Elevated Creatinine Levels Research Articles

The Emergent General Surgical Patient: Evaluation Patterns in the Emergency Department.

IntroductionEmergency general surgery patients represent a growing segment of general surgical admissions and national healthcare burden. A paucity of literature exists evaluating the work-up of these patients presenting to the Emergency Department (ED), particularly possible evaluation differentials between emergency physicians and physician assistants or advanced practice registered nurses (PA/ APRNs). The purpose of this study was to evaluate differences in ED work-up of general surgical patients between emergency physicians and PA/APRNs.MethodsA retrospective review was conducted of patients presenting to the ED with the chief complaint of abdominal pain. Demographic data, evaluating provider, laboratory and imaging tests, diagnostic data, and disposition were obtained.ResultsPatient median age was 53.5 years, with 49% male and 81.6% Caucasian. Emergency physicians saw the majority (61.2%) of patients. Emergency physicians saw older patients (62.0 vs. 45.5 years; p = 0.017), and more patients that were anemic (28.3% vs. 14.3%) or with elevated creatinine levels (46.7% vs. 25.7%). There was no significant difference between groups for time in the ED (6.1 ± 2.4 vs. 5.7 ± 2.6 hours; p = 0.519), time to surgical consult (3.4 vs. 3.3 hours; p = 0.298), or time to the operating room (29.5 vs. 12.0 hours; p = 0.075). Patients seen by emergency physicians had a longer length of hospital stay (4.5 vs. 2 days; p = 0.002).ConclusionsTime in the ED and time to surgical consult did not vary between groups although patients first seen by emergency physicians had potentially higher acuity. Decreased hospital length of stay in patients seen by PA/APRNs may reflect disease-specific differences.

Development of a risk score to predict occurrence of deep sternal dehiscence requiring operative debridement

ObjectiveSevere deep sternal wound (DSW) complications after cardiac surgery are a source of cost, morbidity, and mortality. Our objective was to develop and validate a clinical risk score for predicting risk of DSW requiring operative bone debridement, the most severe form of sternal dehiscence. MethodsA retrospective review was conducted of patients who underwent open cardiac surgery at a single institution between October 2007 and March 2019. Primary outcome was DSW requiring sternal bone debridement. Potential risk factors were screened using Least Absolute Shrinkage and Selection Operator (LASSO) and significant covariates were included in a logistic regression prediction model. Interval validation was performed using 10-fold cross-validation. A novel sternal wound dehiscence risk score was derived from the relative parameterization estimates. ResultsOne hundred thirty-four of 8403 patients (1.6%) were identified as having a DSW. Female sex (odds ratio [OR], 2.75; 95% CI, 2.58-2.93), body mass index (OR, 1.0946; 95% CI, 1.09-1.09), percent glycated hemoglobin (OR, 1.31; 95% CI, 1.28-1.33), peripheral vascular disease (OR, 2.38; 95% CI, 2.2005-2.5752), smoking (OR, 1.66; 95% CI, 1.53-1.79) and elevated creatinine level (OR, 1.20; 95% CI, 1.18-1.22) were independent predictors of DSW. Patients were categorized as minimal risk (0%-1%), low risk (2%-3%), intermediate risk (4%-7%), and high risk (9%-64.0%) on the basis of risk score. ConclusionsThis risk stratification model for DSW requiring operative debridement might provide individualized estimates of risk, and guide counseling and potential risk mitigation strategies.

Monoclonal gammopathy of renal significance (MGRS): Real-world data on outcomes and prognostic factors.

Monoclonal gammopathy of renal significance (MGRS) is a recognized clinical entity. Literature regarding treatment and its outcomes in MGRS is sparse due to the rarity and misdiagnosis of MGRS. We retrospectively analyzed 280 adults with an MGRS diagnosis from 2003 to 2020 across 19 clinical centers from 12 countries. All cases required renal biopsy for the pathological diagnosis of MGRS. Amyloidosis‐related to MGRS (MGRS‐A) was present in 180 patients; nonamyloidosis MGRS (MGRS‐NA), including a broad spectrum of renal pathologies, was diagnosed in 100 patients. The median overall survival in the studied cohort was 121.0 months (95% CI: 105.0–121.0). Patients with MGRS‐A had a shorter overall survival than patients with MGRS‐NA (HR = 0.41, 95%CI: 0.25–0.69; p = 0.0007). Both hematologic and renal responses were associated with longer survival. Achievement of ≥VGPR was generally predictive of a renal response (OR = 8.03 95%CI: 4.04–115.96; p < 0.0001), one‐fourth of patients with ≥VGPR were renal nonresponders. In MGRS‐A, factors associated with poor prognosis included elevated levels of creatinine, beta‐2‐microglobulin, and hemodialysis at diagnosis. In MGRS‐NA, only age >65 years was associated with increased risk of death. Treatments provided similar hematologic response rates in both types of MGRS. Autologous stem cell transplantation led to better response than other treatments. This multicenter and international effort is currently the largest report on MGRS.

Gastrointestinal hemorrhage as an acute-on-chronic liver failure trigger in cirrhotic patients.

Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute decompensation of chronic liver disease associated with organ failures and very high short-term mortality. To assess the incidence and factors predisposing to ACLF in patients with liver cirrhosis hospitalized due to acute gastrointestinal bleeding (GIB). We collected and retrospectively analyzed the data of 89 consecutive patients (59 males (66.2%), median age 53 years (range: 44-62 years), mean Model for End-Stage Liver Disease (MELD) score 14.42 ±6.5, median Child-Turcotte-Pugh score 10 (range: 8-11), and acute GIB (72 variceal bleeding and 17 non-variceal bleeding cases). Acute-on-chronic liver failure was diagnosed based on European Association for the Study of the Liver - Chronic Liver Failure Consortium definition. Twenty-seven (30.33%) patients met the criteria of ACLF during hospitalization: 8 (30%) had ACLF grade 1, 13 (48%) had ACLF grade 2 and 6 (22%) had ACLF grade 3. The most frequent organ failures were respiratory (22 (25%)), kidney (18 (20.23%)) and brain (17 (19.1%)) failure. The MELD score value, creatinine level and presence of hepatic encephalopathy (HE) on admission were significant predictors of ACLF in the multivariate logistic regression model with optimal cutoff point for MELD score of 18.313 and optimal cutoff point for creatinine level of 1.35 mg/dL. In-hospital risk of ACLF in cirrhotic patients hospitalized for acute gastrointestinal hemorrhage is high despite successful arrest of bleeding. Elevated creatinine level, MELD score and the presence of HE on admission are the best predictors of ACLF during hospitalization in such patients.

Levamisole causes a transient increase in plasma creatinine levels but does not affect kidney function based on cystatin C

BackgroundIn pediatric patients treated with levamisole to prevent relapses of idiopathic nephrotic syndrome (INS), a transient and non-progressive rise in creatinine levels has been observed. It has been suggested that levamisole affects tubular secretion of creatinine. However, other potential mechanisms — nephrotoxicity and interference with the analytical assay for creatinine — have never been thoroughly investigated.MethodsIn three steroid-sensitive nephrotic syndrome (SSNS) patients with elevated plasma creatinine levels, treated with levamisole 2.5 mg/kg every other day, serum cystatin C was determined. The glomerular filtration rate (GFR) was estimated using the full age spectrum for creatinine and the full age spectrum for cystatin C equations. Interference of levamisole with the enzymatic creatinine assay was tested using spare human plasma of different creatinine concentrations spiked with levamisole (4, 20, and 100 µM).ResultsThree patients who received levamisole with elevated plasma creatinine levels had normal serum cystatin C levels and corresponding estimated GFR. There was no assay interference.ConclusionLevamisole increases plasma creatinine levels, which is most probably due to impaired tubular secretion of creatinine since there was no assay interference and patients had normal eGFR based on serum cystatin C. However, interference of metabolites of levamisole could not be excluded. To monitor GFR, cystatin C in addition to creatinine should be used and be measured before and during levamisole use.

Prognostic Impact and Predictors of New-Onset Atrial Fibrillation in Heart Failure.

Background: The prognostic impact and predictors of NOAF in HF patients are not fully elucidated. This study aims to determine whether new-onset atrial fibrillation (NOAF) affects patient outcome and investigate predictors of atrial fibrillation (AF) in acute heart failure (HF) patients using real-world data. Methods: The factors associated with NOAF in 2894 patients with sinus rhythm (SR) enrolled in the Korean Acute Heart Failure (KorAHF) registry were investigated. Survival was analyzed using AF as a time-dependent covariate. Relevant predictors of NOAF were analyzed using multivariate proportional hazards models. Results: Over 27.4 months, 187 patients developed AF. The median overall survival time was over 48 and 9.9 months for the SR and NOAF groups, respectively. Cox regression analysis with NOAF as a time-dependent covariate showed a higher risk of death among patients with NOAF. Multivariate Cox modeling showed that age, worsening HF, valvular heart disease (VHD), loop diuretics, lower heart rate, larger left atrium (LA) diameter, and elevated creatinine levels were independently associated with NOAF. Risk score indicated the number of independent predictors. The incidence of NOAF was 2.9%, 9.4%, and 21.8% in the low-risk, moderate-risk, and high-risk groups, respectively (p < 0.001). Conditional inference tree analysis identified worsening HF, heart rate, age, LA diameter, and VHD as discriminators. Conclusions: NOAF was associated with decreased survival in acute HF patients with SR. Age, worsening HF, VHD, loop diuretics, lower heart rate, larger LA diameter, and elevated creatinine could independently predict NOAF. This may be useful to risk-stratify HF patients at risk for AF.

Comparison of biochemical characteristics between an endemic and a nonendemic area for CKDu Sri Lanka

Introduction: Chronic kidney disease with uncertain etiology (CKDu) was first recognized in the 1990s in Sri Lanka. Considering the distribution of CKDu in the country, clusters of endemic and nonendemic areas can be identified. This study was carried out to compare the biochemical characteristics between CKDu endemic and nonendemic areas in Sri Lanka. Materials and Methods: A cross-sectional study was carried out among randomly selected males between the age category of 30 and 60 years in selected villages of Wilgamuwa (endemic) and Hanguranketha (nonendemic), located in the dry and wet zone, respectively. Results: The total participation percentage from the endemic area was 74.7% (224 out of 300 invitees). Out of 150 participants invited from the nonendemic area, only 100 participated in the study cohort. There was a striking difference between the two areas in serum creatinine levels (P = 0.001). When considering the behavioral patterns of the two study areas, the main occupation was farming and there was no significant difference between the behaviors of the people in the selected areas. A significant number of participants (n = 31, 13.8%) from the endemic area had high serum creatinine levels with a mean of 109 μmol/L (standard deviation [SD] = 66.41) (normal: 90–116 μmol/L). Whereas, in the nonendemic area, only 3 (3%) participants had elevated creatinine levels with a mean value of 85.41 μmol/L (SD = 18.78). A significant difference was observed in the two groups in the mean values of serum creatinine levels (P = 0.001). The mean value of random blood sugar (RBS) was 113.56 mg/dL (SD = 44.38) and 119.10 mg/dL (SD = 50.48) in endemic and nonendemic areas, respectively. There was no significant difference between the mean values of RBS (P = 0.2). The mean serum cholesterol was slightly higher in Wilgamuwa (119.26 mg/dl, SD = 45.31) compared to Hanguranketha (189.02 mg/dl, SD = 45.09). However, that was not statistically significant (P = 0.6). Conclusions: Serum creatinine is remarkably increased in CKDu endemic areas. RBS and serum cholesterol are less significant according to the endemicity of CKDu.

Development of a Risk Stratification Scoring System to Predict General Surgical Complications for Patients Undergoing Foot and Ankle Surgery.

Preventing postoperative complications is crucial for patients, surgeons, and health care facilities. We developed a risk stratification scoring system to optimize postoperative outcomes for patients undergoing foot and ankle surgery. A total of 35,580 patients who underwent foot and ankle procedures from 2005 to 2017 were identified as part of the American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP). To assess the risk of a postoperative complication, we identified several independent risk factors associated with 30-day postoperative complications, then proceeded to develop a point-based risk scoring system. To validate our scoring system, we used it on a cohort of patients from the database who underwent foot and ankle surgery. Risk factors that correlated with postoperative complications included tobacco abuse, age (≥65 years), diabetes mellitus, hypertension, elevated creatinine level (≥1.3 mg/dL), hypoalbuminemia (<3.5 g/dL), chronic obstructive pulmonary disease (COPD), congestive heart failure (CHF), hyponatremia (<135 mEq/L), and anemia (hematocrit value, men <42%; women <38%). Point scores for each factor were: anemia, +10; hypoalbuminemia, +9; elevated creatinine level, +6; CHF, +4; diabetes mellitus, +3; hyponatremia, +3; COPD, +2; hypertension, +2; age, +1; and tobacco abuse, +1. For the validation cohort, we stratified patients according to risk as low (0-20 points), medium (21-30 points), and high (≥31 points) risk. In terms of having a postoperative complication, compared with low-risk patients, patients who were at medium risk had an odds ratio of 4.7 (95% CI, 2.8-7.9) and those at high risk had an odds ratio of 8.3 (95% CI, 4.8-14.5). [Orthopedics. 2022;45(3):139-144.].

A Cross-sectional Study on the Development of Diabetic Cardiovascular Complications in Type 2 Diabetes Mellitus in a South Indian Tertiary Care Hospital

Background: Diabetic cardiovascular complication is a familiar macrovascular complication of Type 2 Diabetes mellitus (T2DM). Cardiovascular disease (CVD) is the major cause of morbidity and mortality for people with diabetes.&#x0D; Objective: The aim of this study was to evaluate the parameters related to diabetic cardiovascular complication in patients with T2DM.&#x0D; Methodology: This study was conducted on 530 subjects (171 with or 359 without diabetic cardiovascular complication). Prevalence of diabetic cardiovascular complication was measured, risk factors for diabetic cardiovascular complications, and drug utilization pattern was assessed.&#x0D; Results: Cardiovascular complication was significantly higher in the subjects who are poorly educated, nature of work (house wives) and risk factors were pre-existing conditions (Hypertension, Cardiac, endocrine and other diseases), habit of smoking (past smoker), tea/coffee (twice without sugar), poor glycemic control, elevated triglyceride levels, elevated creatinine levels, duration of diabetes (5-10 years; &gt;10 years).&#x0D; Conclusion: Combination of Glimepiride and Metformin (35.10%), Metformin (34.04%), combination of insulin isophane and insulin regular (23.40%), Insulin Regular (11.70%) were the anti-diabetic drugs widely prescribed to the T2DM patients with cardiovascular complications. Significant risk factors for development of diabetic cardiovascular complication were multiple.

Efficacy of cisplatin plus vinorelbine adjuvant chemotherapy with split-dose administration of cisplatin after complete resection of stage II-IIIA non-small cell lung cancer.

Although co-administration of cisplatin (CDDP) and vinorelbine (VNR) has been established as a standard of care adjuvant chemotherapy for non-small cell lung cancer (NSCLC), there is a lack of clinical data on its safety and efficacy in Japanese patients receiving split-dose administration of CDDP. The present study analyzed patients who received CDDP + VNR with split-dose administration of CDDP after undergoing complete resection of NSCLC. Patients received four courses of CDDP (40 mg/m2) and VNR (25 mg/m2) on days 1 and 8, every 3 weeks. There were 27 male and 13 female patients; the mean age was 65 years (range 38-78 years), the postoperative disease staging distribution was IIA/IIB/IIIA: 14/8/18 patients, and histological distribution was adenocarcinoma/squamous cell carcinoma/others: 24/12/4 patients, respectively. Of the 40 patients, 28 (70%) completed the four courses of treatment. The mean total dose administered was 279 mg/m2 CDDP (87.2%) and 172 mg/m2 VNR (86%). The major adverse events included Grade (G) 3 or higher neutropenia (80%), G3 phlebitis (5%) and vomiting (2.5%). There was no G2 or higher serum creatinine level elevation, G3 or higher anorexia and nausea, or any treatment-related deaths. The overall completion rate of four courses was 70 and 62.5% for patients aged 70 years and older, whereas the overall percentage of patients that could complete three or more courses was 85 and 87.5% for patients aged 70 years and older. The relapse-free survival rate was 60% at 3 years and 57.5% at 5 years. Overall survival rate was 80% at 3 years and 60% at 5 years. The present study demonstrated the sufficient tolerability, safety and efficacy of combined CDDP + VNR adjuvant chemotherapy with split-dose administration of CDDP, with a low risk of gastrointestinal toxicities or nephrotoxicity.

Xanthine Oxidoreductase Inhibitors Suppress the Onset of Exercise-Induced AKI in High HPRT Activity Urat1-Uox Double Knockout Mice.

Hereditary renal hypouricemia type 1 (RHUC1) is caused by URAT1/SLC22A12 dysfunction, resulting in urolithiasis and exercise-induced AKI (EIAKI). However, because there is no useful experimental RHUC1 animal model, the precise pathophysiologic mechanisms underlying EIAKI have yet to be elucidated. We established a high HPRT activity Urat1-Uox double knockout (DKO) mouse as a novel RHUC1 animal model for investigating the cause of EIAKI and the potential therapeutic effect of xanthine oxidoreductase inhibitors (XOIs). The novel Urat1-Uox DKO mice were used in a forced swimming test as loading exercise to explore the onset mechanism of EIAKI and evaluate related purine metabolism and renal injury parameters. Urat1-Uox DKO mice had uricosuric effects and elevated levels of plasma creatinine and BUN as renal injury markers, and decreased creatinine clearance observed in a forced swimming test. In addition, Urat1-Uox DKO mice had increased NLRP3 inflammasome activity and downregulated levels of Na+-K+-ATPase protein in the kidney, as Western blot analysis showed. Finally, we demonstrated that topiroxostat and allopurinol, XOIs, improved renal injury and functional parameters of EIAKI. Urat1-Uox DKO mice are a useful experimental animal model for human RHUC1. The pathogenic mechanism of EIAKI was found to be due to increased levels of IL-1β via NLRP3 inflammasome signaling and Na+-K+-ATPase dysfunction associated with excessive urinary urate excretion. In addition, XOIs appear to be a promising therapeutic agent for the treatment of EIAKI.

Risk factors for polymyxin B-associated acute kidney injury

ObjectivesThis study aimed to assess the current incidence and risk factors for polymyxin B-associated acute kidney injury (AKI) in Chinese hospitals for a more effective clinical use for polymyxin B. MethodsThis multicenter, retrospective cohort study included patients from 14 Chinese teaching hospitals who received polymyxin B therapy. Univariate and multivariate logistic regression models were used to determine the factors associated with polymyxin B-associated incident AKI. Furthermore, a multivariate logistic regression model was used to identify the independent risk factors for AKI. ResultsA total of 251 patients were included in the analysis. The overall incidence of AKI was 33.5%. A multivariate logistic regression model identified the loading dose (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.01–3.38; P = 0.0491) and the use of two or more nephrotoxic drugs (HR, 3.56; 95% CI, 1.55–8.18; P = 0.0029) as independent risk factors for the occurrence of AKI. Meanwhile, the estimated glomerular filtration rate had a protective effect (HR, 0.99; 95% CI, 0.98–0.99; P = 0.0006) on the occurrence of AKI. The daily dose, cumulative dose, and treatment duration of polymyxin B did not affect the occurrence of AKI. ConclusionsThe use of polymyxin B loading doses and the combined use of multiple nephrotoxic drugs are independent risk factors for polymyxin B-associated AKI. The severity of AKI may be higher in patients with elevated baseline creatinine levels.

Gender Differences in Coronary Profiles of Chronic Coronary Syndrome Patients

Background: Chronic coronary syndrome (CCS) is a recently defined entity that necessitates evaluating individual clinical risk factors in this cohort. Objective: The objective of the present study was to evaluate patients with CCS and examine their coronary profiles in order to delineate differences between genders. Methods: A cross-sectional analysis was conducted on 51 patients who met the criteria of CCS and have undergone both coronary angiography and CT coronary angiography. Analyses were conducted using univariate statistics. Results: The cohort consisted of mainly Kuwaiti nationals with an average age of 61 ± 10 years. Females consisted 41% of the cohort, were older by an average of 9 years (P = 0.001), and were overweight (67% vs. 44%). Males were more likely to be cigarette consumers (47% vs. 14%; P = 0.022). Females had more comorbidities such as hypertension (86% vs. 80%) and atrial fibrillation (24% vs. 10%), excluding stroke (0% vs. 3.3%), and coronary artery disease (71% vs. 83%). Males had an elevated level of creatinine (88 vs. 72 umol/L; P = 0.045). Other results were not significantly different between genders. Males were more likely to be prescribed aspirin upon admission (100% vs. 81%; P = 0.026), however, this difference decreased upon discharge (97% vs. 86%; P = 0.297). Recurrent ischemia (12%; n = 6) was the most common major outcome recorded. Conclusions: This study shows that females were more likely to be older than their male counterparts whereas males were more often on aspirin and more likely to be cigarette smokers. We found no significant differences in comorbidities, admission laboratory and imaging results, nor outcomes between genders.

Prediction of Acute Renal Failure in Dengue Fever Patients

Background: Dengue virus (DENV) infection is caused by an arboviral strain and is transmitted by the mosquito Aedes aegypti which is found in Sudan especially Red Sea and Kassala states in the east. The disease is known to cause renal disturbances and a thorough understanding of that will potentially help in the prediction, diagnosis and treatment of the disease. Methods: This study is a prospective observational cross sectional study conducted in the Eastern Sudan College of Medical Science and Technology and Port Sudan Teaching Hospital. 200 confirmed Dengue virus infected patients along with 200 healthy appearing adults (control) were enrolled for the study. Statistical analysis was carried out after the collection of patients’ demographic, clinical, and investigational data including serum urea and creatinine values. Ethical approval was obtained from the ministry of health, Red Sea state and informed written consent was obtained from each participant. Results: The highest incidence of DENV infection was observed in individuals of the middle age group (29%). Elevated blood urea levels were detected in 10 (5%) patients while elevated creatinine levels were seen in 17 (8.5%) patients. Although fallen within reference ranges found in the literature, mean blood urea and creatinine values differed significantly between patients and controls and between different categories of the disease. Mean blood urea concentration showed a statistically significant difference between the control (22.3 mg/dl) and the test (28.4 mg/dl) (P value < 0.001). Similarly, mean serum creatinine in the control (0.70 mg/dl) differed significantly (P value < 0.001) from test (0.94 mg/dl). Clinically, fever was present in 97.5% of patients, headache in 95.5%, joints pain in 71%, lethargy in 67%, vomiting in 49%, skin rash in 40%, abdominal pain in 24% and bleeding in 17.5%. Conclusion: We strongly conclude that renal involvement is not uncommon in Dengue fever and that blood urea and creatinine evaluation should be considered in the counseling of DENV infection patients. Patients need to be subjected to necessary laboratory investigations associated with acute kidney injury to decrease the rate of morbidity and mortality associated with the disease.

Investigation of the nephroprotective effect of dexmedetomidine on colistin-induced nephrotoxicity in rats.

There are very few studies in the literature focusing on whether dexmedetomidine exerts a protective effect on colistin nephrotoxicity. Our study aims to investigate the nephroprotective effect of dexmedetomidine in an experimental model of nephrotoxicity in rats. The control group was administered saline (SF) intraperitoneally twice a day. The colistin group received an intraperitoneal (ip) injection of 10 mg/kg of colistin twice a day. The DX10 group received 10 mg/kg of colistin 20 minutes after the intraperitoneal injection of 10 mcg/kg of dexmedetomidine. The DX20 group received 10 mg/kg of colistin 20 minutes after the intraperitoneal injection of 20 mcg/kg of dexmedetomidine. Applications were continued for 7 days, twice a day. All rats were sacrificed on the 8th day after blood and kidney tissue samples were taken. BUN, Creatine, KIM-1 and Endothelin-1 were studied in blood samples. There was a significant difference in the median values of Urea, BUN and Creatine between the groups (p<0.001, p<0.001, p<0.001, respectively). There was a significant difference in the median values of KIM-1 and Endothelin-1 between the groups (p=0.009, p=0.001, respectively). A significant difference was observed between the histopathological scores of the groups (p<0.001). Dexmedetomidine significantly decreased the elevated levels of BUN, Creatinine, KIM-1, and Endothelin-1 induced by colistin. Dexmedetomidine, at both doses, histopathologically prevented apoptosis and reduced the number of necrotic cells in the kidneys. Dexmedetomidine provides renoprotective effects, therefore it is a valuable sedation agent for clinicians working in intensive care units (Tab. 2, Fig. 4, Ref. 19). Text in PDF www.elis.sk Keywords: rat, colistin, nephrotoxicity, dexmedetomidine.

Boldine provides protective effect against nephrotoxicity induced by cisplatin in Wistar rats: Role of oxidative stress, inflammation and caspase-3

Side effects of cisplatin, especially dose-dependent nephrotoxicity, are major factors limiting its use in cancer. Boldine ((S)-2, 9-dihydroxy-1, 10-dimethoxy-aporphine) is a natural alkaloid known for its strong antioxidant activity present in leaves/bark of boldo tree (Peumus boldus Molina), a native tree in Chile. Here, we aimed to investigate the nephroprotective effect of boldine and its underlying mechanisms on cisplatin-induced rat renal injury. Thirty Wistar albino rats divided into 5 groups (Control, Cis, Bold.40, Cis + Bold.20, Cis + Bold.40 groups) were used. Rats received boldine (20 or 40 mg/kg/day), or vehicle (saline) intraperitoneal for 14 days and a single dose cisplatin (7 mg/kg, ip) was applied on the 10th day to induce nephrotoxicity. Rats and kidney tissue were weighed to determine kidney index. Blood urea nitrojen (BUN) and creatinine levels, the amount of thiobarbituric acid reactive substances (TBARS, an index of lipid peroxidation), superoxide dismutase (SOD), glutathione peroxidase (GPx) enzyme activities and tumor necrosis factor alpha (TNF-α) levels were measured and histopathologic examination was performed. Inducible nitric oxide synthase (iNOS) and caspase-3 expressions were detected immunohistochemically. Nephrotoxicity induced by cisplatin was apparent by elevated levels of BUN, creatinine, kidney index, TBARS and TNF-α, and decreased body weight, SOD and GPx enzyme levels. Pretreatment with boldine protected the renal function at both boldine doses by fixing the renal damage markers, oxidative stress, caspase-3 and iNOS expression. Histopathological findings supported biochemical findings. Taken together these findings indicate that boldine has promising protective effect against cisplatin nephrotoxicity by improving oxidative stress, inflammation, histopathological alterations and by alleviating caspase 3 expression.

Histological, ultrastructural, and biochemical studies on the expected role of thyme oil on ameliorating renal toxicity induced by doxorubicin in female albino rats

Doxorubicin is antibiotics anticancer drug which proved to be useful in treatment of cancer, but it has bad effect on healthy body organs. Thymus vulgaris (thyme) cultivated around the world for cosmetic, cooking, and medical uses. So, the present work aims to investigate the possible ameliorating effect of thyme oil on renal toxicity induced by doxorubicin. Adult female albino rats (Rattus norvegicus) were randomly divided into four groups (5 rats/group): control group, thyme group received orally 0.5 mL thyme oil/kg body weight once/week for 6 consecutive weeks, doxorubicin group received intraperitoneally 2 mg doxorubicin/kg body weight once/week for 6 consecutive weeks, and doxorubicin + thyme group received both doxorubicin and thyme oil once/week for 6 consecutive weeks. A significant rising in urea and creatinine level in the sera of rats injected with doxorubicin was recorded. Moreover, their kidney sections showed degenerated, vacuolated and little hemorrhage glomeruli, abnormal renal tubular cells, aggregation of mononuclear leucocytes and hyaline cast. Ultrastructure examination showed degenerated glomerular endothelial, untypical filtrating barrier, degenerated podocyte, mesangial cell, pathological proximal and distal tubular cell with damage microvilli. Treating rats with thyme oil after doxorubicin decreases the elevated levels of urea and creatinine. The glomeruli, Podocyte, intraglomerular mesangial cells and glomerular filtration barrier approximately restored its typical structure, the winding in Bouma’s space is disappeared. Most tubular cells have normal nuclei and cytoplasm. Thyme oil can improve renal functions, histological and ultrastructural changes induced by doxorubicin. So, it can be used to decrease its side effect on kidney. Keywords: Doxorubicin, Histology, Ultrastructure, Thyme oil, urea, creatinine.

Therapeutic management of cystitis ascending to acute renal failure in a dog- a case report

A thirteen-year-old spayed female Doberman with a history of incontinence urination, blood at the end of urine stream for about three months. Clinical examination showed normal vital parameters with abnormal urine. Haemogram and serum biochemistry revealed severe anemia, neutrophilia, lymphocytopenia, thrombocytopenia, and elevated Blood Urea Nitrogen and creatinine level, respectively. Ultrasonographic examination revealed thickened bladder wall indicating severe cystitis. The pale yellow, cloudy urine sample and urinary sediments revealed numerous neutrophils, lymphocytes, and epithelial cells. The urine sample was subjected to culture, and an anti-microbial susceptibility test showed the presence of a gram-negative coccobacillus organism. The organism in the urine sample was sensitive to ciprofloxacin, norfloxacin, and chloramphenicol while intermediately sensitive to cefotaxime and amikacin. The animal was diagnosed with cystitis with acute renal failure and was treated with ciprofloxacin, nephrotec, citralka, and advised to feed a special homemade renal diet. The dog has recovered with the given therapy, and renal values were also reduced.

Perioperative Serum Creatinine Change and Delayed Urologic Complications Following Total Laparoscopic Hysterectomy for Benign Indications.

Objectives:The objective of the study was to investigate the association between perioperative serum creatinine change and delayed urologic complications following total laparoscopic hysterectomy (TLH) for benign indications.Materials and Methods:A total of 510 cases (503 cases without delayed urologic injuries and 7 cases with delayed urologic injuries) in which TLH was performed for benign indications were retrospectively reviewed. The patient characteristics and surgical outcomes were compared between patients with and without delayed urologic injuries. Laboratory markers (serum creatinine level at the preoperative and postoperative periods, white blood cell [WBC] ratio, and C-reactive protein [CRP] ratio) were analyzed to evaluate the diagnostic value of these laboratory markers.Results:There were no statistically significant differences in age, parity, body mass index, the presence of diabetes mellitus, preoperative GnRH agonist use, previous history of abdominal surgery or the performance of adnexal surgery, ASRM score, the presence of cul-de-sac obliteration, operative time, blood loss or weight of the resected specimens between the two groups. The proportions of patients who showed an elevated creatinine level on postoperative day 1 was significantly higher in the delayed urologic injury group (9.9% vs. 57%, P < 0.001). The combination of the three laboratory markers yielded an area under the ROC curve value of 0.75 (95% confidence interval, 0.491–1) in the detection of delayed urologic injuries.Conclusion:A change in the serum creatine level over baseline after surgery may indicate the possibility of urologic injuries. The combination of creatinine change and other factors, such as WBC or CRP would be helpful for detecting urologic complications after TLH.

Catastrophic antiphospholipid syndrome presented with coronary thrombosis, renal impairment, and suspected diffuse alveolar hemorrhage treated with rituximab biosimilar (CT-P10)

Catastrophic antiphospholipid syndrome (CAPS) is a lethal disease that occurs suddenly and progresses to multi-organ failure. We present a case of CAPS successfully treated with the rituximab biosimilar CT-P10. A 38-year-old man was referred with a sustained fever and unexplained elevated creatinine levels. Cardiac arrest by ventricular fibrillation occurred upon arrival at the hospital. We diagnosed probable CAPS because of coronary thrombus, renal impairment, suspected diffuse alveolar hemorrhage, and positive anticardiolipin antibody immunoglobulin G. We performed percutaneous coronary intervention for the cardiac arrest, and treated him with extracorporeal membrane oxygenation, mechanical ventilation, and continuous renal replacement therapy. When CAPS was diagnosed, we administered CT-P10 after administering high-dose glucocorticoid. Our case suggests that the use of a rituximab biosimilar is economically efficient in the treatment of CAPS, as in other rheumatic diseases. The patient was cured without recurrence at the 2-year follow-up.