Renal Derangement Research Articles

Pharmacological inhibition of CK2 by silmitasertib mitigates sepsis-induced circulatory collapse, thus improving septic outcomes in mice

Casein kinase II (CK2) has recently emerged as a pivotal mediator in the propagation of inflammation across various diseases. Nevertheless, its role in the pathogenesis of sepsis remains unexplored. Here, we investigated the involvement of CK2 in sepsis progression and the potential beneficial effects of silmitasertib, a selective and potent CK2α inhibitor, currently under clinical trials for COVID-19 and cancer. Sepsis was induced by caecal ligation and puncture (CLP) in four-month-old C57BL/6OlaHsd mice. One hour after the CLP/Sham procedure, animals were assigned to receive silmitasertib (50 mg/kg/i.v.) or vehicle. Plasma/organs were collected at 24 h for analysis. A second set of experiments was performed for survival rate over 120 h. Septic mice developed multiorgan failure, including renal dysfunction due to hypoperfusion (reduced renal blood flow) and increased plasma levels of creatinine. Renal derangements were associated with local overactivation of CK2, and downstream activation of the NF-ĸB-iNOS-NO axis, paralleled by a systemic cytokine storm. Interestingly, all markers of injury/inflammation were mitigated following silmitasertib administration. Additionally, when compared to sham-operated mice, sepsis led to vascular hyporesponsiveness due to an aberrant systemic and local release of NO. Silmitasertib restored sepsis-induced vascular abnormalities. Overall, these pharmacological effects of silmitasertib significantly reduced sepsis mortality. Our findings reveal, for the first time, the potential benefits of a selective and potent CK2 inhibitor to counteract sepsis-induced hyperinflammatory storm, vasoplegia, and ultimately prolonging the survival of septic mice, thus suggesting a pivotal role of CK2 in sepsis and silmitasertib as a novel powerful pharmacological tool for drug repurposing in sepsis.

A Prospective Study to Evaluate the Use of Neutrophil-to-Lymphocyte Ratio as a Prognostic Marker for Severe Acute Cholecystitis

Abstract Context: Acute cholecystitis (AC) is one of the most common afflictions of the gastrointestinal system presenting to hospitals whose delayed diagnosis can lead to severe complications. Neutrophil-to-lymphocyte ratio (NLR) is a new and inexpensive predictor of severe AC that can be used as prognostic biomarker for the stratification of patients for appropriate management. Aims: The aims of the study are to determine the usefulness of the NLR as a prognostic marker and to find range that distinguishes between grades of AC and to compare NLR use with white blood cell, high sensitivity C-reactive protein, and radiological modalities in the diagnosis of severe AC. Settings and Design: This is a 1-year prospective observational study in tertiary care center. Subjects and Methods: Demographic data, investigations, and management of 110 patients diagnosed with AC were collected. Categorization in mild, moderate, or severe AC group was based on Tokyo guidelines and NLR was calculated as absolute neutrophil count/absolute lymphocyte count. Statistical Analysis Used: One-way analysis of variance. Results: Sixty-four were male and 46 were female. 23.64% had severe AC, 30.91% had moderate, and 45.45% had mild AC. Mean hospital stay and intensive care unit stay were more in severe cholecystitis group. Diabetes mellitus was commonly associated comorbidity in severe cholecystitis (35.48%). As per the study, NLR ranges <6.5 in mild, 6.5–10 in moderate, and >10 in severe AC (sensitivity of 97% and specificity of 88%). The cardiovascular system was most commonly affected in severe AC, followed by renal derangement. Conclusions: NLR has proved to be a prognostic marker to determine disease severity in patients with AC which will help in appropriate management and better patient outcome.

Evaluation of hematological and biochemical factors of hypertension during the induction chemotherapy for childhood acute lymphoblastic leukemia

Background: Acute lymphoblastic leukemia (ALL) is a prevalent childhood cancer, accounting for approximately 25% of all pediatric cancer cases. The incidence of hypertension in ALL patients is significantly higher compared to the general pediatric population, emphasizing the need for a better understanding and management of this condition. The aim of the study was to evaluate hematological and biochemical factors of hypertension during the induction of chemotherapy for childhood ALL. Methods: This prospective observational study was conducted in the Department of Pediatric Hematology and Oncology at BSMMU from July 2017 to June 2018. The study included 93 newly diagnosed cases of ALL in children aged 1 to 17.9 years, excluding those below 1 year and above 18 years, known cases of hypertension, patients with pre-existing hypertension before chemotherapy, and old or relapse cases of ALL. Results: The study found that 17.2% of the study population experienced renal derangement during the induction remission phase, while the majority (82.8%) did not. The presence of renal derangement was not significantly associated with hypertension. However, patients who developed tumor lysis syndrome (TLS) had a higher percentage (12.5%) of hypertension compared to the non-hypertensive group (1.3%). Febrile neutropenia, convulsion, and coagulopathy were also observed in patients who developed hypertension more frequently. The median time to detect hypertension during induction chemotherapy was on day 8, with a mean duration of 13.6 days. Conclusions: In this study, hypertension is observed in 17.2% of patients during induction chemotherapy for ALL with higher frequency in the second week and associations with tumor lysis syndrome, febrile neutropenia, convulsion, and coagulopathy.

Characterization of multiple organ failure after ruptured abdominal aortic aneurysm repair

BackgroundMultiple organ failure (MOF) is associated with poor outcomes and increased mortality in sepsis and trauma. There are limited data regarding MOF in patients after ruptured abdominal aortic aneurysm (rAAA) repair. We aimed to identify the contemporary prevalence and characteristics of patients with rAAA with MOF. MethodsWe retrospectively reviewed patients with rAAA who underwent repair (2010-2020) at our multihospital institution. Patients who died within the first 2 days after repair were excluded. MOF was quantified by modified (excluding hepatic system) Denver, Sequential Organ Failure Assessment (SOFA) score, and Multiple Organ Dysfunction Score (MODS) for postoperative days 3 to 5 to determine the prevalence of MOF. MOF was defined as a Denver score of >3, dysfunction in two or more organ systems by SOFA score, or a MODS score of >8. Kaplan-Meier curves and log-rank testing were used to evaluate differences in 30-day mortality between multiple organ failure and patients without MOF. Logistic regression was used to assess predictors of MOF. ResultsOf 370 patients with rAAA, 288 survived past two days (mean age, 73±10.1 years; 76.7% male; 44.1% open repair), and 143 had data for MOF calculation recorded. From postoperative days 3 to 5, 41 (14.24%) had MOF by Denver, 26 (9.03%) by SOFA, and 39 (13.54%) by MODS criteria. Among these scoring systems, pulmonary and neurological systems were impacted most commonly. Among patients with MOF, pulmonary derangement occurred in 65.9% (Denver), 57.7% (SOFA), and 56.4% (MODS). Similarly, neurological derangement occurred in 92.3% (SOFA) and 89.7% (MODS), but renal derangement occurred in 26.8% (Denver), 23.1% (SOFA), and 10.3% (MODS). MOF by all three scoring systems was associated with increased 30-day mortality (Denver: 11.3% vs 41.5% [P < .01]; DOFA: 12.6% vs 46.2% [P < .01]; MODS: 12.5% vs 35.9% [P < .01]), as was MOF by any criteria (10.8% vs 35.7 %; P < .01). Patients with MOF were more likely to have a higher body mass index (55.9±26.6 vs 49.0±15.0; P = .011) and to have had a preoperative stroke (17.9% vs 6.0%; P = .016). Patients with MOF were less likely to have undergone endovascular repair (30.4% vs 62.1%; P < .001). Endovascular repair was protective against MOF (any criteria) on multivariate analysis (odds ratio, 0.23; 95% confidence interval, 0.08-0.64; P = .019) after adjusting for age, gender, and presenting systolic blood pressure. ConclusionsMOF occurred in only 9% to 14% of patients after rAAA repair, but was associated with a three-fold increase in mortality. Endovascular repair was associated with a reduced MOF incidence.

Obesity, Preserved Ejection Fraction Heart Failure, and Left Ventricular Remodeling.

Owing to the overwhelming obesity epidemic, preserved ejection fraction heart failure commonly ensues in patients with severe obesity and the obese phenotype of preserved ejection fraction heart failure is now commonplace in clinical practice. Severe obesity and preserved ejection fraction heart failure share congruent cardiovascular, immune, and renal derangements that make it difficult to ascertain whether the obese phenotype of preserved ejection fraction heart failure is the convergence of two highly prevalent conditions or severe obesity enables the development and progression of the syndrome of preserved ejection fraction heart failure. Nevertheless, the obese phenotype of preserved ejection fraction heart failure provides a unique opportunity to assess whether sustained and sizeable loss of excess body weight via metabolic bariatric surgery reverses the concentric left ventricular remodeling that patients with preserved ejection fraction heart failure commonly display.

Hepatik Ensefalopati Tip C Hastalarında Tetikleyici Faktörler ve Kliniko-Endoskopik Çalışma

Introduction: Hepatic encephalopathy (HE) is a decline in brain function as a result of severe liver disease and its inadequacy to remove toxins from the body. It is characterized by personality changes, intellectual impairment, and loss of consciousness. This study was conducted to determine the precipitating factors and endoscopic features of hepatic encephalopathy in patients with liver cirrhosis and evaluate the associated clinical features admitted in a tertiary hospital in Central India. Materials and Methods: This hospital-based descriptive cross-sectional study was conducted from November 2016 to October 2018 on 102 patients with hepatic encephalopathy type C, aged above 18. All patients were carefully examined, relevant investigations performed, and data collected through pre-designed proforma. They were sent for statistical analysis where categorical outcomes were compared between study groups using the Chi-square test /Fisher's Exact test. Results: The prevalence of HE was 19.6% in our study. In this study, we observed that constipation (26.5%), electrolyte imbalance (21.6%), renal failure (18.6%), and upper GI bleeding (18.6%) be among the leading precipitants for HE. Besides liver failure, the associated abnormalities in various factors like coagulation abnormalities, renal derangement, and changes in serum sodium levels can lead to the progression of HE to higher grades. Conclusion: It is essential to identify the different factors like constipation, electrolyte imbalance, renal failure, and upper GI bleeding early in the course of cirrhosis to help prevent the development of HE.

Protection Against Post-resuscitation Acute Kidney Injury by N-Acetylcysteine via Activation of the Nrf2/HO-1 Pathway.

Background and ObjectiveAcute kidney injury (AKI), the common complication after cardiopulmonary resuscitation (CPR), seriously affects the prognosis of cardiac arrest (CA) patients. However, there are limited studies on post-resuscitation AKI. In addition, it has been demonstrated that N-acetylcysteine (N-AC) as an ROS scavenger, has multiorgan-protective effects on systemic and regional ischaemia-reperfusion injuries. However, no studies have reported its protective effects against post-resuscitation AKI and potential mechanisms. This study aimed to clarify the protective effects of N-AC on post-resuscitation AKI and investigate whether its potential mechanism was mediated by activating Nrf-2/HO-1 pathway in the kidney.MethodsWe established cardiac arrest models in rats. All animals were divided into four groups: the sham, control, N-AC, and ZnPP groups. Animals in each group except for the ZnPP group were assigned into two subgroups based on the survival time: 6 and 48 h. The rats in the control, N-AC, and ZnPP groups underwent induction of ventricular fibrillation (VF), 8 min untreated VF and cardiopulmonary resuscitation. Renal function indicators, were detected using commercial kits. Renal pathologic changes were assessed by haematoxylin–eosin (HE) staining. Oxidative stress and inflammatory responses were measured using the corresponding indicators. Apoptosis was evaluated using terminal uridine nick-end labeling (TUNEL) staining, and expression of proteins associated with apoptosis and the Nrf-2/HO-1 pathway was measured by western blotting.ResultsN-AC inhibited post-resuscitation AKI. We observed that N-AC reduced the levels of biomarkers of renal function derangement; improved renal pathological changes; and suppressed apoptosis, oxidative stress, and inflammatory response. Additionally, the production of ROS in the kidneys markedly decreased by N-AC. More importantly, compared with the control group, N-AC further upregulated the expression of nuclear Nrf2 and endogenous HO-1 in N-AC group. However, N-AC-determined protective effects on post-resuscitation AKI were markedly reversed after pretreatment of the HO-1 inhibitor zinc protoporphyrin (ZnPP).ConclusionsN-AC alleviated renal dysfunction and prolonged survival in animal models of CA. N-AC partially exerts beneficial renal protection via activation of the Nrf-2/HO-1 pathway. Altogether, all these findings indicated that N-AC as a common clinical agent, may have the potentially clinical utility to improve patients the outcomes in cardiac arrest.

Hyperglycemia on Admission Predicts Acute Kidney Failure and Renal Functional Recovery among Inpatients.

Background: Hyperglycemia is associated with adverse outcomes in hospitalized patients. We aimed to assess the impact of glucose levels upon admission on the subsequent deterioration or improvement of kidney function in inpatients with a focus on diabetes or reduced baseline kidney function as possible modifiers of this effect. Methods: Running a retrospective cohort analysis, we compared patients with normal vs. high glucose levels upon admission. We applied multivariable logistic regression models to study the association between baseline glucose levels with subsequent renal and clinical outcomes. Interaction terms were used to study a possible modifier effect of diabetes. Results: Among 95,556 inpatients (52% males, mean age 61 years), 15,675 (16.5%) had plasma glucose higher than 180 mg/dL, and 72% of them were diabetics. Patients with higher glucose at presentation were older, with a higher proportion of co-morbid conditions. Rates of acute kidney injury (AKI), acute kidney functional recovery (AKR), and mortality were proportional to reduced renal function. AKI, AKR, and mortality were almost doubled in patients with high baseline glucose upon admission. Multivariable analysis with interaction terms demonstrated an increasing adjusted probability of all events as glucose increased, yet this association was observed principally in non-diabetic patients. Conclusions: Hyperglycemia is associated with AKI, AKR, and mortality in non-diabetic inpatients in proportion to the severity of their acute illness. This association diminishes in diabetic patients, suggesting a possible impact of treatable and easily reversible renal derangement in this population.

Frequency of deranged renal profile in patients with COVID-19: Tertiary Care Experience from a developing country.

Coronavirus disease-2019 (COVID-19) is a global pandemic, also affecting Pakistan with its first case reported on February 26, 2020. Since then, it has been declared a pandemic by the World Health Organization. Our study aimed to evaluate the renal derangements associated with COVID-19 infection in our population. A retrospective, observational study was conducted to include all the admitted patients having COVID-19 positive, and evaluated those for derangements of renal function (n = 362). Out of the 362 patients, 229were admitted in the ward, 133 were in intensive care unit (ICU), 258 of them recovered, while 104 deaths reported. At admission, the renal profile was deranged in almost one-half of ICU admissions and mortalities which increased to two-third during the hospital stay, with around 80% of deaths reported with increased urea and creatinine levels. Among the deceased patients, around one-third of the mortalities developed renal profile derangements during the hospital stay although they were admitted with a normal renal profile. An estimated glomerular filtration rate showed a mean increase of 13.37 mL/min/1.73 m2 during the hospital stay of surviving patients, while a decline of 19.92 in nonsurviving patients. A hazard ratio of 3.293 (P <0.001) for admitting serum urea and 3.795 (P = 0.009) at discharge and for serum creatinine at 5.392 (P <0.001) on discharge was associated significantly with mortality. Kaplan-Meier plot showed a significant decline in days of survival with deranged urea and creatinine (P <0.001). The deranged renal function in COVID-19 patients is associated with an increased number of ICU admissions as well as mortalities.

Simulation of hemo- and biochemical toxicities associated with chronic inhalation exposure to 2,2-Dichlorovinyl dimethyl phosphate (DDVP) in Wistar rat

DDVP is a commonly used pesticide in Nigeria and those involved with DDVP manufacturing, packaging or utilizing facilities seldom use PPE to limit pesticide exposure. The study aim was to determine the impact of chronic exposure to DDVP by monitoring hematological and biochemical changes in Wistar rats. Male rats (n = 60; 150−180 g) were exposed to graded DDVP concentrations (0%, 20 %, 40 %, 60 %, 80 % and 100 %) via inhalation route for 60 days. Body weights were initially measured and then at 20-day intervals. Blood samples were collected for hematology and serum biochemistry on day 61. Results showed significant (p < 0.05) polycythemia, neutrophilia, thrombocytosis, hepatic and renal derangement in rats exposed to DDVP. Also, albumin, AST, ALP, creatinine, blood urea nitrogen, bilirubin levels and dyslipidemia significantly increased. Cholinergic signs and stunted growth were observed in higher concentrations. Study emphasized hazards of DDVP mishandling and risks of non-compliance with PPE use by workers in-contact with DDVP, as well as misuse/abuse in animals.

The Effects of Chronic Low Dose Exposure of Chlorpyrifos on the Rat Kidney

Introduction: An increased incidence of chronic kidney disease (CKD) was reported among agricultural workers who were exposed to organophosphates (OP). There is little information on the effects of chronic low OP exposure on kidney in experimental animals. Chlorpyrifos (CPF) is a common type of OP used in agriculture. Thus, the aim of this study was to assess the effects of chronic low subcutaneous exposure of CPF on the kidney. Methods. Eighteen male Sprague Dawley rats were divided into three groups, with six rats in each group. Group 1 served as a control group, and groups 2 and 3 received a subcutaneous vehicle (3% dimethyl sulfoxide + 97% v/v soy oil) or CPF (18.0 mg/kg) respectively, every other day for 180 days. Serum urea, creatinine, uric acid, cystatin C, electrolyte levels, acetylcholinesterase (AChE), and arylesterase (ArE) activities were measured. Histopathological changes in the kidney tissues were examined. Results. Urea, creatinine, uric acid, and cystatin C levels were significantly increased (p &lt; 0.05), while electrolytes were reduced (p &lt; 0.05) in the CPF-treated rats. Both AChE and ArE activities were depressed in the CPF group (p &lt; 0.01 and p &lt; 0.001, respectively). Diffuse necrosis of proximal tubules and glomerular hypercellularity were observed in the kidney in the CPF group. Conclusion. A chronic low dose of CPF via subcutaneous exposure caused considerable renal tubular necrosis and derangement of glomerular function. These findings suggest that chronic occupational OPs exposure can cause kidney damage.

Contrast Induced Nephropathy- A Single Centre Observational Study

Background: CIN is an important cause of morbidity and mortality post cardiac procedures. Renal derangement and diabetes being the most important risk factors. Multifactorial causation of the disorder led us to study the risk factors associated with CIN.&#x0D; Methods: All patients who underwent cardiac procedures between March 2019 and March 2020 were screened for CIN and included in the study. Out of the 3192 patients screened 99 patients were diagnosed with CIN. Parameters such as diabetes mellitus, hypertension, CKD, anemia, duration of hospital stay, cardiogenic shock, number of stents, amount and type of contrast, Ejection Fraction, creatinine clearance before and after the procedure, concomitant nephrotoxic drugs were also recorded. &#x0D; Results: Ninety-nine patients developed CIN amounting to 3% of the total procedures, 11% expired, 18% required dialysis, average creatinine clearance before the procedure was 53.15 ml/min/1.73 m2 and post procedure it was 29.16 ml/min/1.73 m2, 51.5% of cases had creatinine clearance prior to procedure &lt;60 ml/min/1.73 m2, 60.6% were diabetic, 81.8% were hypertensive, 30.3% were anaemic, 15% had heart failure, 33% required ventilatory assistance, average haemoglobin level was 11.83 mg/dl, 33% received iso-osmolar contrast and 45% had EF of 35% or less.&#x0D; Conclusions: CIN has a multifactorial causation most common being prior renal derangement and diabetes mellitus. This is one of a kind study in this part of country among cardiac patients. Newer biomarkers of kidney injury could also be studied in future.

Fibrates in Chronic Kidney Disease Patients: A Controversial Issue

Background: Fenofibrates were not previously known to affect renal function tests until some reports indicated that these drugs may lead to a decrease in renal function. Likewise, the nephrotoxic effect of fibrates remains to be vague and unclear. Guidelines regarding fenofibrate dosing in renal impairment vary internationally. Patients and methods: A prospective cohort study over 6 months with a total of 80 patients on fibrates divided into 2 groups, 40 of which received statins, and the other 40 continued on fibrates. All patients were subjected to full history, clinical examination, and complete baseline labs. The KFTs including serum creatinine and eGFR were measured at 0, 1, 2, and 6-months intervals and lipid profile at 0,3,6 months serially in both groups. Results: Out of the baseline values of KFTs, the statin group showed a significant decrease in all kidney function values including mean serum creatinine by (0.9mg/dL, P=0.001) and an increase in eGFR (8.9 mL/min/1.73 m2, P<0.001). Whilst in patients who continued to receive fibrates the KFTs continued to rise as serum creatinine showed a significant increase in their mean serum Cr levels (by 0.9 mg/dL or 20%, P=0.001), and a significant decrease in their mean eGFR values (by 8.2 mL/min/1.73 m2 or 20.55%, P<0.001). On the other hand, total and LDL Cholesterol were significantly lower in the statin group at all follow-up intervals. Also, triglycerides were significantly higher in the Statin group at the end of month-6 from baseline. Conclusion: In our study fibrates administration showed a short-term state of renal insufficiency. The long-term effects of fibrates versus variable renal derangement are yet to be identified.

Mitigating Perspectives of Asiatic Acid in the Renal Derangements of Streptozotocin-Nicotinamide Induced Diabetic Rats.

The present study was conducted to evaluate the mitigating effects of Asiatic Acid (AA), on the changes in carbohydrate metabolism, insulin signaling molecules and renal function markers in Streptozotocin (STZ)-Nicotinamide (NAD) induced diabetic rats. AA (20 mg/kg BW) was supplemented orally to the diabetic rats for 42 days. The levels of plasma glucose, Hemoglobin (Hb), glycosylated hemoglobin (HbA1c) insulin and renal function markers, carbohydrate metabolic enzymes in the kidney and insulin signaling molecules in skeletal muscle were measured. The administration of AA elicited a significant decrease in the levels of plasma glucose, insulin resistance, HbA1c, urea, uric acid, creatinine, glycogen, glycogen synthase, glucose-6- phosphatase, and fructose-1,6-bisphosphatase and a significant increase of body weight development, insulin, Hb, hexokinase, and glycogen phosphorylase and mRNA expressions of insulin signaling molecule like insulin receptor 1, insulin receptor 2 and glucose transporter-4 in the STZ-NAD induced diabetic rats. Further, the protective effect of AA was evidenced by its histological annotation of the kidney tissues. Hence, this study concluded that AA can protect against renal dysfunction by attenuating carbohydrate metabolic disorder and subsequently enhances glucose utilization and renal function in STZ-NAD-induced diabetic rats.

The Malaria-High Blood Pressure Hypothesis: Revisited.

Malaria etiologies with pathophysiological similarities to hypertension currently constitute a major subject of research. The malaria-high blood pressure hypothesis is strongly supported by observations of the increasing incidence of hypertension in malaria-endemic, low- and middle-income countries with poor socioeconomic conditions, particularly in sub-Saharan African countries. Malnutrition and low birth weight with persistent symptomatic malaria presentations in pregnancy correlate strongly with the development of preeclampsia, gestational hypertension and subsequent hypertension in adult life. Evidence suggest that the link between malaria infection and high blood pressure involves interactions between malaria parasites and erythrocytes, the inflammatory process, effects of the infection during pregnancy; effects on renal and vascular functions as well as effects in sickle cell disease. Possible mechanisms which provide justification for the malaria-high blood pressure hypothesis include the following: endothelial dysfunction (reduced nitric oxide (NO) levels), impaired release of local neurotransmitters and cytokines, decrease in vascular smooth muscle cell viability and/or alterations in cellular calcium signaling leading to enhanced vascular reactivity, remodeling, and cardiomyopathies, deranged homeostasis through dehydration, elevated intracellular mediators and proinflammatory cytokine responses, possible genetic regulations, activation of the renin-angiotensin-aldosterone system mechanisms and renal derangements, severe anemia and hemolysis, renal failure, and end organ damage. Two key mediators of the malaria-high blood pressure association are: endothelial dysfunction (reduced NO) and increased angiotensin-converting enzyme activity/angiotensin II levels. Sickle cell disease is associated with protection against malaria infection and reduced blood pressure. In this review, we present the state of knowledge about the malaria-blood pressure hypothesis and suggest insights for future studies.

Outcomes of locally advanced cervical cancer presenting with obstructive uropathy: An institutional audit.

There is paucity of outcome data of patients with cervical cancer presenting with malignant obstructive uropathy. The present retrospective study describes outcomes of patients with cervical cancer who presented with obstructive uropathy at the time of diagnosis and underwent urinary diversion with percutaneous nephrostomy (PCN) before/during treatment. Patients who underwent PCN from January 2010 to June 2015 were included. Intent of treatment (radical or palliative) was decided within multidisciplinary team depending on disease stage, Karnofsky performance status (KPS), and degree of renal derangement. Treatment and outcome details were retrieved from electronic records. Time to normalization of creatinine, feasibility of delivering planned treatment, and overall survival (OS) were determined. Impact of various prognostic factors on outcomes was determined using univariate or multivariate analysis. After PCN and double-J stenting, 50% were eligible for (chemo) radiation. All radically treated patients (26/52) received brachytherapy. The median EQD2 to point A was 78 Gy (72-84 Gy). The median OS was 10 (0.5-60) months. Patients who completed chemoradiation had median OS of 31 months. Those receiving radical radiation and palliative radiation had median OS of 11 and 6 months, respectively. On univariate analysis, smaller tumor size (p = 0.03), high KPS (P = 0.04), and radical intent of treatment (P = 0.05) predicted for OS. Patients presenting with obstructive uropathy have median OS less than a year despite urinary diversion. Select cohort with good performance status, small tumor size, and serum creatinine of ≤3 mg/dL may be selected for diversion procedures and potential radical treatment.

Evaluation of Extra Corporeal Membrane Oxygenation Support in Adult Cardio Respiratory Failure-An Observational Study.

Abstract Extracorporeal life support is a rescue therapy when mechanical ventilation is unable to maintain adequate tissue oxygenation in the setting of acute cardiac or respiratory failure. Outcome is influenced not only by factors independent of ECMO but also by the potential complications related to ECMO. The study is designed to understand the outcomes of Extracorporeal membrane oxygenation in the management of Acute Cardio Respiratory failure in adult population. The study is analytical and the data is prospectively collected from a local registry of ECMO patients and ICU clinical database. Further, clinical details were obtained from prospective review of patient medical records. The study period is from November 2013 and November 2015. A total of 30 patients were included in the study 36.7% were weaned off ECLS and 33.3% survived to hospital discharge. Incidence of Heparin Induced Thrombocytopenia was observed in 3 patients. 27 patients went into renal dysfunction. Both ICU duration (p-0.945) and duration of ECMO (0.736) support did not prove to be significant in predicting mortality. No cannula related vascular complications leading to limb ischemia or need for vascular repair were encountered in any patient. Mean number of blood transfusions required during ECMO support were 15.17 units. Infections acquired on ECMO support, p=0.052; 95% CI=0.007-1.707. Our results endorse the use of ECMO as a rescue therapy in adults, although there are some risks associated with a learning curve as well as an important increase in the days of patient stay. However, ECMO is still marred by frequent and significant complications such as renal derangement, bleeding and nosocomial infections.

Biochemical and Histological Changes Associated with Azo Food Dye (Tartrazine) in Male Albino Rats

Aim: To study the effect of chronic exposure of tartarzine at ADI doses on some biochemical parameters of male albino rats.&#x0D; Study Design: The design involved chronic study. In the study, the experiment was divided into phase 1, 2, and 3 which lasted for 30, 60 and 90 days respectively. In each phase, 40 rats were used and were divided into treatment and control groups. The treated groups were given 7.5 mg/kg of tartrazine orally on daily basis over the stipulated periods while the control groups were not treated with tartrazine.&#x0D; Place and Duration of Study: The study was carried out in the Department of Medical Laboratory Science, Rivers State University, Port Harcourt, Nigeria within a period of 12 months (December 2017 – December 2018).&#x0D; Methodology: At the end of the chronic study, 5mls of whole blood specimens was collected by means of cardiac puncture into Lithium Heparin bottles and fluoride oxalate bottles (for glucose only). The collected specimens were spun, plasma collected and analyzed for glucose, Lipase, AST, ALT, ALP, total protein, albumin and globulin. Renal, hepatic, and pancreatic tissues collected were fixed in 10% formol saline and later examined histologically using H&amp;E stain. Statistical analysis was performed using GraphPad Prism version 5.03 (San Diego, California, USA).&#x0D; Results: In the chronic treatment, glucose indicated significant increases after 30, 60, and 90 days of chronic treatment at ADI doses. Urea, AST, and ALT showed significantly higher values after 60 of treatment while creatinine, ALP, total protein, albumin and globulin indicated significantly higher values after 90 days of treatment. However, lipase did not show any significant difference after 30, 60, and 90 days of treatment. Histologically, hepatic distortions such as fatty degeneration, vacuolation, pcynosis, and compression of central vein were seen in the liver section. In the renal section, hyaline cast in proximal tubules, hypercellularity of messengial cells, and inflammation of the glomerulus were observed in the treated rats while the histology of the pancreas indicated mild vacuolation of the islet region. However, the pancreatic ducts and acinar cells were not distorted.&#x0D; Conclusion: The administration of tartrazine over a period of 30 days at ADI dose did not indicate hepatocellullar and renal derangements as well histological distortions in liver, pancreas and kidneys. However, after 60 and 90 days, mild hepatocellular, pancreatic, and renal derangements were seen.

Cardiovascular risk prediction in the elderly.

Heart failure (HF) in the elderly, besides being a leading cause of mortality and morbidity, is rapidly increasing in prevalence with patients aged 65 and older accounting for more than 75% of heart failure hospitalizations. Elderly patients have historically been unrepresented in clinical HF trials and often present with multiple comorbidities, including frailty, depression, nutritional, functional and cognitive impairments. Additionally, pharmacologic challenges such as adherence to therapy, polypharmacy, altered drug pharmacokinetics and/or renal derangements make them less likely to receive guideline-directed medical therapies for HF. Recognition of these various interrelated domains is key and should prompt a multidisciplinary, holistic management approach so as to optimize prognosis in this vulnerable subset of the population.

Bilateral renal denervation does not prevent the kidney damage caused by a high fat diet in rats

One of the hallmarks of the metabolic syndrome (MS) is the increase of renal sympathetic nerve activity (RSNA), which leads to the upregulation of the renin‐angiotensin system (RAS). Interestingly, the sympathetic hyperactivity in the kidney of obese humans often occurs in absence of overt systemic hypertension. The stimulation of RSNA contributes to the glomerular lesions and the progressive loss of nephron functionality, resulting in acute renal injury (AKI) and, in the long term, chronic kidney disease (CKD), which represent the most common complication of MS. Clinical evidence and animal models of MS have shown that renal sympathetic denervation (RSDN) induces a transient attenuation of the hypertensive symptoms, while the markers of kidney damage continue worsening. Therefore, it is likely that the renal derangement in MS might also depend on the metabolic impairment, such as the upregulation of plasma leptin and insulin, independently from the RSNA. To investigate this issue, we explored the effect of MS over blood pressure and kidney functionality, in intact and renal denervated rats. For that, animals were either fed with a standard diet (SD) or a high‐fat diet for 12 weeks (HFD), with or without bilateral renal denervation performed at the beginning of protocol (n = 6). Results indicate that, as expected, HFD in intact animals promotes fat accumulation, glucose intolerance and hypertension, but also decreases water consumption and induces marked proteinuria from week 7, slight hematuria from week 9, with respect to SD rats. Remarkably, the renal denervation prevents the changes that HFD triggered in blood pressure and renal parameters only in the short and medium term, but it is ineffective in the long term. On the bases of these results, we suggest that the hypertension associated to MS is not only due to hyperactivation of RSNA, but it could involve hormonal/hemodynamic factors, typical of metabolic impairment, which could contribute to renal injury.Support or Funding InformationCONACYT‐CB‐243298This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.