Abstract. Increased arterial stiffness is a risk factor for mortality in adults over 40 yr of age with end-stage renal disease (ESRD). As no data exist on vascular changes in young adults with ESRD since childhood, a long-term outcome study was performed. All living Dutch adult patients with onset of ESRD between 1972 and 1992 at age 0 to 14 yr were invited for carotid artery and cardiac ultrasound and BP measurements. Data on clinical characteristics were collected by review of all medical charts. Carotid ultrasound data were compared with those of 48 age-matched and gender-matched healthy controls. Carotid artery and cardiac ultrasound was performed in 130 out of 187 eligible patients. Mean age was 29.0 (20.7 to 40.6) yr. Compared with controls, patients had a similar intima media thickness but a reduced mean arterial wall distensibility DC (40.0 versus 45.0 kPa Ϫ1 · 10 Ϫ3 ; 95% CI, Ϫ9.1 to Ϫ0.8; P Ͻ 0.001), an increased stiffness parameter ␤ (4.2 versus 3.8; 95% CI, 0.05 to 0.68; P ϭ 0.02), an increased elastic incremental modulus E inc (0.35 versus 0.27 kPa · 10 3 ; 95% CI, 0.02 to 0.12; P Ͻ 0.001). Multiple regression analyses in all subjects revealed that ESRD was associated with an increase in ␤ and E inc . Arterial wall properties of patients currently on dialysis and transplanted patients were comparable. In all patients, current systolic hypertension was associated with increased E inc and decreased DC. In conclusion, carotid arterial wall stiffness is increased in young adult patients with pediatric ESRD. Hypertension is a main determinant and might be a target for treatment of these potentially lethal arterial wall changes.Cardiovascular disease is the main cause of death in adults with end-stage renal disease (ESRD) (1-4). Cardiovascular causes of death are relatively uncommon under the age of 40 yr in the general population. Yet, cardiovascular diseases also account for most deaths in patients with ESRD aged between 25 and 44 yr (1). There are indications that even in children and young adults with ESRD since childhood, cardiovascular disease is the main cause of death, similar to older ESRD patients. We performed a long-term follow up study on the somatic, social, and psychologic outcome of children with ESRD. Over 25% of all patients had died, all of them under the age of 36 yr. We found cardiovascular disease to be the most important cause of death in the whole group, and cardiac death most prominent in those patients who died more than 10 yr after beginning renal replacement therapy (RRT) (5).Clinical studies have shown that increased stiffness of the large arteries independently contributes to the high mortality in dialysis patients over 40 yr of age (6 -8). Recently, studies performed with electron beam CT have shown coronary calcifications in adolescents and young adults with ESRD (9 -11). However, these studies concern only a few patients; to date, no data exist on arterial wall distensibility in young adult patients with ESRD since childhood. The purpose of this study was to assess the pre...

No abstract

Recent studies indicate that eculizumab is often given in excess to atypical hemolytic uremic syndrome (aHUS) patients. Individualization of treatment is thus highly requested; however, data on the pharmacokinetics and pharmacodynamics of eculizumab remain limited. We analyzed 11 patients during induction (weekly), maintenance (2-weekly), and tapering (every 3-8 weeks) phases of treatment. The trough eculizumab levels increased with each additional dose during the induction phase (depending on body weight). During maintenance, high eculizumab concentrations of up to 772 μg/mL were observed. The levels decreased with each following dose during tapering (3- and 4-week intervals); however, three patients maintained target eculizumab levels over long time periods (30-48 weeks). At intervals of 6-8 weeks, target eculizumab levels were no longer attained. Serum samples with eculizumab concentrations ≥50 μg/mL showed adequate complement blockade. Our data provide essential insight for optimization of eculizumab dosing schemes and lessening of therapy burden for the patients and cost of the treatment.

This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

Genetic alterations in the complement system have been linked to a variety of diseases, including atypical hemolytic uremic syndrome (aHUS), C3 glomerulopathy (C3G), and age‐related macular degeneration (AMD). We performed sequence analysis of the complement genes complement factor H (CFH), complement factor I (CFI), and complement C3 (C3) in 866 aHUS/C3G and 697 AMD patients. In total, we identified 505 low‐frequency alleles, representing 121 unique variants, of which 51 are novel. CFH contained the largest number of unique low‐frequency variants (n = 64; 53%), followed by C3 (n = 32; 26%) and CFI (n = 25; 21%). A substantial number of variants were found in both patients groups (n = 48; 40%), while 41 (34%) variants were found only in aHUS/C3G and 32 (26%) variants were AMD specific. Genotype‐phenotype correlations between the disease groups identified a higher frequency of protein altering alleles in short consensus repeat 20 (SCR20) of factor H (FH), and in the serine protease domain of factor I (FI) in aHUS/C3G patients. In AMD, a higher frequency of protein‐altering alleles was observed in SCR3, SCR5, and SCR7 of FH, the SRCR domain of FI, and in the MG3 domain of C3. In conclusion, we observed a substantial overlap of variants between aHUS/C3G and AMD; however, there is a distinct clustering of variants within specific domains.