Increased Plasma Creatinine Research Articles

Doxycycline treatment reestablishes renal function of Wistar rats in experimental envenomation with Bothrops jararacussu venom

Acute kidney injury is one of the main complications of ophidian accidents and the leading cause of death in patients who survive the initial damage effects of venom. The hypothesis proposed in this investigation is that the pharmacological repositioning of doxycycline (doxy) attenuates renal injury provoked by Bothrops jararacussu (Bj) venom. Male Wistar rats were subjected or not (control) to experimental envenomation with Bj venom (3.5 mg/kg, im). Doxy (3 mg/kg, ip) was administered 2 h after envenoming. Envenomation with Bj venom promoted tissue damage in the renal cortex (moderate degree, score 3) in 24 h associated with decreased glomerular and tubular function, which promoted proteinuria and polyuria. Doxy treatment prevented the increase in urinary volume in 3 times, the increase in plasma creatinine in 33%, the increase in blood urea-nitrogen accumulation in 65%, the increase in urinary Na+ excretion in 2 times, marked proteinuria and kidney cortex injury induced by Bj envenomation. Bj venom promoted increase in protein content (66%) and reduction of 45% (Na++K+)-ATPase activity in the renal cortex. The enzyme was detected mainly in the luminal membrane. Doxy treatment was effective in preventing the mentioned alterations, maintaining (Na++K+)-ATPase in the basolateral membranes.

(+)-trans-Cannabidiol-2-hydroxy pentyl is a dual CB1R antagonist/CB2R agonist that prevents diabetic nephropathy in mice

Natural cannabidiol ((-)-CBD) and its derivatives have increased interest for medicinal applications due to their broad biological activity spectrum, including targeting of the cannabinoid receptors type 1 (CB1R) and type 2 (CB2R). Herein, we synthesized the (+)-enantiomer of CBD and its derivative (+)-CBD hydroxypentylester ((+)-CBD-HPE) that showed enhanced CB1R and CB2R binding and functional activities compared to their respective (-) enantiomers. (+)-CBD-HPE Ki values for CB1R and CB2R were 3.1 ± 1.1 and 0.8 ± 0.1 nM respectively acting as CB1R antagonist and CB2R agonist. We further tested the capacity of (+)-CBD-HPE to prevent hyperglycemia and its complications in a mouse model. (+)-CBD-HPE significantly reduced streptozotocin (STZ)-induced hyperglycemia and glucose intolerance by preserving pancreatic beta cell mass. (+)-CBD-HPE significantly reduced activation of NF-κB by phosphorylation by 15% compared to STZ-vehicle mice, and CD3+ T cell infiltration into the islets was avoided. Consequently, (+)-CBD-HPE prevented STZ-induced apoptosis in islets. STZ induced inflammation and kidney damage, visualized by a significant increase in plasma proinflammatory cytokines, creatinine, and BUN. Treatment with (+)-CBD-HPE significantly reduced 2.5-fold plasma IFN-γ and increased 3-fold IL-5 levels compared to STZ-treated mice, without altering IL-18. (+)-CBD-HPE also significantly reduced creatinine and BUN levels to those comparable to healthy controls. At the macroscopy level, (+)-CBD-HPE prevented STZ-induced lesions in the kidney and voided renal fibrosis and CD3+ T cell infiltration. Thus, (+)-enantiomers of CBD, particularly (+)-CBD-HPE, have a promising potential due to their pharmacological profile and synthesis, potentially to be used for metabolic and immune-related disorders.

SRT1720 Administration Attenuates Albuminuria and Renal Fibrosis on Adriamycin‐Induced Glomerulosclerosis

The focal segmental glomerulosclerosis (FSGS) is the leading cause of progression of chronic kidney disease (CKD) and its responsible for the increasing number of cases of dialysis and kidney transplants worldwide. The lack of knowledge about the mechanisms underlying the progression of FSGS makes it difficult to develop therapeutic approaches with regarding the proteinuria and CKD progression. The aim of the study is to investigate the role of SIRT1 on FSGS induced by adriamycin, focusing on renoprotective responses. For this we used a synthetic SIRT1 agonist, the SRT1720. Male Balb/c mice aged 5 weeks were organized into two treatment groups: 48h and 14 days, being thus distributed in four experimental conditions: control (vehicle), adriamycin (ADR, 10 mg/kg), treated with SRT1720 (20 mg/kg/day) and treated with ADR+SRT1720. After the treatment, physiological parameters such as body weight, renal weight, weight gain, and plasma parameters such as creatinine, urea and osmolarity were evaluated. The glomerulosclerosis index was assessed by quantifying the renal sections stained with periodic acid-schiff (PAS). Urinary albumin was detected after staining the SDS-polyacrylamide gel. For the 48h group, the expression of mRNA was performed by quantitative real time PCR. For the 14-day group, GRP78, claudin-1, phospho eIF2αSer51 and phospho AMPKαThr172 protein expression were evaluated by immunoblotting. Type-IV collagen and nephrin staining were verified by immunofluorescence using confocal microscopy. The results indicate that for the ADR 48h group there was a decrease in final body weight, renal weight and an increase in plasma creatinine concentration compared to the control group. Administration of SRT1720 mitigates part of these effects, improving renal function. Our data indicate that although there is no positive stain for glomerulosclerosis in PAS or differences in the gene expression of Kim1, Tnf and Nphs1, the animals already have significant albuminuria within 48 hours after ADR administration in comparison to control, group, which suggests an initial damage on glomerular ultrafiltration barrier. Regarding the 14-day group, a decrease in final weight, an increase in renal weight, an increase in plasma creatinine, a significant increase in urinary albumin and the glomerulosclerosis index for ADR animals are observed, and this effect was clearly reversed by administration of SRT1720. There were no changes in creatinine clearance between groups after 14 days of treatment, despite an increase in urinary flow for the ADR + SRT1720 group. Although there were no significant differences on GRP78, phospho eIF2αSer51 or claudin-1 protein expression, the ADR+SRT1720 group showed an increase on phospho AMPKαThr172. Type IV collagen deposition was observed in ADR mice, as well as an important reduction in glomerular nephrin marking. These effects were partially reversed by the administration of the SRT1720. In conclusion, our data indicate that SRT1720 administration, a synthetic SIRT1 agonist, can improve renal function, mainly by partially preserving the glomerular ultrafiltration barrier and inhibiting renal fibrosis.

Plasma volume expansion is impaired in pregnancy after recovery from renal ischemia reperfusion injury

Healthy pregnancy is characterized by plasma volume expansion resulting in a significant increase in renal demands. Low plasma volume expansion during pregnancy is associated with poor fetal outcomes, including intrauterine growth restriction, and is also associated with decreased maternal renal function. Previous studies in our laboratory report that after recovery from renal ischemia reperfusion (IR) injury, female Sprague Dawley rats fail to increase renal function during pregnancy with poor maternal and fetal outcomes. The goal of the current study was to assess plasma volume and renal changes during pregnancy in our model of pregnancy after IR. We hypothesized that plasma volume expansion is impaired in pregnancy in dams after recovery from IR injury. Female Sprague Dawley rats (12 weeks of age, n=4-6) were randomized to receive either 45 minutes of warm, bilateral renal ischemia or sham surgery. IR injury was confirmed by a significant increase in plasma creatinine 24 hours after surgery (compared to sham controls). Rats were then given one month to recover. Full recovery from IR was confirmed by return of plasma creatinine and urinary protein excretion to baseline levels. Control and IR rats were randomized to either be mated with age-matched males with pregnancy confirmed by vaginal cytology or serve as virgin controls. Plasma volume was measured during late pregnancy on gestational day 20 by the Evans blue method in the pregnant rats and in age-matched virgin controls. Kidneys were collected for histological analysis by H&E staining, and glomerular area was measured in 20 glomeruli/kidney. Plasma volume increased during pregnancy in both control and IR dams compared to virgin controls, but the increase was greater in control dams than IR dams (Table, 2-Way ANOVA, Ppregnancy <0.01, PIR <0.01, PInteraction <0.01). Pregnancy also resulted in an increase in glomerular size in both control and IR dams compared to virgin controls, but this increase was also greater in the controls dams (Table, 2-Way ANOVA, Ppregnancy <0.01, PIR =0.01, PInteraction =0.02). These data suggest that despite recovery from IR injury, female rats fail to increase plasma volume in pregnancy along with failure to increase glomerular size. We propose that this failure to increase plasma volume in pregnancy is responsible for the poor fetal outcomes observed in this model. Further studies will examine the mechanisms responsible for plasma volume expansion in pregnancy, and why plasma volume fails to expand after recovery from IR injury.

Inhibition of 12/15 Lipoxygenase (12/15 LOX) Improves Renal Recovery and Function Post Renal Ischemia Reperfusion (IR) injury in Male Spontaneous Hypertensive Rats (SHR)

Acute kidney injury (AKI) due to ischemia reperfusion (IR) is a serious complication in clinical settings and the male gender is often associated with greater severity and mortality following AKI vs. age-matched females. Recent clinical and basic science studies further suggest that renal ischemic injury increases the likelihood of developing hypertension and hypertensive subjects are likely to have greater AKI severity. Despite the widespread prevalence of hypertension and AKI, what mediates renal IR injury leading to increased risk of later developing cardiovascular and renal diseases in either sex is poorly understood. Elevated 12/15-LOX activity has been reported in hypertension and in many kidney diseases. The goal of the current study was to test the hypothesis that enhanced activation of 12/15-LOX in hypertensive males results in greater increases in endoplasmic reticulum (ER) stress and tubular cell death leading to impaired post recovery compared females following renal IR. 13-week old male and female SHR were subjected to sham or 30-minute warm bilateral IR (n=6/group). Blood and urine were collected 24 hrs and 7 days after IR; kidneys were harvested 7 days post-IR for biochemical, histological, and Western blot analysis. IR increased plasma creatinine (Pcr) and blood urea nitrogen (BUN) in both male and female SHR compared to respective sham controls at 24 hrs (PIR =0.0001; Psex*IR=0.2). At 7 days post-IR, Pcr and BUN remained elevated in male SHR but returned to baseline levels in females (Pcr: PIR =0.03; Psex*IR=0.04; BUN: PIR <0.05; Psex*IR=0.05). Histological examination of kidneys 7 days post-IR showed increases in damaged tubules (PIR=0.0003, Psex*IR=0.0019) and tubular cell death (PIR=0.001; Psex*IR=0.001) in males vs. females SHR. Delayed recovery of renal function in male SHR was associated with an upregulation of renal 12/15-LOX protein (PIR<0.05; Psex*IR=0.008), increased lipid peroxidation (PIR=0.008; Psex*IR=0.018), and ER stress protein levels (PIR=0.05; Psex*IR=0.01) compared to sham-controls. To assess the contribution of 12/15 LOX on impaired recovery from IR in male SHR, additional rats were randomized to receive vehicle or the specific 12/15-LOX inhibitor ML355 (30 mg/kg i.p.; n=5/group) 1 hr prior to sham/IR and every other day up to 7 days. Treatment with ML355 1) reduced lipid peroxidation (PIR*TxT =0.02) and ER stress protein levels (PIR*TxT =0.05), 2) prevented IR-induced tubular damage (PIR*TxT=0.02) and tubular cell death (PIR*TxT=0.04), and 3) improved renal function (Pcr: PIR*TxT =0.0067; BUN: PIR*TxT =0.042) compared to vehicle-treated males following IR. In conclusion, our data demonstrate that enhanced activation of 12/15-LOX in the kidney contributes to impaired renal recovery post-IR in male SHR.

Mild increases in plasma creatinine after intermediate to high-risk abdominal surgery are associated with long-term renal injury

BackgroundThe potential relationship between a mild acute kidney injury (AKI) observed in the immediate postoperative period after major surgery and its effect on long term renal function remains poorly defined. According to the “Kidney Disease: Improving Global Outcomes” (KDIGO) classification, a mild injury corresponds to a KIDIGO stage 1, characterized by an increase in creatinine of at least 0.3 mg/dl within a 48-h window or 1.5 to 1.9 times the baseline level within the first week post-surgery. We tested the hypothesis that patients who underwent intermediate-to high-risk abdominal surgery and developed mild AKI in the following days would be at an increased risk of long-term renal injury compared to patients with no postoperative AKI.MethodsAll consecutive adult patients with a plasma creatinine value ≤1.5 mg/dl who underwent intermediate-to high-risk abdominal surgery between 2014 and 2019 and who had at least three recorded creatinine measurements (before surgery, during the first seven postoperative days, and at long-term follow up [6 months-2 years]) were included. AKI was defined using a “modified” (without urine output criteria) KDIGO classification as mild (stage 1 characterised by an increase in creatinine of > 0.3 mg/dl within 48-h or 1.5–1.9 times baseline) or moderate-to-severe (stage 2–3 characterised by increase in creatinine 2 to 3 times baseline or to ≥4.0 mg/dl). The exposure (postoperative kidney injury) and outcome (long-term renal injury) were defined and staged according to the same KDIGO initiative criteria. Development of long-term renal injury was compared in patients with and without postoperative AKI.ResultsAmong the 815 patients included, 109 (13%) had postoperative AKI (81 mild and 28 moderate-to-severe). The median long-term follow-up was 360, 354 and 353 days for the three groups respectively (P = 0.2). Patients who developed mild AKI had a higher risk of long-term renal injury than those who did not (odds ratio 3.1 [95%CI 1.7–5.5]; p < 0.001). In multivariable analysis, mild postoperative AKI was independently associated with an increased risk of developing long-term renal injury (adjusted odds ratio 4.5 [95%CI 1.8–11.4]; p = 0.002).ConclusionsMild AKI after intermediate-to high-risk abdominal surgery is associated with a higher risk of long-term renal injury 1 y after surgery.

The association between bloodwork, signalment, and urolithiasis in guinea pigs (Cavia porcellus)

ABSTRACT Urolithiasis represents a common, potentially life-threatening condition in pet guinea pigs (Cavia porcellus). The purpose of this study is to determine the potential association between signalment, packed cell volume, total solids, selected biochemical parameters, and imaging evidence of urolithiasis in client-owned guinea pigs presented to two veterinary teaching hospitals. Medical record databases from two veterinary teaching hospitals were searched for cases of client-owned guinea pigs that had both a plasma biochemistry panel and an imaging study performed during one medical event. Other parameters including age, sex, weight, packed cell volume, and total solids were also recorded. Of the 81 guinea pigs that met the inclusion criteria, 32 animals (40%) had evidence of urolithiasis present on at least one of their imaging modalities. The odds for the imaging presence of urolithiasis increased with a decreasing packed cell volume, an increasing plasma creatinine concentration, and with a decreasing plasma phosphorus concentration. While these variables were statistically significant and associated with imaging presence of urolithiasis, they had low predictive value to discriminate between guinea pigs with and without imaging evidence of urolithiasis. Given the relatively high prevalence of urolithiasis in guinea pigs in this study, imaging is strongly recommended for every animal with suspected affliction.

POS-082 EARLY TYPE 1 DIABETES AGGRAVATES ISCHEMIA/REPERFUSION-INDUCED ACUTE KIDNEY INJURY

Acute kidney injury (AKI) due to ischemia/reperfusion (IR) is a major cause of progression to chronic kidney injury and consequent loss of kidney function. Studies suggest that diabetes is an independent risk factor for AKI, however, the mechanisms by which diabetes influences the severity of AKI remain unknown. Thus, it may be useful to evaluate the interference of diabetes in pathophysiology of IR-induced AKI. The protocols are in accordance with CEUA (nº 12/2017). C57BL/6J mice, aged 60 days, were randomly grouped into: 1) Vehicle and sham surgery; 2) Vehicle and renal IR surgery (bilateral, 30 minutes); 3) streptozotocin (STZ - 55 mg/Kg/day - for five consecutive days) and sham surgery; 4) STZ and renal IR surgery. On the fifth day after the last STZ injection, animals with blood glucose ≥ 250 mg/dL were considered diabetic. On the 12th day after the last STZ injection, the animals were submitted to surgical procedures and, after 48 hours, to euthanasia. Renal function was assessed by plasma creatinine and urea levels. Proteinuria was evaluated using a commercial kit. At the end, the kidneys were used to evaluate tissue morphology, gene expression by qPCR, and protein expression by Western Blotting. Statistical analysis was performed by two-way analysis of variance (ANOVA). When interaction was statistically significant, Bonferroni post-test was performed for multiple comparisons. Values of p<0.05 were considered statistically significant. STZ treatment resulted in hyperglycemia, but did not induce changes in renal function. In non-diabetic animals, renal IR resulted in increased plasma creatinine and urea levels, decreased nephrin mRNA expression, increased Kim-1 and Ki-67 mRNA expression, and augmented gene expression of pro-inflammatory and pro-fibrotic factors. STZ treatment aggravates IR-induced AKI mainly by exacerbating glomerular and tubular injury, inflammation, and pro-fibrotic processes. Our results suggest that early diabetes aggravates IR-induced AKI and that patients with type 1 diabetes affected by renal IR may be more likely to develop chronic kidney injury and end-stage renal disease.

Extract of varieties of guava (Psidium guajava L.) leaf modulate angiotensin-1-converting enzyme gene expression in cyclosporine-induced hypertensive rats

BackgroundHypertension has become a serious health problem with which people have to live day by day, it sometimes results in severe organ damage with a dead end. Management with Psidium guajava L. (guava) leaf extract through modulation of angiotensin-converting enzyme (ACE) mRNA expression would give succor to patients with hypertension. However, there are several reports on medicinal efficacy of guava leaf with dearth of information on its varieties. HypothesisElevation of the ACE mRNA level in the kidney plays a primary role in the acceleration of local angiotensin II formation and thus sustain hypertension. Studies have shown the significance of investigating the molecular mechanism of ACE activities in pathophysiological states, this work sought to investigate the modulatory effect of aqueous extract of leaf from different varieties of guava on ACE mRNA gene expression in cyclosporine-induced hypertensive rats. MethodsHypertension was induced via intraperitoneal (i.p) administration of cyclosporine (25mg/kg/day); an aqueous extract of leaves from white, red, and pink guava was prepared, 250 and 500mg/kg body weight of the extracts were administered to the rats by oral gavage for 7 days. The systolic (SBP) and diastolic (DBP) blood pressure was measured, ACE mRNA expression level was determined using RT-qPCR, with kidney function markers in plasma (creatinine, urea, and uric acid), plasma nitric oxide level, the kidney histopathology, as well as phenolic characterization of the guava leaves. ResultsThe results showed a significant (p<0.05) increase in SBP, DBP, plasma creatinine, urea, and uric acid concentration, as well as nitric oxide level with up-regulation of ACE gene expression in the rats' kidneys with severe glomerular damage, necrosis, and capillary collapse. However, a significant (p<0.05) down-regulation of ACE mRNA expression level, reduced serum creatinine, urea, and uric acid concentration with mild-moderate kidney damage was observed in the treated rats. The leaves extract characterization and quantification revealed chlorogenic acid, rutin, vanillic acid, and quercetin as the most abundant phenolic compounds in the leaves. ConclusionsThe oral administration of the aqueous extract of different varieties of guava leaf (rich in phenolics), reduced SBP, DBP, kidney function markers concentration in the plasma, with increased plasma nitric oxide level, ameliorate kidney damage, and down-regulate renal ACE gene expression with no significant (p>0.05) difference in activities of extracts from different varieties of guava leaves used for this study. This could be a useful therapeutic measure for the treatment/management of hypertension.

Soluble Epoxide Hydrolase Inhibition Prevents Experimental Type 4 Cardiorenal Syndrome.

Objectives: Cardiovascular diseases (CVD) remain the leading cause of morbimortality in patients with chronic kidney disease (CKD). The aim of this study was to assess the cardiovascular impact of the pharmacological inhibition of soluble epoxide hydrolase (sEH), which metabolizes the endothelium-derived vasodilatory and anti-inflammatory epoxyeicosatrienoic acids (EETs) to dihydroxyeicosatrienoic acid (DHETs), in the 5/6 nephrectomy (Nx) mouse model. Methods and Results: Compared to sham-operated mice, there was decrease in EET-to-DHET ratio 3 months after surgery in vehicle-treated Nx mice but not in mice treated with the sEH inhibitor t-AUCB. Nx induced an increase in plasma creatinine and in urine albumin-to-creatinine ratio as well as the development of kidney histological lesions, all of which were not modified by t-AUCB. In addition, t-AUCB did not oppose Nx-induced blood pressure increase. However, t-AUCB prevented the development of cardiac hypertrophy and fibrosis induced by Nx, as well as normalized the echocardiographic indices of diastolic and systolic function. Moreover, the reduction in endothelium-dependent flow-mediated dilatation of isolated mesenteric arteries induced by Nx was blunted by t-AUCB without change in endothelium-independent dilatation to sodium nitroprusside. Conclusion: Inhibition of sEH reduces the cardiac remodelling, and the diastolic and systolic dysfunctions associated with CKD. These beneficial effects may be mediated by the prevention of endothelial dysfunction, independent from kidney preservation and antihypertensor effect. Thus, inhibition of sEH holds a therapeutic potential in preventing type 4 cardiorenal syndrome.

Adverse Maternal and Fetal Outcomes in a Novel Experimental Model of Pregnancy after Recovery from Renal Ischemia-Reperfusion Injury.

Recent clinical studies report that women with a history of AKI have an increased incidence of maternal and fetal adverse outcomes during pregnancy, despite fully recovering renal function prior to conception. The mechanisms contributing to such adverse outcomes in pregnancy after AKI are not yet understood. To develop a rodent model to investigate fetal and maternal outcomes in female animals with a history of AKI, we used ischemia-reperfusion injury as an experimental model of AKI in female Sprague Dawley rats. The 12-week-old animals underwent warm bilateral ischemia-reperfusion surgery involving clamping of both renal arteries for 45 minutes or sham surgery (control). Rats were allowed to recover for 1 month prior to mating. Recovery from ischemia-reperfusion injury was confirmed by measurements of plasma creatinine and urinary protein excretion. We assessed maternal and fetal outcomes during late pregnancy on gestational day 20. After recovery from ischemia-reperfusion injury, compared with healthy sham-surgery controls, dams exhibited pregnancy-induced renal insufficiency with increases in plasma creatinine and urea, along with increased urinary protein excretion. Additionally, recovered ischemia-reperfusion dams experienced worse fetal outcomes compared with controls, with intrauterine growth restriction leading to higher rates of fetal demise and smaller pups. In this rat model, despite biochemical resolution of ischemia-reperfusion injury, subsequent pregnancy resulted in maternal renal insufficiency and significant impairments in fetal growth. This mirrors findings in recent reports in the clinical population, indicating that this model may be a useful tool to further explore the alterations in kidney function after AKI in women.

Acute kidney injury prevalence in patients with colorectal cancer undergoing surgery with curative intent.

Acute kidney injury (AKI) is a frequent postoperative complication. However, data on the incidence of AKI in patients with colorectal cancer (CRC) undergoing surgery with curative intent are still limited. We examined the relationship between postoperative AKI among CRC surgery patients and preoperative therapy or no prior therapy. A total of 326 consecutive patients from the regional oncology center undergoing CRC surgery in the period January to December 2019 were included in the observational cohort study. We defined AKI as a 50% increase in plasma creatinine or initiation of renal replacement therapy within 7 days after surgery or an absolute increase in creatinine of 0.3 mg/dl within 48 hours. Acute kidney injury occurred in 36 patients (11%), 27 of whom underwent rectum resection, and 9 underwent colon resection. The incidence of AKI was identical in both types of surgery. Among 54 patients undergoing neoadjuvant radiochemotherapy, 6 patients (11%) developed AKI, while there was no case of AKI in 31 patients with neoadjuvant radiotherapy. Among 36 patients with AKI, 33 had hypertension, 27 had diabetes and 18 had at least stage 3 of chronic kidney disease before the surgery. Acute kidney injury after surgery for CRC is a relatively frequent postoperative complication, in particular, in patients with prior impairment in kidney function and comorbidities such as hypertension and diabetes. Appropriate preoperative therapy, including optimal hydration, withdrawal of potentially nephrotoxic drugs, etc., may reduce the incidence of AKI.

Suppression of Adenosine Deaminase and Xanthine Oxidase Activities by Mineralocorticoid and Glucocorticoid Receptor Blockades Restores Renal Antioxidative Barrier in Oral Contraceptive-Treated Dam.

Objective We tested the hypothesis that postpartum combined oral contraceptive (COC) treatment would induce oxidative stress via the adenosine deaminase-xanthine oxidase pathway in the kidney. We also sought to determine whether mineralocorticoid receptor (MR) or glucocorticoid receptor (GR ) blockade would suppress the activities of ADA and xanthine oxidase caused by postpartum COC treatment in the kidney. Methods Twenty-four Wistar dams were randomly assigned to 4 groups (n = 6/group). Dams received vehicle (po), COC (1.0 μg ethinylestradiol and 5.0 μg levonorgestrel; po), COC with GR blockade (mifepristone; 80.0 mg/kg; po), and COC with MR blockade (spironolactone; 0.25 mg/kg; po) daily between 3rd and 11th week postpartum. Results Data showed that postpartum COC caused increased plasma creatinine and urea, increased renal triglyceride/high-density lipoprotein ratio, free fatty acid accumulation, alanine aminotransferase, gamma-glutamyltransferase, uric acid, and activities of renal XO and ADA. On the other hand, postpartum COC resulted in decreased plasma albumin, renal glutathione, and Na+-K+-ATPase activity with no effect on lactate production. However, MR or GR blockade ameliorated the alterations induced by postpartum COC treatment. The present results demonstrate that MR or GR blockade ameliorates postpartum COC-induced increased activities of ADA and xanthine oxidase and restores glutathione-dependent antioxidative defense. Conclusion These findings implicate the involvements of GR and MR in renal dysfunctions caused by COC in dams via disrupted glutathione antioxidative barrier.

Low serum 25-OH vitamin D levels are associated with increased D/P creatinine ratio in peritoneal dialysis patients

Low 25-OH vitamin D levels have been linked to peritonitis and cardiovascular mortality in peritoneal dialysis (PD) patients. In this study we aimed to investigate the association of 25-OH vitamin D levels with peritoneal membrane characteristics in chronic PD patients. Consecutive 103 PD patients were enrolled in this retrospective study. Peritoneal dialysate to plasma (D/P) creatinine increase more than 0.1 with time were accepted as significant according Roc curve analysis. Patients with and without an increase in the D/P creatinine ratio of 0.1 were classified as Group 1 and Group 2, respectively. The relationship between baseline 25-OH vitamin D and peritoneal membrane characteristics were investigated. Mean age of the patients was 53.4±14.9 years and duration of PD was 72.1±50.3 months. There were thirty (29.1%) patients in Group 1. The duration of PD [73.5 (52.3-133.8) vs 49.0 (33.5-94.0) months, p:0.008]; hemoglobin [11.4 (10.4-12.2) vs. 10.2 (9.4-11.0) g/dL, p:0.001]and PTH [500.5 (254.5-748.3) vs 329.0 (205.0-549.5)ng/mL, p:0.047] levels were significantly higher in Group 1, whereas 25-OH vitamin D levels [5.0 (3.0-9.3) vs 7.8 (4.5-11.1)μg/L, p:0.027] and CRP [4.0 (3.0-7.2) vs. 8.0 (3.0-13.5)mg/L, p:0.028] were significantly lower. Multivariate analysis revealed duration of PD [Exp(B):1.012 (95%CI:1.001-1.022), p:0.028]; hemoglobin [Exp(B):1.756 (95%CI:1.199-2.571), p:0.004]; C-reactive protein (CRP) [Exp(B):0.882 (95%CI:0.789-0.985), p:0.026] and 25-OH vitamin D [Exp(B):0.853 (95%CI:0.754-0.965), p:0.012] were independent predictors of an increase in D/P creatinine ratio in PD patients. Increased D/P creatinine ratio was negatively correlated with 25-OH vitamin D level (r: -0.217, p:0.028). Lower levels of initial 25-OH vitamin D were associated with an increase in D/P creatinine ratio over-time.

Effect of heat stress and feeding management on growth performance and physiological responses of finishing pigs.

This study aimed to determine whether pig responses to heat stress (HS) were directly due to heat exposure (regardless of feeding level and pattern) or were indirectly due to the reduction of feed intake (FI) and to determine if increasing feeding frequency (splitting heat increments) can improve pig response to HS. A total of 48 pigs (66.1 ± 1.7 kg) were allocated to four groups in three replicates. After 7 d in thermoneutral (TN) conditions (22 °C; period 1 [P1; day -7 to -1]), pigs were placed in either TN or HS (32 °C) conditions for 20 d (period 2 [P2; day 0 to 19]). The diet was provided either ad libitum (AL; 2 distributions/d) or pair-fed (PF8; 8 distributions/d) using HS-AL pigs as the reference group. Thus, the four experimental groups were TN-AL, HS-AL, TN-PF8, and HS-PF8. The daily ration of PF8 pigs was distributed at every 90-min intervals from 0900 to 1930 hours. Data were analyzed using the PROC MIXED procedure with replicate (n = 3), experimental group (n = 4), and their interactions as fixed effects, and the REPEATED statement was used for repeated measures data. Pigs had a similar average daily feed intake (ADFI) during P1 (P > 0.05). In P2, HS-AL and PF8 pigs had lower ADFI (-19%), average daily gain (-25%), and final body weight (-6.1 kg) than TN-AL pigs (P < 0.01). TN-AL pigs had thicker backfat than TN-PF8 pigs (P < 0.05), while the HS pigs had intermediate results. HS pigs had a higher perirenal fat percentage based on the contrast analysis between PF8 pigs (P < 0.05). Thermoregulatory responses of pigs increased with HS exposure but did not differ between HS or between TN groups (P > 0.05). For TN pigs, variation in muscle temperature (Tmuscle) depended on feeding and physical activity, while for HS pigs, Tmuscle gradually increased throughout the day. The Tmuscle of PF8 pigs increased with each additional meal but plateaued earlier for HS-PF8 than TN-PF8 pigs; an increase in Tmuscle per meal was also lower in HS-PF8 than TN-PF8 (P < 0.05). Exposure to HS decreased plasma T3 and T4 (P < 0.05) and increased plasma creatinine (P < 0.05). Between the PF8 groups, HS pigs also had a transient increase in plasma insulin on day 8 (P < 0.05). The effect of HS on FI decreased the growth rate of pigs but there are heat-induced effects, such as altered physiological responses, which might explain the direct HS effects seen in other literature especially in terms of increased adiposity. The increased feed provision frequency in the present study did not improve the HS response of pigs.

Anti- diabetic activity of new Synthesized Flavonoid compound

Background: Diabetes mellitus (DM) is associated with long-term damage, dysfunction, of various organs. Objectives: Study aims to assess the role of new Synthesized Flavonoid compound on experimentally induced diabetes. Methods: 50 adult male albino rats divided into 5 groups. Group 1 (control group, rats were orally administered with 1 ml saline daily). Group 2 (DMSO group, rats were orally administered with 0.2 % DMSO for 60 day orally). Group 3 (positive control, animals were injected intraperitoneally with 60 mg/kg b.wt streptozotocin followed by intraperitoneal injection with 120 mg/kg b.wt of Nicotinamide after 15 minute).Group 4 (standard group, diabetic animals treated with 100 mg/kg b.wt of metformin for 60 day orally). Group 5 (therapeutic group, diabetic rats treated with 50 mg /kg b.wt of Ethyl 2-amino-4-phenyl-4H-benzo(h)chromene-3-carboxylate for 60 day orally). At the end of experimental period blood serum & plasma samples, liver, kidney and pancreatic tissues were collected. Results: diabetic rats showed significant increase in plasma glucose, serum urea, creatinine, cholesterol and triglyceride . Also significant increase in mean level of Fetuin A and Netrin-1 in serum and different organs (Liver, kidney, Pancreas) in compared to control group. Oral administration of Ethyl 2-amino-4-phenyl-4H-benzo(h)chromene-3-carboxylate cause decrease in elevated biochemical parameters. Also, decrease Fetuin A and Netrin-1 levels when compared with diabetic rats. Molecular docking studies confirmed binding of compound with Fetuin A and Netrin-1 proteins in terms of energy and revealed of the existence of hydrogen bond ,hydrophobic interaction,Our results were confirmed by histopathological examination of pancreatic tissue. Conclusion: this study suggests that Ethyl 2-amino-4-phenyl-4H-benzo(h)chromene-3-carboxylate exihibits antihyperglycemic activity in streptozotocin- induced diabetic rats.

COVID-19 patients in intensive care develop predominantly oliguric acute kidney injury.

BackgroundAcute kidney injury (AKI) is a syndrome of reduced glomerular filtration rate and/or reduced urine flow associated with mortality in corona virus disease 2019 (COVID‐19). AKI is often associated with renal tissue damage, which may lead to chronic kidney disease. Biomarkers of tissue damage may identify patients of particular risk.MethodsIn a prospective observational study of 57 patients admitted to intensive care, AKI incidence and characteristics was evaluated according to KDIGO criteria and related to days after admission. Urinary albumin, Neutrophil Gelatinase‐Associated Lipocalin (NGAL), Kidney Injury Molecule 1 (KIM‐1) and Plasma Tissue Inhibitor of MetalloProteinase 2 (TIMP‐2) were analysed in 52 patients at admission.The majority (n = 51, 89%) of patients developed AKI, and 27 (47%) patients had predominantly oliguric AKI where oliguria was more severe than plasma Creatinine increase. Severe oliguria within first 2 days after admission was common (n = 37, 65%), whereas stage 2 and 3 AKI due to Creatinine occurred later than day 2 in 67% (12/18) of cases. Renal replacement therapy was started in 9 (16%) patients, and 30‐day mortality was 28%. Urinary biomarkers were increased in a majority of patients, but did not robustly predict KDIGO stage. Most patients had microalbuminuria, and severe albuminuria (albumin Creatinine ratio > 30 mg/mmol) was found in n = 9 (17%) patients.ConclusionsA majority of patients with COVID‐19 admitted to the ICU develop AKI. The functional deficit is often low urinary volume, and initial levels of biomarkers are generally increased without clear relation to final AKI stage.

A greener protocol for the synthesis of phosphorochalcogenoates: Antioxidant and free radical scavenging activities.

In this contribution, a metal- and base-free protocol has been developed for the synthesis of phosphorochalcogenoates (Se and Te) by using DMSO as solvent at 50°C. A variety of phosphorochalcogenoates were prepared from diorganyl dichalcogenides and H-phosphonates, leading to the formation of a Chal-P(O) bond, in a rapid procedure with good to excellent yields. A full structural elucidation of products was accessed by 1D and 2D NMR, IR, CGMS, and HRMS analyses, and a stability evaluation of the phosphorochalcogenoates was performed for an effective operational description of this simple and feasible method. Typical 77Se{1H} (δSe=866.0ppm), 125Te{1H} (δTe=422.0ppm) and 31P{1H} (δP=-1.0,-13.0 and-15.0ppm) NMR chemical shifts were imperative to confirm the byproducts, in which this stability study was also important to select some products for pharmacological screening. The phosphorochalcogenoates were screened invitro and exvivo tests for the antioxidant potential and free radical scavenging activity, as well as to investigation toxicity in mice through of the plasma levels of markers of renal and hepatic damage. The pharmacological screening of phosphorochalcogenoates indicated that compounds have antioxidant propriety in different assays and not changes plasma levels of markers of renal and hepatic damage, with excision of 3g compound that increased plasma creatinine levels and decreased plasma urea levels when compared to control group in the blood mice. Thus, these compounds can be promising synthetic antioxidants that provide protection against oxidative diseases.

Kidney Ischemia-Reperfusion Decreases Hydrogen Sulfide and Increases Oxidative Stress in the Heart.

Patients with acute kidney injury (AKI) have an increased risk of cardiovascular disease. The underlying mechanism of AKI-induced heart injury is not well-understood. Hydrogen sulfide (H2S), at physiological concentrations, has been implicated in cardiovascular protection through redox balance and vessel relaxation. Cystathionine gamma-lyase (CSE) plays an essential role in H2S production in the heart. The present study investigated the effect of AKI on H2S production and oxidative stress in the heart. AKI was induced by kidney ischemia-reperfusion in male and female Sprague-Dawley rats, which led to an increase in plasma creatinine and blood urea nitrogen levels. There was a significant increase in lipid peroxidation and a decrease in glutathione (antioxidant) levels in the plasma and heart, indicating systemic and cardiac oxidative stress. Kidney ischemia-reperfusion reduced CSE expression and H2S production in the heart. There was a decrease in antioxidant transcription factor Nrf2 level in the nucleus and an increase in inflammatory cytokine (IL-6, TNF-α) expression in the heart. These results suggest that AKI can down-regulate CSE-mediated H2S production, reduce glutathione levels and increase oxidative stress in the heart. This may contribute to an increased risk of cardiovascular disease in AKI.

Investigating Risk Factors for the Development of BK Virus Infection in Kidney Transplant Recipients in Guilan Province during 2007-2015.

Polyomavirus nephropathy has been recognized as an important cause of silent loss of kidney transplant function in up to 50% of kidney recipients (1). The present study aimed to evaluate the risk factors associated with BK virus infection in kidney transplant recipients. Clinical information, urinary Decoy cells, and blood polymerase chain reaction (PCR) tests were collected for polyomavirus infection in 223 kidney transplant recipients undergoing surgery at Razi hospital at Guilan University of Medical Sciences between 2007 and 2015. Kidney biopsies were performed in patients with BKPyV- DNAemia more than 10,000 Copies/ml or increased plasma creatinine. Among 223 patients, 116 (52%) were male. The mean age of participants was 49.57±13.48 years. Out of 223 participants, 41 (18.4%) had Decoy cells in their urine, and 182 (81.6%) did not, 15 of whom (6.7%) had viral genome in their blood. Only did 3 patients out of 10 have BK Virus nephropathy in their kidney biopsy. Among risk factors, it was found that post-transplant duration (P< 0.001) and the use of anti-thymocyte globulin (P= 0.001) were the most significant risk factors for finding decoy cells in patients' urine. Post-transplant time, particularly the first 6 months, was found as the most important risk factor for the reactivation of polyomavirus infection in our patients because of strong immunosuppression and use of anti-thymocyte globulin (for prophylaxis or rejection treatment). It is concluded that kidney transplant recipients should be monitored in episodically after transplantation.