HDL in Children with CKD Promotes Endothelial Dysfunction and an Abnormal Vascular Phenotype

Endothelial dysfunction begins in early CKD and contributes to cardiovascular mortality. HDL is considered antiatherogenic, but may have adverse vascular effects in cardiovascular disease, diabetes, and inflammatory conditions. The effect of renal failure on HDL properties is unknown. We studied the endothelial effects of HDL isolated from 82 children with CKD stages 2–5 (HDL^CKD), who were free of underlying inflammatory diseases, diabetes, or active infections. Compared with HDL from healthy children, HDL^CKD strongly inhibited nitric oxide production, promoted superoxide production, and increased vascular cell adhesion molecule-1 expression in human aortic endothelial cells, and reduced cholesterol efflux from macrophages. The effects on endothelial cells correlated with CKD grade, with the most profound changes induced by HDL from patients on dialysis, and partial recovery observed with HDL isolated after kidney transplantation. Furthermore, the in vitro effects on endothelial cells associated with increased aortic pulse wave velocity, carotid intima-media thickness, and circulating markers of endothelial dysfunction in patients. Symmetric dimethylarginine levels were increased in serum and fractions of HDL from children with CKD. In a longitudinal follow-up of eight children undergoing kidney transplantation, HDL-induced production of endothelial nitric oxide, superoxide, and vascular cell adhesion molecule-1 in vitro improved significantly at 3 months after transplantation, but did not reach normal levels. These results suggest that in children with CKD without concomitant disease affecting HDL function, HDL dysfunction begins in early CKD, progressing as renal function declines, and is partially reversed after kidney transplantation.Patients with CKD no longer die from renal failure but from cardiovascular disease. There is an independent, graded association between a reduced eGFR and the risk of death and cardiovascular events.¹ Typically, patients with CKD develop calcification in the tunica media of their arteries,² but a concomitant process of endothelial damage leading to atherosclerosis is also³ present beginning in predialysis CKD.^4,5LDL is crucially involved in the pathogenesis of atherosclerotic cardiovascular disease in the general population,⁶ whereas HDL is thought to be antiatherogenic by promoting reverse cholesterol transport and exerting direct protective endothelial effects.⁷ HDL from healthy participants increases the bioavailability of nitric oxide (NO) by activating endothelial NO synthase inducing vasodilation and decreasing arterial BP. Moreover, HDL diminishes the production of reactive oxygen species such as superoxide (SO) radicals, which have been demonstrated to reduce NO bioavailability leading to endothelial dysfunction and promoting atherogenesis. However, recent evidence suggests that HDL may lose its vasoprotective properties in patients with manifest cardiovascular disease (e.g., coronary artery disease), diabetes, or inflammatory disease states (e.g., antiphospholipid syndrome).^8–10 Similarly, in adults on dialysis, HDL has reduced cholesterol efflux capacity and proinflammatory effects on mononuclear cells.^11–13 Observational studies have shown a strong association between high HDL levels and reduced risk of cardiovascular disease in the general population¹⁴ but not in dialysis patients.¹⁵Cardiac and vascular damage has also been documented in children on dialysis,^2,16,17 and cardiovascular disease accounts for the majority of deaths in pediatric dialysis patients.¹⁷ In contrast with adult patients with CKD, in whom cardiovascular risk factors such as diabetes dyslipidemia, hypertension, and smoking are highly prevalent,¹⁸ CKD in children is mainly caused by inherited disorders such as malformations of the kidney or urinary tract.¹⁸ Accordingly, examining HDL function in children who are free of “traditional” cardiovascular risk factors and underlying inflammatory diseases and who are nonsmokers gives us an unique opportunity to study the effects of renal failure on the vascular functions of HDL.We studied the endothelial properties of HDL in a cohort of children at different stages of CKD on dialysis and after transplantation and compared them with healthy children. Furthermore, to determine the clinical relevance of in vitro effects of HDL, we examined its relationship with clinical measures of the vascular phenotype as well as circulating markers of endothelial dysfunction. Finally, to show a causal link between renal function and HDL properties, we examined children on dialysis and 3 months after kidney transplantation. This study allowed us to examine when HDL dysfunction develops during the natural history of renal decline, its effects on vascular function, and the potential for recovery after kidney transplantation.     

Outcome of deceased donor renal transplantation in patients with an ileal conduit

Renal transplantation in recipients with an ileal conduit is uncommon and occasionally controversial as it has been associated with high morbidity and mortality rates. We report on 17 patients with an ileal conduit who received a deceased donor renal transplant at our institution between January 1986 and December 2012. We retrospectively reviewed their allograft and surgical outcome. There were four mortalities at five, five, 39, and 66 months post‐transplant. Sixteen of 17 grafts functioned immediately; one patient had primary non‐function secondary to vascular thrombosis. Thirteen of 17 (76.5%) grafts were functioning at a mean follow‐up period of 105 months. The mean serum creatinine at follow‐up was 111 μM (±38.62). Five patients had seven episodes of urosepsis requiring hospital admission, and five patients received treatment for renal stone disease. We conclude that given improvements in immunosuppression, surgical technique, infection treatment, and selection criteria, we believe that renal transplantation in the patient with an ileal conduit yields excellent graft survival, although there is a high morbidity rate in this cohort of patients in the long term.     

Are computed tomography scans adequate in assessing cervical spine pain following blunt trauma?

Good quality three-view radiographs (anteroposterior, lateral, and open-mouth/odontoid) of the cervical spine exclude most unstable injuries, with sensitivity as high as 92% in adults and 94% in children. The diagnostic performance of helical computed tomography (CT) scanners may be even greater, with reported sensitivity as high as 99% and specificity 93%. Missed injuries are usually ligamentous, and may only be detected with magnetic resonance imaging (MRI) or dynamic plain radiographs. With improvements in the accessibility of advanced imaging (helical CT and MRI) and with improvements in the resolution of such imaging, dynamic screening is now used less commonly to screen for unstable injuries. This case involves a patient with an unstable cervical spine injury whose cervical subluxation was only detected following use of dynamic radiographs, despite a prior investigation with helical CT. In this way, the use of dynamic radiographs following blunt cervical trauma should be considered an effective tool for managing acute cervical spine injury in the awake, alert, and neurologically intact patient with neck pain.     

Radiological imaging of a massive dermoid in the male pelvis

A dermold cyst, arising from the posterior aspects of the prostate and seminal vesicles, and extending into the pelvis to masquerade as a full bladder, must be exceedingly rare. Ultrasound, computed tomography and especially magnetic resonance imaging (MRI) proved to be invaluable in making the diagnosis, and MRI in particular was very useful in providing an anatomical road map for surgery.