Martial Moonen

Cholecalciferol in haemodialysis patients: a randomized, double-blind, proof-of-concept and safety study

BACKGROUND The role of cholecalciferol supplementation in end-stage renal disease (ESRD) patients has been questioned. The objective of this randomized double-blinded study is to assess whether cholecalciferol therapy can increase serum 25-hydroxyvitamin D [25(OH)D] levels in haemodialysed patients and the safety implications of this therapy on certain biological parameters and vascular calcifications score. METHODS Forty-three haemodialysis patients were randomized to receive placebo or cholecalciferol (25,000 IU) therapy every 2 weeks. The biological parameters, serum calcium, phosphorus, 25(OH)D and parathormone (PTH) levels, were monitored monthly for 12 consecutive months. Vascular calcifications were assessed by lateral X-ray radiography. RESULTS At baseline, the mean serum 25(OH)D levels were low and similar in both groups. Thirty patients (16 treated and 14 placebo) completed the study: 11 patients died (5 placebo and 6 treated), 1 patient dropped out and 1 patient was transplanted (both from the placebo group). After 1 year, the percentage of 25(OH)D deficient patients was significantly lower in the treated group. None of the patients developed hypercalcaemia. The PTH levels tended to increase over the study period under placebo and to decrease in the cholecalciferol group. The median changes in PTH levels from baseline to 1 year were statistically different between the two groups [+80 (-58 to 153) and -115 (-192 to 81) under placebo and cholecalciferol treatment, respectively, P=0.02].The calcification scores increased equivalently in both groups (+2.3 per year). CONCLUSIONS Cholecalciferol is effective and safe, and does not negatively affect calcium, phosphorus, PTH levels and vascular calcifications. Additional studies are needed to compare the impacts of nutritional and active vitamin D agents on vascular calcification and mortality.

Dephosphorylated-uncarboxylated Matrix Gla protein concentration is predictive of vitamin K status and is correlated with vascular calcification in a cohort of hemodialysis patients

BackgroundMatrix Gla protein (MGP) is known to act as a potent local inhibitor of vascular calcifications. However, in order to be active, MGP must be phosphorylated and carboxylated, with this last process being dependent on vitamin K. The present study focused on the inactive form of MGP (dephosphorylated and uncarboxylated: dp-ucMGP) in a population of hemodialyzed (HD) patients. Results found in subjects being treated or not with vitamin K antagonist (VKA) were compared and the relationship between dp-ucMGP levels and the vascular calcification score were assessed.MethodsOne hundred sixty prevalent HD patients were enrolled into this observational cohort study, including 23 who were receiving VKA treatment. The calcification score was determined (using the Kauppila method) and dp-ucMGP levels were measured using the automated iSYS method.Resultsdp-ucMGP levels were much higher in patients being treated with VKA and little overlap was found with those not being treated (5604 [3758; 7836] vs. 1939 [1419; 2841] pmol/L, p <0.0001). In multivariate analysis, treatment with VKA was the most important variable explaining variation in dp-ucMGP levels even when adjusting for all other significant variables. In the 137 untreated patients, dp-ucMGP levels were significantly (p < 0.05) associated both in the uni- and multivariate analysis with age, body mass index, plasma levels of albumin, C-reactive protein, and FGF-23, and the vascular calcification score.ConclusionWe confirmed that the concentration of dp-ucMGP was higher in HD patients being treated with VKA. We observed a significant correlation between dp-ucMGP concentration and the calcification score. Our data support the theoretical role of MGP in the development of vascular calcifications. We confirmed the potential role of the inactive form of MGP in assessing the vitamin K status of the HD patients.Trial registrationB707201215885

Clinical and Biological Determinants of Sclerostin Plasma Concentration in Hemodialysis Patients

Background: Sclerostin is a potent inhibitor of bone formation, but the meaning of its serum levels remains undetermined. We evaluated the association between sclerostin levels and clinical or biological data in hemodialyzed patients (HD), notably parathormone (PTH), biomarkers of bone turnover, vascular calcifications and mortality after 2 years. Methods: 164 HD patients were included in this observational study. The calcification score was assessed with the Kauppila method. Patients were followed for 2 years. Results: Median sclerostin levels were significantly (p < 0.0001) higher in HD versus healthy subjects (n = 94) (1,375 vs. 565 pg/ml, respectively). In univariate analysis a significant association (p < 0.05) was found between sclerostin and age, height, dialysis vintage, albumin, troponin, homocysteine, PTH, C-terminal telopeptide of collagen type I, bone-specific alkaline phosphatase and osteoprotegerin, but not with the calcification score. In a multivariate model, the association remained with age, height, dialysis vintage, troponin, homocysteine, phosphate, PTH, but also with vascular calcifications. Association was positive for all variables, except PTH and vascular calcifications. The baseline sclerostin concentration was not different in survivors and non-survivors. Conclusions: We confirm a higher concentration of sclerostin in HD patients, a positive association with age and a negative association with PTH. A positive association with phosphate, homocysteine and troponin calls for additional research. The clinical interest of sclerostin to assess vascular calcifications in HD is limited and no association was found between sclerostin and mortality.

Unusual complication after percutaneous dilatational tracheostomy: pneumoperitoneum with abdominal compartment syndrome.

Sir: We read with interest the recently published paper by Walz and Schmidt, who reported anterior tracheal lesion caused by percutaneous dilatational tracheostomy (PDT) in post-mortem examination [1]. We report the first case of posterior tracheal lesion with pneumoperitoneum after PDT. A 59-year-old woman was admitted to the ICU for Guillain-BarrØ syndrome requiring mechanical ventilation. Eleven days later, PDT was performed using Ciaglias technique (Cook, Bloomington,Ind.). The patient was ventilated via laryngeal mask without any problem [2]. After progressive dilatation of the trachea with dilators of increasing size, a Shiley-8 tracheal cannula was inserted but seemed to be obstructed and it had to be removed. A second attempt to place the tracheal cannula was successful. Twenty-four hours later, chest X-ray showed a pneumomediastinum (Fig. 1) but CT scan did not reveal any cause for this. Tracheo-bronchoscopy was also normal. The tracheal tube cuff was left in place and fully inflated. The patient improved until day 4 when diuresis and total pulmonary static compliance abruptly dropped with concurrent abdominal air distention. An increase in intra-abdominal pressure (20 mmHg) and tension pneumoperitoneum was confirmed on abdominal CT (Fig.2). As a rigid esophago-tracheobronchoscopy demonstrated a leak in the posterior tracheal wall, 4.5 cm below the tracheostomy stoma, a reinforced tracheal tube was inserted just above the carina in order to cover this leak. The pneumoperitoneum was evacuated using a 16 gauge catheter and pulmonary compliance and diuresis returned to normal values. The tracheal tube was left in place for 10 days until the leak closed spontaneously as demonstrated by tracheoscopy. A tracheal cannula was then inserted. No related infectious complication occurred. The patient was transferred from the ICU, but died 1 month later from cardiac arrest on a general ward. Although subcutaneous, mediastinal emphysema and pneumothorax have already been reported as a perioperative complication of PDT, this is the first report of pneumoperitoneum as a complication of PDT [2]. One case of pneumoperitoneum has been reported in the literature following surgical tracheostomy, but considered as a consequence of barotrauma [3]. In the present case, the origin of the pneumoperitoneum was a breach probably occurring during the last insertion of the cannula over its dilator. Barotrauma related to mechanical ventilation is unlikely to have been responsible for the pneumoperitoneum since intrathoracic pressure was kept in the low range during the procedure. The use of a laryngeal mask could also have contributed to this complication owing to a minimum fixation of the trachea. Indeed, Kaloud et al.[4] also reported a case of full length rupture of the membranous wall after a PDT with laryngeal mask. The narrower diameter of the female trachea should be considered in the occurrence of the lesion. Although the use of fiberoptic bronchoscope for guidance and control of puncture was mandatory, this case seems to demonstrate that it is not sufficient to prevent all posterior wall lesions. Reviewing the chest X-ray and clinical evolution revealed no preliminary sign and we suspected that the interval of time between the pneumomediastinum and the pneumoperitoneum occurrence was explained by an almost complete closing of the hole by the cuff. However no satisfactory explanation was found for this prolonged time delay. This time interval could 1334

NGAL Usefulness in the Intensive Care Unit Three Hours after Cardiac Surgery

Objective. Neutrophil gelatinase-associated lipocalin (NGAL) measured by a research ELISA is described as an early marker of acute kidney injury (AKI). The aim of this study is to define the usefulness of plasma NGAL (pNGAL) and urine NGAL (uNGAL) measured with platform analysers to detect AKI 3 hours after cardiac surgery in fifty adult patients. Methods and Main Results. pNGAL and uNGAL were measured before and 3 hours after cardiac surgery. AKI, defined following the acute kidney injury network definition, was observed in 17 patients. pNGAL was >149 ng/mL in 8 patients with AKI, two of them died in the follow-up. We also observed elevated pNGAL in 8 patients without AKI. Only one uNGAL was >132 ng/mL among the 15 AKI patients. Sensitivity of pNGAL for prediction of AKI is 47% and specificity is 75.7%. The positive likelihood ratio (LR+) is 1.9 and negative likelihood ratio (LR−) is 0.7. uNGAL performance is slightly improved when reported to urinary creatinine. Following this study, a ratio >62 ng/mg assure a sensitivity of 66.6% and a specificity of 78.5%. LR+ is 3 and a LR− is, 0.42. Conclusions. Three hours after cardiac surgery, pNGAL predicts AKI with a low sensitivity and specificity.

Variations of parathyroid hormone and bone biomarkers are concordant only after a long term follow-up in hemodialyzed patients

End-stage renal disease is associated with mineral and bone disorders. Guidelines recommending therapies should be based on serial assessments of biomarkers, and thus on variations (Δ), rather than scattered values. We analyzed the correlations between ΔPTH and Δbone biomarkers such as bone-specific alkaline phosphatase (b-ALP), Beta-CrossLaps (CTX), osteocalcin, intact serum procollagen type-1 N-propeptide (P1NP), and tartrate-resistant acid phosphatase 5B (TRAP-5B) at different time-points. In this prospective observational analysis, variations of biomarkers were followed after 6-week (n = 129), 6-month (n = 108) and one-year (n = 93) period. Associations between variations were studied by univariate linear regression. Patients followed for one-year period were classified (increaser or decliner) according to variations reaching the critical difference. Over the 6-week period, only ΔCTX was correlated with ΔPTH (r = 0.38, p < 0.0001). Over the one-year period, correlations between ΔPTH and Δbone biomarkers became significant (r from 0.23 to 0.47, p < 0.01), except with ΔTRAP-5b. Correlations between Δbone biomarkers were all significant after one-year period (r from 0.31 to 0.68, p < 0.01), except between Δb-ALP and ΔTRAP-5b. In the head-to-head classifications (decliners/increasers), the percentage of concordant patients was significantly higher over the one-year than the 6-week period. A concordance between ΔPTH and Δbone biomarkers is observed in dialysis patients, but only after a long follow-up.