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Eastwood J.B.,St Georges, University of London | Kerry S.M.,St Georges, University of London | Plange-Rhule J.,St Georges, University of London | Micah F.B.,Komfo Anokye Teaching Hospital | And 4 more authors.
Nephrology Dialysis Transplantation | Year: 2010

Background. Equations for estimating glomerular filtration rate (GFR) have not been validated in Sub-Saharan African populations, and data on GFR are few.Methods. GFR by creatinine clearance (Ccr) using 24-hour urine collections and estimated GFR (eGFR) using the four-variable Modification of Diet in Renal Disease (MDRD-4)[creatinine calibrated to isotope dilution mass spectrometry (IDMS) standard], Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) and Cockcroft-Gault equations were obtained in Ghanaians aged 40-75. The population comprised 1013 inhabitants in 12 villages; 944 provided a serum creatinine and two 24-hour urines. The mean weight was 54.4 kg; mean body mass index was 21.1 kg/m2.Results. Mean GFR by Ccr was 84.1 ml/min/1.73 m2; 86.8% of participants had a GFR of ≥60 ml/min/1.73 m 2. Mean MDRD-4 eGFR was 102.3 ml/min/1.73 m2 (difference vs. Ccr, 18.2: 95% CI: 16.8-19.5); when the factor for black race was omitted, the value (mean 84.6 ml/min/1.73 m2) was close to Ccr. Mean CKD-EPI eGFR was 103.1 ml/min/1.73 m2, and 89.4 ml/min/1.73 m2 when the factor for race was omitted. The Cockcroft-Gault equation underestimated GFR compared with Ccr by 9.4 ml/min/1.73 m2 (CI: 8.3-10.6); particularly in older age groups. GFR by Ccr, and eGFR by MDRD-4, CKD-EPI and Cockcroft-Gault showed falls with age: MDRD-4 5.5, Ccr 7.7, CKD-EPI 8.8 and Cockcroft-Gault 11.0 ml/min/1.73 m2/10 years. The percentage of individuals identified with CKD stages 3-5 depended on the method used: MDRD-4 1.6% (7.2 % without factor for black race; CKD-EPI 1.7% (4.7% without factor for black race), Ccr 13.2% and Cockcroft-Gault 21.0%.Conclusions. Mean eGFR by both MDRD-4 and CKD-EPI was considerably higher than GFR by Ccr and Cockcroft-Gault, a difference that may be attributable to leanness. MDRD-4 appeared to underestimate the fall in GFR with age compared with the three other measurements; the fall with CKD-EPI without the adjustment for race was the closest to that of Ccr. An equation tailored specifically to the needs of the lean populations of Africa is urgently needed. For the present, the CKD-EPI equation without the adjustment for black race appears to be the most useful. © The Author 2010.

Cunningham J.,University College London | Zehnder D.,Clinical science Research Institute
Kidney International | Year: 2011

Vitamin D compounds have been used successfully to treat secondary hyperparathyroidism for almost three decades. Side effects of increased levels of serum calcium and phosphate and potential complications have increasingly been recognized as problematic, and this has become an even more difficult clinical challenge with the desire to capitalize on some of the pleiotropic effects of vitamin D. Nonclassical nuclear vitamin D receptor (VDR) effects on the cardiovascular system, kidneys, and immune system, with the prospect of improved patient survival, have moved to center stage. Selective vitamin D compounds with minimal effects on mineral metabolism and with maximal cardiovascular and renal benefits are now needed. New vitamin D compounds already in clinical use, which have an improved side-effect profile and differential nonclassical effects compared with calcitriol, are limited to the three licensed pharmaceuticalsparicalcitol, 22-oxacalcitriol, and doxercalciferol. Other compounds are under early development and it is anticipated that these novel therapeutic concepts will result in new vitamin D therapies that will help to reduce the high mortality rate patients with kidney disease experience. © 2011 International Society of Nephrology.

Al-Daghri N.M.,King Saud University | Alkharfy K.M.,King Saud University | Al-Othman A.,King Saud University | El-Kholie E.,King Saud University | And 7 more authors.
Cardiovascular Diabetology | Year: 2012

Background: Vitamin D deficiency has been associated with impaired human insulin action, suggesting a role in the pathogenesis of diabetes mellitus type 2 (T2DM). In this prospective interventional study we investigated the effects of vitamin D3 supplementation on the metabolic profiles of Saudi T2DM subjects pre- and post-vitamin D supplementation over an 18-month period.Methods: T2DM Saudi subjects (men, N = 34: Age: 56.6 ± 8.7 yr, BMI, 29.1 ± 3.3 kg/m2; women, N = 58: Age: 51.2 ± 10.6 yr, BMI 34.3 ± 4.9 kg/m2;) were recruited and given 2000 IU vitamin D3 daily for 18 months. Anthropometrics and fasting blood were collected (0, 6, 12, 18 months) to monitor serum 25-hydroxyvitamin D using specific ELISA, and to determine metabolic profiles by standard methods.Results: In all subjects there was a significant increase in mean 25-hydroxyvitamin D levels from baseline (32.2 ± 1.5 nmol/L) to 18 months (54.7 ± 1.5 nmol/L; p < 0.001), as well as serum calcium (baseline = 2.3 ± 0.23 mmol/L vs. 18 months = 2.6 ± 0.1 mmol/L; p = 0.003). A significant decrease in LDL- (baseline = 4.4 ± 0.8 mmol/L vs. 18 months = 3.6 ± 0.8 mmol/L, p < 0.001] and total cholesterol (baseline = 5.4 ± 0.2 mmol/L vs. 18 months = 4.9 ± 0.3 mmol/L, p < 0.001) were noted, as well as a significant improvement in HOMA-β function (p = 0.002). Majority of the improvements elicited were more prominent in women than men.Conclusion: In the Saudi T2DM population receiving oral Vitamin D3 supplementation (2000 IU/day), circulating 25-hydroxyvitamin D levels remained below normal 18 months after the onset of treatment. Yet, this " suboptimal" supplementation significantly improved lipid profile with a favorable change in HDL/LDL ratio, and HOMA-β function, which were more pronounced in T2DM females. © 2012 Al-Daghri et al.; licensee BioMed Central Ltd.

Rafnsson S.B.,University of Edinburgh | Saravanan P.,Clinical science Research Institute | Bhopal R.S.,University of Edinburgh | Yajnik C.S.,Diabetes Unit
European Journal of Nutrition | Year: 2011

Purpose: To assess the prior hypothesis that low blood vitamin B12, partly through hyperhomocysteinemia and partly through direct effects, increases the risk of cardiovascular diseases and diabetes. As background, we also extracted all-cause mortality from the studies that met our criteria. Methods: A systematic review of prospective cohort studies identified through searching six electronic databases, screening of reference lists, and citation search. Included studies reported data on the association between vitamin B12 blood levels, or other appropriate surrogate biological markers e.g. holotranscobalamin or serum/urine methylmalonic acid, and fatal or non-fatal incident diabetes and cardiovascular events. Results: Seven studies were included. Studies differed regarding the population studied, length of follow-up, study outcomes, and data analysis - a narrative synthesis approach was performed to examine the results. Most studies met few of the quality assessment criteria which were adapted from the Scottish Intercollegiate Guidelines Network (SIGN). Only one high-quality study reported that low B12 increased the risk of incident cerebral ischaemia (RR = 1.76; 95% CI = 1.16-2.68). After controlling for homocysteine, the association persisted although weakened (RR = 1.57; 95% CI = 1.02-2.43), suggesting that the effects of low B12 were only partly mediated by homocysteine. In two studies, higher B12 levels were associated with a greater risk of total mortality (RR = 1.00; 95% CI = 1.00-1.00 and HR = 1.15; 95% CI = 1.08-1.22, respectively) and combined fatal and non-fatal coronary events (RR = 1.00; 95% CI = 1.00-1.00). No association between study outcomes and vitamin B12 levels was found in four other studies. Conclusions: Surprisingly, there is only very limited evidence that vitamin B12 deficiency predisposes to the risk of mortality and morbidity from either cardiovascular diseases or diabetes in adults. Current data do not support vitamin B12 supplementation to reduce the risk of cardiovascular diseases or diabetes. © Springer-Verlag 2010.

Gallos I.D.,University of Oxford | Sivakumar K.,Clinical science Research Institute | Kilby M.D.,University of Birmingham | Coomarasamy A.,University of Birmingham | And 2 more authors.
BJOG: An International Journal of Obstetrics and Gynaecology | Year: 2013

Background Elevated triglycerides are a feature of the metabolic syndrome, maternal obesity, maternal vasculitis (i.e. systemic lupus erythematosus) and diabetes mellitus. These conditions are all known risk factors for pre-eclampsia. Hypertriglyceridaemia therefore may be associated with pre-eclampsia and indeed this may precede the presence of overt disease. Objective In this study we determine the association between hypertriglyceridaemia and pre-eclampsia in pregnant women. Search strategy We searched MEDLINE, EMBASE, Web of Science, Excerpta Medica Database, ISI Web of Knowledge, Cumulative Index to Nursing and Allied Health Literature, Cochrane Library from inception until June 2012 and reference lists of relevant studies. Selection criteria Two reviewers independently selected studies on pregnant women where triglycerides were measured and women were followed up until the development of pre-eclampsia or selected on the basis of presence of pre-eclampsia and compared with controls. Data collection and analysis We collected and meta-analysed the weighted mean differences (WMDs) of triglyceride levels from individual studies using a random effects model. Main results We found strong evidence from meta-analysis of 24 case-control studies (2720 women) that pre-eclampsia is associated with higher levels of serum triglycerides (WMD 0.78 mmol/l, 95% confidence interval 0.6-0.96, P < 0.00001). This finding is also confirmed in five cohort studies, that recruited 3147 women in the second trimester before the onset of pre-eclampsia, which proves that hypertriglyceridaemia precedes the onset of pre-eclampsia (WMD 0.24 mmol/l, 95% confidence interval 0.13-0.34, P < 0.0001). Author's conclusions Hypertriglyceridaemia is associated with and precedes the onset of pre-eclampsia. Further research should focus on defining the prognostic accuracy of this test to identify women at risk and the beneficial effect of triglyceride-lowering therapies in pregnancy. © 2013 RCOG.

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