bluuebunny/crossref_metadata_2025_split huggingface dataset:
#1091 Quantifying the potential contribution of drugs to the occurrence of acute kidney injury in patients with chronic kidney disease
Authors: Liabeuf Sophie , Massy Ziad , Gras-Champel Valérie , Frimat Luc , Laville Maurice , Jacquelinet Christian , Pecoits-Filho Roberto , de Pinho Natalia Alencar , Hamroun Aghilès , Laville Solene M 
Published: May 2024

Abstract

Background and Aims
Patients with CKD have high risk of AKI. Quantifying the contribution of drugs to the occurrence of AKI in this population and assessing its risk factors is important to design preventive interventions. We sought to comprehensively describe drug-related components associated with AKI in patients with CKD. We documented the incidence of drug-related AKI, the proportion of preventable AKI, identified the various drugs potentially associated with it, explored the risk factors, and assessed the one-year incidences of the recurrence of drug-related AKI, kidney failure, and death.

Method
The CKD-REIN study is a national prospective cohort of 3,033 nephrology outpatients with a confirmed diagnosis of CKD (eGFR &lt;60 mL/min/1.73 m²) in France. AKIs and adverse drug reactions (ADRs) were prospectively identified from hospital charts, medical records, and patient interviews. Nephrologists used the Kidney Disease: Improving Global Outcomes criteria to adjudicate all stages of AKI, and expert pharmacologists used validated tools to adjudicate ADRs (including drug-related AKIs). A drug-related AKI was considered serious when the outcome is death, a life-threatening situation, hospital admission, disability, permanent damage, or another important medical event. We used cause-specific Cox proportional hazard models to investigate the patients’ baseline clinical characteristics associated with the risk of drug-related AKI.

Results
Over a median [interquartile range] period of 4.9 [3.4-5.1] years, 832 cases of AKI were reported in 639 (21%) of the 3,033 study participants. Over a quarter of the AKI events were drug-related (n = 236, 28%); from those, 47% were hospital- and 53% community-acquired AKI. From the 168 serious drug-related AKI events, 28% were considered preventable or potentially preventable. The three most frequently implicated drug classes were diuretics, renin-angiotensin system inhibitors, and contrast agents. At least two concomitant medications were implicated in more than half of the AKIs with a drug-related component, RASis and diuretics, two diuretics, and diuretics and antibiotics were the 3 most frequent associations (Figure). A history of cardiovascular events, and the presence of diabetes, lower levels of hemoglobin and eGFR, poor medication adherence, and ≥5 drugs being taken daily were associated with a greater risk of drug-related AKI. The one-year cumulative incidences of recurrent drug-related AKI, kidney replacement therapy, and death were 7%, 15%, and 11%, respectively, after the first drug-related AKI.

Conclusion
Drug-related AKI is prevalent among patients with CKD. Further training in drug management for both CKD patients and healthcare professionals involved in their care might mitigate the incidence of drug-related AKI.
#2593 Comparison of four predictive scoring models as assessment tools for cardiac surgery-associated acute kidney injury in post cardiac surgery patients
Authors: Iway Cathleen 
Published: May 2024

Abstract

Background and Aims
Cardiac surgery-associated acute kidney injury (CSA-AKI) is a predominant contributor to hospital-acquired AKI in ICU following sepsis. Despite a rising frequency of CSA-AKI, currently examined predictive models have not consistently delivered accurate stratification. Utilizing risk stratification systems offers clinicians the opportunity to identify patients at high risk, extend monitoring intervals, facilitate timely referral to nephrology services, and promptly initiate effective preventive and therapeutic interventions known to enhance renal function. This study seeks to identify the most effective model by comparing four established predictive scoring systems.
The objective of this single-center retrospective, cross sectional study is to compare the clinical values of the Cleveland Clinical Score, Mehta Score, Simplified Renal Index and Acute Kidney Injury following Cardiac Surgery (AKICS) Score in predicting CS-AKI among patients who underwent cardiac surgery.

Method
A comprehensive examination of medical records was conducted for all individuals who underwent open-heart surgery between January 2010 and January 2019. Those patients who had CSA-AKI were subsequently identified. These identified individuals underwent assessment using the four predictive scoring models, leading to their categorization into high or low-risk groups for AKI development. Binary logistics regression was then used to describe the association between CSA-AKI development and the four scoring methods as predictors.

Results
Among the 114 cases of open-heart surgeries, 86 were eligible for inclusion in the study. Half of the patients, specifically 43 individuals (50%), developed CS-AKI, with 5 requiring renal replacement therapy. Among the four scoring methods evaluated, only the Mehta score (95% CI, p 0.019) and AKICS score (95% CI, p 0.011) demonstrated statistical significance in predicting CS-AKI. The odds ratios for both the Mehta Score (1.10) and AKICS Score (1.19) exceeded 1, suggesting that an increase in either score is associated with a higher likelihood of AKI occurrence. Conversely, the Cleveland Clinical Score (p 0.106) and Simplified Renal Index (p 0.399) were not found to be predictive.

Conclusion
In this single-center study, both the Mehta score and the AKICS scoring system demonstrated predictability for AKI after open-heart surgery. However, the Cleveland Clinical Scoring and Simplified Renal Index did not exhibit predictive capability in this context.
#2564 Terlipressin given by continuous infusion versus boluses in the treatment of hepatorenal syndrome: a systematic review and meta-analysis
Authors: Villavicencio Jayson , Panganiban Bea Regine , Villanueva Cary Amiel , Lao Janice Jill 
Published: May 2024

Abstract

Background and Aims
Hepatorenal syndrome (HRS) is one of the complications among patients with cirrhosis. Available guidelines recommended terlipressin with albumin as part of HRS management. To date there is no consensus on whether terlipressin should be given via bolus or continuous intravenous infusion. This study aims to compare the effectiveness and safety of continuous intravenous infusion versus intravenous boluses of terlipressin in the treatment of patients with HRS and cirrhosis.

Method
A comprehensive search for databases of randomized controlled trials (RCTs) comparing continuous intravenous infusion versus intravenous boluses of terlipressin among adult patients with hepatorenal syndrome was done. PubMed, EMBASE, the Cochrane Library, and ClinicalTrials.gov were searched using relevant terms including hepatorenal syndrome, acute kidney injury, cirrhosis, terlipressin, bolus, and continuous infusion until December 2023. Response to therapy defined as decrease in serum creatinine or regression of acute kidney injury was the primary outcome of interest, while safety in terms of drug-related events, mortality, and transplant-free survival were the secondary outcomes. Data extraction was performed using a standardized data form. The reviewers independently screened the studies and assessed the methodological quality using the Cochrane Risk of Bias tool and any discrepancies were resolved by consensus among the authors. Random-effects meta-analysis was done using Review Manager 5.4.

Results
A total of three studies, one high quality and two moderate quality RCTs, were included in the review, involving a total of 240 patients. Pooled analysis showed that continuous infusion was as effective or better than bolus infusion in achieving the primary outcome (RR 1.12, 95% CI 0.95-1.32, I2 = 0%). In one study, 28- and 90-day mortality were not significantly different, while 90-day transplant-free survival was not significantly different between continuous and bolus groups from another trial (53% vs 69% p = 0.26). Higher incidence of adverse events were also reported in the bolus group, RR 0.37, 95% CI 0.13-1.04 (p = 0.06).

Conclusion
There is limited evidence to suggest that continuous infusion of terlipressin may demonstrate resolution of acute kidney injury more frequently than bolus infusion, and that continuous infusion is associated with decreased adverse events. Larger randomized controlled trials with higher quality are needed to ascertain the effects on mortality, need for renal replacement therapy, and transplant-free survival.
#59 Fibroblast Growth factor 23 for prediction of outcome in community-acquired acute kidney injury: a prospective observational study
Authors: Elkot Mahmoud , Sayed-Ahmed Nagy , Ahmed  , Nassar Mohammed Kamal 
Published: May 2024

Abstract

Background and Aims
Serum FGF23 level has been found to be elevated in AKI through multiple previous studies. Moreover, higher FGF23 level was associated with mortality and adverse outcomes in critically ill patients and patients undergoing cardiac surgery who developed AKI suggesting that FGF23 can have a prognostic value in AKI. The current study aims to investigate the association of serum FGF23 levels with morbidity and mortality in patients with community-acquired AKI.

Method
A longitudinal prospective study was carried out that included 64 patients who presented with community-acquired AKI to Mansoura Nephrology and Dialysis Unit (MNDU) at Mansoura University Hospital. Serum intact FGF23 level was measured after admission. patients were followed up during hospital stay and then at 90-day after admission. The primary outcomes were hospital and 90-day mortality and renal recovery.

Results
In this study, nine of the studied 64 AKI patients (14.1%) died during hospital admission and 18 out of 62 AKI patients (29%) died during the 90-day follow up period including those who died during hospital admission. Hospital mortality was significantly higher in patients with shock, sepsis, hypoalbuminemia, or high FGF23 in univariate analysis (p &lt; 0.05). However, when binary logistic regression was carried out, shock was the only significant independent predictor for mortality [p value = 0.015; adjusted odds ratio = 12.465], while serum FGF23 did not independently predict in-hospital [p value = 0.589; adjusted odds ratio = 1.001] or 90-day mortality [p value = 0.055; adjusted odds ratio = 1.003] when entered in the regression equation together with the other confounders. Serum FGF23 in this study was not also associated with renal recovery, need for renal replacement, or the duration from peak serum creatinine to renal recovery (p &gt; 0.05).

Conclusion
This research showed that serum iFGF23 could not predict mortality, renal recovery, or need for renal replacement therapy in patients with community-acquired AKI.
#2136 Hyponatremia as a presenting symptom of secondary adrenal insufficiency induced by immune checkpoint inhibitors
Authors: Glezerman Ilya 
Published: May 2024

Abstract

Background and Aims
Endocrinopathies are common complication of treatment with immune checkpoint inhibitors (ICI). Adrenal axis may be affected through either direct adrenal toxicity leading to primary hypoadrenalism or due to pituitary dysfunction resulting in secondary adrenal insufficiency. Patients with secondary insufficiency may have variable presentation and, in some cases, initially present with hyponatremia only. This abstract reports a cohort of patients who developed hyponatremia as initial symptom of secondary adrenal insufficiency.

Method
After obtaining approval from the institutional review board, medical records of the nephrology service at a large cancer center were reviewed. Patient is well included in the study if they developed moderate (plasma Na &lt;130 mEq/L) and severe (plasma Na &lt;120 mEq/L) hyponatremia during treatment with ICI and met a biochemical criterion for adrenal insufficiency (morning serum cortisol level &lt;3.0 mcg/dL).

Results
Nine patients who met the criteria were identified (Table 1). There were 5 males and four females. Mean age was 67.6 year. Median number of ICI therapy cycles was 10 but treatment number ranged from 2-84. For patient's would treat with combination of CTLA-4 and PD 1 inhibitors and 5 patients were treated with PD 1 inhibitor alone. Four patients had severe hyponatremia and five presented with moderate hyponatremia. All patients were normotensive on presentation. All patients had low morning cortisol level but only two patients had low ACTH level. All patients had low normal ACTH levels. One patient underwent ACTH stimulation test which was negative. Additionally for patient has had normal thyroid function. Eight patients underwent an MRI and 4 of them had evidence of possible pituitary inflammation. All patients were started on physiologic corticosteroid replacement with prompt resolution of hyponatremia. All patients required ongoing corticosteroid replacement therapy.

Conclusion
Secondary adrenal insufficiency in the setting of ICI toxicity can present with initial diagnosis of hyponatremia. Patients in this cohort were normotensive on presentation despite adrenal insufficiency and therefore required high index of suspicion for the diagnosis. Most patients in the study also had low normal ACTH levels however responded clinically to treatment with corticosteroid replacement indicating that adrenal sufficiency was the cause of hyponatremia. ACTH test may be falsely negative in these patients if adrenal insufficiency developed less than six weeks prior and adrenal atrophy did not occur yet.
#1651 Urinary oxygen partial pressure: closely associated with hourly urine output induced by furosemide in patients with acute renal injury
Authors: MA Yixin , Yuan Siyi , Hu Rongrong , Chen Ronping , Chen Limeng 
Published: May 2024

Abstract

Background and Aims
Urine oxygen level, an indicator of kidney medullar oxygenation, is promising for predicting the onset of acute kidney injury (AKI). Furosemide, a commonly used diuretic in ICU, significantly increases urine output and is believed to change kidney medullar oxygenation. We monitored the longitudinal change of urinary oxygen partial pressure during bolus or pump administration of furosemide, aiming to describe the reaction pattern in an AKI-susceptible patient population.

Method
The prospective observational pilot study included seven adult patients in the ICU because of cardiac surgery or sepsis. We monitored the continuous urinary oxygen partial pressure for 8-24 hours through a device placed between the urinary catheter and collecting bag during furosemide administration, recorded hourly urine output simultaneously from a urine bag, and followed the patients in the hospital for the onset and development of AKI.

Results
We recruited three female patients and four male patients with an average age of 54 years and a medium of 5 days in ICU with an AKIN stage I of AKI during their hospital stay. None of them developed more severe stage AKI or required any kidney replacement therapy. We found a reverse correlation pattern between hourly urine output and urinary oxygen partial pressure. Specifically, the urine oxygen level dropped during urine volume increase caused by furosemide bolus administration and abolished by furosemide administration through a pump with more stable urine output. The paired t-test showed a significant increase in average urine oxygen level (mean difference = 21.2 mmHg, p = 0.044) recorded during the “high hourly urine output” period compared to the “low hourly urine period”.

Conclusion
We first found a drop in urinary oxygen partial pressure during the high urine output period elicited by bolus furosemide administration. It shed light on the confounding factors in AKI predicating during possible furosemide administration.
#2232 Personalized kidney replacement therapy in critically ill patients: unity makes strength!
Authors: Castro Ana , Dias Bruno Fraga , Sala Inês , Braga Beatriz Gil , Fernandes João , Queirós José , Freitas Cristina 
Published: May 2024

Abstract

Background and Aims
The complexity of the critically ill patient with kidney disease has increased in recent years. A holistic and multidisciplinary approach is, therefore, necessary in order to provide the best therapeutic guidance. Multiple modalities of kidney replacement therapies (KRT) are available in this setting, namely continuous kidney replacement therapies (CKRTs) and hybrid therapies, also such as sustained low-efficiency dialysis (SLED) and slow continuous ultrafiltration (SCUF). These techniques can be used in conjunction with other extracorporeal clearance therapies such as plasmapheresis (PF), and immunoadsorption (IA). Their prescription must be individualized according to the characteristics of each patient. In our hospital all KRT and extracorporeal techniques used are reviewed daily by a nephrologist. This study aims to describe the 20-year experience of our centre in individualized KRT prescription in intensive care.

Methods
A retrospective cohort, single centre study was conducted. We reviewed adult patients (age ≥18 years) admitted in all the ICUs of our hospital centre between January 2002 and December 2022, who required a KRT.
We aimed to describe demographic data, different stages of kidney disease [AKI, AKI in CKD, chronic hemodialysis (HD), peritoneal dialysis (PD), kidney transplant (KT), rapidly progressive kidney failure (RPKF), other causes], the KRT used and the main outcomes.

Results
During the study period, 1578 patients who required a KRT were admitted to the ICU. Median age was 65 (IQR: 45-81) years old and 59.9% were male. Among these patients 715 (45.3%) had AKI, 380 (24.1%) were in HD, 315 (20%) had AKI in CKD, 130 (8.2%) had a KT and 31 (2%) were in PD. Four patients had RPKF and 3 patients had other causes for KRT, such as hyperammonemia and sodium valproate poisoning. The main KRT performed were: SLED—1365 (86.5%) patients; continuous venovenous hemodiafiltration (cvvHDF)—120 (7.6%) patients; SLED + cvvHDF—66 (4.2%). Other KRT executed were SLED + PF (11 patients), continuous venovenous hemofiltration (cvvHF) (8 patients) and SCUF (2 patients). Among all patients mortality rate was 42.3%, 33% had renal recovery and 7.4% started chronic HD. In AKI group the median age was 64 (IQR: 48-80) years and 56.3% were male. 576 (80.7%) performed SLED, 91 (12.7%) did cvvHDF and 36 (5.0%). Mortality rate was of 52.1%, renal recovery 45% and 2.9% started chronic HD.

Conclusion
Our ICU multidisciplinary approach model with a critical care nephrology specialists team translates into a large amount of accumulated experience with SLED. Our results are comparable to centres that predominantly use CKRTs. The range of different techniques used reflects the fact that KRT has become a complex treatment for critically ill patients, which allows for the prescription to be precisely tailored to the different daily clinical needs.
#2062 Protein interactome and trafficking of uromodulin in HEK and MDCK cell model
Authors: Parveen Humaira , Boder Philipp , Mary Sheon , Van Agtmael Tom , Delles Christian 
Published: May 2024

Abstract

Background and Aims
Uromodulin (UMOD) is a kidney-specific glycoprotein and the most abundant urinary protein in healthy individuals. Genome-wide association studies have shown an association between UMOD variants, kidney diseases, and hypertension. UMOD exhibits bidirectional secretion as it releases into the renal interstitium and circulation. However, the molecular trafficking of UMOD and its interaction remains poorly defined. We aimed to establish a stable Human Embryonic Kidney (HEK293) cell line expressing human UMOD to identify the potential regulators of UMOD expression or secretion. This study will provide significant implications for conditions such as hypertension, chronic kidney diseases, acute kidney injury, or UMOD-autosomal dominant tubulointerstitial kidney disease (UMOD-ADTKD).

Method
A HEK-UMOD-expressing cell line was generated by introducing human UMOD transcript 1 expression and using a tetracycline-inducible expression vector (pcDNA™FRT⁄TO vector) with yellow fluorescent protein tag at the C-terminal and previously established MDCK-UMOD cell line was also used. An untargeted proteomic approach was used to identify proteins, using GFP trap co-immunoprecipitation assay followed by mass spectrometry analysis.

Results
We identified 1367 and 1140 UMOD interacting proteins in HEK and MDCK cell models respectively. There were 620 proteins common to both these models. Through gene ontology, we unravel the molecular mechanisms involved in the biosynthesis, folding, and transport of UMOD. We observed several proteins associated with clathrin-mediated transporting. To study the role of clathrin in UMOD transport, we treated the polarised MDCK-UMOD cells with pitstop 2. There was significantly more secretion of UMOD with pitstop 2 treatment in the apical compartment compared to untreated cells however there was no significant difference in UMOD secretion in the basolateral compartment.

Conclusion
These results suggested that clathrin-coated vesicles are involved in transporting and sorting UMOD. Further studies need to investigate the functional importance of these proteins in UMOD trafficking and their implications in different physiological processes.
#821 Kibra mediates the activation of hippo by classic signal pathway related to NPHP1 defect
Authors: Yang Yichen , Sun Liangzhong 
Published: May 2024

Abstract

Background and Aims
Nephronophthisis (NPH) is an autosomal recessive cystic kidney disease, which is the most common genetic cause of end-stage renal disease (ESRD) in children. The pathogenesis of NPH has not been clear yet. There are more than 20 different pathogenic genes identified at present, among which NPHP1 is the most prevalent one. Hippo signal pathway has been suggested to be involved in the pathogenesis of NPH cause by NPHP4 and NPHP9 defects, respectively. In the present study, we attempted to explore the state of hippo signal pathway in NPHP1 defect in both MDCK cells and C57/6j mice.

Method
NPHP1 knockout (NPHP1KO) MDCK cells and NPHP1KO C57BL/6J mice were constructed by CRISPR/Cas9 technology. Recombined kibra knockdown siRNA, kibra knockdown AAV9 (AAV9-Kibra-KD) and NPHP1 overexpress AAV9 construct (AAV9-NPHP1-OE) were constructed, respectively. The expression and phosphorylation of core molecules of hippo pathway in different group of MDCK cells and the kidney C57BL/6J mice were investigated through Real-time Quantitative PCR, western blotting, immunofluorescence. The renal pathology of the mice kidney was also observed.

Results
In NPHP1KO MDCK cells and the kidney of NPHP1KO mice, the expression of KIBRA, p-MST, p-LATS and p-Yap were increased, which indicates the activation of hippo signal pathway. The activation of hippo pathway could be suppressed partially by NPHP1 re-expression both in NPHP1KO MDCK cells and the kidney of NPHP1KO mice, which means the activation of hippo pathway was related to NPHP1 defect both in vitro and in vivo. Moreover, the kidney pathological changes were improved by NPHP1 re-expression.
Kibra is the upper regulator of hippo signal pathway, we observed that kibra knockdown inhibited the activation of hippo pathway both in NPHP1KO MDCK cells and the kidney of NPHP1KO mice, which indicates that kibra mediates the activation of hippo pathway related to NPHP1 defect both in vitro and in vivo. As well, kibra knockdown ameliorated renal fibrosis CTGF expression, interstitial inflammation and renal cyst formation in NPHP1KO mice.

Conclusion
We conclude that NPHP1 defect activates hippo pathway which involves in the pathogenesis of NPH. Kibra mediates the activation of hippo related to NPHP1 defect by classic signal pathway. Hippo signal maybe a target for the treatment of NPHP1 defect NPH.