Increase In Serum Creatinine Research Articles

Acute kidney injury after catheter ablation of atrial fibrillation: comparison between different energy sources

Abstract Introduction Pulsed field ablation (PFA) is an innovative technology recently adopted for the treatment of atrial fibrillation (AF). Preclinical and clinical studies have reported a reassuring safety profile, because of its tissue specific effect, sparing adjacent tissues. However, two cases of acute kidney injury (AKI) secondary to hemolysis after PFA have recently been reported. Purpose To compare the incidence of AKI and hemolysis after catheter ablation of AF using radiofrequency energy (RFA), cryo-balloon energy (CBA) and PFA using a pentaspline catheter. Method Patients undergoing catheter ablation of AF were consecutively enrolled in a prospective registry in a tertiary referral center between April 2010 and January 2024. Blood samples including renal parameters and hemolysis indicators were obtained prior to the procedure and the day after the procedure. AKI was defined as an increase in serum creatinine by 26.5 µmol/L within up to 10 days after the procedure . Results A total of 2602 patients (median age 64 years, 29.4% female) underwent catheter ablation for AF. 1707 (66.4%) were treated with RFA, 557 (21.7%) using CBA and 306 (11.9%) using PFA. Median net duration of ablation was 1669 (IQR 1207, 2164) seconds for RFA, 1046 (IQR 840, 1451) seconds for CBA and, 80 (IQR 48, 85) seconds (32 (IQR 19, 34) applications) for PFA. AKI was found in 21 (0.012%), 1 (0.002%) and 1 (0.003%) patients treated with RFA, CBA and PFA, respectively, p=0.245. The case with AKI after PFA received a total of 86 PFA applications. There was a significant positive correlation for the RFA group between the ablation duration and the creatinine level after the procedure, while there was no positive correlation for the CBA and PFA group (Figure). At least one hemolysis indicator (Bilirubin, LDH or Urea levels) was elevated the day after the procedure in 53.1%, 50.1% and 46.5% in the RFA, CBA and PFA group, respectively, p=0.12. Conclusion AKI appears to be very rare after PFA and comparable to thermal energy forms. Hemolysis does not seem to be dependent on the used energy source for pulmonary vein isolation. Minimal hemolysis occurs when PFA is applied as recommended by the manufacturer.Graphical Abstract

The use of allopurinol in prophylaxis against contrast-induced nephropathy in patients undergoing percutaneous coronary intervention

Abstract Background Contrast-induced nephropathy (CIN) is a serious complication after percutaneous coronary intervention (PCI). Inflammation and development of reactive oxygen species are among the postulated mechanisms of CIN. Allopurinol with anti-inflammatory action could be a preventive method of CI-AKI. Aim of the work To determine the effect of adding allopurinol to hydration in the prevention of CIN in patients undergoing PCI, with or without hyperuricemia. Methods One hundred and seven patients with moderate to high Mehran score undergoing elective PCI were randomly allocated to the allopurinol (n=52) or the control group (n=55). Those in the allopurinol group (hyperuricemic n=25, and normouricemic n= 27) received allopurinol 300 mg one day and one hour before PCI beside intravenous hydration (1 ml/kg/hour) normal saline, a maximum of 100 ml/hour for 12 hours pre and post coronary angiography. Patients in the control group (hyperuricemic n=26 and normouricemic n=29), received the same intravenous hydration only. Serum creatinine and urea were measured before and 48 hours after the procedure while the uric acid level was measured before the procedure only. CIN was defined by a percentage increase in serum creatinine of ≥25% or absolute serum creatinine ≥0.5 mg/dl, 48 hours after PCI. Results The mean age of the studied patients was 59.6 ± 9.1 years old, 59% were male. No difference between both groups regarding baseline characteristics or medications. Average Mehran score was 9.0 ± 1.2. CIN was observed in 5 patients in the allopurinol group (9.6%) and 15 patients in the control group (27.3%) (P = 0.017). There was no significant difference between both groups regarding the contrast volume (179.8 ± 68.1 vs. 153.8 ± 57.9 ml, p: 0.052). Hyperuricemia had no significant effect on increasing the incidence of CI-AKI either in patients with or without CKD (p=0.964). Conclusion Allopurinol on the top of hydration was found to decrease the incidence of CIN following PCI in patients with moderate to high Mehran score for CIN. The anti-inflammatory action of allopurinol could be the mechanism of this favorable effect, as baseline uric acid didn't affect the results. Further multi-center study with a larger sample size is needed to offer more definite results.

Risk factors for access site-related complications after distal transradial catheterization

Abstract Introduction Distal transradial catheterization (dTRA) has emerged as a viable alternative to conventional transradial access for various interventional procedures. Purpose This study aims to identify the risk factors associated with access site-related complications following dTRA. Methods A total of 4,977 patients who underwent dTRA were included in this retrospective study. The patients were divided into two groups based on the occurrence of access site-related complications: Complication(+) group (n=272) and Complication(-) group (n=4,705). Various demographic, clinical, and procedural parameters were analyzed to identify potential risk factors. Univariate and multivariate logistic regression models were employed to determine the adjusted odds ratios (ORs) and 95% confidence intervals (CIs) for each risk factor. Results The Complication(+) group exhibited a higher prevalence of male gender (53.7% vs. 68.4%, p<0.001), older age (68.140 ± 11.46 vs. 66.33 ± 11.90, p=0.014), lower body mass index (BMI) (24.35 ± 3.54 vs. 24.97 ± 3.55, p=0.005), larger sheath size (2.45 ± 0.24 vs. 2.40 ± 0.24, p<0.001), increased serum creatinine (Cr) levels (1.33 ± 1.76 vs. 1.10 ± 1.46, p=0.013), longer access time (209.26 ± 237.72 vs. 149.26 ± 143.98, p<0.001), prolonged hemostasis time (257.64 ± 202.40 vs. 197.60 ± 133.39, p<0.001), and extended procedure time (32.24 ± 29.07 vs. 23.04 ± 26.19, p<0.001). Additionally, the Complication(+) group received higher heparin doses (6275.48 ± 2971.05 vs. 5282.74 ± 2952.31, p<0.001) and had a higher incidence of multiple antiplatelet therapy (73.2% vs. 51.3%, p<0.001). However, no significant differences were observed in hypertension, dyslipidemia, diabetes mellitus, or smoking history between the two groups. The multivariate analysis identified male gender (adjusted OR: 2.073, 95% CI: 1.376 - 3.123, p<0.001), and increased Cr levels (adjusted OR: 1.083, 95% CI: 1.024 - 1.144, p=0.005) as independent risk factors for access site-related complications after dTRA. Moreover, the use of multiple antiplatelet therapy was found to be significantly associated with an increased risk of complications (adjusted OR: 1.948, 95% CI: 1.420 - 2.671, p<0.001). Conclusion In patients undergoing dTRA, male gender, increased serum creatinine levels, and the use of multiple antiplatelet therapy were identified as independent risk factors for access site-related complications. These findings highlight the importance of careful patient selection and procedural optimization to minimize complications during dTRA.

Impact of neutrophil-to-lymphocyte ratio on clinical outcomes in patients with or without chronic kidney disease undergoing percutaneous coronary intervention

Abstract Background Neutrophil-to-lymphocyte ratio (NLR) has recently emerged as inexpensive inflammatory biomarker associated with worse cardiovascular outcomes. However, little is known about its role in risk stratification of patients with both chronic kidney disease (CKD) and coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). Purpose We aimed to evaluate the clinical impact of baseline NLR in patients with and without CKD undergoing PCI. Methods We retrospectively evaluated all consecutive patients undergoing PCI between 2012-2022 in a large tertiary US center. We excluded patients without available NLR and those who were deemed to have active hematological or infective diseases, including patients with extremely low or high lymphocyte and neutrophil counts or with hs-CRP above 10 mg/L. Quartiles of NLR were derived in the overall population and patients were stratified according to presence of CKD (eGFR < 60 ml/min). Within each group, we estimated the risk of adverse events using the lowest NLR quartile as reference. The primary endpoint was 12-month incidence of major adverse cardiovascular events (MACE), defined as the composite of all-cause death, myocardial infarction, or stroke. Secondary endpoints included incidence of clinically relevant bleeding and contrast-associated acute kidney injury (CA-AKI), defined as ≥ 0.3 mg/dL or ≥ 50% serum creatinine increase from baseline. Results A total of 7,287 patients were included in the analysis; of these 2,008 (27.6%) had CKD and 5,279 (72.4%) did not. CKD patients (mean eGFR 40.8±16.1 ml/min) were older, had more comorbidities, and presented with higher hs-CRP levels and a greater estimated risk of CA-AKI. Overall, patients with elevated NLR had more severe CAD and underwent more complex PCI. In CKD patients, incidence of adverse events increased stepwise and those in the 4th NLR quartile had the highest adjusted risks of MACE (HRadj 1.86, 95% CI 1.12-3.08; P=0.012), all cause death (HRadj 2.44, 95% CI 1.18-5.05; P=0.003) and bleeding (HRadj 1.74, 95% CI 1.07-2.84; P=0.002) at 1 year, as compared to those in the lowest quartile (Table 1). In patients without CKD, MACE and all-cause death incidences were numerically higher in the 4th quartile but risk estimates were no longer statistically significant after adjustment. The overall incidence of CA-AKI was much greater in the CKD group. When compared to the lowest quartile, patients in the 4th NLR quartile showed a trend for higher risk of CA-AKI in CKD group, while they had a significant increased risk in non-CKD group (Figure 1). Conclusions Elevated NLR is strongly associated with higher risk of MACE and all-cause mortality in CKD patients. Conversely, the risk of bleeding and CA-AKI is increased with elevated NLR in both CKD and non-CKD patients. Thus, NLR may further inform risk stratification of CKD patients undergoing PCI.

A new hydration strategy can reduce contrast-induced acute kidney injury after PCI in patients with chronic heart failure and chronic kidney disease: a two-center randomized controlled trial

Abstract Backgrounds Adequate hydration is crucial for preventing contrast-induced acute kidney injury (CI-AKI), particularly in patients with chronic kidney disease (CKD). The current guidelines recommend half-volume hydration for patients with chronic heart failure (CHF) to prevent pulmonary edema. Thus, it is challenging to administer hydration therapy in patients with CHF and CKD. This study was aimed to compare different hydration strategies in this subset of patients. Methods This two-center, open-label, randomized clinical trial enrolled 303 CHF (patients with elevated natriuretic peptide levels and/or objective evidence of pulmonary or systemic congestion) patients with CKD (estimated glomerular filtration rate [eGFR] of 15-60 mL/min/1.73m2) undergoing selective coronary angiography (CAG) from two tertiary hospitals from October 2020 to December 2023. Patients were randomized into three groups: half-volume hydration group (HH group, 0.5 mL/Kg/h hydration), standard hydration group (SH group, 1 mL/Kg/h hydration), and standard hydration with diuretic group (SH+D group, 1 mL/Kg/h hydration + immediate postoperative intravenous injection of furosemide 20 mg). All patients received hydration from 6 to 12 hours before to 24 hours after the procedure. The primary endpoint was CI-AKI, defined as a serum creatinine (SCr) increase of more than 0.3 mg/dL or 1.5-1.9 times greater than the baseline 48-72 hours after CAG. Safety endpoints included pulmonary edema during hydration, perioperative mortality, and the need for dialysis. Results A total of 101 patients were included in each group. Baseline characteristics (mean age, proportion of males, left ventricular ejection fraction and eGFR) were similar among groups. SCr, cystatin C levels, and SCr level changes between 48 and 72 hours after procedure did not significantly differ among groups (P > 0.05). The incidence of CI-AKI was highest in the HH group (22.8%), lowest in the SH+D group (11.9%), and intermediate in the SH group (17.8%) (P = 0.041). Regarding safety endpoints, there were 2 patients in the HH group, 3 patients in the SH group and 1 patient in the SH+D group experienced heart failure or pulmonary edema during hydration, with no statistically significant differences among the groups (P = 0.874). Perioperative mortality occurred in 1 patient in the HH group and 2 patients in the SH+D group, with no statistically significant differences (P = 0.776). No patient required renal replacement therapy. Conclusions In CHF patients with CKD, the half-volume hydration regimen recommended by guidelines was associated with a higher incidence of CI-AKI compared to standard hydration. However, standard hydration combine with diuretic fails to reduce the risk of heart failure during hydration or perioperative mortality, even if this novel strategy does not increase the risk of CI-AKI compared to standard hydration therapy.

INCIDENCE OF CONTRAST-INDUCED NEPHROPATHY FOLLOWING CHRONIC TOTAL OCCLUSION PERCUTANEOUS CORONARY INTERVENTION

Contrast-induced nephropathy (CIN) is a potentially serious complication following percutaneous coronary intervention (PCI), particularly in patients with chronic total occlusion (CTO). It is characterized by an acute deterioration in renal function after exposure to contrast media. CIN is associated with increased morbidity, hospital stays, and long-term renal outcomes, making it crucial to identify and mitigate its incidence. This study aimed to evaluate the incidence of CIN in patients undergoing CTO-PCI and its associated complications. Objective: To assess the incidence of contrast-induced nephropathy (CIN) following percutaneous coronary intervention (PCI) for chronic total occlusion (CTO) and evaluate in-hospital complications, hospital stay duration, and short-term mortality. Methods: This cross-sectional study was conducted with ethical approval at a tertiary care hospital, including 118 patients who underwent PCI for CTO at the Department of Cardiology, Lady Reading Hospital Peshawar, Pakistan from 10th June 2023 to 09th June 2024. Standardized pre- and post-procedural hydration protocols were implemented to reduce the risk of CIN, and non-ionic, iso-osmolar contrast agents were used. CIN was defined as a 25% increase in serum creatinine or an absolute increase of ≥0.5 mg/dL within 48–72 hours post-procedure. Data on demographic characteristics, complications, and mortality were collected and analyzed using SPSS Version 25, with categorical variables expressed as percentages and continuous variables as means. Chi-square tests were used to assess statistical significance, with P-values < 0.05 considered significant. Results: Of the 118 patients included, the mean age was 56.34 years, and 52.5% were male. Age distribution showed that 43.2% were between 51-60 years, while 33.1% were between 61-70 years. CIN was observed in 6.8% of patients, with 9.7% of males and 3.6% of females affected (P=0.188). In-hospital complications included arrhythmias in 4.2% of patients, heart failure in 0.8%, and mortality in 0.8%. Hospital stay averaged 5.94 days, with no significant differences in CIN incidence across age groups (P=0.186). Conclusion: The incidence of contrast-induced nephropathy following PCI for chronic total occlusion is a clinically significant issue, affecting 6.8% of patients despite preventative measures. This emphasizes the need for ongoing risk assessment, monitoring, and the implementation of effective prevention strategies. Further research is warranted to refine risk stratification tools and develop targeted interventions to minimize CIN incidence, particularly in high-risk patient populations.

Primary and "Pre-Primary" Aldosteronism in Resistant Hypertension: A Practical, Pragmatic, and Prudent Approach in Resource-Limited Milieu.

Introduction Primary aldosteronism (PA), once considered rare, is now recognized as the most common cause of secondary hypertension, accounting for almost a quarter of resistant hypertension (RH) cases. Despite this, PA remains underdiagnosed, with an extremely low percentage of RH patients undergoing screening. Methods In a specialty diabetes-endocrinology clinic, the aldosterone:renin ratio (ARR) was assessed in 115 consecutive RH patients (ages 21-93 years; 47% male; 87% with type 2 diabetes). Fasting blood samples were drawn in a standing position after 30 minutes of walking. Adrenal imaging (CT/MRI) was performed for those with an ARR >20. Results ARR values ranged from 0.4 to 227 (ARR <10 (35%); 11-20 (19%), 21-40 (25%), and >40 (21%)), with corresponding stepwise decreasing plasma renin activity (PRA) (P= 1E-6) and increasing serum aldosterone (SA) (P= 8E-7). Increasing ARR tended to be associated with an increase in serum creatinine (R= 0.23; P= 0.03) and a decrease in estimated glomerular filtration rate (eGFR) (R= -0.24; P= 0.02) and an increase in urine albumin: creatinine ratio. The ARR> 40 group displayed the highest serum creatinine, lowest eGFR, higher urine albumin: creatinine ratio, highest serum sodium, lowest serum potassium, and highest (44%) abnormal adrenal imaging (bilateral hyperplasia diffuse/nodular; solitary adenoma), reflecting a later stage of the pathological spectrum. PA treatment with mineralocorticoid receptor antagonists (MRAs) had a salutary effect. Conclusions Our observations further reinforce that PA is not a binary condition, but exists as a spectrum disorder responsive to MRAs, even in patients with mildly elevated or normal aldosterone levels. Early disease detection/recognition ("renin-independent aldosterone production") can be facilitated by marking "pre-primary" aldosteronism (ARR 11-20), followed by monitoring progression (periodic rescreening) and optimizing treatment, with hopeful mitigation of end-organ damage in RH.

Molecular mechanisms of endoplasmic reticulum stress-mediated acute kidney injury in juvenile rats and the protective role of mesencephalic astrocyte-derived neurotrophic factor.

This study examined the role of endoplasmic reticulum stress in pediatric acute kidney injury and the therapeutic effect of midbrain astrocyte-derived neurotrophic factor. Two-week-old Sprague-Dawley rats were divided into: Sham, ischemia-reperfusion injury-induced acute kidney injury (AKI), mesencephalic astrocyte-derived neurotrophic factor (MANF)-treated, tauroursodeoxycholic acid (TUDCA)-treated. Analyses were conducted 24h post-treatment. Serum creatinine, cystatin C, Albumin, MANF levels were measured, cytokine concentrations in serum and renal tissues were determined using a Luminex assay. Histopathology was assessed via light and electron microscopy. Western blotting and RT-qPCR analyzed markers for oxidative stress, apoptosis, endoplasmic reticulum (ER) stress, and autophagy. HK-2 cells underwent hypoxia/reoxygenation (H/R) to simulate AKI and were treated with MANF or TUDCA. AKI rats had increased serum creatinine, cystatin C, and inflammatory cytokines, along with significant renal damage, and showed loose and swollen ER structures, reduced cell proliferation, and elevated levels of IRE1, PERK, ATF6, CHOP, LC3-II/I, KIM-1, TLR4, JNK, and NF-κB. MANF treatment reduced these biomarkers and protein levels, improved ER structure and cell proliferation, alleviated oxidative stress, apoptosis, ER stress, and inhibited JNK/TLR4/NF-κB signaling. In HK-2 cells, MANF reduced ER stress and inflammation post-H/R exposure. MANF treatment alleviates ER stress, oxidative stress, apoptosis, and inflammation in pediatric AKI, improving renal function and morphology.

Role of AhR-Hsp90-MDM2-mediated VDR ubiquitination in PM2.5-induced renal toxicity

Background and objectivesThe kidney is a primary target for the accumulation of particulate matter (PM2.5). This study aimed to investigate PM2.5-induced renal toxicity mechanisms, focusing on the aryl hydrocarbon receptor (AhR)-Hsp90-MDM2 axis and its impact on vitamin D receptor (VDR) ubiquitination. MethodsPM2.5's role in activating the AhR and its downstream pathways was investigated using in vitro and in vivo models. Renal damage and therapeutic effects in PM2.5-exposed and paricalcitol-treated mice were evaluated using weight measurements, histopathology, and scanning electron microscopy. AhR, Hsp90, and VDR localization and expression in renal cells were assessed using FISH and Western blot. Protein interactions were examined using co-immunoprecipitation. Differentially expressed gene (DEG) analysis of GEO datasets was used to identify related proteins and genes. ResultsPM2.5 exposure caused significant renal damage in mice, including increased serum creatinine, albuminuria, and histopathological deterioration, which were alleviated by paricalcitol. PM2.5 induced the nuclear translocation of AhR and Hsp90 and reduced nuclear VDR expression; paricalcitol reversed these effects. Immunohistochemistry confirmed these findings. PM2.5 upregulated the NLRP3/caspase-1/IL-1β/IL-18 axis, which was reversed by paricalcitol treatment. Inhibition of Hsp90 increased nuclear VDR expression through MDM2 mediation. DEG analysis identified VDR-regulated genes; PM2.5 increased the mRNA levels of IL-6, IL-2, and CXCL8, which were downregulated by Hsp90 and MDM2 inhibitors, with VDR agonists further decreasing these levels. ConclusionThis study reveals a novel mechanism of PM2.5-induced renal toxicity through the AhR-Hsp90-MDM2 axis, promoting VDR ubiquitination and degradation and increasing inflammation. These findings provide a foundation for future studies and lay the groundwork for developing targeted interventions to mitigate the public health impact of PM2.5 exposure.

Assessment of Neutrophil Gelatinase Associated Lipocalin in Children with Acute Gastroenteritis and Dehydration to Identify Early Signs of Acute Kidney Injury

Background: Gastroenteritis often correlates with acute kidney injury (AKI) in children who are hospitalized. The primary diagnostic test for acute kidney injury (AKI) in modern times is serum creatinine (SCr), which increases in the presence of AKI and is eliminated by glomerular filtration. SCr is an unsuitable biomarker for renal sickness because it lacks specificity and a slow response to disease severity or treatment changes. NGAL, or neutrophil gelatinase-associated lipocalin, is a molecular weight of 25 kDa protein and forms a covalent bond with neutrophil gelatinase. Elevations in NGAL levels due to kidney injury have important predictive value and may forecast the onset of acute kidney injury (AKI) 24-72 hours before an increase in diagnostic serum creatinine (SCr) values. Aim and objectives: This study aims to determine whether plasma NGAL concentrations in mild, moderate, or severe dehydrated acute gastroenteritis patients may indicate acute kidney damage (AKI). The research will investigate whether acute renal injury and plasma NGAL concentrations are connected. Patients and methods: The cross-sectional design was employed in this study and included 80 patients who attended the pediatric gastrointestinal clinic at Babylon Children's Hospital. Between November 2022 and June 2023, all patients had gastroenteritis symptoms accompanied by different dehydration levels. Results: Patients with severe dehydration had considerable higher level of NGAL than those with mild to moderate dehydration (p&lt;0.001). There was a notable inverse relationship (p = 0.046) between the NGAL level and potassium but a considerable direct link (p&lt;0.001) between the NGAL level and creatinine. However, no significant correlation was seen between the NGAL level and urea (p = 0.404 and 0.062, respectively). The confidence range for the area under the curve (AUC) is 0.940 to 0.981, with a confidence level of 95%. The p-value is less than 0.001. The sensitivity is 88%. An accuracy of 88.4% has been attained. The NGAL cut-off point is 3.9832. Conclusion: An analysis of plasma neutrophil gelatinase-associated lipocalin (NGAL) in individuals with gastroenteritis and varied degrees of dehydration indicated a clear and direct link between the two parameters. Specifically, when dehydration worsened, the average NGAL value increased

Maribavir use in pediatric immunocompromised hosts: A case series to talk about real-world experience

Abstract Background Cytomegalovirus (CMV) is a common infection affecting pediatric immunocompromised hosts. The treatment of CMV in solid organ (SOT) or hematopoietic stem cell transplant (HSCT) patients is challenged by the toxicities associated with antiviral therapies (myelosuppression with valganciclovir, ganciclovir and cidofovir; nephrotoxicity with foscarnet and cidofovir) and the prevalence of resistant/refractory CMV. Maribavir, a novel benzimidazole, competitively inhibits CMV UL97 protein kinase to inhibit DNA synthesis and block nuclear exit of viral particles from CMV-infected cells. It is FDA approved for use in patients at least 12 years of age and weighing at least 35 kg. The use of maribavir in pediatric patients is of interest due to its availability as an oral dosage formulation and improved side effect profile. To date, there are no pediatric case series or studies describing the use of maribavir for CMV treatment. Methods This study is a retrospective case series compiling the findings the first pediatric patients at Children’s National Hospital, DC that received maribavir. We included children who received maribavir from 01/2017 – 10/2023. Patients were included if they were on maribavir monotherapy, or combination therapy with additional anti-CMV agent(s). The medical records were reviewed for indication of medication use, viral response to therapy and side effects. Side-effects review specifically evaluated for increased LFTs, increased serum creatinine, and decreased absolute neutrophil count or factors that may contribute to early discontinuation of maribavir. Results (table) Maribavir was used in three male patients with varied conditions – including solid organ transplant (SOT), hematopoietic stem cell transplant (HSCT) and Severe Combined Immunodeficiency (SCID) s/p HSCT. Two cases had signs of CMV disease, and one had CMV viremia. All cases included documented CMV resistance (n=2) or refractory CMV (n=1) and had previously been receiving at least one antiviral with CMV activity for at least 14 days and had increasing CMV DNA-emia in the blood. None of the patients had side effects such as nephrotoxicity, liver toxicity or myelosuppression that aggravated after starting maribavir. Dosing of 400mg BID (range 12mg/kg/day to 55mg/kg/day) was used. Once started, maribavir was continued until CMV quantitative levels were undetectable for two weeks. Clearance of CMV and was achieved in all the patients on maribavir or combination of maribavir with other drugs (n=1). Duration of maribavir treatment ranged from 4.2 to 6.2 weeks. Conclusion This is the first case series describing use of maribavir in a pediatric population. In this small cohort maribavir is effective and well tolerated. Further studies are needed to better CMV care in children with immunocompromised conditions.

β-carotene protects against α-amanitin nephrotoxicity via modulation of oxidative, autophagic, nitric oxide signaling, and polyol pathways in rat kidneys

Alpha-amanitin (α-AMA), a toxic component of Amanita phalloides, causes severe hepato- and nephrotoxicity. This study investigated the protective effects of βeta-carotene (βC) against α-AMA-induced kidney damage in rats. Thirty-two male Sprague-Dawley rats were divided into four groups: Control, βC (50 mg/kg/day), α-AMA (3 mg/kg), and βC+α-AMA. βC was administered orally for 7 days before α-AMA injection. Renal function, oxidative stress markers, histopathological changes, and enzyme activities were evaluated 48 h post-α-AMA administration. α-AMA significantly increased serum creatinine and urea levels, decreased glutathione and catalase activity, and increased malondialdehyde levels (P < 0.001). βC pretreatment attenuated these changes (P < 0.05). Histopathological examination revealed reduced tubular degeneration in the βC+α-AMA group (P < 0.001). Immunohistochemical analysis showed increased LC3B and Beclin-1 expression in α-AMA-treated rats, indicating enhanced autophagy, partially reversed by βC. Additionally, α-AMA reduced nitric oxide synthase (NOS) activity and increased aldose reductase (AR) activity, both normalized by βC pretreatment (P < 0.01). βC demonstrates protective effects against α-AMA-induced nephrotoxicity through antioxidant action, modulation of autophagy, and regulation of NOS and AR pathways, suggesting its potential as a therapeutic agent in α-AMA poisoning.

Effects of normal saline versus lactated Ringer’s solution on organ function and inflammatory responses to heatstroke in rats

BackgroundHeatstroke is a life-threatening condition characterized by severe hyperthermia and multiple organ dysfunction. Both normal saline (NS) and lactated Ringer’s solution (LR) are commonly used for cooling and volume resuscitation in heatstroke patients; however, their specific impacts on patient outcomes during heatstroke management are poorly understood. Given that the systemic inflammatory response and multiple-organ damage caused by heat toxicity are the main pathophysiological features of heatstroke, the aim of this study was to evaluate the effects of NS and LR on the production of inflammatory cytokines and the functional and structural integrity of renal and cardiac tissues in a rat model of heatstroke.MethodsFifty-five male Sprague‒Dawley rats were randomly divided into four groups: cold NS or LR infusion postheatstroke (4 ℃, 4 ml/100 g, over 10 min) and NS or LR infusion without heatstroke induction (control groups). Vital signs, arterial blood gases, inflammatory cytokines, and renal and cardiac function indicators, such as serum creatinine and cTnI, were monitored after treatment. Tissue samples were analysed via HE staining, electron microscopy, and fluorescence staining for apoptosis markers, and protein lysates were used for Western blotting of pyroptosis-related proteins.ResultsCompared with LR-treated heatstroke rats, NS-treated heatstroke rats presented lower mean arterial pressures, worsened metabolic acidosis, and higher levels of IL-6 and TNF-α in both the serum and tissue. These rats also presented increased serum creatinine, troponin, catecholamines, and NGAL and reduced renal clearance. Histological and ultrastructural analyses revealed more severe tissue damage in NS-treated rats, with increased apoptosis and increased expression of NLRP3/caspase-1/GSDMD signalling molecules. Similar differences were not observed between the control groups receiving either NS or LR infusion. One NS-treated heatstroke rat died within 24 h, whereas all the LR-treated and control rats survived.ConclusionsNS resuscitation in heat-exposed rats significantly promotes metabolic acidosis and the inflammatory response, leading to greater functional and structural organ damage than does LR. These findings underscore the necessity of selecting appropriate resuscitation fluids for heatstroke management to minimize organ damage and improve outcomes.

5065 Cyproterone Acetate Versus Spironolactone In Transgender Women Commencing Estradiol: A Randomized Controlled Trial

Abstract Disclosure: L.M. Angus: Advisory Board Member; Self; Kirin Brewery. Speaker; Self; Kirin Brewery. S. Leemaqz: None. A. Kasielska-Trojan: None. M. Mikołajczyk: None. J. Doery: None. J.D. Zajac: None. A.S. Cheung: None. Background: Transgender women commonly use cyproterone acetate or spironolactone as anti-androgens with estradiol to assist with feminization. However, the optimal anti-androgen is unclear. We aimed to assess the effect of these anti-androgens on breast development and hypothesized that cyproterone acetate would result in greater breast development than spironolactone due to greater androgen receptor antagonism and suppression of serum total testosterone. Design: Double-blind, randomised controlled trial Methods: Transgender women newly commencing estradiol were randomized to spironolactone 100mg daily or cyproterone acetate 12.5mg daily for six months. The primary outcome was measurement of breast development via breast chest distance with secondary outcomes of estimated breast volume using the BreastIdea Volume Estimator application and serum total testosterone using LCMS. Results: Fifty-five participants were included in per protocol analysis (cyproterone acetate group n=28, spironolactone group n=27). Baseline age, body mass index, breast indices, serum estradiol and serum total testosterone were comparable. At six months, the mean (standard deviation) breast chest distance was 9.2cm (3.0) in the cyproterone group versus 8.3cm (2.7) in the spironolactone group (p=0.27). The mean (SD) estimated breast volume was 190.25 mL (158.60) in the cyproterone acetate group and 157.84mL (112.03) in the spironolactone group (p=0.39) with significant inter-individual variation (range 20.27 - 787.77 mL). The mean (SD) serum total testosterone was 1.48 nmol/L (3.45) in the cyproterone acetate group and 4.29 nmol/L (5.44) in the spironolactone group (p=0.04). Serum estradiol levels were comparable. Use of cyproterone acetate was associated with mild hyperprolactinaemia and spironolactone with an increase in serum urea and creatinine. Conclusions: Choice of anti-androgen should be individualised based on clinician and patient preference, with consideration of associated side effects. Further research is needed to optimise breast development in transgender women. Presentation: 6/3/2024

A-309 Multicenter Performance Evaluation of the ProNephro AKITM Assay and Sample Stability in Pediatric Patients

Abstract Background Acute Kidney Injury (AKI), defined by increased serum creatinine or decreased urine volume, is highly prevalent in critically ill pediatric patients. Those who develop AKI experience worsened outcomes, raising the need for accurate and early biomarkers for AKI. Relying in serum creatinine for AKI diagnosis is unreliable due to its diagnostic inaccuracy and delayed rise in the AKI pathophysiology. Neutrophil Gelatinase-Associated Lipocalin (NGAL) is a novel and widely studied biomarker for early identification of AKI. During pathological progression, NGAL is elevated in blood and urine within two hours of the insult, making it useful for early diagnosis and management of kidney injury in critically ill children. This study aims at evaluating the performance characteristics of a quantitative test for NGAL in urine intended for use in critically ill pediatric patients, and investigating the stability of NGAL in pediatric urine. Methods The ProNephroAKITM is a particle-enhanced turbidimetric immunoassay on the Roche cobas® c501 analyzer to measure NGAL quantitatively in urine in pediatric patients 3 months to 21 years of age. These studies were approved by the respective institutional review boards. The limits of blank (LOB), detection (LOQ) and quantitation (LOQ) were determined following CLSI EP17A2. Linearity was assessed across the measurement range (MR) of 50-3000 ng/mL. The assay repeatability, between-run, between-day and total imprecision were determined in pediatric urine samples (n=9, covering the MR) and controls (n=2) following CLSI EP5-03 guidelines. Likewise, multisite reproducibility was evaluated in pediatric urine (n=7, covering the MR) and controls (n=2) in 3 laboratories and alternating operators. The assay specificity was assessed in the presence of several endogenous and exogeneous substances (e.g. drugs, contrast agents), potential related cross-reactant molecules, and several pH-values. The stability of NGAL in urine was evaluated using freshly collected pediatric urine samples covering the MR from 16 consented patients after storage at ambient (15-30°C), refrigerated (2-8°C), and frozen temperatures (≤-70°C), and following 3 freeze/thaw cycles. Results The ProNephroAKITM is linear across the MR of 50-3000 ng/mL. The LOB, LOD and LOQ were 9, 14 and 18 ng/mL, respectively. The coefficients of variation (CVs) for repeatability, between-run, between-day and total precision were ≤5.0%, ≤3.1%, ≤1.7% and ≤4.9%, respectively in urine and control samples. The reproducibility across 3 independent laboratories was ≤6.6%. The recovery of NGAL was not significantly affected by endogenous substances, contrast agents, pH (3.3-10.3), and common and special pharmaceutical compounds (exception: very high Cefepime concentrations may decrease NGAL), and potential cross-reactants. Freshly collected urine samples spanning concentrations from 71-2,373 ng/mL were stable (±10% recovery) for 2 days at ambient, 4 days refrigerated and 13 months frozen, and after 3 freeze/thaw cycles. Conclusions We report the performance characteristics of the ProNephroAKITM assay, including excellent precision and adequate reproducibility across 3 laboratories, sensitivity, specificity, and urine sample stability. The test was determined to meet the analytical performance required for clinical use in critically ill pediatric patients at risk of developing or having persistent AKI.

Galangin prevents gentamicin-induced nephrotoxicity by modulating oxidative damage, inflammation and apoptosis in rats.

The well-known antibiotic gentamicin (GEN) works well against a variety of pathogenic bacteria, nevertheless its therapeutic use might be limited by the possibility of nephrotoxicity. The naturally occurring flavonoid galangin (GAL) has several interesting anti-inflammatory and antioxidant properties. The present study evaluated the nephroprotective effect of GAL on GEN-induced renal injury. Rats received GAL for 14 days and GEN from day 8 to day 14. There was a significant increase in serum urea and creatinine along with several histopathological changes in the kidney following GEN administration. GEN-treated rats also showed increased levels of kidney MDA and NO, and decreased GSH content and activities of antioxidant enzymes. Rats received GEN also demonstrated increased NF-κB p65, iNOS, TNF-α, IL-1β and IL-6 levels in the kidney. GAL remarkably prevented tissue injury, attenuated MDA and NO levels, improved antioxidants, and decreased levels of inflammatory mediators in the kidney of GEN-treated rats. Furthermore, GEN-administrated rats exhibited increased Bax and caspase-3 with concomitant decline in Bcl-2 levels in the kidney, an effect that GAL attenuated. In conclusion, GAL prevents GEN-induced nephrotoxicity by attenuating oxidative stress, inflammation, and apoptosis and augmenting antioxidant defense, suggesting its therapeutic potential against drug nephrotoxicity.

The Association Between Vasopressin and Adverse Kidney Outcomes in Children and Young Adults Requiring Vasopressors on Continuous Renal Replacement Therapy.

Continuous renal replacement therapy (CRRT) and shock are both associated with high morbidity and mortality in the ICU. Adult data suggest renoprotective effects of vasopressin vs. catecholamines (norepinephrine and epinephrine). We aimed to determine whether vasopressin use during CRRT was associated with improved kidney outcomes in children and young adults. Secondary analysis of Worldwide Exploration of Renal Replacement Outcomes Collaborative in Kidney Disease (WE-ROCK), a multicenter, retrospective cohort study. Neonatal, cardiac, PICUs at 34 centers internationally from January 1, 2015, to December 31, 2021. Patients younger than 25 years receiving CRRT for acute kidney injury and/or fluid overload and requiring vasopressors. Patients receiving vasopressin were compared with patients receiving only norepinephrine/epinephrine. The impact of timing of vasopressin relative to CRRT start was assessed by categorizing patients as: early (on or before day 0), intermediate (days 1-2), and late (days 3-7). None. Of 1016 patients, 665 (65%) required vasopressors in the first week of CRRT. Of 665, 248 (37%) received vasopressin, 473 (71%) experienced Major Adverse Kidney Events at 90 days (MAKE-90) (death, renal replacement therapy dependence, and/or > 125% increase in serum creatinine from baseline 90 days from CRRT initiation), and 195 (29%) liberated from CRRT on the first attempt within 28 days. Receipt of vasopressin was associated with higher odds of MAKE-90 (adjusted odds ratio [aOR], 1.80; 95% CI, 1.20-2.71; p = 0.005) but not liberation success. In the vasopressin group, intermediate/late initiation was associated with higher odds of MAKE-90 (aOR, 2.67; 95% CI, 1.17-6.11; p = 0.02) compared with early initiation. Nearly two-thirds of children and young adults receiving CRRT required vasopressors, including over one-third who received vasopressin. Receipt of vasopressin was associated with more MAKE-90, although earlier initiation in those who received it appears beneficial. Prospective studies are needed to understand the appropriate timing, dose, and subpopulation for use of vasopressin.

Metformin and vitamin D combination therapy ameliorates type 2 diabetes mellitus-induced renal injury in male Wistar rats.

Diabetic kidney disease is a major microvascular diabetes mellitus (DM) complication clinically associated with a gradual renal function decline. Although metformin is a common drug for managing DM, however, monotherapy treatment with any antidiabetic drug will necessitate dosage increment since type 2 DM (T2DM) deteriorates over time due to the increasing pancreatic β-cell dysfunction and will eventually require a combination therapy approach with another antidiabetic medication. Vitamin D is a food supplement that has been proven to have antidiabetic and reno-protective activities. Hence, we explore the combination of vitamin D and metformin on T2DM-induced renal dysfunction. Thirty male Wistar rats were randomized into five (5) groups: control, diabetes untreated, diabetics treated with metformin, vitamin D, and vitamin D + metformin. Vitamin D and metformin significantly reversed DM-induced hyperglycemia, electrolyte imbalance, and dyslipidemia. Also, vitamin D and metformin reversed T2DM-induced increase in serum creatinine and urea and renal lactate, LDH, and oxido-inflammatory response. These observed alterations were accompanied by an increase in proton pump activities and modulation of Nrf2/Nf-κB and XO/UA signaling. This study revealed that vitamin D and/or metformin ameliorated T2DM-induced renal injury.

Safety of In-hospital Parenteral Antiosteoporosis Therapy Following a Hip Fracture: A Retrospective Cohort

Abstract Purpose To assess the safety of zoledronic acid (ZOL) and denosumab (Dmab) administered following hip fracture in a hospital setting. Methods Patients older than 65 years were treated by a fracture liaison service following hip fracture. Generally, patients who had a glomerular filtration rate (eGFR) &amp;gt; 35 mL/min were treated with ZOL, whereas patients who had previously received bisphosphonates or had a eGFR between 20 and 35 mL/min were treated with Dmab. Adverse events included hypocalcemia (calcium corrected for albumin less than 8.5 mg/day), renal functional impairment (0.5 mg/dL or more increase in serum creatinine) within 30 days of treatment, or a fever (&amp;gt;38 °C) within 48 hours of drug administration. Results Two hundred twenty-eight and 134 patients were treated with ZOL and Dmab, respectively. Mean body temperature was elevated following ZOL administration (0.18 °C P &amp;lt; .001) but remained below 38 °C. Hypocalcemia occurred in 18% and 29% of the ZOL and Dmab groups, respectively (P = .009). Renal functional impairment was observed in 9 and 6 patients (4% and 5%) in the ZOL and Dmab groups, respectively (P = .8). Pretreatment calcium above 9.3 mg/dL was associated with a lower risk of posttreatment hypocalcemia (odds ratio 0.30, 95% confidence interval 0.13-0.68, P = .004). While the absolute risk of hypocalcemia was higher in the Dmab group, multivariate analysis did not find that the choice of drug was predictive of hypocalcemia. Conclusion In-hospital parenteral osteoporosis treatment was rarely associated with fever or renal function impairment but was associated with hypocalcemia. Posttreatment hypocalcemia risk did not vary significantly between patients receiving ZOL or Dmab.

Surgical Management of Canine Transmissible Venereal Tumor with Adjunctive Chemotherapy Combination

One male and a female 2-year-old Neapolitan Mastiff dogs weighing 41 and 40 kg, respectively, were presented to the University Veterinary Teaching Hospital, Jos, Nigeria, with complaints of continuous bleeding from the prepuce and vulva which were first observed about 2 months before presentation. Clinical examination revealed preputial bleeding of the male dog and serosanguinous vulva discharges with the presence of palpable masses with multiple nodules that were cauliflower-like. Cytological evaluations of smears from preputial and vaginal swabs revealed characteristic round cells with large eccentric nuclei, large nuclear-cytoplasmic ratio, and intracytoplasmic vacuolations as well as anisocytosis and anisokaryosis. Based on these cytological features, a diagnosis of canine transmissible venereal tumor (CTVT) was made in each case. Blood samples were collected for hematology and clinical chemistry. Debulking of the masses was carried out under general anesthesia using atropine sulfate and chlorpromazine as pre-anesthetics and Ketamine hydrochloride as induction and maintenance anesthetics. Following debulking, the resulting defect was reconstructed and the surgical wound was managed by daily wound cleaning and the administration of vincristine sulfate (0.025 mg/kg) slowly intravenously, ivermectin (0.3 mg/kg) subcutaneously, and piroxicam (0.3 mg/kg) and 20% amoxicillin (20 mg/kg) intramuscularly. There were no observed known vincristine sulfate-associated adverse effects as the dogs recovered and were discharged 3-week post-tumor debulking with no recurrence within 6 months of follow-up examinations. The debulked mass histologically showed several sheets of round neoplastic cells with prominent nuclei, mitotic figures, and infiltrating lymphocytes. Based on these findings, a diagnosis of CTVT was further confirmed. The hemogram showed moderate leukocytosis at day 1 in the bitch with a mild left shift at days 1 and 14 while clinical chemistry showed a marked increase in alkaline phosphatase, moderate increase in serum creatinine, and mild hypoproteinemia. In conclusion, management of CTVT with adjunctive vincristine sulfate and ivermectin combination resulted in complete healing with amelioration of known associated adverse effects.