Altered Morphologic Properties of Large Arteries in Children with Chronic Renal Failure and after Renal Transplantation

Abstract

Increased intima-media thickness of the carotid arteries (cIMT) has been found in young adults with childhood-onset chronic kidney disease (CKD). The disease stage at which these patients first develop abnormalities of arterial texture is unknown. The objective of this study was to determine the onset and character of arterial changes in children aged 10 to 20 yr with different stages of CKD and to identify risk factors for early arteriopathy. High-resolution ultrasonography was conducted of common cIMT and femoral superficial artery IMT. Fifty-five children with stages 2 to 4 CKD (GFR 51 ؎ 31 ml/min per 1.73 m 2 ), 37 on dialysis, and 34 after renal transplantation (Rtx; GFR 73 ؎ 31 ml/min per 1.73 m 2 ) were studied. Control subjects were 270 healthy children, matched for age and gender. Compared with control subjects, cIMT, femoral superficial artery IMT (both as absolute values and as SD score of median of normal value), wall cross-sectional area, and lumen cross-sectional area of carotid artery were significantly increased in all patient groups and most markedly abnormal in dialysis patients. cIMT in CKD and Rtx patients was significantly lower in comparison with dialysis patients. cIMT correlated with mean past serum Ca ؋ P product, the cumulative dose of calcium-based phosphate binders, and the time-averaged mean calcitriol dose. The cumulative phosphate binder intake, time-averaged Ca ؋ P product, and young age were independent predictors of an increased cIMT. In children with CKD, thickening of IMT occurs early in the course of disease and is most marked in dialyzed patients. The changes may be partly reversible after Rtx.

Carotid Intima-Media Thickness in Children with CKD

“…Other investigators have similarly demonstrated that children with varying degrees of kidney dysfunction have higher cIMT than the general population, with dialysis patients having the most extremely elevated measurements (17,18). What makes our results particularly striking is that this finding still holds among children without extreme kidney dysfunction or ESRD compared with normative data obtained in a more racially diverse, representative group of healthy controls.…”

“…However, there is a growing body of literature demonstrating increased cIMT in children with CKD (17,18). In addition, among children, increased cIMT is associated with hypertension, obesity, diabetes, and metabolic syndrome and is affected by interventions to decrease cardiovascular risk such as statin therapy, diet, and exercise (15).…”

Long-term outcome of chronic dialysis in children

“…Analysing the USRDS database, Parekh et al reported that 311 of the 1,380 (22.5%) deaths in patients aged 0-30 years who had undergone dialysis between 1990 and 1996 were from a cardiac cause [60]. Similarly, ANZDATA [3], the Dutch cohort [4], and German [11] and Polish [61] single-centre studies reported cardiovascular disease as the single most common cause of death in their CKD patients. Chavers et al presented the largest study on cardiovascular morbidity in children on dialysis from the Medicare database [62].…”

“…Studies of children with stages 2-4 CKD and on dialysis have shown that increased intima-media thickness of the carotid artery [61,67,103] (a measure of structural changes in the vessel wall), increased pulse wave velocity [67,104,105] (a measure of stiffness or loss of compliance of the vessel) and presence of coronary and valvular calcification on CT scan [67,82,106] are present as early as the first decade of life. Secondary hyperparathyroidism, with the associated increase in calcium and phosphate levels [64], and renal bone disease [107], as well as its treatment with calcium-based phosphate binders [61,108] and vitamin D [61,67,103], have been implicated as major cardiovascular risk factors.…”

“…Vascular calcification is accelerated on dialysis [11,61,103,104,106,108]: worsening hyperparathyroidism and renal bone disease [63,107], the presence of 'damageinducing' inflammatory mediators, oxidative stress and advanced glycation end-products [68,69], coupled with a loss of the naturally occurring inhibitors of calcification (such as fetuin-A) [110], all play a role in accelerating vascular calcification. The time on dialysis is a strong independent predictor of vascular damage and calcification.…”