Disturbances In Renal Function Research Articles

Comparison of the efficacy of aescin and diclofenac sodium in the management of postoperative sequelae and their effect on salivary Prostaglandin E2 and serum C–reactive protein levels after surgical removal of impacted mandibular third molar: a randomized, double-blind, controlled clinical trial.

Introduction Surgical removal of an impacted third molar is one of the most common oral surgical procedures performed in dental offices. The postoperative phase is often associated with severe inflammation. Non-steroidal anti-inflammatory drugs (NSAIDs) are usually prescribed to manage postoperative discomfort. NSAIDs have been associated with gastrointestinal bleeding, renal function disturbances, and platelet count reductions. Thus, the present study demonstrates the utility of aescin in managing postoperative discomfort after the surgical removal of impacted mandibular third molars. This study aimed to correlate salivary PGE2 levels and serum C-reactive protein levels with subjective and objective symptoms after surgical extraction of the mandibular third molar and their relationship with drug therapy. Methods The planned study is a single-center, double-blind, randomized, parallel, prospective clinical trial. Each patient will be prescribed either diclofenac sodium 150 mg/day or aescin (escin) 120 mg/day to be taken orally in divided doses for five days after surgically removing the impacted mandibular third molar. Pain will be assessed using a visual analog scale. Facial swelling and mouth opening will be recorded using a metric scale with standardized reference points. ELISA (enzyme-linked immunosorbent assay (ELISA) will be employed to measure salivary Prostaglandin E2 and serum C–reactive protein levels. All parameters will be recorded preoperatively (T0) on the second postoperative day (T1) and fifth postoperative day (T2). Conclusion The proposed study is expected to show a favorable response to the administration of aescin for the management of postoperative discomfort compared to diclofenac sodium after third molar surgery. The proposed study is expected to positively manipulate the levels of salivary Prostaglandin E2 and serum C–reactive protein, which are reliable inflammatory markers. The outcome of this study may provide an efficacious and safe alternative to conventional nonsteroidal anti-inflammatory drugs for managing postoperative discomfort following third molar surgery.

Effects of conditioned media derived from human Wharton’s jelly mesenchymal stem cells on diabetic nephropathy and hepatopathy via modulating TGF-β and apelin signaling pathways in male rats

BackgroundDiabetic nephropathy and hepatopathy are health problems described by specific renal and hepatic structure and function disturbances. The protective effects of the stem cell secretome have been shown in several kidney and liver diseases. The current study aims to evaluate the capability of conditioned media derived from human Wharton’s jelly mesenchymal stem cells (hWJ-MSCs-CM) to alleviate diabetic complications.MethodsTwenty Sprague Dawley rats were made diabetic through injection of STZ (60 mg/kg, i.p.). At week 8, diabetic rats were divided into two groups: treated [DM + hWJ-MSCs-CM (500 µl/rat for three weeks, i.p.)] and not treated (DM). At the 11th week, three groups (control, DM, and DM + hWJ-MSCs-CM) were kept in metabolic cages, and urine was collected for 24 h. The serum samples were maintained for measuring fasting blood glucose (FBG) and kidney and liver functional analysis. The left kidney and liver parts were kept at -80 °C to assess apelin and transforming growth factor-beta (TGF-β) expression. The right kidney, pancreas, and liver parts were used for histopathologic evaluation.ResultsDM was detected by higher FBG, microalbuminuria, increased albumin/creatinine ratio, and pancreas, renal, and hepatic structural disturbances. Diabetic hepatopathy was determined by increasing liver enzymes and decreasing total bilirubin. The TGF-β gene expression was significantly upregulated in the diabetic kidney and liver tissues. Apelin gene expression was significantly downregulated in the diabetic liver tissue but did not change in kidney tissue. Administration of hWJ-MSCs-CM improved renal and hepatic functional and structural disturbances. Moreover, CM therapy significantly decreased TGF-β expression and enhanced apelin expression in the kidney and liver tissues.ConclusionHuman WJ-MSCs-CM may have protective effects on diabetic renal and hepatic complications. These effects may happen through the regulation of TGF-β and apelin signaling pathways.

Uric acid elevations differ between equivalent hydrochlorothiazide and indapamide doses

Introduction: Thiazide diuretics are among the major anti-hypertensive medications. Hydrochlorothiazide and indapamide are among the most commonly used thiazides. Common side effects include impaired renal function and electrolyte disturbances. Whether hydrochlorothiazide and indapamide cause the same amount of disturbance at equivalent doses is uncertain.
 
 Methodology: Patient data from four different clinics was analyzed. Patients whose thiazide diuretic was initiated or dose escalated were included if they met the inclusion criteria. Patient characteristics, including demographics, comorbidities, medications, renal function, and electrolyte values at the initial visit and control visit, and hydrochlorothiazide or indapamide exposure per milligram, were acquired. Indapamide doses were multiplied by ten to convert into equivalent thiazide doses. Changes in renal function and electrolyte values, and renal function and electrolyte changes per equivalent thiazide exposure, were calculated.
 
 Results: The uric acid increase and potassium decrease were different for the indapamide and hydrochlorothiazide groups. However, when these changes were analyzed per equivalent thiazide exposure, potassium was not different, but the uric acid increase was still significantly different between indapamide and hydrochlorothiazide (.05(.08) vs .03 (.08) mg/dL per equivalent mg thiazide, p = .049).
 
 Discussion: This study demonstrated that indapamide’s hyperuricemic effect is more profound than that of hydrochlorothiazide. Choosing hydrochlorothiazide instead of indapamide may be more appropriate in patients with higher initial uric acid levels.

Traumatic Kidney Injury: A 6-Year Retrospective Study in Childhood and Adolescence.

Traumatic kidney injuries are the most common urinary tract injuries. Pediatric patients are more susceptible to renal injury from blunt trauma than adults because of anatomic factors. The aim of this publication was to provide a reference for traumatic kidney injury in the pediatric group based on the study in our center. A retrospective study was conducted from January 2014 to December 2019 to review medical records of children admitted with renal trauma. Relevant findings including demographics, mechanisms and grades of injury, clinical parameters, interventions, and outcomes were recorded. Thirty-three pediatric patients were investigated. Males experienced traumatic kidney injury more often than the females with a ratio of 10:1. Most cases occurred during the adolescent (12-18) years (81.82%). Left-side kidney injury (63.64%) was more frequent than right side (36.36%). Most cases (96.97%) were caused by blunt trauma, mainly traffic accidents (81.82%). Most patients (90.91%) had stable hemodynamics. Grade IV kidney injury was the most frequently found injury (39.39%). The cause of renal function disturbance was based on the blood urea nitrogen/creatinine (BUN/Cr) ratio with 21.87% of patients suffering from intra-renal causes and 12.5% from pre-renal causes. No significant association between different grades and BUN/creatinine ratio was found. Isolated renal injuries were found in 54.54% of patients. Most patients were treated conservatively (87.88%), and survival was 96.97%. Non-operative management is safe and yields good outcomes in kidney trauma patients with stable hemodynamics. Renal trauma severity is not associated with the BUN/Cr ratio.

Blood analysis for screening of electrolyte and kidney function alterations in patients with febrile urinary tract infection.

To describe the prevalence, severity, risk factors, and clinical relevance of electrolyte disturbances and acute kidney injury (AKI) during febrile urinary tract infection (fUTI). Retrospective observational study of well/fair-appearing patients between 2 months and 16 years, with no previous relevant medical history, diagnosed with fUTI in the paediatric emergency department (PED) with subsequent microbiological confirmation. Analytical alteration (AA) data were considered: AKI (creatinine elevation × 1.5 the median for age), plasma sodium alteration (≤130 or ≥150 mEq/L), and potassium alteration (≤3 or ≥6 mEq/L). We included 590 patients, 17.8% presented AA (13 hyponatremia, 7 hyperkalaemia, and 87 AKI). No patient presented severe analytic alterations or a higher frequency of symptoms potentially attributable to these alterations (seizures, irritability, or lethargy). Risk factors associated with these AA were clinical dehydration (OR = 3.5 95% CI: 1.04-11.7; p = 0.044) and presenting a temperature >39°C (OR = 1.9 95% CI: 1.14-3.1; p = 0.013). Electrolyte and renal function disturbances are infrequent in the previously healthy paediatric population with a fUTI. If present, they are asymptomatic and not severe. Based on our results, performing systematic blood analysis to rule out AA appears no longer justified, especially in the absence of risk factors.

#6153 SODIUM-GLUCOSE COTRANSPORTER 2 INHIBITORS VERSUS DIPEPTIDYL PEPTIDASE 4 INHIBITORS AS STABILIZERS OF HIF PATHWAY IN DIABETIC NEPHROPATHY RATS

Abstract Background and Aims With the diabetes pandemic, chronic kidney disease is a burden, with diabetic nephropathy (DN) being the primary leading cause of end-stage renal disease. Antidiabetic drugs have shown renoprotective effects via different mechanisms, and among those are SGLT2 inhibitors and DPP-4 inhibitors. Hypoxia-inducible factor (HIF) pathway, a significant contributor to inflammation development in the kidneys, is a major pathway that regulates erythropoietin synthesis. Prolyl hydroxylase domain (PHD) decreases erythropoietin synthesis by inhibiting HIFs. PHD inhibitors are anticipated to have additional effects, such as protection against metabolic diseases, due to HIF's impact on many genes. The diabetic kidney is characterized by enhanced HIF-1α activation but decreased HIF-2α activity. These actions may significantly contribute to glomerular and renal tubular dysfunction, renal inflammation and fibrosis, and decreased erythropoietin synthesis observed in DN. This work aims to test the renoprotective effect of SGLT2 inhibitors and DPP-4 inhibitors by controlling the proinflammatory and anti-inflammatory domains of the HIF pathway. Method Type 1 DM rat model was induced in 24-hour-fasted Sprague Dawley rats by a single intraperitoneal injection of 45 mg/kg streptozotocin (STZ). DM was verified by measuring blood glucose seven days following STZ injection, and only animals with glucose levels of ≥15 mM were included (n = 24), randomly and equally distributed, then received either saline or vildagliptin (3 mg/Kg) or empagliflozin (30 mg/Kg) once daily by oral gavage for three months. An additional group was used as a non-diabetic control. At the end of the experiment, rats were placed in metabolic cages for 24-h urine collection, then sacrificed. Blood samples and kidney tissue were collected. Kidney function was assessed by measuring serum creatinine and urinary albumin: creatinine ratio. HIF1α, HIF2α, and PHD3 mRNA expression in kidney tissues were assessed using quantitative real-time PCR, and to indirectly assess HIF2α protein stability, immunohistochemical staining for PHD3 was also performed. Results Vildagliptin and empagliflozin could significantly ameliorate the diabetic disturbance of renal function, as demonstrated in serum creatinine (F = 23.518, p<0.001) with a non-significant difference between both treated groups, and in the significantly reduced albumin/creatinine ratio (F = 14.453, p<0.001), with a significantly lower ratio for empagliflozin (4.73±0.54) than vildagliptin-treated group (9.09±1.04). Regarding the HIF pathway as a potential mechanism, empagliflozin-treated groups showed a significantly higher HIF2α gene expression in kidney tissue samples (0.98±0.10) than the vildagliptin-treated group (0.58±0.05). For the expression of its regulator, PHD3, there was a significant difference between groups (F = 5.694, p = 0.005). However, the vildagliptin-treated group (0.65±0.06) didn′t differ significantly from the untreated group (0.60±0.03), in contrast to the empagliflozin-treated group (2.01±0.50), which showed a significantly higher expression than the other groups (Figure 1). Conclusion Empagliflozin significantly increased the level of HIF-2α in renal tissue. In addition, it nearly neutralizes the tubular expression of PHD3 compared to non-treated and vildagliptin-treated rats. SGLT2 inhibition is effective for correcting the proinflammatory/anti-inflammatory imbalance in DN.

Frequency of Acute Kidney Injury with Hypoxic Ischemic Encephalopathy Staging in Neonates with Perinatal Asphyxia: An Observational Study (Descriptive Case Series)

Perinatal asphyxia affects almost all the organs in neonates, kidneys being one of commonly affected organs. Early recognition of disturbances in renal function is important for early intervention to prevent irreversible damage to kidneys. Objective: In this study we observed the frequency of acute kidney injury (AKI) in neonates with clinical staging of hypoxemic ischemic encephalopathy (HIE) in neonates with perinatal asphyxia. Methodology: An overall number of 145 term neonates with perinatal asphyxia admitted at nursery of Liaquat University Hospital, Hyderabad from February-2019 to july-2019 were included in this study. Urine output was monitored from day one and serum creatinine was sent on third day of life. Serum creatinine was sent early of those neonates having low urine output. Results: The average birth weight was 2.72±2.67 kg. There were 106 (73.1%) males and 39 (26.9%) females. Most neonates were born via simple vaginal delivery 100 (68.97%) and few via caesarian section 45 (31.03%). Out of 145 neonates 38 (26.21%) were in stage I, 95 (65.52%) in stage II and 12 (8.28%) in stage III HIE. Frequency of AKI in neonates with perinatal asphyxia was 55 (37.93%). Incidence of AKI was significantly high in stage II 45(81.8%) as compare to stage I 0(0%) and stage III 10(18.2%) (p=0.0005). Conclusion: AKI is a common complication of perinatal asphyxia. Further multicenter based and studies on large scale need to be done to identify the inter-relationship between maternal factors and perinatal asphyxia associated AKI to prevent neonatal morbidity and mortality. Keywords: Acute kidney injury, perinatal asphyxia, hypoxic ischemic encephalopathy.

Renal Disturbances during and after Radioligand Therapy of Neuroendocrine Tumors-Extended Analysis of Potential Acute and Chronic Complications.

Neuroendocrine tumors (NEN) are a group of neoplasms that arise from hormonal and neural cells. Despite a common origin, their clinical symptoms and outcomes are varied. They are most commonly localized in the gastrointestinal tract. Targeted radioligand therapy (RLT) is a treatment option which has proven to be successful in recent studies. However, the possible outcomes and true safety profile of the treatment need to be fully determined, especially by new, more sensitive methods. Our study aimed to present an extended analysis of acute and chronic renal complications during and after radioligand therapy using, for the first time in the literature, innovative and complex renal parameters. Forty patients with neuroendocrine tumors underwent four courses of radioligand therapy with [177Lu]Lu-DOTATATE or [177Lu]Lu/[90Y]Y-DOTATATE. Radioisotopes were administrated in intervals of 8-12 weeks, with concurrent intravenous nephroprotection. New detailed and sensitive renal parameters were used to determine the renal safety profile during and after radioisotope therapy for standard treatment of NEN. During the first and fourth courses of RLT, no change in the glomerular filtration rate (GFR) was observed. However, long-term observations one year after the treatment showed a 10% reduction in the GFR. During the first course of treatment, the fractional urea and calcium excretions increased, while the fractional potassium concentration decreased. The fractional calcium excretion remained highly increased in long-term observations. Decreases in urine IL-18, KIM-1 and albumin concentrations were observed during RLT. The concentrations of IL-18 and KIM-1 remained low even a year after therapy. The ultrasound parameters of renal perfusion changed during treatment, before partially returning to the baseline one year after therapy, and were correlated with the biochemical parameters of renal function. A permanent increase in diastolic blood pressure was correlated with the decrease in the GFR observed during the study. In this innovative and complex renal assessment during and after RLT, we found a permanent 10% per year decrease in the GFR and noticeable disturbances in renal tubule function. The diastolic blood pressure also increased.

Intrarenal Doppler ultrasonography in patients with HFrEF and acute decompensated heart failure undergoing recompensation

ObjectivesRenal venous congestion due to backward heart failure leads to disturbance of renal function in acute decompensated heart failure (ADHF). Whether decongestion strategies have an impact on renal venous congestion is unknown. Objective was to evaluate changes in intrarenal hemodynamics using intrarenal Doppler ultrasonography (IRD) in patients with heart failure with reduced ejection fraction (HFrEF) and ADHF undergoing recompensation.MethodsProspective observational study in patients with left ventricular ejection fraction (LV-EF) ≤ 35% hospitalized due to ADHF. IRD measurement was performed within the first 48 h of hospitalisation and before discharge. Decongestion strategies were based on clinical judgement according to heart failure guidelines. IRD was used to assess intrarenal venous flow (IRVF) pattern, venous impedance index (VII) and resistance index (RI). Laboratory analyses included plasma creatinine, eGFR and albuminuria.ResultsA number of 35 patients with ADHF and LV-EF ≤ 35% were included into the study. IRD could be performed in 30 patients at inclusion and discharge. At discharge, there was a significant reduction of VII from a median of 1.0 (0.86–1.0) to 0.59 (0.26–1.0) (p < 0.01) as well as improvement of IRVF pattern categories (p < 0.05) compared to inclusion. Albuminuria was significantly reduced from a median of 78 mg/g creatinine (39–238) to 29 mg/g creatinine (16–127) (p = 0.02) and proportion of patients with normoalbuminuria increased (p = 0.01). Plasma creatinine and RI remained unchanged (p = 0.73; p = 0.43).DiscussionThis is the first study showing an effect of standard ADHF therapy on parameters of renal venous congestion in patients with HFrEF and ADHF. Doppler sonographic evaluation of renal venous congestion might provide additional information to guide decongestion strategies in patients with ADHF.Graphical abstract

PROTECTIVE EFFECT OF ROSMARINUS OFFICINALIS EXTRACT ON THE NEPHROTOXICITY CAUSED BY NICKEL CHLORIDE IN WISTAR RATS

Nickel is a common environmental pollutant inducing nephrotoxicity. Oxidative stress has been proposed as a possible mechanism involved in this toxicity. The present study aimed to elucidate the potential protective effect of methanolic extract of Rosmarinus officinalis (RO) against nephrotoxicity induced by Nickel Chloride (NiCl2). The antioxidant activity and the metal chelating power of the plant extract were evaluated. An in vivo study on 28 rats divided into equal four groups including the first group as the control; the second received 100 mg/kg bw of RO extract; the third was exposed to 10 mg/kg bw of NiCl2, and the last was treated with the combination of the extract and NiCl2 by gavage for 28 days. Oxidative stress parameters, biochemical biomarkers, and histopathological examination of the kidney were determined. Analysis of the results showed that the plant has significant antioxidant and metal-chelating power. In addition, exposure of rats to NiCl2 caused a disturbance of renal function (urea, creatinine, and uric acid). This exposure also induced a renal oxidative stress, which results in increased MDA level and GST activity a decrease in antioxidant status (CAT, GPx, and SOD activity), and alteration in tissue architecture of kidney was observed. Co-administration of RO (extract and NiCl2) restored most of the parameters cited above to values close to normal. Therefore, the present study revealed the ability of RO to bind to NiCl2 and protect kidney tissue from NiCl2-induced oxidative damage.

A facile strategy for comprehensive proteome analysis of urine using ultracentrifugation fractionation, solid-phase alkylation based sample preparation and liquid chromatography-mass spectrometry

In this work, a facile strategy with combination of ultracentrifugation fraction, solid-phase alkylation sample preparation and liquid chromatography-mass spectrometry (LC-MS) was developed to achieve comprehensive proteome profiling of urine (CPU). By this strategy, a total of 1659 proteins could be identified using a short LC gradient of ∼1h, 2.3 times more than those (730) obtained from raw urine without fractionation. Compared to the current existing methods for urine sample preparation, not only the analysis time could be greatly shortened by 3–4 times, but also the identification coverage of urine proteome was increased by 130%–160%. Such a method was further combined with label-free quantification for the comparative proteome analysis of urine from IgA nephropathy (IgAN) patients and healthy donors, 227 differentially expressed proteins were identified. In addition to 90 proteins that were reported to be closely related to IgAN, we found that multiple members of solute carrier family 22 (SLC22) were up-regulated in IgAN, which might be related to the disturbance of renal metabolic function in patients. All these results demonstrated that our developed method would provide a promising tool for discovering disease related biomarkers in urine.

Evaluation of Kidney Function in Patients with COVID-19 at the Epidemiological Treatment Centre in CHNU Fann

Alteration of renal function during SARS-CoV-2 infection is frequent and is associated with excess mortality. It is multifactorial, involving mechanisms more specific to COVID-19: viral invasion, endothelitis and thrombosis, activation of the renin-angiotensin-aldosterone system, and elevation of pro-inflammatory cytokines. Thus, the objective of this work was to assess renal function in patients with moderate and severe forms of COVID-19. This was a prospective cross-sectional study of patients with COVID-19. The parameters studied were age, sex, uremia, creatinine and glomerular filtration rate (GFR). All biological parameters were measured with the A15 Biosystems automated system (Barcelona, Spain) and the GFR was calculated according to the MDRD formula. Data processing was carried out with the SPSS (Statistical Package for Social Sciences) software version 23. Our study population consisted of 192 subjects with COVID-19, of which 111 were moderate and 81 were severe. The mean age of our subjects was 60 years and a sex ratio of 1.02. GFR assessment showed that 28% of the population had a lowered GFR (2). Analysis of the results according to the clinical forms showed frequencies of 19% of disturbance of renal function for the moderate forms against 40% for the severe forms. Impaired renal function appears to be frequent in patients with severe SARS-CoV-2 infection and is associated with a bad prognosis. Any patient hospitalized with SARS-CoV-2 should benefit from an initial nephrological assessment which could be used as a marker to dictate the prognosis of the severity of COVID-19.

88 Tubulointerstitial nephropathy and uveitis (TINU syndrome): a paediatric case report

IntroductionTINU (Tubulo-interstitial Nephritis and Uveitis) or oculo-renal syndrome was first described by Dobrin et al. in 1975. >100 cases (mostly paediatric) have been reported since then. It should be considered as diagnosis of elimination, as some iatrogenic, infectious, or systemic diseases may cause similar oculo-renal manifestations. There is no clear therapeutic consensus. However, the rapid initiation of high-dose corticosteroid therapy was associated with favorable outcome in the majority of published cases, as well as in our patient.Case reportWe report the case of an acute tubulointerstitial nephritis associated with uveitis in 11-year-old girl who presented with abdominal pain, vomiting and asthenia of one month. Laboratory tests revealed acute renal failure with proteinuria and aseptic leucocyturia. An inflammatory syndrome was found with erythrocyte sedimentation rate of 92 mm and inflammatory anaemia. Hypoproteinemia and polyclonal hypergamma-globulinaemia was found. No aetiology was found. The renal biopsy revealed a tubulo-nephritis with an interstitial inflammatory infiltrate of lymphoid cells and normal glomeruli. The patient was treated with high-dose of steroids (Methylprednisolone pulse followed by oral Prednisone 1 mg/kg/d with gradual weaning). We noted a progressive improvement of the renal function and the appearance of ocular pain and a decrease in visual acuity. The ophthalmological examination revealed bilateral uveitis. The diagnosis of TINU syndrome was confirmed and the patient received steroids with progressive resolution of the uveitis.ConclusionIn the presence of any uveitis of unknown cause associated with disturbed renal function the diagnosis of TINU syndrome should be considered. This syndrome requires more precise diagnostic criteria and standardized management.Disclosure of InterestNone declared

Clinical implications and indicators of mortality among patients hospitalized with concurrent COVID-19 and myocardial infarction.

Acute ischemic cardiac events can complicate coronavirus disease 2019 (COVID-19). We report the in-hospital characteristics of patients with acute myocardial infarction and concomitant COVID-19. This was a registry-based retrospective analysis of patients admitted with positive COVID-19 tests who suffered acute myocardial infarction either before or during hospitalization; from 1 March 2020 to 1 April 2020 in a tertiary cardiovascular center-Tehran Heart Center. We performed an exploratory analysis to compare the clinical characteristics of patients who died during hospitalization or were discharged alive. In March 2020, 57 patients who had acute myocardial infarction and a confirmed diagnosis of COVID-19 were included in the study. During hospitalization, 13 patients (22.8%) died after a mean hospital stay of 8.4 days. The deceased were older than the survivors. No significant association between mortality and sex or length of hospital stay was observed. Hypertensive individuals were more likely to have a fatal outcome. Previously receiving angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers did not show any association with mortality. Regarding the laboratory data during hospitalization, higher cardiac troponin T, neutrophil count, C-reactive protein, urea, and blood urea nitrogen/creatinine ratio were observed in the mortality group. The deceased had a lower lymphocyte count than the survivors. Markers of worsening renal function and immune system disturbance seem to be associated with mortality in concurrent acute myocardial infarction and COVID-19. Optimizing the management of acute coronary syndrome complicating COVID-19 requires addressing such potential contributors to mortality.

Assessment of serum biochemical derangements and associated risk factors of chronic kidney disease

ObjectiveChronic kidney disease and/or disturbance in renal excretory function may lead to nitrogenous waste collection beyond the term as well as derangements of several serum biochemicals. There is no previous study from Pakistan that reveals serum electrolyte derangements in confirmed chronic kidney disease (CKD) patients and other biochemicals associated with CKD. This study aims to examine the derangements of serum biochemicals and the association of several risk factors with CKD. MethodsThe study enrolled 612 confirmed CKD patients with a glomerular filtration rate (GFR) < 15 ml/min that were treated as a part of the integrated care programme at Mayo Hospital Lahore (one of the largest hospitals in Pakistan). Serum biochemicals were estimated on AU 680 (Beckman Coulter) using the spectrophotometric technique. ResultsAll the CKD patients had elevated creatinine and urea levels, but only 63.4% were suffering from hyperuricemia. The incidence of diabetes and malnutrition assessed by serum albumin (hypoalbuminemia) was 27.4% and 72%, respectively. Among electrolyte disorders, hyperphosphatemia (71.8%) and hypocalcaemia (61.9%) were found to be more prevalent. Furthermore, gender, malnutrition, diabetes, hyperuricemia, and phosphorus and magnesium derangements were found to be statistically significant risk factors for CKD, whereas malnutrition and magnesium derangement were associated with hyperuricemia. ConclusionIt is imperative to improve dietary protein and monitor serum electrolyte concentration in renal dysfunction patients to slow the progression of CKD to end-stage renal disease (ESRD) and other serious complications.

Electrolyte and renal disorders in patients with newly diagnosed glioblastoma.

Purpose: Disturbances of electrolytes and renal function have been linked to the prognosis of critically ill patients and recently also of cancer patients. This study aimed to assess electrolyte and renal disorders in glioblastoma patients and evaluate their prognostic effect. Methods: Medical records of patients with newly diagnosed glioblastoma between 2005 and 2018 were retrospectively reviewed for electrolyteand renal function parameters and for demographic, clinical and outcome parameters. Results: Electrolyte and renal function disorders were associated with poorer survival in univariate and Kaplan-Meier analysis. Multivariate analysis revealed hypochloremia as an independent prognostic factor for overall and 1-year survival. Conclusion: Only hypochloremia showed an association with glioblastoma prognosis, independentof other known prognostic factors, as age or molecular status.

The adverse effect of long term intake of Monosodium Glutamate on kidney performance

Monosodium glutamate (MSG) is a food additive that is considered as a water and environmental pollutant and affects the tissues of the living being. This study was aimed to find the effect of long-term administration of MSG on the mass of mesangial cells of the kidneys. Forty adult male rats were divided into four groups (10 each). Control groups 1&2 were supplied orally with distilled water for 30 and 60 days, respectively. Treatment groups 1&2 were supplied orally with 15 mg/kg Bwt of MSG for 30 & 60 days, respectively. Control and treatment groups were sacrificed, specimens of kidneys were obtained, fixed with 10% neutral buffered formalin, processed by Routine histological techniques, stained by Hematoxylin and eosin, and PAS (Periodic Acid-Schiff) stains then examined under the light microscope. The result found enlargement in a mesangial mass represented by hypertrophy and hyperplasia of mesangial cells leading to mesangial proliferative glomerulonephritis. Accordingly, the study showed an increase in creatinine values, indicating a disturbance in renal function. This will lead to a decrease in the sizes of the glomeruli of renal corpuscles and a relative increase of Bowman’s space. With the time of the experiment, the glomerular capillaries and gates of basement membranes will be closed, resulting in renal filtration disorders. It was concluded that the long-term intake of MSG leads to indirect narrowing of the glomerular capillary lumen, causing kidney failure.

Применение диуретиков при застойной сердечной недостаточности: официальное заявление Ассоциации сердечной недостаточности Европейского общества кардиологов

Для большинства эпизодов острой сердечной недостаточности характерно усиление симптомов и признаков застойных явлений с объемной перенагрузкой. Цель терапии у таких пациентов заключается в облегчении застойных явлений путем достижения нормоволемии, главным образом с помощью терапии диуретиками. Однако должное применение диуретиков остается сложным, особенно при ухудшении функции почек, резистентности к диуретикам и нарушениях баланса электролитов. В этом официальном заявлении рассматривается применение диуретиков при застойной сердечной недостаточности. В работе рассматриваются распространенные проблемы, такие как: 1) оценка застойных явлений и клинической нормоволемии; 2) оценка ответа на диуретики/резистентности к диуретикам при лечении острой сердечной недостаточности; 3) подход к поэтапным фармакологическим стратегиям применения диуретиков на основе ответа на диуретики; 4) лечение распространенных нарушений баланса электролитов. Рекомендации приведены в соответствии с доступними руководствами, свидетельствами и экспертными выводами.

Ренин-ангиотензиновая система в регуляции экскреторной функции почек при экспериментальном сахарном диабете

Целью исследования было изучение роли ренин-ангиотензиновой системы в нарушении экскреторной функции почек в динамике аллоксан-индуцированного экспериментального сахарного диабета. Материалы и методы. Исследования выполнены на 78 нелинейных половозрелых самцах белых крыс с 11-, 26- и 46-дневным экспериментальным сахарным диабетом, вызванным внутрибрюшинным введением аллоксана (160 мг/кг), на фоне фармакологической блокады внутрипочечной ренин-ангиотензиновой системы, индуцированной внутрибрюшинным введением каптоприла (10 мг/кг). Изучение экскреторной функции почек осуществляли клиренс-методом в условиях водного индуцированного 2-часового диуреза с определением клиренса эндогенного креатинина, скорости клубочковой фильтрации, относительной реабсорбции воды, содержания белка в моче, его экскреции. Результаты. Анализ изменений функции почек после фармакологической блокады ренин-ангиотензиновой системы у крыс на 11-й день аллоксанового диабета показал достоверное возрастание диуреза, скорости клубочковой фильтрации, концентрационного индекса эндогенного креатинина, а также экскреции белка. При этом фармакологическая блокада ренин-ангиотензиновой системы практически не влияла на интенсивность относительной реабсорбции воды у аллоксан-диабетических крыс. На 26-й день развития аллоксанового диабета после введения каптоприла наблюдалось незначительное уменьшение объема конечной мочи, интенсивности гломерулярной фильтрации, относительной реабсорбции воды, концентрационного индекса эндогенного креатинина. Вместе с тем каптоприл не вызывал антипротеинурического эффекта, а экскреция белка даже продемонстрировала тенденцию к увеличению. На 46-й день аллоксан-индуцированного диабета после введения каптоприла достоверно снижались диурез крыс, клиренс эндогенного креатинина и скорость клубочковой фильтрации, а также концентрация белка в моче и его экскреция. Выводы. Результаты исследования позволяют сделать вывод о том, что начальный этап формирования ренальных нарушений при аллоксан-индуцированном экспериментальным сахарным диабетом связан с гемодинамически-гиперперфузионным характером функционирования почек при сохранном почечном функциональном резерве и структуре клубочково-канальцевого аппарата почки, авторегуляторных механизмов. Указанные компенсаторно-функциональные изменения функций почек постепенно осложняются истощением почечного функционального резерва и патологической активацией внутрипочечной ренин-ангиотензиновой системы с последующим прогрессированием гиперперфузионно-ишемического поражения почек, уменьшением массы функционирующих нефронов.

Epigenetic regulation of TXNIP-mediated oxidative stress and NLRP3 inflammasome activation contributes to SAHH inhibition-aggravated diabetic nephropathy

S-adenosylhomocysteine (SAH) is hydrolyzed by SAH hydrolase (SAHH) to homocysteine and adenosine. Increased plasma SAH levels were associated with disturbed renal function in patients with diabetes. However, the role and mechanism of SAHH in diabetic nephropathy is still unknown. In the present study, we found that inhibition of SAHH by using its inhibitor adenosine dialdehyde (ADA) accumulates intracellular or plasma SAH levels and increases high glucose-induced podocyte injury and aggravates STZ-induced diabetic nephropathy, which is associated with Nod-like receptor protein 3 (NLRP3) inflammasome activation. Inhibition or knockout of NLRP3 attenuates SAHH inhibition-aggravated podocyte injury and diabetic nephropathy. Additionally, SAHH inhibition increases thioredoxin-interacting protein (TXNIP)-mediated oxidative stress and NLRP3 inflammasome activation, but these effects were not observed in TXNIP knockout mice. Mechanistically, SAHH inhibition increased TXNIP by inhibiting histone methyltransferase enhancer of zeste homolog 2 (EZH2) and reduced trimethylation of histone H3 lysine 27 and its enrichment at promoter of early growth response 1 (EGR1). Moreover, EGR1 is activated and enriched at promoters of TXNIP by SAHH inhibition and is essential for SAHH inhibition-induced TXNIP expression. Inhibition of EGR1 protected against SAHH inhibition-induced NLRP3 inflammasome activation and oxidative stress and diabetic nephropathy. Finally, the harmful effects of SAHH inhibition on inflammation and oxidative stress and diabetic nephropathy were also observed in heterozygote SAHH knockout mice. These findings suggest that EZH2/EGR1/TXNIP/NLRP3 signaling cascade contributes to SAHH inhibition-aggravated diabetic nephropathy. Our study firstly provides a novel insight into the role and mechanism of SAHH inhibition in diabetic nephropathy.