Kidney Markers Research Articles

POS-251 THE PREVALENCE, PATTERN AND PREDICTORS OF HYPOVITAMINOSIS D IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A STUDY IN A TERTIARY HOSPITAL IN NIGERIA

Hypovitaminosis D is associated with the progression of chronic kidney disease (CKD) and its complications, particularly the cardiovascular events. Studies about the pattern of occurrence of hypovitaminosis D and its relationship with other characteristics among patients with CKD in Nigeria is required to inform optimal care and improve outcomes. In this study, we determined the prevalence of hypovitaminosis D and its relationship with kidney function and markers of cardiovascular disease. This was a hospital-based cross-sectional study of 135 patients with CKD and 135 age- and sex-matched control participants. Clinical history, blood pressure and anthropometric measurements were documented using standard procedures. CKD was defined as estimated glomerular filtration rate (GFR) of < 60 ml/min/1.73m2 and/or persistent albuminuria (urine albumin excretion rate [AER] ≥ 30 mg/24 hours or urinary albumin-creatinine ratio (uACR) of ≥ 30mg/g) for ≥ 3 months. Estimated GFR was calculated using the CKD-EPI equation and patients were stratified into the stages of CKD accordingly. Serum vitamin D was measured and the study participants’ vitamin D status was categorized as; optimal, insufficiency, mild and severe deficiency based on its levels (NKF/KDOQI guidelines). Urinary albumin-creatinine ratio (uACR) and other laboratory parameters were assayed and echocardiography was conducted to document the left ventricular mass index (LVMI) and ejection fraction. We assessed the relationship between vitamin D and socio-demographic, clinical and laboratory parameters by Pearson’s correlation analysis and determined independent predictors of hypovitaminosis D by multivariate linear regression. The prevalence of hypovitaminosis D amongst the patients was 82.2% (48.1% had vitamin D insufficiency, 28.1% mild deficiency and 5.9% with severe deficiency) compared to 45.2% in the control participants (p value < 0.001). Serum vitamin D correlated inversely with LVMI (r= - 0.555, p value < 0.001), uACR (r = -0.367, p value < 0.001) and systolic blood pressure (r = -0.244, p value = 0.004); and positively with eGFR (r = 0.354, p value < 0.001). The major predictors of hypovitaminosis D were; eGFR (strongest), uACR, and the LVMI with an overall coefficient of determination (R2) of 0.391, p = 0.001. Hypovitaminosis D is significantly higher amongst patients with CKD compared with age- and sex-matched control participants in our centre and the predictors were eGFR (strongest), LVMI and uACR. Larger studies are required to determine the role of vitamin D on cardiovascular (CV) outcomes in these patients.

Late Health Effects of Partial Body Irradiation Injury in a Minipig Model Are Associated with Changes in Systemic and Cardiac IGF-1 Signaling

Clinical, epidemiological, and experimental evidence demonstrate non-cancer, cardiovascular, and endocrine effects of ionizing radiation exposure including growth hormone deficiency, obesity, metabolic syndrome, diabetes, and hyperinsulinemia. Insulin-like growth factor-1 (IGF-1) signaling perturbations are implicated in development of cardiovascular disease and metabolic syndrome. The minipig is an emerging model for studying radiation effects given its high analogy to human anatomy and physiology. Here we use a minipig model to study late health effects of radiation by exposing male Göttingen minipigs to 1.9–2.0 Gy X-rays (lower limb tibias spared). Animals were monitored for 120 days following irradiation and blood counts, body weight, heart rate, clinical chemistry parameters, and circulating biomarkers were assessed longitudinally. Collagen deposition, histolopathology, IGF-1 signaling, and mRNA sequencing were evaluated in tissues. Our findings indicate a single exposure induced histopathological changes, attenuated circulating IGF-1, and disrupted cardiac IGF-1 signaling. Electrolytes, lipid profiles, liver and kidney markers, and heart rate and rhythm were also affected. In the heart, collagen deposition was significantly increased and transforming growth factor beta-1 (TGF-beta-1) was induced following irradiation; collagen deposition and fibrosis were also observed in the kidney of irradiated animals. Our findings show Göttingen minipigs are a suitable large animal model to study long-term effects of radiation exposure and radiation-induced inhibition of IGF-1 signaling may play a role in development of late organ injuries.

Matlodextrin-cinnamon essential oil nanoformulation as a potent protective against titanium nanoparticles-induced oxidative stress, genotoxicity, and reproductive disturbances in male mice

Recently, bio-nanofabrication becomes one of the widest methods for synthesizing nanoparticles (NPs); however, there is scanty literature exploring the toxicity of these green NPs against living organisms. This study aimed to evaluate the potential protective role of encapsulated cinnamon oil (ECO) against titanium oxide nanoparticle (TiO2NP)-induced oxidative stress, DNA damage, chromosomal aberration, and reproductive disturbances in male mice. Sixty male Balb/c mice were distributed into six groups treated orally for 3 weeks and included control group, TiO2NP-treated group (25 mg/kg b.w), ECO at low or high dose-treated groups (50 or 100 mg/kg b.w), and the groups that received TiO2NPs plus ECO at a low or high dose. The results of GC-MS revealed the isolation of 21 compounds and the majority was cinnamaldehyde. The average size zeta potential of TiO2NPs and ECO were 28.9 and 321 nm and -33.97 and -17.35 mV, respectively. TiO2NP administration induced significant changes in liver and kidney function, decreased antioxidant capacity, and increased oxidative stress markers in liver and kidney, DNA damage in the hepatocytes, the number of chromosomal aberrations in the bone marrow and germ cells, and sperm abnormalities along with histological changes in the liver, kidney, and testis. Co-administration of TiO2NPs and ECO could alleviate these disturbances in a dose-dependent manner. It could be concluded that ECO is a promising and safe candidate for the protection against the health hazards of TiO2NPs.

Serum Creatinine and Serum Cystatin C are Both Relevant Renal Markers to Estimate Vancomycin Clearance in Critically Ill Neonates

Purpose: Serum creatinine (SCr) is used as a marker of kidney function to guide dosing of renally eliminated drugs. Serum Cystatin C (S-CysC) has been suggested as a more reliable kidney marker than SCr in adults and children. Purpose of this study was to investigate S-CysC as alternative renal marker to SCr for estimating vancomycin clearance in neonates undergoing intensive care. Methods: Vancomycin pharmacokinetics (PK), SCr and S-CysC data were collected in patients undergoing vancomycin treatment in the neonatal intensive care unit of Robert Debré Hospital - Paris. A population PK analysis was performed utilizing routine therapeutic drug monitoring samples. S-CysC and SCr were compared as covariates on vancomycin clearance using stepwise covariate modeling (forward inclusion [p < 0.05] and backward elimination [p < 0.01]). Model performance was evaluated by graphical and statistical criteria. Results: A total of 108 vancomycin concentrations from 66 patients (postmenstrual age [PMA] of 26–46 weeks) were modeled with an allometric one-compartment model. The median (range) values for SCr and S-CysC were 41 (12–153) µmol/l and 1.43 (0.95–2.83) mg/l, respectively. Following stepwise covariate model building, SCr was retained as single marker of kidney function (after accounting for weight and PMA) in the final model. Compared to the final model based on SCr, the alternative model based on S-CysC showed very similar performance (e.g. BIC of 578.3 vs. 576.4) but included one additional covariate: impact of mechanical ventilation on vancomycin clearance, in addition to the effects of size and maturation. Conclusion: ill neonates. However, if using S-CysC for this purpose mechanical ventilation needs to be taken into account.

Kidney function and markers of renal damage after renal denervation. Does method of measurement matter? The Reshape CV‐Risk Study

Data suggest that renal denervation (RDN) in treatment‐resistant hypertension (TRHT) is safe in terms of renal function. However, most studies report kidney function as creatinine‐based estimated glomerular filtration rate (eGFR), which may be biased by non‐renal factors. Damage markers other than albuminuria have never been evaluated after RDN. In this non‐randomized RDN trial, we studied changes in kidney function, assessed as measured GFR (mGFR) and various GFR estimates, six months and two years after RDN. We also examined changes in albuminuria and a biomarker of tubular dysfunction. Adult non‐diabetic patients with TRHT and eGFR ≥45 ml/min/1.73 m2 were recruited from hypertension clinics. Before bilateral RDN, mGFR was measured by iohexol clearance. We estimated eGFR from serum creatinine and cystatin C (eGFRcrea, eGFRcys, and eGFRcreacys), and albumin‐creatinine ratio (ACR) and N‐acetyl‐β‐D‐glucosaminidase (NAG)‐creatinine ratio (NAG‐CR) were measured in spot urines. All measurements were repeated after six and twenty‐four months.Twenty patients, mean age 54 (±9) years and baseline mGFR 83 (±20) ml/min/1.73 m2 underwent RDN. After six months, mGFR fell, eGFRcrea remained unchanged, whereas eGFRcys and eGFRcreacys increased. At 2 years’ follow‐up, eGFRcreacys was significantly lower than at baseline. mGFR was 78 (±28) ml/min/1.73 m2. Change in ambulatory systolic BP predicted change in eGFRcrea. Urinary NAG‐CR, but not ACR, increased during follow‐up.Different GFR assessments gave diverging results after RDN. Therefore, care should be taken to method when evaluating kidney function after RDN. Increases in a tubular dysfunction biomarker suggest that kidney damage may occur. Long‐term renal follow‐up is needed after RDN.

Borate Ameliorates Sodium Nitrite-Induced Oxidative Stress Through Regulation of Oxidant/Antioxidant Status: Involvement of the Nrf2/HO-1 and NF-κB Pathways.

The widespread industrial use of nitrite in preservatives, colorants, and manufacturing rubber products and dyes increases the possibilities of organ toxicity. Lithium borate (LB) is known as an antioxidant and an oxidative stress reliever. Therefore, this study is aimed at examining the effect of LB on nitrite-induced hepatorenal dysfunction. Twenty-eight male Swiss mice were divided into four equal groups. Group 1, the control group, received saline. Group 2 received LB orally for 5 consecutive days at a dose of 15 mg/kg bw. Group 3, the nitrite group, received sodium nitrite (NaNO2) on Day 5 (60 mg/kg bw intraperitoneally). Group 4, the protective group (LB + NaNO2 group), received LB for 5 days and then a single dose of NaNO2 intraperitoneally on Day 5, the same as in Groups 2 and 3, respectively. Samples of blood and kidney were taken for serum analysis of hepatorenal biomarkers, levels of antioxidants and cytokines, and the expression of genes associated with oxidative stress and inflammation. NaNO2 intoxication increased markers of liver and kidney functions yet decreased reduced glutathione (GSH), superoxide dismutase (SOD), and catalase activities in blood. NaNO2 also increased the expression of tumor necrosis factor (TNF-α), interleukin-1β and interleukin-6 (IL-1β and IL-6). Pre-administration of LB protected mice from oxidative stress, lipid peroxidation, and the decrease in antioxidant enzyme activity. Moreover, LB protected mice from cytokine changes, which remained within normal levels. LB ameliorated the changes induced by NaNO2 on the mRNA of nuclear factor erythroid 2-related factor 2 (Nfr2), heme oxygenase-1 (HO-1), nuclear factor-kappa B (NF-κB), transforming growth factor-beta 2 (TGF-β2), and glutathione-S-transferase (GST) as determined using quantitative real-time PCR (qRT-PCR). These results collectively demonstrate that LB ameliorated NaNO2-induced oxidative stress by controlling the oxidative stress biomarkers and the oxidant/antioxidant state through the involvement of the Nrf2/HO-1 and NF-κB signaling pathways.

A Review of the Effects of Gold, Silver, Selenium, and Zinc Nanoparticles on Diabetes Mellitus in Murine Models.

Diabetes mellitus is a disease that presents great challenges for healthcare systems worldwide, and the identification of alternative therapies for the treatment of this disease is of vital importance. Metallic nanoparticles (gold, silver, and selenium) and metallic oxide (ZnO) have been studied in different areas such as medicine, biotechnology, the environment, and the food industry with promising results. In medicine, current research has revealed these nanoparticles' anti-diabetic properties thanks to the implementation of animal models. This review will address the existing antecedents and the effects of gold, silver, selenium, and zinc oxide nanoparticles in diabetes administered alone, functionalized with other molecules, or combined with drugs that have shown promising therapeutic effects. The anti-diabetic effects of these nanoparticles are related to the regulation of glucose, insulin, and lipid profiles. In addition, oxidative stress markers, liver and kidney markers, the reduction of inflammation, apoptosis of the pancreas, and the restoration of normal liver and kidney histology are also reported in the literature after using these nanoparticles. However, the therapeutic effects that these nanoparticles provide are limited due to the lack of specific protocols dictated by international organizations to evaluate the risks of using these nanoparticles.

Acute and Sub-chronic Toxicity Studies on Methanol Stem Bark Extract of Frankincense Tree (Boswellia dalzielii) and Leaves Extract of Kenaf (Hibiscus cannabinus)

Aim: Frankincense tree (Boswellia dalzielii) and Kenaf (H. cannabinus) are plants abundantly found in north-western Nigeria. These plants are very popular among the locals as potent sources of ethno medicine. The present study investigates the oral acute toxicity potentials of methanolic stem bark extract of frankincense tree and Kenaf leaves, as well as sub-chronic toxicity potentials of the plants extracts on the kidney and liver of Albino rats.&#x0D; Study Design: Laboratory-experimental design was used for this study.&#x0D; Place and Duration of Study: This study was carried out between September 2019 and November&#x0D; 2019 at Biochemistry laboratory, Sokoto State University, Sokoto, Nigeria.&#x0D; Methodology: For the oral acute toxicity study, the revised “Up and Down” test (Limit Dose Test) was used to determine the LD50 of the extracts. For sub-chronic toxicity study, twenty albino rats were used for each plant, and were divided into four groups of five animals each. Group I (control), Group II (received 200 mg extract/kg body weight), Group III (received 400 mg extract/kg body weight) and Group IV (received 800 mg extract/kg body weight). All administrations were given orally for 28 days. Liver and kidney markers were determined using standard methods.&#x0D; Result: The oral acute toxicity test of the plant extracts at 3000 mg/kg body weight showed no mortality for 24 hours and subsequent 14days of administration. LD50 for both plants is therefore greater than 3000 mg/kg. The result shows no significant differences (p &gt; 0.05) on liver and kidney function biomarkers investigated when Group II, III and IV are compared with control.&#x0D; Conclusion: This suggests that Frankincense stem bark and kenaf leaves extracts may be safe in rats at doses less than or equal 3000 mg/kg.

Placenta Morphological and Amniotic Fluid Biochemical Changes Associated with Mid-Gestation Single and Twin Pregnancies in Red Sokoto Goats

Fetal fluids and placentas, which are important in feto-maternal homeostasis, could be affected by the number of developing fetuses. Therefore, placenta morphological and amniotic fluid biochemical changes associated with single and twin pregnancies in Red Sokoto goats were studied. Using Richardson’s formula, 2.1 × [CRL (cm) + 17], 12 intact gravid uteri (7 single-pregnant and 5 twin-pregnant) from mid-gestation [≈70-100 days gestational age (dGA)] pregnant goats were purposively selected. Feto-maternal biometrics [gravid uterine weight (GUW), total placental fluid volume (TPFV), average placentome diameter (APD), mean crown-rump length (MCRL), mean gestational age (MGA), mean fetal weight (MFW), total placentome number (TPN), and average interplacentomal distance (AID)]; amniotic fluid electrolytes [sodium (Na), potassium (K), chloride (Cl), calcium (Ca) and phosphorus (P)]; total protein; glucose; liver markers (AST and ALT); kidney markers (urea and creatinine), and cortisol concentrations were measured. The histology of the placentomes and the interplacentomal areas was also studied. The twin-pregnant (TP) goats had significantly higher (P&lt;0.05) GUW, TPFV, APD, amniotic fluid glucose and cortisol; and lower (P&lt;0.05) Ca levels. The rest of the parameters assessed did not differ between the TP and single-pregnant (SP) groups. Placentomes and the interplacentomal areas from the TP group had more diffuse villous inter-digitations and thicker luminal endothelium, respectively. It was concluded that TP Red Sokoto goats regulated placentome morphology, calcium, glucose and cortisol levels in order to achieve optimal conditions for the dams and the fetuses.

Restoration of plasma kidney and liver biomarkers in doxorubicin-treated Wistar rats by aqueous extracts of Pleurotus tuberregium sclerotia and Cnidoscolus aconitifolius leaves.

The ability of aqueous extracts of sclerotia of Pleurotus tuberregium and leaves of Cnidoscolus aconitifolius to regulate plasma markers of kidney and liver function/integrity was investigated in doxorubicin-treated Wistar rats. Doxorubicin (dissolved in normal saline) was injected intraperitoneally (15 mg/kg body weight) into the rats; metformin was daily administered orally at 250 mg/kg, while the extracts were daily administered orally at doses of 50, 75, and 100 mg/kg. Compared to the test control, in both the doxorubicin pre-treatment (or ameliorative) study and the extract pre-treatment (protective) studies, the extracts and metformin-treated groups had significantly lower (P < 0.05) plasma levels of alkaline phosphatase, alanine transaminase and aspartate transaminase, and concentrations of creatinine, urea, and blood urea nitrogen. However, the plasma globulin, albumin, and total protein concentrations and the albumin/globulin ratio of the extract and metformin-treated groups were significantly higher (P < 0.05). The extracts prevented (in the protective study) or attenuated (in the ameliorative study) doxorubicin-induced increase in the levels of plasma markers of kidney and liver function/integrity, and afforded protection or recovery towards near-normal values.

CER-001 ameliorates lipid profile and kidney disease in a mouse model of familial LCAT deficiency

ObjectiveCER-001 is an HDL mimetic that has been tested in different pathological conditions, but never with LCAT deficiency. This study was designed to investigate whether the absence of LCAT affects the catabolic fate of CER-001, and to evaluate the effects of CER-001 on kidney disease associated with LCAT deficiency. MethodsLcat−/− and wild-type mice received CER-001 (2.5, 5, 10 mg/kg) intravenously for 2 weeks. The plasma lipid/ lipoprotein profile and HDL subclasses were analyzed. In a second set of experiments, Lcat−/− mice were injected with LpX to induce renal disease and treated with CER-001 and then the plasma lipid profile, lipid accumulation in the kidney, albuminuria and glomerular podocyte markers were evaluated. ResultsIn Lcat−/− mice a decrease in total cholesterol and triglycerides, and an increase in HDL-c was observed after CER-001 treatment. While in wild-type mice CER-001 entered the classical HDL remodeling pathway, in the absence of LCAT it disappeared from the plasma shortly after injection and ended up in the kidney. In a mouse model of renal disease in LCAT deficiency, treatment with CER-001 at 10 mg/kg for one month had beneficial effects not only on the lipid profile, but also on renal disease, by limiting albuminuria and podocyte dysfunction. ConclusionsTreatment with CER-001 ameliorates the dyslipidemia typically associated with LCAT deficiency and more importantly limits renal damage in a mouse model of renal disease in LCAT deficiency. The present results provide a rationale for using CER-001 in FLD patients.

Climate change causes changes in biochemical markers of kidney disease

BackgroundClimate change is a significant threat to the health of the Ghanaian people. Evidence abounds in Ghana that temperatures in all the ecological zones are rising, whereas rainfall levels have been generally reducing and patterns are increasingly becoming erratic. The study estimated the impact of climate variation between seasons on biochemical markers of kidney disease.MethodsThis study conveniently recruited 50 apparently healthy peasant farmers and hawkers at Wa in the Upper West Region of Ghana. A pre-study screening for hepatitis A and C, Diabetes mellitus, hypertension was done. Serum creatinine and urea levels were analyzed to rule out kidney preexisting kidney disease. Baseline data was collected by estimating urea, creatinine, sodium, potassium, eGFR (estimated glomerular filtration rate) as well as for hemoglobin (Hb) and hematocrit (Hct) concentrations. Anthropometric data such as height, weight and blood pressure were measured by trained personnel. The study participants were closely followed and alerted deep in the dry season for the second sampling (urea, creatinine, hemoglobin, hematocrit, blood pressure, anthropometry).ResultsThis study recruited more males (58.82%) than females (41.15%), majority (52.92%) of which were aged 25–29 years with the youngest being 22 years and the eldest being 35 years. The study found body mass index (p < 0.001), systolic blood pressure (p = 0.019), creatinine (p < 0.001), urea (p = 0.013) and eGFR (p < 0.001) to be significantly influenced by climate change. Stage 1 hypertension was predominant among the study participants during the dry season, 8 (15.69%) than was observed during the rainy season, 4 (7.84%) nonetheless the number of participants with normal BMI rose from 49.02% in the rainy season to 62.75% during the dry reason. Additionally, the study observed that the impact of climate change on systolic blood pressure and urea varied based on age and sex.ConclusionThis study revealed that climatic changes cause variations in various biochemical parameters used to assess kidney function. Public health education on climatic changes and its implication including precautionary measures should be done among inhabitants of Wa and its environs to reduce its effect. Additionally, appropriate dietary patterns should also be advised to avoid the development of non-communicable diseases such as hypertension and obesity that are known principal causes of Chronic Kidney Disease (CKD).

Naringin attenuates renal interstitial fibrosis by regulating the TGF-β/Smad signaling pathway and inflammation.

Interstitial fibrosis is a typical feature of all progressive renal diseases. The process of fibrosis is frequently coupled with the presence of pro-fibrotic factors and inflammation. Naringin is a dihydroflavone compound that has been previously reported to exhibit anti-fibrotic effects in the liver, where it prevents oxidative damage. In the present study, a rat model of renal interstitial fibrosis and fibrosis cell model were established to evaluate the effects of naringin on inflammatory proteins and fibrosis markers in kidney of rats and NRK-52E cells, and to elucidate the role of the TGF-β/Smad signaling pathway in this mechanism. Compared with those in fibrotic NRK-52E cells that were stimulated by transforming growth factor-β (TGF-β), gene expression levels of α-smooth muscle actin (α-SMA), collagen 1 (COL1A1), collagen 3 (COL3A1), interleukin (IL)-1β, IL-6 and tumor necrosis factor-α (TNF-α) were all found to be significantly decreased in fibrotic NRK-52E cells following treatment with naringin (50, 100 and 200 ng/ml). Results from the histopathological studies showed that naringin treatment preserved the renal tissue structure and reduced the degree of fibrosis in the kidney tissues of rats that underwent unilateral ureteral obstruction (UUO). In addition, naringin administration reduced the expression of α-SMA, COL1A1, COL3A1, IL-1β, IL-6 and TNF-α in the kidneys of rats following UUO. The current study, using western blot analysis, indicated that naringin also downregulated the activation of Smad2/3 and the expression of Smad4, high-mobility group protein B1, activator protein-1, NF-κB and cyclooxygenase-2 whilst upregulating the expression of Smad7 in fibrotic NRK-52E cells and rats in the UUO group. In conclusion, naringin could antagonize renal interstitial fibrosis by regulating the TGF-β/Smad pathway and the expression of inflammatory factors.

KIM-1 (kidney injury molecule 1) in the urine of renal cell carcinoma patients

Objective: to assess the potential clinical significance of KIM-1 (kidney injury molecule 1) as a urinological marker for kidney cancer.Materials and methods. An enzyme-linked immunosorbent assay was used to assess urinary KIM-1 (uKIM-1 — kidney injury molecule 1) levels in 67 patients with renal cell carcinoma (RCC) and 36 healthy volunteers (a control group).Results. Both in patients and in healthy individuals, uKIM-1 levels were age independent. A difference between mean uKIM-1 values in RCC patients (2.4 ± 0.2 ng/ml) and the control group (0.7 ± 0.1 ng/ml) was statistically significant (p &lt;0.0001). In RCC patients the higher uKIM-1 level was observed at more advanced clinical disease stages: the values increasedfrom 2.0 ± 0.2 ng/ml at the stage I and 3.0 ± 0.5 ng/ml at the stage II—III to 4.4 ± 1.2 ng/ml at the stage IV. In the group of patients with stage IRCC, most representative by the number of cases (n = 44) the uKIM-1 levels correlated with the tumor size and were increased in patients with different histological subtypes of the tumor, including clear cell, papillary and chromophobe RCC. After nephrectomy, a monotonous decrease in uKIM-1 level was observed, and after 6 days its values approached the mean value in the control group. Two days after kidney resection, uKIM-1 increased and then decreased, remaining elevated after 6 days.Conclusion. This study demonstrates that uKIM-1 can be attributed to potentially significant urine tumor-associated markers of RCC.

Longitudinal evolution of nutritional status, and markers of kidney and liver function in finnish adults with intestinal failure

Rationale: The development of complications related to intestinal failure (IF) in the Finnish adult population is unknown. This study aimed to investigate the longitudinal changes over time in nutritional status, and renal and liver biomarkers in adults with IF.

Safely effective hypoglycemic action of stevia and turmeric extracts on diabetic Albino rats.

The potentiality of Stevia leaves and turmeric roots as remedies against diabetes mellitus type 2 was tested in this study. Stevia leaves and turmeric roots were extracted with ethanol:water (80:20 v/v) and analyzed by HPLC. Turmeric extract (TUE) was rich in; curcumin, gallic acid, and eugenol. Stevia extract (STE) contained 28 known compounds, including glycosides, aromatic organic acids, and catechin. Fifty rats were divided into five groups (10 rats each); the control group were fed with feed and water ad libitum. Forty rats were injected a single dose of alloxan, then treated with either 10mg/kg glibenclamide (GLI), 300mg/kg STE, or 200mg/kg TUE or water (positive control) through daily gastric oral gavages for 56days. Treating diabetic rats with TUE significantly reduced serum glucose and glycated hemoglobin down to the negative control levels. Both GLI and STE produced similar but less effective actions. Animals treated with either STE or TUE exhibited reduced levels of liver and kidney markers compared to the negative control, while GLI increased them significantly. It could be concluded that turmeric roots and stevia leaves extracts can be used treatment for type 2 diabetes. PRACTICAL APPLICATIONS: Turmeric roots and stevia leaves extracts may be used as a remedy for type 2 diabetic patients as aiding substituting treatments under medical supervision. The two plant sources can be used as raw materials for the extracts, which can be used under medical supervision as a gradual replacement of the synthetic antidiabetic drugs. These extracts can be used after a preliminary clinical study to determine the dose and frequency of administration. Stevia extract can be incorporated in drinks as a sweetener and drug. Turmeric extract has a bitter taste, so it may be incorporated in some foods such as bread, which is a traditional practice in some kinds of bread in Egypt. But its content in the bread and the acceptability of the taste should be adjusted. Alternatively, this food can incorporate both TUE and STE to get the best biological action and to conceal the bitter taste of turmeric.

Effects of calcifediol supplementation on markers of chronic kidney disease-mineral and bone disorder in dogs with chronic kidney disease.

BackgroundChronic kidney disease‐mineral and bone disorder (CKD‐MBD) in dogs is associated with hypovitaminosis D, increased parathyroid hormone (PTH), and increased fibroblast growth factor‐23 (FGF‐23) concentrations. Best practice for vitamin D metabolite supplementation in CKD‐MBD remains unknown.ObjectiveTo provide an extended‐release calcifediol supplement to dogs with CKD and to measure its effects on variables indicative of CKD‐MBD.AnimalsTen dogs with International Renal Interest Society stages 2 and 3 CKD.MethodsIn a prospective study, dogs received a calcifediol supplement for 84 days. Serum 25‐hydroxyvitamin D (25[OH]D), 1,25‐dihydroxyvitamin D (1,25[OH]2D), 24,25‐dihydroxyvitamin D (24,25[OH]2D), creatinine, calcium, phosphorus, PTH, plasma FGF‐23 concentrations, and urine profiles were measured monthly during supplementation. Urine calcium to creatinine (UCa/Cr) ratios and fractional excretion of calcium, phosphorus, and sodium were determined.ResultsAll serum vitamin D metabolite concentrations increased significantly by day 84 (P < .001): [25(OH)D (median 249.9 ng/mL; range, 149.7‐469.9 ng/mL) compared to baseline (median 50.2 ng/mL; range, 31.3‐66.0 ng/mL); 1,25(OH)2D (median 66.1 pg/mL; range, 56.9‐88.1 pg/mL) compared to baseline (median 37.3 pg/mL; range, 29.3‐56.7 pg/mL); 24,25(OH)2D (median 81.4 ng/mL; range, 22.1‐151.7 ng/mL) compared to baseline (median 15.4 ng/mL; range, 6.9‐40.6 ng/mL)]. There were no significant differences in calcium, phosphorus, PTH concentrations, UCa/Cr or fractional excretion of calcium. No dog developed ionized hypercalcemia. Plasma FGF‐23 concentrations increased by day 84 (median 1219 pg/mL; range, 229‐8824 pg/mL) compared to baseline (median 798 pg/mL; range, 103‐4.145 pg/mL) (P < .01).Conclusions and Clinical ImportanceCalcifediol supplementation for 84 days was well‐tolerated in dogs with IRIS stages 2 and 3 CKD. It remains to be determined how long‐term supplementation would affect CKD progression and QOL.

Interleukin-6 Receptor Antibodies for Modulating the Systemic Inflammatory Response after Out-of-Hospital Cardiac Arrest (IMICA): study protocol for a double-blinded, placebo-controlled, single-center, randomized clinical trial

BackgroundResuscitated out-of-hospital cardiac arrest (OHCA) patients who remain comatose at admission are at high risk of morbidity and mortality. This has been attributed to the post-cardiac arrest syndrome (PCAS) which encompasses multiple interacting components, including systemic inflammation. Elevated levels of circulating interleukin-6 (IL-6), a pro-inflammatory cytokine, is associated with worse outcomes in OHCA patients, including higher vasopressor requirements and higher mortality rates. In this study, we aim to reduce systemic inflammation after OHCA by administering a single infusion of tocilizumab, an IL-6 receptor antibody approved for use for other indications.MethodsInvestigator-initiated, double-blinded, placebo-controlled, single-center, randomized clinical trial in comatose OHCA patients admitted to an intensive cardiac care unit. Brief inclusion criteria: OHCA of presumed cardiac cause, persistent unconsciousness, age ≥ 18 years. Intervention: 80 patients will be randomized in a 1:1 ratio to a single 1-h intravenous infusion of either tocilizumab or placebo (NaCl). During the study period, patients will receive standard of care, including sedation and targeted temperature management of 36 ° for at least 24 h, vasopressors and/or inotropes as/if needed, prophylactic antibiotics, and any additional treatment at the discretion of the treating physician. Blood samples are drawn for measurements of biomarkers included in the primary and secondary endpoints during the initial 72 h. Primary endpoint: reduction in C-reactive protein (CRP). Secondary endpoints (abbreviated): cytokine levels, markers of brain, cardiac, kidney and liver damage, hemodynamic and hemostatic function, adverse events, and follow-up assessment of cerebral function and mortality.DiscussionWe hypothesize that reducing the effect of circulating IL-6 by administering an IL-6 receptor antibody will mitigate the systemic inflammatory response and thereby modify the severity of PCAS, in turn leading to lessened vasopressor use, more normal hemodynamics, and better organ function. This will be assessed by primarily focusing on hemodynamics and biomarkers of organ damage during the initial 72 h.In addition, pro-inflammatory and anti-inflammatory cytokines will be measured to assess if cytokine patterns are modulated by IL-6 receptor blockage.Trial registrationClinicalTrials.gov Identifier: NCT03863015; submitted February 22, 2019, first posted March 5, 2019.EudraCT: 2018-002686-19; date study was authorized to proceed: November 7, 2018.

Critical appraisal and meta-analysis of biological variation estimates for kidney related analytes.

Kidney markers are some of the most frequently used laboratory tests in patient care, and correct clinical decision making depends upon knowledge and correct application of biological variation (BV) data. The aim of this study was to review available BV data and to provide updated BV estimates for the following kidney markers in serum and plasma; albumin, creatinine, cystatin C, chloride, potassium, sodium and urea. Relevant studies were identified from a historical BV database as well as by systematic literature searches. Retrieved publications were appraised by the Biological Variation Data Critical Appraisal Checklist (BIVAC). Meta-analyses of BIVAC compliant studies with similar design were performed to deliver global estimates of within-subject (CVI) and between-subject (CVG) BV estimates. Out of the 61 identified papers, three received a BIVAC grade A, four grade B, 48 grade C, five grade D grade and one was not appraised as it did not report numerical BV estimates. Most studies were identified for creatinine (n=48). BV estimates derived from the meta-analysis were in general lower than previously reported estimates for all analytes except urea. For some measurands, BV estimates may be influenced by age or states of health, but further data are required. This review provides updated global BV estimates for kidney related measurands. For all measurands except for urea, these estimates were lower than previously reported. For the measurands analyzed in this review, there are sufficient well-designed studies available to publish a trustworthy estimate of BV. However, for a number of newly appearing kidney markers no suitable data is available and additional studies are required.

An investigation into the molecular basis of cancer comorbidities in coronavirus infection.

Comorbidities in COVID-19 patients often worsen clinical conditions and may represent death predictors. Here, the expression of five genes, known to encode coronavirus receptors/interactors (ACE2, TMPRSS2, CLEC4M, DPP4 and TMPRSS11D), was investigated in normal and cancer tissues, and their molecular relationships with clinical comorbidities were investigated. Using expression data from GENT2 databases, we evaluated gene expression in all anatomical districts from 32 normal tissues in 3902 individuals. Functional relationships with body districts were analyzed by chilibot. We performed DisGeNet, genemania and DAVID analyses to identify human diseases associated with these genes. Transcriptomic expression levels were then analyzed in 31 cancer types and healthy controls from approximately 43000 individuals, using GEPIA2 and GENT2 databases. By performing receiver operating characteristic analysis, the area under the curve (AUC) was used to discriminate healthy from cancer patients. Coronavirus receptors were found to be expressed in several body districts. Moreover, the five genes were found to associate with acute respiratory syndrome, diabetes, cardiovascular diseases and cancer (i.e. the most frequent COVID-19 comorbidities). Their expression levels were found to be significantly altered in cancer types, including colon, kidney, liver, testis, thyroid and skin cancers (P<0.0001); AUC>0.80 suggests that TMPRSS2, CLEC4M and DPP4 are relevant markers of kidney, liver, and thyroid cancer, respectively. The five coronavirus receptors are related to all main COVID-19 comorbidities and three show significantly different expression in cancer versus control tissues. Further investigation into their role may help in monitoring other comorbidities, as well as for follow-up of patients who have recovered from SARS-CoV-2 infection.