Katherine Wesseling-Perry

University of California, Los Angeles, Los Ángeles, California, United States

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Publications (46)179.38 Total impact

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    [Show abstract] [Hide abstract] ABSTRACT: [This corrects the article DOI: 10.1371/journal.pone.0152871.].
    Preview · Article · May 2016 · PLoS ONE
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    [Show abstract] [Hide abstract] ABSTRACT: Pediatric renal osteodystrophy (ROD) is characterized by changes in bone turnover, mineralization, and volume that are brought about by alterations in bone resorption and formation. The resorptive and formative surfaces on the cancellous bone are separated from the marrow cavity by canopies consisting of a layer of flat osteoblastic cells. These canopies have been suggested to play a key role in the recruitment of osteoprogenitors during the process of bone remodeling. This study was performed to address the characteristics of the canopies above bone formation and resorption sites and their association with biochemical and bone histomorphometric parameters in 106 pediatric chronic kidney disease (CKD) patients (stage 2-5) across the spectrum of ROD. Canopies in CKD patients often appeared as thickened multilayered canopies, similar to previous reports in patients with primary hyperparathyroidism. This finding contrasts with the thin appearance reported in healthy individuals with normal kidney function. Furthermore, canopies in pediatric CKD patients showed immunoreactivity to the PTH receptor (PTHR1) as well as to the receptor activator of nuclear factor kappa-B ligand (RANKL). The number of surfaces with visible canopy coverage was associated with plasma parathyroid hormone (PTH) levels, bone formation rate, and the extent of remodeling surfaces. Collectively, these data support the conclusion that canopies respond to the elevated PTH levels in CKD and that they possess the molecular machinery necessary to respond to PTH signaling.
    Preview · Article · Apr 2016 · PLoS ONE
  • Isidro B. Salusky · Katherine Wesseling-Perry
    [Show abstract] [Hide abstract] ABSTRACT: The association between kidney disease, bone disease, and hyperplasia of the parathyroid glands has been recognized for decades. Through signaling mechanisms between bone, kidney, and parathyroid glands, alterations in kidney function lead to changes in circulating biochemical values and to progressive skeletal disease. Early in the course of chronic kidney disease (CKD), at a time when serum calcium and phosphorus concentrations are still within the normal range, changes in circulating calciotropic hormones are evident. Elevated levels of parathyroid hormone (PTH) in blood are common in patients with decreased kidney function; however, end-organ resistance to the actions of PTH also occurs in patients with CKD, necessitating increased concentrations of PTH to maintain normal rates of bone turnover. Persistently increased PTH concentrations in CKD (secondary hyperparathyroidism, 2°HPT) have been associated with abnormal bone metabolism, with subsequent bony deformities, pain, fractures, and (in children) growth failure. Thus, considerable efforts have been devoted to the elucidation of the pathogenesis of secondary hyperparathyroidism.
    No preview · Chapter · Dec 2015
  • Renata C Pereira · David S Bischoff · Dean Yamaguchi · Isidro B Salusky · Katherine Wesseling-Perry
    [Show abstract] [Hide abstract] ABSTRACT: Background and objectives: Computed tomography (CT) measurements can distinguish between cortical and trabecular bone density in vivo. High-resolution CTs assess both bone volume and density in the same compartment, thus potentially yielding information regarding bone mineralization as well. The relationship between bone histomorphometric parameters of skeletal mineralization and bone density from microcomputed tomography (μCT) measurements of bone cores from patients on dialysis has not been assessed. Design, setting, participants, & measurements: Bone cores from 68 patients with ESRD (age =13.9±0.5 years old; 50% men) and 14 controls (age =15.3±3.8 years old; 50% men) obtained as part of research protocols between 1983 and 2006 were analyzed by bone histomorphometry and μCT. Results: Bone histomorphometric diagnoses in the patients were normal to high bone turnover in 76%, adynamic bone in 13%, and osteomalacia in 11%. Bone formation rate did not correlate with any μCT determinations. Bone volume measurements were highly correlated between bone histomorphometry and μCT (bone volume/tissue volume between the two techniques: r=0.70; P<0.001, trabecular thickness and trabecular separation: r=0.71; P<0.001, and r=0.56; P<0.001, respectively). Osteoid accumulation as determined by bone histomorphometry correlated inversely with bone mineral density as assessed by μCT (osteoid thickness: r=-0.32; P=0.01 and osteoid volume: r=-0.28; P=0.05). By multivariable analysis, the combination of bone mineral density and bone volume (as assessed by μCT) along with parathyroid hormone and calcium levels accounted for 38% of the variability in osteoid volume (by histomorphometry). Conclusions: Measures of bone volume can be accurately assessed with μCT. Bone mineral density is lower in patients with excessive osteoid accumulation and higher in patients with adynamic, well mineralized bone. Thus, bone mineralization may be accurately assessed by μCT of bone biopsy cores. Additional studies are warranted to define the value of high-resolution CT in the prediction of bone mineralization in vivo.
    No preview · Article · Dec 2015 · Clinical Journal of the American Society of Nephrology
  • [Show abstract] [Hide abstract] ABSTRACT: Background: Fibroblast growth factor-23 (FGF23) levels are elevated in cardiopulmonary bypass (CPB)-associated acute kidney injury (AKI); however, it is unknown how much of the circulating FGF23 is intact and bioactive. Hypoxia may induce FGF23 production, yet its impact in humans is unknown. Pediatric cardiac surgery patients have both a high incidence of CPB-associated AKI and a high prevalence of chronic hypoxemia. Methods: We assessed the effects of hypoxemia and CPB-associated AKI on C-terminal FGF23 (cFGF23) and intact FGF23 (iFGF23) levels in 32 pediatric cardiac surgery patients with normal estimated glomerular filtration rate (eGFR). Plasma cFGF23 and iFGF23 were measured preoperatively and serially postoperatively. Results: Despite normal renal and ventricular function, preoperative cFGF23 levels were high and elevated out of proportion to iFGF23 levels. Preoperative oxygen saturation measurements correlated inversely with FGF23 levels. Preoperative cFGF23 and oxygen saturation both predicted postoperative AKI. Postoperatively, cFGF23 and iFGF23 increased by 2 h postreperfusion; iFGF23 then returned to baseline, but cFGF23 remained elevated through 24 h postreperfusion. Group status (AKI vs. non-AKI) modified the effect of time on changes in iFGF23 levels but not cFGF23 levels. Conclusions: Preoperative cFGF23 may predict CPB-associated kidney dysfunction. Changes over time in cFGF23 and iFGF23 levels post-CPB differ. Chronic hypoxemia may affect FGF23 production in humans.
    No preview · Article · Nov 2015 · Pediatric Nephrology
  • Katherine Wesseling-Perry
    No preview · Article · Sep 2015 · Kidney International
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    Renata C Pereira · Harald Jüppner · Barbara Gales · Isidro B Salusky · Katherine Wesseling-Perry
    [Show abstract] [Hide abstract] ABSTRACT: Osteocytic protein expression is dysregulated in CKD and is affected by changes in mineral metabolism; however the effects of active vitamin D sterol therapy on osteocyte protein expression in advanced CKD is unknown. Eleven pediatric patients with end stage kidney disease underwent bone biopsy, were treated for 8 months with doxercalciferol, and then underwent a second bone biopsy. Bone expression of fibroblast growth factor 23 (FGF23), dentin matrix protein 1 (DMP1), and sclerostin were determined by immunohistochemistry and quantified by Ariol Scanning. Western blot analysis and qRT-PCR was performed on bone abstracts of a subset of study subjects to determine the nature (i.e. size) of FGF23 and DMP1 in bone before and after therapy. As assessed by immunohistochemistry, bone FGF23, DMP1 and sclerostin protein all increased with therapy. In the case of FGF23, this increase was due to an increase in the full-length molecule without the appearance of FGF23 fragments. DMP1 was present primarily in its full-length form in healthy controls while 57kDa and 37kDa fragments of DMP1 were apparent in bone of dialysis patients at baseline and the 57 kDa appeared to decrease with therapy. Marked changes in osteocytic protein expression accompany doxercalciferol therapy, potentially impacting bone mineralization and the skeletal response to PTH. The effects of these bone changes on long-term outcomes remain to be determined.
    Preview · Article · Mar 2015 · PLoS ONE
  • Katherine Wesseling-Perry
    [Show abstract] [Hide abstract] ABSTRACT: Although traditional diagnosis and treatment of renal osteodystrophy focused on changes in bone turnover, current data demonstrate that abnormalities in skeletal mineralization are also prevalent in pediatric chronic kidney disease (CKD) and likely contribute to skeletal morbidities that continue to plague this population. It is now clear that alterations in osteocyte biology, manifested by changes in osteocytic protein expression, occur in early CKD before abnormalities in traditional measures of mineral metabolism are apparent and may contribute to defective skeletal mineralization. Current treatment paradigms advocate the use of 1,25(OH)2vitamin D for the control of secondary hyperparathyroidism; however, these agents fail to correct defective skeletal mineralization and may exacerbate already altered osteocyte biology. Further studies are critically needed to identify the initial trigger for abnormalities of skeletal mineralization as well as the potential effects that current therapeutic options may have on osteocyte biology and bone mineralization.
    No preview · Article · Feb 2015 · Current Osteoporosis Reports
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    [Show abstract] [Hide abstract] ABSTRACT: Patients with chronic kidney disease (CKD), who usually display low serum 25-hydroxyvitamin D (25D) and 1,25-dihydroxyvitamin D (1,25D), are at high risk of infection, notably those undergoing peritoneal dialysis (PD). We hypothesized that peritoneal macrophages from PD patients are an important target for vitamin D-induced antibacterial activity. Dialysate effluent fluid was obtained from 27 non-infected PD patients. Flow cytometry indicated that PD cells were mainly monocytic (37.9±17.7% cells CD14+/CD45+). Ex vivo analyses showed that PD cells treated with 25D (100 nM, 6 hrs) or 1,25D (5 nM, 6 hrs) induced mRNA for antibacterial cathelicidin (CAMP) but conversely suppressed mRNA for hepcidin (HAMP). PD cells from patients with peritonitis (n = 3) showed higher baseline expression of CAMP (18-fold±9, p<0.05) and HAMP (64-fold±7) relative to cells from non-infected patients. In 12 non-infected PD patients, oral supplementation with a single dose of vitamin D2 (100,000 IU) increased serum levels of 25D from 18±8 to 41±15 ng/ml (p = 0.002). This had no significant effect on PD cell CD14/CD45 expression, but mRNA for HAMP was suppressed significantly (0.5-fold, p = 0.04). Adjustment for PD cell CD14/CD45 expression using a mixed linear statistical model also revealed increased expression of CAMP (mRNA in PD cells and protein in effluent) in vitamin D-supplemented patients. These data show for the first time that vitamin D supplementation in vitro and in vivo promotes innate immune responses that may enhance macrophage antibacterial responses in patients undergoing PD. This highlights a potentially important function for vitamin D in preventing infection-related complications in CKD.
    Full-text · Article · Dec 2014 · PLoS ONE
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    [Show abstract] [Hide abstract] ABSTRACT: Osteocytes regulate bone turnover and mineralization in chronic kidney disease. As osteocytes are derived from osteoblasts, alterations in osteoblast function may regulate osteoblast maturation, osteocytic transition, bone turnover, and skeletal mineralization. Thus, primary osteoblast-like cells were cultured from bone chips obtained from 24 pediatric ESKD patients. RNA expression in cultured cells was compared with RNA expression in cells from healthy individuals, to RNA expression in the bone core itself, and to parameters of bone histomorphometry. Proliferation and mineralization rates of patient cells were compared with rates in healthy control cells. Associations were observed between bone osteoid accumulation, as assessed by bone histomorphometry, and bone core RNA expression of osterix, matrix gla protein, parathyroid hormone receptor 1, and RANKL. Gene expression of osteoblast markers was increased in cells from ESKD patients and signaling genes including Cyp24A1, Cyp27B1, VDR, and NHERF1 correlated between cells and bone cores. Cells from patients with high turnover renal osteodystrophy proliferated more rapidly and mineralized more slowly than did cells from healthy controls. Thus, primary osteoblasts obtained from patients with ESKD retain changes in gene expression ex vivo that are also observed in bone core specimens. Evaluation of these cells in vitro may provide further insights into the abnormal bone biology that persists, despite current therapies, in patients with ESKD.Kidney International advance online publication, 29 October 2014; doi:10.1038/ki.2014.347.
    Full-text · Article · Oct 2014 · Kidney International
  • Catarina G Carvalho · Renata C Pereira · Barbara Gales · Isidro B Salusky · Katherine Wesseling-Perry
    [Show abstract] [Hide abstract] ABSTRACT: Background Cortical bone represents nearly 80 % of human bone mass and is the major determinant of bone strength; however, cortical bone parameters and their relationship to trabecular bone in the pediatric chronic kidney disease (CKD) population have not been evaluated. Methods Biochemical values and cortical and trabecular bone parameters were assessed in 22 pediatric dialysis patients: 12 with high and 10 with normal to low trabecular bone turnover. Results Trabecular bone turnover and osteoid volume correlated with parathyroid hormone (PTH) levels (r = 0.86, p
    No preview · Article · Sep 2014 · Pediatric Nephrology
  • Nadine M Khouzam · Katherine Wesseling-Perry · Isidro B Salusky
    [Show abstract] [Hide abstract] ABSTRACT: Cardiovascular disease is the leading cause of death in pediatric patients with chronic kidney disease (CKD), and vascular calcifications start early in the course of CKD. Based on the growing body of evidence that alterations of bone and mineral metabolism and the therapies designed to treat the skeletal consequences of CKD are linked to cardiovascular calcifications, the Kidney Disease, Improving Global Outcomes (KDIGO) working group redefined renal osteodystrophy as a systemic disorder of mineral and bone metabolism due to CKD, and this newly defined disorder is now known as "chronic kidney disease-mineral bone disorder (CKD-MBD)". Elevated fibroblast growth factor 23 (FGF23), a bone-derived protein, is the first biochemical abnormality to be associated with CKD-MBD, and high FGF23 levels correlate with increased cardiovascular morbidity and mortality, suggesting that bone is central to both initiating and perpetuating the abnormal mineral metabolism and vascular disease in CKD. The current standard therapies for CKD-MBD affect FGF23 levels differently; non-calcium-based binders with or without concurrent use of dietary phosphate restriction reduce FGF23 levels, while calcium-based binders seem to either increase or have no effect on FGF23 levels. Active vitamin D sterols increase FGF23 levels, whereas therapy with calcimimetics decreases FGF23 levels. Thus, the appropriate therapy that will minimize the rise in FGF23 and prevent cardiovascular morbidity remains to be defined.
    No preview · Article · Aug 2014 · Pediatric Nephrology
  • Katherine Wesseling-Perry · Hejing Wang · Robert Elashoff · Barbara Gales · Harald Jüppner · Isidro B Salusky
    [Show abstract] [Hide abstract] ABSTRACT: Context: 1,25(OH)2vitamin D (1,25D) administration and long-term increases in phosphate, PTH and calcium concentrations are associated with increases in circulating FGF23; however, the whether or not acute changes in serum calcium modulate short-term FGF23 release is unknown. Objective/Design: To assess the direct effect of acute changes in calcium and PTH on circulating FGF23 levels. Setting: University clinical and translational research center Patients/Participants: Twelve healthy volunteers and 10 dialysis patients Interventions: Calcium gluconate and sodium citrate were infused for 120 minutes on two consecutive days. Main Outcome Measures: Serum levels of ionized calcium, phosphorus, PTH, 1,25D, and plasma C-terminal FGF23 levels were obtained at 0, 13, 30, 60, 90, and 120 minutes during the infusions. Results: During the calcium infusion, serum calcium concentrations increased from 1.33 ± 0.01 mmol/L to 1.57 ± 0.04 mmol/L and from 1.20 ± 0.05 mmol/L to 1.50 ± 0.03 mmol/L (p<0.05 from baseline in both groups) in healthy subjects and in dialysis patients, respectively while serum calcium values decreased from 1.33 ± 0.01 mmol/L to 1.03 ± 0.02 mmol/L and from 1.26 ± 0.04 mmol/L to 1.07 ± 0.03 mmol/L in the two groups, respectively (p<0.05 in both groups) during the sodium citrate infusion. PTH levels decreased from 35 (29, 57) pg/ml to 8 (2,10) pg/ml (healthy subjects) and from 292 (109, 423) pg/ml to 44 (28, 86) pg/ml (dialysis patients) (p<0.05 in both groups) during the calcium infusion and rose from 31 (25, 56) pg/ml to 122 (95, 157) pg/ml and from 281 (117, 607) pg/ml to 468 (169, 928) pg/ml (p<0.05 in both groups) during sodium citrate infusion. Serum 1,25D levels and plasma FGF23 values remained unchanged during both infusions in both groups. Conclusions: Short-term changes in calcium and PTH levels do not affect FGF23 concentrations in either healthy volunteers or in dialysis patients.
    No preview · Article · Jul 2014 · Journal of Clinical Endocrinology & Metabolism
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    Katherine Wesseling-Perry
    [Show abstract] [Hide abstract] ABSTRACT: This Commentary highlights the article by Andersen et al, which describes structural changes in bone associated with increased bone resorption in osteoporotic post-menopausal women.
    Preview · Article · Feb 2014 · American Journal Of Pathology
  • [Show abstract] [Hide abstract] ABSTRACT: Habitual short sleep duration appears to increase the risk of obesity. The objective of this paper is to investigate the association of habitual sleep duration with objective measures of energy balance. One hundred twelve African-American and 111 non-Hispanic whites aged 21-69 y participated in a cross-sectional study of dietary assessment and biomarkers. Participants reported the mean number of hours per day spent sleeping over the past year. Short sleep duration was defined as ≤6 h/d of sleep. Energy intake (kilocalories) was objectively assessed using the 2-point doubly labeled water technique to determine total energy expenditure, which is approximately equal to energy intake. Physical activity energy expenditure (kilocalories) was estimated as total energy expenditure minus each participant's calculated basal metabolic rate and the thermogenic effect of food. Compared with participants who slept ≤6 h, individuals who slept 8 h were significantly less likely to be obese (OR: 0.33; 95% CI: 0.14, 0.79). However, this association was not linear across 6-9 h of sleep (P-trend = 0.16). There was an inverse association between sleep and energy intake (P-trend = 0.07): compared with ≤6 h/d, adults who reported ≥9 h sleep consumed 178 fewer kcal/d. There was also an inverse association between sleep and physical activity (P-trend = 0.05): compared with ≤6 h/d of sleep, adults who reported 9 h of usual sleep expended 113 fewer kcal/d in physical activity. These data indicate that, compared with longer sleep duration, adults who report habitual short sleep duration have somewhat higher physical activity energy expenditure but considerably higher energy intake. Habitual short sleep duration appears to be 1 of the facets of modern life leading to a mismatch between energy intake and physical activity.
    No preview · Article · Feb 2014 · Journal of Nutrition
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    [Show abstract] [Hide abstract] ABSTRACT: Fibroblast growth factor 23 (FGF23) levels are elevated in chronic kidney disease (CKD) and elevated values have been associated with both heart disease and mortality. Recent studies show that FGF23, a protein synthesized by osteocytes, is also present in calcified atherosclerotic plaques and may be induced by heart disease. Whether vascular expression of FGF23 is associated with progressive CKD, however, remains unknown. Therefore, the relationship between kidney function, vascular calcification and FGF23 expression was evaluated in patients with heart disease. Immunohistochemistry for FGF23 was performed in coronary arteries of all patients undergoing heart transplantation at UCLA between February 2008 and 2010. Immunohistochemical staining for Klotho, DMP1, FGFR1, and FGFR3; calcium deposition; and RNA expression of Klotho and DMP1 were assessed in a subset of eight samples. FGF23 was detected by immunohistochemistry in 56% of the coronary artery specimens. Vascular FGF23 expression correlated with declining kidney function, as evidenced by reduced creatinine clearance. FGFR1 and FGFR3 were detected throughout the vascular tissue and in calcified plaques. Calcium deposition, Klotho expression and DMP1 expression correlated with FGF23 immunoreactivity. The findings suggest that the Klotho-FGF23-FGFR system is active in coronary arteries and its upregulation correlates with impaired renal function and matrix calcium deposition.
    Preview · Article · Jan 2014 · Nephrology Dialysis Transplantation
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    [Show abstract] [Hide abstract] ABSTRACT: In children with CKD, information is limited regarding the prevalence and determinants of fibroblast growth factor 23 excess and 1,25-dihyroxyvitamin D deficiency across the spectrum of predialysis CKD. This study characterized circulating concentrations of fibroblast growth factor 23 and 1,25-dihyroxyvitamin D, and investigated their interrelationships and associations with GFR and secondary hyperparathyroidism in children with CKD who were enrolled in the Chronic Kidney Disease in Children observational cohort study. Plasma fibroblast growth factor 23 concentrations and determinants of mineral metabolism were measured in 464 children ages 1-16 years with predialysis CKD. GFR was measured by plasma disappearance of iohexol in 70% of participants and estimated by the Chronic Kidney Disease in Children estimating equation using serum creatinine and cystatin C concentrations in the remainder of the participants. Participants were grouped according to CKD stage and by 10-ml/min categories of GFR. Median GFR for the cohort was 45 ml/min per 1.73 m(2) (interquartile range=33-57; range=15-109). Plasma fibroblast growth factor 23 concentration was above the normal range in 67% of participants (with higher levels observed among participants with lower GFR) before higher levels of serum parathyroid hormone and phosphorus were observed. Plasma fibroblast growth factor 23 levels were 34% higher in participants with glomerular disease than in participants with nonglomerular disease, despite similar GFR. Serum phosphorus levels, adjusted for age, were significantly lower at GFR of 60-69 ml/min per 1.73 m(2) than higher GFR, but thereafter they became higher in parallel with fibroblast growth factor 23 as GFR declined. Serum 1,25-dihyroxyvitamin D concentrations were lower in those participants with low GFR values, high fibroblast growth factor 23 levels, 25-hydroxyvitamin D deficiency, and proteinuria. Secondary hyperparathyroidism was present in 55% of participants with GFR<50 ml/min per 1.73 m(2). In children with predialysis CKD, high plasma fibroblast growth factor 23 is the earliest detectable abnormality in mineral metabolism, and levels are highest in glomerular diseases.
    Preview · Article · Dec 2013 · Clinical Journal of the American Society of Nephrology
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    [Show abstract] [Hide abstract] ABSTRACT: The antibacterial protein hepcidin regulates the absorption, tissue distribution, and extracellular concentration of iron by suppressing ferroportin-mediated export of cellular iron. In CKD, elevated hepcidin and vitamin D deficiency are associated with anemia. Therefore, we explored a possible role for vitamin D in iron homeostasis. Treatment of cultured hepatocytes or monocytes with prohormone 25-hydroxyvitamin D or active 1,25-dihydroxyvitamin D decreased expression of hepcidin mRNA by 0.5-fold, contrasting the stimulatory effect of 25-hydroxyvitamin D or 1,25-dihydroxyvitamin D on related antibacterial proteins such as cathelicidin. Promoter-reporter and chromatin immunoprecipitation analyses indicated that direct transcriptional suppression of hepcidin gene (HAMP) expression mediated by 1,25-dihydroxyvitamin D binding to the vitamin D receptor caused the decrease in hepcidin mRNA levels. Suppression of HAMP expression was associated with a concomitant increase in expression of the cellular target for hepcidin, ferroportin protein, and decreased expression of the intracellular iron marker ferritin. In a pilot study with healthy volunteers, supplementation with a single oral dose of vitamin D (100,000 IU vitamin D2) increased serum levels of 25D-hydroxyvitamin D from 27±2 ng/ml before supplementation to 44±3 ng/ml after supplementation (P<0.001). This response was associated with a 34% decrease in circulating levels of hepcidin within 24 hours of vitamin D supplementation (P<0.05). These data show that vitamin D is a potent regulator of the hepcidin-ferroportin axis in humans and highlight a potential new strategy for the management of anemia in patients with low vitamin D and/or CKD.
    Full-text · Article · Nov 2013 · Journal of the American Society of Nephrology
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    [Show abstract] [Hide abstract] ABSTRACT: The utilization of short-term daily hemodialysis has increased over the last few years, but little is known on its effects on the control of serum phosphate and fibroblast growth factor 23 (FGF23) levels. We therefore performed a cross-sectional study to compare FGF23 levels as well as other biochemical variables between 24 patients undergoing short daily hemodialysis using the NxStage System® and 54 patients treated with conventional in-center hemodialysis. FGF23 levels were measured using the second-generation Immutopics® C-terminal assay. Short daily hemodialysis patients were younger than patients on conventional hemodialysis but there were no differences between groups in the duration of end-stage renal disease nor in the number of patients with residual renal function. A greater number of short daily hemodialysis patients received vitamin D sterol therapy than did conventional in-center hemodialysis patients while there were no differences in the use of different phosphate binders and calcimimetic therapy between groups. Overall serum calcium, phosphorus and intact parathyroid hormone levels were similar between groups. While serum phosphorus levels correlated with FGF23 concentrations in each group separately [r = 0.522 (P < 0.01) and r = 0.42 (P < 0.01) in short daily and conventional in-center hemodialysis, respectively], FGF23 levels were lower [823 RU/mL (263, 2169)] in the patients receiving short daily hemodialysis than in patients treated with conventional hemodialysis [2521 RU/mL (909, 5556)] (P < 0.01 between groups). These findings demonstrate that FGF23 levels are significantly lower in short daily hemodialysis patients and suggest that FGF23 levels may be a more sensitive biomarker of cumulative phosphate burden than single or multiple serum phosphorus determinations in patients treated with hemodialysis.
    Preview · Article · Sep 2013 · Nephrology Dialysis Transplantation
  • [Show abstract] [Hide abstract] ABSTRACT: The relationship between fibroblast growth factor 23 (FGF23) and vitamin D production and catabolism post-renal transplantation has not been characterized. Circulating creatinine, calcium, phosphorus, albumin, parathyroid hormone, FGF23, and 1,25(OH)2 vitamin D (calcitriol) values were obtained pre-transplantation, daily post-operatively for 5 days, and at 6 months post-transplantation in 44 patients aged 16.4 ± 0.4 years undergoing renal transplantation at UCLA from 1 August 2005 through to 30 April 2007. 25(OH) Vitamin D and 24,25(OH)2 vitamin D concentrations were obtained at baseline and on post-operative days 5 and 180, and urinary concentrations of creatinine, phosphorus, and FGF23 were measured on post-operative days 1, 3, 5, and 180. Circulating phosphate concentrations declined more rapidly and the fractional excretion of phosphorus was higher in the first week post-transplantation in subjects with higher FGF23 values. Fractional excretion of FGF23 was low at all time-points. Circulating 1,25(OH)2 vitamin D levels rose more rapidly and were consistently higher in patients with lower FGF23 values; however, 25(OH) vitamin D and 24,25(OH)2 vitamin D values were unrelated to FGF23 concentrations. Inhibition of renal 1α-hydroxylase, rather than stimulation of 24-hydroxylase, may primarily contribute to the relationship between FGF23 values and calcitriol. The rapid decline in FGF23 levels post-transplantation in our patient cohort was not mediated solely by the filtration of intact FGF23 by the new kidney.
    No preview · Article · Jul 2013 · Pediatric Nephrology