bluuebunny/crossref_metadata_2025 huggingface dataset:
A study of the high-inclination population in the Kuiper belt – IV. High-order mean-motion resonances in the classical region
Authors: Li Jian , Lawler S M , Lei Hanlun
Published: June 2023

In our previous study of Neptune’s 4:7 mean-motion resonance (MMR), we discovered that its resonant angle can only librate within a specific eccentricity (e) versus inclination (i) region, determined by a theoretical limiting curve. This ‘permissible region’ is independent of time and encompasses the entire possible stable region. We now generalize this theory to investigate all high-order MMRs embedded in the main classical Kuiper belt (MCKB). We first consider the second-order 3:5 MMR in the framework of planet migration and resonance capture, and have further validated our limiting curve theory for both captured and observed 3:5 resonators. It suggests that only the (e, i) pairs inside the individual permissible regions should be chosen as initial conditions for studying the in situ evolution of high-order resonators. With such a new setting, we proceed to explore the long-term stability (for 4 Gyr) of different resonant populations, and our simulations predict that (1) the 3:5 and 4:7 resonators are comparable in number, and they could have inclinations up to 40°, (2) the populations of objects in the higher order 5:9, 6:11, 7:12, and 7:13 resonances are about 1/10 of the 3:5 (or 4:7) resonator population, and nearly all of them are found on the less inclined orbits with i < 10°, and (3) for these high-order resonances, almost all resonators reside in their individual permissible regions. In summary, our results make predictions for the number and orbital distributions of potential resonant objects that will be discovered in the future throughout the MCKB.
#3295 RAPIDLY PROGRESSIVE AUTOSOMAL DOMINANT POLYCYSTIC KIDNEY DISEASE : RISK FACTORS FOR DISEASE SEVERITY DURING CHILDHOOD AND EARLY ADULTHOOD
Authors: Wigerinck Stijn , Schellekens Pieter , Dachy Angélique , Chedid Maroun , Hanna Christian , Jouret François , Harris Peter , Bammens Bert , Chebib Fouad , Mekahli Djalila
Published: June 2023

Background and Aims

Autosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease and is characterized by genetic complexity and phenotypic variability. The age of reaching kidney failure (KF) is variable and covers the complete age-spectrum. There is an unmet need for early biomarkers to differentiate between rapid and slow progressors. The PROPKD score identified hypertension before the age of 35 years as a risk factor for rapid kidney function decline. We aim to identify earlier risk factors for rapid disease progression by studying a population of ADPKD patients who reached kidney failure (KF) before the age of 40y.

Method

This multicentric retrospective study focusses on a unique population (n = 200) of ADPKD patients who reached KF before 40y. Kidney failure (KF) was defined as CKD5 or start of Kidney Replacement Therapy (KRT), whichever came first. Longitudinal data on childhood history, comorbidities and kidney function were collected. Life table and Proportional Hazards analysis were used to assess associations between clinical parameters and time to KF.

Results

Median age of ADPKD diagnosis was 22.3 (16.5 – 28.6) and median age of KF onset was 36.2 years (32.9-38.7 years). Fourty-seven patients were genotyped (23.5%) of which 38 patients (81.0%) were PKD1T and 8 (17.0%) were PKD1NTand only 1 patient (2.1%) was PKD2. Median age at first urological event was 27.0 (20.7 – 32.0) years. 71 patients (35.5%) had history of UTI's, 67 patients (33.5%) had hemorrhagic cysts on abdominal imaging, 66 patients (33.0%) presented with gross hematuria and 40 patients (25.0%) presented with kidney stones. There was a high prevalence of hypertension (N = 128, 64.0%). Four patients (N = 4/128, 3.1%) had a very early diagnosis of hypertension before the age of 10 years. Hypertension-onset before the age of 18 years correlated with a significantly faster progression (UV HR: 2.07 (1.32 – 3.25)).

Conclusion

This study describes a unique cohort of ADPKD patients with rapid disease progression. Hypertension at young age (<18) correlated with rapid disease progression, suggesting that ambulatory blood pressure in children might be useful to identify patients at risk for rapidly progressive ADPKD.
#5528 FIBROBLAST GROWTH FACTOR 21 PREDICTS ARTERIOVENOUS FISTULA FUNCTIONAL PATENCY LOSS AND MORTALITY IN PATIENTS UNDERGOING MAINTENANCE HEMODIALYSIS
Authors: Hu Xinhui , Wei Qing , Wang Bin , Liu Hong
Published: June 2023

Background and Aims

Arteriovenous fistula (AVF) dysfunction is a common complication in patients undergoing maintenance hemodialysis (MHD). Elevated serum level of fibroblast growth factor 21 (FGF21) was associated with atherosclerosis and cardiovascular mortality. However, its association with vascular access outcomes remains elusive. In this study, we aimed to evaluate the relationship of serum FGF21 levels with AVF dysfunction and all-cause mortality in patients undergoing MHD.

Method

We performed a study of patients undergoing MHD who received AVF creation at a tertiary medical center in China from January 2018 to December 2019. Serum FGF21 concentration was detected by enzyme-linked immunosorbent assay (ELISA). Patients were followed-up to record two clinical outcomes, including AVF functional patency loss and all-cause mortality. The follow-up period ended at April 30, 2022. Kaplan-Meier curves were used to analyze AVF dysfunction events and mortality. Univariate and multivariate Cox proportional risk model analyses were used to calculate risk ratios (HR) and 95% CI and independent prognostic factors. The receiver operating characteristic (ROC) curve and area under the curve (AUC) were used to analyze the predictive value of FGF21 in AVF functional patency loss and all-cause mortality.

Results

Among 147 patients, the mean age was 58.49±14.41 years, and 58.50% of them were males. The median serum level of FGF21 was 150.15 (70.57-318.01) pg/ml. During median follow-up period of 40.83 months, the serum level of FGF21 was an independent predictor for AVF functional patency loss (per 1 pg/mL increase, HR 1.002 [95% CI: 1.001-1.003, P = 0.003]. Besides, patients with higher serum level of FGF21 was more likely to suffer from all-cause mortality (per 1 pg/mL increase, HR 1.002 [95% CI: 1.000-1.003, P = 0.014]. The optimal cutoffs for FGF21 to predict AVF functional patency loss and all-cause mortality in patients undergoing MHD were 149.98 pg/ml and 146.43 pg/ml, with an AUC of 0.701 (95% CI 0.606-0.796, P = 0.001) and 0.677 (95% CI 0.566-0.788, P = 0.006), respectively.

Conclusion

Serum FGF21 level was an independent risk factor and predictor for AVF functional patency loss and all-cause mortality in patients undergoing MHD.
#6257 PROGNOSTIC VALUE OF A POSITIVE CROSSMATCH BEFORE DESENSITIZATION IN A COHORT OF HIGHLY-SENSITIZED PATIENTS
Authors: Noble Johan , Malvezzi Paolo , Jouve Thomas , Bardy Beatrice , Rostaing Lionel , Dard Celine
Published: June 2023

Background and Aims

Human Leukocyte antigen (HLA) sensitization in patients is a barrier for Kidney Transplantation (KT) access, and highly-sensitized patients remain on the waiting list longer than other patients which results in a higher morbidity and mortality. Desensitization may be an option to increase their access to KT. All patients transplanted in this context have a negative Complement-Dependent Cytotoxicity crossmatch (CDC-CM) the day of KT. However, the stratification of the long-term risk of graft loss according to flow cytometry crossmatch (FC-CM) and to CDC-CM during the desensitization period remains unknown.

Method

In this retrospective study, all highly-sensitized patients (Panel Reactive Antigen (PRA) ≥ 85) in our center were included. CDC-CM and FC-CM were performed on samples before and during the desensitization period and clinical follow-up data were retrieved. Pre-KT desensitization strategy consisted in two Rituximab infusions (375mg/m2) and a variable number of apheresis (mostly semi-specific immunoadsorption) associated with a classical immunosuppression-based regimen (tacrolimus, mycophenolate and steroids).

Results

A total of 183 highly-sensitized recipients received a KT between 2014 and 2022. Of these, 23 were desensitized prior to KT and among them 18 had a positive FC-CM before KT and 5 had no positive FC-CM on all assessed serums. Mean age was 52.9 ± 13 years. Mean follow-up was 5.2±4 and 3±2 years for non-desensitized and desensitized patients respectively. PRA before desensitization was higher in desensitized patients (98%) versus non-desensitized patients (95%) and the mean time on the waiting list was 5.8±4 versus 7.5±4 years respectively. Death-censored graft survival and patient's raw survival, using cox-survival analysis, were not statistically different between the desensitized kidney transplanted patients and the highly-sensitized patients without desensitization (p = 0.77 and p = 0.57 respectively). In sub-group analyses, the positivity of FC and/or CDC-CM did not add an additional risk of graft loss or patient mortality.

Conclusion

Desensitization allows highly-sensitized patients to access KT with an HLA-incompatible graft (with a positive CDC or FC-CM on the serum collected prior to desensitization), with the same graft survival as similarly sensitized patients transplanted with an HLA-compatible graft without desensitization.
#6496 CYCLIN D1 AMELIORATES ACUTE KIDNEY INJURY BY IMPROVING FATTY ACID OXIDATION VIA AMPK PATHWAY
Authors: Huang Yuliang , Chen Junzhe , Shao Xiaofei , LI Jinxiang , Tang Ying
Published: June 2023

Background and Aims

Acute Kidney Injury (AKI) is a critical condition that is caused by the absence of oxygen during the acute ischemic phase, leading to energy metabolism disturbance and kidney tubular epithelial cell damage. Fatty Acid Oxidation (FAO) is the main source of energy production of renal proximal tubular epithelial cells. Timely promoting FAO, increasing supplies of energy, and promoting cell proliferation are essential to improve kidney injury. However, there is no clinically recognized effective treatment for this. Cyclin D1(CCND1), a member of the cell cycle family, plays a vital role in cell proliferation. Our previous study showed that CCND1 improved AKI by increasing FAO. This study aimed to investigate the role and molecular basis of CCND1 involvement in fatty acid oxidation of AKI.

Method

CCND1 was evaluated in human kidney proximal tubular epithelial cells (HK-2 cells) and in male C57BL/6J mice (wild type). We investigated the protective role of CCND1 in AKI using a mouse model of ischemia-reperfusion injury, which was treated by transferring CCND1-expressing plasmids in male C57BL/6J mice (wild type) by ultrasound and microbubble-mediated delivery. Eight-week-old male C57BL/6J mice (wild type) were subjected to bilateral renal artery occlusion for 30min followed by 24h of reperfusion. We evaluated FAO, proliferation, and autophagy in vitro and in vivo. In addition, we evaluated the concentrations of blood urea nitrogen and creatinine, evaluated kidney ultrastructure and so on.

Results

In vivo studies showed that activation of CCND1 prevented AKI-induced lipid accumulation, kidney tubule injury and kidney function declined after ischemia-reperfusion injury. Compared to test control, the treatment significantly (p<0.05) reduced the concentrations of blood urea nitrogen and creatinine. Kidney-specific overexpression of CCND1 increased FAO, promoted proliferation and reduced apoptosis. Mechanistically, CCND1 activated the AMPK pathway, which increased the expression of phosphorylation AMP activated protein kinase (p-AMPK) and upregulated FAO. On the other hand, inhibiting the expression of CCND1 worsened the impairment of FAO and disturbed energy metabolism.

Conclusion

CCND1 improved FAO and reduced lipid accumulation through the active AMPK pathway in kidney proximal tubular epithelial cells (PTECs). Hence, restoring of the expression of CCND1 may offer a novel therapeutic strategy for treating AKI.
#6709 DONOR-DERIVED CELL-FREE DNA (DD-CDNA) AS A NON-INVASIVE BIOMARKER OF KIDNEY ALLOGRAFT REJECTION IN PEDIATRIC KIDNEY TRANSPLANTATION
Authors: Hogan Julien , George Roshan , Winterberg Pamela , Hayes Carissa , Fan Chris , Kamel Margret , Garro Rouba
Published: June 2023

Background and Aims

Rejection remains the first cause of allograft loss in pediatric kidney transplant (pkTx) recipients. Detection of rejection currently relies on kTx biopsies performed either because of allograft dysfunction with the risk of late diagnosis or per surveillance protocols allowing early detection of subclinical rejection but resulting in many unnecessary biopsies. Dd-cfDNA was reported as a new non-invasive biomarker with the potential to improve rejection detection and guide biopsy indications. We aim to assess the association of dd-cfDNA levels with biopsy results in a large cohort of pediatric kTx recipients.

Method

All pediatric kTx patients with at least one dd-cfDNA assessment at the time of a biopsy at a single pediatric transplant center were included. Clinical, biological and histological data were collected from medical reports. Dd-cfDNA were retrospectively measured from plasma samples biobanked at the time of allograft biopsy between 2015 and 2020 or collected in patients who received regular dd-cfDNA testing as part as clinical care between 2021 and 2022.

Results

170 cfDNA measurements in 132 pkTx recipients were available at the time of a biopsy, including 100 performed for surveillance. Mean age at biopsy was 16 years with a median time from kTx of 21 [11;38] months. Median eGFR was 62 [48;83] mL/min/1.73 m2, median UPCR 0,21 [0,14;0,36] g/g, and 20% had DSA at the time of the biopsy. Biopsy findings included: 109 normal, 30 borderline, 15 TCMR, 11 AMR and 5 mixed rejections. Median cfDNA level was 0,64 [0,31;1,80] %. We found a strong association between cfDNA levels and active tubule-interstitial and microvascular Banff lesions (Figure 1). cfDNA levels were significantly increased in cases with rejection (Figure 2). Using the proposed cut-off of 0.5%, performances of the test to detect rejection were Se 84%, Spe 51%, PPV 33%, NPV 92%. Among the borderline cases, 17 (57%) had cfDNA>0.5%.

Conclusion

We confirm in the largest pediatric kTx cohort to date, the association of dd-cfDNA levels with allograft rejection and its potential interest as a non-invasive biomarker in children. Further studies are needed to assess the added value of dd-cfDNA monitoring to the current standard of care and its ability to reduce unnecessary surveillance biopsies and improve outcomes.
#2837 ANGIOTENSIN II TYPE 1A RECEPTOR IN KIDNEY PERICYTES MEDIATES TERTIARY LYMPHOID TISSUE FORMATION AFTER ACUTE KIDNEY INJURY
Authors: Chou Yu-Hsiang , Shao Yu-Han , Chen Yung-Ming , Lin Shuei-Liong
Published: June 2023

Background and Aims

Tertiary lymphoid tissues (TLTs) have been demonstrated as a major cause of sustained inflammation after acute kidney injury (AKI), indicating a possible contribution of ensuing chronic kidney disease (CKD). And heterogeneous fibroblasts play the crucial role of induction of TLT by secretion of chemokines. Angiotensin II receptors also express on fibroblasts including pericytes. Our study aimed to investigate whether the blockade of angiotensin II receptor could attenuate TLT formation and ensuing CKD after AKI.

Method

Ischemia-reperfusion injury (IRI) was used as AKI model. In vivo, systemic angiotensin II receptor blockade was performed by administration of an angiotensin II receptor antagonists called losartan after the recovery of AKI. Cell-specific angiotensin II receptor blockade was performed using Gli1-CreERT2;AT1Rfl/fl mice to knockout angiotensin II type 1a receptor in pericytes. We also investigated the effect of angiotensin II receptor blockade using 3T3 fibroblasts cell line.

Results

During the 8-month follow-up period after IRI, the activity of intra-renal renin–angiotensin system (RAS) elevated without treatment of losartan. We also displayed that multiple TLTs developed in ensuing CKD after IRI both in a CD-1 and C57BL/6J mice model, which were confirmed by staining of CD3 and B220 representing T and B lymphocytes, respectively. Notably, losartan could not only reduce the size and number of TLT, but also downregulate proinflammatory cytokines such as CXCL13, CCL21 and CCL19 which trigger the initiation of TLT. In vitro, using 3T3 fibroblasts cell line and primary pericytes isolated from kidney after IRI, angiotensin II administration could induce the development of fibroblasts with distinct phenotypes and stimulate production of aforementioned proinflammatory cytokines, particularly CCL19. Additionally, we discovered that angiotensin II-stimulated fibroblasts induced migration of lymphocytes via CCL19 production. Using Gli1-CreERT2;AT1Rfl/fl mice, we found that TLT formation decreased after IRI compared to control groups.

Conclusion

Losartan can reduce ensuing CKD and TLT formation. Distinctive pericytes inhibition by losartan is the plausible mechanism of amelioration of TLT formation. As a result, losartan might be the promising therapeutic agent to prevent AKI-CKD continuum.
#5215 OFATUMUMAB AS A RESCUE THERAPY FOR PATIENTS WITH MEMBRANOUS NEPHROPATHY
Authors: Podesta Manuel Alfredo , Portalupi Valentina , Gennarini Alessia , Tomatis Federica , Villa Alessandro , Rubis Nadia , Remuzzi Giuseppe , Ruggenenti Piero
Published: June 2023

Background and Aims

Rituximab is the first-line treatment for patients with primary membranous nephropathy (MN) and nephrotic syndrome (NS) at high risk of progression to end-stage kidney disease. However, this drug is effective only in approximately two thirds of treated patients, and repeated rituximab infusions may be complicated by hypersensitivity reactions, which contraindicate retreatment. Ofatumumab, a fully human anti-CD20 antibody, could overcome these limitations.

Method

We retrospectively evaluated the response to a single 50–300 mg dose of intravenous ofatumumab in 17 MN patients referred to our institution who either experienced hypersensitivity reactions (rituximab-intolerant, n = 5) or failed to achieve NS remission after rituximab infusion (rituximab-resistant, n = 12).

Results

Over a median [IQR] follow-up of 5.0 [3.0-9.8] months, ten (58.8%) patients—five rituximab-resistant (41.7%) and all five rituximab-intolerant—achieved complete or partial NS remission, defined as proteinuria <0.3 g/day or proteinuria <3.5 g/day with ≥50% reduction from baseline, respectively. Ofatumumab infusion induced a progressive reduction in 24-hour urinary protein and IgG excretion, and a sharp increase in serum albumin and IgG levels. Peripheral B cells were depleted in all patients and started reconstituting by 3 months from baseline. Seven of the 12 subjects with PLA2R-related disease (i.e. with baseline anti-PLA2R antibody levels >2.7 RU/mL by ELISA) achieved antibody depletion during the follow-up (half of rituximab-resistant and all rituximab-intolerant). There were 14 non-serious infusion-related adverse events in nine patients, all of which completely resolved with temporary interruption of ofatumumab infusion.

Conclusion

Ofatumumab may be an effective and safe treatment option for all rituximab-intolerant and a substantial proportion of rituximab-resistant MN patients.
#6071 RITUXIMAB FOR MAINTENANCE OF REMISSION IN ADULT MINIMAL CHANGE DISEASE
Authors: Tsiakas Stathis , Theodoridis Ioannis , Kapsia Eleni , Skalioti Chrysanthi , Boletis Ioannis , Marinaki Smaragdi
Published: June 2023

Background and Aims

Maintaining remission in a minority of adult patients with minimal change disease remains challenging. Prolonged corticosteroid use is associated with severe adverse effects. A limited number of observational studies suggest that rituximab may be an alternative therapeutic option for remission maintenance, allowing steroid withdrawal.

Method

We retrospectively analysed the data of all adult patients with minimal change disease, who received rituximab in our centre between 2017 and 2022.

Results

A total of 14 adults with minimal change disease were treated with rituximab, six of whom had childhood-onset nephrotic syndrome. Six patients were steroid dependent. The median number of relapses was 6.5 (IQR 4.5-15.2) prior to rituximab. Thirteen patients had received at least ≥ 2 different immunosuppressive agents during their disease. Corticosteroid-related adverse events, including osteopenia, hypertension, cataract and diabetes mellitus were observed in 10 subjects. Rituximab was administered in a median time of 10.6 years (IQR 4.5-16.3) after diagnosis. All patients received 2 doses of 1g rituximab 2 weeks apart. The median age at rituximab administration was 31 years (IQR 18.7-49.0); all patients were in remission. Besides corticosteroids, concomitant immunosuppressive therapy included calcineurin inhibitors (n = 6) and mycophenolate acid analogues (n = 1). The median follow-up time after the first dose of rituximab was 44 months (IQR 9.5-67.2). Relapses occurred in 6/14 patients in a median time of 17.5 months (IQR 10.2-26.5). The number of relapses per year decreased to 0.27 from 0.87 (p < 0.001) after rituximab. Six patients received a repeat course of rituximab. One patient developed Pneumocystis Jirovecii pneumonia, that was successfully treated with cotrimoxazole. At the last follow-up visit, corticosteroids were discontinued in 8 out of 14 patients and calcineurin inhibitors in 3 out of 7 patients.

Conclusion

Rituximab is a reasonable therapeutic approach for maintaining remission and avoiding steroid toxicity in adult minimal change disease. Randomized controlled studies are needed to further evaluate the safety and efficacy of rituximab in these patients.
#6584 WEEKEND EFFECT IN ACUTE KIDNEY INJURY ADMISSIONS AND 1-YEAR RENAL OUTCOME
Authors: Da Silva Bernardo Marques , Pais Telma , Oliveira José , Marchão Natália , Pereira Marta Sofia Henriques , Fonseca José Agapito , Jorge Sofia , Nogueira Estela , Godinho Iolanda , Rodrigues Natacha , Amaral Tiago , Gameiro Joana , Lopes José António
Published: June 2023

Background and Aims

The “weekend effect” is the finding of worse outcomes in hospital admissions occurring over weekends. The reasons for this are still unclear but shorter staffing has been suggested to contribute. Little is known about the impact of the “weekend effect” on renal outcomes. We aim to analyze the impact of the weekend effect on patients admitted with acute kidney injury (AKI). We evaluated one-year renal outcome and mortality in patients admitted for AKI over weekends and weekdays.

Method

We conducted a retrospective analysis of all adult patients admitted in a tertiary medical center in Portugal over a period of 6 months with a diagnosis of AKI. Variables were retrieved using clinical and laboratory data. AKI was defined and severity was accessed according to Kidney Disease Improving Global Outcomes classification. Patients were categorized according to weekdays or weekend admission. Outcomes were in-hospital mortality, hemodialysis (HD) requirement and one-year mortality. Statistical significance was defined as a P-value <0.05

Results

We included 163 patients with mean age of 69.8±16.2 years and 52.7% were male. The majority of patients were admitted on weekdays (74.2%, n = 121). Also, the majority had AKI stage 3 (65.6%, n = 107). Forty eight patients (29.4%) required HD during hospitalization and in-hospital mortality was 24.5%. There were no significant differences in HD requirement (31.4% vs 23.8%, p = 0.434), mortality (25.6% vs 21.4%, p = 0.680) nor HD requirement at discharge (25.6% vs 26.2%, p = 0.681) between weekday or weekend admissions. Of the 123 patients discharged, during the one-year follow-up 30.1% (n = 37) died and 7.3% (n = 9) required HD. There were no differences between weekdays or weekend admissions concerning mortality (32.2% vs 24.2%, p = 0,507) and HD requirement (7.8% vs 6.1%, p = 0,746)

Conclusion

In this cohort of patients with AKI there was no “weekend effect”, which reflects the adequacy of care independently of the day of admission. The retrospective design with a limited number of patients may have influenced the results. Further studies focusing on renal outcomes are required to better understand the occurence of the weekend effect and its long-term impact.
#6858 GRAFT SURVIVAL IN MULTIPLE KIDNEY TRANSPLANT RECIPIENTS FROM CHILDHOOD TO ADULTHOOD: AN ERA STUDY FROM 1978 UNTIL 2019
Authors: Preka Evgenia , Bonthuis Marjolein , Marks Stephen , Kramer Anneke , Stel Vianda , Harambat Jerome , Jager Kitty J
Published: June 2023

Background and Aims

Knowledge regarding graft survival after transplantation in European children with multiple kidney transplants followed from childhood into adulthood including factors affecting these outcomes is lacking.

Method

Using ERA Registry data, we investigated all patients on kidney replacement therapy (KRT) who received their first kidney transplant (KT) before 20 years of age between 1978 and 2019. Graft survival after first, second and third KT were studied alongside their risk factors, using Kaplan-Meier survival analysis and multivariable Cox regression models.

Results

Among 10012 paediatric KT candidates, 8601, 1962 and 412 received at least one, two and three KTs. Graft survival at 5 and 10 years was 80.6% and 65.7% for first KTs, 71.3% and 53.7% for second KTs and 67.1 and 49.5% for third KTs. Factors associated with increased graft failure risk were having glomerulonephritis or a recurrent disease as cause of kidney failure for first KT recipients (aHR 1.24, 95%CI 1.12-1.37 and aHR 1.24, 95%CI 1.13-1.37, respectively). Patients whose first KT lifespan was between 0–30 days or more than 5 years presented lower graft failure risks regarding their second KT compared to patients whose KT survived between 1–5 years (aHR 0.79, 95%CI 0.64-0.98 and aHR 0.73, 95%CI 0.61-0.88, respectively). Similar results were found for third KT recipients whose second KT lived for more than 5 years (aHR 0.61, 95%CI 0.41-0.92). Patients who were transplanted for the first and second time before 2007 presented a higher graft failure risk compared to patients who received their KT between 2016–2019 (aHR 2.09, 95%CI 1.65-2.65 and aHR 1.63 95%CI 1.29-2.06 for the transplantation era before 2000 and between 2000–2007 concerning the first KT; and aHR 1.69, 95%CI 1.15-2.47 and aHR 1.51, 95%CI 1.06-2.16, respectively for the era before 2000 and between 2000–2007 concerning the second KT). Pre-emptive KTs presented less graft failure compared to patients who received dialysis > 1 year for first and second KT (aHR 0.89, 95%CI 0.81-0.98 and aHR 0.63, 95%CI 0.51-0.78,respectively). Patients having received a LD KT had less chances for graft failure for first and second KT (aHR 0.77, 95%CI 0.7-0.84 and aHR 0.71 (0.6-0.85, respectively). Having a second LD KT (no matter the donor type for first KT) was advantageous compared to having a second DD.

Conclusion

Graft outcomes after pediatric kidney (re)transplantation have improved significantly over time for all recipient subgroups, especially for patients with LD KT, longer previous KT lifespan and pre-emptive KT. Patients with GN and recurrent diseases as causes of their kidney failure showed the poorest outcomes, highlighting the need for continued progress in this field.
#2511 ASSOCIATION OF CONSTIPATION, MICROBIAL TRANSLOCATION, AND INFLAMMATION IN HD PATIENTS
Authors: Chang Yu-Kang , Lim Paik Seong
Published: June 2023

Background and Aims

Increased gut permeability and intestinal dysbiosis may contribute to chronic inflammation, leading to accelerated atherosclerosis and cardiovascular complications in patients on haemodialysis (HD). Constipation is highly prevalent in HD patients and growing evidence suggested constipation can aggravate gut microbiota dysbiosis and gut inflammation. The aim of this study was to evaluate the association between markers of microbial translocation, intestinal permeability and inflammation in HD patients with and without constipation.

Method

A cross-sectional, observational study was conducted and 200 stable prevalent HD were enrolled. Serum zonulin, eotaxin-1, amyloid A, intestinal fatty acid-binding protein (iFABP), IL-6, endotoxin core antibodies (EndoCAb) and lipopolysaccharide binding protein (LBP) levels were measured. Functional constipation was defined according to the Rome IV criteria.

Results

Serum levels of zonulin and eotaxin-1 but not LPS, endo-Cab IgG, amyloid A and IL-6 were significantly higher in HD patients with constipation than in non-constipated HD controls. The multiple logistic regression analysis in constipated HD patients after adjustment for age, and BMI demonstrated that serum zonulin and eotaxin-1 were independently associated with constipation with an odds ratio (OR) of 1.24 (95% CI = 1.09-1.42, p = 0.0016) and 1.02 (95% CI = 1.01-1.03, p = 0.0001), respectively.

Conclusion

We demonstrate that there was association between serum eotaxin-1 and zonulin levels in constipated HD patients. This may indicates that increased intestinal inflammation or intestinal permeability in these patients but the significance of these findings need further investigation.
#2533 PROGNOSTIC SIGNIFICANCE OF ARTERIOLAR C4D POSITIVITY AS A MARKER OF MICROANGIOPATHY IN ANCA-ASSOCIATED VASCULITIS
Authors: Gentile Micaela , Maggiore Umberto , Manenti Lucio , Fenaroli Paride , Delsante Marco , Fiaccadori Enrico , Rossi Giovanni Maria
Published: June 2023

Background and Aims

ANCA-associated vasculitis (AAV) represent a group of systemic autoimmune diseases characterized by necrotizing inflammation of small to medium-size blood vessels frequently associated with anti-neutrophil cytoplasmic antibody (ANCA) positivity. Another term they are commonly referred with is “paucimmune vasculitis”, reflecting the lack of immune complex deposition on histological samples, in contrast with other small vessel vasculitis, e.g. cryoglobulinemic vasculitis. The absence or the paucity of deposition of immunoglobulins and complement components was interpreted in the past as a lack of complement cascade involvement in the pathogenesis of AAV. Only in relatively recent times the possible role of complement in AAV was investigated. A few studies proved the relationship between C3 hypocomplementemia and worse renal outcome[1]. Moreover, the overactivation of the alternative complement pathway (ACP) in AAV could be responsible for thrombotic microangiopathy (TMA). A strong association between low serum C3 and histologic signs of thrombotic microangiopathy on renal biopsy was shown in patients with AAV, with a worse renal prognosis. Currently, there are no clear early histological markers of endothelial damage that allow to identify high-risk patients, other than the seldom not identified or misidentified presence of TMA. The association between renal arteriolar C4d deposition (as a vicariate of TMA) has been already described in several glomerulonephritis, including IgA nephropathy [2], but its prognostic meaning has not yet been explored [3]. Our study aims to explore the predictive role of arteriolar C4d in ANCA-associated GN.

Method

All patients with ANCA-associated GN who underwent a kidney biopsy between January 1990 and June 2021 at the Renal Unit of Parma University Hospital, Parma, Italy with at least 6 months follow-up data were included. All histology slides were retrieved and reviewed by experienced nephropathologists. Percent IFTA, percent global glomerulosclerosis, Brix score, the presence or absence of TMA, the positivity or negativity of C4d (immunohistochemical staining on paraffin-embedded formalin-fixed slides) were taken note of. C4d positivity was correlated with the presence of TMA and patients outcome (Fig. 1).

Results

We identified 58 patients who met our criteria. 14 patients were excluded because biopsy specimens were not available for histologic review. Clinical and laboratory baseline and follow-up data for the remaining 44 patients were thus collected.

Conclusion

C4d and TMA were independently associated (p = 0.003). A tendency towards association between C4d and death-censored ESRD was observed (Fig. 2), although not statistically significant (p = 0.434), likely due to the limited sample size. In order to test our hypothesis, validation on a larger cohort is currently underway.
#2543 NEPHROFLOW FOR ESTIMATION OF VASCULAR ACCESS FLOW FOR HEMODIALYSIS: WHEN TO MEASURE?
Authors: Coronado Pablo Alejandro Sarduy , Rivas José Luis Merino , Peña Cecilia Peña , Abad Noelia , Antúnez Blanca Bueno , Marchante Beatriz Espejo , Martin-Centellas Jesus , Paraíso Vicente
Published: June 2023

Background and Aims

Current guidelines emphasize the need for surveillance of vascular access (VA) for hemodialysis (HD), especially arteriovenous fistulas (AVF). Detecting a reduction in VA flow is auseful tool to anticipate the complications of VA as thrombosis. The DMed NephroFlow(NIPRO®) system, based on ultrasound dilution (UD) methods, has been shown tobe comparable to the classic Transonic® measurement system for estimating VA flow and canbe applied for VA surveillance. Our objetctive is to determine if there are significant differences when performing flow measurements with NephroFlow® between the first hour and the second hour of the HD session, as well as between any of the three days in which the patient attends HD.

Method

For two consecutive weeks, patients with AVF or graft (gAVF) on HD in our unit underwent VA flow measurements using the NephroFlow® system at the first and second hour of HD, on the 3 days that they attended HD sessions. Interspersing the first hour with the second each week to avoid significant loss in HD quality. For the study, we proceeded according to the usual recommendations of stable flow at 250 ml/min, corresponding ultrafiltration rate, needles in the same vein, without change in dry weight, with the same nurse staff, and transferring all patients to conventional HD.

Results

Twenty-one patients have been included, 13 male and 8 female, mean age 68±12.3 years. The mean time on HD was 36±23 months. The type of VA was: 10 patients presented a radiocephalic AVF, 5 brachiocephalic AVF, 2 patients a brachiobasilic AVF, and 4 patients a gAVF. The estimated mean flow obtained by NephroFlow ® in the first hour of all sessions and in the second hour was 1056 ± 754 and 1130.16 ± 769 ml/min, respectively; intraclass correlation index was 0.737 and K-W Test H 0.349 (p≤0.05). The mean flow on the first day was 1129±794.5ml/min, ICC = 0.662; second day 1027.5±729ml/min, ICC = 0.812; third day 1121.5±±ml/min, ICC = 0.774. In all cases p<0.05.

Conclusion

No significant differences have been observed in the VA flow estimated with the NephroFlow® ultrasound dilution system, neither at measurement time (the first or the second hour of HD session) nor day of performance (first, second or third day of HD session of the week). NephroFlow® UD system may be a useful tool for VA surveillance and could be applied when is necessary.
#2594 ELEVATED SERUM IL-17 LEVEL IS ASSOCIATED WITH THE PERSISTENCE OF POST-COVID SYNDROME AND VACCINATION STATUS IN HEMODIALYSIS PATIENTS
Authors: Stepanova Natalia , Driianska Victoria , Rysyev Andriy , Kholod Valeriia , Savchenko Viktoriia , Kolesnyk Mykola
Published: June 2023

Background and Aims

Interleukin-17 (IL -17) is thought to play an important role in the immune response and severity of coronavirus disease 2019 (COVID-19). In addition, elevated serum IL -17 levels have been detected in the general population of SARS-CoV-2-infected patients with post-COVID syndrome. Although hemodialysis (HD) patients belong to the high-risk group COVID-19 with an attenuated immune response to mRNA vaccination and a high incidence rate of post-COVID syndrome, IL-17 has never been studied in this cohort.

Method

A total of 80 HD patients aged 56 (44-63.2) years with a dialysis vintage of 40 (23-74) months who had experienced COVID-19 at least 5 months before enrollment were included in this cross-sectional cohort study. Aiming to analyze serum IL -17 according to the persistence of post-COVID syndrome, the patients we divided into 2 groups: post-COVID with (n = 36) and without (n = 44) sequelae. IL-17 was measured at 2-time points: at 5 (n = 30) and 10 months (n = 50) after acute SARS-CoV-2 infection using an ELISA assay. Data were expressed as median (Me) and interquartile ranges (Q25-Q75) and compared with the Mann-Whitney test.

Results

Serum IL-17 ranged from 0.01 to 15.14 pg/mL and was significantly elevated in HD patients with post-COVID sequelae compared to fully recovered patients: 0.45 (0.08-1.6) vs 0.08 (0.025-0.15) pg/mL, p = 0.0002. In the general cohort of HD patients with a 5-month interval between acute SARS-CoV-2 infection and blood collection, IL-17 was statistically greater than in patients with a 10-month interval: 0.24 (0.06-1.2) vs 0.11 (0.03-0.37) pg/mL, p = 0.04. In subgroup analysis, the patients with post-COVID sequelae had higher IL-17 levels than fully recovered patients at both time points (Fig. 1). Notably, mRNA-vaccinated HD patients with post-COVID sequelae had significantly higher IL-17 levels than unvaccinated patients at both time points: 3.83 (0.47-6.47) vs 0.88 (0.04-1.5) pg/mL, p = 0.03 and 0.57 (0.09-5.3) vs 0.08 (0.03-0.13) pg/mL, p = 0.01, respectively.

Conclusion

Serum IL-17 level is associated with the persistence of post-COVID syndrome in HD patients even 10 months after acute COVID-19 and is significantly higher in mRNA-vaccinated HD patients with post-COVID sequelae compared to unvaccinated patients. Further studies are needed to postulate IL-17 as a useful biomarker for post-COVID syndrome in HD patients.
#2654 USE OF SUPERVISED DEEP LEARNING ALGORITHM TO PREDICT RISK OF RENAL REPLACEMENT THERAPY(RRT) IN PATIENTS WITH CHRONIC KIDNEY DISEASE (CKD)
Authors: Leung Ka Chun , Ng Wing-Sze , Siu Yui-Pong , Hau Kai-Ching , Lee Hoi-Kan
Published: June 2023

Background and Aims

Chronic kidney disease (CKD) is one of the most common causes of mortality, affecting around 10% adults worldwide [1]. Although statistical models for predicting risk of renal replacement therapy (RRT) have been developed for a decade [2], referral of patients with CKD to nephrology service is often based on clinical experience of primary care physicians. The use of deep learning algorithms (DLAs) allow clinicians to capture complex, multidimensional, non-linear relationships instead of relying on linear relationships between independent variables and outcome. Our study aims to develop a DLA that has at least non-inferior performance compared to the Kidney Failure Risk Equation (KFRE), which is a well-established and validated risk prediction tool [3].

Method

This is a retrospective cohort study carried out in 3 major acute hospitals in Hong Kong providing a total of 3000 beds from Jan 1, 2009 to Mar 31, 2022. All patients aged > 18 with an estimated glomerular filtration rate (eGFR)<30ml/min/1.73 m2 according to the CKD-EPI formula, who attended follow-up for at least 3 months in nephrology clinic of the 3 hospitals, were recruited. Those who were on chronic RRT, received renal transplantation or had an eGFR<15 ml/min/1.73 m2 before referral were excluded. Supervised DLAs of different structures and their combinations were created and trained. Data in the test set were fed into models to predict the risk of requiring RRT in 2 years and 5 years. Predictive performance of these models were compared with that of KFRE [3].

Results

4992 patients were recruited in the study. Data of 499 patients were isolated as test set and were not used for model training. 1576 patients progressed to stage 5 CKD during their follow-up, and 989 patients required initiation of RRT during the study timeframe. When compared with KFRE (4-variable: ROC-AUC = 0.84, 95%CI:0.835-0.852; 8-variable: ROC-AUC = 0.84, 95%CI:0.830-0.847), almost all DLAs showed statistically significant superior robustness in predicting the risk of requiring RRT (Figure 1). No significant difference was found between performance of DLAs combining different neural network layers and those with single structures (CNN+LSTM+ANN layers ROC-AUC = 0.90, 95%CI:0.896-0.902; CNN ROC-AUC = 0.91, 95%CI:0.907-0.914) (Table 1).

Conclusion

The use of DLAs provided better prediction in the risk of requiring RRT when compared with KFRE.
#2710 SEX DIFFERENCE IN CARDIOVASCULAR RISK IN PATIENTS WITH CHRONIC KIDNEY DISEASE: A POOLED ANALYSIS OF FOUR COHORT STUDIES
Authors: Borrelli Silvio , Garofalo Carlo , Pirozzi Valentina , Palumbo Felicia , Cascone Francesco , DI Martino Luigi , Foderini Andrea , De Nicola Luca , Minutolo Roberto
Published: June 2023

Background and Aims

Progression of chronic kidney disease (CKD) has proven to be faster in men than in Women [1-3]. Whether the same holds true for cardiovascular risk remains ill-defined.

Method

We conducted a pooled analysis of 4 cohort studies from 40 nephrology clinics in Italy including patients with CKD (estimated GFR<60 ml/min/1.73m2 or higher if proteinuria >0.15 g/day). The aim was to compare multivariable-adjusted risk (Hazard Ratio, 95% Confidence Interval) of a composite cardiovascular endpoint (cardiovascular death and non-fatal myocardial infarction, congestive heart failure, stroke, revascularization, peripheral vascular disease, and nontraumatic amputation) in women (n = 1,192) versus men (n = 1,635).

Results

At baseline, women had slightly higher systolic blood pressure (SBP) as compared with men (139±19 vs 138±18 mmHg, P = 0.049), lower eGFR (33.4 vs 35.7 mL/min/1.73 m2 , P = 0.001) and lower urine protein excretion (0.30 g/day vs 0.45 g/day in men, P<0.001). Women did not differ from men in age and prevalence of diabetes while having a lower prevalence of cardiovascular disease, left ventricular hypertrophy and smoking habit. During a median follow-up of 4.0 years, 517 fatal and non-fatal cardiovascular events were registered (199 in women and 318 in men). The adjusted risk of cardiovascular events was lower in women (0.73, 0.60-0.89, P = 0.002) than in men; however, the cardiovascular risk advantage of women progressively diminished as SBP (as continuous variable) increased (P for interaction = 0.021; Figure 1). Similar results were obtained when considering SBP categories; when compared to men, women had a lower cardiovascular risk for SBP <130 mmHg (0.50, 0.31-0.80; P = 0.004) and between 130–140 mmHg (0.72, 0.53-0.99; P = 0.038), while no difference was observed for SBP>140 mmHg (0.85, 0.64-1.11; P = 0.232).

Conclusion

Higher BP levels abolish the cardiovascular protection seen in female vs male patients with overt CKD. This finding supports the need for higher awareness of hypertensive burden in women with CKD.
#2749 QUANTIFICATION OF URINE PROTEINS FOR DISCOVERY OF BIOMARKERS FOR KIDNEY INJURIES BY DIA-PROTEOMICS
Authors: Yamamoto Keiko , Yamamoto Tadashi
Published: June 2023

Background and Aims

Recent advances in proteomics have enabled to quantify proteins comprehensively. We aimed to establish a platform of urine quantitative proteomics for selection of the biomarkers and assessment of health conditions. Since plasma proteins of varying amounts of were present in urine especially from proteinuric patients, we subtracted the plasma protein conteents from total urine proteomes after the quantitative proteomics for discovery of biomarkers for kidney injuries. On the other hand, urine proteins excreted from plasma may be indicators of pathophysiological conditions in the body, suggesting that the urine proteome profiles figure out health conditions and early discovery of any diseases in the future.

Method

More than 120,000 urine samples (∼10 ml each) have been collected from ∼15,000 patients with various diseases and healthy volunteers (HV) and stored in -20C freezers. In this study, urine samples were selected from HV, diabetic patients (DM) with or without microalbuminuria and other CKD patients. Proteins were precipitated by a methanol/chloroform precipitation method from 1 ml urine. The protein fractions were digested with trypsin and the tryptic peptides were purified by C18 column chromatography. The tryptic peptides of 200 ng each were analyzed by LC-MS (tims-TOFpro, Bruker) by quantitative Data-independent acquisition (DIA) proteomics and proteins were quantified by the DIA-nn tool. Major top 30 plasma proteins were removed from the quantitative proteomics data and kidney- and other urinary tract organ-derived proteins were normalized to compare their proportions in urine.

Results

Approximately 2,500 proteins were quantified by the DIA analysis. In urine from HV, proportions of plasma proteins were small, however, in urine from DM patients with microalbuminuria or CKD patients, the plasma protein contents were increased, resulting in relative decreases of urine proportions of other proteins derived from the kidney or other urinary tract organs. By subtraction of the plasma proteins from total urine proteins, protein proportions were comparable to select candidates of biomarkers for kidney injuries. Comparison of total urine protein profiles between HV and DM elucidated their differences, which might indicate changes of pathophysiological conditions.

Conclusion

By recent quantitative proteomics urine proteins were quantified comprehensively, facilitating discovery of biomarkers for kidney injuries and also evaluation of health conditions in the body.
#2846 DEVELOPMENT OF THE JAPANESE VERSION OF THE BASEL ASSESSMENT OF ADHERENCE TO IMMUNOSUPPRESSIVE MEDICATIONS SCALE
Authors: Kosoku Akihiro , Iwai Tamoaki , Masuda Hiroo , Kabei Kazuya , Nishide Shunji , Maeda Keiko , Yoshikawa Yuki , Nakamura Yasutaka , De Geest Sabina , Uchida Junji
Published: June 2023

Background and Aims

One of the major barriers for long-term transplant outcomes in kidney transplant recipients is medication non-adherence, which is a risk factor for de novo donor-specific antibody development leading to antibody-mediated rejection and graft loss. Identifying non-adherent patients is the first step in minimizing the risk of complications of medication non-adherence. However, to date, there is no validated Japanese self-report instrument to evaluate the MA for transplant patients. This study aimed to determine the reliability and validity of the Japanese version of the Basel Assessment of Adherence to Immunosuppressive Medications Scale (J-BAASIS).

Method

We conducted a single-center cross-sectional study for kidney transplant recipients who visited our hospital. The eligible and willing participants were randomly assigned to two groups, the J-BAASIS group and the J-BAASIS+MEMS group, with random numbers generated by computer. All participants filled out a questionnaire including the J-BAASIS (the first survey). They filled out a questionnaire again including the J-BAASIS in similar conditions during their following outpatient visit 4-6 weeks later (the second survey). The participants in the J-BAASIS+MEMS group took the methylprednisolone tablets daily using the MEMS until the second survey. We analyzed the reliability (test-retest reliability and measurement error) and validity of the J-BAASIS (concurrent validity with the medication event monitoring system (MEMS) and the 12-item Medication Adherence Scale) referring to the COSMIN Risk of Bias tool.

Results

A total of 106 kidney transplant recipients (the J-BAASIS group, 56; the J-BAASIS+MEMS group, 50) were included in this study. In the analysis of test-retest reliability, Cohen's kappa coefficient was 0.62. In the analysis of measurement error, the positive and negative agreement were 0.78 and 0.84, respectively. In the analysis of concurrent validity with the MEMS, sensitivity and specificity were 0.84 and 0.90, respectively. In the analysis of concurrent validity with the 12-item Medication Adherence Scale, the point-biserial correlation coefficient for the “medication compliance” subscale was 0.38 (p<0.001).

Conclusion

The J-BAASIS was determined to have good reliability and validity. Using the J-BAASIS to evaluate medication adherence may help clinicians to identify non-adherent transplant patients and institute appropriate corrective measures to improve transplant outcomes. Moreover, this study, which demonstrated the concurrent validity with the MEMS, the gold standard for measuring medication adherence, further strengthens the evidence for the psychometric properties of the original BAASIS.