Acid Excretion Research Articles

The role of connective tissue biopolymers in the pathogenesis of dog bronchopneunmonia and cat brochnial asthma

The aim: to analyze the pathogenetic role of connective tissue biopolymers in canine pneumonia and feline asthma.
 Materials and methods. The study was conducted by analyzing the sources of scientific literature: PubMed, Elsevier, electronic resources of the National Library, named after V.I. Vernadsky and the results of our own scientific and clinical experience.
 Results. Studies on the pathogenetic justification of the role of biochemical indicators of the connective tissue in the diagnosis and treatment of diseases of the respiratory system of dogs and cats were conducted. This is due to the need to expand knowledge about the peculiarities of the course, to determine the leading pathogenetic links of the most common pathologies –bronchopneumonia and bronchial asthma, which are found in clinical veterinary practice.
 Conclusions. In bronchopneumonia of dogs on the background of severe clinical symptoms (cough, fever, wheezing in the lungs), radiological signs (inhomogeneous compaction of the lung tissue, lack of clear contours of the bronchi), anemic syndrome, general and neutrophilic leukocytosis, lymphocytopenia, hypoalbuminemia, dysproteinemia (increased concentration of α2- and β-globulins in the blood serum), hypercholesterolemia, hyper-β-lipoproteinemia, hyperfermentemia (increased activity of AST and alkaline phosphatase,) there is an increase in serum glycoproteins and chondroitin sulfates, sialic acids, total glycosaminoglycans (GAG) due to the chondroitin-4-sulfate fraction; urinary excretion of oxyproline and uronic acids increases. Disorders of connective tissue metabolism in dogs with bronchopneumonia are caused by an acute inflammatory process in the lungs with the development of pulmonary fibrosis.
 Bronchial asthma in cats is manifested by intermittent cough, shortness of breath, hypochromic normocytic anemia, leukocytosis, eosinophilia and lymphocytopenia, increased serum activity of AST and alkaline phosphatase, haptoglobin content, glial acid concentration sulfate; urinary excretion of oxyproline and uronic acids increases. Connective tissue disorders in cats with bronchial asthma are caused by increased mucus excretion with a high content of GAG, as well as chronic inflammation of the bronchial mucosa and their fibrosis

Children with lysinuric protein intolerance: Experience from a lower middle income country.

BACKGROUNDLysinuric protein intolerance (LPI) is an inborn error of metabolism consequential to recessive mutations in the SLC7A7 gene. The metabolic imbalance in absorption and excretion of dibasic amino acids is considered the basis of LPI. The disease results from protein intolerance with signs and symptoms oscillating from cerebral impairment, respiratory involvement, renal failure and autoimmune complications.AIMTo determine biochemical and clinical presentation of cases with biochemical picture suggestive of LPI in Pakistani children.METHODSThe study was conducted at the Biochemical Genetic Lab, Department of Pathology and Laboratory Medicine, AKU Plasma, and urine amino acid quantification data from January 2013 to October 2018 was included in this study. The amino acids were analyzed by high performance liquid chromatography. Prestructured requisition forms were used to obtain the clinicopathological data. Statistical analysis was done by Microsoft Excel 2017.RESULTSA total of 6 patients were recognized. All the patients were male (100%). The mean age was 24 mo ± 10 d. All the patients had low plasma concentration of lysine, ornithine and arginine, whereas increased levels of lysine, ornithine and arginine in urine were observed in 2 patients. History of consanguineous marriage was present in all patients (100%). The most observed clinical symptom was feeding difficulty followed by failure to thrive (83.3%) and developmental delay (66.6%). Hepatomegaly was present in all patients (100%). No mutation analysis was done.CONCLUSIONThis study portrays the biochemical and clinical spectrum of LPI in Pakistan. Although clinical manifestations appeared in the first 2 years of life, most of them suffered a delay in undergoing diagnostic workup.

Acid-Mediated Kidney Injury Across the Spectrum of Metabolic Acidosis.

Metabolic acidosis affects about 15% of patients with chronic kidney disease. As kidney function declines, the kidneys progressively fail to eliminate acid, primarily reflected by a decrease in ammonium and titratable acid excretion. Several studies have shown that the net acid load remains unchanged in patients with reduced kidney function; the ensuing acid accumulation can precede overt metabolic acidosis, and thus, indicators of urinary acid or potential base excretion, such as ammonium and citrate, may serve as early signals of impending metabolic acidosis. Acid retention, with or without overt metabolic acidosis, initiates compensatory responses that can promote tubulointerstitial fibrosis via intrarenal complement activation and upregulation of endothelin-1, angiotensin II, and aldosterone pathways. The net effect is a cycle between acid accumulation and kidney injury. Results from small- to medium-sized interventional trials suggest that interrupting this cycle through base administration can prevent further kidney injury. While these findings inform current clinical practice guidelines, large-scale clinical trials are still necessary to prove that base therapy can limit chronic kidney disease progression or associated adverse events.

Regulation of Acid-Base Balance in Patients With Chronic Kidney Disease.

Normallly the kidneys handle the daily acid load arising from net endogenous acid production from the metabolism of ingested animal protein (acid) and vegetables (base). With chronic kidney disease, reduced acid excretion by the kidneys is primarily due to reduced ammonium excretion such that when acid excertion falls below acid porduction, acid accumulation occurs. With even mild reductions in glomerular filtration rate (60 to 90 ml/min), net acid excretion may fall below net acid production resulting in acid retention which may be initially sequestered in interstitial compartments in the kidneys, bones, and muscles resulting in no fall in measured systemic bicarbonate levels (eubicarbonatemic metabolic acidosis). With greater reductions in kidney function, the greater quantities of acid retained spillover systemically resulting in low pH (overt metabolic acidosis). The evaluation of acid-base balance in patients with CKD is complicated by the heterogeneity of clinical acid-base disorders and by the eubicarbonatemic nature of the early phase of acid retention. If supported by more extensive studies, blood gas analyses to confirm the acid-base disorder and newer ways for assessing the presence of acidosis such as urinary citrate measurements may become routine tools to evaluate and treat acid-base disorders in individuals with CKD.

Dietary Contributions to Metabolic Acidosis.

Eating a net acid-producing diet can produce an "acid stress" of severity proportional to the diet net acid load, as indexed by the steady-state renal net acid excretion rate. Depending on how much acid or base is ingested or produced from endogenous metabolic processes and how well our homeostatic mechanisms can buffer or eliminate the additional acids or bases, we can alter our systemic acid-base balance. With increasing age, the kidney's ability to excrete daily net acid loads declines (a condition similar to that of mild CKD), invoking increased utilization of potential base stores (eg, bone, skeletal muscle) on a daily basis to mitigate the acid accumulation, thereby contributing to development of osteoporosis, loss of muscle mass, and age-related renal insufficiency. Patients suffering from more advanced CKD often present with more severe acid stress or metabolic acidosis, as the kidney can no longer excrete the entire acid load. Alkaline diets based on fruits and vegetables may have a positive effect on long-term preservation of renal function while maintaining nutritional status. This chapter discusses the biochemistry of dietary precursors that affect acid or base production.

SAT187 - Dual ileal/renal-liver bile acid transporter inhibitors with different transporter selectivity in vitro differentially increase faecal and urinary bile acid excretion in organic anion transporting polypeptide 1a/1b knockout mice in vivo

SAT187 - Dual ileal/renal-liver bile acid transporter inhibitors with different transporter selectivity in vitro differentially increase faecal and urinary bile acid excretion in organic anion transporting polypeptide 1a/1b knockout mice in vivo

Effect of High-altitude Hypoxia Environment on Uric Acid Excretion, Desmin Protein Level in Podocytes, and Na+-K+- ATPase Activity.

To investigate the oxidative stress and adaptive compensation of kidneys in rats in high-altitude hypoxia environments, 20 Wistar rats (3 months) were randomly and equally grouped. The rats in the test group were fed in a low-pressure oxygen chamber, and those in the control group (controls) were fed in a normal environment. On the 5th, 10th, 20th, and 30th day, the excretion of uric acid in rats was detected by a biochemical analyzer, the level of desmin protein in rat podocytes was detected by immunohistochemistry, and the activity of Na+-K+- ATPase in rat proximal tubular epithelial cells was measured by liquid scintillation method. The results showed that with the increased time, the level of uric acid in the blood of rats in the test group increased dramatically (P<0.05). On the 30th day, the blood uric acid content of the test group was 52.33μmol/L, and that of the control group was 38.43μmol/L. The blood uric acid content in the test group was dramatically increased relative to the control group. Immunohistochemistry showed that the desmin protein in podocytes of the test group (0.14) was considerably higher than that in the control group (P<0.05). The Na+-K+- ATPase activity of proximal renal tubular epithelial cells in the test group was 611.2 pmol pi/mg protein/h, which was considerably lower than the versus control group (P<0.05). In summary, in high altitude hypoxia environment, uric acid accumulated in the body, and renal filtration and excretion ability was limited.

Effect of sodium-glucose co-transporter inhibitors on blood pressure values. A new class of diuretic drugs?

New sodium-glucose co-transporter (SGLT 2) inhibitors are already widely used in patients with diabetes mellitus and in patients with heart failure. From the beginning of their use, it has been noticed that they slightly but statistically significantly lower both systolic blood pressure (SBP) and diastolic blood pressure (DBP). The antidiabetic activity of these drugs is based on the inhibition of the reabsorption of glucose and partially sodium in the renal tubules, which leads to an increase in the amount of urine excreted. Most likely, increased diuresis is responsible for the drop in blood pressure (BP). So far, numerous meta-analyses confirming the reduction of BP in diabetic patients have already been published, for both office BP and home BP, twenty-four hour BP and ambulatory central blood pressure. The action of SGLT 2 inhibitors, after a single administration, extends over 24 hours and there are already the first successful attempts to use them in hypertension in the course of diabetes mellitus with obstructive sleep apnea. The action of SGLT 2 inhibitors is pleiotropic and, apart from the diuretic effect, they slightly reduce the patient’s weight, reduce the activity of the sympathetic nervous system, restore the normal function of the endothelium, increase uric acid excretion, and reduce blood vessel stiffness. All these factors are responsible for the drop in BP. These favorable properties of SGLT 2 inhibitors indicate that these drugs will be increasingly used, probably not only in diabetes.

Katsuwonus pelamis Peptide and its Complexes Protect Zebrafish and Mice From Hyperuricemia Through Promoting Kidney Excretion of Uric Acid and Inhibiting Liver Xanthine Oxidase Activity.

Katsuwonus pelamis peptide and its complexes have the effect of lowering uric acid (UA)-levels. To identify the effect and possible mechanisms, different concentrations of Katsuwonus pelamis peptide and its complexes were administered to the zebrafish and mice hyperuricemia models, and the UA level was measured. Meanwhile, the hyperuricemic mice were treated orally at 0.83, 1.67, and 5.00 mg/g body weight for 7 days with Katsuwonus pelamis peptide and the complexes groups, separately. The levels of serum UA (SUA), urinary UA (UUA), serum creatinine (SCR), blood urine nitrogen (BUN), and xanthine oxidase (XOD) activities were detected in each group. The results showed that the Katsuwonus pelamis peptide (125 μg/ml) and its complexes (83.3 and 250 μg/ml) effectively reduced UA level in zebrafish with hyperuricemia (p < 0.05). The Katsuwonus pelamis peptide at high concentration (5.00 mg/g) decreased the SUA level, SCR level, BUN level, and hepatic XOD activity, and the complexes (1.67 and 5.00 mg/g) significantly reduced the SUA level and hepatic XOD activity (p < 0.05) in the hyperuricemic mice. In addition, in a hyperuricemic mouse model, the UUA level was increased after treatment with Katsuwonus pelamis peptide and its complexes at high concentrations (p < 0.05). The total therapeutic effects in the Katsuwonus pelamis peptide complex group were better than those in the Katsuwonus pelamis peptide group. Thus, Katsuwonus pelamis peptide and its complexes may possibly be used to prevent hyperuricemia via promoting urate secretion and inhibiting XOD activity production.

Effects of Sporisorium reiliana polysaccharides and Phoenix dactylifera monosaccharides on the gut microbiota and serum metabolism in mice with fructose-induced hyperuricemia.

In recent decades, the prevalence of hyperuricemia has increased, and dietary fructose is an important risk factor for the development of this disease. This study investigated and compared the effects of Sphacelotheca reiliana polysaccharides and Phoenix dactylifera monosaccharides on a series of physiological and biochemical indicators and on the metagenomes and serum metabolites in mice with hyperuricemia caused by a high-fructose diet. S. reiliana polysaccharides inhibited uric acid biosynthesis and promoted uric acid excretion, thereby alleviating the hyperuricemia phenotype. In addition, hyperuricemia was closely related to the gut microbiota. After treatment with S. reiliana polysaccharides, the abundances of Bacteroidetes and Proteobacteria in the mouse intestines were decreased, the expression of genes involved in glycolysis/gluconeogenesis metabolic pathways and purine metabolism was downregulated, and the dysfunction of the gut microbiota was alleviated. With regard to serum metabolism, the abundance of hippuric acid, uridine, kynurenic acid, propionic acid and arachidonoyl decreased, and the abundances of serum metabolites in inflammatory pathways involved in kidney injury and gout, such as bile acid metabolism, purine metabolism and tryptophan metabolism pathways, decreased. P. dactylifera monosaccharides aggravated hyperuricemia. This research provides a valuable reference for the development of sugar applications.

Trends in the Contribution of Genetic Susceptibility Loci to Hyperuricemia and Gout and Associated Novel Mechanisms.

Hyperuricemia and gout are complex diseases mediated by genetic, epigenetic, and environmental exposure interactions. The incidence and medical burden of gout, an inflammatory arthritis caused by hyperuricemia, increase every year, significantly increasing the disease burden. Genetic factors play an essential role in the development of hyperuricemia and gout. Currently, the search on disease-associated genetic variants through large-scale genome-wide scans has primarily improved our understanding of this disease. However, most genome-wide association studies (GWASs) still focus on the basic level, whereas the biological mechanisms underlying the association between genetic variants and the disease are still far from well understood. Therefore, we summarized the latest hyperuricemia- and gout-associated genetic loci identified in the Global Biobank Meta-analysis Initiative (GBMI) and elucidated the comprehensive potential molecular mechanisms underlying the effects of these gene variants in hyperuricemia and gout based on genetic perspectives, in terms of mechanisms affecting uric acid excretion and reabsorption, lipid metabolism, glucose metabolism, and nod-like receptor pyrin domain 3 (NLRP3) inflammasome and inflammatory pathways. Finally, we summarized the potential effect of genetic variants on disease prognosis and drug efficacy. In conclusion, we expect that this summary will increase our understanding of the pathogenesis of hyperuricemia and gout, provide a theoretical basis for the innovative development of new clinical treatment options, and enhance the capabilities of precision medicine for hyperuricemia and gout treatment.

An integrated study of Shenling Baizhu San against hyperuricemia: Efficacy evaluation, core target identification and active component discovery

Ethnopharmacological relevanceShenling Baizhu San (SLBZ) is a famous Traditional Chinese Medicine (TCM) formula that strengthens the spleen for replenishing qi, removing dampness, and inducing diuresis to relieve diarrhea. Combining the TCM interpretation that dampness is a vital pathogenesis factor in hyperuricemia occurrence and development, SLBZ has excellent potential against hyperuricemia from the perspective of TCM theories. Aim of the studyThis study aimed to investigate the efficacy of SLBZ against hyperuricemia and its possible mechanism with emphasis on the active components and the core targets. Materials and methodsIn the present study, we employed meta-analysis and a hyperuricemia quail model to evaluate the uric acid-lowering effect of SLBZ. Bodyweight, serum uric acid, and excreta uric acid levels in quails were assessed. Subsequently, we analyzed the potential active components and core targets of SLBZ against hyperuricemia by network pharmacology and calculated their interaction using molecular docking. Furthermore, the hyperuricemia rats treated with interfering agents of core targets were established to determine the central role of selected targets in hyperuricemia progression. Besides, we isolated and characterized the primary renal tubular epithelial cells of quails to verify the active components and core targets of SLBZ against hyperuricemia. Western blotting was used to observe the expression of core targets treated with active components under the stimulation of interfering agents. ResultsData from meta-analysis and animal experiments showed that SLBZ could work effectively against hyperuricemia. Hyperuricemia quails treated with SLBZ displayed significantly reduced serum uric acid levels accompanied by increased excretion of uric acid. According to network pharmacology and molecular docking results, 34 potential active components and the core target peroxisome proliferator-activated receptor gamma (PPARγ) for SLBZ against hyperuricemia were identified. The decreased serum uric acid levels in hyperuricemia rats treated with rosiglitazone, an agonist of PPARγ, confirms the essential role of PPARγ in the pathological process of hyperuricemia. Moreover, we first successfully isolated and characterized the primary renal tubular epithelial cells of quails and observed enhanced phosphorylation of PPARγ at Ser273 in cells handled with high-level uric acid. Whereas, the enhanced expression of p-PPARγ Ser273 could be down-regulated by luteolin and naringenin, two active components of SLBZ against hyperuricemia. ConclusionIn summary, SLBZ is a promising anti-hyperuricemia agent, and luteolin and naringenin are the active components for SLBZ against hyperuricemia by down-regulating phosphorylation of PPARγ at Ser273.

Synthesis and bioactivity evaluation of novel nuciferine derivatives with antihyperuricemia and nephroprotective effects

Hyperuricemia is a common metabolic disease with a series of complications. Nuciferine, a typical aporphine alkaloid natural compound extracted from the leaves of Nelumbo nucifera Gaertn., was confirmed to have an antihyperuricemia effect. In the present study, 30 novel nuciferine derivatives were designed and synthesized. The effects of all derivatives on the regulation of URAT1 were studied in a uric acid-induced HK-2 cell model with benzbromarone as a positive control. The results indicated that Compound 1j showed the optimal URAT1 inhibitory activity through repressing PI3K/Akt pathway in HK-2 cells and the inhibitory effect was similar to that of benzbromarone. In addition, in vivo experiments demonstrated that Compound 1j could reduce uric acid levels and ameliorate kidney damage in hyperuricemic mice. On the one hand, Compound 1j could inhibit the expression of URAT1 and GLUT9 to increase the uric acid excretion index. On the other hand, Compound 1j could regulate the TLR4/IκBα/NF-κB signaling pathway to reduce the levels of inflammatory cytokines, thereby alleviating kidney damage. Meanwhile, a molecular docking assay revealed the potential molecular binding power (-9.79 kcal/mol) between Compound 1j and URAT1, which was more tightly bound than the lead compound nuciferine (-7.44 kcal/mol). Based on these results, Compound 1j may be a future drug for the development of new potential antihyperuricemia and nephroprotective drug candidates.

407-P: Skin Autofluorescence Is Associated with Tubular Injury Represented by Urinary Excretion of Liver-Type Fatty Acid–Binding Protein in People with Diabetes

Background: Advanced glycation end product (AGE) accumulation is thought to be an independent predictor for cardiovascular disease in people with diabetes and renal failure. Since it has remained unclear whether AGE has a clinical impact on diabetic kidney disease (DKD) , the aim of this study was to determine the association between AGE accumulation, measured as skin autofluorescence (AF) , and the progression of DKD. Methods: Skin AF was measured by AGE reader® and spot urine biomarkers, including albumin and liver-type fatty acid-binding protein (L-FABP) , were determined as the urine albumin-to-creatinine ratio (uACR) and the urine L-FABP-to-creatinine ratio (uL-FABPCR) in 300 Japanese people with diabetes (173 males and 127 females, mean age, 67.8 ± 10.7 years) . The relationships between skin AF and those urine biomarkers of DKD were statistically evaluated. Results: Simple regression analysis showed that skin AF was associated with uACR (p&amp;lt;0.05) , log-transformed uACR (p&amp;lt;0.01) and uL-FABPCR (p&amp;lt;0.001) . On the other hand, multivariate regression analysis including clinical confounding factors showed that skin AF independently contributed to the increment of uL-FABPCR (P &amp;lt;0.05) but not to that of uACR (P=0.399) or log-transformed uACR (P=0.315) . Conclusion: Skin AF was associated with urinary L-FABP but not with albuminuria in people with diabetes. The results suggest that skin AF can serve as a novel predictive factor for the development of diabetic tubular injury. Disclosure H.Yamagami: None. T.Yuasa: None. S.Yoshida: None. A.Kuroda: None. M.Matsuhisa: Research Support; Nissui , Sysmex Corp., Speaker's Bureau; Astellas Pharma Inc., Eli Lilly and Company, Merck Sharp &amp; Dohme Corp., Mitsubishi Tanabe Pharma Corporation, Novo Nordisk, Sanofi, Sumitomo Dainippon Pharma Co., Ltd., Takeda Pharmaceutical Company Limited. I.Endo: None. K.Aihara: None. M.Abe: None. S.Yasui: None. M.Hosoki: None. T.Hori: None. T.Hara: None. Y.Mitsui: None. K.Kurahashi: None. S.Nakamura: None. T.Otoda: None.

A critical review on the experimental model of animal for antigout drugs

In this era where the pharmaceutical companies and products are hiking in its need and production it is inevitable to document the safety and toxicity along with the indications of the same. This is where the experimental study has a vital role to play. Experimental pharmacology is the science where the drug interaction with different receptors and target sites in living organism are explained. This article reviews about the different aspects of experimental pharmacology and its uses. Gout is an acute inflammatory disease characterized by the presence of uric acid crystals in the joint. This event promotes neutrophil infiltration and activation that leads to tissue damage. Mice received oral administration of BL or saline daily for 7 days and then were injected with MSU in the knee cavity. The present review aims to provide an updated overview on history, types, uses and mechanism of drug treatment for gout (hyperuricemia) with the detail review on information about experimental model of antigout drugs, their operating procedure, these agent works correct overproduction or under excretion of uric acid.

Plasma Levels and Renal Handling of Amino Acids Contribute to Determination of Risk of Mortality or Feed of Ventilation in Patients with COVID-19.

COVID-19 infection may lead to serious complications, e.g., need for mechanical ventilation or death in some cases. A retrospective analysis of patients referred to our COVID Emergency Department, indiscriminately, was performed. A routine lab analysis measured amino acids in plasma and urine of patients. Data of surviving and deceased patients and those requiring or not requiring mechanical ventilation were compared, and logistic regression analyses have been performed. Deceased patients were older, had higher blood glucose, potassium, AST, LDH, troponin, d-dimer, hsCRP, procalcitonin, interleukin-6 levels (p < 0.05 for all). They had lower plasma serine, glycine, threonine, tryptophan levels (p < 0.01), higher tyrosine and phenylalanine levels (p < 0.05), and higher fractional excretion of arginine, methionine, and proline (p < 0.05) than survivors. In a regression model, age, severity score of COVID-pneumonia, plasma levels of threonine and phenylalanine were predictors of in-hospital mortality. There was a difference in ventilated vs. non-ventilated patients in CT-scores, glucose, and renal function (p < 0.001). Using logistic regression, CT-score, troponin, plasma level, and fractional excretion of glycine were predictors of ventilation. Plasma levels and renal excretion of certain amino acids are associated with the outcome of COVID-19 infection beside other parameters such as the CT-score or age.

Plasma and Whole Blood Taurine Concentrations in Dogs May Not Be Sensitive Indicators of Taurine Deficiency When Dietary Sulfur Amino Acid Content Is Reduced

BackgroundTaurine status is impacted by dietary supply of methionine and cysteine (SAA) and possibly intestinal microbial activity, where plasma and whole blood taurine concentrations are currently used to evaluate taurine status.ObjectiveWe determined effects of dietary SAA restriction on rate and extent of taurine depletion of blood and skeletal muscle in dogs of two body sizes, and whether oral antibiotic administration affected the taurine depletion and fecal bile acid excretion of the dogs.MethodsAdult, male, Beagles (n = 6; 10.1–13.1 kg) and larger mixed-breed dogs (n = 6; 28.5–41.1 kg) were given four dry-expanded diets, whereby each successive diet contained lower protein and/or SAA concentration. After receiving the final diet for 44 weeks, all dogs were orally administered a mixture of ampicillin, neomycin sulfate, and metronidazole for 12 weeks. Taurine concentrations were determined every 2–4 weeks in venous blood and voided urine and every 4 to 16 weeks in biopsied semimembranosus muscle. Fecal bile acid excretion before and after antibiotics administration were quantified.ResultsWhen given for 36 weeks the lowest SAA diet, 3.4% methionine and 2.9% cystine, taurine concentrations in whole blood were not different between groups, while taurine in plasma declined (P < 0.05) in large but not in small dogs, and taurine in biopsied muscle decreased (P < 0.05) by 50% in large and by 37% in small dogs. Concentrations of taurine in muscle were lower (P < 0.01) and fecal bile acids greater (P = 0.001) in large than small dogs. Antibiotic administration restored plasma and muscle taurine to initial concentrations and halved fecal bile acid excretion by dogs of both groups.ConclusionsBlood taurine concentration may not be a sensitive indictor of taurine depletion caused by low intake of bioavailable SAA in dogs, especially in large dogs. Taurine status and dietary SAA requirements of dogs may substantively depend on taurine loss mediated by intestinal microbiota.

Pharmacological overview for therapy of gout and hyperuricemia

Hyperuricemia &amp; gout are disease conditions marked by over production and reduced excretion of uric acid. These conditions are linked with unhealthy lifestyle, Hypertension, Diabetes Mellitus, Metabolic syndrome, Cardiovascular &amp; Chronic renal disease. Thus controlling &amp; monitoring uric acid level becomes important. Development in the technology have led to greater insights into the pathophysiology of gout &amp; hyperuricemia. Now we have a better understanding of involvement of interleukin 1β in inflammatory process of gout. Thus with better understanding newer therapeutic targets are being explored for treatment of gout &amp; hyperuricemia. The armamentarium of drugs being used in therapy of acute gout here been expanded with recent addition by interleukin-1 inhibitors especially for refractory patients and patients with comorbidities. As these new therapies are evolving we need to focus on improving the use of Allopurinol through patient education and training of physicians in order to minimize development of Allopurinol hypersensitivity syndrome (AHS). Further pretesting of Human leukocyte Antigen- B ( HLA-B*5801*) should be considered in Asian population. Febuxostat being critically new drug needs cautious approach, proper education of patients and Adverse Drug Reaction (ADR) reporting. With entry of Pegloticase there is a new class of drug added for treating hyperuricemia.

FC012: Urinary Lithogenic Profile in Patients with Non-Alcoholic Fatty Liver Disease

Abstract BACKGROUND AND AIMS Several epidemiological studies have observed an increased risk for nephrolithiasis in patients affected by non-alcoholic fatty liver disease (NAFLD). However, the urinary lithogenic risk profile for patients with NAFLD is currently unknown. METHOD We systematically analysed the urinary metabolic profile of patients affected by NAFLD and liver cirrhosis (LC), followed at the hepatology outpatient clinic of our institution, compared to healthy individuals. A complete metabolic work-up for kidney stone disease was performed in all subjects. Multivariable linear regression models adjusted for age, sex, body mass index, eGFR and diabetes, were applied to assess differences in urinary lithogenic risk factors between healthy individuals and patients affected by NAFLD and LC. RESULTS A total of 42 patients and 12 healthy individuals were included in the analysis. No differences in age, sex and BMI were found among patients affected by NAFLD and LC, whereas the latter were more diabetic (71.4% versus 14.3%). After adjusting for multiple confounders, patients with NAFLD and LC had lower urinary magnesium (−55 mg/24 h; 95% CI −104, −6; P = 0.03 and −63 mg/24 h; 95% CI −121, −6; P = 0.03, respectively) and borderline oxalate (−1.21 mg/24 h; 95% CI −2.42, −0.01; P = 0.05 and −1.42 mg/24 h; 95% CI −2.79, −0.04; P = 0.04, respectively) excretions, compared with healthy controls. Compared with LC patients, NAFLD patients showed higher urinary ammonia (539 mEq/24 h; 95% CI 245, 833; P &amp;lt; 0.01), ammonia/net acid excretion ratio (0.40; 95% CI 0.18, 0.62; P &amp;lt; 0.01), urine pH (1.16; 95% CI 0.44, 1.88; P = 0.05) and lower urinary uric acid excretion (−210 mg/24 h; 95% CI −419, −0.29; P &amp;lt; 0.01) and titratable acidity (−9.7 mEq/24 h; 95% CI −19.0, −0.4; P = 0.04). CONCLUSION Altered urinary ammonia and magnesium excretions seems to be involved in the higher risk for stone formation found in patients with NAFLD. More studies are needed to investigate stone phenotypes and renal handling of ammonia in this setting.

Changing the Trajectory of Heart Failure and Kidney Disease: A Call for Action.

Changing the Trajectory of Heart Failure and Kidney Disease: A Call for Action.