Bone ultrastructure and x-ray microanalysis of aluminum-intoxicated hemodialyzed patients

Bone ultrastructure and x-ray microanalysis of aluminum-intoxicated hemodialyzed patients. In hemodialyzed patients aluminum (Al) intoxication may induce osteomalacic lesions which are mainly observed when plasma immunoreactive parathyroid hormone (iPTH) concentrations are low, and osteitis fibrosa absent. In this study, the bone tissue of eight hemodialyzed patients with elevated plasma and bone Al concentrations was examined by histomorphometry, electron microscopy, and x-ray microanalysis. Five patients (group 1) had osteomalacia and minimal osteitis fibrosa, three patients (group 2) had severe osteitis fibrosa. In group 1, Al was concentrated at the mineralizing front, in hexagonal structures measuring 200 to 1,000 Å which also contained phosphorus, but not calcium. Hydroxyapatite needles had a normal aspect. Osteoblasts appeared inactive. In group 2, Al was also present at the mineralizing layer of osteoid, but, in these cases, in small clusters next to abnormal calcium deposits. Osteoblasts appeared very active. Their mitochondria contained calcium and phosphorus granules, or amorphous material, measuring 1,500 to 2,000 Å, emitting x-rays characteristic for Al and phosphorus. These results suggest that secondary hyperparathyroidism, by stimulating the cellular activity, may increase the uptake and release of Al by the osteoblasts. The presence of Al within the mitochondria of these cells may be one of the factors inducing the mineralization defect.Ultrastructure et microanalyse x du tissu osseux de malades hémodialysés intoxiqués par l'aluminium. Chez des malades hémodialysés l'intoxication par l'aluminium (Al) peut induire des lésions ostéomalaciques qui s'observent principalement quand la concentration plasmatique de l'hormone parathyroïdienne immunoréactive (iPTH) est peu augmentée, et en l'absence d'ostéite fibreuse. Dans cette étude le tissu osseux de huit malades hémodialysés dont la concentration plasmatique et osseuse de l'Al était élevée, a été examiné par l'histomorphométrie, la microscopie électronique et la microanalyse x. Cinq malades (groupe 1) avaient une ostéomalacie et des lésions minimes d'ostéite fibreuse, trois malades (groupe 2) avaient une ostéite fibreuse sévère. Dans le groupe 1, l'Al était concentré entre ostéoïde et tissu minéralisé, dans des structures hexagonales mesurant 200 à 1000 Å, qui contenaient également du phosphore, mais pas de calcium. Les aiguilles d'hydroxyapatite avaient un aspect normal. Les ostéoblastes paraissaient peu actifs. Dans le groupe 2, l'Al était aussi présent entre ostéoïde et tissu minéralisé, mais, dans ce cas, sous forme de petits amas, près de dépôts anormaux de calcium. Les ostéoblastes semblaient très actifs. Leurs mitochondries contenaient des granules de calcium et de phosphore ou bien du matériel amorphe, mesurant 1500 à 2000 Å, dont l'émission x était caractéristique de l'Al et du phosphore. Ces résultats suggèrent que l'hyperparathyroïdie secondaire, en stimulant l'activité cellulaire, favorise la captation et le dépôt de l'Al par les ostéoblastes. La présence d'Al dans les mitochondries de ces cellules pourrait être un des facteurs à l'origine du trouble de la minéralisation

Haemoglobin trajectories in chronic kidney disease and risk of major adverse cardiovascular events

International audienceBackground Trajectories of haemoglobin in patients with chronic kidney disease (CKD) have been poorly described. In such patients, we aimed to identify typical haemoglobin trajectory profiles and estimate their risks of major adverse cardiovascular events (MACE). Methods We used 5-year longitudinal data from the CKD-REIN cohort patients with moderate to severe CKD enrolled from 40 nationally representative nephrology clinics in France. A joint latent class model was used to estimate, in different classes of haemoglobin trajectory, the competing risks of (i) MACE + defined as the first event among cardiovascular death, non-fatal myocardial infarction, stroke or hospitalization for acute heart failure, (ii) initiation of kidney replacement therapy (KRT), and (iii) non-cardiovascular death. Results During the follow-up, we gathered 33 874 haemoglobin measurements from 3 011 subjects (median, 10 per patient). We identified five distinct haemoglobin trajectory profiles. The predominant profile (n = 1885, 62.6%) showed an overall stable trajectory and low risks of events. The four other profiles had nonlinear declining trajectories: early strong decline (n = 257, 8.5%), late strong decline (n = 75, 2.5%), early moderate decline (n = 356, 11.8%) and late moderate decline (n = 438, 14.6%). The four profiles had different risks of MACE, while the risks of KRT and non-cardiovascular death consistently increased from the haemoglobin decline. Conclusion In this study, we observed that two third of patients had stable haemoglobin trajectory and low risks of adverse events. The other third had a nonlinear trajectory declining at different rates, with increased risks of events. A better attention to dynamic changes of haemoglobin in CKD should be paid