bluuebunny/crossref_metadata_2025 huggingface dataset:
#3795 EARLY AND LATE PATIENT OUTCOMES IN URGENT-START PERITONEAL DIALYSIS: A PROSPECTIVE STUDY OF UNPLANNED INITIATION OF CHRONIC DIALYSIS
Authors: Ghita Elbardai , Chouhani Basmat Amal , Kabbali Nadia , Houssaini Tarik Sqalli
Published: June 2023

Background and Aims

Peritoneal dialysis (PD) has become a well-established complementary alternative to hemodialysis (HD) as the first-line renal replacement modality. Unlike the temporary catheter for hemodialysis that can be used immediately after implementation, the PD catheter usage period remains controversial. The aim of this study was to compare the short- and long-term outcomes in patients under peritoneal dialysis according to the delay of starting the dialysis after catheter placement.

Method

This observational prospective study was conducted over an eight-year and four-month period (from April 2014 to August 2021), including all patients treated with peritoneal dialysis for 18 months (from April 2014 to October 2015). The patients were divided into two groups according to whether the catheter was used during the first 15 days (PD-E) or 15 days after (PD-L) catheter placement. The primary outcomes were early complications (mechanical and infectious) within 90 days. Secondary outcomes included technique survival.

Results

Among the 36 patients included in the study, 14 started PD early (38.8%), while 22 started it 15 days after catheter placement (61.2%). The mean age between the two groups was not significantly different (41 ± 17 years vs 35 ± 16 years, p: not significant). There were no significant differences in the Charlson comorbidity index or the degree of autonomy. The incidence of infections was not significantly different between the two groups (13.6% in PD-L vs 21.4% in PD-E, p: not significant). The total number of mechanical complications was not significantly higher in the PD-E group compared to the PD-L group (42.8% vs 27.3%, respectively, p: not significant). Kaplan-Meier estimates of technique survival were comparable between the groups (log Rank: 1.908, p: 0.67).

Conclusion

Our study showed no increase in the risk of complications associated with early use of the PD catheter and no difference in technique survival. PD can be used as first-line renal replacement therapy in the unplanned initiation of chronic dialysis.
#3802 ROLE OF NEUTROPHIL EXTRACELLULAR TRAPS IN DIABETIC KIDNEY DISEASE: DATA FROM INTEGRATION OF BULK RNA AND SINGLE-NUCLEUS RNA SEQUENCING ANALYSES
Authors: Xie Ruiyan , Zhu Litong , Jason Sher Ka Ho , Yap Desmond
Published: June 2023

Background and Aims

Neutrophil extracellular traps (NETs) is an important immune response against infections that is implicated in various immune-mediated conditions. Growing evidence shows that inflammation has key pathogenic contributions in diabetic kidney disease (DKD) but the role of NETs remains unclear.

Method

We evaluated the differentially expressed genes (DEGs) of NETs in human DKD using the bulk RNA sequencing datasets of kidney biopsy from DKD patients (GSE30528 and GSE30529). The candidate genes were further selected based on the machine learning algorithms (LASSO and SVM-RFE). The single-nucleus RNA sequencing (GSE195460 and GSE131882) and DKD bulk RNA sequencing (GSE30122) were used to validate the results. Receiver Operating Characteristics (ROC) curve were constructed to assess the diagnostic performance of the identified genes for DKD. Candidate drugs were further screened from the DSigDB database.

Results

Three characteristic genes (ITGAM, ITGB2 and TLR7) were selected using machine learning approach, which were all upregulated in human DKD glomerular and tubulointerstitial portion compared to healthy controls (all P <0.05). Single-cell analysis further demonstrated that ITGAM, ITGB2 and TLR7 were mainly overexpressed in leucocytes. ITGAM, ITGB2 and TLR7 expression in tubulointerstitial compartment also showed good diagnostic performance for DKD (ROC AUC 0.983, 0.975 and 0.958 respectively). Candidate drugs that target ITGAM, ITGB2 or TLR7 genes in DKD include ropivacaine, lidocaine and sulfasalazine.

Conclusion

ITGAM, ITGB2 and TLR7 may serve as biomarkers for DKD and drugs that target these genes may have therapeutic potential for DKD.
#3804 ASSOCIATION BETWEEN PLASMA XOR AND OUTCOMES IN CKD PATIENTS
Authors: Makino Shuzo , Okushima Hiroki , Kani Nao , Hashimoto Nobuhiro , Iio Rei , Ueda Yoshiyasu , Hayashi Terumasa
Published: June 2023

Background and Aims

Plasma xanthine oxidoreductase (pXOR) is an enzyme plays a key role in uric acid (UA) production and produces reactive oxygen species (ROS), and it has been reported that pXOR activity is related with cardiovascular events in the general population. However, the relationship between pXOR activity and prognosis in patients with chronic kidney disease (CKD) remains unclear.

Method

We measured pXOR activity by Liquid chromatography tandem quadruple mass spectrometer (LC-TQMS method) in 415 outpatients with CKD, and compared demographic and laboratory data between two groups based on the median pXOR activity. Furthermore, we examined the association between pXOR activity and outcomes; renal replacement therapy (RRT), major adverse cardiovascular events (MACE), and all-cause mortality, using multivariate Cox proportional hazards model.

Results

Median age and eGFR were 71 years old and 21.6 ml/min/1.73 m2, respectively. Median pXOR activity is 3.33 pmol/h/ml and 26.3 pmol/h/ml in the lower and higher pXOR activity groups, respectively. eGFR was significantly lower and UA was significantly higher in the lower pXOR activity group compared with the higher pXOR group (eGFR, 18.9 vs 27.4, P, <0.001; UA, 5.7 vs 6.1, P, <0.001). During the follow-up period of 38 months, the incidence of each outcome including RRT, MACE, or all-cause mortality were significantly higher in the lower pXOR group (log rank test, P<0.001). Multivariate Cox proportional hazards analysis including eGFR and UA levels showed that lower pXOR activity was significantly associated with poor renal? outcome (HR, 1.4; 95% CI, 1.0-2.1; P, 0.038). Furthermore, in subgroup analysis with or without antihyperuricemic use, univariate Cox analysis showed similar association between pXOR and each outcome.

Conclusion

In patients with CKD, lower pXOR activity has a significantly higher risk of all outcome (RRT, MACE, and all-cause mortality).
#3812 ARE KIDNEY CYSTS MORE COMMON IN PEOPLE WITH COL4A3/COL4A4 PATHOGENIC VARIANTS?
Authors: Teran Melissa Pilco , Furlano Monica , Pybus Marc , Jiménez Víctor Martínez , Peris Asunción Rius , Gomez Maria Vanessa Perez , Redondo Gerson Berna , De Arizon Leonor Fayos , Ars Elisabet , Torra Roser
Published: June 2023

Background and Aims

Individuals with pathogenic heterozygous variants in the COL4A3/COL4A4 genes are usually asymptomatic or present only with microhaematuria, although some may develop proteinuria and chronic kidney disease (CKD). Simple renal cysts are common in healthy individuals, with an increasing incidence with age and CKD grade. A possible association between pathogenic variants of collagen type IV and renal cysts has been described. This study investigates the presence of renal cysts in a large cohort of individuals with heterozygous pathogenic variants in COL4A3/COL4A4.

Method

We evaluated the presence of kidney cysts, kidney size and lithiasis by ultrasound in 162 individuals with pathogenic variants in COL4A3/COL4A4 without kidney replacement therapy. The correlation between kidney cysts and age, proteinuria, eGFR, causing gene and type of variant, was analysed. Genetic testing had been performed in index cases by next generation sequencing (NGS) of a kidney-disease gene panel containing more than 400 genes including COL4A3, COL4A4 and COL4A5 genes.

Results

153 patients with a heterozygous disease-causing variant in COL4A3 or COL4A4 and 9 patients with digenic/complex inheritance were included. The mean age at renal ultrasound was 46.19 years (SD 14.93) and the mean eGFR was 75 ml/min/1.73 m2 (SD 35 ml/min/1.73 m2). Renal cysts were present in 50% of patients (81/162) and were bilateral in 30.25%. The mean age of patients with renal cysts was 53.26 years vs. 39.12 years for those without, and the mean eGFR was 60ml/min/1.73 m2 vs. 89ml/min/1.73 m2 for patients with and without renal cysts. Only 2.5% (4/162) of patients had renal lithiasis. The mean kidney size was 104.05 mm (SD 13.86 mm) for the right kidney and 104.98 mm (SD 13.94 mm) for the left kidney. Cystic nephromegaly was observed in 3.7% (6/162). No correlation was found between renal cysts and gender (p = 0.632). Age and CKD stage had a positive correlation with the development of renal cysts (p = <0.001) (Tables 1 and 2). Proteinuria was more common in individuals with renal cysts 61% vs 39% (p = 0.012), but was related to age and CKD stage. The presence of a kidney cyst did not correlate with the mutated gene or the type of variant.

Conclusion

Individuals with COL4A3/COL4A4 pathogenic variants develop kidney cysts at a higher rate than age-matched healthy individuals, and their presence is also related to ageing, as in the general population. Gender is not relevant for the development of renal cysts, in contrast to the general population cohorts. Proteinuria and CKD grade correlate with the development of renal cysts but nephromegaly is rare. Renal cysts in heterozygous carriers of COL43 or COL4A4 pathogenic variants are common but have no clinical consequences.
#3823 CAN HLA MOLECULAR MISMATCH GUIDE CLINICAL DECISION IN PAEDIATRIC KIDNEY TRANSPLANT RECIPIENTS: A RETROSPECTIVE STUDY
Authors: Gramkow Ann-Maria , Baatrup Johanne , Thiesson Helle Charlotte , Koefoed-Nielsen Pernille
Published: June 2023

Background and Aims

Optimizing graft survival and diminishing anti-HLA sensitization are essential in paediatric kidney transplant recipients (KTRs) facing multiple retransplantations. Improved pretransplant risk stratification and donor selection using in silico molecular HLA matching could enhance personalized immunosuppression and improve outcomes. HLA EMMA is a new in silico method to predict B cell epitope mismatches, and its clinical applicability needs confirmation in paediatric transplantation. We investigated the association of HLA B cell epitope (HLA EMMA) and predicted HLA T cell epitope (PIRCHE) mismatches with de novo donor specific antibodies (dnDSA), anti-HLA antibodies, rejection, and graft survival.

Method

We retrospectively analysed 49 consecutive paediatric KTRs aged 1 to 16 transplanted from 2009-2020 at a single Danish centre. The centre has a long tradition of steroid-free kidney transplantations in immunologically uncomplicated recipients, and 80% of the KTRs did not receive steroids. Donors and recipients were all high-resolution HLA typed, and HLA EMMA (v 1.00) and PIRCHE (v 3.3.60) predicted the molecular mismatches. KTRs were screened with mixed and single bead antigen kits after the transplantation. Logistic regression analyses were performed to explore the association of molecular mismatches and dnDSA, sensitization, graft loss, and rejection.

Results

The median age of the KTRs was 11 years (IQR 8), with a median follow-up time of 5 years (IQR 5). 11.36% developed dnDSA (60% class II, 40% class I and II) within a median of 3.91 years (IQR 2.28; range: 2.22-9.20). 57.45% had detectable anti-HLA antibodies during follow-up. Six KTRs lost their graft. None of the graft losses were related to alloimmunity, and 5-year death censored (one KTR died) graft survival was 88%. The cumulative incidence of rejection was 4% (95% CI: -1.5; 5.5) after one year and 10% (95% CI: 1.6; 18.7) after five years. The mean PIRCHE score was 368.47 (95% CI: 316.79; 420.15), the mean HLA EMMA class I mismatch was 20.33 (95% CI: 17.56; 23.09), and the mean HLA EMMA class II mismatch was 30.02 (95% CI: 24.99; 35.05). We found no association between PIRCHE or HLA EMMA with dnDSA, sensitization, graft loss, or rejection in the logistic regression models. We did see a tendency towards an increased odds ratio in PIRCHE predicting dnDSA (odds ratio: 1.31 (95% CI: 0.96; 1.80)) (Figure 1).

Conclusion

We did not find evidence to support the inclusion of the prediction of molecular mismatches in our clinical practice. The role of molecular mismatches in a clinical setting has yet to be established.
#3839 THERAPEUTIC TARGETS OF ARSENIC TRIOXIDE IN LUPUS NEPHRITIS – DATA FROM BIOINFORMATICS ANALYSIS AND IN VITRO STUDIES
Authors: Xie Ruiyan , Zhu Litong , Jason Sher Ka Ho , Yap Desmond
Published: June 2023

Background and Aims

Patients with systemic lupus erythematosus (SLE) are at an increased risk of developing lupus nephritis (LN), which results in high morbidity and mortality. There is preliminary data showing the efficacy of low dose of Arsenic Trioxide (ATO) in reducing renal flares amongst LN patients, but the underlying mechanism for such benefit remains unclear.

Method

We performed bioinformatic analysis and network pharmacology to elucidate the potential targets from differentially expressed genes (DEGs) of human SLE and LN peripheral blood mononuclear cells (PBMCs) datasets and pharmacological databases. The relationship between the potential targets and immune cells was further analyzed.

Results

Twelve intersection genes of DEGs in SLE, predicting targets of ATO and immune related genes were identified. KEGG pathway analysis suggested that the mechanisms of ATO in SLE were associated with IL-17 signalling pathway (p = 1.67E-18), TNF signalling pathway (p = 5.77E-11) and

NOD-like receptor signalling pathway (p = 1.93E-09). Ten types of immune cells showed significant difference with intersection genes expression in SLE using ssGSEA approach. MMP9 was the most significantly associated with immune cells and showed positive correlations with macrophages and neutrophils. A significant TF-MMP9-miRNA regulatory network was constructed using cytoscape software. Pilot data from our in vitro studies suggested that ATO might downregulate MMP9 expression in PBMCs obtained from LN patients during disease remission (n = 3).

Conclusion

ATO interacts with immune cells in LN patients via different inflammatory pathways and may downregulate MMP9 expression in PBMCs.
#3841 ASSOCIATION BETWEEN BODY MASS INDEX, WAIST CIRCUMFERENCE AND CLINICAL OUTCOMES IN KOREAN ADVANCED CHRONIC KIDNEY DISEASE PATIENTS
Authors: Kim Ji Hye , Im Dha Woon , Park Yeongwon , Kim Minsang , Kang Eunjeong , Jeong Yujin , Lee Hyanglim , Oh Kook-Hwan
Published: June 2023

Background and Aims

This study analysed the association between body mass index (BMI) and waist circumference (WC) with all-cause death, 3-point major cardiovascular event (MACE), end-stage kidney disease (ESKD) and total composite events in nation-wide cohort of Korean advanced chronic kidney disease (CKD) patients.

Method

This nationwide cohort study, using the National Health Insurance Database, included adult health examinees who received two or more check-ups from 2009 to 2012. Among them, CKD patients (N = 325,657, stage G3a, G3b and 4) were identified. Patients were classified into three groups for BMI (<18.5, 18.5-25 [reference] and ≥25) and four groups for WC (female; <75 cm or male; <85 cm [WC1], female; 75 cm≤WC<85 cm or male; 85 cm≤WC<95 cm [reference], female; 85 cm≤WC<95 cm, male; 95 cm≤WC<105 cm [WC2] and female; ≥95 cm, male; ≥105 cm [WC3]). Risks were evaluated using Cox proportional hazard analysis.

Results

Patients (58.6±7.7 years) had mean eGFR of 54.32±5.83ml/min/1.73 m2. The underweight (BMI<18.5) group had increased risks of death [HR 1.757, 95% CI (1.573-1.964)] and total events [HR 1.244, (1.144-1.353)]. Overweight (BMI≥25) group showed lower risks of death [HR 0.888, (0.86-0.917)], ESKD [HR 0.855, (0.788-0.927)] and total events [HR 0.975, (0.956-0.995)]. However, the risk was increased for 3-point MACE [HR 1.056, (1.031-1.081)]. For the association between WC and clinical outcomes, the low WC group (WC1) had increased risk of death [HR 1.129, (1.089-1.17)] and reduced risk for 3-point MACE [HR 0.92, (0.894-0.947)]. In higher WC groups, increased risks were observed for death [WC2: HR 1.052, (1.008-1.098), WC3: HR 1.32, (1.213-1.437)], 3-point MACE [WC2: HR 1.071, (1.038-1.104), WC3: HR 1.104, (1.036-1.176)] and total events [WC2: HR 1.049, (1.022-1.077), WC3: HR 1.12, (1.062-1.181)].

Conclusion

In CKD patients, both lower BMI and WC were risk factors for mortality and ESKD. However, compared to the reference group, higher BMI group exhibited better outcomes while higher WC groups exhibited poorer outcomes. As increased WC is more specifically related to central obesity, we need different approaches to interpreting clinical risks associated with different BMI and WC criteria.
#3849 PERITONEAL DIALYSIS CATHETER LOCK: PREVENTING RELAPSES
Authors: Marin Jorge , Huete M Jose Espigares , Escolano Francisco Javier Ruiz , Pérez Elisa Pereira , Galindo Pilar
Published: June 2023

Background and Aims

The incidence of peritonitis has markedly decreased in the last decades, nevertheless it remains one of the main causes of catheter removal and subsequent dialysis modality change. In the long-term severe peritonitis and relapses can lead to peritoneal membrane failure. Some bacteria can form biofilms in the peritoneal catheter lumen granting them resistance against antibiotics and thus being one of the causes for infection recurrences. To find a viable way to avoid or/and eradicate the bacterial biofilm in the peritoneal catheters given the importance of infections.

Method

We present the experience in our peritoneal dialysis unit in the coadjuvant treatment of peritoneal dialysis-associated peritonitis with peritoneal catheter locks in the past few years. We used two kinds of peritoneal catheter lock depending on the isolated germ and divided them in two groups. Group I for the gram-positive staphylococcus group and Group II for gram-negative germs, specifically pseudomona. We reported 12 cases from which 10 were the first episode of gram-positive staphylococcus (epidermidis and Aureus) peritonitis. For the treatment we locked the catheter with 350mg of daptomycin in 7ml of saline solution once a week without using the catheter for 12 hours. For the other 2 cases of pseudomona peritonitis we locked the catheter with taurolidine/urokinase during the exchange with icodextrin twice a week with a 12 hours dwell time until 9 locks were archived.

Results

We treated 12 patients (Table 1). Peritonitis was resolved without recurrences in 9 of 10 patients in group I. In one case were a Methicillin-resistant Staphylococcus aureus was involved there was no response to the treatment and the peritoneal catheter was removed. In Group II both patients resolved their peritoneal infection without recurrences.

Conclusion

In our study peritoneal catheter locking seems to avoid the biofilm and reduce the peritoneal infection recurrences.
#3882 THE PREVALENCE AND EVOLUTIONARY EFFECTS OF FRAILTY IN PERITONEAL DIALYSIS PATIENTS
Authors: Tingchen Yi , Lai Tai-Shuan , Lin Shuei-Liong , Chen Yung-Ming
Published: June 2023

Background and Aims

Frailty is an age-related condition that predicts adverse outcomes. The clinical effect of frailty in peritoneal dialysis (PD) patients is unmet. The study was aimed to investigate the clinical implications of frailty in PD patients.

Method

In this prospective study, PD patients completed frailty assessment at entry and 6 months by a semiautomated frailty index of 80 risk factors (FI80) which also contained the 5 components of Fried frailty phenotype. A score ≥13/80 (FI80 ≥0.16) or ≥3/5 (frailty phenotype) was designated to define frailty.

Results

A total of 337 PD patients were recruited (new-onset 23.4%, prevalent 76.6%). Two hundred (59.3%) and 163 (48.4%) patients were frail by FI80 and frailty phenotype, respectively. Predictors for frailty were old age, dialysis, diabetes mellitus, gout and sleep disorder. New-onset patients aged <55 years displayed the best evolution of frailty over 6 months (stable or improved, n = 29/47, 61.7% by FI80, p = 0.0293), compared with other groups. Survival analysis found that frail patients exhibited the worse outcomes (overall death and hospitalization) than their robust and prefrail counterparts. Poisson regression showed frailty was associated with increased utilizations of outpatient and ER visit; however multivariate Cox models identified only diabetes, gout history and low body mass index (<19kg/m2), but not frailty, predicted overall death and hospitalizations.

Conclusion

Our data indicate that frailty is a common medical condition in PD patients, and the status of which can be stabilized or improved in new-onset, young patients at least over the short term. Compared with frailty, certain comorbidities (diabetes and gout history) and undernutrition appeared to be more robust in the prediction of adverse outcomes.
#3922 CLINICOPATHOLOGICAL CHARACTERISTICS OF LIGHT AND HEAVY CHAIN DEPOSITION DISEASE: A CASE SERIES FROM A SINGLE CENTER
Authors: Wang Yujie , Liang Shaoshan , Liang Dandan , Xu Feng , Zhang Xiaodong , Chen Dacheng , Lin Yao , Zeng Caihong
Published: June 2023

Background and Aims

Light and heavy chain deposition disease (LHCDD) is the rarest form of monoclonal immunoglobulin deposition disease (MIDD) characterized by the deposition of the monoclonal light chain and heavy chain. At present, the large-scale clinical research data of LHCDD is limited. We explore the clinical-pathologic characteristics and outcome of LHCDD in a single center of China, to obtain a better understanding of this disease.

Method

We reviewed 65291 native kidney biopsies from January 2008 to December 2022. Ten patients with biopsy-proven LHCDD diagnosed were studies retrospectively.

Results

4 males and 6 females, with an average age of 52.5 ± 8.9 years were enrolled. The patients were presented with hypertension (80%), anemia (90%), elevated serum creatinine (70%), proteinuria (100%), nephrotic syndrome (30%) and microscopic hematuria (90%). Serum immunofixation electrophoresis showed that 8 (80%) patients were positive for monoclonal immunoglobulin (IgG-κ/IgG-λ/IgA-λ: 3/2/3). Serum free light chain (FLC) ratio was abnormal in 9 (90%) patients. Among them, 5 patients had an Elevated FLC ratio (κ:λ > 1.65), and an FLC ratio < 0.26 was observed in 4 patients. Two patients were diagnosed with multiple myeloma. Histologically, nodular mesangial sclerosis was identified in 9 (90%) patients. Immunofluorescence showed that 6 patientshad depositions of heavy chain IgG (γ1-κ/γ1-λ/γ2-κ/γ2-λ/γ3-κ:2/1/1/1/1), and 4 patients of heavy chain IgA (α-κ/α-λ:1/3). During a median of 28 months of follow-up (range, 6–104 months) in 9 patients, 8 patients received chemotherapy. Three (33%) patients had complete hematologic remission (CR), 2 (22%) had very good partial hematologic response (VGPR) or partial hematologic response (PR), and 4 (44%) had no response (NR). One (11%) had stable/improved renal function, 6 (67%) had worsening renal function, and 3 (33%) progressed to ESRD. All 9 patients survived.

Conclusion

In this case series of LHCDD in a single center in China, light and heavy chain deposition in renal tissues was most frequent with IgG-κ, followed by IgA-λ, IgG-λ and IgA-κ. More than half patients had hematologic response but poor renal prognosis.
#3934 SAFETY AND EFFICACY OF EVOLOCUMAB AMONG KIDNEY TRANSPLANT PATIENTS AT HIGH CARDIOVASCULAR RISK
Authors: Alotaibi Torki , Nagib Ayman Maher , Aboatya Hasaneen Hasaneen Ahmed Aboatya , Abdulhalim Medhat , Said Tarek , Emam Mohamed , Elsayed Zakaria , Nair Prasad , Gheith Osama Ashry Ahmed
Published: June 2023

Background and Aims

Proprotein convertase subtilisin/Kexin type A(PCSK-9) inhibitors have not been evaluated among kidney transplant recipients (KTR) despite its favorable cardiovascular profile. We aimed to evaluate the safety and efficacy of evolocumab in reducing lipids and cardiovascular events among risky KTR.

Method

One hundred ninety-five KTR - who were followed up in Hamed Al-Essa organ transplant center with high cardiovascular risk score (>20)-were enrolled in this prospective randomized controlled study between June 2017 and June 2018. Patients who received statin and evolocumab (140 mg/ 2 weeks, group1, n = 97) while those maintained on statin alone comprised group 2(n = 98). After 24 months, they were followed up clinically and by laboratory investigations.

Results

The two groups had comparable demographics. Before enrollment in the study, we observed a higher prevalence of NODAT in group 2 and more smokers in group 1(p < 0.05). Basal graft function was significantly higher in group 1, while the type of immunosuppression was equivalent in both groups(p > 0.05). We found no significant differences between the two groups concerning cardiovascular events, and both graft and patient outcomes (p > 0.05). Despite the comparable triglycerides levels, we found significantly higher basal cholesterol in group 1(5.5 vs. 4.7, p < 0.001), which came down significantly in the same group after three months and thereafter (p = 0.031) compared to group 2 and basal values (p < 0.001). We reported 2 cases of acute MI and one atrial fibrillation in group2.

Conclusion

Evolocumab is a promising lipid-lowering agent among risky KTR. Earlier cholesterol reduction was observed in group 1 without significant positive cardiovascular impact.
#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

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 >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

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

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

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

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

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

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

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

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.