Increase In Creatinine Research Articles

Development of a Porcine Model of Arteriovenous Fistula Venous Stenosis Treated with Percutaneous Transluminal Angioplasty

To develop a porcine model for arteriovenous fistula (AVF) venous stenosis treated with percutaneous transluminal angioplasty (PTA) and compare outcomes of plain balloon angioplasty (POBA) to IN.PACT paclitaxel drug-coated balloons (DCB). Twelve castrated male Yorkshire pigs (4-5 months, 35-45kg) underwent renal artery embolization to induce chronic kidney disease (CKD). Twenty-eight days later, AVF was created by anastomosing the left external jugular vein to left common carotid artery. The pigs were divided into a pilot group (n=6) for optimizing the AVF technique (euthanized at day 4) and a definitive group (n=6) for validating PTA outcomes (euthanized at day 42). Stenosis developed at juxta-anastomosis 28 days later and was treated with POBA [pilot group (n=6), definitive group (n=3)] or DCB [definitive group only (n=3)]. Definitive group underwent biweekly 4D Flow MRI scans. All animals developed CKD, with significant increases in BUN (median increase: 2.6 to 3.2 mmol/L, P<0.001) and creatinine (median increase: 100 to 187 μmol/L, P<0.001). In the pilot group, one animal had an infected fistula, and AVF patency was 1/5. In the definitive group, the patency was 5/6 because the AVF technique was modified by resecting the sternomastoid muscle and increasing the spatulation. At day 42 post PTA, DCB treated AVF outflow vein showed increasing blood flow compared to POBA (DCB 209.8 ± 64.42 mm2 vs POBA 170.9 ± 95.52 mm2 p = 0.934). A porcine model of AVF venous stenosis treated with PTA was developed, with blood flow trends favoring DCB over POBA.

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.

Reversible elevation of creatine kinase and creatinine caused by sintilimab-induced hypothyroidism: A case report.

Programmed cell death (PD) -1 inhibitors has significantly improved the prognosis of cancer patients by enhancing antitumor immune responses. However, PD-1 inhibitors are associated with immune-related adverse events, some of which are rare and potentially life-threatening. Thus far, elevated creatine kinase (CK) and creatinine caused by a novel PD-1 inhibitor (sintilimab)-induced hypothyroidism has not yet been reported. A 63-year-old male patient with esophageal cancer who developed hypothyroidism accompanied by unexplained increases in CK and creatinine after sintilimab treatment. Since the increases in CK and creatinine paralleled the decrease in thyroxine, after excluding other potential conditions, we speculated that the muscular and renal dysfunction might be caused by sintilimab-induced hypothyroidism. As the patient's thyroid function improved with levothyroxine replacement therapy, the levels of CK and creatinine concomitantly returned to normal. The elevated CK and creatinine levels in this patient were caused by sintilimab-induced hypothyroidism. Our case highlights the importance of keeping PD-1 induced hypothyroidism in mind when patients present with unexplained increased levels of CK and creatinine. Hypothyroidism-related muscular and renal dysfunctions, which can be restored with thyroid hormone replacement, need to be identified early and treated promptly so that unnecessary examinations and treatments can be avoided in these patients.

Gastrointestinal permeability and kidney injury risk during hyperthermia in young and older adults.

We tested whether older adults, compared with young adults, exhibit greater gastrointestinal permeability and kidney injury during heat stress. Nine young (32±3 years) and nine older (72±3 years) participants were heated using a model of controlled hyperthermia (increasing core temperature by 2°C via a water-perfused suit). Gastrointestinal permeability was assessed using a multi-sugar drink test containing lactulose, sucrose and rhamnose. Blood and urine samples were assayed for markers of intestinal barrier injury [plasma intestinal fatty acid binding protein (I-FABP), plasma lipopolysaccharide binding protein (LBP) and plasma soluble cluster of differentiation 14 (sCD14)], inflammation (serum cytokines), kidney function (plasma creatinine and cystatin C) and kidney injury [urine arithmetic product of IGFBP7 and TIMP-2 (TIMP-2 × IGFBP7), neutrophil gelatinase-associated lipocalin and kidney injury molecule-1]. The lactulose-to-rhamnose ratio was increased in both young and older adults (group-wide: Δ0.11±0.11), but the excretion of sucrose was increased only in older adults (Δ1.7±1.5). Young and older adults showed similar increases in plasma LBP (group-wide: Δ0.65±0.89µg/mL), but no changes were observed for I-FABP or sCD14. Heat stress caused similar increases in plasma creatinine (group-wide: Δ0.08±0.07mg/dL), cystatin C (group-wide: Δ0.16±0.18mg/L) and urinary IGFBP7×TIMP-2 [group-wide: Δ0.64±0.95 (pg/min)2] in young and older adults. Thus, the level of heat stress used herein caused modest increases in gastrointestinal permeability, resulting in a mild inflammatory response in young and older adults. Furthermore, our data indicate that older adults might be more at risk for increases in gastroduodenal permeability, as evidenced by the larger increases in sucrose excretion in response to heat stress. Finally, our findings show that heat stress impairs kidney function and elevates markers of kidney injury; however, these responses are not modulated by age.

Early metabolic and hemodynamic indicators of kidney dysfunction in mice offspring from parental low protein diet

BackgroundParental malnutrition, particularly a low-protein diet (LPD), causes oligonephropathy at birth and predisposes offspring to hypertension and chronic kidney disease later in life. The onset of adult kidney disease varies based on genetics and environmental factors, often with subclinical alterations in kidney function being overlooked. This study aimed to examine changes in kidney morphology before significant kidney function decline in the offspring of mice fed a low-protein diet.MethodsUsing a combination of histological analysis, kidney metabolic and hemodynamic panel assessments, and advanced statistical techniques such as Linear Discriminant Analysis (LDA) and Principal Component Analysis (PCA), we investigated the initial impact of a maternal low-protein diet (LPD) on kidney development and function. Our study utilized 12-week-old F1 mice from F0 parents fed either a low-protein diet (LPD) or a normal-protein diet (NPD) before the onset of hypertension.ResultsThe offspring (F1 generation) of parents (F0 generation) fed an LPD show reduced body weight from birth to P20. The kidney weight was also reduced compared to F1 offspring from parents fed an NPD. At 12 weeks of age, body weight normalized, but kidney weight remained low. Offspring of parents fed an LPD displayed abnormal kidney morphology, including dilated tubules, oligonephropathy, and fluid-filled cysts which had worsened with age. A kidney metabolic panel analysis at 12 weeks revealed a slight but consistent increase in urine albumin, plasma creatinine, mean urea, and BUN concentrations. Although no significant changes in hemodynamic variables were observed, 2/12 mice, both males, showed alterations in systolic blood pressure, suggesting sex-specific effects when comparing F1 mice from F0 fed either diet. Overall, kidney metabolic changes were strongly correlated to parental LPD.ConclusionOur findings indicate that significant kidney damage must accumulate in the F1 generation from parents fed an LPD before any detectable changes in blood pressure occur. Our study suggests that small variations in kidney metabolic function may point to early kidney damage and should not be overlooked in the offspring of these malnourished mice and likely humans.

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

Severe Combined Kidney Injury in an Hiv-Infected Patient Receiving Antiretroviral Therapy (Clinical Observation)

Kidney injury in patients infected with the human immunodeficiency virus (HIV) has a diverse spectrum. Some antiretroviral therapy (ART) drugs have nephrotoxic effects. We present a clinical case of severe combined kidney injury — chronic kidney disease (CKD) and acute kidney disease (AKD) — in a patient with HIV infection. She was on long-term treatment with a fixed-dose combination of rilpivirine, tenofovir, and emtricitabine and had normal pre-treatment renal function (estimated glomerular filtration rate 69 mL/min/1.73m2 ). There was gradual increase in blood creatinine, but the patient did not visit a nephrologist and the ART was not changed. The patient was admitted to the nephrology department two years later because she had arterial hypertension and hyperazotemia (blood creatinine 718 μmol/l). Diagnosis: chronic tubulointerstitial nephritis, CKD G5 taking into account the gradual increase in blood creatinine during long-term ART. The patient was treated with peritoneal dialysis. There was persistent decrease and stabilization of blood creatinine (210-190 μmol/l was) which indicated in AKD. The presented observation demonstrates that ART in an HIVinfected patient can lead to the development of severe combined chronic and acute kidney injury. HIV-infected patients receiving ART require regular monitoring of renal function and follow-up by a nephrologist.

8706 Hypoparathyroidism and Hypercalcemia in Premature Secondary to Excessive Vitamin D: Everything in Excess is Opposed

Abstract Disclosure: D.M. Bastos: None. A. Bastos: None. Introduction: Vitamin D intoxication in children is rare but its incidence is increasing as vitamin D is supplemented more often and in higher doses. Coma, ventricular fibrillation, and acute renal insufficiency are possible life-threatening presentations of vitamin D-induced hypercalcemia. Nephrocalcinosis, renal lithiasis, vascular calcifications, and arterial hypertension are known late complications of severe or longstanding hypercalcemia. The most common causes of vitamin D intoxication in children are manufacturing errors, parental dosing errors, and erroneous medical prescriptions. Case Presentation: A premature girl admitted to the neonatal ICU 3 months ago due to poor weight gain and was taking vitamin D and infant formulas and developed tachycardic heart rhythm with irregular rhythm and kidney changes. The investigation of the condition was re-evaluated, and the patient was seen with hypercalcemia, an increase of more than 100x in the dosage of 25(OH)vitamin D, an increase in the dosage of 1.25(OH)vitamin D, suppressed PTH, an increase in creatinine and urea. In addition, an ultrasound was performed showing the presence of small kidney stones, none of which were obstructive. After discontinuing vitamin D supplementation, the patient progressed satisfactorily with a reduction in cardiac and renal changes. Discussion: Currently, vitamin D supplementation has been carried out more frequently, as, in addition to increasing the absorption of calcium in the body, it reduces the risk of diseases, such as rickets and osteopenia of prematurity. The body is only able to produce vitamin D after exposure to sunlight. In the absence of regular exposure, dietary sources alone are not sufficient to maintain adequate levels. Cases of hypervitamin D generally occur in situations of excessive supplementation. In the present report, the dose used was 40 times higher than recommended. Initial tests revealed elevated calcium and undetectable PTH levels. The diagnosis of vitamin D intoxication is not common in cases of hypercalcemia, as it is infrequent, especially before the advent of vitamin D supplementation. Vitamin D toxicity is usually iatrogenic, or due to accidental overdose. These factors, along with a lack of public education about safe dosing, have likely contributed to the increase in reported cases of vitamin D toxicity. Conclusion: Vitamin D supplementation, especially when using compounded medications, must be adequately monitored due to the potential risk of poisoning. Vitamin D toxicity remains a pressing issue and its incidence will likely continue to grow, primarily because of the widespread availability of over-the-counter formulations and public interest. Presentation: 6/3/2024

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

9330 Atumelnant (crn04894) Induces Rapid And Sustained Reductions In Serum And Urine Cortisol In Patients With Acth-Dependent Cushing Syndrome During A Phase 1b/2a, Single Center, 10-day, Inpatient, Open-Label Study

Abstract Disclosure: H. Elenius: Grant Recipient; Self; Crinetics Pharmaceuticals, Inc. R. McGlotten: Grant Recipient; Self; Crinetics Pharmaceuticals, Inc. C. Moore: Grant Recipient; Self; Crinetics Pharmaceuticals, Inc. Y.B. Omotosho: Grant Recipient; Self; Crinetics Pharmaceuticals, Inc. A. Ayala: Employee; Self; Crinetics Pharmaceuticals, Inc.. Stock Owner; Self; Crinetics Pharmaceuticals, Inc. Y. Wu: Employee; Self; Crinetics Pharmaceuticals, Inc.. Stock Owner; Self; Crinetics Pharmaceuticals, Inc. P.J. Trainer: Employee; Self; Crinetics Pharmaceuticals, Inc.. Stock Owner; Self; Crinetics Pharmaceuticals, Inc. R.S. Struthers: Employee; Self; Crinetics Pharmaceuticals, Inc.. Stock Owner; Self; Crinetics Pharmaceuticals, Inc. A. Krasner: Employee; Self; Crinetics Pharmaceuticals, Inc.. Stock Owner; Self; Crinetics Pharmaceuticals, Inc. S.F. Betz: Employee; Self; Crinetics Pharmaceuticals, Inc.. Stock Owner; Self; Crinetics Pharmaceuticals, Inc. L.K. Nieman: Grant Recipient; Self; Crinetics Pharmaceuticals, Inc.. Atumelnant is a potent, once-daily oral, nonpeptide, first-in-class competitive and selective melanocortin type 2 receptor (MC2R) antagonist that blocks ACTH-mediated G-protein activation and subsequent signaling. It is being developed for the treatment of ACTH-dependent Cushing Syndrome (ADCS) and classic congenital adrenal hyperplasia. We report preliminary data from the first-in-disease, dose-finding study of atumelnant in patients with ADCS (NCT05804669). Inpatient participants with active ADCS (24h urine free cortisol (UFC) &amp;gt;1.3xULN, ACTH &amp;gt;10 pg/mL) received atumelnant 80 mg once daily at 08.00 for 10 days (D1-10) followed by a 4-day washout. Endpoints included changes in UFC (upper limit of normal (ULN) 45 ug/d), early morning cortisol (EMC), and early morning ACTH (EMA, ULN 46 pg/mL). Daily questionnaires assessed adverse events (AEs) and signs and symptoms of adrenal insufficiency (AI) and ADCS. Data are shown as median (range). We report 5 participants (4 men; 4 Cushing disease, 1 ectopic ACTH; age 47 years (34-55)); each completed the study. All participants developed biochemical evidence of AI (EMC &amp;lt;5 mcg/dL) after 2 days (1-10) of atumelnant administration and then commenced physiologic hydrocortisone (HC) add-back. Compared to D1, biochemical disease control (normal UFC plus EMC &amp;lt;5 mcg/dL) was shown on D11 in all participants, while receiving HC replacement: UFC 252 mcg (99-293) vs 24 mcg (3.9-51); EMC 14 mcg/dL (10.7-18.1) vs 1.4 (1.0-4.7). This was associated with an increase in EMA: 52.1 pg/mL (33-1088) vs 78 pg/mL (48.8-4045). HC was discontinued when EMC was ≥7 mcg/dL, on D13 (D12-18). Many pre-existing features of ADCS improved during atumelnant administration, including poor concentration, insomnia (n=3 each); brain fog, anxiety, irritability (n=2 each); fatigue, poor memory, low libido, depression, edema and bloating (n=1 each). Low testosterone, neutrophilia (n=3 each) and leukocytosis (n=2) observed at baseline resolved during atumelnant administration. Anti-hypertensive therapy was paused or reduced in 3 subjects. New fatigue, headache, nausea, anorexia, edema (n=2 for each) all coincided with development of biochemical AI; most symptoms improved with HC add-back. Serious adverse events included AI and one non-treatment related transient GI bleed 19 days after the last dose. All other AEs were mild or moderate: transient increases of creatinine (n=2), and ALT (&amp;lt;3xULN, n=2). In conclusion, the first 5 patients with ADCS to receive once daily, oral atumelnant experienced rapid lowering of serum and urine cortisol and improvement or resolution of some signs and symptoms of ADCS. Atumelnant was generally well-tolerated. The observed compensatory increase in ACTH was not associated with loss of efficacy or clinical sequelae. This ongoing study will further explore the relationship between atumelnant dose, including lower doses, and therapeutic response. Presentation: 6/3/2024

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.

Clinical efficacy and safety of new compound single tablet antiviral drugs in the treatment of HIV/AIDS

AimsGenvoya, Biktarvy and Dovato are novel single-tablet antiretroviral therapy(ART). The aim of this study is to explore the therapeutic effects of these novel drugs on HIV/AIDS. Main methodsThis retrospective cohort study, conducted at a single center, included a total of 200 HIV-treated patients who transitioned to these new antiretroviral drugs from July 2021 to August 2023. Data were extracted from electronic medical records at Ditan Hospital. The Genvoya group comprised 22 patients, and all subsequent switches in this group were to Biktarvy. The primary HAART group consisted of 178 patients initially treated with a first-line triple Highly Active Antiretroviral Therapy (HAART) regimen during the same period. This group was further subdivided into HAART+Dovato, HAART+Biktarvy, and HAART+Genvoya groups based on the switching regimen. The primary outcomes focused on changes in viral load and immune efficacy, while secondary safety indicators included blood/liver function, lipid parameters, renal function, blood glucose, blood uric acid, etc. Key findingsThe viral suppression rate was 100 % after the drug change treatment, and CD4+ T cell counts increased significantly across all four groups. Over the 6-month treatment period, there were increases in creatinine (Cr), low-density lipoprotein (LDL), high-density lipoprotein (HDL), erythrocyte count, and glomerular filtration rate (eGFR). Conversely, Alanine transaminase (ALT), Aspartate aminotransferase (AST), C-reactive protein (CRP), albumin (ALB), and blood glucose (Glu) levels decreased. SignificanceGenvoya, Biktarvy and Dovato are recommended for the treatment of HIV/AIDS and have a good safety profile.

Characterization and Clinical Significance of Hemolysis After Pulsed Field Ablation for Atrial Fibrillation: Results of a Multicenter Analysis.

Pulsed field ablation (PFA) is increasingly used in clinical practice for the treatment of atrial fibrillation. While the susceptibility of erythrocytes to electroporation is well established, the effect of cardiac PFA technologies on hemolysis has remained underreported. The aim of this study was to investigate the incidence, severity, and clinical impact of PFA-induced hemolysis. We included n=145 patients undergoing atrial fibrillation catheter ablation with a pentaspline PFA catheter (biphasic, bipolar pulses of 2 kV) and n=70 patients receiving radiofrequency ablation (40-90 W) at 4 high-volume European centers. The lesion set comprised pulmonary vein isolation for paroxysmal atrial fibrillation and pulmonary vein isolation±additional lesions for persistent atrial fibrillation. Hemolysis and renal function biomarkers were analyzed in blood samples at baseline, at the end of ablation, and 24 hours after the procedure. Baseline characteristics were well balanced between groups (overall mean, 65.7±9.4 years; 69.3% male). The ablation procedures comprised a mean of 61.6±27.4 PFA deliveries and 26.3±15.0 minute RF duration. Hemolysis was detected in 94.3% versus 6.8% of patients after PFA versus radiofrequency ablation (P<0.001): PFA was associated with significantly lower haptoglobin levels (0.5±0.4 versus 1.0±0.4 g/L), while free plasma hemoglobin (592.8±330.6 versus 147.8±183.0 mg/L), bilirubin (21.3±11.3 versus 14.8±8.8 µmol/L), and LDH (lactate dehydrogenase, 352.7±115.7 versus 253.2±56.5 U/L) were significantly higher after PFA versus radiofrequency ablation (all P<0.001). Hemolysis correlated with the number of PFA deliveries (r=0.62 [95% CI, 0.33-0.80]; P<0.001), with the highest severity occurring ≥54 PFA deliveries. After PFA, hemoglobinuria occurred in 36.4%, while creatinine increase was higher in patients with baseline glomerular filtration rate <50 mL/min versus baseline glomerular filtration rate >50 mL/min (Δcrea, 27.0±103.1 versus -0.2±12.1 µmol/L; P=0.010). Intravascular hemolysis is a frequent finding after PFA and increases with the number of PFA deliveries. Until the clinical impact of PFA-associated hemolysis is fully elucidated, a careful titration of PFA deliveries during the ablation procedure is warranted.

Agreement between different eGFR equations in diagnosing contrast-induced acute kidney injury in patients undergoing elective coronary or peripheral angiography

Abstract Background In the present study, we aimed to compare CKD-EPI, MDRD, CKD-EPI creatinine-cystatin C equations and serum cystatin C and NGAL levels changes in assessing the occurrence of contrast-induced acute kidney injury (CI-AKI) in patients undergoing coronary and peripheral angiography and to evaluate the agreement between the CKD-EPI formula and the other parameters. Methods A cross-sectional study was performed in patients hospitalized with stable coronary artery disease and/or peripheral vascular disease, who underwent diagnostic and/or therapeutic invasive angiography using iodinated contrast agents. Standard laboratory parameters, NGAL, cystatin C levels, and eGFR were evaluated at admission and 48 hours after contrast substances exposure. Results Per different proposed definitions for CI-AKI, 7 patients (17.5 %) had a more than &gt; 0.3 mg/dl increase in serum creati-nine, 1 (2.5 %) had a &gt; 25 % increase in serum cystatin C and 9 (22.5 %) had a &gt; 25% increase in serum NGAL. The agreement between attributions based on CKD-EPI was excellent with MDRD (K coefficient 0.875), and modest with CKD-EPI creatinine-cystatin, which had also a modest agreement with MDRD (K coefficient 0.285). An increase in cystatinc C of more than 25% from baseline was not in concordance with a significant decrease in eGFR calculated with any equation, and the same was observed for NGAL. Conclusions In the present study, the performance of the CKD-EPI equation in diagnosing CI-AKI was not significantly better or worse than MDRD, CKD-EPI creatinine-cystatin, serum creatinine, NGAL or cystatin C increase.

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.

Assessment of Predictors of Acute Kidney Injury and Progression to Chronic Kidney Disease Following Bariatric Surgery

BackgroundDespite the overall safety of metabolic and bariatric surgery (MBS), the potential for postoperative complications such as acute kidney injury (AKI) remains a critical concern. Decade-old studies from our institution reported rates of AKI following MBS between 5.8% and 8.6%, with factors such as higher body mass index (BMI), diabetes, and hypertension identified as potential contributors. However, the incidence and factors associated with AKI following MBS have remained underexplored in contemporary literature. ObjectiveTo investigate the incidence and risk factors associated with postoperative AKI, as well as the potential for progression to CKD and renal failure. SettingQuaternary academic medical center with a high-volume MBS practice. MethodsA retrospective review of adult patients undergoing primary laparoscopic MBS between 2008 and 2022 to identify patients who developed AKI, defined as postoperative increase in serum creatinine (sCr) by 0.3 mg/dL within 72 hours. A multivariable logistic regression was constructed to identify potential AKI risk factors. ResultsAmong 1697 patients, the incidence of AKI was 3.0% (n=51). The distribution of AKI was not significantly different between procedure types. There was no significant correlation between anesthesia medications given and the occurrence of AKI. Male gender was the most significant predictor of AKI (adjusted odds ratio [aOR] = 3.87, 95% CI [2.14 – 6.99]), followed by hypertension (aOR = 2.12, 95%CI [1.03 – 4.83]) and longer surgical duration (aOR = 1.19, 95% CI [1.05 – 1.35]) per 30 minutes. Of those who developed AKI, 7 (13.7%) required dialysis acutely for management, while 3 patients (5.9%) progressed to chronic renal failure and required transplant. ConclusionAKI is a rare but serious complication following MBS that occurs in approximately 3% of cases. AKI incidence is higher in male patients, those with hypertension, insulin-requiring diabetes, renal insufficiency, and longer procedure durations. Heightened awareness of the identified risk factors should help guide patient selection, and additional efforts should be directed towards refining postoperative follow-up.

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.

Combined strategy of device-based contrast minimization and urine flow rate-guided hydration to prevent acute kidney injury in high-risk patients undergoing coronary interventional procedures.

Contrast-associated acute kidney injury (CA-AKI) is a major complication following coronary procedures. We aimed to evaluate the effectiveness of a combination of urine flow rate-(UFR) guided hydration (RenalGuardTM) and device-based contrast media (CM) reduction (DyeVertTM) in CA-AKI prevention. Stable high-risk patients undergoing coronary procedures with the use of DyeVertTM and RenalGuardTM were prospectively included (Combined group) and matched with a similar cohort of patients treated only with RenalGuardTM in whom CM volume was controlled by operator-dependent strategies (Control group). CA-AKI was defined as a serum creatinine increase ≥0.3 mg/dL at 48 h. Overall, 55 patients were enrolled and matched with comparable controls. Patients in the Combined group were exposed to a lower CM dose (Control: 55 [30-90] mL vs. Combined: 42.1 [24.9-59.4] mL; p = 0.024). A significant interaction was found between treatment allocation and serum creatinine changes (p = 0.048). CA-AKI occurred in five (9.1%) patients in the Combined group and in 14 (25.4%) patients in the Control group (OR 0.29, 95% CI [0.09-0.88]). A combined strategy of device-based CM reduction plus UFR-guided hydration is superior to operator-dependent CM sparing strategies plus UFR-guided hydration in preventing CA-AKI in high-risk patient.