Free vitamin D is independently associated with systolic blood pressure in diabetic patients with impaired kidney function.

Vitamin D contributes to blood pressure (BP) regulation. We compared the association of BP in diabetic patients with either total vitamin D - the standard way of analyzing the vitamin D status - or free vitamin D, because only free vitamin D passes the cell membrane and interacts with the nuclear vitamin D receptor (VDR). An analytical cross-sectional study was conducted with 178 diabetic patients with impaired kidney function. Free and total vitamin D concentrations were measured in all patients. Multiple linear regression analysis considering patient age, sex, body mass index, height, smoking and drinking situation, the use of antihypertensive drugs, cholecalciferol treatment, C-reactive protein and estimated glomerular filtration rate as confounding factors were conducted to compare the association of free and total vitamin D with systolic and diastolic blood pressure (SBP and DBP). Multiple linear regression analysis revealed that neither SBP nor DBP was correlated with total vitamin D (SBP, 95% CI -0.405 ~ 0.159, p = 0.390; DBP, 95% CI -0.131 ~ 0.142, p = 0.933) (Table 2). However, the concentration of free vitamin D was independently associated with SBP (95% CI -2.691 ~ -0.210; p = 0.022) (Table 3), but not with DBP (95% CI -0.934 ~ 0.285; p = 0.293). In conclusion, free - but not total - vitamin D serum concentrations in patients with diabetes and impaired kidney function are inversely correlated with SBP. This study suggests that free vitamin D measurements might be more clinically relevant - as compared to measurements of total vitamin D - to adjust vitamin D therapy in diabetic patients with impaired kidney function.

Opposite correlation of 25-hydroxy-vitamin D- and 1,25-dihydroxy-vitamin D-metabolites with gestational age, bone- and lipid-biomarkers in pregnant women.

25-Hydroxyvitamin D (25OHD) and 1,25-dihydroxyvitamin D (1,25(OH)2D) need to be bound to carrier proteins to be transported to their target cells. The majority of either 25OHD or 1,25(OH)2D is bound to vitamin D-binding protein (DBP), a smaller fraction is bound to albumin and only very small amounts of 25OHD or 1,25(OH)2D are free. Albumin-bound 25OHD or 1,25(OH)2D is relatively easily available after dissociation from albumin. Thus, the sum of free and albumin-bound forms is called bioavailable 25OHD and bioavailable 1,25(OH)2D. Total 25OHD and 1,25(OH)2D are defined as the sum of free, albumin-bound and DBP-bound 25OHD and 1,25(OH)2D, respectively. This cross-sectional study in 427 pregnant women compared the correlation of the six vitamin D compounds with biomarkers of bone health, lipid metabolism, kidney function, endocrine parameters, and group B water-soluble vitamins. Among the 25OHD metabolites analysed, total 1,25(OH)2D showed clearly the best correlation with calcium, bone-specific alkaline phosphatase, adiponectin, LDL, HDL, urea, thyroxine, and group B water-soluble vitamins. When comparing the three 25OHD metabolites, both free 25OHD and bioavailable 25OHD showed overall good correlations with calcium, bone-specific alkaline phosphatase, adiponectin, LDL, HDL, urea, thyroxine, triiodothyronine, and group B water-soluble vitamins, The correlations of 1,25(OH)2D and 25OHD metabolites went always in opposite directions. Only PTH correlates always inversely with all six vitamin D compounds. In conclusion, free 25(OH)D and bioavailable 25(OH)D are more precise determinants of the vitamin D status than total 25(OH)D in normal pregnancy, whereas total 1,25(OH)2D is superior to free and bioavailable 1,25(OH)2D. Except for PTH, correlations of 25(OH)D and 1,25(OH)2D metabolites with typical clinical chemistry readouts go in opposite directions.

Sulforaphane and Vitamin E Protect From Glucotoxic Neurodegeneration and Lifespan Reduction In C. Elegans.

Caenorhabditis elegans is an established model organism in neurodegeneration and aging research. Oxidative stress and formation of advanced glycation endproducts (AGEs), as they occur under hyperglycemic conditions in diabetes mellitus, contribute to neuronal damage and lifespan reduction. Sulforaphane (SFN) is an indirect antioxidant, alpha-tocopherol (vitamin E) is a direct antioxidant that acts as a free radical scavenger. Aim of this study is to investigate the protective effects of SFN and vitamin E against glucotoxic damages to the neuronal system and lifespan in C. elegans. Culture conditions that mimic clinical hyperglycemia increased the formation of reactive oxygen species (ROS) (p<0.001) and the accumulation of methylglyoxal-derived advanced glycation endproducts (MG-derived AGEs) (p<0.01) with subsequent neuronal damage and neuronal dysfunction, ultimately leading to a significant shortening of lifespan (p<0.01). Treatment with both, 20 µmol/l SFN and 200 µg/ml vitamin E, completely prevented the increase in ROS and MG-derived AGEs, abolished the glucotoxic effects on neuronal structure and function, and preserved lifespan, resulting in a life expectancy similar to untreated controls. These data emphasize the relevance of indirect and direct antioxidants as potential therapeutic options for the prevention of glucotoxic pathologies.

Neuro-Endocrine Recovery After Pituitary Apoplexy: Prolactin as a Predictive Factor.

OBJECTIVE: Pituitary apoplexy is a serious medical complication of a pre-existing pituitary adenoma characterized by a variety of clinical symptoms ranging from mild headache to neurologically impaired and finally comatose patients. Management options are surgery or conservative treatment (e. g., with dexamethasone). Surgery is commonly performed in case of severe acute neurological and visual symptoms. However, prospective studies demonstrating a benefit of surgery over conservative treatment in terms of visual, neurological and even endocrine outcomes are lacking. Decision making is still controversial, and recommendations for surgery are based on low evidence grades and focus on visual impairment. Endocrine function and especially markers identifying patients with potential for pituitary recovery after surgery are not well described in the literature. PATIENTS AND DESIGN: We analysed data from 24 patients (m:f/16:8) with a median age of 64 yrs (38 to 83yrs) that underwent surgery for pituitary apoplexy regardless of time from symptom onset. Apoplexies were necrotic in 14 cases and haemorrhagic in 10 cases. RESULTS: Preoperatively, 7 patients (29.2%) showed complete anterior pituitary insufficiency, 16 patients (66.6%) had partial anterior pituitary insufficiency and one patient (4.17%) had normal pituitary functions. Persistent panhypopituitarism was found in 7 patients (29.2%), whereas an overall improvement of pituitary function was noted in 13 (57.1%) patients. Preoperative prolactin (PRL) levels were significantly associated with recovery of endocrine functions, whereas specifically all patients with preoperative PRL levels of at least 8.8 ng/ml recovered partially or fully. Time to surgery (0-7 days vs. 1-4 weeks vs.>4 weeks) was not significantly associated with outcome. CONCLUSIONS: Our data emphasize that normal and high preoperative PRL levels are associated with better endocrine outcome after surgery. We conclude that patients benefit from surgical intervention even after delayed diagnosis with the serum PRL levels is being a valid biomarker for clinical decision making.

[Update on Diabetic Nephropathy 2018]. / Update Diabetische Nephropathie 2018.

UPDATE ON DIABETIC NEPHROPATHY 2018: The prevalance of elevated albuminuria in patients with diabetes is decreasing, while that of reduced eGFR is increasing, probably owing to more stringent blood pressure and blood glucose control.Well validated online score calculators for risk for renal replacement therapy, cardiovascular events and death are available online.Clinical variables remain more suited than histology for predicting end stage renal disease. Extracapillary hypercellularity, segmental sclerosis and exsudative lesions could represent a distinct risk phenotype.SGLT-2-inhibitors and GLP-1 analogues provide significant reductions of micro- and macrovascular end points. SGLT-2-inhibitors can only be prescribed at eGFR > 60 ml/min/1,73 m2, GLP-1 analogues and metformin at eGFR > 30 ml/min/1,73 m2.The ACC/AHA guideline 2017 defines arterial hypertension at blood pressure ≥ 130/80 mmHg, the ESC/ESH guideline 2018 at ≥ 140/90 mmHg. The blood pressure goal for patients with diabetes is < 130/80 mmHg, if well tolerated. ESC/ESH 2018 recommend not lowering blood pressure lower than 120/70 mmHg, in persons aged ≥ 65 years, systolic blood pressure 130 - < 140 mmHg is recommended.

Identification of a urine metabolite constellation characteristic for kidney allograft rejection.

INTRODUCTION: Allograft rejection is still an important complication after kidney transplantation. Currently, monitoring of these patients mostly relies on the measurement of serum creatinine and clinical evaluation. The gold standard for diagnosing allograft rejection, i.e. performing a renal biopsy is invasive and expensive. So far no adequate biomarkers are available for routine use. OBJECTIVES: We aimed to develop a urine metabolite constellation that is characteristic for acute renal allograft rejection. METHODS: NMR-Spectroscopy was applied to a training cohort of transplant recipients with and without acute rejection. RESULTS: We obtained a metabolite constellation of four metabolites that shows promising performance to detect renal allograft rejection in the cohorts used (AUC of 0.72 and 0.74, respectively). CONCLUSION: A metabolite constellation was defined with the potential for further development of an in-vitro diagnostic test that can support physicians in their clinical assessment of a kidney transplant patient.