Transient Renal Impairment Research Articles

Dehydration and Suboptimal Sleep Aggravate Early Renal Impairment in Children: Longitudinal Findings from the PROC Study

Background: While dehydration is associated with pediatric renal impairment, the regulation of hydration status can be affected by sleep. However, the interaction of hydration and sleep on kidney health remains unclear. Methods: We conducted a cohort study among 1914 healthy primary school children from October 2018 to November 2019 in Beijing, China. Four-wave urinary β2-microglobulin and microalbumin excretion were assayed to assess transient renal tubular and glomerular impairment, and specific gravity was measured to determine hydration status with contemporaneous assessment of sleep duration, other anthropometric, and lifestyle covariates. We used generalized linear mixed-effects models to assess longitudinal associations of sleep duration and hydration status with renal impairment. Results: We observed 1378 children with optimal sleep (9–<11 h/d, 72.0%), 472 with short sleep (<9 h/d), and 64 with long sleep (≥11 h/d, 3.3%). Over half (55.4%) of events determined across 6968 person-visits were transient dehydration, 19.4% were tubular, and 4.9% were glomerular impairment events. Taking optimal sleep + euhydration as the reference, the results of generalized linear mixed-effects models showed that children with long sleep + dehydration (odds ratio [OR]: 3.87 for tubular impairment [tubules] and 3.47 for glomerular impairment [glomerulus]), long sleep + euhydration (OR: 2.43 for tubules), optimal sleep + dehydration (OR: 2.35 for tubules and 3.00 for glomerulus), short sleep + dehydration (OR: 2.07 for tubules and 2.69 for glomerulus), or short sleep + euhydration (OR: 1.29 for tubules) were more likely to present transient renal impairment, adjusting for sex, age, body mass index z-score, systolic blood pressure z-score, screen time, physical activity, and Mediterranean diet adherence. Conclusions: Dehydration and suboptimal sleep aggravate transient renal impairment in children, suggesting its role in maintaining pediatric kidney health.

Perioperative regional anaesthesia in kidney transplantation

Background. Postoperative analgesia in kidney transplant recipients is challenging due to potential nephrotoxicity of nonsteroidal anti-inflammatory drugs and the reduced clearance of opioid metabolites during transient renal impairment. Opioid-sparing multimodal postoperative analgesia using regional analgesia methods could provide better pain control and early activation after kidney transplantation.Aim. To evaluate the clinical results of treatment using regional pain management methods in kidney transplant recipients.Material and methods. A single-center study was conducted at Republican Research Center of Emergency Medicine from 2020 to 2022. The study included 97 patients who underwent heterotopic kidney transplantation from a living related donor. Patients were divided into 3 groups. In group 1 (31 patients), general anesthesia was used. For postoperative analgesia opioid analgesics in combination with metamizole 1000 mg were used. In group 2 (33 recipient patients), a combination of general anesthesia and open transversus abdominis plane block was used. In group 3 (33 recipient patients), a combination of general anesthesia and erector spine plane block was performed. Opioid analgesics were used as a "rescue analgesia" when necessary. The primary study end points were the pain intensity assessed by a visual analogue scale and opioid consumption on the first day after surgery. Secondary endpoints were the time of intestinal motility recovery, the presence of nausea and vomiting, the Intensive Care Unit length of stay and the hospital length of stay.Results. Pain intensity 6 hours after surgery in patients of group 1 was 13.5% and 24.6% higher than in patients of group 2 and 3, respectively. In group 2, pain intensity was 12.8% higher compared to group 3 (p=0.0017). At 12 hours after surgery, the pain intensity was 42% higher in group 1 compared to group 2 and group 3 (p<0.0001). After 18 hours, the pain score in group 3 was 48.5% and 35.7% lower compared to groups 1 and 2, respectively (p<0.0001 and p=0.0016). 24 hours after surgery, the sensation of pain was 18.6% and 65.3% higher in group 1 compared to groups 2 and 3 (p<0.0001). The mean dose of narcotic analgesic equivalent to morphine in group 1 was 22.6±8.6 mg, which was 18.5% higher than in group 2 patients. In group 3, it was 12.0±4.3 mg and was 47% lower compared to group 1 (p<0.0001) and 34.7% lower compared to group 2 (p<0.0001) (all comparisons are statistically significant). The adequacy of analgesia and less opioid consumption contributed to the absence of postoperative nausea and vomiting in 75% of cases, early restoration of intestinal motility in 63% compared with the group of patients where opioid analgesics were used for postoperative pain relief.Conclusion. The combined use of general anesthesia and erector spine plane block may be recommended as a method of effective perioperative analgesia in kidney transplantation.

Perinatal asphyxia does not influence presepsin levels in neonates: A prospective study.

To compare Presepsin (presepsin) levels in plasma and urine of uninfected newborn infants with perinatal asphyxia with those of controls. In this prospective study, we enrolled 25 uninfected full-term infants with perinatal asphyxia and 19 controls. We measured presepsin levels in whole blood or urine. In neonates with perinatal asphyxia, we compared presepsin levels in blood and urine at four time points. In neonates with perinatal asphyxia, blood and urinary presepsin levels matched each other at any time point. At admission, the median presepsin value in blood was similar in both groups (p = 0.74), while urinary levels were higher in hypoxic neonates (p = 0.05). Perinatal asphyxia seemed to increase serum CRP and procalcitonin levels beyond normal cut-off but not those of presepsin. In uninfected neonates with perinatal asphyxia, median blood and urinary presepsin levels matched each other at any point in the first 72 h of life and seemed to be slightly affected by the transient renal impairment associated with perinatal hypoxia in the first 12 h of life. Perinatal asphyxia did not influence presepsin levels within the first 72 h of life, while those of CRP and procalcitonin increased.

Impact of renal impairment on dihydropyrimidine dehydrogenase (DPD) phenotyping

The chemotherapeutic agent 5-fluorouracil (5-FU) is catabolized by dihydropyrimidine dehydrogenase (DPD), the deficiency of which may lead to severe toxicity or death. Since 2019, DPD deficiency testing, based on uracilemia, is mandatory in France and recommended in Europe before initiating fluoropyrimidine-based regimens. However, it has been recently shown that renal impairment may impact uracil concentration and thus DPD phenotyping. The impact of renal function on uracilemia and DPD phenotype was studied on 3039 samples obtained from three French centers. We also explored the influence of dialysis and measured glomerular filtration rate (mGFR) on both parameters. Finally, using patients as their own controls, we assessed as to what extent modifications in renal function impacted uracilemia and DPD phenotyping. We observed that uracilemia and DPD-deficient phenotypes increased concomitantly to the severity of renal impairment based on the estimated GFR, independently and more critically than hepatic function. This observation was confirmed with the mGFR. The risk of being classified 'DPD deficient' based on uracilemia was statistically higher in patients with renal impairment or dialyzed if uracilemia was measured before dialysis but not after. Indeed, the rate of DPD deficiency decreased from 86.4% before dialysis to 13.7% after. Moreover, for patients with transient renal impairment, the rate of DPD deficiency dropped dramatically from 83.3% to 16.7% when patients restored their renal function, especially in patients with an uracilemia close to 16 ng/ml. DPD deficiency testing using uracilemia could be misleading in patients with renal impairment. When possible, uracilemia should be reassessed in case of transient renal impairment. For patients under dialysis, testing of DPD deficiency should be carried out on samples taken after dialysis. Hence, 5-FU therapeutic drug monitoring would be particularly helpful to guide dose adjustments in patients with elevated uracil and renal impairment.

PD17-03 REDOX IMBALANCE AND MAPK ACTIVATION MEDIATES PNEUMOPERITONEUM-INDUCED KIDNEY INJURY DURING MINIMALLY INVASIVE SURGERY

You have accessJournal of UrologyCME1 Apr 2023PD17-03 REDOX IMBALANCE AND MAPK ACTIVATION MEDIATES PNEUMOPERITONEUM-INDUCED KIDNEY INJURY DURING MINIMALLY INVASIVE SURGERY Charbel Chalouhy, Nassim Fares, Youakim Saliba, Pedro Maria, Ahmed Aboumoouhamed, Marwan Kassis, Alexander Small, and Justin Loloi Charbel ChalouhyCharbel Chalouhy More articles by this author , Nassim FaresNassim Fares More articles by this author , Youakim SalibaYouakim Saliba More articles by this author , Pedro MariaPedro Maria More articles by this author , Ahmed AboumoouhamedAhmed Aboumoouhamed More articles by this author , Marwan KassisMarwan Kassis More articles by this author , Alexander SmallAlexander Small More articles by this author , and Justin LoloiJustin Loloi More articles by this author View All Author Informationhttps://doi.org/10.1097/JU.0000000000003272.03AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookLinked InTwitterEmail Abstract INTRODUCTION AND OBJECTIVE: Given the widespread use of laparoscopic and robotic surgeries, the effects of pneumoperitoneum (PNP) during minimally invasive surgery on kidney function become of great interest. PNP during laparoscopy causes transient renal functional impairment via various detrimental factors, such as oxidative stress. We, therefore, investigated the oxidative signaling pathways inherent to PNP-induced kidney injury. METHODS: PNP was established at an intraperitoneal CO 2 pressure of 12 mmHg in Wistar rats randomly allocated into three groups: Sham, PNP1, and PNP24. PNP1 and PNP24 animals were sacrificed at one and 24 hours following PNP deflation, respectively. Renal histology, function, redox status, and signaling pathways were assessed. RESULTS: PNP induced kidney injury and dysfunction with altered KIM-1 profile. Both expression and activity of antioxidant (CAT, SOD1/2) and oxidant (NOS3) enzymes, lipid peroxidation, and renal RNA/DNA damage biomarkers revealed redox imbalance after PNP, with an excess H2O2 production. Moreover, the antioxidant gene regulators FoxO3a and Nrf2 were activated. Nevertheless, PNP had no effect on the cellular apoptotic pathways Bcl2, Bid, Caspase 3 and 8. Finally, PNP stimulated the p38 and JNK mitogen-activated protein kinase (MAPK) pathways in the kidney. CONCLUSIONS: Our results demonstrate for the first time that PNP induces acute kidney injury due to renal redox imbalance linked to MAPK activation. These insights may open the way for further investigation into the renal therapeutic impact of managing PNP-associated oxidative stress during robotic surgery and explore procedure-specific kidney function recovery patterns i.e. after robotic partial nephrectomy or robotic kidney transplant. Source of Funding: none © 2023 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 209Issue Supplement 4April 2023Page: e495 Advertisement Copyright & Permissions© 2023 by American Urological Association Education and Research, Inc.MetricsAuthor Information Charbel Chalouhy More articles by this author Nassim Fares More articles by this author Youakim Saliba More articles by this author Pedro Maria More articles by this author Ahmed Aboumoouhamed More articles by this author Marwan Kassis More articles by this author Alexander Small More articles by this author Justin Loloi More articles by this author Expand All Advertisement PDF downloadLoading ...

Good Adherence to the Mediterranean Diet Lowered Risk of Renal Glomerular Impairment in Children: A Longitudinal Study.

Healthy diet patterns have a positive effect on chronic non-communicable diseases in the pediatric population, but the evidence is limited on the association between kidney impairment and adherence to a Mediterranean diet. We aim to determine the associations between Mediterranean diet adherence and longitudinal tubular and glomerular impairment in children. Based on four waves of urine assays conducted from October 2018 to November 2019, we assayed urinary β2-microglobulin (β2-MG) and microalbumin (MA) excretion to determine transient renal tubular and glomerular impairment during the follow-up of the child cohort (PROC) study in Beijing, China. We assessed Mediterranean diet adherence using the 16-item Mediterranean Diet Quality Index in children and adolescents (KIDMED) among 1914 primary school children. Poor, intermediate, and good adherence rates for the Mediterranean diet were 9.0% (KIDMED index 0–3), 54.4% (KIDMED index 4–7) and 36.5% (KIDMED index 8–12), respectively. A short sleep duration was more prevalent in children with lower Mediterranean diet adherence, with no significant differences presenting in the other demographic and lifestyle covariates. The results of linear mixed-effects models showed that a higher urinary MA excretion was inversely associated with a higher KIDMED score (β = −0.216, 95%CI: −0.358, −0.074, p = 0.003), after adjusting for sex, age, BMI z-score, SBP z-score, screen time, sleep duration and physical activity. Furthermore, in generalized linear mixed-effects models, consistent results found that transient renal glomerular impairment was less likely to develop in children with intermediate Mediterranean diet adherence (aOR = 0.68, 95%CI: 0.47, 0.99, p = 0.044) and in children with good Mediterranean diet adherence (aOR = 0.60, 95%CI: 0.40, 0.90, p = 0.014), taking poor Mediterranean diet adherence as a reference. We visualized the longitudinal associations between each item of the KIDMED test and kidney impairment via a forest plot and identified the main protective eating behaviors. Children who adhere well to the Mediterranean diet have a lower risk of transient glomerular impairment, underscoring the necessity of the early childhood development of healthy eating patterns to protect kidney health.

Revised cardiac score index is a predictor of long-term outcomes after carotid endarterectomy.

Background: Cardiac complications represent the main cause of mortality after non-cardiac surgery and the Revised Cardiac Risk Index (RCRI) was created to estimate the perioperative risk of these events. It considers history of ischaemic heart disease, congestive heart failure, diabetes requiring preoperative insulin, stroke or transient ischaemic attack and renal impairment. We aim to describe the accuracy of the RCRI for predicting perioperative major adverse cardiovascular events (MACE) - a composite of heart failure, ischemic events and all-cause death. Also, the authors aimed to review the score for better prediction of cardiovascular outcomes. Patients and methods: From January 2012 to January 2020, patients who underwent Carotid endarterectomy (CEA) with regional anaesthesia (RA) were selected. RCRI was calculated for each case. Estimated and reported cardiovascular complications were compared using multivariate logistic regression and cox proportional hazards. An alternative and optimized carotid-RCRI (CtRCRI) was obtained. Overall predictive accuracy was assessed and compared by measuring model discrimination. Adjustments for overfitting and evaluation of the new model were performed by bootstrap. Results: 186 patients were selected, of which 80% were male with a mean age of 70.0±9.05 years old. The median follow-up was 50 months, interquartile range 21-69 months. None of the scores were able to predict MACE in the perioperative period. Both were associated with 30-day Clavien-Dindo ≥2 (p=0.022 and p=0.041, respectively). Regarding long-term prognosis, both were able to predict MACE (RCRI: hazard ratio (HR) 3.54 (95% confidence interval [CI] 1.04-11.48) vs. CtRCRI: HR 2.08 (95%CI 1.08-3.98) and all-cause mortality (RCRI: HR 3.33, 95%CI 0.99-11.11 vs. CtRCRI: HR 1.57, 95%CI 1.14-7.04). Conclusions: RCRI and CtRCRI did not predict MACE in the perioperative period but are good predictors of 30-day complications (Clavien-Dindo ≥2). Both RCRI and CtRCRI have good prognostic value as predictors of long-term cardiovascular events.

Oxidative stress and motion sickness in one crew during competitive offshore sailing

Competitive Offshore Ocean Sailing is a highly demanding activity in which subjects are exposed to psychophysical stressors for a long time. To better define the physiological adaptations, we investigated the stress response of subjects exposed to 3-days long ocean navigation with disruption of circadian rhythms. 6 male subjects were involved in the study and provided urine and saliva samples before setting sail, during a single day of inshore sailing, during 3-days long ocean navigation, and at the arrival, to measure oxidative stress, cortisol, nitric oxide metabolites (NOx) and metabolic response. Motion Sickness questionnaires were also administered during the navigation. The crew suffered a mean weight loss of 1.58 kg. After the long navigation, a significant increase in ROS production and decrease in total antioxidant capacity and uric acid levels were observed. Lipid peroxidation, NO metabolites, ketones, creatinine, and neopterin levels were also increased. Furthermore, a significant increase in cortisol levels was measured. Finally, we found a correlation between motion sickness questionnaires with the increase of NOx, and no correlation with cortisol levels. Physical and psychological stress response derived from offshore sailing resulted in increased oxidative stress, nitric oxide metabolites, and cortisol levels, unbalanced redox status, transient renal function impairment, and ketosis. A direct correlation between motion sickness symptoms evaluated through questionnaires and NOx levels was also found.

Acute Tramadol Ingestion With Transient Acute Kidney Injury in an Adolescent Female.

Renal toxicity has been described with tramadol overdoses; however, it is typically associated with rhabdomyolysis, multiorgan failure and/or mortality. Our patient was a 16-year-old female who was evaluated following an intentional tramadol ingestion, estimated 27.8 to 37 mg/kg, and had a seizure prior to arriving at our health care facility. Her symptoms were consistent with a tramadol ingestion; however, she developed transient acute renal impairment (peak serum creatinine, 4.04 mg/dL), which improved over 6 days with minimal intervention. No other causes were identified to explain her acute renal impairment thus it was attributed to the tramadol overdose. Providers should be aware that transient acute renal impairment could occur with an intentional tramadol ingestion and may not require aggressive intervention.

Fast-track off-pump coronary artery bypass: single-center experience.

The primary goal of the study was to perform retrospective analysis of fast-track coronary artery bypass grafting at our institute to identify risk factors for prolonged hospital stay. A secondary goal was to identify and compare survival statistics with those published in literature. We performed a retrospective analysis of patients enrolled in our fast-track coronary artery bypass protocol. There were 709 patients with a mean age of 58.85 ± 8.9 years; 572 were men. The mean EuroSCORE II was 2.02% ± 2.64%. Of these 709 patients, 538 (76%) met the requirements for discharge within 100 hours. Prolonged ventilation or reintubation, major pulmonary complications, gastrointestinal and neurological complications were the strongest predictors of fast-track failure. Persistent atrial fibrillation, postoperative transient renal impairment, requirement for noninvasive ventilation > 3 times, sternal wound infection, insulin-dependent diabetes mellitus, preoperative intraaortic balloon pump for chest pain or ST changes, preoperative severe left ventricular dysfunction, preoperative severe renal impairment, and peripheral arterial disease were also found to be significant risk factors for fast-track failure. Cumulative survival at 66 months of follow-up was 90.2% ± 0.02%. The risk factors listed above were associated with fast-track failure. Smoking cessation helps to nullify the factor of chronic obstructive pulmonary disease. Intraoperative elective insertion of a balloon pump does not affect the fast-track protocol. Survival was comparable to that described in the literature.

Renal safety of short-term empiric gentamicin therapy in aged patients.

To determine the incidence of acute kidney injury (AKI) in aged patients receiving empiric gentamicin therapy. Patients aged ≥65 years receiving gentamicin upon admission between 2013 and 2015 at two Australian hospitals were retrospectively studied. AKI was defined as a rise in creatinine by ≥50% and/or ≥26.5 μmol/L. Most patients (95%) received a single dose of gentamicin. The incidence of AKI was 15% (36/242 patients). A composite outcome of persistent kidney injury, requirement for renal replacement therapy or inpatient death in a patient with AKI occurred in 10 (4%) patients. Patients who developed AKI were older (median 80.5 vs 78 years, P = 0.03), had higher Charlson Co-morbidity Index (median 7 vs 5, P = 0.0004) and had more advanced chronic kidney disease at baseline (Stages IV and V) (OR 4.38, 95% confidence interval 1.45-13.2, P = 0.01). Empiric gentamicin use in patients with advancing age is associated with low rates of predominantly transient renal impairment.

Abstract 243: Contrast Induced Nephropathy; Out of Sight, Out of Mind

Objectives: Same day cardiac interventions are increasing; concerns that are not immediately apparent may be neglected. We sought to determine if pts at higher risk of contrast nephropathy are identified, appropriately treated and followed. Background: Contrast induced nephropathy [CIN] impacts on mortality risk; ranging from transient renal impairment with full recovery, to cumulative impairment, to renal failure and the need for permanent dialysis. Preprocedural modifiable [hydration status, contrast reexposure <72 hrs, nephrotoxic medications], partially modifiable [hypotension & heart failure], and non-modifiable [baseline renal function [eGFR<60], age >75 yrs] risk factors influence risk. Procedural factors [contrast volume, hypotension, IABP patients] increase risk. CIN risk is decreased by optimizing risk factors and hydration, minimizing contrast. Post procedure the Mehran CIN predictor is calculated and a 48 hr post IP or 7 day OP creatinine is obtained to identify CIN. Procedure: From 2016-17 pts undergoing interventional procedures exceeding the lab standard for radiation exposure were selected for review as representing a cohort likely to have increased contrast exposure. Results: There were 3,996 procedures [2,436 diagnostic, 1,560 interventions] performed in the reviewed period. Of 56 outlier pts, 11 were treated for structural heart disease and 45 underwent coronary angioplasty. Pre procedure risk factors included: age >75 [19/56], DM [19/56], HF [25/56], CKD 3 [12/55; 1 pt on HD]. Opportunities for decreasing contrast: LV gram 7/45, prior contrast exposure within 72 hrs 5/45, multivessel intervention 15/45. Few [7/45] of the pts received periprocedural hydration as recommended by the EHR power plan [cited reason heart failure 25/45]. Contrast use was as high as 475 cc; use of biplane imaging was infrequent. The Mehran CIN risk score was low in 13/55 [7.5% CIN/0.04% HD], intermediate in 36/55 [14.0% CIN/ 0.12 HD], high in 7/55 [26.1-57.3% CIN/ 1.09-12.6% HD]. Pre procedure creatinine was not available in 1 pt and volume of contrast administered undocumented in another pt. 48 hr creatinine was documented in 33/56 pts; 10 of the 33 pts developed post procedure CIN. Conclusions: Shortened hospitalizations decrease the awareness of and preventive treatment for CIN. A multidisciplinary team has identified multiple opportunities for practice improvement: provider education, review of the EHR power plan [for modification of pre and intraprocedural risk factors, implementation of correctly dosed fluid repletion with renal consultation for high risk patients, appropriate follow-up of creatinine], Preprocedural calculation and intraprocedural monitoring to achieve low risk contrast volume [(ml)/eGFR <3.7}, interventional report embedding CIN risk score, EHR tracking and audit to ensure implementation with appropriate feedback as necessary.

Mitral valve replacement in severely calcified mitral valve annulus: a 10-year experience.

Severe calcification in the mitral valve annulus is a challenging problem during mitral valve surgery. We describe our experience with mitral valve replacement in severely calcified mitral valve without decalcification of the annulus. Between April 2001 and July 2011, 61 patients underwent mitral valve replacement with severe mitral annulus calcification without decalcification of the annulus. This retrospective study was performed to assess the surgical and the long-term postoperative outcomes in this group. The mean age of the patients was 75.2 ± 9.2 years. Twenty-four patients (53%) were in New York Heart Association Class III/IV. Twenty-six patients (58%) had good left ventricular function. Mean logistic EuroSCORE was 8.75. Isolated mitral valve replacement was performed in 12 patients (27%). Coronary artery bypass grafting was done in 13 patients (29%). In-hospital mortality was 4.9% (3 patients). Postoperative morbidity included re-exploration for bleeding in 3 patients (7%) and transient renal impairment in 10 patients (22%). Three patients required intra-aortic balloon pump (7%) for low cardiac output syndrome. Seven patients (16%) required permanent pacemaker, and 1 patient (2%) had thromboembolic event. The 1-year survival was 93.3%, and the 5-year survival was 78.8%. The mean echocardiography follow-up was 40 months. There was no paravalvular leak detected in any patient in the long-term follow-up. None of the patients had valve-related reoperation. Mitral valve replacement without annular decalcification in severely calcified mitral valve annulus is a safe and an effective approach and has good long-term outcome.

Association of Serum Creatinine and Electrolyte Abnormalities in Preterm Low Birth Weight Neonates

Introduction: Being born prematurely is a threat to survival and the subsequent quality of life ICDDR,B Health and Science Bulletin published in March 2006 reported that prematurity and low birth weight contributes to 27.8% of neonatal deaths in rural areas of Bangladesh Premature infant are at increased risk of developing dehydration or over hydration. Therefore, high index of suspicion, prompt recognition and thorough understanding of common electrolyte abnormalities are necessary to improve neonatal outcome. The investigation of renal function in pretenn neonate is complicated because of continuing renal development, rise in creatinine is transient and may not be clinically significcmt. Serum creatinine is most widely used marker of renal function in adults and children but its validity as a marker of GFR/ renal function is doubtful a few studies have been conducted on assessment of renal function and electrolytes in the context of prematurity in Bangladesh. But it seems to be essential for immediate management for planning appropriate fluid and electrolyte therapy and thereby for improved outcome. Information was collected who gave consent and participated in the study willingly. The sample size was 50. Duration of data collection was approximately 6 (Six) months.Patients admitted to the Holy Family Red Crescent Medical College and hospital and after meeting the inclusion and exclusion criteria a simple random sampling technique was applied for selecting the sample patients. Total 50 pretenn LBW neonates fulfilling the inclusion criteria were studied during this study period. Mean creatinine level was .82 mmoKrange was 0.40-1.90 mg/d1. Abnormal electrolytes were documented in 20(40%) pretenn LBW neonates of which hyperkalemia was the predominant electrolyte abnormality found in 8(16.0%) neonates, hyponatremia was found in 7 (14.0%), hypokalemia in 3 (6.0%) and hypernatremia 2 (4.0%). In the present study 20 of preterm LBW babies have electrolyte abnormalities. Hyperkalemia was found in 8(16.0%) babies in this study from above findings it is evident that prematurity causes transient renal impairment, in preterm neonates which is inversely related to gestational age. Renal impairment should be suspected if the serum creatinine rises or fails to show normal post-natal fall. It was observed that electrolyte abnormalities are common in preterm LBW neonates and transient renal failure also occurs in a large number of preterm LBW babies. So, identification of renal failure and associated electrolyte abnormalities and proper management of fluid and electrolytes and close monitoring are important.

Deferasirox in the Treatment of Iron Overload during Myeloproliferative Neoplasms (MPN)

Background Deferasirox (DFX) is an oral iron chelator widely employed in the treatment of iron overload during thalassemic syndromes and myelodysplastic syndromes.Aim At present, very few data are available on the treatment with DFX in patients with Ph- Myeloproliferative Neoplasms(MPN) and transfusional requirement.Methods To address this issue, we report here on 41 patients (M 31; F 10) with MPN and iron overload secondary to transfusional requirement enrolled in the database of our regional cooperative group who received a treatment with DFX. Of them, 36 had a primary Myelofibrosis, 4 a post Essential Thrombocythemia myelofibrotic phase and 1 a post Polycythemia Vera myelofibrotic phase.Results According to IPSS classification, 8 patients (19.5%) resulted low/intermediate-1 risk, 14 (34.1%) intermediate-2 risk and 19 (46.4%) high-risk. The main features of the patients at diagnosis and at baseline of DFX treatment are reported in the Table.Treatment with DFX was started after a median interval from diagnosis of 13.3 months [interquartile range (IR) 7.3 - 41.1] and from start of transfusion dependence of 11.5 months (IR 5.8 - 20.2), with a median of 27 packed red cells units received (IR 18 - 37). The starting DFX dose was 20 mg/Kg in 16 patients (39.1%), 15 mg/Kg in 20 patients (48.8%) and 10 mg/Kg in 5 patient (12.1%). All patients were evaluable for toxicity:extra-hematological toxicity of all WHO grades was reported in 20/41 patients (48.8%) and consisted of gastro-intestinal symptoms in 7 patients, transient renal impairment in 10 patients and skin reactions in 3 patients: however, only 3 patients (7.3%) needed a permanent discontinuation for toxicity. Thirty-nine out 41 patients were evaluable for response (> 6 months of treatment). As to chelation efficacy, after a median treatment period of 15.4 months (IR 8.1 - 22.3), 4 patients achieved ferritin levels < 500 ng/ml, 10 patients ferritin levels < 1,000 ng/ml and 2 patients presented a reduction > 50% of basal ferritin but with levels > 1,000 ng/ml, with a global response rate of 16 out 39 patients (41.0%): among the remaining 23 patients, 2 discontinued for early toxicity, 20 did not have any ferritin reduction and 1 had an early unrelated death (< 6 months of treatment). As to hematological improvement, 7/39 patients (17.9%) showed an unexpected and persistent rise of Hb levels > 1.5 g/dl, with disappearance of transfusional requirement in 5 cases. The median overall survival of the whole cohort from DFX initiation was 20.7 months (95% CI 16.0 - 25.3): the median overall survival from DFX initiation in patients with chelation response was 46.9 months (95% CI 10.7 - 83.0) compared to 14.0 months (95% CI 5.6 - 22.3) in patients without chelation efficacy (p=0.002).Conclusions Treatment with DFX is feasible and effective in MPN with iron overload. Moreover, also in this setting an hematological improvement can occur in a sizeable rate of patients. [Display omitted] DisclosuresBreccia:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Ariad: Honoraria; Pfizer: Honoraria. Latagliata:Novartis: Consultancy, Honoraria; Bristol Myers Squibb: Honoraria; Celgene: Honoraria; Janssen: Consultancy, Honoraria; Shire: Honoraria.

Response to treatment with azacitidine in children with advanced myelodysplastic syndrome prior to hematopoietic stem cell transplantation.

Advanced myelodysplastic syndrome harbors a high risk of progression to acute myeloid leukemia and poor prognosis. In children, there is no established treatment to prevent or delay progression to leukemia prior to hematopoietic stem cell transplantation. Azacitidine is a hypomethylating agent, which was shown to slow progression to leukemia in adults with myelodysplastic syndrome. There is little data on the efficacy of azacitidine in children. We reviewed 22 pediatric patients with advanced myelodysplastic syndrome from a single center, diagnosed between January 2000 and December 2015. Of those, eight patients received off-label azacitidine before hematopoietic stem cell transplantation. A total of 31 cycles were administered and modification or delay occurred in four of them due to cytopenias, infection, nausea/vomiting, and transient renal impairment. Bone marrow blast percentages in azacitidine-treated patients decreased significantly from a median of 15% (range 9-31%) at the start of treatment to 5.5% (0-12%, P=0.02) before hematopoietic stem cell transplantation. Following azacitidine treatment, four patients (50%) achieved marrow remission, and none progressed. In contrast, three untreated patients (21.4%) had progressive disease characterized by >50% increase in blast counts or progression to leukemia. Azacitidine-treated patients had significantly increased 4-year event-free survival (P=0.04); predicted 4-year overall survival was 100% versus 69.3% in untreated patients (P=0.1). In summary, azacitidine treatment prior to hematopoietic stem cell transplantation was well tolerated in pediatric patients with advanced myelodysplastic syndrome, led to partial or complete bone marrow response in seven of eight patients (87.5%), and correlated with superior event-free survival in this cohort.

Effects of Mountain Ultra-Marathon Running on ROS Production and Oxidative Damage by Micro-Invasive Analytic Techniques.

PurposeAiming to gain a detailed insight into the physiological mechanisms involved under extreme conditions, a group of experienced ultra-marathon runners, performing the mountain Tor des Géants® ultra-marathon: 330 km trail-run in Valle d’Aosta, 24000 m of positive and negative elevation changes, was monitored. ROS production rate, antioxidant capacity, oxidative damage and inflammation markers were assessed, adopting micro-invasive analytic techniques.MethodsForty-six male athletes (45.04±8.75 yr, 72.6±8.4 kg, 1.76±0.05 m) were tested. Capillary blood and urine were collected before (Pre-), in the middle (Middle-) and immediately after (Post-) Race. Samples were analyzed for: Reactive Oxygen Species (ROS) production by Electron Paramagnetic Resonance; Antioxidant Capacity by Electrochemistry; oxidative damage (8-hydroxy-2-deoxy Guanosine: 8-OH-dG; 8-isoprostane: 8-isoPGF2α) and nitric oxide metabolites by enzymatic assays; inflammatory biomarkers (plasma and urine interleukin-6: IL-6-P and IL-6-U) by enzyme-linked immunosorbent assays (ELISA); Creatinine and Neopterin by HPLC, hematologic (lactate, glucose and hematocrit) and urine parameters by standard analyses.ResultsTwenty-five athletes finished the race, while twenty-one dropped out of it. A significant increase (Post-Race vs Pre) of the ROS production rate (2.20±0.27 vs 1.65±0.22 μmol.min-1), oxidative damage biomarkers (8-OH-dG: 6.32±2.38 vs 4.16±1.25 ng.mg-1 Creatinine and 8-isoPGF2α: 1404.0±518.30 vs 822.51±448.91 pg.mg-1Creatinine), inflammatory state (IL-6-P: 66.42±36.92 vs 1.29±0.54 pg.mL-1 and IL-6-U: 1.33±0.56 vs 0.71±0.17 pg.mL1) and lactate production (+190%), associated with a decrease of both antioxidant capacity (-7%) and renal function (i.e. Creatinine level +76%) was found.ConclusionsThe used micro-invasive analytic methods allowed us to perform most of them before, during and immediately after the race directly in the field, by passing the need of storing and transporting samples for further analysis. Considered altogether the investigated variables showed up that exhaustive and prolonged exercise not only promotes the generation of ROS but also induces oxidative stress, transient renal impairment and inflammation.

Following specific podocyte injury captopril protects against progressive long term renal damage

Background: Angiotensin converting enzyme inhibitors (ACEi) reduce proteinuria and preserve kidney function in proteinuric renal diseases. Their nephroprotective effect exceeds that attributable to lowering of blood pressure alone. This study examines the potential of ACEi to protect from progression of injury after a highly specific injury to podocytes in a mouse model.Methods: We created transgenic (Podo-DTR) mice in which graded specific podocyte injury could be induced by a single injection of diphtheria toxin. Transgenic and wild-type mice were given the ACEi captopril in drinking water, or water alone, commencing 24h after toxin injection. Kidneys were examined histologically at 8 weeks and injury assessed by observers blinded to experimental group.Results: After toxin injection, Podo-DTR mice developed acute proteinuria, and at higher doses transient renal impairment, which subsided within 3 weeks to be followed by a slow glomerular scarring process. Captopril treatment in Podo-DTR line 57 after toxin injection at 5ng/g body weight reduced proteinuria and ameliorated glomerular scarring, matrix accumulation and glomerulosclerosis almost to baseline (toxin: 17%; toxin + ACEi 10%, p<0.04; control 7% glomerular scarring). Podocyte counts were reduced after toxin treatment and showed no recovery irrespective of captopril treatment (7.1 and 7.3 podocytes per glomerular cross section in water and captopril-treated animals compared with 8.2 of wild-type controls, p<0.05).Conclusions: Observations in Podo-DTR mice support the hypothesis that continuing podocyte dysfunction is a key abnormality in proteinuric disease. Our model is ideal for studying strategies to protect the kidney from progressive injury following podocyte depletion. Demonstrable protective effects from captopril occur, despite indiscernible preservation or restoration of podocyte counts, at least after this degree of relatively mild injury.

Following specific podocyte injury captopril protects against progressive long term renal damage.

Angiotensin converting enzyme inhibitors (ACEi) reduce proteinuria and preserve kidney function in proteinuric renal diseases. Their nephroprotective effect exceeds that attributable to lowering of blood pressure alone. This study examines the potential of ACEi to protect from progression of injury after a highly specific injury to podocytes in a mouse model. We created transgenic (Podo-DTR) mice in which graded specific podocyte injury could be induced by a single injection of diphtheria toxin. Transgenic and wild-type mice were given the ACEi captopril in drinking water, or water alone, commencing 24h after toxin injection. Kidneys were examined histologically at 8 weeks and injury assessed by observers blinded to experimental group. After toxin injection, Podo-DTR mice developed acute proteinuria, and at higher doses transient renal impairment, which subsided within 3 weeks to be followed by a slow glomerular scarring process. Captopril treatment in Podo-DTR line 57 after toxin injection at 5ng/g body weight reduced proteinuria and ameliorated glomerular scarring, matrix accumulation and glomerulosclerosis almost to baseline (toxin: 17%; toxin + ACEi 10%, p<0.04; control 7% glomerular scarring). Podocyte counts were reduced after toxin treatment and showed no recovery irrespective of captopril treatment (7.1 and 7.3 podocytes per glomerular cross section in water and captopril-treated animals compared with 8.2 of wild-type controls, p<0.05). Observations in Podo-DTR mice support the hypothesis that continuing podocyte dysfunction is a key abnormality in proteinuric disease. Our model is ideal for studying strategies to protect the kidney from progressive injury following podocyte depletion. Demonstrable protective effects from captopril occur, despite indiscernible preservation or restoration of podocyte counts, at least after this degree of relatively mild injury.

Methotrexate Associated Renal Impairment Is Related to Delayed Elimination of High-Dose Methotrexate.

Although Methotrexate (MTX) is an effective drug for the treatment of acute lymphoblastic leukemia (ALL), the toxicity remains a significant problem. In this prospective study, fifty-four patients with ALL were enrolled. 3 g or 5 g MTX/m2 was administered over 24 hours. Serum MTX concentrations were determined in 24, 48, and 96 hours after MTX infusion. Serum creatinine concentrations and creatinine clearance rate (CCR) were determined before and 24 and 48 hours after MTX infusion. A total of 173 courses of MTX infusion were administered. The serum creatinine concentrations did not change much after MTX infusion while the CCR was gradually decreased. MTX clearance status was independently related to CCR decrease, with the risk of 8.07 to develop renal impairment in patients with delayed MTX elimination. Serum creatinine concentration, serum creatinine ratio, CCR, and CCR ratio at 24 hours were all related to MTX elimination delay. Patients with serum creatinine level >35.0 μmol/L, creatinine ratio >1.129, or CCR <100.0 mL/min were more likely to undergo MTX elimination delay. In conclusion, MTX could induce transient renal impairment and compromised renal function will delay MTX clearance. The serum creatinine concentration and the ratio and CCR are useful tools for evaluating MTX elimination status.