Prenatal effects of natural calcium supplement on Wistar rats during organogenesis period of pregnancy

The potential of oral exposure to calcium and magnesium citrate, a natural product obtained from dolomite, to initiate teratogenesis was analyzed in Wistar rats. Animals received calcium and magnesium citrate oral doses of 250, 500 and 1000 mg/kg during the period of gestation from day 6 to 17 post conception. Maternal, embryo and fetal toxicity was evaluated. Calcium and magnesium citrate exposure did not produce maternal toxicity assessed by clinical observations, body weight gain, food intake, hematology, biochemical parameters and necropsy finding. Signs of embryo–fetal toxicity were not observed. Skeletal and visceral malformations were seen occasionally in all drug-treated and control groups. Skeletal and visceral variations were similar in control and drug-treated groups except for incomplete ossification rib. These finding was spontaneous and unrelated to the drug. In conclusion, in this study we found that the oral exposure to rats of up to 1000 mg/kg of calcium and magnesium citrate during organogenesis did not induce significant maternal and embryo–fetal toxicity. The experimentally derived NOAEL for developmental toxicity was 1000 mg/kg.     

Pregnancy and liver adenoma management: PALMstudy

ABSTRACT: BACKGROUND: Hepatocellular adenoma (HCA) in pregnant women requires special considerations because of the risk of hormone induced growth and spontaneous rupture, which may threaten the life of both mother and child. Due to scarcity of cases there is no evidence-based algorithm for the evaluation and management of HCA during pregnancy. Most experts advocate that women with HCA should not get pregnant or advise surgical resection before pregnancy. Whether it is justified to deny a young woman a pregnancy, as the biological behavior may be less threatening than presumed depends on the incidence of HCA growth and the subsequent clinical events during pregnancy. We aim to investigate the management and outcome of HCA during pregnancy and labor based on a prospectively acquired online database in the Netherlands. Methods/design The Pregnancy And Liver adenoma Management (PALM) - study is a multicentre prospective study in three cohorts of pregnant patients. In total 50 pregnant patients, [greater than or equal to] 18 years of age with a radiologically and/or histologically proven diagnosis of HCA will be included in the study. Radiological diagnosis of HCA will be based on contrast enhanced MRI. Lesions at inclusion must not exceed 5 cm. The study group will be compared to a healthy control group of 63 pregnant patients and a group of 63 pregnant patients with diabetes mellitus without HCA. During their pregnancy HCA patients will be closely monitored by means of repetitive ultrasound (US) at 14, 20, 26, 32 and 38 weeks of gestation and 6 and 12 weeks postpartum. Both control groups will undergo US of the liver at 14 weeks of gestation to exclude HCA lesions in the liver. All groups will be asked to fill out quality of life related questionnaires. DISCUSSION: The study will obtain information about the behaviour of HCA during pregnancy, the clinical consequences for mother and child and the impact of having a HCA during pregnancy on the health related quality of life of these young women. As a result of this study we will propose a decision-making model for the management of HCA during pregnancy. Trial registration Dutch trial register: NTR3034.     

A Randomized Trial of Dietary Sodium Restriction in CKD

There is a paucity of quality evidence regarding the effects of sodium restriction in patients with CKD, particularly in patients with pre-end stage CKD, where controlling modifiable risk factors may be especially important for delaying CKD progression and cardiovascular events. We conducted a double-blind placebo-controlled randomized crossover trial assessing the effects of high versus low sodium intake on ambulatory BP, 24-hour protein and albumin excretion, fluid status (body composition monitor), renin and aldosterone levels, and arterial stiffness (pulse wave velocity and augmentation index) in 20 adult patients with hypertensive stage 3–4 CKD as phase 1 of the LowSALT CKD study. Overall, salt restriction resulted in statistically significant and clinically important reductions in BP (mean reduction of systolic/diastolic BP, 10/4 mm Hg; 95% confidence interval, 5 to 15 /1 to 6 mm Hg), extracellular fluid volume, albuminuria, and proteinuria in patients with moderate-to-severe CKD. The magnitude of change was more pronounced than the magnitude reported in patients without CKD, suggesting that patients with CKD are particularly salt sensitive. Although studies with longer intervention times and larger sample sizes are needed to confirm these benefits, this study indicates that sodium restriction should be emphasized in the management of patients with CKD as a means to reduce cardiovascular risk and risk for CKD progression.Cardiovascular disease (CVD) is the leading cause of premature mortality in the CKD population.^1,2 CVD risk increases with only mild kidney impairment (estimated GFR [eGFR] <60 ml/min per 1.73 m²) and further escalates as CKD progresses,³ making early intervention to reduce CVD risk of utmost importance.⁴Dietary sodium intake shows great promise as a modifiable risk factor for reducing the risks of cardiovascular disease and CKD progression.^5,6 Extensive research has demonstrated the effect of sodium intake on fluid overload and hypertension,^7,8 which are predictors of cardiac and vascular remodeling.⁹ Trials in sodium restriction recently showed significant reductions in proteinuria and albuminuria,^7,10,11 which are strong predictors of CKD progression and CVD events.¹² In addition, excessive sodium intake is thought to have direct toxic effects on blood vessels through mediating factors such as oxidative stress, inflammation, endothelial cell dysfunction, and vascular stiffness.^13–15The available evidence detailing the effects of sodium restriction in CKD patients is of poor quality, lacks randomization,^16–18 a control group,¹⁷ or blinding,^10,11 or does not use gold-standard measurement techniques (e.g., using clinic instead of ambulatory BP).^10,11 Furthermore, several studies failed to either evaluate or adjust for the influence of key confounding factors, such as potassium intake or body weight,^{10,11,19–22} thereby making it difficult to assess whether the observed results can be solely attributed to dietary sodium.The aim of this double-blind placebo-controlled randomized crossover study was to evaluate the effects of dietary sodium intake on BP, proteinuria, extracellular fluid volume, and arterial stiffness as markers of risks of cardiovascular and CKD progression. We hypothesized that a low sodium intake would decrease 24-hour BP, fluid volume, and 24-hour urinary protein and albumin compared with high sodium intake in patients with moderate-to-severe CKD.     

Live donor study – implications of kidney donation on cardiovascular risk with a focus on lipid parameters including lipoprotein a

In this prospective observational cohort study, we evaluate the change in cardiovascular risk parameters, with a focus on lipids, in live kidney donors 1 year post donation. Body mass index, systolic/diastolic blood pressure, kidney function (chromium‐51 ethylenediaminetetraacetic acid estimated glomerular filtration) and lipid parameters were measured at baseline and 1 year. Data on 87 live kidney donors were collected. Body mass index increased from 26.5 ± 2.7 pre to 27.4 ± 3.0 kg/m² post donation (p < 0.0001). Chromium‐51 ethylenediaminetetraacetic acid estimated glomerular filtration decreased from 111.8 ± 20.0 pre to 72.1 ± 13.1 mL/min/1.73 m² post donation (p < 0.0001). Serum triglyceride levels increased from 0.8 (interquartile range 0.6–1.3) pre to 1.0 mmol/L (interquartile range 0.7–1.6) post donation (p = 0.0004). Statin use increased from 11.5% pre to 21% post donation (p < 0.005). Low‐density lipoprotein remained stable, and other lipids (high‐density lipoprotein, apolipoprotein B and lipoprotein a) did not change post donation.     

Is mycophenolate mofetil less safe than azathioprine in elderly renal transplant recipients?

BACKGROUND: Mycophenolate mofetil (MMF) is a potent immunosuppressive agent that has been shown to be superior to azathioprine in preventing early acute rejection in the general renal transplant population. However, it is uncertain whether these benefits also apply to older renal transplant recipients, who are known to be more susceptible to infectious complications and have considerably lower rates of rejection and immunological graft loss. METHODS: A retrospective analysis was undertaken of all elderly (> or =55 years old) renal transplant recipients who underwent renal transplantation at the Princess Alexandra Hospital (1994-2000) and received either MMF (n=60) or azathioprine (n=55) in combination with prednisolone and cyclosporin. Data were analyzed on an intention-to-treat basis using a multivariate Cox proportional hazards model. RESULTS: The azathioprine- and MMF-treated groups were well matched at baseline with respect to demographic characteristics, end-stage renal failure causes and transplant characteristics. Compared with the MMF cohort, azathioprine-treated patients experienced a shorter time to first rejection [hazard ratio (HR) 4.47, 95% CI 1.53-13.1, P<0.01]. However, azathioprine-treated patients were also less likely to develop opportunistic infections (HR 0.11, 95% CI 0.03-0.41, P=0.001). No differences were observed between the two groups with respect to hospitalization rates, intensive care admissions, hematological complications, or posttransplant malignancies. Actuarial 2-year survival rates for the azathioprine- and MMF-treated patients were 100 and 87%, respectively (P<0.001). The principal cause of death in the MMF cohort was infection. Using a multivariate Cox regression analysis of patient survival, an adjusted hazard ratio of 0.01 (95% CI 0.001-0.08, P=0.001) was calculated in favor of azathioprine. Overall graft survival also tended to be better in patients receiving azathioprine (HR 0.27, 95% CI 0.06-1.33, P=0.11), CONCLUSIONS: In elderly renal transplant recipients, the combination of MMF, cyclosporin, and prednisolone appears to result in a worse outcome compared with the less potent combination of azathioprine, cyclosporin, and prednisolone. Future prospective studies need to specifically evaluate the risk/benefit ratios of newer, more potent immunosuppressive protocols, such as MMF-based regimens, in this important and sizeable patient subgroup.