bluuebunny/crossref_metadata_2025_split huggingface dataset:
#1200 Coronary artery calcium modifies the relationship between blood pressure and adverse kidney outcome: results from KNOW-CKD
Authors: Han Seung Hyeok , Joo Young Su , Koh Hee Byung , Park Jung Tak , Yoo Tae-Hyun , Oh Kook-Hwan , Kang Shin-Wook 
Published: May 2024

Abstract

Background and Aims
Previous studies evidenced that elevated coronary artery calcium (CAC) score is associated with higher chronic kidney disease (CKD) progression. However, the use of CAC score to guide CKD management has not been adequately evaluated. Here, we evaluated whether presence of CAC modify the association between systolic blood pressure (SBP) and CKD progression in patients with CKD.

Method
We analyzed 1693 participants with CKD stages G1 to G5 from the KoreaN cohort study for Outcome in patients With Chronic Kidney Disease (KNOW-CKD). Key exclusion criteria were kidney failure with replacement therapy (KFRT) and missing data for CAC and SBP information. We categorized participants according to baseline SBP and CAC score (Controlled BP, SBP &lt; 120 mmHg; Elevated BP without CAC, SBP 120-140 mmHg and CAC score = 0; Elevated BP with CAC, SBP 120-140 mmHg and CAC score &gt;0; Uncontrolled BP, SBP &gt;140 mmHg) and compared the CKD progression. The CKD progression was defined as a composite of halving eGFR from baseline value or onset of KFRT.

Results
During 10,023 person-years of follow-up (median 6.2 years), the composite outcome occurred in 689 (40.7%) participants, and 108 (6.4%) participants died among the KNOW-CKD participants. There was significant interaction between CAC score and SBP for CKD progression (P &lt; 0.001). There were 181/568 (31.9%), 167/424 (39.4%), 128/314 (40.8%) 213/387 (55.0%), composite outcomes in controlled BP, elevated BP without CAC, elevated BP with CAC, uncontrolled BP group, respectively. In crude Cox regression, compared to controlled BP, elevated BP with CAC group showed similar CKD progression risk (Hazard ratio [HR], 1.17; 95% confidence interval [CI], 0.95-1.44), whereas other strata group showed increased risk of CKD progression (elevated BP with CAC; HR, 1.59; 95% CI 1.31-1.94 and uncontrolled BP, HR, 1.94; 95% CI 1.56-2.41). Similar elevated risk in elevated BP with CAC was observed even after adjustment of age, sex, diabetes mellitus, estimated glomerular filtration ratio, and proteinuria (HR, 1.26; 95% CI, 1.02-1.56). However, the risk of CKD progression in elevated BP without CAC group was comparable to controlled BP group (HR, 1.20; 95% CI, 0.87-1.66).

Conclusion
Elevated SBP was more strongly associated with an increased risk of adverse kidney outcomes in patients with coronary calcification.
#770 Urinary PTM3 Fetuin-A in CKD patients with and without diabetic kidney disease
Authors: Musolino Michela , D'agostino Mario , Tripodi Loredana , Zicarelli Mariateresa , Cianfrone Paola , Andreucci Michele , Coppolino Giuseppe , Bolignano Davide 
Published: May 2024

Abstract

Background and Aims
Fetuin-A is a member of the cystatins superfamily, primarily synthesized in the liver, which is involved in multiple physiological processes including calcium homeostasis, cell signaling, calcification inhibition and the regulation of insulin sensitivity. Diabetes mellitus may impact upon Fetuin-A regulation and kidney tubular cells produce Fetuin-A as part of stress and inflammatory response and release it in urine in case of kidney damage.
A novel post-translational modification (PTM) fragment derived from the cleavage of Fetuin-A (PTM3) has recently emerged as a very sensitive biomarker for early kidney damage, but its usefulness in the context of CKD has not been assessed yet. In this study, we aimed at evaluating the clinical significance of urinary PTM3 fetuin A in a pilot cohort of CKD patients with or without diabetic kidney disease (DKD).

Method
We enrolled 47 adult patients with CKD (mean CKD-Epi 40.10 ± 16.5 mL/min/1.73 m2) due to DKD (n = 34) or other causes (n = 13). PTM3 levels were measured in the urine (uPTM3) using a commercially available ELISA kit. 15 healthy individuals served as controls. Clinical, anthropometric and laboratory parameters were also recorded.

Results
Collectively, all CKD patients displayed higher levels of uPTM3 than the ones of control group (0.84 [0.10-1.15] vs 29.68 [2.50-55.16] ng/mL p = 0.0005).
Moreover, uPTM3 values were higher in DKD patients than in non-DKD CKD patients (39.4 [4.20-28.2] vs. 4.15 [0.29-1.38] p &lt; 0.01).
uPTM3 had a remarkable diagnostic capacity at ROC analysis to discriminate CKD patients from controls (AUC 0.776; p &lt; 0.001; Fig. 1) and, within CKD patients, to discriminate between DKD and non-DKD patients (AUC 0.673; p = 0.02; Fig. 2). At multivariate correlation analyses, only proteinuria (β = 0.442; p = 0.02) and BMI (β = 0.334; p = 0.04) values remained significantly associated with uPTM3 Fetuin-A in the whole cohort, thus indicating that renal damage following metabolic syndrome may play a significant impact on the overall balance of this protein.

Conclusion
uPTM3 could be a novel sensitive biomarker reflecting renal damage in CKD patients and could also represent an additional tool for assessing the renal involvement in diabetic patients.
Further studies are needed to evaluate whether uPTM3 measurement may predict different disease evolution in these patients.
#2169 Transplant renal artery stenosis in recipients with resistant arterial hypertension
Authors: Smaliakova Maria , Kalachyk Aleh , Komissarov Kirill , Kozak Oleg , Liovina Darya , Plaksa Dzmitry 
Published: May 2024

Abstract

Background and Aims
Transplant Renal Artery Stenosis (TRAS) is a vascular complication after kidney transplantation. It worsens the prognosis of the graft and the patient's life.
The aim was to study the incidence of TRAS as a cause of resistant arterial hypertension in kidney transplant recipients in the Republic of Belarus and the efficiency of its endovascular treatment.

Method
The study included 187 kidney transplant recipients. Blood pressure of 72 (38.5%) patients was less than 130/80 mmHg without taking antihypertensive drugs. Arterial hypertension was diagnosed in 115 (61.5%) recipients. The study included clinical, laboratory and instrumental methods (24-hour blood pressure monitoring, Doppler ultrasound, graft scintigraphy with captopril).

Results
31 (16.6%) recipients needed to take one antihypertensive drug, 43 (23.0%)—2 drugs, 41 (21.9%)—3 or more.
17 (9.1%) recipients did not have target blood pressure correction while taking more than 4 antihypertensive drugs. There was decreased blood flow in the graft artery with a peak systolic velocity &gt; 200 cm/s in 14 (7.5%) cases. These patients were submitted to the graft nephroscintigraphy with caplopril where 8 grafts (4.3%) were diagnosed signs of TRAS. These recipients were submitted to the renal angiography with the injection of 150 (100; 200) ml of contrast agent.
5 (2.7%) recipients were diagnosed with hemodynamically significant TRAS of more than 70 (65; 75) % and received percutaneous transluminal angioplasty and stenting. All these patients had a decrease of glomerular filtration rate and resistant arterial hypertension before operation. The average age of the patients with TRAS was 57.4 ± 11.0 years, the period after transplantation was 11 ± 3 months. Their blood tests did not show dyslipidemia, but 4 out of 5 cases had diabetes mellitus. Their postoperative period had no complications. The patient was placed on dual antiplatelet therapy with aspirin and clopidogrel. There was an increase in glomerular filtration rate by 27 ± 7 ml/min/1.73 m2 and a decrease in systolic blood pressure by 40 (40; 45) mm Hg in the early postoperative period. Graft artery stenting allowed reducing the number of antihypertensive drugs to one tablet in 4 out of 5 patients.

Conclusion
Transplant Renal Artery Stenosis is a rare but significant complication of the late postoperative period that may cause resistant hypertension in kidney transplant recipients. Timely identification and stenting of the graft artery improves the graft functioning and reduces blood pressure.
#554 Baseline neutrophil gelatinase-associated lipocalin (NGAL) levels for early prediction and ruling out future contrast nephropathy
Authors: Shacham Yacov , Banai Shmuel , Frydman Shir 
Published: May 2024

Abstract

Background and aims
Neutrophil gelatinase-associated lipocalin (NGAL), is an early marker of acute kidney injury (AKI). There is only limited data, however, on the optimal timing for assessment, the cut-off values and its utilization for ruling out AKI We aimed to investigate the diagnostic utility of sequential NGAL measurements for both prediction and ruling out of AKI among patients with ST segment elevation (STEMI) undergoing primary coronary intervention (PCI).

Methods
We included 133 patients with STEMI treated with PCI. Blood samples for plasma NGAL were drawn immediately before PCI (NGAL 0) and 24 hours after PCI (NGAL 24). Optimal threshold for the development of AKI were determined using receiver operating characteristic curves (ROC). Patients were also assessed for the dynamics between NGAL 0 and NGAL 24 levels.

Results
Mean age was 62 ± 13 years and 78% were men, and a total of 20 (15%) developed AKI. Patients with AKI demonstrated higher plasma NGAL 0 levels (164 ± 42 vs. 95 ± 30 ng/mL; p &lt; 0.001) as well as NGAL 24 levels (142 ± 41 vs. 93 ± 36 ng/mL; p &lt; 0.001). There were no significant changes between NGAL 0 & 24 hours within the 2 groups (Fig. 1). According to the ROC curve analysis NGAL 0 performed better than NGAL 24 for AKI prediction (Fig. 2). The optimal NGAL 0 level for AKI prediction was &gt;125 ng/mL (AUC 0.841, 95% CI 0.801–0.961, p &lt; 0.001), with a sensitivity of and specificity of 70% and 84% respectively, while the negative predictive value of NGAL 0&lt;125 ng/mL was 94%.

Conclusions
Among STEMI patients, NGAL levels before primary PCI may be utilized both for ruling out and for the prediction of AKI.
#1771 ANXA13 protects against acute kidney injury by inhibiting TGF-β/Smad3 pathway
Authors: Jiaxiao Li , Chen Junzhe , Tang Ying , Huang Xiaoru , Lan Hui Yao 
Published: May 2024

Abstract

Background and Aims
Acute kidney injury (AKI) is a common clinical syndrome characterized by rapid loss of kidney function but with limited diagnostic and treatment options. Annexins (ANXA) are a superfamily of calcium-dependent and lipid-binding proteins involved in multiple intracellular and extracellular functions. As a founding member of ANXA, ANXA13 is considered the prototype of a conserved evolutionary property of the annexin superfamily and is restricted to kidney and intestinal epithelial cells. However, it is currently unclear whether ANXA13 is a key regulator of AKI. Therefore, we aimed to investigate the role of ANXA13 in AKI.

Method
Kidney biopsy tissues from AKI patients were collected for immunohistochemical examination and ELISA method was used to detect the concentration of ANXA13 in serum and urine. A mouse model of AKI induced by ischemia-reperfusion injury (IRI) was established to verify the role of ANXA13 in AKI. RNA sequencing was also used to explore the mechanism of ANXA13 in AKI, and this result was further confirmed using Smad3 wild-type (WT) and knockout (KO) mice.

Results
AKI patients had reduced serum ANXA13 levels and increased urinary ANXA13 levels compared with healthy controls. The levels of ANXA13 in both serum and urine are related to serum creatinine (Scr). In kidney tissue, ANXA13 was significantly reduced in both AKI patients and IRI-AKI mice. By overexpressing ANXA13 by specifically transferring ANXA13-expressing plasmid into IRI-AKI mice via ultrasound microbubble-mediated kidney, we found that ANXA13 reduced Scr and blood urea nitrogen (BUN) levels and renal function in IRI-AKI mice. damage. In contrast, knockdown of ANXA13 by shANXA13 plasmid significantly exacerbated renal injury. Mechanistically, we found that the protective mechanism of ANXA13 was related to the inhibition of the TGF-β/Smad3-p21 cell cycle arrest pathway, and the aggravating effect of shANXA13 was reversed in Smad3 knockout mice. In turn, activation of Smad3 also suppresses ANXA13 mRNA and protein levels in vivo and in vitro.

Conclusion
ANXA13 can intervene in AKI by inhibiting the TGF-β/Smad3-p21 cell cycle blocking pathway. In turn, activation of Smad3 inhibits ANXA13 expression. Therefore, ANXA13 may be a new therapeutic target for AKI.
#2512 Behaviour of Human Proenkephalin A 119-159 (penKid) in an in vitro model of hemoadsorption
Authors: Perin Natascha , Lorenzin Anna , de Cal Massimo , Morisi Niccolò , Brendolan Alessandra , Lentini Paolo Luca Maria , Zanella Monica , Ronco Claudio 
Published: May 2024

Abstract

Background and Aims
Proenkephalin A 119-159 (penKid) is a stable surrogate marker for enkephalins (endogenous opioids regulating kidney function).
Different clinical studies have shown severity-dependent increased penKid levels in patients with sepsis-associated acute kidney injury (AKI), indicating that penKid can be used for prediction and diagnosis of AKI and need of renal replacement therapy (RRT) and even subclinical forms of AKI. In the absence of targeted therapies, organ support in terms of RRT is the ultimate treatment in severe AKI cases. Hemoadsorption is utilized as an adjunctive therapy in septic patients.
The aim of this study is to define the penKid removal ratio in conditions of in vitro hemoadsorption (HA) using a synthetic microporous hemo-compatible resin.

Method
The lyophilized peptide was solved in 20 mM Dipotassium phosphate, 6 mM Disodium EDTA [pH 8], avoiding concentrations higher than 1 mg/mL.
The compound was diluted in 50 mL of plasma to ensure homogeneous distribution.
A batch of blood of 1000 mL with adjusted hematocrit at 30% and albumin concentration of 3 g% was utilized.
Blood was spiked with lyophilized synthetic penKid to achieve the target concentration of 600 pmol/L. Blood was adjusted for a volume of 1000 mL, maintained at 37° and continuously stirred during the experiment.
HA was performed with QB = 150 mL/min in a closed-loop configuration. A sorbent minimodule of HA380 (Jafron, Zhuhai, People Republic of China) was utilized. Samples were taken at 5, 15, 30, 60 and 120 minutes from the initiation of the circulation. Total removal and reduction ratios were calculated to assess the adsorption.
This procedure was repeated three times.

Results
Initial penKid concentrations in blood corresponded to the desired target.
In the three experiments penKid concentrations displayed a consistent decrease that approached 75% removal ratio at 120 minutes (Figs 1 and 2). Minimal variability was observed confirming a consistent behavior of the interaction between the sorbent and the molecule.

Conclusion
The results suggest that penKid is effectively removed during hemoadsorption and its levels should be evaluated in light of these results when in vivo hemoadsorption is carried out in critically ill patients.
#3018 Aciclovir or valaciclovir neurotoxicity in renal patients: increasing number of neurotoxicity cases are diagnosed in Sweden by a blood test
Authors: Helldén Anders 
Published: May 2024

Abstract

Background and Aims
Kidney transplant patients are at high risk for developing zoster infections, as well as patients with impaired renal function. Aciclovir (ACV) and its prodrug valaciclovir are effective medications to treat these herpes infections. The medications typically have mild side effects such as nausea and vomiting, headache, and skin rash. More uncommon but serious side effects include elevated creatinine, acute kidney failure, and aciclovir-induced neuropsychiatric symptoms (AINS). The latter is difficult to distinguish from the viral infection treated, thus prolonged treatment with ACV may cause further deterioration and increase the chance for coma and need for intensive care treatment. ACV is excreted by glomerular filtration and tubular secretion and should be doses according to renal function. A small part is metabolized by alcohol dehydrogenase and aldehyde dehydrogenase to its main metabolite 9-carboxymethoxymethylguanine (CMMG), but as renal function decreases more CMMG is found in the urine, serum, and CSF. We have earlier shown that a serum CMMG cut-off level of 10.8 µmol/L is predictive of AINS. Hemodialysis alleviates the symptoms dramatically, but AINS need to be diagnosed first. The knowledge about our method has increased in Sweden, but has more AINS cases been diagnosed in Sweden now than for 10 years ago?

Method
Data from our therapeutic drug monitoring (TDM) database of ACV and CMMG levels were studied during the period 2013 to 2023. Serum samples with a CMMG concentration above 10.8 µmol/L were collated and compared to the total number of samples per year. Some patients were monitored with more than one blood sample during the treatment period and the number of single patients was also included.

Results
The database consisted of 4521 serum ACV and CMMG samples during the study period with 727 samples with a CMMG concentration above 10.8 µmol/L. The number of CMMG serum samples increased from 278 in 2013 to 601 in 2023. A total of 363 patients had at least one sample above 10.8 µmol/L. A median of 33 (range 17 to 59) single patients were diagnosed with AINS per year.

Conclusion
Measurement of both ACV and CMMG has increased the number of AINS cases in Sweden and are requested to a higher extent now than 10 years ago. Two more laboratories in Sweden measure or will start to measure ACV and CMMG, one laboratory in Bristol have had the method since 2007, but there are too few laboratories performing the analysis in other countries, causing severe suffering for patients and high costs for healthcare.
#1954 Effects of lanosterol synthase (LSS) gene on the development of acute kidney injury after cardiac surgery
Authors: Simonini Marco , Cocchini Lorenzo , Lanzani Chiara Livia , Raimondo Davide , D'urbano Luca , Citterio Lorena , Zagato Laura , Vezzoli Giuseppe , Manunta Paolo 
Published: May 2024

Abstract

Background and Aims
Acute kidney injury (AKI) is a common post-cardiac surgery complication, significantly affecting morbidity and mortality. Recent studies reported that high plasma levels of endogenous ouabain (EO), a stress hormone secreted by the adrenal glands, are associated to worse kidney outcomes after cardiac surgery. Our group demonstrated that EO activity is affected by a missense variant (rs2254524, C -&gt; A, Val642Leu) in Lanosterol Synthase (LSS) gene, an enzyme implicated in EO synthesis. The aim of this work is to analyze the relationship between this LSS polymorphism and the development of AKI after cardiac surgery.

Method
1237 patients undergoing elective cardiac surgery were enrolled in the study. Preoperative biological samples were collected (Table 1). LSS genotypes were determined for each patient. The primary outcome was AKI development, according to KDIGO 2012 guidelines.

Results
21.4% of patients developed AKI. Different preoperative clinical variables were analyzed, identifying five independent risk factors significantly correlated to AKI development in multivariate logistic regression analysis: age (p &lt; 0.001), FE (p = 0.005), NYHA class (p &lt; 0.001), reoperation (p = 0.002) and complex surgical intervention (p &lt; 0.001), Table 2. No significant differences were observed between preoperative EO plasma levels and allelic variants of LSS gene and patients with the less common A allele were not associated to a more severe preoperative clinical presentation, expressed as EuroScore II value (AA 2.54 ± 3.86 vs AC 2.15 ± 2.52 vs CC 2.04 ± 2.73; p = ns). LSS minor variants turned out significantly associated with the incidence of AKI (AA = 29.3%; AC = 25.3%; CC = 17.2%; X2 p &lt; 0.001—Fig. 1). This evidence remains significant after correction for covariates associated to AKI previously reported (Log regression p = 0.002; RR for AA variant: 2.09 (IC95% 1.15-3.78))

Conclusion
Patients with at least one mutated allele of LSS variant have a higher probability of developing AKI after cardiac surgery. We think these results could be of interest to further understand cellular mechanisms underlying AKI development, especially in the cardiac surgery field.
#2886 Machine learning-based assessment of serum creatinine and NT-proBNP levels for predicting mortality in patients with heart failure and kidney injury
Authors: Đurović Vladimir , Petrović Milovan , Ilić Aleksandra , Milosavljević Anastazija Stojšić , Milovančev Aleksandra , Velicki Lazar , Maksimović Snežana Čemerlić , Popović Milica , Majstorović Gordana Stražmešter , Golubović Sonja , Knežević Violeta , Petrović Lada 
Published: May 2024

Abstract

Background and Aims
In a population hospitalized for acute heart failure, about 20% are affected by acute kidney injury, a significant independent factor linked to increased mortality both during hospitalization and within one year. While existing research offers insights, crafting a precise model to predict mortality in heart failure cases remains a complex task, primarily due to the difficulties in pinpointing critical determinants and achieving high accuracy. The aim of our research was to assess the efficacy of serum creatinine and NT-proBNP levels as predictors for mortality in heart failure patients, using machine learning.

Method
In our retrospective cross-sectional study, we examined the records of 1,042 patients hospitalized due to acute heart failure at the Institute of Cardiovascular Diseases of Vojvodina, spanning the period from January 1, 2021, to December 31, 2022. The data was initially cleaned, after which we employed a Random Forest model for our analysis. The dataset was partitioned into a training subset, constituting 70% of the data, and a testing subset, comprising the remaining 30%. To achieve optimal precision, we ran the model 100 times. Key performance metrics, including mean sensitivity, specificity, accuracy, F1 score, Matthew's correlation coefficient (MCC), and the area under the Receiver Operating Characteristic (ROC) curve (AUC), were derived from the model to assess its efficacy.

Results
Following data cleansing, the dataset encompassed a total of 389 patients, of which 58% were male. The median age in this cohort was 71 years, with an interquartile range (IQR) of 63 to 79 years. Key laboratory findings included a median serum creatinine level of 111 µmol/L (IQR: 85-167 µmol/L) and a median NT-proBNP level of 6,589 pg/mL (IQR: 2,822-15,608 pg/mL). After the partition, the median number of patients in the training set was 272 and the testing set comprised 117 patients. The performance of the Random Forest model was characterized by a sensitivity of 0.530, specificity of 0.916, an overall accuracy of 0.856, and an F1 score of 0.516. The MCC stood at 0.439 with the AUC under the ROC curve being 0.713.

Conclusion
While the relatively low sensitivity observed in our model could be attributed to the generally lower levels of serum creatinine upon admission and the retrospective nature of the study, which may have influenced the model's ability to identify all true positive cases effectively, serum creatinine and NT-proBNP levels hold promise as effective predictors for mortality in heart failure patients.