bluuebunny/crossref_metadata_2025_split huggingface dataset:
#5454 DESIGN AND OPTIMIZATION OF DRUG COMBINATION THERAPIES FOR OSTEOPOROSIS VIA SIMULATIONS OF BONE TURNOVER
Authors: Joerg David , Fuertinger Doris , Kotanko Peter 
Published: June 2023

Abstract

Background and Aims
Many chronic kidney disease (CKD) patients suffer from mineral and bone disorders like osteoporosis, which also affects a huge part of the general population, predominantly postmenopausal women. For the treatment of osteoporosis, several drug types with different mechanisms of action are available, such as bisphosphonates, PTH analogs, RANKL inhibitors and sclerostin inhibitors (some of which are contraindicated for CKD patients beyond CKD stage 3). Different drugs can be given individually or combined in various ways, simultaneously or sequentially, resulting in a huge number of theoretically possible drug combinations that are practically impossible to study in clinical studies. We aimed to study using simulations whether there are combination therapies that would work considerably better than those tested and employed in clinical practice. If so, this could be beneficial for the treatment of a large number of osteoporosis patients by leading to a higher increase in bone strength and a higher reduction in bone fracture risk than standard therapies.

Method
We developed a physiology-based mathematical model that simulates the process of bone renewal in the human body and can predict how different osteoporosis drugs (including bisphosphonates, PTH analogs, RANKL inhibitors, and sclerostin inhibitors) affect this process, alone and in combination [1].

Results
The model was validated on over 30 clinical osteoporosis studies with about 90 study arms. It predicted the time courses of bone mineral density and bone turnover markers with a high degree of accuracy based on the knowledge of the used drugs and dosing schemes alone. We used the model to study how treatment results changed when merely reshuffling the order in which different drugs were given. For example, for 3-year drug therapies involving alendronate, denosumab and romosozumab (1 year each), our simulations showed that the order in which these drugs were given can have a considerable effect on short- and long-term therapy success [1]. This is due to different drugs favorably interacting when applied in the right sequence.

Conclusion
Our findings indicate that some osteoporosis drug administration schemes are superior to others while relying on the exact same types and amounts of drugs. Therefore, there is a large potential to improve pharmacologic therapies of osteoporosis using physiological simulations. For renal patients beyond CKD stage 3, a restricted set of drug types may be considered to account for contraindications related to impaired renal clearance. If translated into clinical practice, findings obtained using our model could give rise to novel treatments using combinations of existing drugs for osteoporosis that lead to a lower bone fracture risk than standard treatments. Moreover, our model could serve as a basis for personalizing osteoporosis therapy to individual patients.
#5465 RACE-FREE EGFR EQUATION IN KIDNEY RECIPIENTS: A DEVELOPMENT AND VALIDATION STUDY
Authors: Raynaud Marc , Alawadhi Solaf , Jurić Ivana , Divard Gillian , Lombardi Yannis , Basic-Jukic Nikolina , Aubert Olivier , Dubourg Laurence , Masson Ingrid , Mariat Christophe , Prié Dominique , Pernin Vincent , Larson Timothy , Stegall Mark , Bikbov Boris , Ruggenenti Piero , Mesnard Laurent , Matas Arthur , Nankivell Brian , Bakker Stephan J L , Legendre Christophe , Kamar Nassim , Vincenti Flavio , Remuzzi Giuseppe , Bentall Andrew , Lefaucheur Carmen , Loupy Alexandre 
Published: June 2023

Abstract

Background and Aims
To assess the performances of the current eGFR equations, including the race-free CKD-EPI-2021, in the kidney transplant population, and compare these performances to a race-free kidney-recipient-specific (KRS) GFR equation.

Method
We included adult kidney recipients transplanted between 01/01/2000 and 01/01/2021 in 17 academic cohorts in Europe, the USA and Australia comprising 14 transplant centres and three clinical trials. Measured GFRs (mGFR) were assessed using 51Cr-EDTA, 99Tc-DTPA, inulin, iothalamate or iohexol clearance, according to the local practice. A KRS GFR equation was developed using additive and multiplicative stepwise linear regressions and its performance was compared to those of the current GFR equations. The performances were assessed with the P30 and the correct classification of chronic kidney disease (CKD) stage metrics.

Results
The study included 15 489 patients, having 50 464 GFR values both measured and estimated by creatinine-based equations. Among the current GFR equations, race-free CKD-EPI-2021 equation showed the lowest performance compared with MDRD and CKD-EPI-2009 equations. We then built a race-free KRS GFR equation based on an additive model including creatinine, age, and sex. We showed that using race did not increase the performance of the equation. We found that the race-free KRS GFR equation showed significantly improved performance compared with the race-free CKD-EPI-2021 equation and performed well in the external validation cohorts (P30 ranging from 73.0% to 91.3%). Finally, we showed that the race-free KRS GFR equation performed well in a series of kidney transplant recipient subpopulations stratified by race, sex, age, body mass index, donor type, therapeutics, creatinine and GFR measurement methods and timing. Based on these results we developed an online application that estimates GFR based on recipient age, sex and creatinine: https://transplant-prediction-system.shinyapps.io/eGFR_equation_KTX/

Conclusion
Using multiple, international cohorts of kidney recipients, we developed and validated a new race-free KRS GFR equation that demonstrated high accuracy and outperformed the race-free CKD-EPI-2021 equation developed in individuals with native kidneys.
#5492 TRANSCRIPTOME ANALYSIS IN LUPUS NEPHRITIS: DIFFERENCES IN GENE EXPRESSION BETWEEN DIAGNOSIS AND RENAL REMISSION IN KIDNEY TISSUE
Authors: Rodríguez-Garcia Eva , Salman Tarek Carlos , Gimeno Javier , Marquez Eva , Sans Laia , Ribas Andres , Barrios-Barrera Clara , Riera Marta , Pascual Julio , Crespo Marta 
Published: June 2023

Abstract

Background and Aims
Transcriptome analysis in kidney tissue from lupus nephritis patients (LN) provide useful information about gene expression. We designed a pilot study in paraffin-embedded kidney tissue (FFPE) from LN patients to evaluate differences between gene expression at diagnosis (kidney biopsy diagnosis) and 2 years after achieve a complete renal response (protocol kidney biopsy). We evaluated if transcriptome analysis results could be verified through immunofluorescence staining (IF) in kidney biopsies (diagnosis biopsy vs protocol biopsy).

Method
We included diagnosis and protocol biopsies from 16 LN patients with class III and/or IV. All patients received prednisone (0.5 mg/kg) plus mycophenolic acid. Complete renal remission was defined as normal renal function, uPCOR &lt; 300 mg/gr and inactive urine sediment. RNA Sequencing (RNA-Seq) was performed in FFPE, Human MSigDB Collections were used for gene enrichment analysis and Gene sets derived from the Biological Process Gene Ontology (GO) V7.2 is the library used in the study.

Results
16 LN patients were included, Class III (43.8%), Class IV (43.8%) and Mixed Class (12.5%). 100% patients were women and Caucasian with mean age 40.9±7.1 years. RNA-Seq showed 2 overexpressed groups of genes (GO) in diagnosis biopsies, expression of this GO was not detected in protocol biopsies: GO-Complement_activation (NES 2.26, p = 4.2E -0.5): Properdin, Ficolin, C3, Factor B, C3AR1, C4 y CDC59.
GO- Humoral_Inmune_Response_Mediated_Circulating_Inmunoglobulin (NES 2.10, p = 7,6E -0.6): IgG1, IgG2, IgA, chemokine receptors 2 y 7 and receptor 13 TNF.
Results were verified using IF staining in kidney biopsies, in protocol biopsies were observed a significant reduction in C1q and C3 complement proteins staining: C1q (78% vs 22.2%, p = 0,006), C3 (73.3% vs 27.8%, p = 0.005); results in immunoglobulins staining also agree with transcriptome analysis results, so that we observed significant reduction in IgA and IgG: IgG (69% vs 36.4%, p = 0.009) and IgA (83.3% vs 16.7%, p = 0.02) while IgM staining not showed differences between diagnosis biopsy and protocol biopsy (43.8% vs 45.5%).

Conclusion
Transcriptome analysis in kidney tissue from LN patients, identified complement proteins and humoral mediators overexpressed at LN diagnosis and infraexpressed at complete renal remission; the results could help nephrologist to investigate the role of these protein as LN biomarkers.
#5500 THE IMPACT OF CHRONIC KIDNEY DISEASE-ASSOCIATED PRURITUS RELIEF ON SKINDEX-10 DISEASE AND SOCIAL FUNCTIONING DOMAINS
Authors: Ständer Sonja , Schaufler Thilo , Ruessmann Despina , Morin Isabelle , Menzaghi Frederique , Wen Warren , Mccafferty Kieran 
Published: June 2023

Abstract

Background and Aims
Chronic kidney disease-associated pruritus (CKD-aP) is a serious condition that greatly impacts patients’ quality of life (QoL). Moderate-severe pruritus affects up to 47% of patients undergoing haemodialysis (HD) [1]. The aim of this analysis was to assess the impact of itch relief on the disease and social functioning domains of the Skindex-10 questionnaire in a post hoc analysis of the difelikefalin (DFK) Phase 3 studies in patients with CKD-aP undergoing HD.

Method
Patients with moderate-to-severe CKD-aP (mean Worst Itch Numerical Rating Scale [WI-NRS] score ≥4 [KALM-1] or ≥5 [Study 3105 and KALM-2]) undergoing HD were enrolled and randomised 1:1 to receive intravenous DFK 0.5 µg/kg or placebo (KALM-1 and -2) or open-label DFK (Study 3105) 3 times/week for 12 weeks. Data from all patients who completed the studies were included in the present analysis irrespective of study drug exposure; data were pooled for patients receiving DFK and placebo from the KALM studies. The 12-week change from baseline in the Skindex-10 questionnaire subdomains were assessed for disease (Q1–3) and social functioning (Q7–10). Change from baseline in the mood/emotional distress domain has previously been reported (Q4–6) [2].

Results
Skindex-10 scores were available for 914 patients (KALM studies: n = 720; Study 3105: n = 194). At Week 12, patients with a clinically relevant (WI-NRS ≥3-point) change (decrease) in itch (KALM: n = 305; 3105: n = 143) reported a relative mean (± standard error) corresponding improvement of 59.7%±2.0 (KALM) and 65.9%±2.6 (3105) from baseline in the disease domain of Skindex-10, compared with 18.4%±2.3 and 30.7%±4.4 of patients with &lt;3-point WI-NRS improvement (KALM: n = 415 [Figure A]; 3105: n = 51 [Figure B]). In addition, a much greater improvement in QoL was reported for the social functioning domain for patients with ≥3-point WI-NRS improvement, compared with patients with &lt;3-point improvement (66.2%±3.5 vs 11%±7.6 in the KALM studies; 75.5%±4.0 vs 49.4%±8.5 in Study 3105). Overall, the patients with ≥3-point WI-NRS change reported relative mean improvement from baseline ranging from 64%±2.3 to 70.2%±2.6 across the total Skindex-10 scale compared with 15.1%±4.8 to 35.4%±5.5 of patients with &lt;3-point improvement at Week 12 across all studies.

Conclusion
In this post hoc analysis, patients with CKD-aP undergoing HD who reported a clinically meaningful reduction in itch intensity also achieved a substantially greater improvement in both the disease and social functioning domains of Skindex-10, as well as overall itch-related QoL.
#5506 NATIVE KIDNEY BIOPSY: A NATIONAL SURVEY ON, DIAGNOSES AND OUTCOMES
Authors: Mcquarrie Emily , Bell Samira , Campbell Jacqueline , Watters Chrissie , Lakey Joe , Metcalfe Wendy , Hunter Robert , Stevens Kate , Traynor Jamie , Cousland Zoe , Joss Nicola , Walbaum David , Kipgen David , Crosby Jana , Kelly Michael , Dey Vishal , Buck Kate , Methven Shona , Stewart Graham , Murugan Kiru , Henderson Lorna , Conway Bryan , Geddes Colin C 
Published: June 2023

Abstract

Background and Aims
Since 2014, all adult native kidney biopsies undertaken in Scotland have been recorded by the Scottish Renal Registry (SRR). We aimed to report current data on indications for kidney biopsy, and outcomes following biopsy including requirement for kidney replacement therapy (KRT) and mortality.

Method
All 9 adult nephrology centres covering a population of over 5 million people report complete data on all kidney biopsies undertaken to the SRR. This includes indication, age, gender and diagnosis. The SRR collects requirement for KRT and death. Death or KRT at 6 months, 1 year and 2 years from date of first native kidney biopsy in patients with IgAN, MGN or ATIN were recorded.

Results
5095 native kidney biopsies undertaken in 4702 patients between 01/01/2014 and 31/12/2021 were included. This averages 117.1 biopsies per million population / year. 54.7% were male with mean age 57.2 (SD 17.2) years. 98.2% of kidney biopsies were deemed adequate for diagnosis. Data completeness is over 99%. The commonest indications for native kidney biopsy were acute kidney injury query cause (AKI - 30.0%), chronically reduced eGFR (CKD) (28.1%) and nephrotic syndrome (19.7%). Overall, the commonest diagnoses made were: IgA nephropathy (IgAN 13.1%), tubulointerstitial nephritis (ATIN 8.5%) and membranous nephropathy (MGN 7.2%). Table 1 shows diagnoses made by biopsy indication.

Conclusion
In a complete national dataset, AKI is the commonest indication for native kidney biopsy and most commonly leads to a diagnosis of ATIN. IgAN remains the commonest primary glomerulopathy diagnosed on kidney biopsy, with MGN being the most likely diagnosis in patients biopsied for indication of nephrotic syndrome. Kidney and patient survival varies at 2 years depending on diagnosis. Table 2 shows that at 2 years the cmortality rate (Fig. 1) is highest in patients with MGN (11.4%) and risk of KRT highest in patients with IgAN (10.2%).
#5598 MULTICENTER STUDY TO ASSESS THE FREQUENCY OF ADVERSE EVENTS FROM VACCINATION AGAINST SARS-COV2 IN PATIENTS WITH PAUCI-IMMUNE GLOMERULONEPHRITIS
Authors: Sardeli Angeliki , Ntounousi Evangelia , Galitsiou Dimitra , Kantartzi Konstantina , Kriki Pelagia , Liakopoulos Vassilios , Marinaki Smaragdi , Vaios Vasileios , Petrou Dimitra , Gkika-Zervou Louisa , Kalogeropoulos Petros , Nikolopoulos Petros , Boletis Ioannis , Moustakas Georgios , Panagoutsos Stylianos , Lionaki Sophia 
Published: June 2023

Abstract

Background and Aims
The present study aims to investigate the frequency of adverse events of SARS-CoV2 vaccination in patients with pauci-immune glomerulonephritis.

Method
Patients with pauci-immune glomerulonephritis who were vaccinated with the SARS-CoV2 vaccine were retrospectively studied. Patients who had reached end-stage kidney disease before the vaccine were excluded. The histopathological diagnosis of pauci-immune glomerulonephritis, immunosuppressive regimens, resulting outcome, timing, doses, adverse effects of the vaccine and its potential effect on the clinical course of pauci-immune glomerulonephritis were recorded.

Results
To date, 67 patients with pauci-immune glomerulonephritis with a mean age of 59.6 (±17.5) years have been included in the study, of whom 36 (53.7%) were females. 34 (50.7%) of the patients had a medical history of arterial hypertension and 16 (23.9%) of diabetes mellitus with an average duration of 9 and 10 years respectively. 66 (98.5%) received induction therapy and 87.7% achieved remission. 50 (74.6%) received maintenance therapy and 50 (94.3%) were vaccinated against SARS-CoV2 at a mean time of 79.5 (±70.8) months from diagnostic biopsy with 3.2 (± 1.0) doses. 90% of patients were in remission and 44% were receiving immunosuppressive therapy at the time of vaccination. 26% of patients reported systemic adverse events related to vaccination and 62% local reactions at the administration site. 2 (4.3%) patients experienced pauci-immune glomerulonephritis relapse with a mean time to relapse of 5.7 (±3.4) months from the 1st dose.

Conclusion
Based on the results from this cohort of patients with pauci-immune glomerulonephritis, the SARS-CoV2 vaccine appears safe, with no significant impact on the likelihood of pauci-immune glomerulonephritis relapse for patients in remission.
#5688 CLINICAL PROFILE AND OUTCOMES OF DENGUE-INDUCED ACUTE KIDNEY INJURY (DAKI): A TERTIARY CENTRE EXPERIENCE FROM SOUTH INDIA
Authors: Kosaraju Aiswarya , Suresh Sandhya , Elumalai Ramprasad , Matcha Jayakumar , S Manikantan 
Published: June 2023

Abstract

Background and Aims
Dengue is currently the most relevant viral infection transmitted by a mosquito bite that represents a major threat to public health worldwide. While Dengue-Associated Acute Kidney injury (DAKI) is a lethal complication, it remains as one of the least studied complications.

Method
This is a retrospective observational study amongst adult hospitalized Dengue patients admitted at a tertiary care hospital between January 2019 and December 2019. We estimated the prevalence of Acute Kidney Injury (AKI) using KDIGO AKIN (Acute Kidney Injury Network) criteria. Outcomes were analyzed during the time of discharge.

Results
Out of the 1550 hospitalized patients, majority of the patients were males – 1005 (64.9%). Most common age group was between 20 to 40 years. 85 (5.48%) of the total study patients developed DAKI. Older age groups were found to be more at risk for concurrent bacterial infections and higher mortality rate. Most patients had stage 1 AKI (70.1%). Overall mortality in patients with AKI was 20.3% and 80.5% in those requiring dialysis. The incidence of DAKI risk was increased by as much as 4.5-fold in the presence of hemoconcentration (or hematocrit &gt; 46.5%). Older age, Male sex, co-existing viral hepatitis, Dengue Hemorrhagic Fever, Dengue Shock Syndrome, Rhabdomyolysis, Multiple Organ Dysfunction Syndrome were found to be independent risk factors for DAKI. Presence of DAKI was associated with higher mortality and longer hospital stay.

Conclusion
In our study population, we found a low prevalence of AKI but Mortality was high in patients requiring ICU care and dialysis. Prompt recognition and identification of the at-risk population and administration of appropriate supportive treatment should be aimed to reduce the morbidity and mortality associated with this common and very important tropical disease.
#5711 MYOCARDIAL PERFORMANCE EVOLUTION AT 6 MONTHS FROM COVID-19 IN CKD PATIENTS
Authors: Țăpoi Laura , Vasiliu Vlad , Diaconu Anca , Stefan Anca , Dodi Gianina , Apetrii Mugurel , Nistor Ionut , Voroneanu Luminita , Onofriescu Mihai , Hogas Simona Mihaela , Statescu Cristian , Sascau Radu , Covic Adrian 
Published: June 2023

Abstract

Background and Aims
COVID-19 is associated with myocardial injury and in previous studies, patients with right ventricular dysfunction had an increased risk of all-cause death. In the general population, there is evidence that right ventricular strain improves at 6 months after COVID-19, but data about the course of other myocardial performance parameters are limited.

Method
CARDIO-SCARS in CKD is a currently ongoing observational cohort study that aims to assess the cardiovascular risk in a CKD (stages 3 to 5), dialysis and kidney transplant population following SARS-CoV2 infection, by using clinical evaluation, various techniques and both endothelial dysfunction and myocardial injury biomarkers (ClinicalTrial.gov Identifier NCT05125913). We hereby report the evolution of the main echocardiographic myocardial performance parameters at 6 months from COVID-19 disease.

Results
Our study included 222 patients (134 in the COVID-19 group and 88 in the control group). In the COVID-19 group, the echocardiography was performed at a mean distance of 2.21±1.9 months after testing positive for SARS-CoV-2. The mean age at baseline was 58.81±15.2 years and 53.41±14.14 years for the COVID-19 group and control group respectively. Atrial fibrillation, heart failure, ischemic heart disease and diabetes were more prevalent in the COVID-19 group. When analyzing the mean absolute difference between baseline and 6 months echocardiographic parameters using a two-sample t-Test, statistically significant results were observed for the left ventricular (LV) ejection fraction (EF), LV Tei Index, right ventricular (RV) Tei Index and RV free wall longitudinal strain (RVFWLS) as follows: Δ LVEF was 0.70±7.97% and -2.44±7.30% (p = 0.005), ΔLV Tei index was -0.04±0.19 and 0.0007± 0.11 (p = 0.024), Δ RV Tei index was -0.04±0.17 and 0.009±0.20 (p = 0.034) and ΔRVFWLS was -1.68±4.36% and -0.32±3.34% (p = 0.039) for the COVID-19 group and the control group respectively.

Conclusion
Our study is the first to describe the evolution of echocardiographic parameters post-COVID in a CKD population. Despite worse demographic and echocardiographic characteristics at baseline, patients from the COVID-19 group had a better evolution at 6 months, when compared to the control group. Both right and left ventricular myocardial performance indices improved for the COVID-19 patients and worsened for the control group.
#5733 NIERKEUZE.NL: A WEB-BASED APPLICATION TO SUPPORT THE SHARED DECISION PROCESS FOR KIDNEY REPLACEMENT THERAPY BASED ON OUTCOME DATA IN THE NETHERLANDS
Authors: Peters-Sengers H , Coster Roelof , Gomes-Neto António W , Scholten-Greben Henriette , Bart Hans , Dam Marc Ten , Heuveling Lara , Hemke Aline , de Ruiter Han , Berger Stefan P 
Published: June 2023

Abstract

Background and Aims
Access to individualized, evidence-based prognostics is needed to facilitate shared decision making about the clinical implications of whether to opt for kidney transplantation or long-term dialysis. We aim to implement a data-driven support tool (Nierkeuze.nl) that incorporates basic patient characteristics and treatment options.

Method
Consecutive patients (N = 14.275) above 18 years of age with end-stage-renal-disease (ESRD) who were eligible candidates for their first kidney transplantation and started renal replacement therapy between 2000 and 2019 were included from the national registries RENINE and NOTR. SF-12 quality of life data was obtained from RENINE and a local transplant database. Several algorithms were developed to predict waiting time, short- and long-term patient survival, graft survival, and quality of life according to factors that are known at ESRD. Probabilities of 3- and 5-year mortality were calculated using two-stage distinct Cox regression: 1) waitlist-mortality according to median time on the waiting list, 2) mortality after transplantation in remaining follow-up. Product and complement rules defined the final probabilities. No mortality on the waiting list was assumed for living donor transplants. Missing data were imputed. Model performance was evaluated by internally validated C-statistics and calibration plots.

Results
We included 4.889 deceased donor transplants, of which 990 were within the Eurotransplant Senior allocation Program (ESP), and 6.251 living donor transplants. Discrimination varied for patient survival models (C-stats: 0.68 deceased-ETKAS-TX; 0.58 for deceased-ESP-TX; 0.74 for living-TX; 0.64 for waitlisted-candidates). Survival models achieved good calibration by visual inspection across the range of predicted probabilities. Figure 1 illustrates a clear 5-year survival benefit of transplantation (living and deceased donor groups) compared with wait-listed candidates for a 65-year-old male with glomerulonephritis. Other developed algorithms of the support tool will be presented with an overview of the first experiences in the kidney failure clinic.

Conclusion
Nierkeuze.nl depicts the influence of anticipated waiting time, patient characteristics, kidney allocation program, and donor type on survival outcome of the different treatment options. Incorporating this individualized quantitative outcome information may provide valuable support for an informed choice by patients and potential living donors.