Changes In Fibroblast Growth Factor 23 Levels Research Articles

Exploring the implications of blocking renin-angiotensin-aldosterone system and fibroblast growth factor 23 in early left ventricular hypertrophy without chronic kidney disease.

Whether fibroblast growth factor 23 (FGF23) directly induces left ventricular hypertrophy (LVH) remains controversial. Recent studies showed an association between FGF23 and the renin-angiotensin-aldosterone system (RAAS). The aim of this study was to investigate changes in FGF23 levels and RAAS parameters and their influences on LVH. In the first experiment, male C57BL/6J mice were divided into sham and transverse aortic constriction (TAC) groups. The TAC group underwent TAC at 8 weeks of age. At 1, 2, 3, and 4 weeks after TAC, the mice were sacrificed, and blood and urine samples were obtained. Cardiac expressions of FGF23 and RAAS-related factors were evaluated, and cardiac histological analyses were performed. In the second experiment, the sham and TAC groups were treated with vehicle, angiotensin-converting enzyme (ACE) inhibitor, or FGF receptor 4 (FGFR4) inhibitor and then evaluated in the same way as in the first experiment. In the early stage of LVH without chronic kidney disease, serum FGF23 levels did not change but cardiac FGF23 expression significantly increased along with LVH progression. Moreover, serum aldosterone and cardiac ACE levels were significantly elevated, and cardiac ACE2 levels were significantly decreased. ACE inhibitor did not change serum FGF23 levels but significantly decreased cardiac FGF23 levels with improvements in LVH and RAAS-related factors, while FGFR4 inhibitor did not change the values. Not serum FGF23 but cardiac FGF23 levels and RAAS parameters significantly changed in the early stage of LVH without chronic kidney disease. RAAS blockade might be more crucial than FGF23 blockade for preventing LVH progression in this condition.

Significance of changes in FGF23 levels in childhood primary nephrotic syndrome and children who progress to end‑stage renal disease.

Fibroblast growth factor 23 (FGF23) is an important phosphaturic hormone, yet few studies have focused on FGF23 in children with primary nephrotic syndrome (PNS) and children who progressed to end-stage renal disease (ESRD). This cross-sectional study investigated the significance of changes in FGF23 levels in childhood PNS and children who progressed to ESRD. Of the 41 children included in the study, 17 had PNS with proteinuria and normal renal function (PNS group), 4 had ESRD (ESRD group), and 20 were healthy (control group). Following corticosteroid treatment, patients with PNS and proteinuria entered the remission phase. Serum levels of FGF23, phosphate, parathyroid hormone (PTH), 25-hydroxyvitamin D (25-OH-D), and calcium were measured. It was found that FGF23 levels in the PNS and ESRD groups were higher than those in the control group, while serum 25-OH-D levels were lower. Serum PTH levels increased significantly in the ESRD group. In the control group, FGF23 levels were negatively correlated with serum PTH and positively correlated with serum 25-OH-D. FGF23 levels were positively correlated with serum calcium and corrected calcium levels in children with PNS during the remission phase. Increased FGF23 levels in children with PNS, particularly in children who progressed to ESRD. It was also confirmed that serum FGF23 levels begin to rise in children with PNS prior to Stage 1 chronic kidney disease. These findings indicated that increased FGF23 levels may be associated with the progression and severity of nephrosis in children, and that serum FGF23 levels were useful for early detection of abnormal mineral metabolism in children with PNS.

Factors associated with 1-year changes in serum fibroblast growth factor 23 levels in pediatric patients with chronic kidney disease.

Fibroblast growth factor 23 (FGF23) levels increase as kidney function decreases and are associated with increased mortality in patients with chronic kidney disease (CKD). Inflammation has also been shown to increase FGF23 production in adults; however, this has not been validated in pediatric patients with CKD. Furthermore, previous studies on children involved a single measurement of FGF23 without a follow-up, and a few studies have examined changes in FGF23 levels. We measured the levels of serum intact FGF23, tumor necrosis factor-α (TNF-α), and interleukin-6 as parameters of inflammation and other variables related to bone metabolism at baseline and after 1year in 62 pediatric patients with CKD (stages 2-5D, 1-16years old). Factors related to changes in FGF23 levels were investigated. The median age of patients at the evaluation was 10.5years (interquartile range 6.0-14.0), and the estimated glomerular filtration rate (eGFR) was 59.0mL/min/1.73 m2 (45.1-69.3). Primary diseases included congenital anomalies of the kidney and urinary tract, ischemic kidney, and glomerulonephritis. The baseline value of FGF23 was 66.5pg/mL (48.3-96.4), and percent change in FGF23 levels after 1year was 8.5% (-29.9-74.7). The percent change in FGF23 levels showed a negative correlation with that in eGFR (P = 0.010), and a positive correlation with that in TNF-α levels (P = 0.035). A multivariate linear regression analysis identified TNF-α as an independent factor increasing FGF23 levels. An increase in TNF-α levels is associated with elevation of FGF23 levels in pediatric patients with CKD.

MO1012: Variability of Klotho and FGF-23 Levels After Kidney Transplantation Depending on the Glomerular Filtration Rate

Abstract BACKGROUND AND AIMS Klotho is a transmembrane protein expressed mainly in distal tubular epithelial cells of the kidneys. Its gene expression and soluble form levels play a crucial role in the interaction of the aging-inflammation binomial and act as a co-receptor for the phosphaturic fibroblast growth factor 23 (FGF-23). Klotho deficiency, which is the norm in chronic kidney disease (CKD), has been reported as an independent risk factor for cardiovascular disease and subclinical atherosclerosis [1, 2]. This study investigates the evolution of Klotho and FGF-23 levels during the first 2 years after kidney transplantation and their variability depending on the glomerular filtration rate (GFR). METHOD Serum levels of Klotho and FGF-23 were determined in 42 patients right before kidney transplantation (KT) and at 3rd, 12th and 24th month after KT. The measurements were made by ELISA. The GFR of the kidney graft was performed by indirect methods (formula: MDRa and CKD-EPI) at each study visit. Variables were reported as mean ± SD, and a value of P < .05 was considered to be statistically significant for each test. RESULTS KT recipients were divided into two groups arbitrary: the first group with a GFR > 40 mL/min (n = 26) and the other one with a GFR ≤ 40 mL/min (n = 16). At the starting point, there was not found any statistical difference in Klotho and FGF-23 levels between groups (GFR > 40 mL/min: 462.65 ± 264.99 pg/mL and 786.84 ± 521.67 pg/mL, respectively; versus GFR ≤ 40 mL/min: 436.5 ± 189.33 and 779.02 ± 589.86). Those with better kidney function after KT significantly increased Klotho levels on 12th and 24th month of follow-up (baseline 462.65 ± 264.99 versus 12th month 561.96 ± 314.68 and 24th month 581.15 ± 350.10; P = .001), whereas KT recipients with a GFR ≤ 40 mL/min only proved an increase in Klotho levels at 12th month after a non-significant initial decrease at 3rd month (462 ± 204.91 versus 356.96 ± 177.07, respectively; P = .028). This trend was not confirmed at the 24th month (397.12 ± 182.05). Klotho levels were found significantly different at the 24th month between groups (P = .031). See Fig. 1. Figure 2 shows the changes in FGF-23 levels. There are significant differences in both groups from baseline to month 24. (P < .001 group GFR > 40 mL/min and P < .001 group GFR ≤ 40 mL/min). FGF-23 dropped significantly in both groups at the 3rd month (P = .018) and 12th months (P = .003). CONCLUSION Vascular disease and mineral metabolism malfunction are relevant abnormalities in patients with CKD as well as in KT recipients. This study shows that Klotho is increasingly produced after KT in those patients whose allografts achieve a better function. We failed to prove the same effect on those with a GFR < 40 mL/min. Nonetheless, FGF-23 production declines satisfactorily independently of GRF. These results suggest the promotion of cardiovascular health after KT, particularly in those with higher GFR. The clinical and prognostic value of these changes are yet to be determined.

Aldosterone Is Positively Associated With Circulating FGF23 Levels in Chronic Kidney Disease Across Four Species, and May Drive FGF23 Secretion Directly.

BackgroundChronic kidney disease (CKD) is accompanied by increases in circulating fibroblast growth factor 23 (FGF23) and aldosterone levels. Here, we tested the hypothesis that aldosterone may be one of the driving forces behind increased FGF23 secretion in CKD.MethodsUsing data from a prospective study in humans, a retrospective study in dogs and cats, and an experimental study in 5/6-nephrectomized mice, we analyzed the relationship between circulating FGF23 and serum aldosterone levels in CKD across four species. To assess the effects of acute inhibition of aldosterone signaling on circulating FGF23, we acutely treated mice with established CKD with the mineralocorticoid receptor blocker canrenone (50 mg/kg iv/sc), and measured intact FGF23 before and 24 h as well as 72 h after start of administration of the drug.ResultsWe found a tight positive association between circulating intact FGF23 and serum aldosterone in human, canine, and feline CKD patients, as well as in experimental murine CKD (humans: rS = 0.57, p = 0.0368; dogs: rS = 0.66, p = 0.0019; cats: rS = 0.75, p = 0.0003; mice: rS = 0.49, p = 0.0004). Injection of canrenone in mice with established CKD did not lead to changes in FGF23 levels within 24 h, but reduced FGF23 in all mice at 72 h.ConclusionAldosterone may drive enhanced FGF23 secretion in CKD, possibly explaining the tight positive association between circulating intact FGF23 and aldosterone in human, canine, and feline CKD patients as well as in experimental CKD models.

Effect of selected elastic band resistance training on serum levels of fibroblast growth factor 23, TNF-α and hsCRP in overweight elderly women

ntroduction: Chronic inflammation can be the main cause of many common diseases in old age. Elevated level of CRP and proinflammatory cytokines such as TNF-α is positively associated with fibroblast growth factor 23 (FGF23). Therefore, considering the potentially beneficial effect of elastic band resistance training (EBRT) on these variables, this study was performed with aim to investigate the effect of 12 weeks of selected EBRT on serum levels of FGF23, TNF-α and hsCRP in overweight elderly women. Methods: This clinical trial study was performed in 2017 on 28 elderly women in Shahrekord. The subjects were randomly divided into experimental and control groups. EBRT was performed for 12 weeks. Fasting blood samples were taken 24 hours before the first training session and 48 hours after the last training session to measure serum levels of FGF23, TNF-α and hsCRP. Data were analyzed by SPSS software (version 25) and repeated measure two-way ANOVA test. P<0.05 was considered statistically significant. Results: EBRT had no significant effect on serum FGF23 levels, BMI, and Waist-to-hip ratio in elderly women (P>0.05); but serum levels of TNF-α (P=0.046), hsCRP (P=0.037), and also body fat percentage (P=0.023) significantly decreased after EBRT. Conclusion: Regardless to no significant changes in FGF23 levels, it seems that 12 weeks of EBRT can have a significant effect on reducing chronic inflammation in the elderly by reducing the levels of hsCRP and proinflammatory cytokine TNF-α.

The Effect of High Flux versus Low Flux Dialyzers on Serum Fibroblast Growth Factor-23 (FGF-23) and Its Cardiovascular Implications in Prevalent Hemodialysis Patients

Background: Cardiovascular disease is the main cause of death in patients with end stage renal disease. Fibroblastic growth factor- 23 (FGF-23) is a novel phosphaturic hormone produced in the osteocyte. Patients with kidney disease complain of elevated levels of FGF-23 in response to hyperphosphatemia. Patients and Methods: This was a cross-over prospective study conducted on 30 patients on regular hemodialysis. The study period was 6 months, laboratory investigations for FGF-23, complete blood picture, s. urea (pre-dialysis and post-dialysis), serum albumin, serum electrolytes (Ca++ & PO4), alkaline phosphatase, PTH, serum ferritin, and lipid profile as well as echocardiography were obtained in the start of the study, after 3 months on maintained lowflux hemodialysis and 3 months after switching the patients to high-flux hemodialysis. Results: There was a highly significant reduction of FGF-23 level with high-flux dialyzers than with low-flux dialyzers. The adjusted difference in the absolute change in FGF-23 levels between the three months period of lowflux dialysis and the three months period of high-flux dialysis showed a highly significant reduction with high-flux than with low-flux (p= 0.000). There was a significant reduction of serum levels of PTH, calcium, phosphorus levels with high-flux dialyzers than with low-flux dialyzers, the adjusted difference was (p= 0.022), (p= 0.000), and (p= 0.006) respectively. Conclusion: FGF-23 levels were significantly higher in hemodialysis patients than in normal population. FGF-23 was better eliminated by high-flux dialyzers than low-flux dialyzers and high FGF-23 levels were associated with increased incidence of cardiac valve calcification. FGF-23 positively correlated with right ventricular systolic pressure.

Effect of High-Flux Dialysis on Circulating FGF-23 Levels in End-Stage Renal Disease Patients: Results from a Randomized Trial.

BackgroundIn patients undergoing maintenance hemodialysis (HD), increased levels of circulating fibroblast growth factor-23 (FGF-23) are independently associated with cardiovascular events and mortality. Interventional strategies aiming to reduce levels of FGF-23 in HD patients are of particular interest. The purpose of the current study was to compare the impact of high-flux versus low-flux HD on circulating FGF-23 levels.MethodsWe conducted a post-hoc analysis of the MINOXIS study, including 127 dialysis patients randomized to low-flux (n = 62) and high-flux (n = 65) HD for 52 weeks. Patients with valid measures for FGF-23 investigated baseline and after 52 weeks were included.ResultsCompared to baseline, a significant increase in FGF-23 levels after one year of low-flux HD was observed (Delta plasma FGF-23: +4026 RU/ml; p < 0.001). In contrast, FGF-23 levels remained stable in the high flux group (Delta plasma FGF-23: +373 RU/ml, p = 0.70). The adjusted difference of the absolute change in FGF-23 levels between the two treatment groups was statistically significant (p < 0.01).ConclusionsOver a period of 12 months, high-flux HD was associated with stable FGF-23 levels, whereas the low-flux HD group showed an increase of FGF-23. However, the implications of the different FGF 23 time-trends in patients on high flux dialysis, as compared to the control group, remain to be explored in specifically designed clinical trials.Trial RegistrationGerman Clinical Trials Register (DRKS) DRKS00007612.

Dietary phosphorus restriction by a standard low-protein diet decreased serum fibroblast growth factor 23 levels in patients with early and advanced stage chronic kidney disease

Elevated serum fibroblast growth factor 23 (FGF23) levels are associated with mortality, cardiovascular disease, and disease progression in patients with chronic kidney disease (CKD). Although recent studies demonstrated that FGF23 levels decreased in response to dietary restriction of phosphorus and/or use of phosphate binders, research on the effects of a standard low-protein diet is lacking. The effects of a standard low-protein diet on serum FGF23, intact parathyroid hormone, and 1,25-dihydroxyvitamin D levels were investigated in patients with early (n = 15) and advanced (n = 20) CKD. Serum FGF23 levels decreased in both groups. Changes in FGF23 levels correlated with changes in 24 h urinary phosphorus excretion in the advanced CKD group. Decreased serum intact parathyroid hormone levels were observed only in the advanced CKD group and increased serum 1,25-dihydroxyvitamin D levels only in the early CKD group. These findings suggest that consuming standard low-protein diet decreased serum FGF23 levels in patients with CKD. Serum FGF23 levels may therefore be a useful marker to monitor the effects of a low-protein diet in early and advanced stage CKD.

Cinacalcet lowering of serum fibroblast growth factor-23 concentration may be independent from serum Ca, P, PTH and dose of active vitamin D in peritoneal dialysis patients: a randomized controlled study

BackgroundElevated serum level of fibroblast growth factor-23 (FGF23) is associated with adverse outcomes in dialyzed patients.ObjectivesThe CUPID study compared the efficacy of a cinacalcet-based regimen with conventional care (vitamin D and P binders) for achieving the stringent NKF-K/DOQI targets for peritoneal dialysis (PD) patients. Additionally, we analyzed change in FGF23 levels between two treatments to explore the cinacalcet effect in lowering FGF23.DesignMulticenter, open-labeled, randomized controlled study.SettingSeven university-affiliated hospitals in Korea.ParticipantsOverall, 66 peritoneal dialysis patients were enrolled.InterventionSixty six patients were randomly assigned to treatment with either cinacalcet + oral vitamin D (cinacalcet group, n = 33) or oral vitamin D alone (control group, n = 33) to achieve K/DOQI targets. CUPID included a 4-week screening for vitamin D washout, a 12-week dose-titration, and a 4-week assessment phases. We calculated mean values of iPTH, Ca, P, Ca x P, during assessment phase and final FGF23 to assess the outcome.Main outcome measuresAchievement of >30% reduction of iPTH from baseline (primary) and FGF23 reduction (secondary).Results72.7% (n = 24) of the cinacalcet group and 93.9% (n = 31) of the control group completed the study. Cinacalcet group received 30.2 ± 18.0 mg/day of cinacalcet and 0.13 ± 0.32 μg/d oral vitamin D (P < 0.001 vs. control with 0.27 ± 0.18 μg/d vitamin D). The proportion of patients who reached the primary endpoint was not statistically different (48.5% vs. 51.5%, cinacalcet vs. control, P = 1.000). After treatment, cinacalcet group experienced a significant reduction in FGF23 levels (median value from 3,960 to 2,325 RU/ml, P = 0.002), while an insignificant change was shown for control group (from 2,085 to 2,415 RU/ml). The percent change of FGF23 after treatment was also significantly different between the two groups (− 42.54% vs. 15.83%, P = 0.008). After adjustment, cinacalcet treatment was independently associated with the serum FGF23 reduction.ConclusionCinacalcet treatment was independently associated with the reduction of FGF23 in our PD patients.Trial registrationControlled trials NCT01101113

Effects of Dietary Phosphate Restriction and Phosphate Binders on FGF23 Levels in CKD

Elevated levels of fibroblast growth factor 23 (FGF23) are associated with increased risk of adverse outcomes in patients with CKD. Reducing dietary phosphate intake or absorption may decrease FGF23 levels, but data on the combined effects of dietary phosphate restriction and phosphate binders in CKD are limited. In this 2×2 factorial, single-blinded, placebo-controlled, 3-month study, conducted between July 2009 and March 2012, 39 patients with CKD stages 3 or 4 and normal serum phosphate levels were randomly assigned to one of four groups: ad libitum diet plus lanthanum carbonate (LC) placebo (n=10), 900-mg phosphate diet plus LC placebo (n=10), ad libitum diet plus LC (n=11), or 900-mg phosphate diet plus LC (n=8). The dose of LC was 1000 mg three times daily with meals. Dietary restriction was accomplished with outpatient counseling. The primary end point was change in FGF23 levels from baseline. Compared with ad libitum diet, the 900-mg phosphate diet did not significantly reduce FGF23 levels (diet × time interaction, P=0.05). Compared with placebo, LC alone also did not significantly reduce FGF23 levels (LC × time interaction, P=0.21). However, the dual intervention significantly decreased FGF23 levels throughout the study period (diet × LC × time interaction, P=0.02), resulting in a 35% (95% confidence interval, 8%-62%) reduction by study end. The combination of LC plus counseling for a phosphate-restricted diet decreased FGF23 levels in patients with CKD stages 3-4 and normal serum phosphate levels.

Fibroblast growth factor 23 and soluble klotho in children with chronic kidney disease

Fibroblast growth factor 23 (FGF23), a bone-derived phosphaturic hormone, is elevated in chronic kidney disease (CKD). There are scarce data on the levels of its essential co-receptor klotho, and longitudinal changes in FGF23 levels are also unknown. We examined FGF23 and soluble klotho (s-klotho) levels over 1 year in 154 children with CKD Stages 1-5 (CKD1-5), were on dialysis or who have received a transplantation. In children with CKD1-5 and who were receiving dialysis, FGF23 correlated inversely with the estimated glomerular filtration rate (eGFR) (P < 0.001), whereas a decrease in s-klotho was observed with a lower eGFR (P = 0.01). There was no correlation between FGF23 and serum phosphate (P) or parathyroid hormone (PTH) in our cohort wherein 89 and 66%, respectively, had normal levels. FGF23 increased by 6-fold over a 12-month period in children with eGFR of 15-29 mL/min/1.73 m(2), with an overall 5% annual increase in the CKD1-5 and dialysis cohort. High FGF23 levels were seen with high calcium (Ca) levels (P < 0.001). FGF23 levels were high when 25-hydroxyvitamin D [25(OH)D] and 1,25-dihydroxyvitamin D [1,25(OH)(2)D] were deficient (P = 0.05 and P < 0.001, respectively). s-klotho levels correlated positively with 25(OH)D (P < 0.001) and negatively with PTH (P = 0.04) and age (P = 0.03). Multivariate regression analysis demonstrated a strong relationship between FGF23 and eGFR, whereas the association between s-klotho and eGFR as observed in univariate analysis was lost following the adjustment of confounders. In transplanted patients, FGF23 correlated with eGFR (P = 0.02) and 25(OH)D (P = 0.05). This study shows increasing FGF23 and reduced s-klotho levels with progressive renal failure even in a population of children with well-controlled P levels. Novel associations between FGF23 and serum Ca as well as 25(OH)D warrant further investigation.

Comparison of Calcium Acetate and Sevelamer on Vascular Function and Fibroblast Growth Factor 23 in CKD Patients: A Randomized Clinical Trial

Fibroblast growth factor 23 (FGF-23) is a marker of endothelial dysfunction and atherosclerotic complications in patients with chronic kidney disease (CKD). Because previous studies suggested that sevelamer may exert effects on FGF-23 level and endothelial function independently of its phosphate-lowering action, we tested the effect of sevelamer versus calcium acetate on vascular function and FGF-23 levels. Randomized prospective open-label trial. Patients with stage 4 CKD with hyperphosphatemia (n = 100). An 8-week intervention with sevelamer (n = 47) and calcium acetate (n = 53). The primary study outcome was change in flow-mediated vasodilatation in the forearm. The secondary outcome was change in FGF-23 levels. Serum phosphate levels decreased in both treatment arms (P < 0.001), but more markedly in the sevelamer group (P < 0.001). Flow-mediated vasodilatation increased from 6.1% to 7.1% (P < 0.001) in sevelamer-treated patients, whereas it was unchanged in the calcium-acetate group (6.0% vs 6.0%). In a combined analysis, treatment-induced changes in flow-mediated vasodilatation were (P < 0.001) associated with simultaneous changes in FGF-23 levels (-27.1% [-33.2% to -8.8%] for the sevelamer group; 3.5% [-8.4% to 12.1%] for the calcium acetate group), as well as with C-reactive protein and fetuin A levels. These relationships were confirmed in multiple regression analysis adjusting for changes in serum phosphate levels and other factors. Unblinded randomized controlled study that cannot establish mechanisms of effect. In hyperphosphatemic patients with stage 4 CKD, treatment with phosphate lowering induces measurable improvements in flow-mediated vasodilatation. Furthermore, independently of serum phosphate level, FGF-23 level changes induced by phosphate binders are associated with simultaneous changes in flow-mediated vasodilatation. These observations are compatible with the hypothesis that FGF-23 may contribute to vascular dysfunction in this population.

Effects of Cinacalcet and Concurrent Low-Dose Vitamin D on FGF23 Levels in ESRD

Fibroblast growth factor-23 (FGF23) levels are elevated in ESRD and have been associated with adverse outcomes. The effects of various treatments for secondary hyperparathyroidism on FGF23 levels in ESRD have not been examined in a clinical trial. We assessed intact FGF23 levels in 91 subjects over the course of the ACHIEVE trial, which was designed to compare escalating doses of Cinacalcet plus fixed low-dose calcitriol analogs (Cinaclcet-D) with titration of calcitriol analogs alone (Flex-D) to suppress parathyroid hormone. Between-group and within-group changes in log-transformed FGF23 levels were analyzed. Factors associated with change in FGF23 were assessed using a multiple regression model. Intact FGF23 levels were markedly elevated in subjects at baseline. A statistically significant difference in percent change in log FGF23 levels was observed between treatment groups (P < 0.002). The Cinacalcet-D group had a significant decrease in percent change in log FGF23 levels (corrected P = 0.021), whereas FGF23 levels trended toward an increase in the Flex-D group. Change in FGF23 level was significantly associated with changes in levels of phosphate (P < 0.0001) and calcium (P = 0.0002) but not parathyroid hormone. Treatment with Cinacalcet plus low-dose calcitriol analogs results in lower FGF23 levels compared with a treatment regimen using calcitriol analogs alone in ESRD. The mechanisms underlying the differential effects of these treatment regimens on FGF23 levels and the clinical impact of these changes on FGF23 remain to be defined.

Phosphatemic Effect of Cinacalcet in Kidney Transplant Recipients With Persistent Hyperparathyroidism

In kidney transplant recipients, persistent hyperparathyroidism leads to hypercalcemia and increased urinary phosphorus excretion. The calcimimetic drug cinacalcet effectively decreases parathyroid hormone (PTH) levels and corrects hypercalcemia in these patients. The purpose of the present study is to examine the effect of cinacalcet treatment on determinants of renal phosphorus reabsorption under steady-state conditions. Open-label prospective uncontrolled trial. 10 stable kidney transplant recipients with persistent hyperparathyroidism. Cinacalcet, 30 and 60 mg/d, for 2 weeks. Changes in urinary phosphorus excretion in timed urine samples, intact and carboxy-terminal (C-term) fibroblast growth factor 23 (FGF-23), intact PTH, venous pH, and bicarbonate values at defined intervals over 24 hours. Cinacalcet decreased renal phosphorus excretion in the first 8 hours by 30% to 40%, but not from 8 to 24 hours after drug administration. Serum phosphorus levels normalized in all patients. Cinacalcet markedly decreased plasma intact PTH levels (60%; P < 0.001). Cinacalcet also decreased mean intact FGF-23 levels from 67 +/- 8 (SE) to 51 +/- 5 and to 54 +/- 6 pg/mL (P < 0.001) and mean C-term FGF-23 levels from 108 +/- 15 to 87 +/- 9 and to 101 +/- 9 RU/mL (P < 0.01), respectively. There was high correlation between intact FGF-23 and C-term FGF-23 levels (r = 0.598; P < 0.001). Acid-base status was unchanged. This is a small study and does not examine the long-term effect of cinacalcet treatment. Cinacalcet effectively corrected urinary phosphate wasting in kidney transplant recipients, resulting in normalization of serum phosphorus levels. The phosphatemic effects of cinacalcet correlated with a marked decrease in the phosphaturic hormone PTH, rather than with a change in FGF-23 levels or acid-base status, highlighting the importance of PTH in posttransplantation hypophosphatemia.