bluuebunny/crossref_metadata_2025_split huggingface dataset:
#1023 Patient outcomes and graft survival among kidney transplant recipients with chronic hepatitis C infection: a single center study
Authors: Vallarit Michael John , Jamias Jade 
Published: May 2024

Abstract

Background and Aims
Previous studies have shown that kidney transplant_(KT) recipients with chronic hepatitis C (HCV) infection have lower survival rates after transplantation. With the emergence of direct-acting antiviral therapy for HCV infection, the long-term outcomes for these patients are still unknown.
This aims to evaluate the 5-year graft and patient outcomes of kidney transplant recipients with HCV infection at the National Kidney and Transplant Institute.

Method
A retrospective cohort study of HCV-positive KT recipients which were compared to HCV-negative patients in the same post-transplantation period. Data gathered from the patient's in-hospital and outpatient records and MEDSYS database.

Results
Twelve(12) out of 117 KT recipients with HCV infection were included. Half of these patients had detectable HCV RNA before KT. There was no difference in recipients' age, gender, and donor type between the groups. HCV infection is significantly associated with and an independent predictor of graft loss, rejection, and mortality. Patient survival between groups did not show any significant difference. Rates of graft rejection, graft loss, and patient mortality among HCV-positive recipients did not show statistically significant difference between groups. Graft survival rates at 6 months, 1-, 3-, and 5 years post KT were significantly lower among HCV-positive KT recipients compared to HCV-negative recipients. There were no significant differences in renal function, presence of proteinuria, liver enzyme levels, and incidence of cirrhosis between the groups.

Conclusion
Graft survival was shorter in HCV-positive KT recipients. Patient survival, measures of kidney function, and liver-related complications were similar between HCV-positive and HCV-negative KT recipients after transplantation.
#1617 Effect of pre-renal transplant anticoagulation and antiplatelet therapy on post-transplant outcomes: a retrospective single-center study
Authors: Fuentes Cristina , Maldonado Maria , Oliva Maria Ovidia Lopez , Gonzalez Elena , Navas Miguel Angel , Jimenez Carlos 
Published: May 2024

Abstract

Background and Aims
The management of anticoagulation and antiplatelet therapy in stage V chronic kidney disease (CKD) patients undergoing renal transplantation is controversial. While some centers utilize reversal agents or procoagulants before surgery, other experiences suggest that renal transplantation can be safely performed without discontinuation of such treatments. The aim of this study is to assess the incidence of hemorrhagic and thrombotic complications within the first 72 hours post-transplant in anticoagulated or antiplatelet-treated patients compared to those without these treatments (control group).

Method
Retrospective cohort study of patients undergoing renal transplantation at our center between June 2018 and February 2022, with a 6-month post-transplant follow-up. Epidemiological, clinical, and analytical data were collected.

Results
147 patients, predominantly male (60.3%). 8.1% were anticoagulated, and 16.3% were on antiplatelet therapy. Antiplatelet-treated patients were older (63 years) with a higher prevalence of cardiovascular disease history (54.2%). Anticoagulated patients showed a higher frequency of diabetes (50%) and atrial fibrillation (16.7%). The time on dialysis was also longer in anticoagulated or antiplatelet-treated patients (39.5 and 39 vs 33 months). 80.9% were first-time kidney transplant recipients from brain-dead donors, although the donor's age was lower in the control group. Ischemia time was similar in all three groups with no statistically significant differences. However, the length of hospital stay was longer for those receiving anticoagulation or antiplatelet therapy compared to the control group.
58.3% of anticoagulated patients received warfarin (pre-surgery INR of 1.5). In 50% of cases, reversal was performed using coagulation factors, vitamin K, fresh frozen plasma, or combinations of these therapies. 83.3% of antiplatelet-treated patients received aspirin, mainly for secondary prevention (54.2%), and only 8.3% received reversal therapy through plasma administration.
The incidence of hemorrhagic and thrombotic complications was low (&lt;5%) and did not significantly differ between anticoagulated or antiplatelet-treated patients and those without these treatments, although transfusion rates were higher in the anticoagulation group (75%) compared to 51.4% in the control group and 62.5% in antiplatelet-treated patients.

Conclusion
There are no significant differences regarding hemorrhagic and thrombotic complications between anticoagulated or antiplatelet-treated patients and those without these treatments, while the percentage of blood transfusions and hospital stay was higher in anticoagulated or antiplatelet-treated patients.
#2961 Association of polygenic risk scores for blood pressure with incidence of hypertension and chronic kidney disease
Authors: Kwon Soon Hyo , Lee Haekyung , Kim Na Yeon , Lee Seunggeun , Kim Hyoungnae , Jeon Jin Seok , Noh Hyunjin 
Published: May 2024

Abstract

Background and Aims
Genetic risk for elevated blood pressure (BP) has been associated with a higher risk of hypertension and cardiovascular disease. However, the generalizability of previous findings has been limited due to a lack of studies among Asian populations. This study aimed to investigate whether genetic risk for BP predicts the incidence of hypertension and chronic kidney disease (CKD) in Asian populations.

Method
We performed genome-wide association studies for systolic and diastolic BP (SBP and DBP, respectively) using data from the Korean Genome and Epidemiology Study (KoGES). We then meta-analyzed these results with summary statistics from Biobank Japan to construct polygenic risk scores (PRSs) and examined the association between BP PRSs and incident hypertension or CKD. This study included participants without hypertension, cardiovascular disease, or CKD at baseline (n=4349, median age 48.5 years, 48.8% men). Participants were categorized into four groups based on their PRS percentile (&lt;5, 5–50, 50–95, &gt;95).

Results
As the PRS percentile increases, the median SBP and DBP at baseline also increase. Compared to the lowest SBP PRS percentile, higher PRS percentile was associated with increased risk of hypertension (hazard ratio [HR] 1.49, 95% confidence interval [CI] 1.22–1.83 for PRS percentile 5–50, HR 1.94, 95% CI 1.58–2.38 for PRS percentile 50–95, and HR 2.35, 95% CI 1.80–3.07 for PRS percentile &gt;95). Elevated DBP PRS was also associated with higher risk of hypertension (HR 1.27, 95% CI 1.04–1.54 for PRS percentile 5–50, HR 1.72, 95% CI 1.41–2.09 for PRS percentile 50-95, and HR 2.09, 95% CI 1.60–2.72 for PRS percentile &gt;95). The highest PRS percentile for SBP and DBP was associated with earlier onsets of hypertension by median 11 and 9 years, respectively, compared to the lowest PRS percentile for SBP and DBP. However, both SBP and DBP RPSs were not associated with incident CKD.

Conclusion
Genetic risk for elevated BP was associated with a higher risk of incident hypertension and earlier onset of hypertension in the Asian population. However, there was no association between PRS for elevated BP and the incidence of CKD.
#1219 Extracellular vesicles from patients with AMR-induced reprogramming of human podocytes into senescent cells: role of SGLT2i
Authors: Castellano Giuseppe , Armelloni Silvia , Mattinzoli Deborah , LI Min , Ikehata Masami , Alfieri Carlo , Abinti Matteo 
Published: May 2024

Abstract

Background and Aims
Extracellular vesicles (EVs) are organelles released by different cells that deliver biological information into the extracellular space and contribute to several diseases. However, their role in patients with antibody-mediated allograft rejection (AMR) remains uncertain. Our aim was to test the influence of plasma-derived EVs on human conditional immortalized podocytes (PODO) by investigating the possible role of dapagliflozin (Dapa) as a pharmacological agent.

Methods
Twenty-eight Rtx patients were included in the study, 14 with AMR, and 14 control TX patients (RTX). (CTRL). Plasma-derived Evs were used to stimulate PODO for 24 h, followed by exposure to 100 nM Dapa for 24 h. Differential ultracentrifugation at 110,000 g was applied, followed by counting with Nanosight and characterization by high-resolution flow cytometry according to the MISEV2018 criteria. PKH26 dye was used for the EVs-PODO incorporation study using Z-stack microscopy image acquisition. Total RNA and protein were extracted for gene expression and protein analysis, and the cells were fixed for immunostaining evaluation.

Results
We first found that upon activation with EV, PODO incorporated Es and shared them between cells; moreover, AMR-EVs led to an increased expression of tetraspanin marker of cell activation CD9 (p = 0.028) compared with CTRL. Importantly, the incubation of PODO with RTX-EVs induced a senescence-associated secretory phenotype (TNF alpha p = 0.0006, MCP1 p = 0.014); with cytoskeletal dysregulation and increase in gene expression and proteins involved in the epithelial to mesenchymal transition such as VIM (p = 0.026), senescence P21 (p = 0.04), inflammation CD44 (p = 0.034) with downregulation of Klotho (p = 0.002). Interestingly, incubation with Dapagliflozin significantly counteract PODO activation with reduction in P21 expression (p = 0.039) and an increase in Klotho (p = 0.047) abrogating inflammaging.

Conclusions
Our findings demonstrate that plasma EVs of AMR induced cellular senescence in PODO, reprogramming cellular processes such as cytoskeleton shape and composition, secretion of inflammatory cytokines, and decrease of the nephroprotective protein Klotho. This pathogenic process can be efficiently counteracted by SGLT2i.
#1071 The effect and mechanism of SGLT2 inhibitor on improving inflammatory injury of glomerular endothelial cells in diabetes
Authors: Liu Fang , Qin Chunmei 
Published: May 2024

Abstract

Background and Aims
ATP-binding cassette transporter A1 (ABCA1), which reduces intracellular cholesterol accumulation, is highly expressed in the kidney. Studies have shown that sodium-glucose co-transporter 2 inhibitors (SGLT2) inhibitors promote ABCA1 expression in multiple tissues and organs. However, the effect of SGLT2 inhibitors on ABCA1 expression in diabetic kidney disease (DKD) is unclear. In this study, the effect of empagliflozin, an SGLT2 inhibitor, on ABCA1 in glomerular endothelial cells(GECs) of DKD and the possible mechanisms linking ABCA1 to GECs inflammatory injury were investigated.

Method
Kidney tissues were obtained from renal biopsies of patients with early and advanced DKD. db/db mice were used as animal models of type 2 diabetes and the effects of SGLT2 inhibitors on ABCA1 were analyzed by treatment with empagliflozin. The effects of ABCA1 overexpression on glomerular lipid deposition and kidney injury were examined in a type 2 diabetic mouse model with ABCA1 overexpression (db/db + ABCA1 mice), and human renal glomerular endothelial cells (HRGECs) cultured in high glucose and high cholesterol conditions, which simulated type 2 diabetes in vitro.

Results
The expression of ABCA1 in the glomeruli of DKD patients and db/db mice was significantly decreased. Enhancing ABCA1 expression in the kidney tissue of diabetic mice by adenovirus transduction improved renal cholesterol deposition, inhibited the overactivation of C3a/C5a, and improved renal inflammatory injury. In addition, in cultured HRGECs under high glucose and high cholesterol conditions, ABCA1 deficiency increased the deposit of cellular cholesterol, contributed to overactivation of C3a/C5a, and induced inflammatory injury. Overexpression of ABCA1 enhancing cholesterol efflux or inhibition of C3a/C5a activation in vitro significantly protected against glomerular endothelial injury stimulated by high glucose and high cholesterol. Moreover, SGLT2 inhibitor empagliflozin up-regulated the expression of ABCA1 and down-regulated the levels of cholesterol, C3a/C5a and inflammatory cytokines in diabetic mice and HRGECs.

Conclusion
SGLT2 inhibitor (empagliflozin) might play a renal protective role by up-regulating ABCA1-mediated cholesterol outflow, inhibiting the activation of C3a/C5a, and then ameliorating the inflammatory injury of GECs.
#2474 TPPP3 maintains the stability of foot cytoskeleton architecture
Authors: Peng Liping , Chen Qilin 
Published: May 2024

Abstract

Background and Aims
Podocytes have a unique cytoskeleton architecture, and the disturbance of the skeleton architecture can lead to foot processes fusion and then proteinuria. Actin microfilaments dominate the cytoskeleton of the foot process, and microtubules and intermediate filaments dominate the synapses of the foot cells. The structural destruction of foot process actin is closely related to the injury of podocytes. The microtubule and actin often work together in cellular processes through stable connections. As the core structure of the skeleton network, microtubules play a key role in supporting and maintaining the skeleton network. However, the mechanism of microtubule structure destruction and podocyte injury remains unclear.

Method
Immunofluorescence and western blot were used to confirm the correlation between actin injury and decreased acetylation of tubulin in podocytes in vitro and in vivo. Single-cell RNA sequencing comprehensively characterized the expression of TPPP3 in human glomeruli. Immunofluorescence, immunohistochemical, western blot were used to determine the expression of TPPP3, α-tubulin, acetylated tubulin, actin microfilaments.

Results
In the case of podocyte injury, the acetylation level of tubulin decreased (P &lt; 0.05). Reducing tubulin acetylation can lead to microfilaments injury (P &lt; 0.05) and weakened podocyte motility (P &lt; 0.05). TPPP3 was specifically expressed in human glomerular podocytes, and its expression level was significantly decreased after podocyte injury (P &lt; 0.05). Knockdown of TPPP3 leaded to the level of microtubule acetylation decreased (P &lt; 0.05) and microfilaments were damaged (P &lt; 0.05) in podocytes. High acetylation levels of tubulin can partially restore actin microfilament damage caused by TPPP3 reduction in vivo and in vitro (P &lt; 0.05).

Conclusion
TPPP3 is involved in maintaining the normal morphology and function of podocytes by stabilizing the actin microfilament skeleton structure by regulating the acetylation level of microtubules.
#2814 Characterization of cardiological manifestations in patients with sodium-wasting tubulopathies
Authors: Cirillo Luigi , Cocchini Carlotta , Raglianti Valentina , Innocenti Samantha , Landini Samuela , Errichiello Carmela , Buti Elisa , Mazzinghi Benedetta , Francesca Becherucci 
Published: May 2024

Abstract

Background and Aims
Bartter (BS) and Gitelman (GS) syndromes are rare tubulopathies caused by mutations affecting renal NaCl transporters, resulting in similar symptoms like muscle weakness, cramps, and electrolyte imbalances, with GS also presenting with hypomagnesemia. Treatment focuses on electrolyte and fluid balance, using supplements and drugs to inhibit prostaglandin production and RAAS activation. Electrolyte deficits in these conditions can extend the QT interval and increase the risk of potentially fatal cardiac arrhythmias.
This study aims to profile BS and GS patients followed at our hospital, focusing on cardiological phenotyping. We assessed diagnostic, clinical, and lab data, particularly examining the link between electrolyte imbalances (like hypokalemia or hypomagnesemia) and electrocardiographic changes or cardiac symptoms during follow-up.

Method
We screened all BS and GS patients for study inclusion, requiring a genetic diagnosis with disease-causing mutations and comprehensive clinical and electrocardiographic data. We excluded cases lacking sufficient data. We gathered demographic and health information retrospectively, categorizing patients based on electrocardiographic results into groups: 1) persistent long QT interval, 2) transient long QT interval, and 3) no long QT interval. Data were summarized with medians, interquartile ranges, and frequencies.

Results
A total of 27 patients were enrolled in the study, 16 with Bartter Syndrome (BS) and 11 with Gitelman Syndrome (GS); median length of follow-up was 6 years (range 3-19). Only one patient was classified in group 1, with a constant QTc prolongation (446.3 ms); 8 patients (34.8%) fell into group 2 with median QTc values of 420 ms, all exhibiting hypokalemia and hypomagnesemia. The majority (14/23, 61%) were in group 3, with a median QTc of 399.2 ms and 79% displaying hypokalemia and hypomagnesemia. All 9 patients who experienced cardiac-related symptoms were adults, with 8 presenting these symptoms during intercurrent episodes. The study also compared clinical differences between BS and GS patients, noting a higher frequency of hypokalemia and hypomagnesemia in GS, whereas BS patients had more electrocardiographic alterations, although not statistically significant. No echocardiographic abnormalities were detected from the available data, and there were no recorded incidents of malignant arrhythmias or sudden death.

Conclusion
Electrocardiographic abnormalities in BS and GS patients fluctuate, often related to episodic events, with QT prolongation in one-third of cases but no severe cardiac complications, indicating a generally positive prognosis.
#662 Characterization of novel gene mutation sites associated with autosomal dominant polycystic kidney disease on 19 chromosomes
Authors: Zhang Xiao Liang , Yang Junlan 
Published: May 2024

Abstract

Background and Aims
Autosomal dominant polycystic kidney disease (ADPKD) is the most common single-gene inherited kidney disorder, affecting approximately 1 in 500-1000 newborns and often leading to end-stage renal disease. It involves cyst formation in various organs, with renal manifestations including cysts, hematuria, kidney stones, proteinuria, and hypertension. Liver, pancreas, seminal vesicles, spleen, and intracranial aneurysms may also be affected.
Genetic diagnosis, particularly for patients without a family history or with atypical imaging, is considered the gold standard. ADPKD is associated with several pathogenic genes, such as PKD1 and PKD2, as well as others like HNF-1B, GANAB, DNAJB11, SEC63, ALG8, ALG9, PRKCSH, LRP5, SEC61B, and SEC63. Understanding the genetic basis is crucial for early diagnosis and identifying high-risk individuals.
This study, based on genetic data from patients with renal polycystic kidney disease at Zhong Da Hospital Southeast University, identified novel ADPKD gene mutations. It explored structural changes in proteins, predicting effects on phenotype, to contribute to the enrichment of the ADPKD gene database.

Method
In a single-center cross-sectional retrospective study, patients with renal multiple cysts diagnosed from January 2019 to February 2023 at the Zhong Da Hospital Southeast University were included. Genetic and clinical data of patients and their families were collected. Unreported novel gene mutation sites associated with ADPKD were identified, and AlphaFold v2.3.1 was employed to predict protein structures. Changes in protein structure before and after mutations were compared to explore genotype-phenotype correlations and enrich the ADPKD gene database.

Results
The study included 96 patients with renal multiple cysts and their relatives from 62 families. Twelve mutated genes associated with renal cysts were detected in 52 families. Nineteen novel gene mutation sites associated with ADPKD were identified (Table 1, Fig. 1) , including 17 mutations in the PKD1 gene (1 splicing mutation, 7 frameshift mutations, 4 nonsense mutations, 1 whole-codon insertion, and 4 missense mutations), 1 ALG9 missense mutation, and 1 chromosomal structural variation. Truncating mutations in the PKD1 gene were correlated with a more severe clinical phenotype, while non-truncating mutations were associated with greater clinical heterogeneity.

Conclusion
Numerous novel gene mutation sites associated with ADPKD remain unreported. It is essential to analyze the pathogenicity of these novel mutation sites, establish genotype-phenotype correlations, and enrich the ADPKD gene database.
#1232 Integrating genotype and phenotype data is required for renal survival prediction in autosomal dominant polycystic kidney disease
Authors: Evangelou Eirini , Konsta Maria , Vasileiou Kyriaki , Poula Angeliki , Markou Niki , Poulli Tsielestina , Lazaros Leandros , Gkalitsiou Dimitra , Liaveri Paraskevi , Tsirpanlis George 
Published: May 2024

Abstract

Background and Aims
Autosomal dominant polycystic kidney disease (ADPKD) is the cause for 5-10% of end stage kidney disease (ESKD) worldwide. Accurate renal prognosis is essential for effective disease management. Investigation of the prognostic value of combining genetic and phenotypic characteristics in a cohort of ADPKD patients is attempted.

Method
In 66 ADPKD patients (mean age 33 ± 12 years, 32 males) the genetic diagnosis (using targeted Next Generation, tNGS, or Sanger Sequencing or Multiplex ligation-dependent probe amplification, MLPA) and the Mayo Clinic Imaging Category (MCIC) (through Renal Magnetic Resonance Imaging, MRI, for Total Kidney Volume measurement) were assessed. The prediction of ESKD was performed using the Mayo Clinic formula (Irazabal MV et al JASN, 2015). The calculation incorporated variables such as sex, age, e-GFR, and the MCIC. The PROPKD score was derived by considering both phenotypic factors (sex, hypertension and urologic events before the age of 35 years) and genetic data (PKD1-truncating, PKD1-nontruncating and PKD2).

Results
Adjusted for age, the e-GFR was on average, 26 and 27 ml/min higher in PKD2 patients compared to ADPKD-PKD1-truncating and ADPKD-PKD1-non-truncating patients, respectively (p = 0.001). The median prediction of ESKD for ADPKD-PKD1-truncating, ADPKD-PKD1-non-truncating and PKD2 patients was 22 (11-31) years, 22 (11-34) years and 31 (21-59) years, respectively (NS). In patients categorized as high risk according to PROPKD (score 7-9) the predicted time to ESKD was 16 (9-30) years, for those at intermediate risk (score 4-6), 25 (13-34) years and for those at low risk (score 0-3), 28 (16-55) years (NS). Finally, the PROPKD score showed an inverse correlation to the years of ESKD prediction, as determined by the Mayo Clinic formula; a higher PROPKD score was associated with a shorter prediction period for ESKD (Spearman r = −0.3, p = 0.04).

Conclusion
Prognosis of renal survival in ADPKD patients requires not only a specific genetic diagnosis but also consideration of the phenotypic data, as incorporated in the PROPKD score, enhancing the accuracy of renal survival prediction.