bluuebunny/crossref_metadata_2025_split huggingface dataset:
#3949 NPY GENE POLYMORPHISMS ARE STRONGLY LINKED TO CKD PROGRESSION: A MENDELIAN RANDOMIZATION STUDY
Authors: Spoto Belinda , Mallamaci Francesca , Politi Cristina , Parlongo Rosa , Tripepi Giovanni Luigi , Leonardis Daniela , Capasso Giovambattista , Zoccali Carmine 
Published: June 2023

Abstract

Background and Aims
Neuropeptide Y (NPY) is a 36 amino-acid neuropeptide that regulates various physiological processes in both the central and peripheral nervous systems, including cardiovascular and metabolic control. We showed that high plasma NPY predicts CKD progression (NDT 2018;33:1805-1812) in a cohort of 735 patients with stage G2-5 CKD. Whether this association is causal in nature is undetermined.

Method
In the same cohort of the previous study, we tested the relationship between NPY gene variability, as assessed by six single nucleotide polymorphisms (SNPs) representative of the gene haploblock structure which explained about 80% of gene variability, and the incidence rate of renal events (dialysis/transplantation/eGFR reduction &gt;30%) over a median follow up of 36 months (inter-quartile range 35-37 months).

Results
Three variants [rs16131 (TT, n = 563; CT+CC, n = 172), rs16140 (CG+GG, n = 413; CC, n = 322), rs16148 (CT+CC, n = 456; TT, n = 279)] coherently associated to the incidence rate of renal events (HR ranging from 1.36 to 1.57, P≤0.029). A dose response relationship was found between the number of risk variants and renal events, the HR for this outcome being highest in patients with three risk genotypes (HR: 1.66, 95% 1.05-2.61). In a multivariate model adjusting for traditional risk factors (age, gender, smoking, diabetes, cholesterol, systolic BP and background cardiovascular comorbidities) and factors peculiar to CKD (haemoglobin, eGFR, albumin, phosphate, and C-reactive protein), the association remained highly significant (P for trend = 0.001). In a separate analysis including the three variants simultaneously, only the rs16131 variant maintained an independent association with the risk for renal events (HR: 1.58, 95% CI 1.11-2.24, P = 0.01).

Conclusion
This Mendelian randomization study based on three gene variants is fully in line with findings indicating that high plasma NPY predicts a high risk for renal events and lends support to the hypothesis that NPY is causally involved in CKD progression. Establishing the functional significance of the rs16131 variant is a clinical research priority. Drugs antagonizing circulating NPY or its receptors, indeed, might favourably impact on CKD progression.
#3958 PROTON PUMP INHIBITORS AND THE RISK OF ACUTE KIDNEY INJURY IN PATIENTS RECEIVING IMMUNE CHECKPOINT INHIBITORS: A POPULATION-BASED COHORT STUDY
Authors: Munch Philip Vestergaard , Nørgaard Mette , Heide-Jørgensen Uffe , Jensen Simon Kok , Birn Henrik , Christiansen Christian Fynbo 
Published: June 2023

Abstract

Background and Aims
Proton pump inhibitors (PPI) are commonly used in cancer patients. Multiple studies have found that PPI use is associated with a more than 2-fold increased risk of acute kidney injury (AKI) in patients treated with immune checkpoint inhibitors (ICI). However, this association could possibly be explained by confounding by indication for PPI use.

Method
In a population-based cohort study, we compared the risk of AKI in users and non-users of PPI among cancer patients treated with ICI in Denmark during 2011-2021. We assessed exposure to PPI by filled prescriptions for PPI within 90 days before ICI initiation and identified AKI events within the first year after ICI initiation using plasma creatinine measurements from laboratory databases. We included information on potential confounders including important comorbidities and comedication. We estimated the propensity score for PPI use using logistic regression and calculated unweighted and standardized mortality ratio (SMR)-weighted absolute risks and hazard ratios (HRs) of AKI. To address any switch in PPI exposure during follow-up, we did an additional per-protocol analysis censoring patients upon switch in PPI exposure. We furthermore applied inverse probability of censoring (IPC) weights to mitigate informative censoring.

Results
We included 9,955 cancer patients treated with ICI. Among these, 2,668 (26.8%) were users of PPI. During the first year of follow-up, AKI occurred in 1,932 of the included patients, yielding an overall unweighted incidence rate of 30.1 per 100 person-years and a 1-year AKI risk of 21.3%. PPI users had an increased risk of AKI compared with non-users (1-year risk, 24.4% versus 20.2%; HR, 1.37 [95% CI, 1.24-1.51]); however, this association attenuated when accounting for confounders by SMR weighting (SMR-weighted 1-year risk, 24.0% versus 23.3%; SMR-weighted HR, 1.05 [95% CI, 0.93-1.18]). In the per-protocol analysis, the unweighted HR was 1.82 (95% CI, 1.60-2.07), while the SMR- and IPC-weighted HR was 1.22 (95% CI, 1.03-1.45).

Conclusion
PPI use at the time of ICI initiation was not associated with an increased risk of AKI after SMR weighting. When considering switching of PPI exposure during follow-up, we observed that PPI use was associated with an increased risk of AKI; however, the association was much weaker than previously reported.
#3968 DIFFERENCES IN MENTAL HEALTH STATUS DURING COVID-19 PANDEMIC BETWEEN IN-CENTER HEMODIALYSIS AND PERITONEAL DIALYSIS PATIENTS
Authors: Bouwmans Pim , Skalli Zeinab , Vernooij Robin , Hemmelder Marc , Konijn Wanda , Lips Joy , Mulder Janneke , Bonenkamp Anna , Van Jaarsveld Brigit , Abrahams Alferso C 
Published: June 2023

Abstract

Background and Aims
Results from previous studies suggest that mental health of dialysis patients was unaffected during the first wave of the COVID-19 pandemic. However, the location of dialysis treatment might have had a different impact on patients during the ongoing COVID-19 pandemic, especially at time of restrictions. Studies comparing the mental health of ICHD and PD patients during the pandemic are scarce. Therefore, we aimed to assess whether dialysis modality differently affected the mental health of patients during the COVID-19 pandemic.

Method
This study used data of patients participating in the Dutch nOcturnal and hoME dialysis Study To Improve Clinical Outcomes (DOMESTICO). We conducted repeated cross-sectional analyses between ICHD and PD patients from the start of the COVID-19 pandemic in March 2020 until August 2021. For this, we divided the study period into six periods of three months. The year before the pandemic was used as reference period. Mental health-related quality of life (HRQOL) was assessed using the mental component summary (MCS) score of the 12-item Short Form (SF-12) health survey. The presence of mental symptoms was determined using the Dialysis Symptom Index (DSI). Both questionnaires were provided at start of dialysis, at 3 months, 6 months and each 6 months thereafter. Patients were included for analysis if a questionnaire was available in at least one period. MCS scores and the prevalence of mental symptoms between ICHD and PD patients were compared with Student's t-test and Chi-square test, respectively. Moreover, we performed multivariable regression analyses to adjust for possible confounders.

Results
For this analysis, 1274 patients (968 ICHD and 306 PD) were included. Mean age was 65±14 and 64±14 years, respectively. Most patients were male (ICHD: 68%, PD: 61%). Before the pandemic ICHD patients reported similar MCS scores, yet more often reported feeling nervous (32% vs. 22%, P = .03) and sad (40% vs. 29%, P = .03). During the pandemic, mean MCS scores also did not differ between ICHD and PD patients. In contrast, ICHD patients more often reported feeling nervous during period 3 (27% vs 15%, P = .04), feeling irritable and anxious during period 3 (31% vs 18%, P = .03, 26% vs. 9%, P = .002, resp.) and period 4 (34% vs 22%, P = .04, 22% vs 11%, P = .03, resp.), and feeling sad in period 4 (38% vs 26%, P = .04) and period 5 (37% vs 22%, P = .009). In a multivariable regression analysis, these differences persisted after correction for several confounders.

Conclusion
ICHD patients experienced more mental symptoms compared to PD patients in the period September 2020 to June 2021, which corresponds with the second lockdown of the COVID-19 pandemic. This higher prevalence of specific mental symptoms in ICHD patients was not reflected by a decrease in mental HRQoL.
#3971 INJURY INDUCED RENAL FIBROSIS PROMOTES CYSTOGENESIS AND CYST GROWTH IN ADULT MICE WITH AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE
Authors: Xing Yufeng , Wu Ming , Ye Chaoyang 
Published: June 2023

Abstract

Background and Aims
Acute kidney injury (AKI) is not a merely transient event, which can lead to a subsequent progression to chronic kidney disease (CKD). Autosomal dominant polycystic kidney disease (ADPKD) is the most frequent inherited kidney disease caused by mutations in PKD1 or PKD2 gene. Previous studies showed that acute kidney injuries promote cystogenesis in adult mice with ADPKD. Fibrosis is a hallmark of AKI to CKD (AKI-CKD) transition, and positively correlated with renal cyst growth in humans. All these data imply a role of AKI-CKD transition in ADPKD.In this study, we aimed to determine the role of AKI-CKD transition in the ADPKD.

Method
We established AKI-CKD transition model by toxic or surgical injuries, and Pkd gene inactivation in adult mice was performed in different time point of AKI-CKD transition. The progression of renal fibrosis was shown by Western blotting analysis in toxic or surgical injury induced AKI-CKD transition model.

Results
We showed that renal injury before or after Pkd gene inactivation can both induce renal cyst formation in adult Pkd1 or Pkd2 mice, and the extent of cyst formation was correlated with the initial fibrosis level of three hits (injury and gene inactivation). Inactivation of Pkd1 gene at fibrosis recovery stage in surgery induced less cyst formation in adult Pkd1 mice. Enhanced renal fibrosis by repeated toxic injuries before gene inactivation accelerated renal cyst growth in Pkd1 mice. We further showed that the speed of cyst growth at the early stage in adult Pkd1 mice was decided by the baseline of renal fibrosis. Finally, we showed that conditional knockout of Ezh2 gene attenuated renal fibrosis and cyst growth in adult Pkd1 mice with established renal fibrosis.

Conclusion
Fibrotic responses in AKI-CKD transition is a driving force for renal cyst formation and growth in adult kidneys and inhibition of renal fibrosis through targeting EZH2 might be new therapeutic strategy for adult ADPKD.
#3976 THE ROLE OF GENDER DIFFERENCES AND MENOPAUSE IN OBESITY-RELATED RENAL DISEASE, RENAL INFLAMMATION AND LIPOTOXICITY
Authors: Afonso-Alí Aaron , Porrini Esteban , Teixidó-Trujillo Silvia , Perez-Perez Jose Antonio , Luis-Lima Sergio , Acosta-González Nieves Guadalupe , Sosa-Paz Irene , Martin Laura Díaz , Rodríguez-González Covadonda , Rodríguez-Rodríguez Ana Elena 
Published: June 2023

Abstract

Background and Aims
The pathogenesis of obesity related-renal disease is unknown. Gender differences may have a role in renal damage in obesity. In particular, menopause can promote renal disease in obese women. In a previous study we observed that obese male and female mice developed albuminuria, hyperfiltration and glomerulomegaly, and these changes were more severe in those obese ovariectomized females. In this study we evaluated renal inflammation and lipotoxicity in that model.

Method
Twenty-two males and 57 females C57BL6/J mice were randomized to standard diet (SD) or high fat diet (HFD) for six months. A group of female animals on SD o HFD was ovariectomized to induce menopause. In renal tissue we evaluated cytokines: NF-κβ, IL-1β, MCP-1, TNF-α and total lipid content, lipid classes, fatty acid profile and fatty acids in lipid classes. Part of the lipidomic analysis was performed in urine.

Results
Obese males and females showed higher NF-κβ, TNF-α and MCP-1 in renal tissue (Fig. 1). Obese females ovariectomized had higher IL-1β and TNF-α compared with obese female not-ovariectomized (Fig. 1B). Obese animals showed lower pro-inflammatory fatty acids (16:0, 16:1n-7 and 18:2n-6) and higher anti-inflammatory fatty acid (22:6 n-3) (Fig. 2A). This pattern was also observed in specific lipid classes and urine. Finally, obese females ovariectomized had a more exacerbated pattern, with high 18:0 in phosphatidylcholine, high 18:0 DMA phosphatidylethanolamine and low 16:0 in triglycerides (Fig. 2B-D).

Conclusion
In conclusion, obesity induces inflammation and an unbalanced (pro-inflammatory) lipidic profile in renal tissue. This pattern seems to be enhanced in obesity after menopause.
#4013 LIPIDOMIC ANALYSIS OF PFSGS PATIENTS' SERUM TO IDENTIFY POTENTIAL CANDIDATES FOR THE CIRCULATING PERMEABILITY FACTOR(S) IN THE LIPID DOMAIN
Authors: Rother Nils , Rood Ilse , Bekkering Siroon , Riksen Niels , Hilbrands Luuk , Maas Rutger , Nijenhuis Tom , Duivenvoorden Raphael 
Published: June 2023

Abstract

Background and Aims
Patients with primary focal segmental glomerulosclerosis (pFSGS) present with nephrotic syndrome. Whereas the exact pathogenesis is largely unknown, there is strong evidence that one or more circulating permeability factors in the circulation induce podocyte injury. Podocyte injury eventually leads to foot process effacement, massive proteinuria and kidney function loss. Historically, research into the cause of pFSGS has focused primarily on identifying the circulating factor in the protein domain, but reports of successful treatment with lipid apheresis suggest that it could also be a lipid compound. Here, we set out to investigate the lipidome of pFSGS patients’ serum to identify potential candidates for the circulating permeability factor(s) in the lipid domain.

Method
For this lipidomics study, we included 5 patients with pFSGS in whom serum had been collected at the time they presented at our center with active nephrotic syndrome. We compared the serum lipidome of the pFSGS patients with age matched healthy controls (n = 5), and with age matched patients with familial hypercholesterolemia (n = 5) who, like pFSGS patients, have significantly elevated lipid values. Serum was analyzed using the Shotgun Lipidomics platform by Lipotype GmbH (Dresden, Germany), as previously described [1]. The amount of lipids were normalized to the total amount of lipids present within the sample.

Results
The lipidomic profile of patients with pFSGS was markedly different from the profile of healthy controls and patients with hypercholesterolemia. We found differences in various lipid classes in pFSGS patients, including cholesterol esters (CE), lyso-phophatidylcholine (LPC), phophatidylethanolamine (PE), diacylglycerol (DAG) and triacylglycerol (TAG) that were significantly changes compared to both healthy controls and FH patients. Diacylglycerols (DAG) were identified as the most significantly increased lipid species in pFSGS. By analyzing the subspecies we discovered that DAGs with carbon chains greater than 38 carbon atoms in both chains combined (long carbon chain DAGs, lccDAGs) were exclusively present in patients with pFSGS.

Conclusion
Our lipidomics data show that patients with pFSGS have a substantially different lipid profile than healthy controls and patients with familial hypercholesterolemia. We identified lccDAGs as unique lipids in patients with pFSGS, that were not present in controls. This is an interesting finding since the DAG-analogue 1-oleoyl-2-acetyl-sn-glycerol (OAG) is known to be able to induce podocyte injury in vitro [2]. In further research, we will focus on confirming whether lccDAGs are unique to pFSGS patients, whether it is suitable as a biomarker, and whether it plays a causal role in the disease process.
#4027 KIDNEY INJURY MOLECULE 1 (KIM-1): A POTENTIAL BIOMARKER OF ACUTE KIDNEY INJURY AND TUBULOINTERSTITIAL INJURY IN PATIENTS WITH ANCA-GLOMERULONEPHRITIS
Authors: Brilland Benoit , Boud’hors Charlotte , Wacrenier Samuel , Blanchard Simon , Cayon Jérôme , Blanchet Odile , Piccoli Giorgina Barbara , Nicolas Henry , Djema Assia , Coindre Jean-Philippe , Jeannin Pascale , Delneste Yves , Copin Marie-Christine , Augusto Jean-François 
Published: June 2023

Abstract

Background and Aims
Kidney injury molecule 1 (KIM-1) is a transmembrane glycoprotein expressed by proximal tubular cells, recognized as an early, sensitive, and specific urinary biomarker for kidney injury. Blood KIM-1 was recently associated with the severity of acute and chronic kidney damage but its value in ANCA-associated vasculitis with glomerulonephritis (ANCA-GN) has not been studied. Thus, we analyzed its expression at ANCA-GN diagnosis and its relationship with clinical presentation, kidney histopathology, and early outcomes.

Method
We assessed KIM-1 levels and other pro-inflammatory molecules (CRP, IL-6, TNF-α, MCP-1 and PTX3) at ANCA-GN diagnosis and after 6 months in patients included in the Maine-Anjou registry, which gathers data patients from four French Nephrology Centers diagnosed since January 2000.

Results
Blood KIM-1 levels were assessed in 58 patients. Levels were elevated at diagnosis and decreased after induction remission therapy. KIM-1 was associated with the severity of renal injury at diagnosis and the need for KRT. In opposition to other pro-inflammatory molecules, KIM-1 correlated with the amount of interstitial fibrosis and tubular atrophy (IF/TA) on kidney biopsy, but not with glomerular involvement. In multivariable analysis, elevated KIM-1 predicted initial eGFR (β = -19 [-31, -7.6], p = 0.002).

Conclusion
KIM-1 appears as a potential biomarker for acute kidney injury and for tubulointerstitial injury in ANCA-GN. Whether KIM-1 is only a surrogate marker for IF/TA or a key immune player in ANCA-GN pathogenesis remain to be determined.
#4066 EARLY EXPERIENCE OF ENDOVASCULAR CREATION OF ARTERIOVENOUS FISTULA IN SOUTHEAST ASIA
Authors: Loo Kok Pan , Tan Ru Yu , Tan Chee Wooi , Chong Tze Tec , Tay Kiang Hiong , Tay Hsien Tsung , Zhuang Kun Da , Gogna Apoorva , Tan Chieh Suai 
Published: June 2023

Abstract

Background and Aims
Creation of native arteriovenous fistulae(AVF) has been traditionally through open surgical technique. Endovascular creation of AVF (EndoAVF) has been shown to be an effective alternative to open surgery in Europe and North America. In Asia, EndoAVF creation is a novel technique and we report our early experience of EndoAVF creation in a case series of 18 patients.

Method
Between Nov 2021 to Aug 2022, ultrasound vein mapping was performed in a total of 39 patients. Eighteen patients were deemed suitable for EndoAVF and proceed for the procedure. EndoAVF creation was attempted by multidisciplinary team comprising of vascular surgeon, interventional radiologists and nephrologists. The patients were prospectively followed-up for at least 6-months. Baseline demographics, vascular characteristics, unassisted maturation, functional patency and freedom from intervention were studied.

Results
Table 1 shows the baseline demographics of the participants. Twelve patients (67%) were already initiated on hemodialysis via tunneled dialysis catheters during the procedure. EndoAVF was successfully created in 16 (89%) patients. Of which, 13 (72%) were WavelinQ while the remaining 5 (28%) were Ellipsys EndoAVF. The reasons of failures were inability to cannulate artery (n = 1) and vein (n = 1). Minor complications occurred in 6 patients: extravasation in 5 cases and hematoma in 1 patient. The brachial artery flow rates at creation and 1-month post-creation were 558 ± 328 and 583 ± 215 mls/min, respectively. Two participants (11%) underwent interventions to facilitate maturation of the EndoAVF. The median time to maturation was 70 (IQR 49 – 106) days while the median time to first successful 2-needle cannulation was 77 (56 – 127) days. At 6-months, 8 (50%) of EndoAVFs that were successfully created required further intervention to maintain patency, while 1 EndoAVF was abandoned from failure to mature despite intervention

Conclusion
EndoAVF can be created successfully in a Southeast Asian population. Further studies with more patients and longer follow-up periods are needed to assess long-term outcomes.
#4082 TAZ-KNOCKDOWN AFFECTS THE VASOPRESSIN-INDUCED AQUAPORIN-2 (AQP2) TRAFFICKING AND PROTEIN ABUNDANCE IN KIDNEY COLLECTING DUCT CELLS
Authors: Choi Hongseok , Jang Hyo-Ju , Kwon Tae-Hwan 
Published: June 2023

Abstract

Background and Aims
Transcriptional coactivator with PDZ-binding motif (TAZ), a downstream effector of the hippo signaling pathway, regulates the expression of target genes by acting as a transcription cofactor. TAZ KO mice were known to display multicystic kidneys with polyuria. We aimed to study the role of TAZ in vasopressin-induced AQP2 regulation.

Method
1) siRNA-mediated knockdown of TAZ in mpkCCDc11 cells; 2) RT-qPCR, semiquantitative immunoblotting, immunocytochemistry of AQP2; 3) Next Generation Sequencing (NGS) in mpkCCDc11 cells, the mouse collecting duct cell line.

Results
Endogenous AQP2 expression was induced in mpkCCDc11 cells by dDAVP (10−9M) treatment. After starvation for 24 h, dDAVP (10−9M) stimulation for 15 and 30 min induced a significant AQP2 translocation to the cell membrane. In contrast, the dDAVP-induced AQP2 translocation was markedly attenuated in the cells with siRNA-mediated TAZ knockdown (TAZ-KD), despite no changes in cAMP production. Phalloidin staining demonstrated the excessive stress fiber formation in the TAZ-KD. dDAVP (10−9 M) treatment for 24 h induced AQP2 mRNA (12,608 ± 177% of the control) and AQP2 protein abundance (270 ± 18%). In contrast, dDAVP-induced increase of AQP2 mRNA (273 ± 14% of the control) and protein abundance (99 ± 17%) was significantly attenuated in TAZ-KD. Unchanged TonEBP protein abundance was observed in TAZ-KD. NGS identified several potential AQP2 transcription factors (TF), and Klf6, Irf3, Cebpb, and Nr4a1 were selected based on previous in silico database. Among them, Nr4a1 was chosen for further studies due to a significant decrease in the mRNA expression levels in TAZ-KD, as demonstrated by RT-qPCR.

Conclusion
TAZ is likely to affect dDAVP-induced AQP2 trafficking. This is not mediated by the changes in cAMP/PKA pathway, but other non-canonical pathways are involved. TAZ could regulate AQP2 abundance, possibly via an interaction with several TF.