Changing trends in end-stage renal disease patients with diabetes.

Worldwide, diabetes has become the most common cause of end-stage renal disease (ESRD), yet Swiss data are largely lacking. This observational study examined ESRD patients with diabetes mellitus (ESRD-DM) at end of 2009 and 2014. The prevalence and characteristics of ESRD-DM patients were collected in all dialysis facilities in the Canton of Vaud of Switzerland in 2009 and in 2014, and the 5-year mortality rate was assessed. A total of 107 and 140 ESRD-DM patients underwent dialysis at end of 2009 and 2014, respectively. Within the 5-year period a total of 167 incidental ESRD-DM patients required dialysis, corresponding to an estimated incidental rate of 0.84/1000 person-years in the diabetic population. In 2009, all patients with ESRD-DM underwent haemodialysis, decreasing to 96.2% in 2014, with 3.8% on peritoneal dialysis. Age, sex, body mass index, type of diabetes, duration of diabetes, cause of ESRD, dialysis duration, dialysis frequency, vascular access, and glycosylated haemoglobin levels did not differ between 2009 and 2014. In 2014, macrovascular comorbidity was reported more often than in 2009, but not amputations. Haemoglobin level decreased significantly from 117.9 g/l to 112.3 g/l. Calcium-containing phosphate binder and angiotensin-converting enzyme inhibitor use significantly decreased, whereas iron therapy significantly increased with time. The 5-year mortality rate was 61.7%. Five-year survivors were significantly younger and had a higher body mass index. The growing prevalence of ESRD-DM emphasises that prevention of chronic kidney disease and its progression should be a public health priority in Switzerland

Gene regulation contributes to explain the impact of early life socioeconomic disadvantage on adult inflammatory levels in two cohort studies

Individuals experiencing socioeconomic disadvantage in childhood have a higher rate of inflammation-related diseases decades later. Little is known about the mechanisms linking early life experiences to the functioning of the immune system in adulthood. To address this, we explore the relationship across social-to-biological layers of early life social exposures on levels of adulthood inflammation and the mediating role of gene regulatory mechanisms, epigenetic and transcriptomic profiling from blood, in 2,329 individuals from two European cohort studies. Consistently across both studies, we find transcriptional activity explains a substantive proportion (78% and 26%) of the estimated effect of early life disadvantaged social exposures on levels of adulthood inflammation. Furthermore, we show that mechanisms other than cis DNA methylation may regulate those transcriptional fingerprints. These results further our understanding of social-to-biological transitions by pinpointing the role of gene regulation that cannot fully be explained by differential cis DNA methylation

Increased circulating ANG II and TNF-α represents important risk factors in obese Saudi adults with hypertension irrespective of diabetic status and BMI

Central adiposity is a significant determinant of obesity-related hypertension risk, which may arise due to the pathogenic inflammatory nature of the abdominal fat depot. However, the influence of pro-inflammatory adipokines on blood pressure in the obese hypertensive phenotype has not been well established in Saudi subjects. As such, our study investigated whether inflammatory factors may represent useful biomarkers to delineate hypertension risk in a Saudi cohort with and without hypertension and/or diabetes mellitus type 2 (DMT2). Subjects were subdivided into four groups: healthy lean controls (age: 47.9±5.1 yr; BMI: 22.9±2.1 Kg/m2), non-hypertensive obese (age: 46.1±5.0 yr; BMI: 33.7±4.2 Kg/m2), hypertensive obese (age: 48.6±6.1 yr; BMI: 36.5±7.7 Kg/m2) and hypertensive obese with DMT2 (age: 50.8±6.0 yr; BMI: 35.3±6.7 Kg/m2). Anthropometric data were collected from all subjects and fasting blood samples were utilized for biochemical analysis. Serum angiotensin II (ANG II) levels were elevated in hypertensive obese (p<0.05) and hypertensive obese with DMT2 (p<0.001) compared with normotensive controls. Systolic blood pressure was positively associated with BMI (p<0.001), glucose (p<0.001), insulin (p<0.05), HOMA-IR (p<0.001), leptin (p<0.01), TNF-α (p<0.001) and ANG II (p<0.05). Associations between ANG II and TNF-α with systolic blood pressure remained significant after controlling for BMI. Additionally CRP (p<0.05), leptin (p<0.001) and leptin/adiponectin ratio (p<0.001) were also significantly associated with the hypertension phenotype. In conclusion our data suggests that circulating pro-inflammatory adipokines, particularly ANG II and, TNF-α, represent important factors associated with a hypertension phenotype and may directly contribute to predicting and exacerbating hypertension risk

Genetic associations at 53 loci highlight cell types and biological pathways relevant for kidney function.

Reduced glomerular filtration rate defines chronic kidney disease and is associated with cardiovascular and all-cause mortality. We conducted a meta-analysis of genome-wide association studies for estimated glomerular filtration rate (eGFR), combining data across 133,413 individuals with replication in up to 42,166 individuals. We identify 24 new and confirm 29 previously identified loci. Of these 53 loci, 19 associate with eGFR among individuals with diabetes. Using bioinformatics, we show that identified genes at eGFR loci are enriched for expression in kidney tissues and in pathways relevant for kidney development and transmembrane transporter activity, kidney structure, and regulation of glucose metabolism. Chromatin state mapping and DNase I hypersensitivity analyses across adult tissues demonstrate preferential mapping of associated variants to regulatory regions in kidney but not extra-renal tissues. These findings suggest that genetic determinants of eGFR are mediated largely through direct effects within the kidney and highlight important cell types and biological pathways

Pneumonia involving Aspergillus and Rhizopus spp. after a near-drowning incident with subsequent Nocardia cyriacigeorgici and N. farcinica coinfection as a late complication

Reported here is the case of a 22-year-old man who developed pneumonia with unusual pathogens after a near-drowning incident. On day 7 following admission, Rhizopus spp. and Aspergillus fumigatus were cultured from the patient's bronchoalveolar lavage fluid. One week later, sputum cultures revealed N. cyriacigeorgici as well as N. farcinica. The patient recovered fully after prolonged therapy with liposomal amphotericin B, amikacin, meropenem and cotrimoxazole. © Springer-Verlag 2004

Association of 24-Hour Blood Pressure With Urinary Sodium Excretion in Healthy Adults.

While the positive relationship between urinary sodium excretion and blood pressure (BP) is well established for middle-aged to elderly individuals using office BP, data are limited for younger individuals and ambulatory BP measurements. Our analysis included 2,899 individuals aged 18 to 90 years from 2 population-based studies (GAPP, Swiss Kidney Project on Genes in Hypertension [SKIPOGH]). Participants with prevalent cardiovascular disease, diabetes, or on BP-lowering treatment were excluded. In SKIPOGH, 24-hour urinary sodium excretion was used as a measure of sodium intake, while in GAPP it was calculated from fasting morning urinary samples using the Kawasaki formula. Multivariable linear regression models were used to assess the relationships of 24-hour urinary salt excretion with office and ambulatory BP measurements. Mean age, ambulatory BP, sodium excretion, and estimated glomerular filtration rate in GAPP and SKIPOGH were 35 and 44 years, 123/78 and 118/77 mm Hg, 4.2 and 3.3 g/d, and 110 and 99 ml/min/1.73 m2, respectively. A weak linear association was observed between 24-hour ambulatory systolic BP and urinary sodium excretion (β (95% confidence interval [CI]) per 1 g increase in sodium excretion (0.33 % (0.09; 0.57); P = 0.008). No significant relationships were observed for 24-hour ambulatory diastolic BP (β (95% CI) (0.13 % (-0.15; 0.40) P = 0.37). When repeating the analyses in different age groups, all BP indices appeared to have stronger relationships in the older age groups (&gt;40 years). In these large cohorts of healthy adults, urinary sodium excretion was only weakly associated with systolic 24-hour ambulatory BP