGF23. Setting: We describe an 80-year-old woman with stage IV colon adenocarcinoma who presented with severe hypoPhosphatemia (0.4 mg/dL; reference, 2.6–4.5 mg/dL). Results: Fractional Excretion of Phosphate was 34% (reference, <5% in the setting of hypoPhosphatemia), and plasma levels of FGF23 were highly elevated at 674 RU/mL (reference, <180 RU/mL). Immunohistochemical analysis of th...

  • pilot study of dietary phosphorus restriction and phosphorus binders to target fibroblast growth factor 23 in patients with chronic kidney disease
    Nephrology Dialysis Transplantation, 2011
    Co-Authors: Tamara Isakova, Harald Juppner, Kelsey Smith, Orlando M Gutierrez, Michael P Epstein, Leigh Keating, Myles Wolf
    Abstract:

    Background. High levels of fibroblast growth factor 23 (FGF23) are associated with mortality and progression of chronic kidney disease (CKD). Reducing dietary phosphorus intake lowers FGF23 secretion in healthly individuals, but there is little data on its effects in patients with pre-dialysis CKD. Methods. Using a 2 × 2 factorial design, we randomly assigned 16 normophosphataemic CKD stage 3–4 patients to receive a 2-week treatment with either lanthanum carbonate 1000 mg three times daily or placebo, and to ingest a tightly controlled diet containing 750 or 1500 mg of dietary phosphorus daily. We analysed serial measurements of FGF23, parathyroid hormone, serum Phosphate and calcium, and 24-h urinary Phosphate and calcium Excretion using repeated-measures analyses. Results. Compared with the 1500-mg phosphorus diet, patients assigned to the 750-mg diet had greater reduction in 24-h urinary Phosphate Excretion (66% vs. 29%; P < 0.0001). Lanthanum-treated patients experienced a significant reduction in 24-h urinary Phosphate Excretion compared with baseline (64%; P < 0.0001), but the difference compared with placebo did not reach significance (64% vs. 31%). Despite the significant reductions in 24-h urinary Phosphate Excretion, no group demonstrated a significant reduction in FGF23 levels; FGF23 levels actually increased significantly in the 1500-mg diet plus placebo group, suggesting dietary phosphorus loading. Conclusions. Although dietary phosphorus restriction and lanthanum lowered urinary Phosphate Excretion consistent with a rapid decrease in phosphorus absorption, inducing a reduction in FGF23 levels in CKD patients may require interventions with a longer duration than in healthy volunteers.

  • regulation of Phosphate homeostasis by pth vitamin d and fgf23
    Annual Review of Medicine, 2010
    Co-Authors: Clemens Bergwitz, Harald Juppner
    Abstract:

    In contrast to the regulation of calcium homeostasis, which has been extensively studied over the past several decades, relatively little is known about the regulation of Phosphate homeostasis. Fibroblast growth factor 23 (FGF23) is part of a previously unrecognized hormonal bone-parathyroid-kidney axis, which is modulated by PTH, 1,25(OH)2-vitamin D (1,25(OH)2D), dietary and serum phosphorus levels. Synthesis and secretion of FGF23 by osteocytes are positively regulated by 1,25(OH)2D and serum phosphorus and negatively regulated, through yet unknown mechanisms, by the Phosphate-regulating gene with homologies to endopeptidases on the X chromosome (PHEX) and by dentin matrix protein 1 (DMP1). In turn, FGF23 inhibits the synthesis of 1,25(OH)2D, and it may negatively regulate the secretion of parathyroid hormone (PTH) from the parathyroid glands. However, FGF23 synergizes with PTH to increase renal Phosphate Excretion by reducing expression of the renal sodium-Phosphate cotransporters NaPi-IIa and NaPi-IIc...

Edward L Conn - One of the best experts on this subject based on the ideXlab platform.

  • discovery of orally bioavailable selective inhibitors of the sodium Phosphate cotransporter napi2a slc34a1
    ACS Medicinal Chemistry Letters, 2018
    Co-Authors: Kevin J Filipski, Samit Kumar Bhattacharya, Jane Panteleev, Janice A Brown, Matthew F Sammons, Andre Shavnya, Patricia Mccoy L Loria, Aaron Smith, Markus Boehm, Edward L Conn
    Abstract:

    Sodium-Phosphate cotransporter 2a, or NaPi2a (SLC34A1), is a solute-carrier (SLC) transporter located in the kidney proximal tubule that reabsorbs glomerular-filtered Phosphate. Inhibition of NaPi2a may enhance urinary Phosphate Excretion and correct maladaptive mineral and hormonal derangements associated with increased cardiovascular risk in chronic kidney disease–mineral and bone disorder (CKD-MBD). To date, only nonselective NaPi inhibitors have been described. Herein, we detail the discovery of the first series of selective NaPi2a inhibitors, resulting from optimization of a high-throughput screening hit. The oral PK profile of inhibitor PF-06869206 (6f) in rodents allows for the exploration of the pharmacology of selective NaPi2a inhibition.

  • Discovery of Orally Bioavailable Selective Inhibitors of the Sodium-Phosphate Cotransporter NaPi2a (SLC34A1)
    2018
    Co-Authors: Kevin J Filipski, Samit Kumar Bhattacharya, Jane Panteleev, Janice A Brown, Matthew F Sammons, Andre Shavnya, Patricia Mccoy L Loria, Markus Boehm, Aaron C. Smith, Edward L Conn
    Abstract:

    Sodium-Phosphate cotransporter 2a, or NaPi2a (SLC34A1), is a solute-carrier (SLC) transporter located in the kidney proximal tubule that reabsorbs glomerular-filtered Phosphate. Inhibition of NaPi2a may enhance urinary Phosphate Excretion and correct maladaptive mineral and hormonal derangements associated with increased cardiovascular risk in chronic kidney disease–mineral and bone disorder (CKD-MBD). To date, only nonselective NaPi inhibitors have been described. Herein, we detail the discovery of the first series of selective NaPi2a inhibitors, resulting from optimization of a high-throughput screening hit. The oral PK profile of inhibitor PF-06869206 (6f) in rodents allows for the exploration of the pharmacology of selective NaPi2a inhibition

F G Knox - One of the best experts on this subject based on the ideXlab platform.

  • effect of serotonin receptor antagonist on Phosphate Excretion
    Journal of The American Society of Nephrology, 2000
    Co-Authors: Jennifer M Gross, Theresa J Berndt, F G Knox
    Abstract:

    To determine whether endogenous intrarenal 5-hydroxytryptamine affects Phosphate Excretion, the serotonin receptor antagonist methiothepin (20 microgram/kg, +6 microgram/kg per h) was infused into the renal interstitium of rats fed a normal Phosphate diet (0.7% Phosphate [Pi]) in the presence of endogenous parathyroid hormone (PTH). Renal interstitial infusion of methiothepin significantly increased fractional Phosphate Excretion (FE(Pi)) from 23 +/- 4 to 30 +/- 4% (n = 8, P 0.05. In thyroparathyroidectomized rats fed a LPD, methiothepin infusion did not increase Phosphate Excretion (0.8 +/- 0.4 to 1.3 +/- 0.9%, n = 7, P > 0.05). However, the increase in FE(Pi) during PTH infusion was significantly greater in the presence of methiothepin (1.3 +/- 0.9 to 20.0 +/- 4.0%, Delta18.7 +/- 3.5%) than in the vehicle-infused rats (0.5 +/- 0.2 to 8.8 +/- 1.1%, Delta8.3 +/- 1.2%; n = 8, P < 0.05). In conclusion, these observations suggest that endogenous intrarenal serotonin enhances Phosphate reabsorption in Phosphate-replete rats, and attenuates the phosphaturic response to PTH in Phosphate-deprived rats.

  • effect of γ l glutamyl l dopa on Phosphate Excretion
    Journal of Laboratory and Clinical Medicine, 2000
    Co-Authors: Shamim Sadiq, Theresa J Berndt, Karl A Nath, F G Knox
    Abstract:

    Abstract γ- L -glutamyl- L -DOPA (gludopa) is a dopamine prodrug that is relatively specific for the kidney. Because dopamine is phosphaturic, the present study compared the phosphaturic effects of the infusion of equimolar doses of gludopa (n = 8), L -DOPA (n = 8), and γ- L -glutamyl- L -tyrosine (glutyrosine, n = 6). Glutyrosine was used as a control to evaluate the effect of the glutamyl portion of gludopa on Phosphate Excretion. Sprague-Dawley rats (350 to 400 g) were anesthetized with 5-sec-butyl-ethyl-2-thyobarbituric acid (Inactin; 100 mg/kg, IP ) and underwent thyroparathyroidectomy. Clearances were taken during the infusion of normal saline vehicle, followed by the infusion of gludopa, L -DOPA, or glutyrosine, all infused at the rate of 10 nmol/kg bolus and 0.8 nmol/kg/min ( IV ). To determine the contribution of glutamyl derivative to Phosphate Excretion, gludopa or L -DOPA was infused in the presence of SCH23390, a DA-1 receptor antagonist. Gludopa infusion significantly increased dopamine Excretion (from 1.9 ± 0.2 ng/min to 17.0 ± 3.9 ng/min, Δ15.0 ± 3.9 ng/min, P P L -DOPA infusion significantly increased dopamine Excretion (from 1.4 ± 0.4 ng/min to 9.7 ± 1.6 ng/min, Δ8.3 ± 1.5 ng/min, P P P P L -DOPA. We conclude that γ- L -glutamyl- L -DOPA is more phosphaturic than L -DOPA in the rat because of the combined effects of dopamine and the glutamyl moiety. (J Lab Clin Med 2000;135:52-6)

  • effect of renal interstitial adenosine infusion on Phosphate Excretion in diabetes mellitus rats
    American Journal of Physiology-regulatory Integrative and Comparative Physiology, 1998
    Co-Authors: Axel Pflueger, Theresa J Berndt, F G Knox
    Abstract:

    We previously demonstrated an increased sensitivity of the renal vasculature to adenosine (ADO) mediated via ADO A1 receptors in streptozotocin (STZ) diabetic rats. Because ADO stimulates Pi reabso...

  • effect of bromotetramisole on renal Phosphate Excretion
    Experimental Biology and Medicine, 1996
    Co-Authors: Marcine Onsgardmeyer, Angela L Mccoy, F G Knox
    Abstract:

    Levamisole inhibits alkaline phosphatase (ALP) activity in kidney brush border membranes and increases Phosphate Excretion in vivo in dogs and rats. I-p-Bromotetramisole (I-BR) is a more potent analog of levamisole in regard to inhibition of ALP activity in vitro, but had no effect on Phosphate transport by in vitro proximal tubules of the rabbit. Since its effect on Phosphate Excretion in vivo has not been studied, the present study tested the effects of infusion of I-BR on Phosphate Excretion in Sprague-Dawley rats. Fractional Excretion of Phosphate (FEPi) was measured in thyroparathyroidectomized Sprague-Dawley rats before and during a systemic infusion at 0.8 ml/min of 10 mM I-p-Bromotetramisole oxalate (I-BR, n = 6), or the inactive isomer d-p-Bromotetramisole oxalate (d-BR, n = 5). The FEPi increased significantly from 4.7% +/- 0.9% to 13.4% +/- 3.1% in response to I-BR whereas there were no changes in FEPi with inactive d-BR. In conclusion, systemic infusion of I-p-Bromotetramisole increases FEPi in Sprague-Dawley rats.

  • effect of acute hypoxia on Phosphate Excretion in rats
    American Journal of Physiology-regulatory Integrative and Comparative Physiology, 1994
    Co-Authors: Yoshikazu Mimura, F G Knox
    Abstract:

    This study evaluated the effect of acute hypoxia on renal handling of Phosphate in rats in the presence and absence of parathyroid hormone (PTH). Hypoxia causes respiratory alkalosis in spontaneously breathing humans and animals. Respiratory alkalosis has been reported to induce a blunted phosphaturic response to PTH. In this study, to avoid the confounding effect of hypocapnia accompanying the hypoxia on Phosphate Excretion, the rats were ventilated mechanically, and arterial PCO2 levels were controlled. Rats were divided into two main groups depending on the arterial PO2 levels: a hypoxic group (n = 16) and a normoxic group (n = 18). Hypoxia was produced by ventilating with 10% oxygen, and hypocapnia was produced by hyperventilation. In response to PTH, the hypoxic rats without hypocapnia showed a greater increase in fractional Excretion of Phosphate (FEPi; 37.7 +/- 2.6%, mean +/- SE) compared with normoxic rats (27.4 +/- 2.5%, P < 0.02). During hypocapnia, there was no difference in FEPi between hypoxic and normoxic groups (21.2 +/- 1.5 and 19.5 +/- 1.2%, respectively), and both groups showed a significantly blunted phosphaturic response to PTH compared with normocapnia (P < 0.05 and P < 0.01, respectively). Urinary adenosine 3',5'-cyclic monoPhosphate (cAMP) increased similarly after PTH infusion between each group. To test whether the phosphaturic effect of PTH in hypoxia and the blunted phosphaturic effect of PTH in hypocapnia are due to steps beyond the generation of cAMP, the phosphaturic response to cAMP infusion was evaluated in 1) hypoxic and normocapnic rats (n = 6), 2) normoxic and normocapnic (control) rats (n = 6), and 3) normoxic and hypocapnic rats (n = 7).(ABSTRACT TRUNCATED AT 250 WORDS)

Myles Wolf - One of the best experts on this subject based on the ideXlab platform.

  • fibroblast growth factor 23 and a vegetarian diet
    Journal of Renal Nutrition, 2020
    Co-Authors: Shuchi Anand, Ram Jagannathan, Ruby Gupta, Sailesh Mohan, Dorairaj Prabhakaran, Myles Wolf
    Abstract:

    Objective Sparse data exist on population distributions of serum fibroblast growth factor-23 (FGF23) levels from developing, middle-income economies. FGF23 levels may differ substantially across regions based on differences in diet and urbanization. In a population-based study from North India, we tested the hypothesis that urinary Phosphate Excretion and FGF23 levels are lower among rural compared with urban participants, and among vegetarian compared with nonvegetarian participants. Methods We measured 24-hour urinary Phosphate, and serum parathyroid hormone and FGF23 in a subsample of the population-based Cardiometabolic Risk Reduction in South Asia and Indian Council of Medical Research Coronary Heart Disease surveys. We categorized participants according to diet and residence: urban nonvegetarians (n = 70), urban vegetarians (n = 564), and rural vegetarians (n = 558). Using least square means, we compared the groups' 24-hour urinary Phosphate (with urban vegetarians as reference) and FGF23 levels after accounting for age, sex, diabetes, and body mass index. Results Among 1,192 study participants, mean FGF23 was 41 ± 18 pg/mL, median parathyroid hormone was 44 (interquartile range [IQR] 31-60) pg/mL, and median 24-hour urinary Phosphate Excretion was 419 (IQR: 47-622) mg/day. Urinary Phosphate was significantly higher in rural compared with urban vegetarians (median, 503; IQR, 334-543 versus 365; IQR, 199-399 mg/day), but adjusted mean FGF23 levels did not differ across study groups. Conclusion In rural and urban India, urinary Phosphate Excretion was low, but FGF23 levels did not differ by residence or dietary preference. Homogenously low dietary Phosphate intake across different settings and diets may partly explain the lack of differences in FGF23.

  • fibroblast growth factor 23 fgf 23 levels differ across populations by degree of industrialization
    The Journal of Clinical Endocrinology and Metabolism, 2016
    Co-Authors: Shennin N Yuen, Myles Wolf, Holly Kramer, Amy Luke, Pascal Bovet, Jacob Plangerhule, Terrence Forrester, V Lambert, Pauline Camacho, Regina Harders
    Abstract:

    Context: Compensatory increases in fibroblast growth factor 23 (FGF23) with increasing Phosphate intake may adversely impact health. However, population and clinical studies examining the link between Phosphate intake and FGF23 levels have focused mainly on populations living in highly industrialized societies in which Phosphate exposure may be homogenous. Objective: The objective of the study was to contrast dietary Phosphate intake, urinary measures of Phosphate Excretion, and FGF23 levels across populations that differ by the level of industrialization. Design: This was a cross-sectional analysis of three populations. Setting: The study was conducted in Maywood, Illinois; Mahe Island, Seychelles; and Kumasi, Ghana. Participants: Adults with African ancestry aged 25–45 years participated in the study. Main Outcome: FGF23 levels were measured. Results: The mean age was 35.1 (6.3) years and 47.9% were male. Mean Phosphate intake and fractional Excretion of Phosphate were significantly higher in the United...

  • a 12 week double blind placebo controlled trial of ferric citrate for the treatment of iron deficiency anemia and reduction of serum Phosphate in patients with ckd stages 3 5
    American Journal of Kidney Diseases, 2015
    Co-Authors: Geoffrey A Block, Myles Wolf, Steven Fishbane, Mariano Rodriguez, Gerard Smits, Shay Shemesh, Pablo E Pergola, Glenn M Chertow
    Abstract:

    Background Iron deficiency anemia and serum Phosphate levels > 4.0mg/dL are relatively common in chronic kidney disease stages 3 to 5 and are associated with higher risks of progressive loss of kidney function, cardiovascular events, and mortality. Study Design Double-blind, placebo-controlled, randomized trial. Setting & Participants 149 patients with estimated glomerular filtration rates  2 , iron deficiency anemia (hemoglobin, 9.0-12.0g/dL; transferrin saturation [TSAT]≤30%, serum ferritin ≤ 300ng/mL), and serum Phosphate levels ≥ 4.0 to 6.0mg/dL. Use of intravenous iron or erythropoiesis-stimulating agents was prohibited. Intervention Randomization to treatment for 12 weeks with ferric citrate coordination complex (ferric citrate) or placebo. Outcomes & Measurements Coprimary end points were change in TSAT and serum Phosphate level from baseline to end of study. Secondary outcomes included change from baseline to end of treatment in values for ferritin, hemoglobin, intact fibroblast growth factor 23 (FGF-23), urinary Phosphate Excretion, and estimated glomerular filtration rate. Results Ferric citrate treatment increased mean TSAT from 22% ± 7% (SD) to 32% ± 14% and reduced serum Phosphate levels from 4.5±0.6 to 3.9±0.6mg/dL, while placebo exerted no effect on TSAT (21% ± 8% to 20% ± 8%) and less effect on serum Phosphate level (4.7±0.6 to 4.4±0.8mg/dL; between-group P P P P =0.02 vs placebo). The incidence and severity of adverse effects were similar between treatment arms. Limitations The study is limited by relatively small sample size and short duration and by having biochemical rather than clinical outcomes. Conclusions Short-term use of ferric citrate repletes iron stores, increases hemoglobin levels, and reduces levels of serum Phosphate, urinary Phosphate Excretion, and FGF-23 in patients with chronic kidney disease stages 3 to 5.

  • associations of dietary phosphorus intake urinary Phosphate Excretion and fibroblast growth factor 23 with vascular stiffness in chronic kidney disease
    Journal of Renal Nutrition, 2013
    Co-Authors: Jessica Houston, Kelsey Smith, Tamara Isakova, Nicole Sowden, Myles Wolf, Orlando M Gutierrez
    Abstract:

    Objective Elevated serum Phosphate concentrations are established risk factors for cardiovascular disease and mortality in chronic kidney disease (CKD). Independent associations of other indices of phosphorus metabolism, such as phosphorus intake, urinary Phosphate Excretion, or hormones that regulate these systems, like fibroblast growth factor 23 (FGF23), with markers of cardiovascular disease in CKD, have been studied in less detail. Design Cross-sectional study. Participants Seventy-four adult CKD patients with mean creatinine clearance of 51 ± 19 mL/minute. Outcome Augmentation index (AI)—a surrogate marker of arterial stiffness. Results Although serum Phosphate varied little across quartiles of creatinine clearance, average daily phosphorus intake and 24-hour urinary Phosphate Excretion decreased from highest to lowest quartile (by 31% and 60%, respectively, P for trend P = .03) and creatinine clearance (r = −0.4, P = .001), but not with dietary phosphorus or 24-hour urinary Phosphate Excretion ( P > .05 for both). Older age, higher systolic blood pressure, female gender, and black race were independently associated with increased AI. In contrast, there were no associations of serum Phosphate, dietary phosphorus intake, urinary Phosphate Excretion, or FGF23 with AI in multivariate-adjusted models. Conclusions In this sample of patients with CKD, established risk factors for arterial stiffness, but not mediators of phosphorus metabolism, were associated with increased AI. In addition, there were no significant associations between FGF23 and dietary phosphorus or urinary Phosphate Excretion. Future studies are needed to determine the main factors associated with elevations in FGF23 in CKD and to further assess the association of disordered phosphorus metabolism with subclinical markers of vascular disease.

  • pilot study of dietary phosphorus restriction and phosphorus binders to target fibroblast growth factor 23 in patients with chronic kidney disease
    Nephrology Dialysis Transplantation, 2011
    Co-Authors: Tamara Isakova, Harald Juppner, Kelsey Smith, Orlando M Gutierrez, Michael P Epstein, Leigh Keating, Myles Wolf
    Abstract:

    Background. High levels of fibroblast growth factor 23 (FGF23) are associated with mortality and progression of chronic kidney disease (CKD). Reducing dietary phosphorus intake lowers FGF23 secretion in healthly individuals, but there is little data on its effects in patients with pre-dialysis CKD. Methods. Using a 2 × 2 factorial design, we randomly assigned 16 normophosphataemic CKD stage 3–4 patients to receive a 2-week treatment with either lanthanum carbonate 1000 mg three times daily or placebo, and to ingest a tightly controlled diet containing 750 or 1500 mg of dietary phosphorus daily. We analysed serial measurements of FGF23, parathyroid hormone, serum Phosphate and calcium, and 24-h urinary Phosphate and calcium Excretion using repeated-measures analyses. Results. Compared with the 1500-mg phosphorus diet, patients assigned to the 750-mg diet had greater reduction in 24-h urinary Phosphate Excretion (66% vs. 29%; P < 0.0001). Lanthanum-treated patients experienced a significant reduction in 24-h urinary Phosphate Excretion compared with baseline (64%; P < 0.0001), but the difference compared with placebo did not reach significance (64% vs. 31%). Despite the significant reductions in 24-h urinary Phosphate Excretion, no group demonstrated a significant reduction in FGF23 levels; FGF23 levels actually increased significantly in the 1500-mg diet plus placebo group, suggesting dietary phosphorus loading. Conclusions. Although dietary phosphorus restriction and lanthanum lowered urinary Phosphate Excretion consistent with a rapid decrease in phosphorus absorption, inducing a reduction in FGF23 levels in CKD patients may require interventions with a longer duration than in healthy volunteers.