Hypovitaminosis D and its relationship with nutritional status and quality of life in patients undergoing haemodialysis / Hipovitaminosis D y su relación con el estado nutricional y la calidad de vida en pacientes incluidos en un programa de hemodiálisis

Objective: to assess the prevalence of hypovitaminosis D in patients undergoing haemodialysis (HD) and to determine its relationship with nutritional status and quality of life (QoL). Material and methods: 120 patients were included in the study. The Malnutrition-Inflammation Score (MIS) was used to detect nutritional risk. QoL was evaluated by Kidney Disease Quality of Life version 1.2 (KDQOL-SF). Patients were stratified into three groups according to their vitamin D status: sufficiency (≥ 30 ng/dl), insufficiency (29-10 ng/dl) and deficiency (< 10 ng/dl). Results: hypovitaminosis D was detected in 71 % of the patients studied. Multiple linear regression analysis showed that vitamin-D deficiency was the most significant predictor of low KDQOL-SF scores. It explained 21 % of the variance in the Kidney Disease Component Summary, 27 % of that in the Physical Component Summary, and 22 % of that in the Mental Component Summary. Multiple logistic regression analysis showed that only vitamin-D deficiency was significantly associated with malnutrition (OR, 14.6, p < 0.001). Conclusion: HD patients frequently present with hypovitaminosis D. There is a significant correlation between vitamin-D deficiency, poorer nutritional status, and worse QoL in dialysed patients. (AU)

Objetivo: evaluar la prevalencia de la hipovitaminosis D en pacientes en hemodiálisis (HD) y su relación con el estado nutricional y la calidad de vida (CV). Material y métodos: un total de 120 pacientes fueron incluidos. La escala de Malnutrición-Inflamación (MIS) se utilizó para la detección del riesgo nutricional. La CV fue evaluada por el cuestionario Kidney Disease Quality of Life versión 1.2 (KDQOL-SF). Los pacientes fueron estratificados en tres grupos de acuerdo con el estado de la vitamina D: suficiencia (≥ 30 ng/dl), insuficiencia (29-10 ng/dl) y deficiencia (< 10 ng/dl). Resultados: se observó hipovitaminosis D en el 71 % de los pacientes. El análisis de regresión lineal múltiple mostró que la deficiencia devitamina D fue el predictor más significativo de peores resultados en el cuestionario KDQOL-SF. La deficiencia de 25(OH)D explicó el 21 % de la varianza en el componente sumatorio de la enfermedad renal, el 27 % en el componente sumatorio físico y el 22 % en el componente sumatorio mental. Cuando evaluamos el estado nutricional, el análisis de regresión logística multivariante mostró que solo la deficiencia de vitamina D presenta un efecto significativo en la desnutrición (OR: 14.6, p < 0,001). Conclusión: de nuestros hallazgos concluimos que la hipovitaminosis D es muy frecuente entre los pacientes en HD y que su deficiencia está asociada un deterioro del estado nutricional y peor percepción de la calidad de vida. (AU)

Hypovitaminosis D and its relationship with nutritional status and quality of life in patients undergoing haemodialysis.

Introduction: Objective: to assess the prevalence of hypovitaminosis D in patients undergoing haemodialysis (HD) and to determine its relationship with nutritional status and quality of life (QoL). Material and methods: 120 patients were included in the study. The Malnutrition-Inflammation Score (MIS) was used to detect nutritional risk. QoL was evaluated by Kidney Disease Quality of Life version 1.2 (KDQOL-SF). Patients were stratified into three groups according to their vitamin D status: sufficiency (≥ 30 ng/dl), insufficiency (29-10 ng/dl) and deficiency (< 10 ng/dl). Results: hypovitaminosis D was detected in 71 % of the patients studied. Multiple linear regression analysis showed that vitamin-D deficiency was the most significant predictor of low KDQOL-SF scores. It explained 21 % of the variance in the Kidney Disease Component Summary, 27 % of that in the Physical Component Summary, and 22 % of that in the Mental Component Summary. Multiple logistic regression analysis showed that only vitamin-D deficiency was significantly associated with malnutrition (OR, 14.6, p < 0.001). Conclusion: HD patients frequently present with hypovitaminosis D. There is a significant correlation between vitamin-D deficiency, poorer nutritional status, and worse QoL in dialysed patients.

Introducción: Objetivo: evaluar la prevalencia de la hipovitaminosis D en pacientes en hemodiálisis (HD) y su relación con el estado nutricional y la calidad de vida (CV). Material y métodos: un total de 120 pacientes fueron incluidos. La escala de Malnutrición-Inflamación (MIS) se utilizó para la detección del riesgo nutricional. La CV fue evaluada por el cuestionario Kidney Disease Quality of Life versión 1.2 (KDQOL-SF). Los pacientes fueron estratificados en tres grupos de acuerdo con el estado de la vitamina D: suficiencia (≥ 30 ng/dl), insuficiencia (29-10 ng/dl) y deficiencia (< 10 ng/dl) Resultados: se observó hipovitaminosis D en el 71 % de los pacientes. El análisis de regresión lineal múltiple mostró que la deficiencia de vitamina D fue el predictor más significativo de peores resultados en el cuestionario KDQOL-SF. La deficiencia de 25(OH)D explicó el 21 % de la varianza en el componente sumatorio de la enfermedad renal, el 27 % en el componente sumatorio físico y el 22 % en el componente sumatorio mental. Cuando evaluamos el estado nutricional, el análisis de regresión logística multivariante mostró que solo la deficiencia de vitamina D presenta un efecto significativo en la desnutrición (OR: 14.6, p < 0,001). Conclusión: De nuestros hallazgos concluimos que la hipovitaminosis D es muy frecuente entre los pacientes en HD y que su deficiencia está asociada un deterioro del estado nutricional y peor percepción de la calidad de vida.

Dietary salt restriction in hyperthyroid rats. Differential influence on left and right ventricular mass.

This study assessed the impact of salt restriction on cardiac morphology and biochemistry and its effects on hemodynamic and renal variables in experimental hyperthyroidism. Four groups of male Wistar rats were used: control, hyperthyroid, and the same groups under low salt intake. Body weight, blood pressure (BP), and heart rate (HR) were recorded weekly for 4 weeks. Morphologic, metabolic, plasma, cardiac, and renal variables were also measured. Low salt intake decreased BP in T(4)-treated rats but not in controls. Low salt intake reduced relative left ventricular mass but increased absolute right ventricular weight and right ventricular weight/BW ratio in both control and hyperthyroid groups. Low salt intake increased Na(+)/H(+) exchanger-1 (NHE-1) protein abundance in both ventricles in normal rats but not in hyperthyroid rats, independently of its effect on ventricular mass. Mammalian target of rapamycin (mTOR) protein abundance was not related to left or right ventricular mass in hyperthyroid or controls rats under normal or low salt conditions. Proteinuria was increased in hyperthyroid rats and attenuated by low salt intake. In this study, low salt intake produced an increase in right ventricular mass in normal and hyperthyroid rats. Changes in the left or right ventricular mass of control and hyperthyroid rats under low salt intake were not explained by the NHE-1 or mTOR protein abundance values observed. In hyperthyroid rats, low salt intake also slightly reduced BP and decreased HR, proteinuria, and water and sodium balances.

The flavonoid quercetin induces acute vasodilator effects in healthy volunteers: correlation with beta-glucuronidase activity.

UNLABELLED: Quercetin exerts vasodilator, antiplatelet and antiproliferative effects and reduces blood pressure, oxidative status and end-organ damage in hypertensive humans and animal models. We hypothesized that oral quercetin might induce vasodilator effects in humans and that they might be related to the deconjugation of quercetin-3-O-glucuronide (Q3GA). DESIGN: double blind, randomized, placebo-controlled trial. Fifteen healthy volunteers (26±5 years, 6 female) were given a capsule containing placebo, 200 or 400mg of quercetin in random order in three consecutive weeks. At 2h a dose-dependent increase in Q3GA was observed in plasma (∼0.4 and 1µM for 200 and 400mg, respectively) with minor levels of quercetin and isorhamnetin. No changes were observed in blood pressure. At 5h quercetin induced and increase in brachial arterial diameter that correlated with the product of the levels of Q3GA by the plasma glucuronidase activity. There was an increase in urinary levels of glutathione but there was no increase in nitrites plus nitrates. Quercetin and isorhamnetin also relaxed human umbilical arteries in vitro while Q3GA was without effect. In conclusions, quercetin exerts acute vasodilator effects in vivo in normotensive, normocholesterolemic human subjects. These results are consistent with the effects being due to the deconjugation of the metabolite Q3GA.

Preconditioning with triiodothyronine improves the clinical signs and acute tubular necrosis induced by ischemia/reperfusion in rats.

BACKGROUND: Renal ischemia/reperfusion (I/R) injury is manifested by acute renal failure (ARF) and acute tubular necrosis (ATN). The aim of this study was to evaluate the effectiveness of preconditioning with 3, 3, 5 triiodothyronine (T3) to prevent I/R renal injury. METHODOLOGY/PRINCIPAL FINDINGS: The rats were divided into four groups: sham-operated, placebo-treated (SO-P), sham-operated T3- treated (SO- T3), I/R-injured placebo-treated (IR-P), and I/R-injured T3-treated (IR- T3) groups. At 24 h before ischemia, the animals received a single dose of T3 (100 µg/kg). Renal function and plasma, urinary, and tissue variables were studied at 4, 24, and 48 h of reperfusion, including biochemical, oxidative stress, and inflammation variables, PARP-1 immunohistochemical expression, and ATN morphology. In comparison to the SO groups, the IR-P groups had higher plasma urea and creatinine levels and greater proteinuria (at all reperfusion times) and also showed: increased oxidative stress-related plasma, urinary, and tissue variables; higher plasma levels of IL6 (proinflammatory cytokine); increased glomerular and tubular nuclear PARP-1 expression; and a greater degree of ATN. The IR-T3 group showed a marked reduction in all of these variables, especially at 48 h of reperfusion. No significant differences were observed between SO-P and SO-T3 groups. CONCLUSIONS: This study demonstrates that preconditioning rats with a single dose of T3 improves the clinical signs and ATN of renal I/R injury. These beneficial effects are accompanied by reductions in oxidative stress, inflammation, and renal PARP-1 expression, indicating that this sequence of factors plays an important role in the ATN induced by I/R injury.

Long-term consequences of uninephrectomy in male and female rats.

We investigated the effects of uninephrectomy (UNX) in 6-week-old male and female rats on blood pressure (BP), renal sodium handling, salt sensitivity, oxidative stress, and renal injury over 18 months postsurgery, studying control sham-operated and UNX-operated rats at 6, 12, and 18 months postsurgery, evaluating their renal sodium handling, BP, urinary isoprostanes, N-acetyl-ß-D-glucosaminidase, and proteinuria before and after a 2-week high-salt intake period. At 18 months, plasma variables were measured and kidney samples were taken for the analysis of renal morphology and tissue variables. BP was increased at 6 months in male UNX rats versus controls and at 12 and 18 months in both male and female UNX rats and was increased in male versus female UNX groups at 18 months. UNX did not affect water and sodium excretion under basal conditions and after the different test in male and female rats at different ages. However, the renal function curve was shifted to the right in both male and female UNX rats. High-salt intake increased BP in both UNX groups at 6, 12, and 18 months and in the female control group at 18 months, and it increased proteinuria, N-acetyl-ß-D-glucosaminidase, and isoprostanes in both UNX groups throughout the study. Renal lesions at 18 months were more severe in male versus female UNX rats. In summary, long-term UNX increased the BP, creatinine, proteinuria, pathological signs of renal injury, and salt sensitivity. Earlier BP elevation was observed and morphological lesions were more severe in male than in female UNX rats.

Cardiovascular and renal manifestations of glutathione depletion induced by buthionine sulfoximine.

Oxidative stress contributes to the development of several cardiovascular diseases, including diabetes, renal insufficiency, and arterial hypertension. Animal studies have evidenced the association between higher blood pressure (BP) and increased oxidative stress, and treatment with antioxidants has been shown to reduce BP, while BP reduction due to antihypertensive drugs is associated with reduced oxidative stress. In 2000, it was first reported that oxidative stress and arterial hypertension were produced in normal Sprague-Dawley rats by oral administration of buthionine sulfoximine (BSO), which induces glutathione (GSH) depletion, indicating that oxidative stress may induce hypertension. The contribution of several potential pathogenic factors has been evaluated in the BSO rat model, the prototype of oxidative stress-induced hypertension, including vascular reactivity, endothelium-derived factors, renin-angiotensin system activity, TXA(2)-PGH(2) production, sodium sensitivity, renal dopamine-induced natriuresis, and sympathetic tone. This review summarizes the main factors implicated in the pathogenesis of BSO-induced hypertension and the alterations associated with GSH depletion that are related to renal function or BP control.

Contribution of the amiloride-sensitive component and the Na+/H+ exchanger to renal responsiveness to vasoconstrictors.

AIMS: This study analyzed the role of the amiloride-sensitive component and the participation of the Na(+)/H(+) exchanger in renal responsiveness to vasoconstrictors in the isolated perfused rat kidney. METHODS: The renal responses to vasoconstrictors (angiotensin II, phenylephrine, vasopressin and KCl) were studied under baseline conditions and after the administration of amiloride (10 and 100 µmol/l) or the specific Na(+)/H(+) exchange inhibitor ethylisopropylamiloride (EIPA, 10 µmol/l). The effects of amiloride and EIPA on renal responsiveness to vasoconstrictors were also analyzed in endothelium-denuded preparations. RESULTS: Amiloride reduced renal responsiveness to all vasoconstrictors in a dose-related manner, whereas EIPA did not affect the renal pressor response to KCl. The inhibitory effects of amiloride and EIPA on renal responsiveness to vasoconstrictors persisted after endothelium removal. CONCLUSION: These results indicate that the amiloride-sensitive component and the Na(+)/H(+) exchanger play an important role in responsiveness to the main endogenous vasoconstrictors in the renal vasculature. These results also suggest that amiloride might be useful as an inhibitor of renal vasoconstriction, even in diseases with endothelial dysfunction.

Salt sensitivity in experimental thyroid disorders in rats.

This study assessed salt sensitivity, analyzing the effects of an increased saline intake on hemodynamic, morphological, and oxidative stress and renal variables in experimental thyroid disorders. Six groups of male Wistar rats were used: control, hypothyroid, hyperthyroid, and the same groups treated with salt (8% via food intake). Body weight, blood pressure (BP), and heart rate (HR) were recorded weekly for 6 wk. Finally, BP and HR were recorded directly, and morphological, metabolic, plasma, and renal variables were measured. High-salt intake increased BP in thyroxine-treated rats but not in control or hypothyroid rats. High-salt intake increased cardiac mass in all groups, with a greater increase in hyperthyroid rats. Urinary isoprostanes and H(2)O(2) were higher in hyperthyroid rats and were augmented by high-salt intake in all groups, especially in hyperthyroid rats. High-salt intake reduced plasma thyroid hormone levels in hyperthyroid rats. Proteinuria was increased in hyperthyroid rats and aggravated by high-salt intake. Urinary levels of aminopeptidases (glutamyl-, alanyl-, aspartyl-, and cystinylaminopeptidase) were increased in hyperthyroid rats. All aminopeptidases were increased by salt intake in hyperthyroid rats but not in hypothyroid rats. In summary, hyperthyroid rats have enhanced salt sensitivity, and high-salt intake produces increased BP, cardiac hypertrophy, oxidative stress, and signs of renal injury. In contrast, hypothyroid rats are resistant to salt-induced BP elevation and renal injury signs. Urinary aminopeptidases are suitable biomarkers of renal injury.

Effects of clofibrate on salt loading-induced hypertension in rats.

The effects of clofibrate on the hemodynamic and renal manifestations of increased saline intake were analyzed. Four groups of male Wistar rats were treated for five weeks: control, clofibrate (240 mg/kg/day), salt (2% via drinking water), and salt + clofibrate. Body weight, systolic blood pressure (SBP), and heart rate (HR) were recorded weekly. Finally, SBP, HR, and morphologic, metabolic, plasma, and renal variables were measured. Salt increased SBP, HR, urinary isoprostanes, NOx, ET, vasopressin and proteinuria and reduced plasma free T(4) (FT(4)) and tissue FT(4) and FT(3) versus control rats. Clofibrate prevented the increase in SBP produced by salt administration, reduced the sodium balance, and further reduced plasma and tissue thyroid hormone levels. However, clofibrate did not modify the relative cardiac mass, NOx, urinary ET, and vasopressin of saline-loaded rats. In conclusion, chronic clofibrate administration prevented the blood pressure elevation of salt-loaded rats by decreasing sodium balance and reducing thyroid hormone levels.

Role of sympathetic tone in BSO-induced hypertension in mice.

BACKGROUND: We investigated the contribution of the sympathetic tone to the hypertension induced by chronic administration of buthionine sulfoximine (BSO) and characterized this model in mice. METHODS: Three experiments were performed. In experiment I, four groups of CBA-C57 male mice were used: controls and three groups that received oral BSO at 5, 10, or 20 mmol/l. In experiment II, the alpha(1)-adrenergic blocker prazosin was orally administered (10 mg/100 ml) to control and BSO-treated mice. All treatments were maintained for 5 weeks. Body weight (BW), tail blood pressure (BP), and heart rate (HR) were measured weekly. Direct mean arterial pressure (MAP) and morphological, metabolic, plasma, and renal variables were measured at the end of the experiments. In experiment III, the acute response of MAP and HR to the ganglionic blocker pentolinium (10 mg/kg intravenous) was used to further evaluate the sympathetic contribution to BP and HR in control and BSO-treated mice. RESULTS: BSO produced dose-related increases in BP (control, 115 +/- 0.5; BSO-5, 141 +/- 0.5; BSO-10, 151 +/- 0.9; BSO-20, 163 +/- 1.1 mm Hg) and HR and augmented plasma noradrenaline, brainstem isoprostane levels, and total urinary isoprostane excretion. BSO did not produce cardiac hypertrophy and did not modify metabolic or plasma variables, or creatinine clearance, proteinuria, or renal morphology. Chronic prazosin markedly reduced MAP (control, 101 +/- 4.7; prazosin, 95 +/- 1.29; BSO-10, 130 +/- 2.9; BSO-10 +/- prazosin, 98 +/- 0.9) and HR. Acute pentolinium produced a greater percentage MAP (control, 43 +/- 4.2; BSO-10, 66 +/- 4.5) and HR decrease in BSO-treated mice vs. controls. CONCLUSION: Sympathetic tone plays a major role in the increased BP and HR of BSO hypertensive mice.