Significant Reduction In Serum Creatinine Research Articles

An Observational Study on Clinical Benefits of CytoSorb in Patients with Severe Sepsis

Background and Aim: Sepsis is a well-recognized healthcare issue worldwide. Despite research, the ability to positively influence outcome remains limited. Newer evidences have pointed that using adsorption of cytokines is beneficial during endotoxemia and sepsis. Therefore, this study was aimed to determine the clinical benefits of CytoSorb usage in patients with severe sepsis admitted in intensive care units (ICU). Study Design: Prospective, observational, comparative study. Material and Methods: Forty patients with sepsis admitted to ICU were included. The CytoSorb group included 20 patients who received CytoSorb therapy in addition to Standard-care (SOC) and 20 patients in SOC group who received SOC alone as per routine ICU protocols. Clinical and laboratory parameters were analyzed pre/post-treatment in both groups and compared. Results: CytoSorb and SOC groups were comparable at baseline. There was significant reduction in serum creatinine (2.59±2.0 vs. 2.89±1.2, mg/dl; P=0.042), serum lactate (3.26±1.1 vs. 3.27±0.9, mmol/lit; P<0.001), serum procalcitonin (2.75±2.4 vs. 3.39±3.5, ng/ml; P<0.001), serum CRP (90.2±57.4 vs. 175.6±100.9, mg/dl; P<0.001) and serum IL6 (1769.7±4444.1 vs. 256.8±392.4, pg/ml; P=0.03) levels in CytoSorb compared to SOC. There was significant improvement in mean arterial pressure (MAP) (65.75±1.8 vs. 62.75±2.8, mmHg; P<0.001) and reduction in norepinephrine dose (6.47±2.7 vs.10.65±3.6, mcg/min; P<0.001) in CytoSorb group reflecting better hemodynamic stability. The post-treatment increase in SOFA score was lesser in CytoSorb group (11.85±2.9) than SOC group (12.3±2.3), but was not significant (P=0.135). Conclusion: CytoSorb therapy along with SOC was associated with significant improvements in hemodynamic stability, MAP and Norepinephrine requirements than SOC alone in severe sepsis.

Elamipretide mitigates ischemia-reperfusion injury in a swine model of hemorrhagic shock

ischemia-reperfusion injury (IRI) after hemorrhage is potentiated by aortic occlusion or resuscitative endovascular balloon occlusion of the aorta (REBOA). Given the central role of mitochondrial injury in shock, we hypothesized that Elamipretide, a peptide that protects mitochondria, would mitigate IRI after hemorrhagic shock and REBOA. Twelve pigs were subjected to hemorrhagic shock and 45 min of REBOA. After 25 min of REBOA, animals received either saline or Elamipretide. Animals were transfused with autologous blood during balloon deflation, and pigs were resuscitated with isotonic crystalloids and norepinephrine for 4.25 h. Elamipretide-treated animals required less crystalloids than the controls (62.5 [50–90] and 25 [5–30] mL/kg, respectively), but similar amounts of norepinephrine (24.7 [8.6–39.3] and 9.7 [2.1–12.5] mcg/kg, respectively). Treatment animals had a significant reduction in serum creatinine (control: 2.7 [2.6–2.8]; Elamipretide: 2.4 [2.4–2.5] mg/dL; p = 0.04), troponin (control: 3.20 [2.14–5.47] ng/mL, Elamipretide: 0.22 [0.1–1.91] ng/mL; p = 0.03), and interleukin-6 concentrations at the end of the study. There were no differences in final plasma lactate concentration. Elamipretide reduced fluid requirements and protected the kidney and heart after profound IRI. Further understanding the subcellular consequences of REBOA and mitochondrial rescue will open new therapeutic avenues for patients suffering from IRI after hemorrhage.

Impact of preconditioning stem cells with all-trans retinoic acid signaling pathway on cisplatin-induced nephrotoxicity by down-regulation of TGFβ1, IL-6, and caspase-3 and up-regulation of HIF1α and VEGF

The survival reduction after transplantation limited the clinical uses of stem cells so the current study explored preconditioning adipose-derived stem cells (ADMSCs) and all-trans retinoic acid (ATRA) effects on cisplatin that caused acute kidney injury (AKI). One hundred and fifty Sprague–Dawley male rats were distributed into five groups: control group; Cisplatin (CIS) group; CIS and ATRA group; CIS and ADMSC group, and CIS, ATRA, and ADMSCs group. Ten rats were euthanized after 3rd, 7th, and 11th days from CIS injection. Renal function, molecular studies, and histopathological analysis were studied. The preconditioning of ADMSCs with ATRA increased the viability of the cells which was reflected in the amelioration of kidney functions after CIS injection by the significant reduction of serum creatinine, microalbuminuria, as well as NO, and the significant rise of creatinine clearance, as well as SOD compared to the group of cisplatin. ATRA also supported ADMSCs by a significant down-regulation of caspase-3, il-6 and TGFβ1, and a significant up-regulation of HIF1, VEGF and CD31 compared to group of cisplatin which reversed the cisplatin effect. ATRA increased renoprotective properties of ADMSCs against cisplatin- induced AKI by reducing the apoptosis, inflammation, and stimulating angiogenesis.

Effect of domperidone (leisguard\xae) on antibody titers, inflammatory markers and creatinine in dogs with leishmaniosis and chronic kidney disease

BackgroundImmunotherapeutic drugs, such as domperidone, have been shown to be promising treatments against canine leishmaniosis (CanL), but limited data are available. The aim of this pilot study (therapeutic, prospective and non-controlled) was to evaluate the effect of domperidone on serum antibody titers of Leishmania infantum, globulins, gamma globulins, acute-phase proteins (e.g. C-reactive protein [CRP]), big endothelin-1 (big ET-1), serum creatinine (SC) and proteinuria in dogs with leishmaniosis affected by chronic kidney disease (CKD).MethodsDogs were recruited if “exposed” to or “infected” with L. infantum and affected by CKD (IRIS stage 1 [proteinuric] or IRIS stage 2–3a [SC < 3.5 mg/dl; proteinuric or non-proteinuric]). After inclusion, an oral suspension of domperidone was administered, and the dogs were followed up for 180 days, with checks at 30, 60, 90 and 180 days after initial treatment.ResultsOf the 14 recruited dogs, nine showed a statistically significant reduction in SC (χ2 = 9.1, df = 3, P = 0.028), but not in the urine protein/creatinine ratio (χ2 = 6.43, df = 3, P = 0.092). All dogs showed a significant reduction in antibody titers for L. infantum (χ2 = 9.56, df = 2, P = 0.008), globulins (χ2 = 11.08, df = 3, P = 0.011) and gamma globulins (χ2 = 12.38, df = 3, P = 0.006) during the study period. There was also a statistically significant reduction in CRP (χ2 = 16.7, df = 3, P = 0.001), but not in big ET-1 (χ2 = 2.04, df = 3, P = 0.563).ConclusionsThis study provides preliminary results on the ability of domperidone to improve SC and reduce anti-L. infantum antibody titers, globulins, gamma globulins and CRP in dogs with leishmaniosis and CKD.Graphical abstract

Entacapone scavenges peroxynitrite and protects against kidney and liver injuries induced by renal ischemia/reperfusion in rats.

Acute kidney injury (AKI), secondary to renal ischemia/reperfusion (I/R), is a serious problem associated with high mortality. The pathophysiology of AKI after renal I/R involves peroxynitrite production; hence, scavenging this metabolite may rescue AKI. Entacapone is a catechol-O-methyl transferase (COMT) inhibitor which elicits antioxidant activity by scavenging peroxynitrite. Therefore, we hypothesized that the peroxynitrite scavenging activity of entacopone protects against AKI after renal I/R injury in rats. Male Wistar rats were given either entacapone or a well-known peroxynitrite scavenger (FeTPPS) daily for 10days before I/R procedures. I/R was induced by occluding both renal pedicles for 45min followed by reperfusion for 24h. Pre-treatment with either entacapone or FeTPPS improved renal function as indicated by a significant reduction in serum creatinine and urea when compared to I/R group (P < 0.05). I/R injury increased renal levels of NO (4-folds, P < 0.05), iNOS (4-folds, P < 0.05), and 3-nitrotyrosine (5-folds, P < 0.05) compared to sham control. These effects were abrogated in animals pre-treated with entacapone or FeTPPS before being subjected to I/R (P < 0.05). In addition, entacapone or FeTPPS significantly inhibited I/R-induced elevation in renal TNF-α levels (78% and 58%, respectively) and caspase-3 activity (72% and 56%, respectively) indicating the reduction of both inflammation and apoptosis in the kidney (P < 0.05). The two drugs also improved kidney and liver functions in rats with renal I/R injury. Our study showed that entacapone and FeTPPS protected against AKI and remote liver damage associated with renal I/R and this effect might be due to scavenging peroxynitrite and reducing nitrosative stress.

English

Mangifera indica seeds (MIS) are used traditionally for treating multiple ailments including urolithiasis. In current study, aqueous methanolic extract of MIS was examined for antiurolithiatic potential against Calcium oxalate (CaOx) crystals. In vitro analysis (nucleation, aggregation and growth assays) was performed with 20, 40, 60, 80 and 100 mg/mL concentrations of extract against standard drug (cystone). In-vivo CaOx crystals were induced by administration of drinking water comprising 0.75% v/v ethylene glycol (EG) and 1% w/v ammonium chloride (AC) for initial 3 days followed by intake of 0.75% v/v EG for next 25 days. Total 36 rats were allocated into 6 groups receiving vehicle, EG + AC, Cystone and extract (250, 500 and 1000 mg/kg) respectively. Urine and blood samples were collected for biochemical analysis. In in vitro analysis, 1000 mg/mL concentration significantly inhibited crystal formation when compared to standard. While MISE (500 and 1000 mg/kg) produced significant reduction in serum creatinine, BUN and uric acid levels while increased urine volume, Mg, pH and citrate levels of urine in MISE treated rats. The results give a scientific basis for its traditional claims

Registry on extracorporeal multiple organ support with the advanced organ support (ADVOS) system: 2-year interim analysis.

The objective of this registry is to collect data on real-life treatment conditions for patients for whom multiple organ dialysis with Advanced Organ Support (ADVOS) albumin hemodialysis is indicated.This registry was performed under routine conditions and without any study-specific intervention, diagnostic procedures, or assessments. Data on clinical laboratory tests, health status, liver function, vital signs, and examinations were collected (DRKS-ID: DRKS00017068). Mortality rates 28 and 90 days after the first ADVOS treatment, adverse events and ADVOS treatment parameters, including treatment abortions, were documented.This analysis was performed 2 years after the first patient was included on January 18, 2017. As of February 20, 2019, 4 clinical sites in Germany participated and enrolled 118 patients with a median age of 60 (IQR: 45, 69) of whom 70 were male (59.3%). Patients had a median SOFA Score of 14 (IQR: 11, 16) and a predicted mortality of 80%. The median number of failing organs was 3 (IQR: 2, 4).Four hundred twenty nine ADVOS treatments sessions were performed with a median duration of 17 hours (IQR: 6, 23). A 5.8% of the ADVOS sessions (25 of 429) were aborted due to device related errors, while 14.5% (62 of 429) were stopped for other reasons. Seventy nine adverse events were documented, 13 of them device related (all clotting, and all recovered without sequels).A significant reduction in serum creatinine (1.5 vs 1.2 mg/dl), blood urea nitrogen (24 vs 17 mg/dl) and bilirubin (6.9 vs 6.5 mg/dl) was observed following the first ADVOS treatment session. Blood pH, bicarbonate (HCO3-) and base excess returned to the physiological range, while partial pressure of carbon dioxide (pCO2) remained unchanged. At the time of the analysis, 28- and 90-day mortality were 60% and 65%, respectively, compared to an expected ICU-mortality rate of 80%. SOFA score was an independent predictor for outcome in a multivariable logistic regression analysis.The reported data show a high quality and completion of all participating centers. Data interpretation must be cautious due to the small number of patients, and the nature of the registry, without a control group. However, the data presented here show an improvement of expected mortality rates. Minor clotting events similar to other dialysis therapies occurred during the treatments.

Antidiabetic potential of methanolic extracts of Sargassum wightii in streptozotocin induced diabetic mice

Abstract The present study was aimed to explore the bioactivity of Sargassum wightii extracts on the body weight, blood glucose level, serum total cholesterol, HDL-Cholesterol, LDL-Cholesterol, VLDL-Cholesterol, serum triglycerides, serum urea, serum creatinine, SGPT and SGOT levels in diabetes induced mice (induced by Streptozotocin). Diabetic mice treated with 250 mg/kg body weight of methanolic extract of Sargassum wightii for 15 days showed a significant decline in their blood glucose level, total cholesterol, LDL-Cholesterol, VLDL-Cholesterol, and triglycerides and significantly increased HDL-Cholesterol. In diabetic mice, a significant elevated SGPT level was detected but later restored to normal after the intraperitoneal administration of Sargassum wightii extract. The levels of SGOT had a significant rise in diabetic control mice. Subsequently, administration of Sargassum wightii extract was done which resulted in reduced SGOT levels. After 15 days of treatment, a significant reduction in serum creatinine and urea level in treated group was observed in comparison with untreated diabetic control. Thus the present findings suggested that the methanolic extracts of S. wightii had a good antidiabetic potential in ameliorating the diabetic condition in mice.

Berberine alleviates cisplatin-induced acute kidney injury by regulating mitophagy via PINK 1/Parkin pathway.

BackgroundTo study the protective effect of berberine (BBR) on cisplatin-induced acute kidney injury (AKI) and its effect on mitophagy.Methods(I) Male C57BL/6 mice aged 6–8 weeks were randomly divided into control group (saline), cisplatin group (cisplatin), and cisplatin + BBR (5, 10 mg/kg) groups. In the cisplatin group and BBR groups, mice were injected intraperitoneally with 15 mg/kg of cisplatin. Mice in BBR groups were given BBR at 72, 48, 24, 0.5 h before and 24, 48 h after cisplatin injection. Mice were sacrificed 72 h after cisplatin injection, and blood were collected for detecting serum creatinine (SCr) and blood urea nitrogen (BUN) levels. Kidneys were collected for detecting protein expression levels of Kidney injury molecule 1 (KIM-1), LC3 II/LC3 I, p62, PINK 1, Parkin in the renal tissue by Western blotting. The pathological changes in renal tissues were observed using periodic acid-Schiff (PAS) staining. (II) Renal tubular epithelial cells (RTECs) were pretreated with different concentrations (1, 2, and 4 µM) of BBR, and then incubated with cisplatin. Changes in autophagy proteins LC3 II/LC3 I, p62, PINK 1, and Parkin were detected by Western blotting, and changes in cellular reactive oxygen species (ROS) and mitochondrial membrane potential (MMP) were detected by flow cytometry.Results(I) Mice treated with BBR at dosage of 5 and 10 mg/kg for 6 days showed significant reduction in SCr and BUN compared to that in mice treated with cisplatin. PAS staining and immunohistochemistry showed that BBR ameliorated cisplatin-induced nephrotoxicity and reduced cisplatin-induced increase in protein expression levels of KIM-1. Compared to cisplatin-treated mice, the mice treated with BBR showed increased LC3 II/LC3 I, PINK 1, and Parkin, and decreased p62 protein expression. (II) Compared to cisplatin-incubated RTECs, cells pretreated with BBR for 24 h exhibited increased protein expressions of LC3 II/LC3 I, PINK1, and Parkin and decreased protein expression of p62. BBR reversed cellular ROS and cell MMP level induced by cisplatin.ConclusionsBBR plays a protective role in cisplatin-induced AKI by up-regulating mitophagy in RTECs.

Moxibustion as an Adjuvant Therapy for Chronic Kidney Disease: A Systematic Review and Meta-Analysis of 23 Randomized Controlled Trials.

Objective This systematic review aims to investigate the efficacy and safety of moxibustion for chronic kidney disease (CKD). Methods Nine databases were searched to identify relevant evidence up to March 8, 2020. Randomized controlled trials (RCTs) that tested moxibustion + basic treatments versus basic treatments alone for patients with CKD and reported, at least, one of the outcomes of interest were included. In the meta-analyses, the mean differences (MDs) and 95% confidence intervals (CIs) were used to measure the effect size. Results Twenty-three RCTs (n = 1571) with a moderate to high risk of bias were included. The pooled estimates showed that compared with the controls, patients after moxibustion had a significant reduction in serum creatinine (MD −17.34 μmol/L, 95% CI −28.44 to −6.23; I2 = 87%), 24-hour urine protein excretion (MD −0.75 g/h, 95% CI −1.07 to −0.42; I2 = 84%), and blood urea nitrogen (MD −0.63 mmol/L, 95% CI −1.09 to −0.18; I2 = 37%) and a significant improvement in the quality of life (MD 10.18, 95% CI 3.67 to 16.69; I2 = 57%). Moxibustion did not show a significant effect on the estimated glomerular filtration rate (eGFR), creatinine clearance, or hemoglobin. The subgroup analyses showed that a longer course of moxibustion (>8 weeks) and indirect moxibustion had a greater effect on reducing serum creatinine. The effect of moxibustion on blood urea nitrogen changed to be nonsignificant after excluding RCTs with a high risk of bias (MD −0.96 mmol/L, 95% CI −2.96 to 1.03). Only one adverse event of burn was reported. Conclusions This systematic review suggests that, as an adjuvant therapy, moxibustion may improve serum creatinine, urinary protein excretion, blood urea nitrogen, and quality of life in patients with CKD. Moxibustion may not have effects on eGFR, creatinine clearance, or hemoglobin. The quality of evidence is weakened by the limitations of risk of bias, heterogeneity, and imprecision.

Efficacy of Antioxidant Supplements on Prevention and Amelioration of Cisplatin-Induced Nephrotoxicity: A Systematic Review and Meta-analysis of Randomized Controlled Trials

ContextCisplatin is a widely used antineoplastic agent in the treatment of a wide range of malignancies although it is associated with nephrotoxicity. Much clinical evidence supports the use of antioxidant supplements in the prevention of cisplatin-induced nephrotoxicity (CIN). However, conflicting evidence makes us unable to provide any robust results for antioxidants use against CIN.ObjectivesThe study aimed to investigate the efficacy of antioxidant supplements on CIN through a comprehensive meta-analysis of randomized controlled trials. Data Sources: A systematic literature search was conducted in PubMed, EMBASE, Cochrane Library, CPCI-S (Conference Proceedings Citation Index-Science), ICTRP (International Clinical Trials Registry Platform), and Google Scholar until February 2017 by two independent researchers. Various outcomes such as serum creatinine, estimated glomerular filtration rate (eGFR), blood urea nitrogen (BUN), creatinine clearance, and incidence of CIN were assessed. All statistical analyses were performed using RevMan V.5.3ResultsOverall, 672 patients were identified from 10 studies of whom 330 (49.10%) patients received antioxidant treatment. Antioxidant treatment showed a significant reduction in serum creatinine (SMD: -3.40, 95% CI: -5.47 to -1.33, P = 0.001), BUN (SMD = -5.96, 95% CI: -10.07 to -1.86, P = 0.004), and eGFR (SMD = -3.77, 95% CI: -6.16 to -1.38; P = 0.002) when compared to the control group.ConclusionsAntioxidant treatment is associated with a reduced risk of CIN. It also has important clinical implications for CIN patients who are not responding to other therapies such as hydration, diuresis, or magnesium supplementation.

Modulation of Renal Parenchyma in Response to Allogeneic Adipose-Derived Mesenchymal Stem Cells Transplantation in Acute Kidney Injury.

Background and ObjectivesIn regenerative medicine, mesenchymal stem cells derived from adipose tissues (Ad-MSCs) are a very attractive target to treat many diseases. In relation to nephrology, the aim of the current study is to investigate the effects of Ad-MSCs for the amelioration of acute kidney injury and to explore the mechanism of renal parenchymal changes in response to allogeneic transplantation of Ad-MSCs.Methods and ResultsThe nephrotoxicity was induced by cisplatin (CP) in balb/c mice according to RIFLE Class and AKIN Stage 3. PCR, qRT-PCR and fluorescent labeled cells infusion, histopathology, immunohistochemistry, functional analyses were used for genes and proteins expressions data acquisition respectively. We demonstrated that single intravenous infusion of 2.5×107/kg mAd-MSCs in mice pre-injected with CP recruited to the kidney, restored the renal structure, and function, which resulted in progressive survival of mice. The renal tissue morphology was recovered in terms of diminished necrosis or epithelial cells damage, protein casts formation, infiltration of inflammatory cells, tubular dilatation, and restoration of brush border protein; Megalin and decreased Kim-1 expressions in mAd-MSCs transplanted mice. Significant reduction in serum creatinine with slashed urea and urinary protein levels were observed. Anti-BrdU staining displayed enhanced tubular cells proliferation. Predominantly, downgrade expressions of TNF-α and TGF-β1 were observed post seven days in mAd-MSCs transplanted mice.ConclusionsAd-MSCs exerts pro-proliferative, anti-inflammatory, and anti-fibrotic effects. Ad-MSCs transplantation without any chemical or genetic manipulation can provide the evidence of therapeutic strategy for the origin of regeneration and overall an improved survival of the system in functionally deprived failed kidneys.

Protective effect of ivy leaf extract on paracetamol-induced oxidative stress and nephrotoxicity in mice

Introduction: The aim of the study was to evaluate the protective effect of Hedera helix (ivy) leaf extract on paracetamol-induced oxidative stress and renal toxicity in mouse model. Methods: Sixty male Swiss albino mice were randomly divided into six equal groups. Group A: as the control group, received NaCl 0.9%. Group B: received a single (i.p.) injection of paracetamol (600 mg/kg). Pretreatment groups: included T1 (50 mg/kg), T2 (100 mg/kg), T3 (200 mg/kg), and T4 (300 mg/kg) which were treated with ivy leaf extract in different doses. The mice were sacrificed under mild anesthesia and the blood samples were collected to titrate the levels of serum blood urea nitrogen (BUN), creatinine and, uric acid. Kidneys were removed for histopathological examination. Results: Paracetamol administration significantly increased the BUN, creatinine and uric acid levels (P < 0.05). Treatment with Ivy leaf extract resulted in a significant reduction in serum creatinine, uric acid and BUN concentrations in comparison with the paracetamol group. Ivy leaf extract treatment similarly reduced histological alteration induced by paracetamol. Conclusion: This study can be used as prove of reading that ivy leaf extract might be used to prevent renal damage induced by paracetamol.

Interference With Coagulation Cascade as a Novel Approach to Counteract Cisplatin-Induced Acute Tubular Necrosis; an Experimental Study in Rats.

Coagulation system activation plays an important role in the pathophysiology of different diseases. In spite of massive research regarding cisplatin-induced nephrotoxicity, the role of coagulation cascade in such toxicity is still questionable. Here, we aim to investigate the role of activation of coagulation system in the initiation of cisplatin-induced acute renal tubular necrosis. Moreover, the role of the anticoagulant rivaroxaban against such toxicity was investigated. Briefly, animals were classified into seven groups, eight rats each. Group 1 served as normal control group, groups (2–7) received i.p. single doses of cisplatin (6 mg/kg b.w), groups (6–7) were treated with rivaroxaban (5 and 7 mg/kg b.w, p.o., respectively) 7 days before cisplatin injection and completed for 4 days. Animals in groups (2, 3, and 4) were sacrificed after 1, 2 and 3 days of cisplatin injection, respectively, while groups (1, 5, 6, and 7) were sacrificed after 4 days of cisplatin injection. Serum cystatin-c, urea, creatinine and γ-glutamyl transferase, urinary Lipocaline-2, and KIM-1 protein densities, as well as glomerular filtration rate (GFR) were assessed. Immunofluorescence examination of glomeruli fibrin and tissue factor (TF) was also performed coupled with a histopathological study. Cisplatin administration increased expression of fibrin and TF starting 24 h of cisplatin injection even before renal failure markers elevated. Leukocytosis, thrombocytopenia, and increased prothrombin time were also observed. Cisplatin also induced tubular damage evidenced by increased serum cystatin-c, urea, and creatinine with significant decrease in GFR and Gamma glutamyl transferase (GGT) activity. Rivaroxaban significantly decreased elevation of fibrin and TF with significant reduction in serum creatinine, BUN and cystatin-c levels. Rivaroxaban also significantly improved hematological markers and histological features as well. This study showed that activation of coagulation system plays an important role in the pathophysiology of cisplatin-induced acute renal tubular damage. Interference with coagulation cascade may be a promising nephroprotective strategy against chemical nephrotoxicity.

Nephroprotective effect of saxagliptin against gentamicin-induced nephrotoxicity, emphasis on anti-oxidant, anti-inflammatory and anti-apoptic effects

Nephrotoxicity is a serious adverse effect frequently encountered with aminoglycosides administration. Given the value of aminoglycosides in management of serious infections, nephro-protection is highly recommended. The current study investigated the nephro-protective effect of saxagliptin (SAXA) (12.5 mg/kg, I.P.) against gentamicin (GEN)-induced nephrotoxicity in rats. SAXA administration for 14 days conferred significant nephro-protection against GEN-induced nephrotoxicity manifested in decreased kidney/somatic index, enhanced cytoprotection and significant decrease in serum LDH activity together with functional renal improvement; significant increase in creatinine clearance with significant reduction in serum creatinine, BUN, proteinuria and albuminuria. Oxidant/antioxidants hemostasis was significantly improved with SAXA treatment with significant reduction in kidney MDA content and enhancement of GSH concentration and catalase activity. Moreover, kidney content of NO significantly declined with significant decline in kidney tumor necrosis factorα (TNFα), vascular adhesion molecule-1 (VCAM-1) and caspase-3 content. Ultimately, SAXA administration was associated with significant attenuation of GEN-induced necrotic and inflammatory changes. In conclusion; the modulatory effect of SAXA on inflammatory cytokines, its anti-apoptic properties, ameliorative impact on oxidative load and positive impact on host antioxidant defenses accounts for the observed nephro-protective impact.

A PRISMA-compliant systematic review and network meta-analysis on the efficacy between different regimens based on Tripterygium wilfordii Hook F in patients with primary nephrotic syndrome.

The present study aims to comprehensively determine the efficacy of different therapy regimens based on Tripterygium wilfordii Hook F (TwHF) for patients with primary nephrotic syndrome (PNS) using network meta-analysis method. Seven electronic databases were searched to identify randomized controlled trials (RCTs) that compared the differences between different therapy regimens based on TwHF for patients with PNS. The risk of bias in included RCTs was evaluated according to the Cochrane Handbook version 5.2.0. Network meta-analysis was performed to compare different regimens. Primary outcomes were complete remission rate and total remission rate. The secondary outcomes were hr urinary protein excretion, serum albumin, serum creatinine, and urea nitrogen. Data analysis was performed using R software. A total of 40 studies involving 2846 patients with PNS were included. Compared with prednisone, the improvement in total remission rate and complete remission rate was associated with TwHF alone (odds ratio [OR] = 4.80, 95% credible intervals [CrI]: 2.20-10.00; OR = 6.30, 95% CrI: 2.90-13.00, respectively), TwHF+prednisone (OR = 2.10, 95% CrI: 1.30-3.50; OR = 2.40, 95% CrI: 1.50-3.80, respectively), TwHF+CPA (OR = 12.00, 95% CrI: 1.10-150.00; OR = 16.00, 95% CrI: 1.60-170.00, respectively), and TwHF+Cyclosporine A (OR = 28.00, 95% CrI: 3.20-250.00; OR = 35.00, 95% CrI: 4.50-270.00, respectively). Compared with TwHF alone, TwHF+prednisone showed less benefit in improving total remission rate and complete remission rate (OR = 0.44, 95% CrI: 0.21-0.91; OR = 0.38, 95% CrI: 0.19-0.77, respectively). TwHF alone, TwHF+prednisone could significantly reduce hr urinary protein excretion (MD = -0.69, 95% CrI: -1.30 to -0.14; MD = -1.00, 95% CrI: -1.90 to -0.14, respectively) and increase serum albumin (MD = 5.90, 95% CrI: 2.50-9.30; MD = 3.40, 95% CrI: 1.30-5.50, respectively) when compared to prednisone alone. TwHF alone showed significant reduction in serum creatinine when compared to CPA (MD = -19.00, 95% CrI: -37.00 to -0.56). TwHF alone, the addition TwHF to prednisone showed more benefit in improving total and complete remission rate, hr urinary protein excretion, serum albumin, and serum creatinine.

HMG CoA reductase inhibitors (statins) for preventing acute kidney injury after surgical procedures requiring cardiac bypass.

Background Acute kidney injury (AKI) is a common complication of cardiac surgery, with incidence ranging from 1-30%. Cardiac associated AKI has been shown to increase morbidity and mortality, is associated with longer intensive care stays and increased cost, especially when renal replacement therapy (RRT) is required. Cardiopulmonary bypass has been identified as a significant risk factor for AKI. Overall decrease in blood flow has been shown to decrease glomerular filtration rate, but it is also thought that cardiopulmonary bypass triggers an inflammatory response that injures kidney tissue. Statins are widely used as lipid lowering drugs. However they have also been shown to have an anti-inflammatory effect, with some evidence that statin administration prior to cardiac surgery reduces peri procedural cardiovascular events. There is an urgent need for effective therapies in this group because kidney dysfunction after surgery leads to significant morbidity compared to patients who maintain normal kidney function. Evidence indicating that statins help to prevent kidney injury will help to address the gap that exists in effective therapies in the setting of cardiac surgery requiring cardiopulmonary bypass. Objectives To determine whether use of statins was associated with preventing AKI development, determine whether the use of statins was associated with reductions in in-hospital mortality and determine whether the use of statins was associated with reduced need for RRT. Interventions/methods Randomised controlled trials that compared administration of statin therapy with placebo or standard clinical care in adults undergoing surgery requiring cardiopulmonary bypass, and reporting AKI, serum creatinine (SCr) or need for RRT as an outcome were eligible for inclusion. The dose or type of statins used was not restricted. Studies that included patients undergoing cardiac surgery but did not require bypass were excluded. Results Seven studies (662 participants) were included in this review. All except one study was assessed as being at high risk of bias. Three studies assessed atorvastatin, three assessed simvastatin and one investigated rosuvastatin. All studies collected data during the immediate perioperative period only; data collection to hospital discharge and postoperative biochemical data collection ranged from 24 hours to 7 days. Overall, preoperative statin treatment was not associated with a reduction in postoperative AKI, need for RRT or reduction in in-hospital mortality. Only two studies (195 participants) reported postoperative SCr level. In those studies, patients allocated to receive statins had lower postoperative SCr concentrations compared with those allocated to no drug treatment/placebo (MD 21.2 µmol/L, 95% CI -31.1 to-11.1). Adverse effects were adequately reported in only one study; no difference was found between the statin groups compared to placebo. Conclusions Currently available data does not indicate that preoperative statin use is associated with decreased incidence of AKI in adults who required cardiac bypass. A significant reduction in SCr was seen postoperatively in people treated with statins, these results were driven by a single study, with SCr reported as a secondary outcome, meaning there is significant uncertainty regarding the strength of this result. The results of the meta-analysis should be interpreted with caution, few studies were included in subgroup analyses, and significant differences in methodology exist among the included studies. Overall no reduction in mortality or need for RRT was seen in people receiving statin therapy undergoing cardiac surgery requiring bypass.

Postoperative renal function in parturients with severe preeclampsia who underwent cesarean delivery: a retrospective observational study.

Although postoperative renal dysfunction is relatively rare after cesarean delivery, preeclampsia is considered as the high-risk population. On the other hand, hydroxyethyl starch (HES) administration for preventing maternal hypotension induced by spinal anesthesia for cesarean delivery is a common practice. However, the effect of HES administration during cesarean delivery on postoperative kidney function in parturients with severe preeclampsia is not well investigated. We retrospectively reviewed both medical and anesthesia records of patients with severe preeclampsia who underwent cesarean delivery from January 2011 to December 2013. Preoperative blood examinations were compared with postoperative values. All parturients received 6% HES 70/0.5 for preventing anesthesia-induced hypotension or for volume resuscitation during cesarean delivery. A total of 87 severe preeclampsia parturients were underwent cesarean section during the period. The amounts of HES administration were 859 ± 206mL. There was significant reduction in serum creatinine, from 0.70 ± 0.29mg/dL preoperatively to 0.62 ± 0.17mg/dL in 3-7days after the cesarean. Only one patient had postoperatively elevated serum creatinine up to clinically significant level (from 0.64mg/dL to 1.35mg/kg).

The Nephroprotective Effect of N-Acetyl-L-Cysteine and Atorvastatin against Imipenem induced Nephrotoxicity.

Imipenem has played an important role in the treatment of broad-spectrum bacterial infection. However, nephrotoxicity due to imipenem remains an important clinical challenge. The aim of this study is to test the hypothesis stating that N-acetyl-L-cysteine (NAC) and atorvastatin possess a nephroprotective effect against imipenem-induced nephrotoxicity. Adult Sprague Dawley rats were randomly assigned into six groups (n=8-10 rats/group; total n=55). The groups were (control, imipenem only, NAC only, atorvastatin only, NAC with imipenem, and atorvastatin with imipenem). Rats were treated with NAC or atorvastatin for six weeks. Serum and urinary creatinine and blood urea nitrogen (BUN) levels were measured. Additionally, urinary protein, urinary glucose and kidney levels of oxidants/antioxidants biomarkers were measured. The administration of 300mg/kg/d imipenem induced nephrotoxicity as indicated by the significant reduction of serum creatinine, serum BUN and calculated GFR in the imipenem only-treated group compared to the control. These effects of imipenem were normalized by either NAC or atorvastatin. Moreover, the levels of catalase, superoxide dismutase and glutathione peroxidase were significantly reduced in the imipenem group. However, pre-administration of NAC and atorvastatin neutralized the levels of these enzymes and protected against imipenem-induced nephrotoxicity. We concluded that the pre-administration of either NAC or atorvastatin protects the kidneys from imipenem-induced nephrotoxicity, through their antioxidant effects.

Comparative Study between the Effect of Pentoxifylline versus Diltiazem versus Rosuvastatin on the Development and Progression of Nephropathy in Streptozotocin Induced Diabetic Rats

Background. Diabetic nephropathy is the major cause of end stage renal disease especially in developing countries. Reducing proteinuria is the mainstay of therapy in order to delay the progression of chronic kidney disease. Current therapeutic regimens provide only partial renoprotection, and a substantial number of patients who have proteinuria progress to end stage renal disease. Aim. The aim of this study was to evaluate the effects of pentoxifylline and diltiazem versus rosuvastatin on development and progression of nephropathy in streptozotocin induced diabetic rats and possible mechanisms of action. Materials and Methods. Eighty adult albino rats were randomly divided into eight groups: the first and second groups are normal control and diabetic control. Streptozotocin-induced type 1 diabetes mellitus (DM) model was set up in adult male albino rats by single intraperitoneal injection of streptozotocin (65mg/kg, I.P). The third, the fifth, and the seventh groups are non-diabetic groups of rats receiving pentoxifylline (40mg/kg/day, orally), diltiazem (10 mg/kg/day, i.p.), or rosuvastatin (10mg/kg/day, orally), respectively, for eight weeks. The fourth, the sixth, and the eighth groups are diabetic rats receiving pentoxifylline (40 mg/kg per day, orally), diltiazem (10mg/kg per day, i.p.), or rosuvastatin (10mg/kg/day, orally), respectively, for eight weeks. The glomerular filtration rate, serum urea, creatinine, urine albumin, urine volume changes, Na+ excretion level, K+ excretion level, renal blood flow, renal histopathology, and measurement of antioxidant enzymes activity (GSH, superoxide dismutase) of the different groups were tested compared to control group. Results. At the end of the eight weeks, use of pentoxifylline and rosuvastatin induced significant reduction of serum creatinine, urea, and urine albumin. Also, glomerular filtration rate, renal blood flow, and antioxidant enzymes were significantly improved. There were no significant differences between the two drugs, while diltiazem induced insignificant improvement in the previous parameters. Conclusion. The use of pentoxifylline and rosuvastatin is associated with a reduced risk of diabetic nephropathy by improving oxidative stress. Furthermore, diltiazem insignificantly ameliorates diabetic nephropathy.