Urea Creatinine Research Articles

P0448CHARACTERISTICS OF PRIMARY GLOMERULAR DISEASE PATIENTS WITH HEMATURIA IN TURKEY: THE DATA FROM TSN-GOLD WORKING GROUP

Abstract Background and Aims Hematuria is one of the most common laboratory findings in nephrology practice. In different regions of the world, the etiologic causes differ. To date, there is no enough data regarding the clinical and histopathologic characteristics of primary glomerular diseases (PGD) patients with hematuria in our country. Method Data were obtained from national multicenter (47 centers) data entered into the Turkish Society of Nephrology Glomerular Diseases (TSN-GOLD) database between May 2009 and June 2019. The data of all PGD patients over the age of 16 years who were diagnosed with renal biopsy and had hematuria data were included in the study. The biopsy samples were processed using a light microscopy and immunofluorescence examination. Demographic characteristics such as age, sex, indications for biopsy, primary glomerular diseases, comorbidities, laboratory and biopsy findings of all patients were also recorded. Hematuria was defined as the presence of at least 5 red blood cells/hpf. Results Data of 3394 patients were included to the study after the exclusion of patients with secondary glomerulonephritis and patients with missing biopsy findings. While 1699 (50.1%) patients had hematuria, 1695 (49.9%) patients did not have hematuria. Demographic, laboratory, and histopathological characteristics of patients with and without hematuria are given in Table. Patients with hematuria had statistically higher systolic blood pressure (SBP), serum blood urea nitrogen, creatinine, albumin, levels and urine pyuria, however, these patients had statistically lower age, body mass index, presence of hypertension and diabetes, eGFR, 24-hour proteinuria, serum total, HDL and LDL-cholesterol and C3 levels when compared with patients without hematuria. Figure depicted the etiologic causes of patients with and without hematuria. According to histopathological findings, number of global sclerotic glomeruli, cellular and fibrocellular crescents, the levels of mesangial proliferation, endocapillary proliferation, exudative changes in glomeruli, severe tubular atrophy, interstitial inflammation, subendothelial deposition, moderate and severe IgA and C3 deposition were found to be significantly higher and the levels of basal membrane thickening, interstitial fibrosis, subepithelial deposition, severe IgG staining were found to be significantly lower in patients with hematuria. Conclusion This is the first multicenter national report regarding the demographic and histopathologic data of PGD patients with or without hematuria. Hematuria, a feature of nephritic syndrome, was found at a higher than expected in the PGDs presenting with nephrotic syndrome in our national database.

P1154EFFECTS OF SHORT-TERM HEMODIALYSIS WITH CENTRAL VENOUS CATHETER(HD-CVC) ON PATIENTS WITH URGENT-START PERITONEAL DIALYSIS(USPD)

Abstract Background and Aims Urgent-start peritoneal dialysis (USPD) has gained increasing worldwide attention. Studies have suggested that USPD has many advantages concerning the early complications, survival rates and medical expenses. Due to the lack of pre-dialysis education, most patients newly diagnosed with ESRD in China have less knowledge about the dialysis methods, whether HD or PD. So, some patients choose to receive the short-term hemodialysis with central venous catheter (HD-CVC) before USPD. Whether the HD-CVC affected USPD, and whether it was necessary for ESRD patients without indications of emergency dialysis to undergo HD-CVC transition before USPD, were addressed. So we investigate the effects of the HD-CVC on urgent-start peritoneal dialysis. Method Retrospective analysis was performed on patients who received USPD from August 2008 to March 2017 in the first affiliated hospital of Xi'an Jiaotong University. According to whether hemodialysis and central venous catheterization were performed before PD, these patients were divided into two groups: USPD group (HD-CVC was not performed before PD) and HD-PD group (HD-CVC was given after admission, and then the PD catheterization was performed within 2 weeks ). The follow-up time was 1 year. The differences in clinical biochemical indexes, dialysis dose, urine volume, residual renal function, dialysis adequacy, peritoneal dialysis complications and technical survival rate between the two groups were observed. Results 1.A total of 482 patients were enrolled in this study, including 315 in the USPD group (average age 48.56±14.92 years) and 167 in the HD-PD group (average age 48.87±14.49 years). The demographics and clinical biochemical indexes (including creatinine, glomerular filtration rate, and blood potassium before admission) were similar between the two groups, and the differences were not statistically significant(P>0.05).2. After PD for 1month, residual renal function, UKt/V and TKt/V in the USPD group were significantly higher than those in the HD-PD group, blood urea nitrogen and creatinine were significantly lower than those in the HD-PD group (USPD group: 4.41±4.0ml/min, 0.79±0.44, 2.17±1.39, 17.79±4.96mmol/L, 663.15±182.03umol/L; HD-PD group: 3.67±2.39ml/min, 0.64±0.42, 1.92±0.55, 19.08±8.21 mmol/L, 711.02±280.3umol/L), and the differences were statistically significant (P<0.05, respectively).After PD for 6months, the urine volume in the USPD group were significantly higher than those in the HD-PD group(USPD group:964.84±539.95ml/d; HD-PD group 794.39±569.17ml/d), and the difference was statistically significant (P=0.002). 3. During the whole follow-up period, the exit-site infection rate, peritonitis infection rate, mechanical complications and technical survival rate were similar between the two groups, with no statistically significant difference (P>0.05,respectively). Conclusion Hemodialysis with central venous catheter before USPD affected the residual renal function and dialysis adequacy. HD-CVC as a pretreatment is not recommended to the end-stage renal disease patients who required PD but without the indication of emergency dialysis.

P0866EVALUATION OF ERYPTOSIS IN PATIENTS WITH CHRONIC KIDNEY DISEASE

Abstract Background and Aims One of the many factors in the pathogenesis of renal anaemia, is eryptosis. The aim of this study is to evaluate eryptosis in patients with chronic renal disease stage 3-5 and 5 dialysis (5D). Method Patients with CKD who were monitored in our nephrology department were included in the study. The age range of the patient groups was 18-80 years and haemoglobin levels were <13 g / dl in men and <12 g / dl in women. As parameters of eryptosis, flow cytometric annexin V binding and intracellular calcium, and superoxide dismutase (SOD) activity with ELISA method were measured in 59 predialysis patient (eGFR<60 mL / min 1.73 m2), 26 haemodialysis patient, 21 peritoneal dialysis patient and 29 healthy volunteers with similar age (control). Haematological and biochemical tests including complete blood count(CBC), erythrocyte sedimentation rate (ESR), Parathormone (PTH), 25-OH vit D3, Blood urea nitrogen (BUN), Creatinine (Cr), C-reactive protein (CRP), Na, K, phosphor (P), ionized and total Calcium, Ferritin, B12 and Folate, were performed. IBM SPSS Statistics Version 20.0 was used for statistical analysis of the data Results The amount of intracellular calcium were 3.05 ± 1.66 in predialysis group, 2.24 ± 0.99 in haemodialysis group, 2.38 ± 0.87 in peritoneal dialysis group and 1.71 ± 0.46 in control group. For intracellular calcium there was statistically significant difference only between predialysis group and control group (p <0. 000). Annexin V binding were calculated as 1.05 ± 0.99 in predialysis group, 1.15 ± 0.56 in haemodialysis group, 1.06 ± 0.87 in peritoneal dialysis group and 0.88 ± 0.86 in control group. Comparing to control group annexin V binding in predialysis, haemodialysis and peritoneal dialysis groups, were statistically significantly increased (for all p <0.000). SOD activity was 0.07 ± 0.07 in predialysis group, 0.13 ± 0.08 in haemodialysis group, 0.14 ± 0.07 in peritoneal dialysis group and 0.03 ± 0.01 in control group. The difference between the control group and dialysis group was statistically significant (p <0. 00). Comparing to nonusers; patients using calcium channel blockers (CCB) had low annexin V binding level (p = 0.013). Patients using erythropoietin (EPO) had elevated annexin V binding level (p <0.000) and lower intracellular calcium (p = 0.014) according to non- users. Conclusion We determined increased eryptosis in patients with CKD stage 3-5 and 5D in our study. Inflammation and elevated parathormone were also associated with increased eryptosis. Therefore, eryptosis may be an important factor in the pathogenesis of renal anaemia. Inflammation associated CKD may increase eryptosis. In addition, this effect can be taken into consideration in the planning of treatment because of the lower incidence of eryptosis in patients using calcium channel blocker and EPO.

P1278DIALYSIS IN TREATMENT OF CONGESTIVE HEART FAILURE

Abstract Background and Aims The advanced congestive heart failure (CHF), may provoke functional kidney disturbances with insufficient and resistant to conservative therapy water excretion. The treatment of the chronic renal failure (CRF) with active dialysis related to ultrafiltration (UF), may overcome the renal diuretics resistance with diuresis restoration and oedema elimination. The aim of the study was to define the indications for active, discontinued UF in setting of the CHF refractory to drugs, especially in the treatment of oedema. Method We investigated 12 patients, mean age 62,4+/-5,3 years, with incipient renal failure, but advanced congestive heart failure. Seven of them were males and 5 females. The indication for discontinued UF, was the severe expressed heart failure, reduced diuresis and initial renal insufficiency. In all investigated patients, before and after each UF procedure, the serum sodium and potassium, blood urea nitrogen (BUN), creatinin and osmolality were detected. The body weight, abdominal and crural parameters were noted before and after dialysis. Results The recovery was achieved in 10 patients with CHF, but 2 patients out of 12 have not demonstrated satisfactory response to UF. The biochemical features encountered to CHF patients suggest chronic hyponatriemia, hypokalemia and hypovolemia. Proteinuria range 1,2 to 3,6 g/l, was present in 6 patients. The clinical data were performed with oedema formation, reduced diuresis and dispnea. Mean UF rate achieved after several dialysis was 12,4+/- 7,6, lit. Conclusion Chronic heart failure in chronic renal patients, with severe oedemas is an indication for UF therapy, even if the values of BUN and creatinin are not increased. Reduction of the body weight and the extracellular volume, contribute for improved survival in these patients. However the risk of complications is high and not always with successful treatment.

Study of impact of haemodialysis on chronic kidney disease patients in pre and post haemodialysis periods

Chronic kidney disease (CKD) is progressive loss of renal functions. The degree of renal functions impairment correlates with the severity of renal failure. Hence patient needs renal replacement therapy. Haemo dialysis is one of the renal replacement therapy where in body’s waste products including creatinine, urea and excess water are removed. To study impact of haemodialysis on CKD patients in pre and post heamodialysis periods. This prospective study was conducted on 91 CKD patients from Jan 2017 to June 2019 in the department of Pathology and Nephrology, District hospital Vijayapur. All 91 patients renal functions were studied in pre haemodialysis period (before the first cycle of haemodialysis) and post haemodialysis period (After the last haemodialysis cycle after two half year). Regular follow up of these patients done during study period (Two and half years). Renal functions tests of these patients were assessed by testing the blood urea and serum creatinine and measuring urine outflow levels of each individual by using standard techniques in pre haemodialysis period then comparing those parameters with post haemodialysis period. Improved CKD patients and deaths of CKD patients. Acute Kidney disease patients. All 91(100%) patients renal function tests in pre haemodialysis period were highly impaired. 57 (62.6%) patients were having and high blood urea (150 -20 0 mg/ dl), high serum creatinine (11.1 -14 mg/ dl) and low levels urinary flow (ranging 200 -400 ml / 24 hours). 21 (23.1%) patients were ha ving high blood urea (100 -150 mg/ dl), high serum creatinine (8.1 -11 mg/ dl) and low levels urinary flow (ranging 401 -800 ml / 24 hours). 13 (14.3%) patients were havin g high blood urea (50 -100 mg/ dl), high serum creatinine (5.1-8 mg/ dl) and low levels urinary flow (ranging 801 - 1200 ml / 24 hours).All 91(100%) patients in post haemodialysis period, renal function tests were done. It was found 55 (60.4 %) patients renal functions tests shows significant improvement with haemodialysis therapy. 32(41.7%) patients were showed improved blood urea (121-150 mg/dl), creatinine (7.1-9 mg/ dl) levels and urine outflow levels (400 -800 ml /24 hours). 11(12.1%) patients showed improved blood urea (91-120 mg/dl), creatinine (5.1 -7 mg/dl) and urine outflow levels (800 -1200 ml / 24 hours). 12(13.2%) patients showed improved blood urea(61 -90 mg/dl), creatinine (3.1-5 mg/dl) and increased urine outflow levels (1200 -1600 ml /24 hours).There was significant improvement in blood urea, serum creatinine and urine outflow levels in post haemodialysis period of 91 studied CKD patients when compared with pre haemodialysis period parameters.Major underlying cases for CKD were Chronic Glomerulonephritis in 62(68.1%) patients. There is improvement in renal functions after the haemodialysis therapy. Hence haemodialysis will play a significant role in improvement of renal functions in chronic kidney disease patients.

Predictable hematological markers associated with cognitive decline in valid rodent models of cognitive impairment

Endogenous (hyperglycemia) and exogenous (therapeutic, prophylactic, street drugs) factors can considerably contribute to cognitive impairment (CI). Currently, there are few invasive and/or noninvasive markers that correlate with CI and those that do exist require expensive or invasive techniques to predict and accurately measure the cognitive decline. Therefore, we sought to determine hematological markers as predictors of CI in two different chemically induced valid rodent models of CI (streptozotocin induced hyperglycemic model and chemotherapy [doxorubicin/cyclophosphamide] treated rodent model). Hematological markers were analyzed in the above rodent models of CI CI and compared to their respective control groups. There was a significant increase in creatinine kinase, lactate dehydrogenase and aspartate aminotransferase (AST) in the chemotherapy group. Blood urea nitrogen (BUN), alkaline phosphatase (ALP), bilirubin, creatinine and glucose levels were significantly increased in the streptozotocin group. Interestingly, triglycerides were significantly elevated in both the streptozotocin and chemotherapy groups. Previous studies with human subjects have shown a potential link between the increase in triglyceride levels and CI. Likewise, our data indicate a notable correlation with an increase in triglycerides to cognitive impairment in the rodent models. This suggests elevated levels of triglycerides could prove to be a potential noninvasive hematological marker for the increased risk of CI. Further studies are warranted to determine the causal relationship between elevated triglyceride levels and CI.

Nephrectomy Does not Exacerbate Cancellous Bone loss in Thalassemic Mice

Patients with β-thalassemia have an increased risk of developing chronic kidney disease which is associated with osteoporosis and periodontitis. The purpose of this study was to evaluate mandibular and femoral bone change in heterozygous β-globin knockout (BKO) mice following 5/6 nephrectomy (Nx). Female and male BKO mouse blood smears demonstrated microcytic hypochromic anemia. Serum urea nitrogen, creatinine, calcium, and phosphorus levels were not changed in BKO mice. Nx increased the serum levels of urea nitrogen in both wild type (WT) and BKO mice and the level was much higher in BKO males. Serum level of creatinine was increased in Nx WT but not BKO mice. However, serum calcium and phosphorus levels were not altered. Nx induced comparable renal fibrosis in BKO mice and WT controls. Bone loss was observed in mandibular cancellous bone but not cortical bone of both male and female BKO mice. Nx decreased cancellous bone volume and cortical thickness in WT. Interestingly, BKO mice were resistant to Nx-induced cancellous bone loss. However, cortical thickness and cortical bone mineral density were reduced in Nx male BKO mice. Nx increased mRNA levels of type I collagen, Osx and Trap in WT but not BKO mice. Similarly, Nx reduced cancellous bone volume in femurs and increased osteoblast number and osteoclast number in WT not BKO mice. Serum FGF23 and erythropoietin levels were markedly increased in BKO mice. Nx decreased serum erythropoietin but not FGF23 levels. Since WT treated with erythropoietin exhibited a significant reduction in cancellous bone volume, it was possible that lower level of erythropoietin in Nx BKO mice prevented the Nx-induced cancellous bone loss.

Myeloid-related protein complex 8/14 increases in hypertensive patients with excessive renal damage

Hypertension is a complex condition, and it is difficult to know whether inflammation is a cause or an effect. Information on the association between MRP-8/14 (myeloid-related protein) and hypertension is limited. In this study, we aimed to examine the relationship of MRP-8/14 with carotid intima-media thickness (CIMT) and albuminuria in hypertensive patients and to investigate whether early assay of MRP-8/14 levels could be helpful in assessment of renal damage and carotid atherosclerosis among hypertensive patients. 61 hypertensive patients and 40 age-, gender-, and body mass index-matched controls were included into the study. Blood samples including fasting blood glucose, total cholesterol, triglycerides, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total protein, albumin, urea creatinine, uric acid, sedimentation, C-reactive protein (CRP), and MRP-8/14 were collected. 24-hour urine albumin excretion and CIMT measurements were also obtained. All inflammatory variables including uric acid, CRP, sedimentation, MRP-8/14, and CIMT were statistically higher in patients with hypertension than in controls. MRP-8/14 was significantly higher in hypertensive patients with macroalbuminuria than in controls (339.3 (IQR (215.2-661.7)) ng/mL vs. 204.9 (IQR (140.1-339.3)) -ng/mL, p=0.005, respectively). The levels of CIMT were the highest in macroalbuminuric hypertensive patients (controls vs. normoalbuminuria, microalbuminuria, macroalbuminuria groups, 0.57 (0.53-0.67) mm vs. 0.84 (0.76-0.89) mm, p=0.000; 0.57 (0.53-0.67) mm vs. 0.87 (0.67-0.93) mm, p=0.000; 0.57 (0.53-0.67) mm vs. 0.92 (0.85-0.97) mm, p=0.000, respectively). Plasma MRP-8/14 levels were elevated in hypertensive patients with macroalbuminuria, however, it could not serve as an early marker to determine renal damage and carotid atherosclerosis in patients with hypertension. .

The incidence, risk factors, and clinical outcomes of rhabdomyolysis associated with fenoverine prescription: a retrospective study in South Korea (1999\u20132014)

BackgroundFenoverine is a spasmolytic drug that has been used to treat abdominal pain. Although sporadic case reports or case series of rhabdomyolysis associated with fenoverine have been published, there are no studies evaluating the incidence, risk factors, and clinical outcomes of rhabdomyolysis associated with fenoverine prescription.MethodsWe retrospectively reviewed the medical records of 22 patients admitted with rhabdomyolysis associated with fenoverine from January 1999 to December 2014, while excluding other well-known risk factors of rhabdomyolysis. This period was subdivided into two periods, January 1999–December 2007 and January 2008–December 2014. We analyzed the clinical and laboratory characteristics, and the prognosis of fenoverine associated with rhabdomyolysis for these times.ResultsThe incidence of rhabdomyolysis associated with fenoverine was 0.27% during the total period (22/8257), 0.34% in the first period (18/5298), and 0.14% in the second period (4/2959) (p < 0.001). Rhabdomyolysis occurred in 19 liver cirrhosis (LC) patients (2.03%), whereas only 3 cases (0.04%) occurred in non-LC patients (p < 0.001). Drug duration, total dose, muscle enzymes, and clinical characteristics were not different between the LC and non-LC groups. Acute renal failure (ARF) occurred in 5 patients in the LC group and 2 patients in the non-LC group (p = 0.227). Severity of hepatic derangement according to the Child-Pugh classification was not different between the ARF group and non-ARF group (p = 0.227). Four patients died, having complications of oliguric ARF (p = 0.005) and underlying severe LC (p = 0.017). Higher serum lactate dehydrogenase, blood urea nitrogen, creatinine, and potassium levels but lower serum sodium levels were found in the group that died (p = 0.001).ConclusionsPhysicians should carefully prescribe fenoverine because it may cause rhabdomyolysis, especially in patients with LC.

Efek Ekstrak Kunyit Putih (Curcuma Zedoaria) Sebagai Nefroprotektor Pada Tikus Putih Jantan Galur Wistar yang Diinduksi Tembaga

Latar belakang: Pencemaran logam berat meningkat seiring dengan meningkatnya perkembangan industri. Paparan tembaga dalam jumlah besar dapat menyebabkan kerusakan ginjal dan hati. Berdasarkan penelitian terdahulu rimpang kunyit putih (Curcuma zedoaria) memiliki manfaat diantaranya sebagai antioksidan, antiinflamasi, antiproliferasi, antikanker, dan antimikroba. Kurkumin yang terkandung dalam rimpang kunyit putih pada penelitian sebelumnya digunakan sebagai senyawa nefroprotektif.Tujuan: Penelitian ini bertujuan apakah rimpang kunyit putih (Curcuma zedoaria) memiliki efek nefroprotektif dengan paparan CuSO4 pentahidrat. Metode: Penelitian ini adalah penelitian eksperimental dengan rancangan the post test only control group design. Pengambilan sampel pada penelitian ini menggunakan teknik simple random sampling. Tikus putih jantan galur wistar dibagi menjadi enam kelompok; kontrol normal, kontrol kunyit putih (45 mg/ 200 g), kontrol CuSO4 pentahidrat, dan kelompok co-treatment (curcumin selama 14 hari diikuti CuSO4 selama 5 hari). Hasil: Data dianalisis menggunakan uji One Way Anova diikuti uji Post-Hoc LSD. Untuk Kelompok 4 (kelompok preventif) kadar ureum kreatinin serum tidak ada perbedaan yang bermakna dengan Kelompok 1 dan 2 (p &gt; 0,05) dengan kerusakan struktur histologis yang ringan. Namun, didapatkan perbedaan yang bermakna (p &lt; 0,05) pada Kelompok 3, 5, dan 6. Kesimpulan: Dosis ekstrak kunyit putih 45 mg/ 200 g menunjukkan adanya penurunan kadar ureum kreatinin serum dan kerusakan histologi jaringan ginjal yang ringan.

Gum arabic reduces inflammation, oxidative, and nitrosative stress in the gastrointestinal tract of mice with chronic kidney disease.

The aim of this study was to investigate some biochemical indices of inflammation and oxidative and nitrosative stresses in the gastrointestinal tract of mice with experimental chronic kidney disease (CKD) and treated with gum arabic (GA). Male CD1 mice (n = 28) were randomly distributed into four groups and treated for four consecutive weeks: group 1: Control: received the same diet without treatment until the end of the study; group 2: Adenine: switched to a powder diet containing adenine (0.2% w/w in feed); group 3: Gum acacia (GA): given normal feed and GA in drinking water at a concentration of 15% w/v; and group 4: Adenine + GA: given adenine in the feed as in the second group plus GA in the drinking water at concentration of 15% w/v. CKD was induced to mice by adenine feeding and concomitantly treated with the prebiotic dietary fiber gum acacia, GA (15% in drinking water). Duodenal mucosa from CKD mice had significantly higher concentrations of TNF-alfa, IL- 6, and TGF-beta-1 and lipid peroxidation. Moreover, low concentrations of IL-10, some antioxidants (catalase, glutathione reductase, total antioxidant capacity, and superoxide dismutase), and nuclear factor erythroid 2-related factor 2 were found in the duodenum. The levels of nitrosative stress (nitrite, nitrate, and total nitrate) were significantly increased by CKD, as well as the concentrations of ammonia and urea creatinine in the cecal content. Concomitant GA treatment significantly mitigated these harmful effects. Taken together, GA reduces inflammation and duodenal oxidative and nitrosative stress in the gastrointestinal tract of mice with CKD.

Effects of shenkang injection on renal angiogenesis in mice with unilateral ureteral obstruction

This study aimed to investigate effects of shenkang injection on angiogenesis in mice with renal fibrosis. C57BL/6J mice after unilateral ureteral obstruction were administrated with different doses of shenkang injection for two weeks. Losartan-administrated mice and Sham-operation mice were as positive and negative controls, respectively. Renal function and vasculature changes were observed, and expressions of VEGF and VEGFR2 were detected. Shenkang injection reduced serum levels of urea nitrogen, creatinine and cystatin C. Shenkang injection alleviated the loss of microvessels, decreased the deposition of collagen fibers, and increased expressions of VEGF and VEGFR2 in the obstructed kidney. These findings indicate that shenkang injection alleviates renal dysfunction and fibrotic changes in mice with renal fibrosis by regulating renal angiogenesis.&#x0D; Video Clip of Methodology:&#x0D; Renal Vasculature by Angiography: 6 min 41 sec: Full Screen Alternate

Abstract PD2-07: Prediction of CDK inhibitor efficacy in ER+/HER2- breast cancer using machine learning algorithms

Abstract Background: Three cyclin dependent kinase 4/6 inhibitors (CDKIs) are approved by the Food and Drug Administration (FDA) for the treatment of patients with hormone receptor (HR)-positive, human epidermal growth factor receptor 2 (HER2)-negative advanced or metastatic breast cancer in combination with hormonal therapy. However, the choice of when to initiate CDKI therapy (in the first- or second-line setting, or with aromatase inhibitor or fulvestrant) can be clinically challenging as studies have not directly compared these two approaches, nor have studies determined the benefit of continuation of CDKI therapy with changes in hormonal therapy backbone. Methods: Patient-level data from eight randomized controlled pivotal trials submitted to the FDA for new or supplemental marketing applications were pooled. We performed exploratory analyses of the predictive power of the baseline patient and disease characteristic data to forecast outcomes based on a specific treatment pathway. Variables included were: age, race, ethnicity, country and continent of origin, height, weight, body mass index (BMI), menopause status, estrogen receptor (ER) status, progesterone receptor (PR) status, ECOG performance score, histological type, histological grade, and initial disease stage. Additionally, baseline levels at the time of enrollment of alanine aminotransferase (ALT), albumin, alkaline phosphatase, aspartate aminotransferase (AST), bilirubin, blood urea nitrogen (BUN), calcium, creatinine, hemoglobin, magnesium, potassium, sodium, lymphocytes, neutrophils, platelets, and white blood cells. Statistical and machine learning algorithms were used to build predictive models based on the clinical trial results. Results: The pooled studies included 4580 breast cancer patients. Baseline random survival forest models were constructed for patients that received a CDKI plus hormonal therapy and for patients that received hormonal therapy alone. Preliminary findings for these models produced prediction accuracies of 69.2% for the CDKI model and 70.6% for the hormonal therapy alone model. Median predicted survival times for patients were calculated in both treatment scenarios and used to identify those that were more likely to benefit from initial use of CDKIs and those less likely to benefit. Through further analysis of the patients in each group, we identified patient characteristics that are prognostic of survival. Conclusions: This exploratory analysis utilized clinical trial data to create a model where clinical and disease characteristics are entered to come up with an efficacy prediction. Future efforts will extend this model to predict adverse event development. Citation Format: Jeremy Mason, Yutao Gong, Laleh Amiri-Kordestani, Suparna Wedam, Jennifer J Gao, Harpreet Singh, Richard Pazdur, Peter Kuhn, Gideon Blumenthal, Julia A Beaver. Prediction of CDK inhibitor efficacy in ER+/HER2- breast cancer using machine learning algorithms [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr PD2-07.

Ninety-Day Nephrotoxicity Evaluation of 3-MCPD 1-Monooleate and 1-Monostearate Exposures in Male Sprague Dawley Rats Using Proteomic Analysis.

Fatty acid esters of 3-monochloropropane 1,2-diol (3-MCPD esters) are processing-induced food toxicants, with the kidney as their major target organ. For the first time, this study treated Sprague Dawley (SD) rats with 3-MCPD 1-monooleate at 10 and 100 mg/kg BW/day and 1-monostearate at 15 and 150 mg/kg BW/day for 90 days and examined for their potential semi-long-term nephrotoxicity and the associated molecular mechanisms. No bodyweight difference was observed between groups during the study. Both 3-MCPD 1-monooleate and 1-monostearate resulted in a dose-dependent increase of serum urea creatinine, uric acid and urea nitrogen levels, and histological renal impairment. The proteomic analysis of the kidney samples showed that the 3-MCPD esters deregulated proteins involved in the pathways for ion transportation, apoptosis, the metabolism of xenobiotics, and enzymes related to endogenous biological metabolisms of carbohydrates, amino acids, nitrogen, lipids, fatty acids, and the tricarboxylic acid (TCA) cycle, providing partial explanation for the nephrotoxicity of 3-MCPD esters.

Antioxidant and anti-apoptotic effects of vitexilactone on cisplatin-induced nephrotoxicity in rats

ABSTRACTCisplatin (CP) is an antineoplastic drug; however, owing to its nephrotoxicity, its clinical use is limited. We investigated whether vitexilactone (vitex) is a safe and effective treatment for CP induced kidney injury. We allocated Sprague-Dawley rats into six groups: control group, low dose-high dose vitex groups (40 and 80 mg/kg vitex for 6 days before administration of CP), CP group (single 6 mg/kg dose on day 6) and CP + low dose vitex-CP + high dose vitex group (40 and 80 mg/kg vitex for 6 days, and a single 6 mg/kg dose of CP on day 6. Rats were euthanized 5 days after CP treatment. After exposure to CP and/or vitex, total oxidative stress and total antioxidant status were assessed. The histology of the kidney was examined using hematoxylin and eosin, and periodic acid-Schiff. We used immunohistochemical and fluorescence staining to detect expression of caspase-3. We also measured blood urea nitrogen, uric acid and creatinine levels. Nephroprotective effects of vitex were associated with decreased serum toxicity markers and increased antioxidant activity. Vitex also reduced the expression of the apoptosis marker, caspase-3. Treatment with CP increased blood urea nitrogen, uric acid, creatinine levels and total antioxidant status, and decreased total antioxidant status compared to the control group. Use of vitex for protection from CP induced nephrotoxicity appears to be a safe and efficacious alternative for treatment of kidney injury.

Streptomycin induced nephrotoxicity: Generation of free radicals and antioxidant effect of vitamin C

Introduction: Streptomycin is used in many conditions like tuberculosis, plague, tularemia and peritonitis. Kidney damage is one of the feared complications of streptomycin. Free radicals are implicated in many pathology including renal diseases. In vitro studies of aminoglycosides have demonstrated potential to generate free radicals. Aims: The study was aimed at exploring oxidative stress induced during kidney damage by streptomycin and benefit of antioxidant vitamin C. Materials and Methods: Total 28 Wistar male albino rats were used in the study were divided into 4 groups. In two groups saline i.m. 0.3 ml/day or vitamin C i.p.200 mcg/kg/day were given. In another two group Streptomycin 100 mg/kg/day i.m. was given either alone or along with vitamin C. Oxidative stress and generation of free radicals were measured by Serum total antioxidant status (TAS), glutathione peroxidase (GPx), glutathione reductase (GR), while blood urea and serum creatinine were measured for estimation of renal damage. Rat kidneys were examined for hisptopathology. Statistical analysis: The data was subjected to one way ANOVA with post hoc test of significance and the values of P Results: Administration of streptomycin led to significant fall in the values of TAS, GPx and GR while there was significant rise in the value of blood urea and s. creatinine. TAS level was elevated significantly in vitamin C treated group. When vitamin C was given along with streptomycin there was significant prevention of fall in GPx, GR and TAS while rise in blood urea and s. creatinine was prevented. Conclusions: Free radicals are generated during treatment with streptomycin leading to nephrotoxicity which was significantly prevented by coadministration of vitamin C. Keywords: Streptomycin, free radicals, Glutathione peroxidase, Glutathione reductase, Total antioxidant status, Nephrotoxicity.

Repeated administration of fluvoxamine worsens gentamicin-induced nephrotoxicity in rats

Background: Depression is one of the most prevalent and life-threatening forms of mental disorders in chronic kidney disease. Antidepressant agents such as fluvoxamine are broadly prescribed in this situation. This study investigated the effects of fluvoxamine on gentamicin (GEN)-induced nephrotoxicity in rats. Materials and Methods: Twenty-four male Wistar rats were randomly divided into four groups (n = 6) including (1) control group, (2) GEN group, (3) GEN + fluvoxamine (25 mg/kg) group, and (4) GEN + fluvoxamine (50 mg/kg) group. Fluvoxamine was orally given to animals 45 min before GEN was injected (100 mg/kg, intraperitoneally [i.p.]). Blood urea nitrogen (BUN), creatinine (Cr), sodium (Na+), potassium (K+), and malondialdehyde (MDA) levels in serum were measured. Moreover, the glucose (Glu) and protein (Pro) levels in urine and the ratio of kidney to body weight (g/100g body weight) were determined. Histopathological alterations in kidney were evaluated. Results: GEN significantly increased the Cr and BUN serum levels as well as urine Glu and Pro concentrations (P ≤ 0.001). Fluvoxamine exacerbated the elevation in the indicated parameters. GEN also significantly increased the serum MDA levels. Fluvoxamine had no effect on the elevated serum levels of MDA. GEN did not show any effect on the K+ and Na+ serum concentrations. Increased kidney-to-body weight ratio due to GEN nephrotoxicity was further exacerbated by 25 mg/kg of fluvoxamine (P ≤ 0.001). Pathologic findings also confirm the biochemical results. Conclusion: The data suggest that fluvoxamine worsens the nephrotoxicity of GEN. However, further clinical and animal investigations are required to elucidate the mechanism of this interaction.

Sequential development of pathology and pathogenesis of capsular serotype D of Pasteurella multocida of porcine origin in mouse model

To understand the mechanism of host-pathogen interaction during the progression of Pasteurella multocida capsular serotype D of porcine origin causing pneumonia/septicemia, 36 adult Swiss albino mice were intranasally inoculated with 25 μl of P. multocida serotype D@109 CFU/ml and sacrificed at 6, 12, 24, 48, 72 and 96 hours post inoculation. The infected mice showed varied clinical signs of depression, ruffled fur, ocular discharge, watery to mucoid nasal discharge with labored breathing pronounced during 24-48 HPI and declined thereafter. The leucocytosis, anaemia, low PCV, progressive neutrophilia with lymphocytopenia changes in these infected groups of mice paralleled with the clinical signs. The serum biochemical parameters such as total protein, blood urea nitrogen, creatinine, glucose, SGOT, SGPT and C-reactive protein were significantly increased. The higher level of LPO, lower level of antioxidant enzymes (CAT, SOD and GSH) and higher values of proinflammatory cytokine genes (TNF-α, IL-1β and IL-6) in lungs and spleen of the inoculated mice as compared to control mice suggest towards the establishment of pneumonia and sep-ticemia. The lesions of bronchopneumonia, splenitis, nephritis, hepatitis, enteritis and myocarditis along with the demonstration of bacterial antigens in lungs and spleen well correlated with severity of histopathological lesions at different time points. Apoptotic nuclei were detected in infiltrating leukocytes of the lungs and splenocytes on TUNEL staining. The inflammatory lesions as well as the apoptosis were highest during 24-48 HPI followed by gradual decrease till the end of the experiment. This is the first report on elucidating the pathogenesis of P. multocida capsular serotype D of porcine origin.

Effect of sleeve gastrectomy on renal oxidative stress in type 2 diabetic rats

Objective To investigate the changes of oxidative stress in kidney of type 2 diabetic rats after sleeve gastrectomy and its effect on renal function. Methods Twenty male SD rats were fed with high-fat diet and injected with streptozotocin intraperitoneally to induce type 2 diabetes mellitus. Seventeen successful induction models were divided into sham operation group (n=7) and sleeve gastrectomy (SG) group (n=10) by random number table method, and were treated with sham operation and SG respectively. The body weight, 24-hour food intake, fasting blood glucose (FBG)and serum glucagon-like peptide-1 (GLP-1) were measured before and 1, 2, 3 and 4 weeks after operation. The activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px) and malondialdehyde in renal tissue as well as blood urea nitrogen (BUN), creatinine levels and 24-hour urinary microalbumin (UALB) were measured 4 weeks after operation. Masurement data conforming to normal distribution were expressed as Mean±SD, and t-test was used for comparison between two groups. Results At the 1st, 2nd, 3rd, 4th weeks after operation, the levels of FBG in SG group was lower than those in sham operation group [(11.13±3.27) mmol/L vs (16.74±4.10) mmol/L, (9.53±2.82) mmol/L vs (19.31±3.66) mmol/L, (6.69±2.44) mmol/L vs (20.84±2.71) mmol/L, (6.58±2.96) mmol/L vs (19.99±2.85) mmol/L, all P<0.05]. In the same period, the levels of serum GLP-1 in SG group was higher than those in sham operation group [(22.61±2.92) pg/mL vs (15.42±2.39) pg/mL, (24.72±3.02) pg/mL vs (16.20±2.26) pg/mL, (24.59±2.85) pg/mL vs (15.84±2.75) pg/mL, (26.15±3.23) pg/mL vs (15.77±2.79) pg/mL, all P<0.05]. At the 4th week after operation, BUN[(5.34±0.82) mmol/L], creatinine[(39.78±6.13)]μmol/L, UALB[(31.18±6.88) mg/24 h] and renal creatinine[(5.84±0.85) nmol/mg] in SG group were lower than those in sham operation group [BUN (9.08±1.54) mmol/L, creatinine (64.07±8.63) μmol/L, UALB (67.64±9.07) mg/24 h, creatinine (10.78±1.28) nmol/mg], and the differences were statistically significant (all P<0.05). Renal SOD[(620.05±55.98) U/mg], CAT[(24.72±2.28) U/mg] and GSH-Px[(281.53±27.99) U] in SG Group were lower than those in sham operation group [SOD(392.52±45.97) U/mg, catalase (15.62±2.46) U/mg, GSH-Px (164.71±21.83) U], and the differences were statistically significant (all P<0.05). Conclusion Sleeve gastrectomy may improve renal function through reducing oxidative stress in the kidney. Key words: Diabetes mellitus, type 2; Diabetic nephropathies; Superoxides; Sleeve gastrectomy; Oxidative stress

The Effect of Gender on Brain Tissue Changes Induced by Renal Ischemia-Reperfusion Injury in Adult Rats

Background: Renal ischemia-reperfusion (RIR) is a common clinical injury that affects the function of other remote organs such as the brain by initiating a cascade of complex and wide-ranging inflammatory responses. RIR also follows a different course in men and women. Since there is little information on the effect of RIR on the brain as a sensitive organ in both males and females, the present research was performed to investigate the effect of gender on RIR-induced brain tissue alterations in adult rats. Materials and Methods: In this study, 28 Wistar rats (14 female and 14 male rats) weighing 200 ± 20 g were divided into the following groups: 1- male sham (MS), 2- female sham (FS), 3- male ischemia (MI) with 3-hour reperfusion (ISC3hr), and 4- Female ischemia (FI) with 3-hour reperfusion (ISC3hr). Bilateral renal ischemia was induced for 45 minutes and blood samples were taken after reperfusion for the measurements of serum blood urea nitrogen (BUN), creatinine (Cr), malondialdehyde (MDA), and nitrite levels. The left kidney was removed for evaluation of MDA and tissue nitrite levels. Right kidney and brain tissue underwent histological examination. Results: Serum BUN level increased in both genders. Serum nitrite level was significantly different between both genders, meaning that it was increased in the female rats as compared to male ones. Overall brain tissue damage was significantly increased in males compared to females. Conclusion: RIR has an effect on the function and tissue of kidney and brain in both genders. Female rats are more susceptible to the nitric oxide system than the male ones. This study showed that male brain tissue was more susceptible to RIR. Therefore, gender is one of the important factors that should be considered in clinical treatments.