Changes in acid-base status in oxygen toxicity at 230 kPa oxygen as a function of exposure time.

Breathing less than 50 kPa of oxygen over time can lead to pulmonary oxygen toxicity (POT). Vital capacity (VC) as the sole parameter for POT has its limitations. In this study we try to find out the changes of acid-base status in a POT rat model. Fifty male rats were randomly divided into five groups, exposed to 230 kPa oxygen for three, six, nine and 12 hours, respectively. Rats exposed to air were used as controls. After exposure the mortality and behavior of rats were observed. Arterial blood samples were collected for acid-base status detection and wet-dry (W/D) ratios of lung tissues were tested. Results showed that the acid-base status in rats exposed to 230 kPa oxygen presented a dynamic change. The primary status was in the compensatory period when primary respiratory acidosis was mixed with compensated metabolic alkalosis. Then the status changed to decompensated alkalosis and developed to decompensated acidosis in the end. pH, PCO2, HCO3-, TCO2, and BE values had two phases: an increase and a later decrease with increasing oxygen exposure time, while PaO2 and lung W/D ratio showed continuously increasing trends with the extension of oxygen exposure time. Lung W/D ratio was significantly associated with PaO2 (r = 0.6385, p = 0.002), while other parameters did not show a significant correlation. It is concluded that acid-base status in POT rats presents a dynamic change: in the compensatory period first, then turns to decompensated alkalosis and ends up with decompensated acidosis status. Blood gas analysis is a useful method to monitor the development of POT.

Is carbonic anhydrase inhibition useful as a complementary therapy of Covid-19 infection?

The ongoing Covid-19 is a contagious disease, and it is characterised by different symptoms such as fever, cough, and shortness of breath. Rising concerns about Covid-19 have severely affected the healthcare system in all countries as the Covid-19 outbreak has developed at a rapid rate all around the globe. Intriguing, a clinically used drug, acetazolamide (a specific inhibitor of carbonic anhydrase, CA, EC 4.2.1.1), is used to treat high-altitude pulmonary oedema (HAPE), showing a high degree of clinical similarities with the pulmonary disease caused by Covid-19. In this context, this preliminary study aims to provide insights into some factors affecting the Covid-19 patients, such as hypoxaemia, hypoxia as well as the blood CA activity. We hypothesise that patients with Covid-19 problems could show a dysregulated acid-base status influenced by CA activity. These preliminary results suggest that the use of CA inhibitors as a pharmacological treatment for Covid-19 may be beneficial.

Application of Molecular Hydrogen as an Antioxidant in Responses to Ventilatory and Ergogenic Adjustments during Incremental Exercise in Humans.

We investigated effects of molecular hydrogen (H2) supplementation on acid-base status, pulmonary gas exchange responses, and local muscle oxygenation during incremental exercise. Eighteen healthy, trained subjects in a randomized, double-blind, crossover design received H2-rich calcium powder (HCP) (1500 mg/day, containing 2.544 µg/day of H2) or H2-depleted placebo (1500 mg/day) for three consecutive days. They performed cycling incremental exercise starting at 20-watt work rate, increasing by 20 watts/2 min until exhaustion. Breath-by-breath pulmonary ventilation (V˙E) and CO2 output (V˙CO2) were measured and muscle deoxygenation (deoxy[Hb + Mb]) was determined via time-resolved near-infrared spectroscopy in the vastus lateralis (VL) and rectus femoris (RF). Blood gases' pH, lactate, and bicarbonate (HCO3-) concentrations were measured at rest and 120-, 200-, and 240-watt work rates. At rest, the HCP group had significantly lower V˙E, V˙CO2, and higher HCO3-, partial pressures of CO2 (PCO2) versus placebo. During exercise, a significant pH decrease and greater HCO3- continued until 240-watt workload in HCP. The V˙E was significantly lower in HCP versus placebo, but HCP did not affect the gas exchange status of V˙CO2 or oxygen uptake (V˙O2). HCP increased absolute values of deoxy[Hb + Mb] at the RF but not VL. Thus, HCP-induced hypoventilation would lead to lower pH and secondarily impaired balance between O2 delivery and utilization in the local RF during exercise, suggesting that HCP supplementation, which increases the at-rest antioxidant potential, affects the lower ventilation and pH status during incremental exercise. HPC induced a significantly lower O2 delivery/utilization ratio in the RF but not the VL, which may be because these regions possess inherently different vascular/metabolic control properties, perhaps related to fiber-type composition.

Bicarbonate Unlocks the Ergogenic Action of Ketone Monoester Intake in Endurance Exercise.

PURPOSE: We recently reported that oral ketone ester (KE) intake before and during the initial 30 min of a 3 h 15 min simulated cycling race (RACE) transiently decreased blood pH and bicarbonate without affecting maximal performance in the final quarter of the event. We hypothesized that acid-base disturbances due to KE overrules the ergogenic potential of exogenous ketosis in endurance exercise. METHODS: Nine well-trained male cyclists participated in a similar RACE consisting of 3 h submaximal intermittent cycling (IMT180') followed by a 15-min time trial (TT15') preceding an all-out sprint at 175% of lactate threshold (SPRINT). In a randomized crossover design, participants received (i) 65 g KE, (ii) 300 mg·kg-1 body weight NaHCO3 (BIC), (iii) KE + BIC, or (iv) a control drink (CON), together with consistent 60 g·h-1 carbohydrate intake. RESULTS: KE ingestion transiently elevated blood D-ß-hydroxybutyrate to ~2-3 mM during the initial 2 h of RACE (P < 0.001 vs CON). In KE, blood pH concomitantly dropped from 7.43 to 7.36 whereas bicarbonate decreased from 25.5 to 20.5 mM (both P < 0.001 vs CON). Additional BIC resulted in 0.5 to 0.8 mM higher blood D-ß-hydroxybutyrate during the first half of IMT180' (P < 0.05 vs KE) and increased blood bicarbonate to 31.1 ± 1.8 mM and blood pH to 7.51 ± 0.03 by the end of IMT180' (P < 0.001 vs KE). Mean power output during TT15' was similar between KE, BIC, and CON at ~255 W but was 5% higher in KE + BIC (P = 0.02 vs CON). Time to exhaustion in the sprint was similar between all conditions at ~60 s (P = 0.88). Gastrointestinal symptoms were similar between groups. DISCUSSION: The coingestion of oral bicarbonate and KE enhances high-intensity performance at the end of an endurance exercise event without causing gastrointestinal distress.

Enteric-coated sodium bicarbonate supplementation improves high-intensity cycling performance in trained cyclists.

PURPOSE: Enteric-coated sodium bicarbonate (NaHCO3) can attenuate gastrointestinal (GI) symptoms following acute bicarbonate loading, although the subsequent effects on exercise performance have not been investigated. The purpose of this study was to examine the effects of enteric-coated NaHCO3 supplementation on high-intensity exercise performance and GI symptoms. METHODS: Eleven trained male cyclists completed three 4 km time trials after consuming; a placebo or 0.3 g∙kg-1 body mass NaHCO3 in enteric-coated or gelatin capsules. Exercise trials were timed with individual peak blood bicarbonate ion concentration ([HCO3-]). Blood acid-base balance was measured pre-ingestion, pre-exercise, and post-exercise, whereas GI symptoms were recorded pre-ingestion and immediately pre-exercise. RESULTS: Pre-exercise blood [HCO3-] and potential hydrogen (pH) were greater for both NaHCO3 conditions (P < 0.0005) when compared to placebo. Performance time was faster with enteric-coated (- 8.5 ± 9.6 s, P = 0.044) and gelatin (- 9.6 ± 7.2 s, P = 0.004) NaHCO3 compared to placebo, with no significant difference between conditions (mean difference = 1.1 ± 5.3 s, P = 1.000). Physiological responses were similar between conditions, although blood lactate ion concentration was higher with gelatin NaHCO3 (2.4 ± 1.7 mmol∙L-1, P = 0.003) compared with placebo. Furthermore, fewer participants experienced GI symptoms with enteric-coated (n = 3) compared to gelatin (n = 7) NaHCO3. DISCUSSION: Acute enteric-coated NaHCO3 consumption mitigates GI symptoms at the onset of exercise and improves subsequent 4 km cycling TT performance. Athletes who experience GI side-effects after acute bicarbonate loading may, therefore, benefit from enteric-coated NaHCO3 supplementation prior to exercise performance.

Retrospective study of the efficacy of oral potassium supplementation in cats with kidney disease.

OBJECTIVES: The aim of this study was to assess the effect of three oral potassium supplements (potassium gluconate tablets [PGT], potassium gluconate granules [PGG] and potassium citrate granules [PCG]) on hypokalemia and serum bicarbonate in cats with chronic kidney disease (CKD). METHODS: Medical records (2006-2016) were retrospectively searched for cats that had been prescribed an oral potassium supplement for management of their CKD-associated hypokalemia. For inclusion, laboratory work had to be available at the time of hypokalemia diagnosis, and at recheck within 1-6 weeks. Treatment response was defined in three ways: any increase in potassium, an increase in potassium to within the normal reference interval, and an increase to >4 mEq/l. RESULTS: Thirty-seven cats met inclusion criteria (16 PGT, 11 PGG, 10 PCG). Dosing ranged from 0.21 to 1.6 mEq/kg/day for PGT, from 0.25 to 1.48 mEq/kg/day for PGG and from 0.04 to 1.34 mEq/kg/day for PCG. After supplementation, 36/37 cats had an increase in potassium, 34/37 increased to within the reference interval and 24/37 had an increase in potassium to >4 mEq/l. There was a statistically significant difference in serum potassium post-supplementation for all three treatments: PGT (P = 0.0001), PGG (P = 0.001) and PCG (P = 0.002). There was a positive correlation between PGT dose and change in potassium concentration (P = 0.04), but there was no significant correlation for PGG or PCG. In cats that had data available, serum bicarbonate increased >2 mEq/l in 1/6 PGT, 1/6 PGG and 3/4 PCG cats. CONCLUSIONS AND RELEVANCE: All three potassium supplements were effective in treating hypokalemia secondary to CKD in the majority of cats despite variable dosing. Data were limited to assess the alkalinizing effect and prospective studies are needed.

Metabolic acidosis is associated with pulse wave velocity in chronic kidney disease: Results from the KNOW-CKD Study.

Metabolic acidosis is common in chronic kidney disease (CKD) and may have various deleterious consequences. Arterial stiffness in CKD patients is associated with poor cardiovascular outcomes. The present study aimed to evaluate the association between serum bicarbonate and arterial stiffness using the baseline cross-sectional data set of a large-scale Korean CKD cohort. 2,238 CKD patients were enrolled in the KoreaN Cohort Study for Outcome in Patients With Chronic Kidney Disease (KNOW-CKD) from 2011 to 2016. The present study was conducted on 1,659 patients included in this cohort with baseline serum bicarbonate and brachial-to-ankle pulse wave velocity (baPWV) data. Metabolic acidosis was defined as a serum bicarbonate level of <22 mmol/L, and baPWV was used as a surrogate of arterial stiffness. Mean serum bicarbonate was 25.8 ± 3.6 mmol/L. 210 (12.7%) patients had metabolic acidosis. baPWV was significantly higher in patients with metabolic acidosis (P < 0.001) and showed a significant inverse correlation with serum bicarbonate (Unstandardized ß -16.0 cm/sec; 95% CI -20.5, -11.4; P < 0.001) in an unadjusted model, which was retained after adjustment (Unstandardized ß -5.4 cm/sec; 95% CI -9.9, -1.0; P = 0.017). Metabolic acidosis was found to be associated with a high baPWV in pre-dialysis CKD patients.

Serum Biochemical Analytes and Trace Elements in Juvenile Whooping Cranes (Grus americana).

Biochemical and trace element analyses of blood from wild Whooping Cranes (Grus americana) were performed to assess the health of the only self-sustaining, migratory population in North America. Juvenile cranes (n=31) approximately 49-70 d-old were sampled at Wood Buffalo National Park, Northwest Territories, Canada, in midsummer from 2010 to 2012. Archived serum (n=24) and whole blood (n=31) samples from captive juvenile cranes were selected as age-matched controls. Reference values were calculated for serum biochemical analytes and trace elements in whole blood from the captive juvenile Whooping Cranes reared under controlled conditions and with known health histories. Several statistical differences among blood biochemical and trace element values of the wild and captive juveniles were identified and were likely attributable to dietary differences between the populations.

Control of metabolic predisposition to cardiovascular complications of chronic kidney disease by effervescent calcium magnesium citrate: a feasibility study.

AIMS: Cardiovascular (CV) complications are common in chronic kidney disease (CKD). Numerous metabolic disturbances including hyperphosphatemia, high circulating calciprotein particles (CPP), hyperparathyroidism, metabolic acidosis, and magnesium deficiency are associated with, and likely pathogenic for CV complications in CKD. The goal of this feasibility study was to determine whether effervescent calcium magnesium citrate (EffCaMgCit) ameliorates the aforementioned pathogenic intermediates. METHODS: Nine patients with Stage 3 and nine patients with Stage 5D CKD underwent a randomized crossover study, where they took EffCaMgCit three times daily for 7 days in one phase, and a conventional phosphorus binder calcium acetate (CaAc) three times daily for 7 days in the other phase. Two-hour postprandial blood samples were obtained on the day before and on the 7th day of treatment. RESULTS: In Stage 5D CKD, EffCaMgCit significantly increased T50 (half time for conversion of primary to secondary CPP) from baseline by 63% (P = 0.013), coincident with statistically non-significant declines in serum phosphorus by 25% and in saturation of octacalcium phosphate by 35%; CaAc did not change T50. In Stage 3 CKD, neither EffCaMgCit nor CaAc altered T50. With EffCaMgCit, a significant increase in plasma citrate was accompanied by statistically non-significant increase in serum Mg and phosphate. CaAc was without effect in any of these parameters in Stage 3 CKD. In both Stages 3 and 5D, both drugs significantly reduced serum parathyroid hormone. Only EffCaMgCit significantly increased serum bicarbonate by 3 mM (P = 0.015) in Stage 5D. CONCLUSIONS: In Stage 5D, EffCaMgCit inhibited formation of CPP, suppressed PTH, and conferred magnesium and alkali loads. These effects were unique, since they were not observed with CaAc. In Stage 3 CKD, neither of the regimens have any effect. These metabolic changes suggest that EffCaMgCit might be useful in protecting against cardiovascular complications of CKD by ameliorating pathobiologic intermediates.

Home hemodialysis treatment and outcomes: retrospective analysis of the Knowledge to Improve Home Dialysis Network in Europe (KIHDNEy) cohort.

BACKGROUND: Utilization of home hemodialysis (HHD) is low in Europe. The Knowledge to Improve Home Dialysis Network in Europe (KIHDNEy) is a multi-center study of HHD patients who have used a transportable hemodialysis machine that employs a low volume of lactate-buffered, ultrapure dialysate per session. In this retrospective cohort analysis, we describe patient factors, HHD prescription factors, and biochemistry and medication use during the first 6 months of HHD and rates of clinical outcomes thereafter. METHODS: Using a standardized digital form, we recorded data from 7 centers in 4 Western European countries. We retained patients who completed ≥6 months of HHD. We summarized patient and HHD prescription factors with descriptive statistics and used mixed modeling to assess trends in biochemistry and medication use. We also estimated long-term rates of kidney transplant and death. RESULTS: We identified 129 HHD patients; 104 (81%) were followed for ≥6 months. Mean age was 49 years and 66% were male. Over 70% of patients were prescribed 6 sessions per week, and the mean treatment duration was 15.0 h per week. Median HHD training duration was 2.5 weeks. Mean standard Kt/Vurea was nearly 2.7 at months 3 and 6. Pre-dialysis biochemistry was generally stable. Between baseline and month 6, mean serum bicarbonate increased from 23.1 to 24.1 mmol/L (P = 0.01), mean serum albumin increased from 36.8 to 37.8 g/L (P = 0.03), mean serum C-reactive protein increased from 7.3 to 12.4 mg/L (P = 0.05), and mean serum potassium decreased from 4.80 to 4.59 mmol/L (P = 0.01). Regarding medication use, the mean number of antihypertensive medications fell from 1.46 agents per day at HHD initiation to 1.01 agents per day at 6 months (P < 0.001), but phosphate binder use and erythropoiesis-stimulating agent dose were stable. Long-term rates of kidney transplant and death were 15.3 and 5.4 events per 100 patient-years, respectively. CONCLUSIONS: Intensive HHD with low-flow dialysate delivers adequate urea clearance and good biochemical outcomes in Western European patients. Intensive HHD coincided with a large decrease in antihypertensive medication use. With relatively rapid training, HHD should be considered in more patients.

A long term feed supplementation based on phosphate binders in Feline Chronic Kidney Disease.

Chronic kidney disease (CKD) is a very common disorder in elderly cats. A proper renal diet represents the most efficient therapeutic intervention to improve survival and life quality in feline patients with 3 and 4 International Renal Interest Society (IRIS) stages. Twenty cats were selected in this study. Ten were administered the dietary supplementation for 360 days and the other ten, whose owners did not give consent for any supplemental therapies apart from the renal diet, were selected from a clinical database and used as control group. The present study is a long term study (360 days) aiming to evaluate the efficacy and palatability of a dietary supplementation containing calcium carbonate, calcium-lactate gluconate, chitosan and sodium bicarbonate in cats diagnosed with 3 and 4 IRIS stages of CKD. The owners were asked to fill in questionnaires to get information on the cat's appetite, the palatability of the given supplement, the presence of vomit and/or diarrhoea, general health and vitality. Hematochemical, biochemical and urinary analyses were performed on day 0, 30, 60, 90, 120, 150,180 and 360. GraphPad Prism® software was used to perform statistical analysis. Our study shows that the given dietary supplement reduced serum phosphorus and increased serum bicarbonate values in cats with CKD. In turn, this supplement could be used as a support therapy in cats with advanced CKD improving their clinical conditions without any adverse reaction. Finally, it is important to underline that all the animals completed the study and the owners reported a good palatability of the feed supplement.

Weekly Standard Kt/Vurea and Clinical Outcomes in Home and In-Center Hemodialysis.

BACKGROUND AND OBJECTIVES: Patients undergoing hemodialysis with a frequency other than thrice weekly are not included in current clinical performance metrics for dialysis adequacy. The weekly standard Kt/Vurea incorporates treatment frequency, but there are limited data on its association with clinical outcomes. DESIGN, SETTING, PARTICIPANTS, & MEASUREMENTS: We used multivariable regression to examine the association of dialysis standard Kt/Vurea with BP and metabolic control (serum potassium, calcium, bicarbonate, and phosphorus) in patients incidental to dialysis treated with home (n=2373) or in-center hemodialysis (n=109,273). We further used Cox survival models to examine the association of dialysis standard Kt/Vurea with mortality, hospitalization, and among patients on home hemodialysis, transfer to in-center hemodialysis. RESULTS: After adjustment for potential confounders, patients with dialysis standard Kt/Vurea <2.1 had higher BPs compared with patients with standard Kt/Vurea 2.1 to <2.3 (3.4 mm Hg higher [P<0.001] for home hemodialysis and 0.9 mm Hg higher [P<0.001] for in-center hemodialysis). There were no clinically meaningful associations between dialysis standard Kt/Vurea and markers of metabolic control, irrespective of dialysis modality. There was no association between dialysis standard Kt/Vurea and risk for mortality, hospitalization, or transfer to in-center hemodialysis among patients undergoing home hemodialysis. Among patients on in-center hemodialysis, dialysis standard Kt/Vurea <2.1 was associated with higher risk (adjusted hazard ratio, 1.11; 95% confidence interval, 1.07 to 1.14) and standard Kt/Vurea ≥2.3 was associated with lower risk (adjusted hazard ratio, 0.97; 95% confidence interval, 0.94 to 0.99) for death compared with standard Kt/Vurea 2.1 to <2.3. Additional analyses limited to patients with available data on residual kidney function showed similar relationships of dialysis and total (dialysis plus kidney) standard Kt/Vurea with outcomes. CONCLUSIONS: Current targets for standard Kt/Vurea have limited utility in identifying individuals at increased risk for adverse clinical outcomes for those undergoing home hemodialysis but may enhance risk stratification for in-center hemodialysis.

Alkaline Diet and Metabolic Acidosis: Practical Approaches to the Nutritional Management of Chronic Kidney Disease.

The kidneys play an extremely important role in maintaining the body acid-base balance by excreting nonvolatile acids and regenerating and reabsorbing bicarbonate in the kidney tubules. As the individual loses their kidney function, renal excretion of nonvolatile acid produced by metabolism of the diet is impaired, resulting in low-grade metabolic acidosis. With this in mind, it is relevant to better understand the dietary aspects related to the acid-base balance in chronic kidney disease metabolic acidosis and try to provide possible strategies for the nutritional management of these cases. The type of diet can deeply affect the body by providing acid or base precursors. Generally speaking, foods such as meat, eggs, cheese, and grains increase the production of acid in the organism, whereas fruit and vegetables are alkalizing. On the other hand, milk is considered neutral as well as fats and sugars, which have a small effect on acid-base balance. The modern Western-type diet is deficient in fruits and vegetables and contains excessive animal products. Thus metabolic acidosis may be exacerbated by a contemporary Western diet, which delivers a high nonvolatile acid load. The remaining acid is neutralized or stored within the body. Bone and muscle are lost to neutralize the acid and serum bicarbonate falls. Early studies suggest that lowering the dietary acid load with a reduced protein content and vegetable proteins replacements, associated with an increase in fruits and vegetables intake can improve the metabolic parameters of acidosis, preserve bone and muscle, and slow the glomerular filtration rate decline. More studies focusing on the effects of controlled dietary interventions among chronic kidney disease patients are needed to determining the optimal target for nutritional therapy.

Management of the Metabolic Acidosis of Chronic Kidney Disease.

Subjects with CKD and reduced glomerular filtration rate are at risk for chronic metabolic acidosis, and CKD is its most common cause. Untreated metabolic acidosis, even in its mildest forms, is associated with increased mortality and morbidity and should therefore be treated. If reduced glomerular filtration rate or the tubule abnormality causing chronic metabolic acidosis cannot be corrected, it is typically treated with dietary acid (H+) reduction using Na+-based alkali, usually NaHCO3. Dietary H+ reduction can also be accomplished with the addition of base-producing foods such as fruits and vegetables and limiting intake of H+-producing foods like animal-sourced protein. The optimal dose of Na+-based alkali that prevents the untoward effects of metabolic acidosis while minimizing adverse effects and the appropriate combination of this traditional therapy with dietary strategies remain to be determined by ongoing studies. Recent emerging evidence supports a phenomenon of H+ retention, which precedes the development of metabolic acidosis by plasma acid-base parameters, but further studies will be needed to determine how best to identify patients with this phenomenon and whether they too should be treated with dietary H+ reduction.

Acid Load and Phosphorus Homeostasis in CKD.

BACKGROUND: The kidneys maintain acid-base homeostasis through excretion of acid as either ammonium or as titratable acids that primarily use phosphate as a buffer. In chronic kidney disease (CKD), ammoniagenesis is impaired, promoting metabolic acidosis. Metabolic acidosis stimulates phosphaturic hormones, parathyroid hormone (PTH) and fibroblast growth factor 23 (FGF-23) in vitro, possibly to increase urine titratable acid buffers, but this has not been confirmed in humans. We hypothesized that higher acid load and acidosis would associate with altered phosphorus homeostasis, including higher urinary phosphorus excretion and serum PTH and FGF-23. STUDY DESIGN: Cross-sectional. SETTING & PARTICIPANTS: 980 participants with CKD enrolled in the Chronic Renal Insufficiency Cohort (CRIC) Study. PREDICTORS: Net acid excretion as measured in 24-hour urine, potential renal acid load (PRAL) estimated from food frequency questionnaire responses, and serum bicarbonate concentration < 22 mEq/L. OUTCOME & MEASUREMENTS: 24-hour urine phosphorus and calcium excretion and serum phosphorus, FGF-23, and PTH concentrations. RESULTS: Using linear and log-linear regression adjusted for demographics, kidney function, comorbid conditions, body mass index, diuretic use, and 24-hour urine creatinine excretion, we found that 24-hour urine phosphorus excretion was higher at higher net acid excretion, higher PRAL, and lower serum bicarbonate concentration (each P<0.05). Serum phosphorus concentration was also higher with higher net acid excretion and lower serum bicarbonate concentration (each P=0.001). Only higher net acid excretion associated with higher 24-hour urine calcium excretion (P<0.001). Neither net acid excretion nor PRAL was associated with FGF-23 or PTH concentrations. PTH, but not FGF-23, concentration (P=0.2) was 26% (95% CI, 13%-40%) higher in participants with a serum bicarbonate concentration <22 versus ≥22 mEq/L (P<0.001). Primary results were similar if stratified by estimated glomerular filtration rate categories or adjusted for iothalamate glomerular filtration rate (n=359), total energy intake, dietary phosphorus, or urine urea nitrogen excretion, when available. LIMITATIONS: Possible residual confounding by kidney function or nutrition; urine phosphorus excretion was included in calculation of the titratable acid component of net acid excretion. CONCLUSIONS: In CKD, higher acid load and acidosis associate independently with increased circulating phosphorus concentration and augmented phosphaturia, but not consistently with FGF-23 or PTH concentrations. This may be an adaptation that increases titratable acid excretion and thus helps maintain acid-base homeostasis in CKD. Understanding whether administration of base can lower phosphorus concentrations requires testing in interventional trials.

Anesthesia of Epinephelus marginatus with essential oil of Aloysia polystachya: an approach on blood parameters.

This study investigated the anesthetic potential of the essential oil (EO) of Aloysia polystachya in juveniles of dusky grouper (Epinephelus marginatus). Fish were exposed to different concentrations of EO of A. polystachya to evaluate time of induction and recovery from anesthesia. In the second experiment, fish were divided into four groups: control, ethanol and 50 or 300 µL L-1 EO of A. polystachya, and each group was submitted to induction for 3.5 min and recovery for 5 or 10 min. The blood gases and glucose levels showed alterations as a function of the recovery times, but Na+ and K+ levels did not show any alteration. In conclusion, the EO from leaves of A. polystachya is an effective anesthetic for dusky grouper, because anesthesia was reached within the recommended time at EO concentrations of 300 and 400 µL L-1. However, most evaluated blood parameters showed compensatory responses due to EO exposure.

Anesthesia of Epinephelus marginatus with essential oil of Aloysia polystachya: an approach on blood parameters

ABSTRACT This study investigated the anesthetic potential of the essential oil (EO) of Aloysia polystachya in juveniles of dusky grouper (Epinephelus marginatus). Fish were exposed to different concentrations of EO of A. polystachya to evaluate time of induction and recovery from anesthesia. In the second experiment, fish were divided into four groups: control, ethanol and 50 or 300 µL L−1 EO of A. polystachya, and each group was submitted to induction for 3.5 min and recovery for 5 or 10 min. The blood gases and glucose levels showed alterations as a function of the recovery times, but Na+ and K+ levels did not show any alteration. In conclusion, the EO from leaves of A. polystachya is an effective anesthetic for dusky grouper, because anesthesia was reached within the recommended time at EO concentrations of 300 and 400 µL L−1. However, most evaluated blood parameters showed compensatory responses due to EO exposure.

Importancia relativa de los factores determinantes de los niveles séricos de 25-hidroxi-colecalciferol en la enfermedad renal crónica / Relative importance of the determinants of serum levels of 25-hydroxy vitamin D in patients with chronic kidney disease

Introducción: El origen de la carencia de vitamina D en la enfermedad renal crónica (ERC) parece multifactorial, pero es incierta la importancia relativa de cada uno de sus potenciales determinantes. Objetivos: Determinar los factores asociados a los niveles de 25-hidroxi-colecalciferol (25OHD) y su importancia relativa en una cohorte de pacientes con ERC prediálisis. Material y métodos: Se incluyeron pacientes incidentes en una consulta de ERC, excluyendo a aquellos que recibían suplementos de vitamina D o anticonvulsivantes. Además de los datos demográficos y clínicos, se analizó la influencia de la actividad física, estación del año de la extracción, y tratamiento con estatinas, antiangiotensina e inhibidores de la xantino-oxidasa. Para la estimación de la importancia relativa se utilizó el método de ponderación relativa de Johnson, expresando los resultados como porcentajes de contribución al R múltiple. Resultados: Se estudiaron 397 pacientes, de los cuales 30 fueron excluidos. La concentración media de 25OHD fue de 13,7±7,4ng/ml, presentando unos niveles inferiores a 20ng/ml el 81% de los pacientes. Por regresión lineal múltiple y ponderación relativa, los principales determinantes de unos niveles más bajos de 25OHD fueron por orden de importancia: una mayor proteinuria (28,5%), mayor edad (21,4%), disminución de la actividad física (19,4%), sexo femenino (19,3%), y menor bicarbonato sérico (11,4%). Conclusión: La magnitud de la proteinuria y la edad son los factores con mayor importancia relativa como determinantes de los niveles de 25OHD en la ERC (AU)

Introduction: The cause of vitamin D deficiency in chronic kidney disease (CKD) is probably multi-factorial; however, the relative importance of each potential determinant is uncertain. Aims: To determine factors associated with serum levels of 25-hydroxy vitamin D (25OHD) and their relative importance in a cohort of pre-dialysis CKD patients. Material and methods: Incident patients admitted to a CKD outpatient clinic were included. Those who were receiving vitamin D supplements or anticonvulsants were excluded. In addition to demographic and clinical data, information about outdoor physical activity, season of blood collection, prescription of statins, anti-angiotensin drugs and xanthine-oxidase inhibitors were included as potential determinants. Johnson's relative weights analysis was used to estimate the relative importance of each potential determinant and the results were expressed as percentage contribution to multiple R. Results: The study group consisted of 397 patients, 30 of whom were excluded. The mean serum level of 25OHD was 13.7±7.4ng/ml, and 81% of patients had serum levels lower than 20ng/ml. By multiple linear regression and relative weights analyses, the best determinants of low serum 25OHD levels and their relative importance were: higher proteinuria (28.5%), old age (21.4%), low physical activity (19.4%), female gender (19.3%) and low serum bicarbonate levels (11.4%). Conclusions: Proteinuria and age are the determinants with the highest relative importance for predicting 25OHD levels in CKD patients (AU)

Metabolic consequences of ß-alanine supplementation during exhaustive supramaximal cycling and 4000-m time-trial performance.

The present study investigated the effects of ß-alanine supplementation on the resultant blood acidosis, lactate accumulation, and energy provision during supramaximal-intensity cycling, as well as the aerobic and anaerobic contribution to power output during a 4000-m cycling time trial (TT). Seventeen trained cyclists (maximal oxygen uptake = 4.47 ± 0.55 L·min(-1)) were administered 6.4 g of ß-alanine (n = 9) or placebo (n = 8) daily for 4 weeks. Participants performed a supramaximal cycling test to exhaustion (equivalent to 120% maximal oxygen uptake) before (PreExh) and after (PostExh) the 4-week supplementation period, as well as an additional postsupplementation supramaximal cycling test identical in duration and power output to PreExh (PostMatch). Anaerobic capacity was quantified and blood pH, lactate, and bicarbonate concentrations were measured pre-, immediately post-, and 5 min postexercise. Subjects also performed a 4000-m cycling TT before and after supplementation while the aerobic and anaerobic contributions to power output were quantified. ß-Alanine supplementation increased time to exhaustion (+12.8 ± 8.2 s; P = 0.041) and anaerobic capacity (+1.1 ± 0.7 kJ; P = 0.048) in PostExh compared with PreExh. Performance time in the 4000-m TT was reduced following ß-alanine supplementation (-6.3 ± 4.6 s; P = 0.034) and the mean anaerobic power output was likely to be greater (+6.2 ± 4.5 W; P = 0.035). ß-Alanine supplementation increased time to exhaustion concomitant with an augmented anaerobic capacity during supramaximal intensity cycling, which was also mirrored by a meaningful increase in the anaerobic contribution to power output during a 4000-m cycling TT, resulting in an enhanced overall performance.

Therapeutic Effects of Procainamide on Endotoxin-Induced Rhabdomyolysis in Rats.

Overt systemic inflammatory response is a predisposing mechanism for infection-induced skeletal muscle damage and rhabdomyolysis. Aberrant DNA methylation plays a crucial role in the pathophysiology of excessive inflammatory response. The antiarrhythmic drug procainamide is a non-nucleoside inhibitor of DNA methyltransferase 1 (DNMT1) used to alleviate DNA hypermethylation. Therefore, we evaluated the effects of procainamide on the syndromes and complications of rhabdomyolysis rats induced by lipopolysaccharide (LPS). Rhabdomyolysis animal model was established by intravenous infusion of LPS (5 mg/kg) accompanied by procainamide therapy (50 mg/kg). During the experimental period, the changes of hemodynamics, muscle injury index, kidney function, blood gas, blood electrolytes, blood glucose, and plasma interleukin-6 (IL-6) levels were examined. Kidneys and lungs were exercised to analyze superoxide production, neutrophil infiltration, and DNMTs expression. The rats in this model showed similar clinical syndromes and complications of rhabdomyolysis including high levels of plasma creatine kinase, acute kidney injury, hyperkalemia, hypocalcemia, metabolic acidosis, hypotension, tachycardia, and hypoglycemia. The increases of lung DNMT1 expression and plasma IL-6 concentration were also observed in rhabdomyolysis animals induced by LPS. Treatment with procainamide not only inhibited the overexpression of DNMT1 but also diminished the overproduction of IL-6 in rhabdomyolysis rats. In addition, procainamide improved muscle damage, renal dysfunction, electrolytes disturbance, metabolic acidosis, hypotension, and hypoglycemia in the rats with rhabdomyolysis. Moreover, another DNMT inhibitor hydralazine mitigated hypoglycemia, muscle damage, and renal dysfunction in rhabdomyolysis rats. These findings reveal that therapeutic effects of procainamide could be based on the suppression of DNMT1 and pro-inflammatory cytokine in endotoxin-induced rhabdomyolysis.