Iodine status in pregnant women in northern Spain. Effect of iodised salt and iodine supplements on thyroid function.

INTRODUCTION: Iodine deficiency is linked to thyroid dysfunction, particularly in pregnant women. The objective of this study was to ascertain the iodine levels of women in the second trimester of pregnancy, analysing the influence of iodine ingestion on urinary iodine concentration (UIC) and maternal thyroid function. METHODS: A prospective observational study of pregnant women from Health Area IV of Asturias (northern Spain) recruited before 13 weeks of gestation between May and June 2017. A questionnaire on iodine intake was completed at the first visit, and urine and serum samples were collected at baseline and again during the second trimester. UIC, thyroid stimulating hormone (TSH) and free thyroxine (FT4) obtained in the second trimester of gestation were analysed and related to iodine intake. Thyroid autoimmunity was also analysed in half of the pregnant women at baseline. RESULTS: A total of 241 pregnant women were studied. Of these, 56.7% used iodised salt, 46.7% consumed ≥2 servings of dairy products daily and 88.1% took iodine supplements. Median UIC was 191µg/l (135.3-294µg/l), with 68.1% of the women having UIC ≥150µg/l. Only iodised salt consumption provided protection against iodine deficiency (odds ratio 0.35 [0.20-0.63], p=0.001). In women with no autoimmune thyroid disease (n=88), mean levels of TSH were lower in those that consumed iodised salt than in those that did not (respectively, 2.08±0.89mIU/l vs. 2.56±1.02mIU/l, p=0.025). In women with autoimmune thyroid disease (n=30), mean levels of TSH were higher in those that took iodine supplements than in those that did not (respectively, 2.97±1.25mIU/l vs. 1.16±0.41mIU/l, p=0.002). CONCLUSIONS: The pregnant women studied from Health Area IV in Asturias maintain adequate nutritional iodine status in the second trimester of gestation. In our sample, only the consumption of iodised salt was associated with adequate iodine nutrition, without affecting maternal thyroid function. Most of the women used iodine supplements, which was linked to higher levels of TSH in pregnant women with autoimmune thyroid disease.

Serum and Urinary Soluble α-Klotho as Markers of Kidney and Vascular Impairment.

This study was designed to investigate the controversy on the potential role of sKlotho as an early biomarker in Chronic Kidney Disease-Mineral Bone Disorder (CKD-MBD), to assess whether sKlotho is a reliable marker of kidney α-Klotho, to deepen the effects of sKlotho on vascular smooth muscle cells (VSMCs) osteogenic differentiation and to evaluate the role of autophagy in this process. Experimental studies were conducted in CKD mice fed a normal phosphorus (CKD+NP) or high phosphorus (CKD+HP) diet for 14 weeks. The patients' study was performed in CKD stages 2-5 and in vitro studies which used VSMCs exposed to non-calcifying medium or calcifying medium with or without sKlotho. The CKD experimental model showed that the CKD+HP group reached the highest serum PTH, P and FGF23 levels, but the lowest serum and urinary sKlotho levels. In addition, a positive correlation between serum sKlotho and kidney α-Klotho was found. CKD mice showed aortic osteogenic differentiation, together with increased autophagy. The human CKD study showed that the decline in serum sKlotho is previous to the rise in FGF23. In addition, both serum sKlotho and FGF23 levels correlated with kidney function. Finally, in VSMCs, the addition of sKlotho prevented osteogenic differentiation and induced autophagy. It can be concluded that serum sKlotho was the earliest CKD-MBD biomarker, a reliable indicator of kidney α-Klotho and that might protect against osteogenic differentiation by increasing autophagy. Nevertheless, further studies are needed to investigate the mechanisms of this possible protective effect.

Nutritional Iodine Status in Pregnant Women from Health Area IV in Asturias (Spain): Iodised Salt Is Enough.

BACKGROUND: Iodine deficiency during pregnancy may have adverse effects on the neurodevelopment of the foetus. Recent studies of pregnant women in Asturias (Spain) indicate that nutritional iodine levels are sufficient. The objective of this study was to confirm the appropriate nutritional iodine status and to analyse the influence of the ingestion of iodine on maternal urinary iodine concentration (UIC) and thyroid function. METHODS: An observational study was carried out between May and June 2017 on women in the first trimester of pregnancy from Health Area IV in Asturias. The women completed a questionnaire related to their consumption of iodine and samples were taken to analyse UIC and thyroid function. RESULTS: Three hundred and eighteen pregnant women were involved. Of these, 51.10% used iodised salt, 48.90% consumed ≥ 2 servings of dairy products daily and 87.08% took iodine supplements. The median UIC was 171.5 µg/L (116-265 µg/L) and 60.41% of women had UIC ≥ 150 µg/L. Multivariate logistic regression analysis demonstrated that iodised salt had a protective effect on UIC < 150 µg/L (odds ratio (OR) 0.404 (0.237-0.683), p = 0.001), but not iodine supplements (OR 0.512 (0.240-1.085), p = 0.080). The average level of thyroid stimulating hormone (TSH) was 2.26 ± 0.94 mIU/L; 68.40% of pregnant women taking iodine supplements had TSH < 2.5 mIU/L compared to 30.00% of those who were not taking supplements (p = 0.031). CONCLUSIONS: The pregnant women in our health area are maintaining appropriate nutritional iodine levels. The consumption of iodised salt protects against iodine deficiency; thus, iodine supplements should be taken on an individualised basis.

Contribution of phosphorus and PTH to the development of cardiac hypertrophy and fibrosis in an experimental model of chronic renal failure. / Contribución de fósforo y PTH al desarrollo de hipertrofia y fibrosis cardíaca en un modelo experimental de insuficiencia renal crónica.

BACKGROUND AND OBJECTIVE: Adequate serum phosphorus levels in patients with chronic kidney disease is essential for their clinical management. However, the control of hyperphosphatemia is difficult because is normally associated with increases in serum PTH. In the present study, the effects of hyperphosphatemia, in the presence of elevated and normal PTH, on cardiac inflammation, hypertrophy and fibrosis in an experimental renal failure model were analyzed. MATERIALS AND METHODS: Four groups of rats were formed. Two groups underwent total parathyroidectomy (PTx). Rats with Ca < 7.5 mg/dL and PTH < 50 pg/mL underwent 7/8 nephrectomy (CRF) and a subcutaneous pellet was placed that releases PTH 1-34 (5 µg/kg/day). One group received a diet with normal P (NP) (CRF + PTx + rPTH + NP group) and another with a high P diet (0.9% HP) (CRF + PTx + rPTH + HP group). Other two groups that only had CRF received NP (CRF + NP) and HP (CRF + HP) diet. A SHAM group for nephrectomy and parathyroidectomy was also added. After 14 weeks the rats were sacrificed. RESULTS: The groups with a diet high in phosphorus (CRF + H A and CRF + PTx + rPTH + HP) had a significant reduction in creatinine clearance and also in body weight with an increase in serum phosphorus regardless of parathyroidectomy, but not serum levels of calcium, FGF23 and calcitriol that were 2-3 times higher in the group with secondary hyperparathyroidism (CRF + HP). The diameter of the cardiomyocytes was greater in the CRF + HP group, while parathyroidectomy (CRF + PTx + rPTH + HP) significantly reduced them, despite the high and similar serum phosphorus values. TNF-α, Adam17 and cardiac fibrosis at the histological and molecular level showed a similar pattern with increases in the group with severe secondary hyperparathyroidism (CRF + HP). CONCLUSIONS: Hyperphosphatemia confirmed its importance in the genesis of secondary hyperparathyroidism, but also of kidney damage that was independent of PTH levels. However, inflammation, fibrosis, and cardiomyocyte growth were more closely related to PTH levels, since in the presence of similar severe hyperphosphatemia, parathyroidectomy reduced the values of inflammatory parameters, cardiac hypertrophy, and fibrosis.

Contribution of phosphorus and PTH to the development of cardiac hypertrophy and fibrosis in an experimental model of chronic renal failure.

BACKGROUND AND OBJECTIVE: Adequate serum phosphorus levels in patients with chronic kidney disease is essential for their clinical management. However, the control of hyperphosphatemia is difficult because is normally associated with increases in serum PTH. In the present study, the effects of hyperphosphatemia, in the presence of elevated and normal PTH, on cardiac inflammation, hypertrophy and fibrosis in an experimental renal failure model were analyzed. MATERIALS AND METHODS: 4 groups of rats were formed. Two groups underwent total parathyroidectomy (PTx). Rats with Ca <7.5 mg/dL and PTH < 50 pg/mL underwent 7/8 nephrectomy (CRF) and a subcutaneous pellet was placed that releases PTH 1-34 (5 µg/kg/day). One group received a diet with normal P (NP) (CRF + PTx + rPTH + NP group) and another with a high P diet (0.9% - HP) (CRF + PTx + rPTH + HP group). Other 2 groups that only had CRF received NP (CRF + NP) and HP (CRF + HP) diet. A SHAM group for nephrectomy and parathyroidectomy was also added. After 14 weeks the rats were sacrificed. RESULTS: The groups with a diet high in phosphorus (CRF + H A and CRF + PTx + rPTH + HP) had a significant reduction in creatinine clearance and also in body weight with an increase in serum phosphorus regardless of parathyroidectomy, but not serum levels of calcium, FGF23 and calcitriol that were 2-3 times higher in the group with secondary hyperparathyroidism (CRF + HP). The diameter of the cardiomyocytes was greater in the CRF + HP group, while parathyroidectomy (CRF + PTx + rPTH + HP) significantly reduced them, despite the high and similar serum phosphorus values. TNF-α, Adam17 and cardiac fibrosis at the histological and molecular level showed a similar pattern with increases in the group with severe secondary hyperparathyroidism (CRF + HP). CONCLUSIONS: Hyperphosphatemia confirmed its importance in the genesis of secondary hyperparathyroidism, but also of kidney damage that was independent of PTH levels. However, inflammation, fibrosis, and cardiomyocyte growth were more closely related to PTH levels, since in the presence of similar severe hyperphosphatemia, parathyroidectomy reduced the values ​​of inflammatory parameters, cardiac hypertrophy, and fibrosis.