Impact of Parathyroidectomy Versus Oral Cinacalcet on Bone Mineral Density in Patients on Peritoneal Dialysis With Advanced Secondary Hyperparathyroidism: The PROCEED Pilot Randomized Trial.

RATIONALE & OBJECTIVE: Parathyroidectomy and calcimimetics have been used to reduce fracture risk in patients with kidney failure and advanced secondary hyperparathyroidism (SHPT), but direct comparisons of these treatment approaches have not been implemented. This pilot study compared their effects on bone mineral density (BMD) in this patient population. STUDY DESIGN: A prospective pilot open-label randomized trial. SETTING & PARTICIPANTS: 65 patients receiving maintenance peritoneal dialysis with advanced SHPT recruited from 2 university-affiliated hospitals in Hong Kong. INTERVENTIONS: Total parathyroidectomy with forearm autografting versus oral cinacalcet treatment for 12 months. OUTCOME: Prespecified secondary end points including changes in BMD z and T scores of femoral neck, lumbar spine, and distal radius 12 months after treatment initiation and also categorized as osteopenia or osteoporosis according to the World Health Organization. RESULTS: Both total parathyroidectomy and cinacalcet significantly improved BMD of the lumbar spine and femoral neck over 12 months, but the total parathyroidectomy group had a greater increase than the cinacalcet-treated group (P<0.001). The proportion of study participants classified as having osteopenia/osteoporosis by femoral neck T-score fell from 78.2% to 51.7% in the total parathyroidectomy group (P<0.001) and from 65.7% to 52.0% in cinacalcet-treated group after 12 months (P=0.7). The proportion of participants with a T-score at the lumbar spine classified as osteopenia/osteoporosis fell from 53.1% to 31.0% in the total parathyroidectomy group (P=0.01) and from 59.4% to 53.8% with cinacalcet (P=0.3). No significant change was observed in BMD T or z score of the distal radius over 12 months with either intervention. LIMITATIONS: Bone histology was not assessed, and the study duration was 12 months. CONCLUSIONS: A large proportion of peritoneal dialysis patients with advanced SHPT had low bone densities and osteopenia/osteoporosis. Total parathyroidectomy increased the BMD of the lumbar spine and femoral neck and reduced osteopenia/osteoporosis more than oral cinacalcet. FUNDING: Grants from academic (The University of Hong Kong Research) and not-for-profit (Hong Kong Society of Nephrology) entities. REGISTRATION: Registered at Clinicaltrials.gov with study number NCT01447368. PLAIN-LANGUAGE SUMMARY: It is not known whether oral cinacalcet and surgical parathyroidectomy differ in their effects on bone parameters in patients with advanced secondary hyperparathyroidism (SHPT) receiving peritoneal dialysis. This pilot randomized trial evaluated the effect of medical versus surgical therapy on bone mineral densities (BMD) as prespecified secondary study end points. The findings showed that a large proportion of peritoneal dialysis patients with advanced SHPT had low bone densities and osteopenia/osteoporosis. Parathyroidectomy increased the BMD of the lumbar spine and femoral neck more than cinacalcet over 12 months. Parathyroidectomy reduced the proportion of patients with osteopenia/osteoporosis at the lumbar spine and femoral neck more than cinacalcet after 12 months. Neither intervention led to an increase in the BMD of the distal radius over 12 months.

Parathyroidectomy versus oral cinacalcet on cardiovascular parameters in peritoneal dialysis patients with advanced secondary hyperparathyroidism (PROCEED): a randomized trial.

BACKGROUND: This trial aimed to evaluate oral cinacalcet versus total parathyroidectomy (PTx) with forearm autografting on cardiovascular surrogate outcomes and health-related quality of life (HRQOL) measures in dialysis patients with advanced secondary hyperparathyroidism (SHPT). DESIGN: In this pilot prospective randomized trial conducted in two university-affiliated hospitals, 65 adult peritoneal dialysis patients with advanced SHPT were randomized to receive either oral cinacalcet or PTx. Primary endpoints were changes in left ventricular (LV) mass index by cardiac magnetic resonance imaging and coronary artery calcium scores (CACS) over 12 months. Secondary endpoints included changes in heart valves calcium scores, aortic stiffness, biochemical parameters of chronic kidney disease-mineral bone disease (CKD-MBD) and HRQOL measures over 12 months. RESULTS: Changes in LV mass index, CACS, heart valves calcium score, aortic pulse wave velocity and HRQOL did not differ between groups or within groups, despite significant reductions in plasma calcium, phosphorus and intact parathyroid hormone in both groups. Cinacalcet-treated patients experienced more cardiovascular-related hospitalizations than those who underwent PTx (P = .008) but the difference became insignificant after adjusting for baseline difference in heart failure (P = .43). With the same monitoring frequency, cinacalcet-treated patients had fewer hospitalizations due to hypercalcemia (1.8%) than patients who underwent PTx (16.7%) (P = .005). No significant changes were observed in HRQOL measures in either group. CONCLUSIONS: Both cinacalcet and PTx effectively improved various biochemical abnormalities of CKD-MBD and stabilized but did not reduce LV mass, coronary artery and heart valves calcification, or arterial stiffness, or improve patient-centered HRQOL measures in PD patients with advanced SHPT. Cinacalcet may be used in place of PTx for treating advanced SHPT. Long-term and powered studies are required to evaluate PTx versus cinacalcet on hard cardiovascular outcomes in dialysis patients. Trial registration: ClinicalTrials.gov identifier: NCT01447368.

Skin autofluorescence associates with vascular calcification in chronic kidney disease.

OBJECTIVE: This study aims to evaluate the relationship between tissue advanced glycation end products, as reflected by skin autofluorescence, and vascular calcification in chronic kidney disease. APPROACH AND RESULTS: Three hundred patients with stage 3 to 5 chronic kidney disease underwent multislice computed tomography to estimate total coronary artery calcium score (CACS) and had tissue advanced glycation end product assessed using a skin autofluorescence reader. Intact parathyroid hormone (P<0.001) displaced estimated glomerular filtration rate as third most significant factor associated with skin autofluorescence after age (P<0.001) and diabetes mellitus (P<0.001) in multiple regression analysis. On univariate multinomial logistic regression analysis, every 1-U increase in skin autofluorescence was associated with a 7.43-fold (95% confidence intervals, 3.59-15.37; P<0.001) increased odds of having CACS ≥400 compared with those with zero CACS. Skin autofluorescence retained significance in predicting CACS ≥400 (odds ratio, 3.63; 95% confidence intervals, 1.44-9.18; P=0.006) when adjusting for age, sex, serum calcium, phosphate, albumin, C-reactive protein, lipids, blood pressure, estimated glomerular filtration rate, and intact parathyroid hormone but marginally lost significance when additionally adjusting for diabetes mellitus (odds ratio, 2.23; 95% confidence intervals, 0.81-6.14; P=0.1). Combination of diabetes mellitus and higher intact parathyroid hormone was associated with greater skin autofluorescence and CACS versus those without diabetes mellitus and having lower intact parathyroid hormone. CONCLUSIONS: Tissue advanced glycation end product, as reflected by skin autofluorescence, showed a significant novel association with vascular calcification in chronic kidney disease. These data suggest that increased tissue advanced glycation end product may contribute to vascular calcification in chronic kidney disease and diabetes mellitus and warrant further experimental investigation.

Long-Term Effects of Sevelamer on Vascular Calcification, Arterial Stiffness, and Calcification Propensity in Patients Receiving Peritoneal Dialysis: The Randomized Pilot SERENE (Sevelamer on Vascular Calcification, Arterial Stiffness) Trial.

RATIONALE & OBJECTIVE: There is a concern regarding increased risk of vascular calcification with the use of calcium-based phosphorus binders. This study aimed to compare the effects of sevelamer used as a second-line, low-dose therapy with calcium-based phosphorus binders with those of sevelamer used as a first-line, high-dose therapy on coronary artery and heart valve calcification, aortic pulse wave velocity (PWV), and calcification propensity over 2 years in patients with hyperphosphatemia receiving peritoneal dialysis (PD). STUDY DESIGN: A 2-year-long prospective, multicenter, open-label, randomized pilot study. SETTING & PARTICIPANTS: Prevalent patients with hyperphosphatemia receiving PD from 2 university-affiliated hospitals in Hong Kong. INTERVENTIONS: The patients were randomized to receive sevelamer either as a first-line therapy at a high dose of 800 mg thrice daily (can titrate up to 1,200 mg thrice daily as required) or a second-line therapy at a low dose of 400 mg thrice daily with calcium carbonate to achieve a serum phosphorus target of ≤5.5 mg/dL. OUTCOMES: The primary endpoints were changes in coronary artery calcium score and aortic PWV over 104 weeks. The secondary endpoints were changes in heart valve calcium scores, calcification propensity measure, and biochemical parameters of chronic kidney disease-mineral bone disease over 104 weeks. RESULTS: Among 60 prevalent patients receiving PD, with a mean age of 53 ± 10 years and with 57% men, changes in the coronary artery calcium score (median [interquartile range], 225 [79-525] vs 223 [56-1,212], respectively; P = 0.21), aortic PWV (mean ± standard error, 0.3 ± 0.1 vs 0.8 ± 0.2 m/s, respectively; P = 0.31), heart valve calcium score, maturation or transformation time, serum calcium levels, and phosphorus levels over 104 weeks were similar for the second-line, low-dose and first-line, high-dose sevelamer groups. Alkaline phosphatase and intact parathyroid hormone levels increased and low-density lipoprotein cholesterol decreased in both the groups, with no significant between-group differences. LIMITATIONS: The sample size was small, and the dropout rates were relatively high. CONCLUSIONS: Low-dose sevelamer used as a second-line therapy for hyperphosphatemia in combination with a calcium-based phosphorus binder had similar effects on vascular calcification, valvular calcification, and arterial stiffness compared with high-dose sevelamer used as a first-line therapy. This approach may be considered in resource-constrained countries to minimize calcium loading. FUNDING: The study was supported by a competitive grant from SK Yee Medical Foundation. T50 assays and other biochemical assays were funded by a research grant from Sanofi Renal Corporation. TRIAL REGISTRATION: NCT00745589.

Application of intravenous contrast in PET/CT: does it really introduce significant attenuation correction error?

UNLABELLED: The current perception of using contrast-enhanced CT (CECT) for attenuation correction (AC) is that of caution, as it might lead to erroneously elevated (18)F-FDG uptake on the PET scan. This study evaluates in vivo whether an intravenous iodinated contrast agent produces a significant AC artifact in the level of standardized uptake value (SUV) changes in PET/CT. METHODS: Fifty-four patients referred for whole-body (WB) PET/CT scans were enrolled and subdivided into 2 groups. In part I, 26 patients had a single WB PET scan that was corrected for attenuation using noncontrast and intravenous CECT obtained before and after the emission data, respectively. The final PET images were compared for any visual and SUV maximum (SUV(max)) measurement difference. This allowed analysis of the compatibility of the scaling processes between the 2 different CTs and the PET. The SUV(max) values were obtained from ascending aorta, upper lung, femoral head, iliopsoas muscle, spleen, liver, and the site of pathology (total, 193 regions). Part II addressed whether intravenous contrast also influenced the PET emission data. For that purpose, the remaining 28 patients underwent a limited plain CT scan from lung base to lower liver edge, followed by a 1-bed PET scan of the same region and then a WB intravenous contrast CT scan in tandem with a WB PET scan. SUV(max) values were obtained at the lung base, liver, spleen, T11 or T12 vertebra, and paraspinal muscle (total, 135 regions). The data obtained from pre- and post-intravenous contrast PET scans were analyzed as in part I. RESULTS: There was no statistically significant elevation of the SUV level in the measured anatomic sites as a whole (part I: mean SUV(max) difference = 0.06, P > 0.05; Part II: mean SUV(max) difference = -0.02, P > 0.05). However, statistically significant results as a group (mean SUV(max) difference = 0.26, P < 0.05)--albeit considered to be clinically insignificant--were observed for areas of pathology in the part I study. No abnormal focal increased (18)F-FDG activity was detected as a result of the intravenous contrast in both parts of this examination. CONCLUSION: No statistically or clinically significant spuriously elevated SUV level that might potentially interfere with the diagnostic value of PET/CT was identified as a result of the application of intravenous iodinated contrast.

Positron emission tomography/computed tomography true fusion imaging in clinical head and neck oncology: early experience.

PURPOSE: Positron emission tomography-computed tomography (PET-CT) is a new imaging modality that provides simultaneous functional and anatomic information. Its application in head and neck oncology is still evolving. MATERIALS AND METHODS: Five illustrative cases who were scanned with this technique are presented. RESULTS: The clinical application and impact on clinical management are described and discussed. CONCLUSION: Our experience indicates that PET-CT will assume a more important role than either CT, magnetic resonance imaging, or PET alone in head and neck cancer imaging.