Chronic Therapy with Sucroferric Oxyhydroxide Does Not Affect Iron and Anemia Markers in Dialysis Patients.

INTRODUCTION: Sucroferric oxyhydroxide (SOH) is an iron-based phosphate binder (PB), and its use has been widely expanded since its initial approval in 2014. Based on the existing data, however, it remains yet unclear whether its long-term administration is followed by iron overload in dialysis patients. The purpose of this observational study was to evaluate the longstanding effects of SOH on the anemia and iron indices in patients on dialysis. METHODS: A total of 110 patients from 3 dialysis centers were included in the study; 49 were under chronic treatment with SOH (cohort A), while 61 were either receiving other PB or no treatment for hyperphosphatemia (cohort B). We initially compared the hematologic profile of patients in 2 cohorts (phase I), and subsequently, we evaluated modifications of the above parameters in the SOH treated patients over a period of 6 months (phase II). RESULTS: There were no statistically significant differences between 2 cohorts in terms of hemoglobin (Hb; 11.4 ± 1.3 vs. 11.6 ± 0.9 g/dL, p = 0.375), ferritin (473 ± 230 vs. 436 ± 235 ng/mL, p = 0.419) and transferrin saturation (TSAT;26.6 ± 13.2 vs. 26.5 ± 10.6%, p = 0.675), serum phosphate concentration (4.57 ± 1.05 vs. 4.3 ± 0.96 mg/dL, p = ns), and intact PTH (286 ± 313 vs. 239 ± 296 pg/mL, p = ns). Marginally, but significantly higher calcium levels were found in cohort A compared to cohort B (9.18 ± 0.58 vs. 8.9 ± 0.51 mg/dL, respectively, p = 0.008). In phase II, no significant changes were observed in hematological parameters after a 6-month treatment with SOH (Hb: from 11.5 ± 1.1 to 11.4 ± 1.3 g/dL, p = 0.4, serum ferritin levels: from 475 ± 264 to 473 ± 230 ng/mL, p = 0.951, TSAT: from 26.5 ± 16.7 to 26.6 ± 13.2%, p = 0.933). There were also no significant changes in the administration of iron supplements or erythropoietin dose during this period. CONCLUSIONS: SOH is an effective PB, and its long-term use is not complicated by iron overload.

MEIS1 and BTBD9: genetic association with restless leg syndrome in end stage renal disease.

BACKGROUND: Restless legs syndrome (RLS) is a sleep related movement disorder that occurs both in an idiopathic form and in symptomatic varieties. RLS is a frequent and distressing comorbidity in end stage renal disease (ESRD). For idiopathic RLS (iRLS), genetic risk factors have been identified, but their role in RLS in ESRD has not been investigated yet. Therefore, a case-control association study of these variants in ESRD patients was performed. METHODS: The study genotyped 10 iRLS associated variants at four loci encompassing the genes MEIS1, BTBD9, MAP2K5/SKOR1, and PTPRD, in two independent case-control samples from Germany and Greece using multiplex PCR and MALDI-TOF (matrix assisted laser desorption/ionisation time-of-flight) mass spectrometry. Statistical analysis was performed as logistic regression with age and gender as covariates. For the combined analysis a Cochran-Mantel-Haenszel test was applied. RESULTS: The study included 200 RLS-positive and 443 RLS-negative ESRD patients in the German sample, and 141 and 393 patients, respectively, in the Greek sample. In the German sample, variants in MEIS1 and BTBD9 were associated with RLS in ESRD (P(nom)≤0.004, ORs 1.52 and 1.55), whereas, in the Greek sample, there was a trend for association to MAP2K5/SKOR1 and BTBD9 (P(nom)≤0.08, ORs 1.41 and 1.33). In the combined analysis including all samples, BTBD9 was associated after correction for multiple testing (P(corrected)=0.0013, OR 1.47). CONCLUSIONS: This is the first demonstration of a genetic influence on RLS in ESRD patients with BTBD9 being significantly associated. The extent of the genetic predisposition could vary between different subgroups of RLS in ESRD.

Platypnea and orthodeoxia associated with Pneumocystis jiroveci and Cytomegalovirus pneumonia: a case report.

INTRODUCTION: Platypnea-orthodeoxia is an uncommon syndrome characterized by dyspnea and deoxygenation accompanying a change to a sitting or standing posture from a recumbent position. It is usually related to interatrial communications, although several other disorders associated with platypnea-orthodeoxia syndrome have been reported. However, the precise mechanisms are unknown. CASE PRESENTATION: We present the case of a 75-year-old Caucasian woman with chronic renal failure due to vasculitis who was admitted with fever and respiratory failure. She was found to have both Pneumocystis jiroveci and Cytomegalovirus pneumonia. She was HIV negative. Severe platypnea and orthodeoxia were major features of her illness with no history of respiratory, liver or cardiac disease. Further investigation with contrast echocardiography revealed no intracardiac or intrapulmonary shunts. Although one case involving Pneumocystis jiroveci pneumonia and platypnea has been previously reported, to the best of our knowledge, this is the first time that two opportunistic pathogens have been accompanied by platypnea and orthodeoxia. As both lung bases were predominantly affected and no obvious explanation was found, platypnea and orthodeoxia were attributed to significant areas of low or zero ventilation/perfusion (V/Q) ratio. CONCLUSION: Platypnea-orthodeoxia is a rare and usually underestimated syndrome. Intracardiac shunts and anatomic pulmonary vascular shunts are the most common etiologic associations. However, if a detailed examination reveals no obvious intracardiac or intrapulmonary shunting combined with extensive pulmonary lesions, then severe V/Q mismatching should be considered as the probable explanation.

Carotid atherosclerosis is associated with inflammation, malnutrition and intercellular adhesion molecule-1 in patients on continuous ambulatory peritoneal dialysis.

BACKGROUND: Recent evidence suggests that endothelial cell adhesion molecules may participate in the initiation and progression of atherosclerotic vascular damage. The aim of the present report was to investigate serum intercellular adhesion molecule-1 (ICAM-1), vascular cell adhesion molecule-1 (VCAM-1) and E-selectin concentrations and their probable association with atherosclerotic disease in patients on continuous ambulatory peritoneal dialysis (CAPD). METHODS: Sixty-three CAPD patients and 40 age- and sex-matched apparently healthy normotensive controls participated in the study. Atherosclerotic disease in both groups was assessed by measuring the intima-media thickness (IMT) and plaque score of the common carotid arteries using an ultrasound scanner. RESULTS: Compared with controls, CAPD patients had significantly increased IMT and plaque score values (P<0.001 and P<0.0001, respectively), as well as serum ICAM-1, VCAM-1 and E-selectin concentrations (P<0.0001, P<0.0001 and P<0.05, respectively). In univariate analyses, IMT values were significantly correlated with age, systolic blood pressure (BP), logCRP, fibrinogen, albumin and ICAM-1 levels (P = 0.001, P = 0.04, P = 0.01, P = 0.04, P = 0.02 and P = 0.002, respectively). Multivariate analysis showed that ICAM-1 levels were a strong independent correlate of IMT (P = 0.005). Serum albumin also remained independently associated with IMT values (P = 0.03). Plaque score values were significantly correlated with age, systolic BP and fibrinogen (P = 0.002, P = 0.04 and P = 0.01, respectively). Multivariate analysis showed that fibrinogen concentrations were a significant independent contributor to plaque score values (P = 0.002). Adhesion molecule concentrations did not show any relation with plaque score either on univariate or multivariate analyses. CONCLUSIONS: In CAPD patients, carotid atherosclerosis is associated with markers of inflammation, malnutrition and circulating levels of adhesion molecule ICAM-1. Hypoalbuminaemia and ICAM-1 appear independently related with atherogenesis but the mechanisms supporting these associations remain to be identified.

Carotid atherosclerosis is associated with inflammation and endothelial cell adhesion molecules in chronic haemodialysis patients.

BACKGROUND: Recently emerging evidence suggests that endothelial adhesion molecules may participate in atherogenesis. The aim of the present report was to investigate the probable association of circulating ICAM-1, VCAM-1 and E-selectin with atherosclerotic disease in chronic haemodialysis (HD) patients. METHODS: One hundred and twelve HD patients and 50 age- and sex-matched healthy normotensive controls participated in the study. Atherosclerotic disease in both groups was assessed by measuring intima-media thickness (IMT) and plaque score of the common carotid arteries using an ultrasound scanner. In addition, in a follow-up study, the survival of 81 patients after a mean period of 26 months was analysed in relation to ICAM-1 and VCAM-1 levels. RESULTS: IMT and plaque score were significantly higher in HD patients compared with control subjects (P < 0.001 and P < 0.0001, respectively). The above ultrasonographic indices were correlated with age both in controls (P = 0.0001 and P = 0.002, respectively) and HD patients (P = 0.0001 and P = 0.0001, respectively). A significant relationship was observed between IMT and systolic blood pressure (BP) both in controls and in HD patients (P = 0.002 and P = 0.01, respectively). In HD patients, plaque score was also correlated with systolic BP (P = 0.02). In HD patients, IMT and plaque score were correlated significantly with log CRP values (P = 0.01 and P = 0.01, respectively). Multivariate analysis showed that log CRP values were a strong independent contributor to plaque score (P = 0.01). IMT was significantly correlated with ICAM-1 and VCAM-1 concentrations (P = 0.0001 and P = 0.003, respectively). Multivariate analysis showed that ICAM-1 concentrations were a strong independent correlate of IMT (P = 0.001). E-selectin concentrations did not show any relation with IMT or plaque score. During the follow-up period, 13 of the 81 patients died. Survival analyses showed that patients with increased ICAM-1 had a shorter survival than patients with normal ICAM-1 values and that serum ICAM-1 levels were a strong predictor of death. CONCLUSIONS: In HD patients, carotid atherosclerosis is associated with inflammation and circulating levels of soluble adhesion molecules ICAM-1 and VCAM-1. The correlations between serum ICAM-1 and IMT and ICAM-1 and survival may indicate that this molecule could be a marker of a process that contributes to the high mortality of HD patients.