bluuebunny/crossref_metadata_2025 huggingface dataset:
#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

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

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 < 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

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 <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 <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 <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

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

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

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 > 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

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

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.
#5742 MID-ARM CIRCUMFERENCE AS A CORRELATE TO DIFFERENT: ASPECT NEUROCOGNITIVE IMPAIRMENT IN HEMODIALYSIS PATIENTS
Authors: Samaan Emad , Ayman Basma , Shams Amira , Moslam Nada , Eltantawi Mohamed , El Khaligy Mohamed , El-Gamal Mohamed , Shamsuddin Muhammad , Ibrahim Ibtihal , Nagy Eman
Published: June 2023

Background and Aims

Malnutrition is associated with poor cognitive function (CI) in Hemodialysis (HD) patients. Both have multiple ways of assessment scaled from simple bedside screening tests to more sophisticated time- and cost-consuming measures. This work aims to define the best nutritive assessment measure that correlates to the degree of CI.

Method

A cross-sectional study was carried out on 116 patients in 4 different HD units from Delta Nile, Egypt. The nutritional status was examined after the dialysis session in euvolemic patients using (1) anthropometric measurements, including body mass index (BMI), mid-arm circumference (MAC), skin fold thickness (SFT), and mid-arm muscle circumference (MAMC); (2) bioelectrical impedance analysis for assessment of skeletal muscle mass (SMM), skeletal muscle index (SMI), free fat mass (FFM), body fat mass (BFM), and total body water (TBW); (3) Hand grip strength was used to assess muscle power. The assessment of cognition was made using (1) a mini-mental state examination (MMSE) for orientation, registration, attention, recall, language, and copying; (2) Saint Louis University Mental Status Exam (SLUMS) for early CI and executive functioning; (3) Arabic version of Penn Web-Based Computerized Neurocognitive Battery (WebCNP) for those who scored no CI in the previous two tests.

Results

The results of MMSE and SLUMS tests showed that 34.5% of our cohort (n = 40) had no CI, 34.5% (n = 40) had mild to moderate degrees of CI, and 31% (n = 36) had a severe form of CI. Comparing the nutritional assessment parameters between the categories of cognitive scores revealed that there were no significant differences except in significantly lower median values of MAC (P 0.01), SMI in bioelectrical impedance analysis (P0.01), and hand grip strength (P 0.002) in severe CI group than the normal to patients without CI. In correlation statistics, MAC and hand grip strength were negatively correlated to the degree of CI (r = -0.3, P 0.006 and r = -0.26, P 0.009, respectively). MAC was the only parameter correlated with attention, emotional recognition, and differentiation functioning in the forty patients with no CI who underwent computerized neurocognitive assessment. The highest reported positive correlations reported were between the MAC and response time of both emotion recognition (r = 0.57, P <0.001) and differentiation (r = 0.55, P <0.001).

Conclusion

Of the different parameters of nutritional state assessment, MAC, the simple bedside measurement, was the best correlate with the degree of cognitive impairment in HD patients, even in its mild primitive forms.
#5747 COVID VACCINATION RELATED GLOMERULOPATHIES AND INTERSTITIAL NEPHRITIS
Authors: Marchisio Martina , Lalloni Stefania , Morrone Marco , Rabajoli Gianluca , Careddu Andrea , Fenoglio Roberta , Sciascia Savino , Roccatello Dario
Published: June 2023

Introduction

To date, almost 7 billion doses of the different types of vaccine against SARS-CoV-2 have been administered worldwide. Although the severity of new cases of SARS-CoV-2 has progressively decreased, and the pressure on national health systems has declined, the development of de novo glomerular injuries has been suggested.

Methods

This study aimed to examine the patients who were hospitalized in our Unit between April 2021 and January 2023 and underwent renal biopsy for new-onset urinary abnormalities (UA) and/or renal impairment within 3 months of SARS-CoV-2 vaccination.

Results

We identified 22 patients who developed UA and/or renal insufficiency within 3 months of vaccination. Minimal change disease was the most common disease in our cohort (6 patients, 27.3%) followed by membranous nephropathy (MN; 5 patients, 22.7%), acute tubulointerstitial nephritis (TIN; 3 patients, 13.6%) and rapidly progressive IgA nephropathy (3 patients, 13.6%). The other 5 patients had a diagnosis of ANCA-associated vasculitis (2 patient), membranoproliferative glomerulonephritis (1 patient), systemic lupus erythematosus (1 patient) and tip-variant focal segmental glomerulosclerosis (1 patient), respectively. Nine out of the 22 patients (40.9%) developed acute kidney injury. Two patients with acute TIN had to start hemodialysis that was discontinued after 1 and 2 months, respectively, due to the recovery of renal function. Two of the 5 patients who had a diagnosis of MN were positive for anti-PLA2r, while all patients were negative for anti-thrombospondin. All patients underwent treatment with corticosteroids and/or immunosuppressants.

Conclusion

Although it is not possible to conclusively determine whether there is a causal relationship between SARS-CoV-2 vaccination and new-onset nephropathies, based on the appearance of UA and/or renal insufficiency shortly after vaccination, we hypothesize that the immune response to the COVID-19 vaccine may be a trigger of nephropathies. Therefore, our results highlight the need for pharmacovigilance. However, this report should not lead to vaccine hesitation during this pandemic as the benefits of vaccination strongly outweigh the potential risks.
#5761 THE ASSOCIATION OF EGFR SLOPE WITH VISUAL IMPAIRMENT, RETINAL VESSEL DENSITY, AND EYE PATHOLOGIES IN THE EYE DETERMINANTS OF COGNITION (EYEDOC) STUDY
Authors: Scheppach Johannes , Arsiwala Lubaina , Guo Xinxing , Ramulu Pradeep , Abraham Alison
Published: June 2023

Background and Aims

Previous studies have identified chronic kidney disease (CKD) as a risk factor for poor ocular health. However, the effect of faster decline in estimated glomerular filtration rate (eGFR) on visual function, retinal markers, and eye conditions is unclear. We therefore examined the association of eGFR slope with visual function measures, retinal vessel density (VD), and common ocular pathologies in a bi-racial general population cohort.

Method

We studied 823 participants with normal kidney function or mild CKD (eGFR ≥ 60 ml/min per 1.73 m²) at baseline from the Eye Determinants of Cognition (EyeDOC) Study. Exposure was change in eGFR (ml/min per 1.73 m² per year) over 4 study visits between 1996 and 2019, calculated using linear mixed-effect models with unstructured covariance matrix. Outcomes (recorded between 2017 and 2019) were visual function (near visual acuity, presenting distance visual acuity, contrast sensitivity), retinal VD in the superficial, intermediate, and deep capillary plexus layers, and common ocular pathologies, such as retinopathy, age-related macular degeneration, and glaucoma. We used linear regression to model the associations of eGFR slope with visual function and retinal VD. We used logistic regression to study the association of eGFR slope with ocular pathologies. All models were adjusted for age, sex, race, education, smoking, body mass index, diabetes, hypertension, and hyperlipidemia. The models for retinal VD were additionally adjusted for signal strength index.

Results

In our study cohort, the mean age was 79 (±4) years with 62% females and 48% African Americans. The prevalence of diabetes and hypertension was 38% and 82%, respectively. The mean [SD] eGFR slope was −1.6 [0.6] ml/min per 1.73 m² per year. A faster eGFR decline of 1 ml/min per 1.73 m² per year was significantly associated with worse near visual acuity (0.04 logMAR [95% Confidence Interval 0.003; 0.08], p = 0.03), worse contrast sensitivity (−0.03 log [−0.05; −0.001], p = 0.01), lower VD in the deep capillary plexus layer (−0.99% per mm² [−1.96; −0.02], p = 0.04), and higher odds of retinopathy (odds ratio 2.44 [1.06; 6.63], p = 0.04). Associations of eGFR slope with the remaining measures of visual function and eye conditions were not significant.

Conclusion

In our bi-racial general population cohort with an eGFR ≥ 60 ml/min per 1.73 m² at baseline, a faster decline in eGFR was associated with worse visual function, reduced retinal vascular health, and higher odds of retinopathy. Our results support the potential usefulness of eGFR slope for risk assessment of ocular outcomes, even in patients with normal kidney function or mild CKD.
#5774 REAL-WORLD EXPERIENCE WITH COVID-19 THERAPY IN KIDNEY TRANSPLANT PATIENTS DURING THE OMICRON VARIANT PERIOD
Authors: Fernández Florentino Villanego , Alonso Marta , Sánchez Luis Alberto Vigara , Mateos Maria Eugenia Rodríguez , Alonso Myriam Eady , García-Doncel Ana García , Mañanes María del Carmen Mínguez , Escobar María Elisa Montero , Tostón Óscar Segurado , Garcia Teresa , Mazuecos Auxiliadora
Published: June 2023

Background and Aims

The development of new drugs against SARS-CoV-2 has improved the prognosis of COVID-19. Large studies often exclude transplant recipients or patients with chronic kidney disease, so the experience in kidney transplant (KT) patients is very limited.

Method

Retrospective cohort study of KT patients with mild-moderate COVID-19 in our area who were treated from 01/01/2022 to 12/31/2022. The indication to treat was made according to age, post-KT time and comorbidities. The type of drug depended on anti-spike serology and glomerular filtration rate. We did not use nirmatrelvir/ritonavir due to the risk of interactions.

Results

During the period of the study, 106 KT (55 women, 51 men) with mild-moderate COVID-19 were treated, with a mean age of 61 years and a KT vintage at the time of infection of 59 [29-186] months. Of them, 37.7% were diabetics and 83% were fully vaccinated prior to the infection. After the diagnosis, 63 (59.5%) patients received sotrovimab, 33 (31.1%) remdesivir, and 10 (9.4%) molnupiravir. The anti-spike antibody titer prior to the treatment was significantly lower in those patients who received sotrovimab (p = 0.000). The disease progressed requiring admission in 3 patients: 2 treated with sotrovimab and 1 with molnupiravir (admission rate: 3% [2/63] for sotrovimab and 10% [1/10] for molnupiravir). Any patient died. During the study period, 37 admissions due to COVID-19 in KT patients were registered in our area, of which 34 had not received any treatment (91.9%). Of these, 5 died, all of them being untreated patients before admission. The hospitalized patients did not show differences in age, post-RT time and vaccination status compared to the 106 treated with mild-moderate COVID-19.

Conclusion

Our results suggest that treatment of mild-moderate COVID-19 in high-risk KT patients may be effective in preventing progression to severe disease requiring admission. The highest rate of progression was observed in those treated with molnupiravir.
#5783 REAL-LIFE USE OF TOLVAPTAN IN ADPKD: A RETROSPECTIVE ANALYSIS OF A LARGE CANADIAN COHORT
Authors: Calvaruso Luca , Yau Kevin , Akbari Pedram , Nasri Fatemeh , Deng Shirley X , Khowaja Saima , He Ning , Haghighi Amirreza , Khalili Korosh , Pei York
Published: June 2023

Background and Aims

Tolvaptan is the first disease-modifier therapy proven to slow eGFR decline in high-risk patients with ADPKD. However, barriers to its use in real-life settings have not been examined.

Method

Single-center, retrospective study of 523 current or new patients with ADPKD followed at the Center for Innovative Management of PKD in Toronto, Ontario between January 1, 2016 to December 30, 2018. All patients had clinical assessment and total kidney volume measurements; those deemed to be at high risk based on their Mayo Clinic Imaging Class (MCIC) 1C, 1D, or 1E, were offered tolvaptan with their preference (yes or no) and reasons for their choices recorded.

Results

Overall, 315/523 (60.2%) patients had MCIC 1C-1E; however, only 96 (30%) of them were treated with tolvaptan at the last follow-up. Among these high-risk patients, those treated with tolvaptan were more likely to have a higher eGFR (61 ±27 vs. 82 ±26 ml/min/1.73 m2), CKD stages 1–2 (41% vs. 79%), and MCIC 1D-1E (69% vs. 37%). The most common reasons provided for not taking tolvaptan were lifestyle preference related to the aquaretic effect (51%), older age ≥60 (12%), and pregnancy or family planning (6%).

Conclusion

In this real-world experience, at least 60% of patients with ADPKD considered to be at high risk for progression to ESKD by imaging were not treated with tolvaptan; most of them had earlier stages of CKD with well-preserved eGFR. The most common reason for their refusal to consider tolvaptan is a concern for intolerability of the aquaretic side-effect; strategies to mitigate this side-effect may help to reduce the barrier to tolvaptan therapy.
#5867 EFFECT OF SGLT2I ON URIC ACID AND GLUCOSE URINARY FRACTIONAL EXCRETION IN PATIENTS WITH CHRONIC KIDNEY DISEASE AND TYPE 2 DIABETES MELLITUS
Authors: Briales Paula Sanchez , Vidas Maria Marques , López Paula , Illazquez María Victoria López , Ali Aylin Vedat , Portoles Jose
Published: June 2023

Background and Aims

Sodium-glucose cotranspoter type 2 inhibitors (SGLT2i) have demonstrated broad benefits beyond glycemic control, including hypouricemic effects. However, this fact has not been completely validated in chronic kidney disease (CKD). The mechanism by which SGLT2i produces an increase in uric acid elimination is not fully understood and appears to be mediated in part by increased glucose in the renal tubule, which would compete in reabsorption with uric acid through GLUTb transporter. The aim of this study is to analyse the effect of SGLT2i on uric acid and glucose urinary fractional excretion (FE) in type 2 diabetes mellitus (T2DM) + CKD patients.

Method

Retrospective observational single-center study conducted between January18 and December 22 in T2DM-CKD patients on SGLT2i. Subjects on renal replacement therapy, treatment with GLP1 analogues and those for whom we did not have uricosuria prior to the start of iSGLT2 were excluded. Urinary uric acid and glucose FE were analysed at baseline and during follow-up of up to 24 months, with 3, 6 and 12 months cut-offs. Data are described as mean and standard deviation (SD). Statistical analysis was performed using STATA v14 with statistics for paired samples.

Results

82 patients were included in the study, with a mean follow-up of 1.2 years. During follow-up, 23 patients left the study (arGLP1 initiation (n = 9), adverse reactions (n = 4), exitus (n = 2) and loss to follow-up (n = 8). 78.1% were male, mean age 72.7 years (SD 8.5), and main co-morbidities were: obesity 76.8%, arterial hypertension 95%, hyperuricemia 75.6% and congestive heart failure 25.6%. Distribution according SGLT2i drug was: 65.6% dapagliflozin, 25% canagliflozin and 9.4% empagliflozin. eGFR decreased immediately after initiation of SGLT2i with ulterior stabilization as described elsewhere (Table 1). We observed a significant increase on urinary uric acid FE that remain stable along the follow-up: basal 7.4%, 3 months 9.4% (p < 0.001). However, serum uric acid levels did not show significant differences along the study. Urinary glucose FE increase remained stable along the whole observation period in spite of no significant differences from a clinical point of view on % of glycosylated haemoglobin (Table 1).

Conclusion

Despite decreased GFR, T2DM-CKD patients exhibited significant urinary uric acid and glucose FE increase after starting SGLT2i. This increase remained stable for at least 2 years. However, we did not observe significant reductions on uricemia in these patients, implying that increase on urinary uric acid excretion is not enough in this setting to obtain significant modifications on uricemia.
#5871 PERITONEAL DIALYSIS INFECTIONS IN MALTA: AN OVERVIEW OF THIRTEEN YEARS
Authors: Attard Abigail , Grech Edward , Cauchi Angela Borg , Buttigieg Jesmar , Farrugia Emanuel , Borg Michael A
Published: June 2023

Background and Aims

Peritoneal dialysis (PD)-related infections are still associated with an increased risk of morbidity and mortality. We describe an overview of PD peritonitis and catheter-related infection (CRI) rates in Malta over a period of thirteen years.

Method

All patients undergoing PD in Malta from 2008 to 2020 were included. Data from 2008 to 2012 was retrospective (shown as mean), whilst data from 2013 to 2020 was prospective. ISPD guidelines and definitions were followed.

Results

Study population sizes from 2008 to 2020 were as follows: 137 (2008-2012), 91, 80, 126, 117, 102, 103, 101, and 101 respectively. PD peritonitis rates from 2008 to 2020 were 0.38, 0.31, 0.35, 0.46, 0.43, 0.57, 0.54, 0.43, 0.39, 0.40, 0.46, 0.37, and 0.29 episodes/patient/year respectively. Gram-positive peritonitis episodes predominated, the majority of which were Staphylococcal infections. Methicillin-resistant Staphylococcus aureus (MRSA) rates have overall decreased from 0.03 episodes/patient in 2008–2012 to 0.01 episodes/patient in 2020, to no cases in 2016, 2017 and 2019. Coagulase-negative Staphylococcal (CNS) rates also decreased from 0.26 episodes/patient in 2013 to 0.03 in 2017, 0.11 in 2018, 0.04 in 2019, and 0.08 in 2020. With regards to Gram-negative peritonitis, Pseudomonas rates declined from 0.06 episodes/patient in 2008–2012 to 0.03 in 2018. No cases were recorded in 2016, 2019 and 2020. The rate of Escherichia coli-associated peritonitis was 0.03 episodes/patient/year in 2020, and no cases were found in 2016, 2017, 2018, and 2019. Fungal peritonitis rates varied from 0.03 in 2008–2012 to 0.01 episodes/patient/year in 2013, 2018, 2019 and 2020 with no cases being recorded in 2016 and 2017. CRI rates were as follows: 0.39 (2008-2012), 0.35, 0.91, 0.37, 0.38, 0.25, 0.50, 0.29, and 0.22 episodes/patient/year respectively. The incidence of Gram-negative infections from 2013 to 2020 was 49, 51, 52, 65, 58, 66, 48, 41% respectively, with an average rate of 54%. Gram-positive CRIs were mostly Staphylococcal, peaking in 2014 at 0.38 episodes/patient, down to 0.14 in 2019, and 0.10 in 2020. MRSA rates decreased from 0.15 episodes/patient/year in 2014 to 0.01 in 2018, no cases in 2019, and 0.04 in 2020. CRI Pseudomonas rates have overall improved from 0.12 (2008-2012), to 0.06, 0.09, 0.09, 0.14, 0.03, 0.17, 0.06, 0.04 episodes/patient/year from 2013 to 2020.

Conclusion

The Maltese PD cohort has been achieving ISPD target requirements. Both PD peritonitis and catheter-related infection rates declined over the last thirteen years. There was no MRSA peritonitis in 2016, 2017 and 2019, no Pseudomonas peritonitis in 2016, 2019 and 2020, no E. coli in 2016,2017, 2018 and 2019 and no fungal PD peritonitis in 2016 and 2017. Overall CRIs were predominantly Gram-negative, but not in 2019 and 2020.
#5894 HYPOCOMPLEMENTEMIA AT DIAGNOSIS OF ANCA-ASSOCIATED VASCULITIS IS ASSOCIATED WITH SEVERITY AND OUTCOMES
Authors: Lanau Maria , Lorente Loreto Fernandez , Arnedo Mario Perez , Manrique Joaquin
Published: June 2023

Background and Aims

A relationship between antineutrophilic cytoplasmic antibody (ANCA)-associated vasculitis (AAV) and complement has been shown, and complement has an important role in the pathogenesis of AAV [1]. Low serum complement levels (sC3) at diagnosis of AAV has been previously described although clinical characteristics and outcomes of AAV with hypocomplementemia still remain unclear [2]. The aim of this study was to investigate what proportion of patients with AAV have low sC3 at diagnosis, and whether they have different clinical and histological features or experience different outcomes compared to patients with normal sC3.

Method

A total of 93 patients with AAV diagnose (81,3% Anti-MPO and 18,7% anti-PR3) were included in the study from 2000-2022. 12% of them had sC3 values below limit of normal range (i.e., <90 mg/dl). Patients were categorized according to sC3 levels into 2 groups, hypocomplementemic (G1; mean C3: 73.1mg/dl), and normocomplementemic (G2; mean C3: 128.3mg/dl). Histological patterns were based on the Berden score and correlated with clinical features. Main outcomes of interest included severity of acute kidney injury at diagnose (AKI), histopathological patterns, end-stage kidney disease (ESKD) and death in the long term.

Results

No differences were identified in terms of demographics (age, gender, induction treatment). sC3 levels and serum creatinine were statistically associated (r2:-0.40; p<0.001). Patients with low sC3 had more severe renal involvement, at diagnose (G1: sCr 7.6mg/dl vs sCr 3.8mg/dl, p<0.001) without differences in ANCA levels and they were more likely to require acute dialysis around the initial diagnosis (p < 0.01). There were significant differences in sCr levels at diagnose (p<0.001) related to Berden score without differences in sC3 levels (Focal, n = 8 (8.6%), sCr 2.5 mg/dl, sC3 121.1 mg/dl; Crescentic, n = 23 (24.7%), sCr 6.41mg/dl, sC3 119.3 mg/dl; Mixed n = 16 (17.2%), sCr 3.6mg/dl, sC3 118.5 mg/dl; Sclerotic, n = 14 (15.1%) sCr 3.0 C3 129.1mg/dl). 55.5% of G1 patients deceased compared to 28% of G2. Lower sC3 levels (G1) were associated with mortality (log-rank 4.1; p<0.05) and composite outcome of ESKD or death (log-rank 5.9; p<0.05) compared G2 patients.

Conclusion

Hypocomplementemia in AAV at the disease onset was a risk factor for the serious organ damage, and a life prognostic factor. Low C3 levels at diagnosis of AAV is emerging as a predictor of renal outcomes and it is thus very important to pay attention to them. Despite that histologic patterns of the Berden classification were related to the severity of AKI at presentation there was no statistical correlation with sC3 levels. We recommend to pay attention to the levels of complement at the diagnosis of AAV.
#5904 COMPARATIVE TRANSCRIPTOMICS OF THREE CANONICAL MOUSE MODELS OF CHRONIC KIDNEY DISEASE
Authors: Christensen Michael , Marstrand-Jørgensen Adam Bøgh , Sembach Frederikke Emilie , Ougaard Maria , Christensen-Dalsgaard Mikkel , Madsen Martin Rønn , Bak Stine , Jensen Ditte , Hansen Henrik Björk , Dalbøge Louise S
Published: June 2023

Background and Aims

A range of mouse models are available in preclinical chronic kidney disease (CKD) research but differ in their disease etiology and pathological hallmarks. To enable better selection of the mouse CKD model optimal for preclinical drug discovery studies, we characterized the kidney transcriptome signature of three well-established models of CKD induced by unilateral ureter obstruction (UUO), unilateral ischemic reperfusion injury (uIRI) and adenine-supplemented diet feeding (ADI).

Method

Male C57BL/6JRj mice were used in all studies. UUO or sham surgery was performed in 9 weeks old mice, which were terminated two weeks post-surgery. uIRI or sham surgery was performed in 10 weeks old mice terminated 6 weeks post-surgery. 12 weeks old mice received an adenine-supplemented diet or a control diet for 6 weeks. Endpoints included plasma biochemistry, kidney histology and RNA sequencing on kidney samples.

Results

Compared to corresponding controls, plasma urea was only increased in ADI mice. All three models presented with increased inflammation (F4/80, UUO>ADI>uIRI) and fibrosis (COl1A1, UUO = uIRI>ADI) in the histological analysis. Compared to corresponding controls, all three models demonstrated substantial increases in differential expressed genes (DEGs, UUO, n = 12,046; uIRI, n = 12,236; ADI, n = 11,468), with significant overlap in transcriptome signatures between the models. Gene expression markers of inflammation (e.g., Ccl2, Cd68 and Il1b), fibrogenesis (e.g., Tgfb1, Serpine1 and Col1a1) and kidney injury (e.g., Havcr1, Lcn2 and Spp1) supported histological findings in the three models. Interestingly, several molecular targets pursued in CKD drug discovery were significantly regulated, however with different directionality, in UUO (upregulated Atg7, Bax, Ednra/b, Gli2, Ifng, Shh; downregulated Glp1r, Nr3c2, Ptch1, Slc5a2), uIRI (upregulated Ednra, Gli2, Glp1r, Ifng, Nr3c2; downregulated Agt, Egfr, Slc5a2), and ADI mice (upregulated Agt, Atg7, Bax, Ednra; downregulated Ednrb, Egfr, Flt1, Nr3c2, Ptch1, Slc5a2).

Conclusion

UUO, uIRI and ADI mouse models demonstrate histopathological hallmarks of CKD, characterized by increased macrophage infiltration and fibrosis, which was corroborated by their individual transcriptome signatures. Despite similarities in histological phenotype, the models were distinguished based on kidney transcriptome changes, with several current drug targets regulated in a model-specific fashion. In conclusion, the current work will enable researchers to select the mouse model optimal for profiling individual preclinical test drugs with therapeutic potential in CKD. Also, our data may serve to enable further development of CKD mouse models with improved clinical translatability.
#5907 RENAL INJURY IN RELATION TO OBESITY AND THE ADDITIVE EFFECT OF HYPERTENSION IN FEMALE AND MALE OBESE AND LEAN ZSF1 RATS
Authors: Nguyen Isabel T N , Cramer Maarten Jan , Joles Jaap A , Verhaar Marianne
Published: June 2023

Background and Aims

Chronic kidney disease co-exists with heart failure with preserved ejection fraction (HFpEF), which is characterized by the presence of obesity, hypertension, and diabetes mellitus type 2. Obese ZSF1 rats, a model of HFpEF, exhibit multiple of these comorbidities that can disturb cardiac function. Little attention has been paid to how these comorbidities affect renal disease in the ZSF1 rats. HFpEF is found predominantly in women in whom obesity and hypertension are particularly prevalent. Therefore, we aimed to characterize the renal phenotype in female and male, lean and obese, ZSF1 rats and investigated additional effects of worsened hypertension on disease severity.

Method

Systolic blood pressure and renal function were assessed biweekly in female and male, lean and obese, ZSF1 rats from 12 to 26 weeks of age by tail-cuff plethysmography, urine collection via metabolic cages and plasma collection, respectively. From 19 weeks of age, rats were implanted with either a deoxycorticosterone acetate pellet (DOCA) and fed high salt diet (6% NaCl) or with a placebo pellet and fed a normal salt diet. At 26 weeks of age, terminal GFR was assessed via inulin clearance under isoflurane. Renal sections were processed for histological analysis.

Results

Lean and obese placebo ZSF1 rats, both female and male, were mildly hypertensive (systolic blood pressure 140-150 mmHg). All obese rats showed HFpEF, evidenced by elevated E/e’ ratio. In female normoglycemic ZSF1 rats, obesity associates with mild proteinuria, decreased GFR and glomerular hypertrophy. The addition of DOCA-salt worsened hypertension in female obese ZSF1 rats, but not in their lean counterparts. DOCA-salt-worsened hypertension enhanced proteinuria and triggered glomerulosclerosis in female obese rats. Male obese placebo ZSF1 rats were hyperglycemic and showed proteinuria, glomerular hypertrophy and sclerosis, and tubulo-interstitial damage. DOCA-salt worsened hypertension in both male lean and obese rats and further aggravated proteinuria, tubulo-interstitial damage, glomerular hypertrophy and sclerosis in obese male rats. No effect of DOCA-salt was observed on GFR in both male and female ZSF1 rats.

Conclusion

Female obese ZSF1 rats developed mild renal disease and DOCA-salt-worsened hypertension deteriorated renal function and structure in normoglycemic female obese ZSF1 rats similar to hyperglycemic male obese ZSF1 rats.