M-type Phospholipase A2 Receptor Autoantibodies and Renal Function in Patients with Primary Membranous Nephropathy

Background and objectives

Loss of renal function in patients with primary membranous nephropathy cannot be reliably predicted by laboratory or clinical markers at the time of diagnosis. M-type phospholipase A₂ receptor autoantibodies have been shown to be associated with changes in proteinuria. Their eventual effect on renal function, however, is unclear.

Design, setting, participants, & measurements

In this prospective, open, multicenter study, the potential role of M-type phospholipase A₂ receptor autoantibodies levels on the increase of serum creatinine in 118 consecutive patients with membranous nephropathy and positivity for serum M-type phospholipase A₂ receptor autoantibodies was analyzed. Patients were included in the study between April of 2010 and December of 2012 and observed until December of 2013. The clinical end point was defined as an increase of serum creatinine by ≥25% and serum creatinine reaching ≥1.3 mg/dl.

Results

Patients were divided into tertiles according to their M-type phospholipase A₂ receptor autoantibody levels at the time of inclusion in the study: tertile 1 levels=20–86 units/ml (low), tertile 2 levels=87–201 units/ml (medium), and tertile 3 levels ≥202 units/ml (high). The median follow-up time of all patients in the study was 27 months (interquartile range=18–33 months). The clinical end point was reached in 69% of patients with high M-type phospholipase A₂ receptor autoantibodies levels (tertile 3) but only 25% of patients with low M-type phospholipase A₂ receptor autoantibodies levels. The average time to reach the study end point was 17.7 months in patients with high M-type phospholipase A₂ receptor autoantibodies levels and 30.9 months in patients with low M-type phospholipase A₂ receptor autoantibodies levels. A multivariate Cox regression analysis showed that high M-type phospholipase A₂ receptor autoantibodies levels—in addition to men and older age—are an independent predictor for progressive loss of renal function.

Conclusions

High M-type phospholipase A₂ receptor autoantibodies levels were associated with more rapid loss of renal function in this cohort of patients with primary membranous nephropathy and therefore, could be helpful for treatment decisions.     

Childhood Diabetes in the Nordic Countries: A Comparison of Quality Registries

Background:In 2008 a Nordic collaboration was established between the quality registries in Denmark, Iceland, Norway, and Sweden to improve quality of care for children with diabetes. This study aimed to describe those registries and confirm that the registry variables are comparable. Selected variables were used to demonstrate outcome measurements.Methods:The organization of the registries and methodology are described. Cross-sectional data for patients between birth and 14.9 years with type 1 diabetes mellitus in 2009 (n = 6523) from 89 centers were analyzed. Variables were age, gender, and diabetic ketoacidosis at onset, together with age, gender, HbA1c, insulin regimen, and severe hypoglycemia at follow-up in 2009.Results:All 4 registries use a standardized registration at the onset of diabetes and at follow-up, conducted at the local pediatric diabetes centers. Methods for measuring HbA1c varied as did methods of registration for factors such as hypoglycemia. No differences were found between the outcomes of the clinical variables at onset. Significant variations were found at follow-up for mean HbA1c, the proportion of children with HbA1c < 57 mmol/mol (NGSP/DCCT 7.4%), (range 15-31%), the proportion with insulin pumps (range 34-55%), and the numbers with severe hypoglycemia (range 5.6-8.3/100 patient years).Conclusions:In this large unselected population from 4 Nordic countries, a high proportion did not reach their treatment target, indicating a need to improve the quality of pediatric diabetes care. International collaboration is needed to develop and harmonize quality indicators and offers possibilities to study large geographic populations, identify problems, and share knowledge.     

Increasing objectively measured sedentary time increases clustered cardiometabolic risk: a 6 year analysis of the ProActive study

Aims/hypothesis

We aimed to quantify the associations between change in objectively measured sedentary and moderate-to-vigorous physical activity (MVPA) times and self-reported television viewing over 6 years and change in a clustered cardiometabolic risk score (CCMR), including and excluding waist circumference (CCMR without adiposity component, CCMR _{no adip} ), and its individual components, among the adult children of people with type 2 diabetes.

Methods

In 171 adults (mean ± SD age 42.52?±?6.30 years; 46% men) with a parental history of diabetes (ProActive UK), physical activity accelerometer measures and self-reported television viewing were assessed at baseline and a mean ± SD of 6.27?±?0.46 years later. Associations between change in sedentary time, MVPA time and television viewing and cardiometabolic risk and mediation by adiposity change were examined by multiple linear regression and the product of coefficients method, respectively.

Results

Greater increases in sedentary time (h/day) were associated with larger increases in clustered cardiometabolic risk (CCMR: 0.08 [95% CI 0.01, 0.15]; CCMR _{no adip} : 0.08 [0.01, 0.16]) and triacylglycerol (0.15 [0.01, 0.29]), independent of baseline sedentary and MVPA times, change in MVPA time and other confounders. No evidence was found for mediation by change in waist circumference and BMI for the associations with CCMR _{no adip} and triacylglycerol. Greater increases in MVPA time (h/day) were associated with larger decreases in waist circumference (?3.86 [?7.58, ?0.14]), independently of baseline MVPA and sedentary times, change in sedentary time and other confounders. Television viewing was not independently associated with any of the cardiometabolic outcomes.

Conclusions/interpretation

Increasing sedentary time is independently related to increasing clustered cardiometabolic risk and triacylglycerol in adults at high risk of developing diabetes. Strategies to prevent diabetes might target reducing sedentary time. Trial registration ISRCTN61323766     

Global physical activity levels: surveillance progress, pitfalls, and prospects

To implement effective non-communicable disease prevention programmes, policy makers need data for physical activity levels and trends. In this report, we describe physical activity levels worldwide with data for adults (15 years or older) from 122 countries and for adolescents (13-15-years-old) from 105 countries. Worldwide, 31·1% (95% CI 30·9-31·2) of adults are physically inactive, with proportions ranging from 17·0% (16·8-17·2) in southeast Asia to about 43% in the Americas and the eastern Mediterranean. Inactivity rises with age, is higher in women than in men, and is increased in high-income countries. The proportion of 13-15-year-olds doing fewer than 60 min of physical activity of moderate to vigorous intensity per day is 80·3% (80·1-80·5); boys are more active than are girls. Continued improvement in monitoring of physical activity would help to guide development of policies and programmes to increase activity levels and to reduce the burden of non-communicable diseases.     

Neuroendocrine assessment of serotonergic, dopaminergic, and noradrenergic functions in alcohol-dependent individuals

Background: Alcohol dependence has been associated with reduced function of serotonin, dopamine as well as noradrenaline activities in several neuroendocrine studies. To our knowledge, there is, however, no study investigating all these 3 systems with the use of neuroendocrine methods in one and the same alcohol‐dependent individual. Methods: Alcohol‐dependent individuals (n = 42) and controls (n = 28) participated in the neuroendocrine test series. Central serotonergic neurotransmission was assessed by the prolactin (PRL) response to citalopram (CIT). The postsynaptic DRD2 function was measured by the growth hormone (GH) response to apomorphine (APO) and the postsynaptic α2‐adrenoceptor function by GH response to clonidine (CLON). Results: In the alcohol‐dependent individuals, the PRL concentrations were significantly lower at the time points 240 minutes and 300 minutes after CIT administration and mean delta PRL value was significantly reduced by 45% in comparison with controls. There were no significant differences in APO‐GH and CLON‐GH concentrations at any time points or in mean delta GH values between the groups. An impaired monoaminergic profile, including all 3 systems, was significantly more frequent in alcohol‐dependent individuals than controls (43% vs. 6% respectively). Conclusions: The monoaminergic dysfunction was restricted to an impairment of the serotonergic system, suggesting that this system is especially vulnerable to long‐term and excessive alcohol consumption. Moreover, impaired monoaminergic profiles, including low responses in 2 or 3 systems, were more frequently observed in alcohol‐dependent individuals than in controls. Such impaired profiles may be of clinical importance, but further studies are needed.