Comparison of aneroid and oscillometric blood pressure measurements in children.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Limited data exist on the comparison of blood pressure (BP) measurements using aneroid and oscillometric devices. The purpose of the study was to investigate the difference in BP obtained using oscillometric and aneroid BP monitors in 9- to 10-year-old children. A total of 979 children were divided into group O, which underwent two oscillometric BP readings followed by two aneroid readings, and group A, which had BP measured in the reverse order. No significant difference was found between the mean (±standard deviation) of the two systolic BP readings obtained using the oscillometric and aneroid devices (111.5±8.6 vs 111.3±8.1 mm Hg; P=.39), whereas the mean diastolic BP was lower with the oscillometric monitor (61.5±8.0 vs 64.5±6.8 mm Hg; P<.001). A significant downward trend in BP was observed with each consecutive measurement, and agreement between the two monitors was limited. Multiple BP measurements are, therefore, recommended before the diagnosis of elevated BP or hypertension is made with either method.Landspitali - The National University Hospital of Iceland Research Fun

Impact of nephrolithiasis on kidney function.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Kidney stone disease has been associated with reduced kidney function and chronic kidney disease (CKD). The objective of the study was to examine kidney function, body mass index (BMI) and the prevalence of cardiovascular disease, hypertension and diabetes in recurrent kidney stone formers.A cross-sectional, case-control study comparing measures of kidney function, BMI and comorbid conditions was conducted in 195 kidney stone patients aged 18 to 70 years with recurrent clinical stone events and 390 age- and gender-matched controls. Wilcoxon-Mann-Whitney, chi-square tests and analysis of covariance were used to compare serum creatinine (SCr) and estimated glomerular filtration rate (eGFR) between the groups.The median age of stone formers was 51 (range, 19-70) years and 108 (55 %) were males. Seventy patients (36 %) had experienced 2-4 clinical stone events, 41 (21 %) 5-10 episodes and 84 (43 %) more than 10. The median SCr was 75 (41-140) μmol/L in the stone formers and 64 (34-168) μmol/L in the control group (p < 0.001). The mean eGFR was 87 ± 20 and 104 ± 22 mL/min/1.73 m(2) in the stone formers and controls, respectively (p < 0.001). After adjustment for body size and comorbid conditions, the difference in SCr and eGFR between cases and controls remained highly significant (p < 0.001). The prevalence of CKD was 9.3 % among stone formers compared with 1.3 % in the control group (P < 0.001). Hypertension and diabetes were significantly more prevalent among the cases that also had higher BMI than controls.Recurrent kidney stone formers have a significantly lower level of kidney function and a markedly higher prevalence of CKD than age- and gender-matched control subjects. The observed deleterious effect of kidney stones on kidney function appears to be independent of comorbid conditions.Landspitali University Hospital Research Fun

Plasma 25-hydroxyvitamin D2 and D3 levels and incidence of postoperative atrial fibrillation.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Low circulating levels of total 25-hydroxyvitamin D (25(OH)D) have been associated with an increased risk of adverse effects after cardiac surgery. The metabolites, 25(OH)D2 and 25(OH)D3, provide a good index of vitamin D status. In this study, we examined the association between preoperative plasma levels of total 25(OH)D, 25(OH)D2 and 25(OH)D3 and the risk of postoperative atrial fibrillation (POAF) following open heart surgery. The levels of plasma 25(OH)D2 and 25(OH)D3 in 118 patients, who underwent coronary artery bypass grafting and/or valvular surgery, were measured immediately prior to surgery and on postoperative day 3 by liquid chromatography-tandem mass spectrometry. Patients who developed POAF had higher median plasma levels of 25(OH)D2 than those who remained in sinus rhythm (SR) (P = 0·003), but no significant difference was noted in levels of 25(OH)D3 or total 25(OH)D between the two groups (P > 0·05). By univariate analysis, patients with total 25(OH)D and 25(OH)D2 levels above the median had higher frequency of POAF (P < 0·05) and the incidence of POAF increased significantly with each higher quartile of preoperative plasma levels of 25(OH)D2 (P = 0·001), an association that was independent of confounding factors. In both the SR and POAF groups, the median plasma levels of 25(OH)D2, 25(OH)D3 and total 25(OH)D were lower (P < 0·05) on the third postoperative day compared with preoperatively. Our findings demonstrate that higher plasma levels of 25(OH)D2 are associated with increased risk of POAF, while this is not the case for 25(OH)D3 or total 25(OH)D. The reason for these discrepant results is not clear but warrants further study

Does treatment with n-3 polyunsaturated fatty acids prevent atrial fibrillation after open heart surgery?

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldAIMS: To examine the effect of n-3 polyunsaturated fatty acid (PUFA) treatment on the incidence of post-operative atrial fibrillation (POAF). METHODS AND RESULTS: A prospective, randomized, double-blinded, placebo-controlled trial was conducted in patients admitted for coronary artery bypass grafting and/or valvular repair surgery. The patients received either n-3 PUFA capsules, containing a daily dose of 1240 mg eicosapentaenoic acid and 1000 mg docosahexaenoic acid, or olive oil capsules for 5-7 days prior to surgery and post-operatively until hospital discharge. The endpoint was POAF, defined as an episode detected by continuous electrocardiographic monitoring, lasting >5 min. A total of 170 patients were enrolled in the study, and 168 patients underwent surgery. Their median age was 67 (range 43-82) years, and 79.2% were males. There was no difference in baseline characteristics between the n-3 PUFA group (n = 83) and the placebo group (n = 85), and the incidence of POAF was 54.2 and 54.1% (P = 0.99), respectively. Factors associated with POAF included advanced age, peak post-operative C-reactive protein level, valvular surgery, lower body mass index, and non-smoking, but n-3 PUFA concentration in plasma lipids was not associated with POAF. CONCLUSION: There is no evidence for a beneficial effect of treatment with n-3 PUFA on the occurrence of POAF in patients undergoing open heart surgery

Common and rare variants associated with kidney stones and biochemical traits.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Files. This article is open access.Kidney stone disease is a complex disorder with a strong genetic component. We conducted a genome-wide association study of 28.3 million sequence variants detected through whole-genome sequencing of 2,636 Icelanders that were imputed into 5,419 kidney stone cases, including 2,172 cases with a history of recurrent kidney stones, and 279,870 controls. We identify sequence variants associating with kidney stones at ALPL (rs1256328[T], odds ratio (OR)=1.21, P=5.8 × 10(-10)) and a suggestive association at CASR (rs7627468[A], OR=1.16, P=2.0 × 10(-8)). Focusing our analysis on coding sequence variants in 63 genes with preferential kidney expression we identify two rare missense variants SLC34A1 p.Tyr489Cys (OR=2.38, P=2.8 × 10(-5)) and TRPV5 p.Leu530Arg (OR=3.62, P=4.1 × 10(-5)) associating with recurrent kidney stones. We also observe associations of the identified kidney stone variants with biochemical traits in a large population set, indicating potential biological mechanism.Rare Kidney Stone Consortium 5U54DK083908-07 National Center for Advancing Translational Sciences (NCATS) Rare Diseases Clinical Research Network (RDCRN) Rare Kidney Stone Consortiu

Allele frequency of variants reported to cause adenine phosphoribosyltransferase deficiency.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadAdenine phosphoribosyltransferase deficiency is a rare, autosomal recessive disorder of purine metabolism that causes nephrolithiasis and progressive chronic kidney disease. The small number of reported cases indicates an extremely low prevalence, although it has been suggested that missed diagnoses may play a role. We assessed the prevalence of APRT deficiency based on the frequency of causally-related APRT sequence variants in a diverse set of large genomic databases. A thorough search was carried out for all APRT variants that have been confirmed as pathogenic under recessive mode of inheritance, and the frequency of the identified variants examined in six population genomic databases: the deCODE genetics database, the UK Biobank, the 100,000 Genomes Project, the Genome Aggregation Database, the Human Genetic Variation Database and the Korean Variant Archive. The estimated frequency of homozygous genotypes was calculated using the Hardy-Weinberg equation. Sixty-two pathogenic APRT variants were identified, including six novel variants. Most common were the missense variants c.407T>C (p.(Met136Thr)) in Japan and c.194A>T (p.(Asp65Val)) in Iceland, as well as the splice-site variant c.400 + 2dup (p.(Ala108Glufs*3)) in the European population. Twenty-nine variants were detected in at least one of the six genomic databases. The highest cumulative minor allele frequency (cMAF) of pathogenic variants outside of Japan and Iceland was observed in the Irish population (0.2%), though no APRT deficiency cases have been reported in Ireland. The large number of cases in Japan and Iceland is consistent with a founder effect in these populations. There is no evidence for widespread underdiagnosis based on the current analysis.Rare Kidney Stone Consortium, a part of the National Center for Advancing Translational Sciences (NCATS) Rare Diseases Clinical Research Network (RDCRN) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Center for Advancing Translational Sciences (NCATS) United States Department of Health & Human Services National Institutes of Health (NIH) - USA NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) Landspitali University Hospital Research Fun

Association of Variants at UMOD with Chronic Kidney Disease and Kidney Stones—Role of Age and Comorbid Diseases

Chronic kidney disease (CKD) is a worldwide public health problem that is associated with substantial morbidity and mortality. To search for sequence variants that associate with CKD, we conducted a genome-wide association study (GWAS) that included a total of 3,203 Icelandic cases and 38,782 controls. We observed an association between CKD and a variant with 80% population frequency, rs4293393-T, positioned next to the UMOD gene (GeneID: 7369) on chromosome 16p12 (OR = 1.25, P = 4.1×10−10). This gene encodes uromodulin (Tamm-Horsfall protein), the most abundant protein in mammalian urine. The variant also associates significantly with serum creatinine concentration (SCr) in Icelandic subjects (N = 24,635, P = 1.3×10−23) but not in a smaller set of healthy Dutch controls (N = 1,819, P = 0.39). Our findings validate the association between the UMOD variant and both CKD and SCr recently discovered in a large GWAS. In the Icelandic dataset, we demonstrate that the effect on SCr increases substantially with both age (P = 3.0×10−17) and number of comorbid diseases (P = 0.008). The association with CKD is also stronger in the older age groups. These results suggest that the UMOD variant may influence the adaptation of the kidney to age-related risk factors of kidney disease such as hypertension and diabetes. The variant also associates with serum urea (P = 1.0×10−6), uric acid (P = 0.0064), and suggestively with gout. In contrast to CKD, the UMOD variant confers protection against kidney stones when studied in 3,617 Icelandic and Dutch kidney stone cases and 43,201 controls (OR = 0.88, P = 5.7×10−5)

Sequence variants in malignant hyperthermia genes in Iceland: classification and actionable findings in a population database.

To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked DownloadMalignant hyperthermia (MH) susceptibility is a rare life-threatening disorder that occurs upon exposure to a triggering agent. MH is commonly due to protein-altering variants in RYR1 and CACNA1S. The American College of Medical Genetics and Genomics recommends that when pathogenic and likely pathogenic variants in RYR1 and CACNA1S are incidentally found, they should be reported to the carriers. The detection of actionable variants allows the avoidance of exposure to triggering agents during anesthesia. First, we report a 10-year-old Icelandic proband with a suspected MH event, harboring a heterozygous missense variant NM_000540.2:c.6710G>A r.(6710g>a) p.(Cys2237Tyr) in the RYR1 gene that is likely pathogenic. The variant is private to four individuals within a three-generation family and absent from 62,240 whole-genome sequenced (WGS) Icelanders. Haplotype sharing and WGS revealed that the variant occurred as a somatic mosaicism also present in germline of the proband's paternal grandmother. Second, using a set of 62,240 Icelanders with WGS, we assessed the carrier frequency of actionable pathogenic and likely pathogenic variants in RYR1 and CACNA1S. We observed 13 actionable variants in RYR1, based on ClinVar classifications, carried by 43 Icelanders, and no actionable variant in CACNA1S. One in 1450 Icelanders carries an actionable variant for MH. Extensive sequencing allows for better classification and precise dating of variants, and WGS of a large fraction of the population has led to incidental findings of actionable MH genotypes.deCODE Genetics/Amgen Inc

Blood pressure in children and target-organ damage later in life

To access publisher full text version of this article. Please click on the hyperlink in Additional Links fieldThe aim of this study was to examine the association between blood pressure (BP) in children and adolescents and cardiovascular and renal disease in adulthood. This was a retrospective study on patients /= 95th percentile (P = 0.03). Our results suggest that elevated childhood systolic BP may increase the risk of coronary artery disease in adult life. The sample size is a limiting factor, and the study should be carried out in a larger population