Chronic kidney disease (CKD) affects approximately 10% to 15% of the adult general population worldwide. The numbers are increasing owing to the growing aging population and lifestyle changes associated with an increased prevalence of obesity, hypertension, and diabetes.^1-3 The increase in obesity prevalence is reported worldwide and is estimated to further increase by 40% by 2027.⁴ Globally, obesity is associated with a 36% increased risk of CKD in the general population.^5,6 Individuals who are obese have a more than 3-fold higher risk of developing end-stage kidney disease (ESKD) than those with normal body weight.^7-9 End-stage kidney disease and the subsequent kidney replacement therapy represent a major burden for individuals and health care systems.^10,11

Little is known about sex- and age-specific variations and temporal trends in serum uric acid (SUA) concentrations, the prevalence of hyperuricemia and its association with metabolic risk factors in the general population. Between January 1, 1985 and June 30, 2005 146,873 participants (42% women) were recruited. Prevalence of hyperuricemia was estimated applying a common (SUA > 360 µmol/L) and sex-specific cut-off points (women > 340 µmol/L, men > 420 µmol/L). At baseline, mean age was 41.2 years in men and 51.5 years in women, mean SUA concentration was 314.8 µmol/L and 243.6 µmol/L, respectively. Applying a common cut-off point, the prevalence of hyperuricemia was 18.5% in men and 4.4% in women and by sex-specific cut-off points it was 15.1% and 13.8%, respectively. SUA levels increased by 6.7 µmol/L per decade in men, but remained constant in women until the age of 50 years with a sharp increase by approximately 22 µmol/L per decade thereafter. In men and women, hyperuricemia was associated with obesity, hypertriglyceridemia and elevated gamma-glutamyl transferase. With increasing age SUA levels and the prevalence of hyperuricemia rise in a sex-specific manner. Above the age of 65 years, the sex-specific prevalence of hyperuricemia in women outreaches that in men.

Background Calciphylaxis is a life-threatening complication in patients with end-stage renal disease (ESRD). No established therapy exists so far. The aim of the present study was to determine the therapeutic response to a multi-interventional treatment regimen with consistent use of sodium thiosulphate (STS) in an Austrian cohort of calciphylaxis patients. Methods We retrospectively collected demographic, clinical and laboratory data on 27 calciphylaxis patients treated with STS at seven Austrian dialysis centres between June 2004 and November 2010. Results Twenty-seven dialysis patients (68 ± 12 years) were treated with STS for a median (25th, 75th percentile) of 96 (54, 133) days. Seven patients (26%) suffered from proximal-type, and 20 patients (74%) from distal-type calciphylaxis. Fourteen patients (52%) showed a complete remission, five patients (19%) a partial remission and eight patients (30%) progression that resulted in amputation in four patients. During a median follow-up of 101 (79, 273) days, 14 patients died (52%). Non-survivors were older (P = 0.04), showed higher CRP values (P = 0.04), presented more frequently with proximal-type calciphylaxis (P = 0.03), had a higher disease severity score at diagnosis (P = 0.01), were treated more often with antibiotics (P = 0.01) and cinacalcet (P = 0.03) and had a lower remission rate during treatment (P = 0.004) than did survivors. The use of antibiotics and cinacalcet, disease severity at diagnosis and remission rates were found to be significant survival predictors in logistic regression analysis. Conclusions Calciphylaxis remains a serious complication with high mortality. Early and consistent therapy including STS may help to improve the disease outcome.

Rationale: Ambient air pollution exposure has been linked to mortality from chronic cardiorespiratory diseases, while evidence on respiratory infections remains more limited. Objectives: We examined the association between long-term exposure to air pollution and pneumonia-related mortality in adults in a pool of eight European cohorts. Methods: Within the multicenter project ELAPSE (Effects of Low-Level Air Pollution: A Study in Europe), we pooled data from eight cohorts among six European countries. Annual mean residential concentrations in 2010 for fine particulate matter, nitrogen dioxide (NO₂), black carbon (BC), and ozone were estimated using Europe-wide hybrid land-use regression models. We applied stratified Cox proportional hazard models to investigate the associations between air pollution and pneumonia, influenza, and acute lower respiratory infections (ALRI) mortality. Measurements and Main Results: Of 325,367 participants, 712 died from pneumonia and influenza combined, 682 from pneumonia, and 695 from ALRI during a mean follow-up of 19.5 years. NO₂ and BC were associated with 10–12% increases in pneumonia and influenza combined mortality, but 95% confidence intervals included unity (hazard ratios, 1.12 [0.99–1.26] per 10 μg/m³ for NO₂; 1.10 [0.97–1.24] per 0.5 10⁻⁵m⁻¹ for BC). Associations with pneumonia and ALRI mortality were almost identical. We detected effect modification suggesting stronger associations with NO₂ or BC in overweight, employed, or currently smoking participants compared with normal weight, unemployed, or nonsmoking participants. Conclusions: Long-term exposure to combustion-related air pollutants NO₂ and BC may be associated with mortality from lower respiratory infections, but larger studies are needed to estimate these associations more precisely.

Background: Insulin resistance, hypertension, hyperuricemia, and hypercholesterolemia are hypothesized to be important intermediates in the relationship between excess body weight and CKD risk. However, the magnitude of the total effect of excess body weight on ESKD mediated through these four pathways remains to be quantified. Methods: We applied a model for analysis of correlated mediators to population-based data from 100,269 Austrian individuals (mean age 46.4 years). Association of body mass index (BMI) was coalesced with ESKD risk into direct association. Indirect associations were mediated through the triglyceride-glucose (TyG) index (as an indicator of insulin resistance), mean arterial pressure (MAP), uric acid (UA), and total cholesterol (TC). Results: Mean follow-up was 23.1 years with 463 (0.5%) incident ESKD cases. An unhealthy metabolic profile (prevalence 32.4%) was associated with a markedly increased ESKD risk (multivariably adjusted hazard ratio (aHR), 3.57; 95% CI, 2.89 to 4.40), independent of BMI. A 5-kg/m² higher BMI was associated with a 57% increased ESKD risk (aHR_{total association}, 1.57; 1.38 to 1.77). Of this association, 99% (76% to 140%) arose from all mediators jointly; 33% (22% to 49%) through TyG index; 34% (24% to 50%) through MAP; 30% (21% to 45%) through UA; and 2% (−1% to 4%) through TC. The remaining direct association was nonsignificant (aHR_{direct association}, 1.01; 0.88 to 1.14). Conclusions: TyG index, MAP, and UA, but not TC, mediate the association of BMI with ESKD in middle-aged adults. Our findings highlight that in addition to weight reduction, the control of metabolic risk factors might be essential in mitigating the adverse effects of BMI on kidney function.

Background: Hemodialysis patients are at high risk for severe COVID-19. SARS-CoV-2 vaccination related safety and immunogenicity data in these patients are rare.Methods: In this observational study SARS-CoV-2-seronegative hemodialysis patients were vaccinated with two doses of the Pfizer/BioNTech mRNA-BNT162b2 vaccine (COMIRNATY^® 30 µg) and followed for 90 days. Local and systemic side effects were assessed at every dialysis session during the first post-vaccination week after the first and second vaccine dose. Immunogenicity was determined four weeks after vaccination by quantifying anti-SARS-CoV-2 spike protein IgG antibodies (LIAISON^® SARS-CoV-2-TrimericS IgG chemiluminescent immunoassay) expressed in binding activity units per milliliter (BAU/mL) adapted to the WHO International standard.Results: Fifty patients (32% women, 68% men) with a mean (SD) age of 67.6 (14.8) years were included. Mild local reactions occurred in 38% after the first injection, and in 29.2% with mild, in 2.1% with moderate and in 2.1% with severe degree after the second injection. Systemic reactive events occurred less often, with diarrhea (4% mild, 4% moderate) and fatigue (8% mild) being the most frequent ones. After the first injection 42% of the patients developed a positive response using the assay specific cut-off value of 33.8 binding activity units per milliliter (BAU/mL) with a median (Q1, Q3) anti-SARS-CoV-2 spike IgG concentration of 20.0 (11.7, 51.0) BAU/mL. After the second injection the percentage of seropositive patients increased to 97.9% with an anti-SARS-CoV-2 spike IgG concentration of 1075 (290.8, 1735) BAU/mL. Higher age and immunosuppression were associated with lower, calcitriol treatment and prior seroconversion to hepatitis B vaccination with significantly higher antibody concentration.Conclusions: The mRNA-BNT162b2 SARS-CoV-2 vaccine appears to be safe and well-tolerated and shows a high immunogenicity in hemodialysis patients.