Decreased renal function in overweight and obese prepubertal children

BACKGROUND: Obesity is a potentially modifiable risk factor for the development and progression of kidney disease, both in adults and children. We aim to study the association of obesity and renal function in children, by comparing estimated glomerular filtration rate (eGFR) in nonoverweight and overweight/obese children. Secondarily, we aim to evaluate the accuracy of equations on eGFR estimation when compared to 24-h urinary creatinine clearance (CrCl). METHODS: Cross-sectional study of 313 children aged 8-9 y, followed in the birth cohort Generation XXI (Portugal). Creatinine and cystatin C, GFR estimated by several formulas and CrCl were compared in 163 nonoverweight and 150 overweight/obese, according to World Health Organization growth reference. RESULTS: Overweight/obese children had significantly lower eGFR, estimated by all methods, except for CrCl and revised Schwartz formula. Despite all children having renal function in the normal range, eGFR decreased significantly with BMI z-score (differences ranging from -4.3 to -1.1 ml/min/1.73 m(2) per standard deviation of BMI). The Zappitelli combined formula presented the closest performance to CrCl, with higher correlation coefficients and higher accuracy values. CONCLUSION: Young prepubertal children with overweight/obesity already present significantly lower GFR estimations that likely represent some degree of renal impairment associated with the complex deleterious effects of adiposity

Biliary atresia

Biliary atresia (BA) is a rare disease characterised by a biliary obstruction of unknown origin that presents in the neonatal period. It is the most frequent surgical cause of cholestatic jaundice in this age group. BA occurs in approximately 1/18,000 live births in Western Europe. In the world, the reported incidence varies from 5/100,000 to 32/100,000 live births, and is highest in Asia and the Pacific region. Females are affected slightly more often than males. The common histopathological picture is one of inflammatory damage to the intra- and extrahepatic bile ducts with sclerosis and narrowing or even obliteration of the biliary tree. Untreated, this condition leads to cirrhosis and death within the first years of life. BA is not known to be a hereditary condition. No primary medical treatment is relevant for the management of BA. Once BA suspected, surgical intervention (Kasai portoenterostomy) should be performed as soon as possible as operations performed early in life is more likely to be successful. Liver transplantation may be needed later if the Kasai operation fails to restore the biliary flow or if cirrhotic complications occur. At present, approximately 90% of BA patients survive and the majority have normal quality of life

Low vitamin D status is associated with systemic and gastrointestinal inflammation in dogs with a chronic enteropathy

Vitamin D is traditionally known for its role in calcium homeostasis and bone metabolism. However, it has been demonstrated that numerous types of cells express the vitamin D receptor and it is now clear that the physiological roles of vitamin D extend beyond the maintenance of skeletal health. Vitamin D insufficiency, which is typically assessed by measuring the major circulating form of vitamin D, 25 hydroxyvitamin D (25(OH)D), has been associated with a number of disorders in people including hypertension, diabetes, cardiovascular diseases, cancer, autoimmune conditions and infectious diseases. Meta-analyses have demonstrated that serum 25(OH)D concentrations are an important predictor of survival in people with a wide variety of illnesses and have been linked to all-cause mortality in the general human population. The role of vitamin D in non-skeletal disorders in cats and dogs is poorly understood. This is surprising since cats and dogs could act as excellent models for probing the biology of vitamin D. Vitamin D status in people is largely dependent on cutaneous production of vitamin D. This is influenced by many factors such as season, latitude and exposure to ultraviolet (UV) radiation. The interpretation of human studies investigating the effects vitamin D status on disease outcomes are therefore influenced by a number of confounding variables. Unlike humans, domesticated cats and dogs do not produce vitamin D cutaneously and obtain vitamin D only from their diet. The physiological functions and regulation of vitamin D are otherwise similar to humans. Most pets are fed commercial diets containing a relatively standard amount of vitamin D. Consequently, companion animals are attractive model systems in which to examine the relationship vitamin D status and health outcomes. Furthermore, spontaneously occurring model systems which did not require disease to be induced in healthy animals would allow the numbers of animals used in scientist research to be reduced. This thesis aimed to define vitamin D homeostasis in companion animals in three disease settings; in cats with feline immunodeficiency virus (FIV) infection, dogs with chronic enteropathies (CE) and in hospitalised ill cats. Additional aims were to assess the prognostic significance of serum 25(OH)D concentrations in companion animals and the relationship between serum 25(OH)D concentrations and markers of inflammation. The hypothesis of this thesis was that vitamin status D would negatively correlate with presence of disease, markers of inflammation and disease outcomes. As similar findings have been demonstrated in human medicine, the hypothesis was that cats and dogs would be suitable models to investigate the role of vitamin D in human disease. This thesis demonstrates that in dogs with a CE serum 25(OH)D concentrations are negatively correlated with inflammation and are predictive of clinical outcomes. Vitamin D status was also lower in cats with FIV and importantly vitamin D status was predictive of short term mortality in hospitalised ill cats. This research will be of interest to veterinary surgeons and opens the possibility for clinical trials which examine if low vitamin D status is causally associated with ill health and whether vitamin D supplementation results in superior treatment outcomes in companion animals. This thesis also demonstrates the potential of cats and dogs as model systems in which to examine the role of vitamin D in human health