bluuebunny/crossref_metadata_2025 huggingface dataset:
#1474 COVID-19-infection in kidney transplant recipients during the omicron surge, a sigh of relief
Authors: Dawar Rona , Wallquist Carin , Månsson Fredrik
Published: May 2024

Background and Aims

The COVID-19 pandemic had a profound impact on global health, particularly affecting high-risk individuals such as solid organ transplant recipients (SOTRs). SOTRs have an elevated risk of severe COVID-19 disease and increased mortality. Kidney transplant recipients (KTRs) vaccinated with mRNA-based vaccines exhibit a lower response rate and shorter half-time of the serologic conversion. However, the percentage of serologic response improves with increasing number of vaccine doses. Studies also indicate that KTRs with prior COVID-19 infection demonstrate a more robust immune response post-immunization compared to COVID-19 naïve patients. Factors such as age, immunosuppressive regimen, eGFR, time since transplantation also impact vaccination response. This study aims to investigate COVID-19 infection outcome and vaccination response among KTRs during the Omicron surge.

Method

This study is a retrospective single-center cohort study at the Department of Nephrology and Transplantation at Skåne University Hospital in Malmö, Sweden. KTRs infected with COVID-19 during the Omicron surge were included (January 2022 until August 2023).

Results

97 KTRs diagnosed with COVID-19 were included of whom 91 were vaccinated. In average, three doses of COVID-19-vaccine had been given to the patients. 67 KTRs showed seroconversion, 28 remained seronegative and the status of the remaining 2 KTRs was unknown. There was a significant association between lack of antibody production and mycophenolic acid (MPA) treatment (P = 0.019, Chi2 test), however the significance was not retained in a multivariate logistic regression analysis. Among the seroconverted (n = 67), 61 experienced mild infection, 5 moderate infection and 1 severe infection, according to the WHO clinical progression scale. In the seronegative group (n = 28), 25 had mild infection while the remaining three had moderate infection. The median time for viral clearance was examined in 79 KTRs and was 23 days (IQR 18-31). Immunosuppression was adjusted in 34% (n = 33) of cases. 2.1% (n = 2) of KTRs experienced graft rejection post infection.

Conclusion

While most patients experienced a mild infection, unlike during the first surges of the pandemic, the observed subsequent graft rejections emphasize the complexity of COVID-19´s potentially immunologic triggering effect and risk of graft loss in KTRs. The correlation between MPA treatment and a lower degree of serologic conversion after vaccination underscores the need for personalized immunologic follow up and treatment regimen in KTRs.
#515 The clinical utility of systematic screening using aortoiliac CT angiography before kidney transplantation
Authors: Nielsen Marie Bodilsen , Budtz-Lilly Jacob , Dahl Jonathan , Keller Anna , Jespersen Bente , Ivarsen Per , Winther Simon , Birn Henrik
Published: May 2024

Background and Aims

Several guidelines suggest screening for peripheral artery disease before kidney transplantation including the Kidney Disease: Improving Global Outcomes. There is currently no consensus on whom or how to screen for peripheral artery disease. We examined the clinical consequences of systematic screening using aortoiliac computed tomography (CT) angiography in a large cohort of potential kidney transplant candidates.

Method

In a retrospective study, potential kidney transplant candidates underwent aortoiliac CT angiography as pretransplant screening for peripheral artery disease. Screening criteria were patients above 40 years, and/or diabetes, and/or need for dialysis more than 5 years. The prevalence of clinically diagnosed peripheral artery disease and aortoiliac stenosis and calcification of iliac arteries at CT angiographies were assessed. A multidisciplinary team evaluated the CT angiographies in regard to transplantability and surgery planning.

Results

In total, 470 potential kidney transplant candidates were included. Clinically diagnosed peripheral artery disease was present in 14%, aortoiliac stenosis in 16%, and iliac circular calcifications in 21% potential kidney transplant candidates. A change in clinical decision by the multidisciplinary team was recorded in 67 of 429 (16%) patients due to vascular findings including choice of side for implantation in 52 (12%) and transplant-ineligibility in 7 (2%). Six out of seven ineligible patients had clinically diagnosed peripheral artery disease. Any clinical decision-making was recorded in 178 (41%).

Conclusion

Systematic screening using aortoiliac CT angiography may guide the planning of transplant surgery in a large proportion of patients. The effect of transplant outcomes remains to be established.
#1279 Efficacy and safety of non-vitamin K antagonist oral anticoagulants in renal transplant recipients with atrial fibrillation
Authors: Heleniak Zbigniew , Naik Marcel , Eleftheriadis Georgios , Ruszkowski Jakub , Halleck Fabian , Undas Anetta , Dębska-Ślizień Alicja , Budde Klemens
Published: May 2024

Background and Aims

Atrial fibrillation (AF) is associated with increased stroke and bleeding risk in patients with chronic kidney disease (CKD) including renal transplant recipients (RTRs). Little is known about the real-life use of non-vitamin K antagonist oral anticoagulants (NOACs) in RTRs.

Method

In a retrospective cohort study conducted in one academic transplant center, we enrolled consecutive 168 RTRs with AF on NOACs including 139 (82.7%) subjects on apixaban 5 or 10 mg/day, 18 (10.7%) on rivaroxaban 15 or 20 mg/day, 6 (3.6%) subjects on edoxaban 30 mg/day and 5 patients (3.0%) firstly treated with rivaroxaban and then switched to apixaban. Thromboembolic (stroke, transient ischemic attack, systolic embolism) and bleeding events (major and clinically relevant non-major bleeding) were recorded during a median follow-up of 21.2 months. There were no significant differences in demographic, clinical, and laboratory variables at baseline between the 3 treatment groups (Fig. 1).

Results

During follow-up, arterial thromboembolic events occurred in 9 (6.3%) subjects on apixaban and 4 (18.2%) on rivaroxaban. Patients treated with rivaroxaban did not have a significantly higher hazard of arterial thromboembolic events when compared with those on apixaban (hazard ratio [HR] 2.04; 95% CI: 0.68-6.12, p=0.21).

Major bleeding or clinically relevant non-major bleeding occurred in 17 (11.8%) patients receiving apixaban (one experienced both events), 3 (13.0%) patients on rivaroxaban, and 2 (33.3%) on edoxaban. When compared to apixaban, the other NOACs did not significantly differ in the hazard of bleeding [rivaroxaban: HR 0.79 (95% CI: 0.24-2.58; p=0.69); edoxaban: HR 1.90 (95% CI: 0.35-10.27; p=0.46)].

Conclusion

The study suggests that RTRs with AF receiving apixaban and rivaroxaban have a similar risk of thromboembolism and bleeding in the everyday practice of the academic transplantation center. Edoxaban was rarely chosen in this group of patients, therefore evidence is uncertain.
#601 Overweight-obese kidney transplant recipients have altered tacrolimus clearance and need lower doses for target levels with good graft outcomes
Authors: Elsharkawy Magdy , Elbraky Abdelrahman , Abdelmegied Shaimaa Zaki
Published: May 2024

Background and Aims

CYP3A4 which has been associated with altered tacrolimus (Tac) clearance. Clearances for drugs that are CYP3A4 substrates are generally reduced by 10%-35% in obese compared to normal-weight individuals. This study assessed the early and late Tac levels and weight-based total daily dose (TDD) for target Tac level in overweight-obese kidney transplant (KT) recipients and its relation to graft outcomes.

Methods

A retrospective study included 62 live-related KT recipients: overweight-obese KT recipients (N=32) with body mass index (BMI) >25 and normal-weight KT recipients (N=30) with BMI <25. The Tac level and weight-based TDD were examined in the 1st 3 months and 1 year after kidney transplantation with assessment of graft outcome.

Results

The overweight-obese patients' mean BMI was 31.29 and normal-weight patients' mean BMI was 22.20 p-value (0.0001). There was no significant difference between overweight-obese patients and normal-weight patients in mean Tac levels in 1st 3 months and after 1-year (mean 8.902, 6.99 ng/ml versus 8.906, 6.91 ng/ml respectively) p-values (0.992, 0.850) respectively. The weight-based TDD for target Tac level in 1st 3 months and after 1-year was significantly lower in overweight-obese than normal-weight patients (mean 0.108, 0.073 ng/ml versus 0.167, 0.102 ng/ml) respectively with p-value (0. 00035, 0.0076) respectively. KT recipients with BMI >30 showed lower weight-based TDD versus KT recipients with BMI 25-30 in 1st 3 months (0.094 versus 0.131 ng/ml) p-value (0.0255) while no difference after 1-year p-value (0.353). Graft outcomes did not significantly differ between overweight-obese versus normal-weight patients; the mean serum creatinine (1.22 versus 1.27 mg/dl) p-value (0.680) and graft rejection was (6 patients versus 6 patients) p-value (0.104) without graft loss. The weight-based TDD after 1-year was negatively correlated with BMI and transplant duration {r −0.369, p 0.003, r −0.278, p 0.028} respectively.

Conclusion

Overweight-obese patients have altered Tac clearance and they need lower doses to achieve target Tac level in the early and late periods post-transplant which is linked to good graft outcomes. According to these preliminary data the department is planning to study the effect of CYP 3A4/5 genetic polymorphisms on Tac dose requirement in most of these patients.
#2635 A prospective cohort study of sodium-glucose cotransporter 2 inhibitor-treated glomerulonephritis in kidney transplant patients
Authors: Kwon Hyukyong , Son Sung Hyun , Park Youngchan , Jeong Joon Heun , Yoon Chul Soo , Hwang Eun Joo , Kim Sun , Kong Jin Min
Published: May 2024

Background and Aims

Recurrent or de novo glomerulonephritis (GN) after kidney transplantation (KT) is one of the main causes of renal allograft failure without effective treatment. Recent randomized controlled trials have demonstrated the beneficial effects of sodium-glucose cotransporter 2 inhibitors (SGLT2i) in delaying the progression of chronic kidney disease of broad range, including GN.

Method

We conducted a single-center, prospective study on the treatment with SGLT2i in 24 patients with biopsy-proven GN of renal allograft. IgA nephropathy was the most frequent (n=16), followed by focal segmental glomerulosclerosis (n=2), membranous nephropathy (n=2) and others (n=4). Baseline mean eGFR was 58 ± 26 mL/min/1.73 m2. The primary outcome is the change in proteinuria from baseline to 6 and 12 months, and the change in eGFR slope before (−24 to 0 months) and after (3 to 15 months) the initiation of SGLT2i. The secondary outcome is the change in body weight (BW), systolic blood pressure (SBP) and doses of antihypertensives. Adverse reactions were closely observed.

Results

The post-SGLT2i follow-up period was 17.5 (median) ± 14.9 months. The eGFR slope improved from −4.762 ± 1.29 ml/min/1.73 m2/year(before SGLT2i) to −0.667 ± 4.07 (after SGLT2i). The urinary protein-creatinine ratio did not change significantly. BW decreased significantly at 3 months and maintained thereafter. SBP did not change significantly, but the number of antihypertensives decreased. There was no cases of acute pyelonephritis or AKI due to volume depletion.

Conclusion

SGLT2i slowed the eGFR decline of patients with GN of renal allograft and was well-tolerated. Our preliminary results warrant confirmation by further studies with a larger number of patients and prolonged follow-up.
#2784 Deep learning algorithm predicts individual ultrafiltration trajectories for patients on automated peritoneal dialysis 12 weeks ahead
Authors: Eibensteiner Fabian , Unterwurzacher Markus , Herzog Rebecca , Kratochwill Klaus , Aufricht Christoph , Vychytil Andreas
Published: May 2024

Background and Aims

Adequate small solute clearance and ultrafiltration (UF) are the main requirements for fluid and salt homeostasis on peritoneal dialysis (PD). New automated peritoneal dialysis (APD) systems that allow remote patient monitoring in terms of PD treatment analysis have the potential to improve clinical outcomes. UF on APD although dependent on PD prescription, i.e. fill volumes and glucose concentration, exhibits substantial intra- and interindividual variation, even day-by-day. As conventional statistical methods are not able to assess these complex non-linear relationships adequately, we aimed to build a deep learning algorithm to predict ultrafiltration trajectories of individual patients 12 weeks ahead.

Method

Data on daily UF and PD prescriptions (i.e., glucose concentration, fill volumes) was extracted from the APD cycler management software (PD Link, Baxter, IL, USA) and patient charts at the Medical University of Vienna, for a secondary analysis of this cohort. The Keras high-level API for TensorFlow in R software (R Core Team 2023) was used to create a Long Short-Term Memory (LSTM) recurrent neural network based on historic prescription and gcUF data of 26 weeks (after the first 90 days of APD) to predict individual UF trajectories for the following 12 weeks.

Results

APD machine readouts from a total of 123 patients, with a mean time on PD of 117 (±73) days, were retrieved. The final recurrent neural network consisted of four LSTM layers with 64 cells each, sigmoid activation. The final model was fit using 30 epochs, 49 steps per epoch, and recurrent dropout to avoid overfitting. A 40-40-20% data split was used to train, validate, and test the model adequately. This deep learning algorithm was able to predict individual UF values, for each day of the upcoming 12 weeks, with an accuracy of at mean 201ml. Upon visual inspection, predicted individual UF trajectories smoothly resemble the overall day-by-day trajectory of the patient but fail to account for extreme spikes in either direction.

Conclusion

In conclusion, historic daily APD cycler and prescription data in coalescence with respective daily measurements of membrane function (i.e., gcUF) can be used to predict individual daily ultrafiltration values and trajectories of APD patients 12 weeks ahead using a deep learning algorithm. Therefore, continuous collection of PD prescription data and UF measurements may be used to monitor peritoneal membrane function of patients on APD and alert clinical teams upon detection of relevant changes of UF trajectories already 12 weeks ahead to facilitate early intervention. In contrast to current “screening” methods on PD, i.e., Peritoneal Equilibrium Test, these methods could reduce treatment burden.
#3090 Parvovirus infection in renal transplant recipients: a systematic review of clinical profile and treatment strategies
Authors: Subbiah Arunkumar , Govindarajan Srinivasavaradan , Durgam Yashwant
Published: May 2024

Background and Aims

Parvovirus B 19 (PVB-19) virus infection can cause severe, persistent and/or refractory anaemia in kidney transplant recipients (KTR). There is paucity of data on the clinical manifestations, diagnosis and management of this infection and limited to case reports and case series.

Method

We performed a literature search of kidney transplant recipients infected with PVB-19 in MEDLINE, EMBASE and Cochrane databases and 93 articles were identified as suitable for assessment. The review was conducted in accordance with PRISMA statement.

Results

A total of two hundred and eighty-two patients were included from the studies assessed in the review. The mean age of the cohort was 37.05 years. The infection was more common in males when compared to females. The median onset of PVB-19 infection post transplantation was at 5 weeks (2, 15 weeks). One fourth of the recipients had at least one episode of rejection prior to PVB-19 infection. Majority of the patients were on Tacrolimus, MMF and corticosteroids maintenance. One third of the patients had co-infections with other organisms (EBV, CMV, etc.). Anemia and fever were the most common manifestations among all the kidney transplant patients infected with PVB-19 while CNS manifestations and rash were least reported. Hemoglobin was low (<10 mg/dl) in ninety eight percent of the patients (n=151). The lowest hemoglobin reported in the due course of illness was 6 mg/dl (5, 7.2 mg/dl) and with corrected reticulocyte count being only 0.2% (0.1%, 0.6%). The most consistent finding on peripheral smear was normocytic, normochromic anemia while a few reported helmet cells too. Pure Erythroid hypoplasia alone (45.3%) combined with giant pronormoblasts and inclusion bodies (49%) were the most common findings on bone marrow aspirate. Majority of PVB-19 diagnosis was made with the help of multiple methods of detection like IgM assay, PCR—qualitative and quantitative (42.2%). The average PCR copies detected were 1.3*107 (4.28*105, 2.53*109). IVIG only (47.2%) and combined IVIG + immunosuppression reduction (41.2%) was the mainstay of the treatment in majority. The median time to recover was 8 weeks (3, 16 weeks). One fourth of the patients had recurrence after recovery. A majority of the patients (96.7%) recovered from reactivation of PVB-19.

Conclusion

Parvovirus infection is not uncommon in the early post-transplant period. Though data is insufficient, immunosuppression reduction with IVIG remains the treatment of choice for affected patients. Prospective studies to assess the hemoglobin cutoffs and dose of IVIG are needed to frame screening and treatment protocols.
#1214 Post-kidney transplant cancer: incidence, risk factors and future perspectives. Real-world analysis of a single Italian center
Authors: Alfieri Carlo , Sartò Giulia Vanessa Re , Cosmai Laura , Campise Maria Rosaria , Regalia Anna , Verdesca Simona , Molinari Paolo , Pisacreta Anna , Gallieni Maurizio , Castellano Giuseppe
Published: May 2024

Background

Our retrospective observational study aims to describe the epidemiology of cancer after KTx and to investigate its risk factors and the impact on therapeutic management and survival, in a big monocentric cohort of kidney transplant patients (KT-ps). The association between a specific modification of immunosuppressive therapy after cancer diagnosis and survival outcomes will be analyzed.

Methods

Retrospective collection of data in KTx-ps transplanted between January 2004 and December 2021, subjected to outpatient follow-up with a median follow-up of 7 [1-19] years.

Results

We included 930 KTx-ps with mean age at KTx of 49 years. 91% had received pre-TR dialysis, for an average of 52 months. The majority had received KTx from a deceased donor (84%). 74% had undergone induction therapy with Basiliximab and 26% ATG. Maintenance therapy included in most cases the use of steroids (87%), calcineurin inhibitors (tacrolimus 92%, ciclosporin 8%), and mycophenolate (94.6%). Patients with at least one cancer (CAN+) were 177 (19%). The mean time from TR to oncological diagnosis was 83 months. Non-melanoma skin cancers (NMSC) were the most common tumors (55%), while solid tumors were observed in 38.6% of cases. Deceased donor was more represented in CAN+. CAN+ were older and with higher BMI. They had greater presence of vasculitis as basic nephropathy. In the period between 2016 and 2021, induction therapy with ATG was significantly associated with CAN+. In multivariable analysis, ATG emerged as an independent risk factor for CAN+ (p=0.014) and, in survival analyses, ATG was strongly and significantly related to the earlier development of CAN+ (p=0.010). During follow up, cancer-related causes were the second cause of mortality (23%); the average time from cancer diagnosis to death was 23 months. The median survival from TR was 148 (CAN+) and 82 months (CAN−). After oncological diagnosis, significant evidence on tumor survival was derived from the shift to mTOR inhibitors compared to the group with definitive drug suspension (p=0.004).

Conclusion

The data reported by our study confirm the relevance of cancer as a complication in KTx. ATG represent an independent risk factor for cancer; in this context, a personalized choice of immunosuppressive therapy to be proposed at the time of TR represents a crucial point in the prevention of neoplastic risk. In the KTx-ps, therapeutic strategies with antineoplastic agents and management of immunosuppression therapy after malignancy remain important research perspectives in the near future.
#3048 Short and long term follow up of living Tunisian kidney donors
Authors: Dziri Sonia , Awatef Azzabi , Wissal Sahtout , Abdellaoui Imen , Asma Fradi , Sanda Mrabet , Yosra Guedri , Zellama Dorsaf
Published: May 2024

Background and Aims

Over the years, concerns have increased about the harmlessness of kidney donation. This is more relevant in an Arab Muslim developing country like Tunisia, where lack of cadaveric donors is continuously leading to an increase in living donor numbers. The aim of this study is to evaluate the safety of nephrectomy as well as medical and surgical outcomes among LKDs, both short and long terms.

Method

Longitudinal monocentric study, involving a cohort of 106 LKDs in which nephrectomies were performed between November 2007 and April 2015. Donors that attended their follow-up visits after donation as per the European Renal Best Practice group recommendations by the European Renal Disease Association were included.10 Because of the irregularity of visits, we defined visits as follows: M1=from hospital discharge to the 3rd month, M3=from the 3rd month to 6th month, M6=from the 6th month to the 1st year, Y1=from the 1st year to 2nd year, Y2=from the 2nd year to the 4th year, and Y4=4 years and more. At the time of evaluation, we looked for the presence or history of renal events (i.e., elevation of serum creatinine level or proteinuria). We also detected by periodical check- up the presence or history of other physical or biological affections such as the presence of hypertension (HTN), diabetes mellitus (DM), sugar intolerance, hyperlipidemia, or hyper-uricemia (Table 1).

Results

92 donors were included in the follow-up analysis after following exclusion criteria. The mean age at the time of nephrectomy was 42.8 ± 10 years with the sex ratio 0.6. and 27% of our donors were mothers. Twenty-two percent of the donors were obese and 4% were hypertensive. The median initial glomerular filtration rate (GFR) was 105 mL/min/1.73 m2. The surgical approach was costal lumbotomy in 96% of cases and laparoscopy for four cases. The kidneys were removed from the left side in 93% of cases. Postoperative mortality was zero and early postoperative morbidity was low. The median duration of hospital stay was nine days. During follow-up, 14% attended all recommended visits. The median follow- up duration was 26 months. After two years post donation, the prevalence of HTN was 28% and obesity was 26%. The prevalence of GFR decline (50–59 mL/min) was 14% using formula by modification of diet in renal disease. None of our donors reached stage 4 or 5 CKD. Twelve had proteinuria and one donor had diabetes, a comparable prevalence of morbidities to the general population

Conclusion

Our results are strong arguments for harmlessness of renal donation but emphasize the importance of a careful and science-based selection process. Post donation follow-up, seemingly insufficient in our study, is the only guarantor of short- and long-term safety for donors and therefore helps to encourage the act of donating in other potential donors.
#555 Acute graft pyelonephritis in a kidney transplant recipient—a single centre experience in northern India
Authors: Mittal Ankur , Bansal Shyam , Rana Abhyuday Singh , Mahapatra Amit
Published: May 2024

Background and Aims

Urinary tract infections (UTI) are the most common infections after kidney transplantation. Although clinical spectrum of pyelonephritis after kidney transplantation remain less clear. This study was conducted to evaluate the prevalence, clinical and microbiological profile with antibiogram of post-transplant pyelonephritis.

Method

We retrospectively reviewed and analysed the charts of 1684 patients, who underwent kidney transplantation at Medanta—The Medicity between January 2015 and May 2023. Patients were screened for the diagnosis of pyelonephritis and their clinical characteristics and outcome were evaluated.

Results

93/1684 (5.5%) patients with a mean age of 41 ± 13.57 years had developed at least one episode of Pyelonephritis. 68 were males and 25 females. Older age, female gender, hyperglycaemia, use of induction immunosuppression were the risk factors for Pyelonephritis. Median time of occurrence was 44 days after transplantation. Most common symptoms were fever (n=64) followed by dysuria (n=40), and abdominal pain (n=11). Most common organism isolated was Escherichia coli (51.6%) followed by Klebsiella pneumonia (30.1%), and Pseudomonas aeruginosa (11.8%). This study showed a high percentage of resistance to commonly used antibiotics like Carbapenems (61.3%), third generation cephalosporin (49.5%). 41/93 (44%) patients had acute graft dysfunction at the time of presentation. Median duration of hospital stay was 7 days. 90/93 patients had graft recovery and one patient lost his graft after episode of UTI.

Conclusion

Pyelonephritis is a common cause of morbidity after kidney transplantation and occurs in an early post-transplant period. Gram negative bacilli are the major pathogens and carbapenems as an empirical therapy might be useful choice for management of Pyelonephritis and coverage of majority pathogens.
#1511 The immune cell ‘signature’ of incident hypertension
Authors: Murray Eleanor , Delles Christian , Virlan Aysin Tulunay , Nosalski Ryszard , Guzik Tomasz
Published: May 2024

Background and Aims

Hypertension results from complex genetic and environmental interactions, mediated by cardiac, vascular, endocrine, and renal systems. The immune system may modulate all of these, though the exact mechanisms linking immune activation with hypertension and organ damage remain poorly defined. We aimed to identify the immune cell ‘signature’ in patients with newly diagnosed, untreated hypertension (HTN; n=76) compared to normotensive controls (NTN; n=67), as well as in relation to nocturnal dipping status.

Method

Flow cytometry of peripheral blood mononuclear cells (Attune, Thermo Fisher) characterising B cell, T cell, monocyte and dendritic cells (DC) subsets, including activation signature with intracellular staining, in an exploratory comparative analysis.

Results

The proportion of CD4+ naïve T cells (CD45RA+CCR7+) was lower in hypertension, with CD45RO+CD62L+ cells attaining nominal statistical significance between NTN and HTN groups (1.3 ± 1.1 vs 1.2 ± 1.0, p=0.039). CD4+ T central memory cells were expanded (TCM, 23.1 ± 7.2 vs 27.7 ± 10.0, p=0.002, Figure) in HTN along with T effector memory (TEM) cells lacking CD62 in an adjusted model, (TEM, CD4+CD45RA-CCR7-CD62l-; 31.4 ± 7.5 vs 33.7 ± 10.3, p0.035; CD8+CD45RA-CCR7-CD45RO+CD62l− 48.9 ± 10.5 vs 52.2 ± 13.3, p=0.011). Hypertensive group had proportionally fewer CD4+CD28+ cells (95.1 ± 9.8 vs 92.0 ± 13.5, p=0.034) and CD8+CD28+ (68.0 ± 19.7 vs 62.0 ± 21.0, p=0.011), as well as CD8+ TEMRA cells (Figure). In a fully adjusted model, the CCR7-CD45RO-CD62L+ (52.2 ± 14.5 vs 50.2 ± 16.1, p=0.036), and CD8+CD28+CD45RA+CCR7- significantly differed between groups (23.1 ± 14.7 vs 25.0 ± 17.8, p=0.008). On the molecular level, T cells were polarised in HTN towards a Th1/Tc1 and Th17.1/Tc17.1 pro-inflammatory milieu (Figure). No differences were detected in B cell subsets.

The innate immune ‘signature’ was characterised by intermediate monocytes with a differing pattern of CCR2 and CCR5 chemokine receptor expression (Table 1), and alterations in STAT1 and STAT6 phosphorylation cascades. NK cell CD56+Dim expression and fewer CD122-expressing NKT (0.13 ± 0.0 vs 0.08 ± 0.1, p=0.046) and CD122+ T lymphocytes (1.3 ± 3.4 vs 0.6 ± 0.4, p=0.019) further supported pro-inflammatory milieu in hypertension.

Finally, in an exploratory nominal statistical analysis, nocturnal non-dipping was associated with particular changes in immune cell signature, including expanded CD4+TCM (CD4+CD45RO+CD62L-, 9.4 ± 4.3 vs 8.0 ± 3.3, p=0.04) and reduced CD4+TEM and TEMRA compartments; polarisation towards Th17 and Tc1; and altered Monocyte CCR2 and CCR5 expression. Additionally, non-dipping was linked to dendritic cell mannose receptor downregulation e.g. mDC non-dipper 10.9 ± 5.8 vs dipper 13.6 ± 9.7, p=0.03.

Conclusion

These exploratory data support alterations of circulating innate (monocytes) and adaptive (T cells) immune compartments in newly diagnosed untreated, and uncomplicated hypertension.
#1870 Uninephrectomized diabetic rats delay onset of hyperglycemia via down-regulation of SGLT2 mRNA
Authors: Ishizaki Yuri , Kikuchi Masao , Fujimoto Shouichi , Kaikita Koichi
Published: May 2024

Background and Aims

The kidney is essential for glucose metabolism. Reabsorption of almost all the glucose filtered by the glomerulus is performed by the sodium-glucose cotransporters (the SGLTs) in the proximal tubules, with SGLT2 responsible for about 90%. In addition, the kidney, along with the liver, plays an important role in gluconeogenesis, especially in the long fasting state. SGLT2 inhibitors originally developed for the treatment of type 2 diabetes mellitus (DM) are clinically very effective drugs halting chronic kidney disease progression. The underlying mechanisms are, however, not fully understood. Furthermore, SGLT2 expression in diabetic patients has been reported to increase and decrease but remains unclear. Therefore, this study aimed to evaluate how uninephrectomy (UNx) and SGLT2 inhibitor treatment affects the dynamics of blood glucose and SGLTs in SDT fatty rats with obese type 2 DM (leptin receptor mutation), which is hyperglycemic from an early stage.

Method

24 male SDT fatty rats were divided into four groups: sham + placebo group (n=6); sham + dapagliflozin (dapa, 1.5 mg/kg/day) group (n=6); UNx + placebo group (n=6); UNx + dapa group (n=6). UNx or sham operations were undergone at week 6. Measurements included body weight, food intake, water consumption, urine output, blood pressure, serum creatinine, and blood glucose in the experiment. At week 12, the rats were sacrificed, and the kidneys were sampled to measure SGLT1 and SGLT2 mRNA in the renal cortex by real-time PCR quantification.

Results

Blood glucose levels continued to rise from week 7 in the sham + placebo group, but the rate of increase was still slower in the UNx + placebo group, and the increase in blood glucose levels was mostly suppressed with dapa administration (Fig. 1). Only the Sham + placebo group showed increased urinary volume and weight loss after week 10 due to hyperglycemia. There were no significant differences in serum creatinine or blood pressure during the study. Real-time PCR results showed that SGLT2 mRNA in the renal cortex was significantly decreased by 26% in the UNx group (P=0.0386), but SGLT1 mRNA was not significantly different.

Conclusion

Uninephrectomized diabetic rats delayed onset of hyperglycemia and reduced SGLT2 mRNA; SGLT2 inhibitor treatment further delayed the onset of hyperglycemia but did not alter SGLT2 mRNA expression. In animal models of diabetes, renal glucose reabsorption appeared to be a major contributor to the development of hyperglycemia.
#2239 Identification of non-HLA antibodies associated with the development of antibody-mediated damage after kidney transplantation
Authors: Solà-Porta Eulàlia , Pérez-Saéz María José , Redondo-Pachón Dolores , Eguía Jorge , Caro José Luis , Federico-Vega Judith , Gimeno Javier , Buxeda Anna , Burballa Carla , Crespo Marta
Published: May 2024

Background and Aims

Non-HLA antibodies may play a role in the development of antibody-mediated rejection (ABMR) in the presence of donor-specific anti-HLA antibodies (HLA-DSA) or microvascular inflammation (MVI) without HLA-DSA in kidney transplantation (KT). The development of multiplex panels allowed the analysis of multiple antibodies simultaneously and new antibodies potentially related to ABMR/MVI have been identified.

Method

Retrospective study of a cohort of 169 KT recipients with: a) pre- and post-KT sera; b) follow-up HLA antibody monitoring; and c) follow-up biopsies. We determined the presence of 60 non-HLA antibodies in sera using a multiplex test: the Single Non-HLA Beads kit (LIFECODES®) suitable for the SAB assay performed using Luminex® technology.

Results

Pre-KT, we detected non-HLA antibodies in 85% of the recipients, with a median of 3 (2-5) positive antibodies. During follow-up, 73 patients developed ABMR/MVI. Pre-KT, in a univariate analysis including the presence of HLA-DSA (8.3% in the cohort) we detected 7 antibodies individually associated with ABMR/MVI. In multivariate analysis (Figure) GSTT1, NCL, PLA2R1 and Thyroglobulin antibodies together with HLA DSA were significantly associated with the development of ABMR/MVI, although only GSST1 and Thyroglobulin appear in a relevant number of patients (>10 patients) involved in 32 cases of ABMR and 6 cases of MVI. Post-KT, only the detection of anti-GSTT1 antibodies in sera 1- and 3-years post-TR was associated with ABMR/MVI in 3-year biopsies.

Conclusion

Pre-KT the detection of antibodies against GSST1 and Thyroglobulin using a multiplex non-HLA antibody detection panel is independently associated with the development of ABMR/MVI during follow-up. Post-KT detection of GSST1 is also associated with ABMR/MVI in 3-year biopsies.
#1881 Association of circulating autoantibodies to erythropoietin receptor with anaemia in patients with type 2 diabetes and chronic kidney disease
Authors: Oshima Megumi , Toyama Tadashi , Ito Kiyoaki , Kitajima Shinji , Mizushima Ichiro , Hara Akinori , Sakai Norihiko , Shimizu Miho , Wada Takashi , Iwata Yasunori
Published: May 2024

Background and Aims

Anaemia is a risk factor for cardiovascular and kidney prognosis in patients with type 2 diabetes and it is important to identify patients at high risk of anemia. We have previously reported that autoantibodies to erythropoietin receptor (anti-EPOR antibodies) may functionally neutralize the activity of erythropoietin and are associated with haemoglobin (Hb) in patients with lupus nephritis, and hypo responsiveness to erythropoiesis-stimulating agents (ESAs) in patients undergoing haemodialysis. This study assessed the association between anti-EPOR antibodies and anaemia in patients with type 2 diabetes and chronic kidney disease.

Method

This cohort study included patients with type 2 diabetes and chronic kidney disease who were diagnosed between 1989 and 2014 at our hospital. The presence of anti-EPOR antibodies at baseline were assessed by ELISA in stocked serum. To investigate the association between anti-EPOR antibodies and anaemia, odds ratios (ORs) and 95% confidence intervals (CIs) were estimated using logistic regression analysis adjusted for multiple covariates. We then estimated hazard ratios (HR) and 95% CIs using Cox regression models to investigate the association between anti-EPOR antibodies and the risk of iron deficiency, defined as transferrin saturation below 20% in those with follow-up measurements of iron metabolism.

Results

The mean age was 63 years, the mean eGFR was 42 ml/min/1.73 m2 and the median urinary protein to creatinine ratio (UPCR) was 1.8 g/gCr. Anti-EPOR antibodies were detected in 26 out of 110 patients (24%). At baseline, most patients with anti-EPOR antibodies had anaemia (n=24, 92%) and severe anaemia with Hb<10 g/dl (n=16, 62%) and used ESAs (n=16, 62%). The presence of anti-EPOR antibodies was independently associated with severe anaemia (OR 9.3; 1.2-70.1, p=0.03) after adjustment for baseline covariates including HbA1c, eGFR, UPCR, iron, and CRP. During a mean follow-up of 6.5 years, 6 of 10 patients (60%) developed iron deficiency in anti-EPOR antibodies positive patients, while 3 of 20 patients (15%) in negative patients. Patients with anti-EPOR antibodies were associated with an higher risk of iron deficiency compared to those without (HR 76.0; 95% CI 1.2-4721.7, p=0.04).

Conclusion

In patients with type 2 diabetes and chronic kidney disease, the presence of anti-EPOR antibodies was associated with a risk of severe anaemia and iron deficiency independently of kidney function. These results suggest that anti-EPOR antibodies may be useful in predicting the risk of anaemia and establishing therapeutic strategies of anaemia in people with type 2 diabetes.
#1831 Circulating MiRNA 195-5p may be associated with early renal impairment in patients with prediabetes
Authors: Oana Milas , Petrica Ligia , Gadalean Florica , Popescu Roxana , Vlad Daliborca , Marian Catalin , Bob Flaviu , Suteanu-Simulescu Anca , Mogos Maria , Glavan Mihaela , Ienciu Silvia , Balint Lavinia
Published: May 2024

Background and Aims

Type 2 diabetes mellitus (DM) is one of the leading causes of chronic kidney disease worldwide. However, there are few data concerning early kidney impairment in prediabetes patients.

The aim of the study was to demonstrate early kidney damage in patients with prediabetes by assessing proximal tubule (PT) dysfunction, podocytes injury, and miRNA expression.

Method

A cohort of 192 individuals were analysed and divided such as follows: 52-normoalbuminuria-, 48-microalbuminuria-, and 50-macroalbuminuria type 2 DM patients, respectively; 12 patients-prediabetes and 30-healthy controls.

The miRNA profile was assessed by real-time PCR, while PT dysfunction biomarker, N-acetyl-β-D-glucosaminidase (NAG), and podocyte injury biomarker, podocalyxin, were assessed by ELISA technique. The study was conducted in two distinct stages. In the first part of the study was detected a particular miRNAs profile in serum in patients with prediabetes; subsequently, the expression of the most relevant miRNA in patients with prediabetes was identified.

Results

i) in prediabetes patients, serum miRNA195-5p was 2.69 fold change as compared to the control group and correlated with NAG (p<0.05) and podocalyxin (p<0.03); ii) in type 2 DM patients, the expression of serum miRNA195-5p was higher and correlated with NAG (p<0.05), podocalyxin (p<0.04), urinary albumin: creatinine ratio (p<0.001) and with eGFR (p<0.001); iii) urinary NAG and urinary podocalyxin were higher in prediabetes patients and type 2 DM patients, even in the normoalbuminuria stage, as compared to controls (p<0.04; p<0.001).

Conclusion

A panel of molecular biomarkers, such as miRNAs, remain useful tools for the early diagnosis of renal involvement in the course of type 2 DM. MiRNA 195-5p may be associated with PT dysfunction and podocyte damage, and could predict renal dysfunction in both prediabetes and early diabetic kidney disease in type 2 DM patients.
#282 Correction of portal hypertension and renal dysfunction with losartan in patients with liver cirrhosis
Authors: Usmonov Dilshod , Daminov Botir , Abdurazakova Zarifa , Yuldashova Yulduz
Published: May 2024

Background and Aims

To increase the effectiveness of drug correction of portal hypertension, taking into account the functional state of patients with liver cirrhosis, using Angiotensin receptor blockers (ARBs)

Method

The work summarizes the results of an examination of 35 patients with liver cirrhosis (LC) who were treated in the hepatology department. The patients were divided into two subgroups: the first consisted of 21 patients with liver cirrhosis without ascites, Child-Pugh class A, and the second subgroup included 14 patients with liver cirrhosis with ascites, Child-Pugh class B. We evaluated the effect of the orally active angiotensin II receptor antagonist, losartan, on portal pressure in patients with cirrhosis and portal hypertension. Patients with (hepatic venous pressure gradient [HVPG] ≥ 13 mmHg) portal hypertension at baseline measurement were treated with an oral dose of 25 mg losartan once daily for 1 week.

Results

The examined patients were analyzed for the functional state of the kidneys and its relationships with the main parameters of portal hypertension and hepatic cellular failure.

Comparative characteristics of the main indicators of renal function revealed significant differences in functional parameters depending on the degree of hepatic cellular failure.

In the group of patients with cirrhosis with ascites, there was a significant decrease in renal GFR to 77.5 ± 1.4 ml/min, in contrast to the unchanged level of GFR in the group of patients with cirrhosis without ascites - 99.3 ml/min. However, no significant changes in serum creatinine levels were detected.

Therapy with Losartan in patients with Child-Pugh class A liver cirrhosis at a dose of 25 mg/day reduces PV pressure gradient by 18.1%, at a dose of 12.5 mg/day does not significantly affect the level of portal hypertension, but improves the functional state of the kidneys (increases FPR by 56%, EPP by 17.3%).

Conclusion

The present study indicates that angiotensin II blockade with orally administered losartan is safe and highly effective in the treatment of portal hypertension. In patients with liver cirrhosis with the development of impaired renal reabsorption function and a decrease in FPR from 10% to 8% in the treatment of portal hypertension, the drug of choice is an ARBs (losartan 25 mg/day) with blood pressure > 115/60 mmHg.
#1411 Intrarenal hemodynamics in patients with coronary heart disease in the post-COVID-19 period
Authors: Shishkin Alexander , Kniazeva Alena , Pchelin Ivan , Vasilev Petr
Published: May 2024

Background and Aims

Coronary heart disease (CHD) and obesity are common pathologies in patients who have had COVID-19. Endothelial dysfunction (ED) markers determination has been important in such patients due to the high risk of cardiovascular diseases progression and complications development. THE AIM Assessment of endothelial dysfunction severity in patients with CHD and obesity in the post-COVID-19 period to improve the management of these patients.

Method

49 patients were examined, who had COVID-19 a year ago. The first group (n=24) included patients with coronary artery disease in the post-COVID period. The second group (n=25) included patients with CHD and obesity who had COVID-19. We evaluated data from an ultrasound examination of the kidneys with duplex scanning of the renal arteries (resistance index (RI), pulsation index (PI)). We also studied the medical history, performed an objective examination, the results of a biochemical blood test, albuminuria levels.

Results

We demonstrated higher RI and PI of interlobar, segmental arteries in persons of the second group. An increase in RI and PI of segmental arteries accompanied by an increase in uric acid (p=0.001). The average level of microalbuminuria in the first group was 15.71 ± 4.51 μg/l, in the second group it was 24.38 ± 5.38 μg/l (p=0.110). Increasing glucose levels accompanied by an elevation of C-reactive protein levels. Obese patients had significantly higher levels of total cholesterol, triglycerides, low density lipoproteins than patients in the first group.

Conclusion

We observed changes in lipid metabolism, a higher incidence of diabetes mellitus in females, and changes in intrarenal hemodynamic parameters associated with uric acid levels in patients with coronary heart disease and obesity in the post-COVID-19 period.
#1743 Kidney outcomes associated with SGLT2 inhibitors compared to other glucose-lowering drugs: a real-world study from China
Authors: Xiao Xiang
Published: May 2024

Background and Aims

Currently, there is insufficient real-world study on the kidney outcomes of SGLT2i in mainland Chinese patients with type 2 diabetes (T2D) and chronic kidney disease (CKD). This study aimed to investigate the association between the utilization of Sodium-dependent glucose cotransporters inhibitors (SGLT2i) in real-world settings and kidney outcomes in patients with T2D and CKD in mainland China.

Method

In a retrospective analysis of electronic medical records from West China Hospital of Sichuan University, patients with T2D and CKD were included. Patients were divided into two groups, those initiating treatment with SGLT2i and those receiving other glucose-lowering drugs (oGLDs). The primary focus lies in examining the impact of SGLT2i on the decline slope of eGFR and major kidney events in these patients.

Results

We enrolled 944 patients diagnosed with both T2D and CKD. Out of these, 605 patients were prescribed SGLT2i, while the remaining 339 patients received oGLDs. The median follow-up duration were 16.8 months and 20.6 months, respectively. Throughout the follow-up period, we observed a significant decrease in the rate of eGFR decline in patients using SGLT2i (4.94 ml/min/1.73 m2 per year reduction compared to oGLDs, 95% CI: 4.73–5.15). A total of 101 kidney composite endpoint events occurred, with 31 events in the SGLT2i group and 70 events in the oGLDs group. The use of SGLT2i was associated with a 65% decrease in the risk of kidney composite endpoint events (hazard ratio 0.35, 95% CI 0.19–0.63).

Conclusion

In clinical practice, SGLT2i have shown favorable effects on kidney prognosis in patients with T2D and CKD in mainland China. These effects remain consistent across patients with varying risks of CKD progression.
#1772 Comparison of interpretation of acid-base disorder in patients with critical illness: nephrologist versus ChatGPT
Authors: Lee So Young , Koh Eun Sil , Chung Sungjin
Published: May 2024

Background and Aims

The generative pre-trained transformer (GPT), a type of large language model (LLM), is now playing a huge role in driving innovation in fields of medical education, diagnosis and treatment and with a process of continuous improvement it will itself be able to become beacons of sustainability. Medical professionals expect that they may have help from LLMs to diagnose patients more accurately and efficiently, but it is unclear whether current LLMs are well-trained and validated on real-world clinical data. In this study, we compared the performance of ChatGPT, a representative LLM, MDCalc, an online medical calculator, and human nephrologist for their diagnostic accuracies of acid-base gas analysis in critically ill cases.

Method

This study included 130 patients admitted to intensive care unit with varying medical conditions. All variables were obtained during the first 24 hours after admission.

Results

The Fleiss’ Kappa between the interpretations of nephrologist, ChatGPT and MDCalc with the acid-base gas analysis for acid-base disorders showed that Fleiss’ Kappa value was −0.138 (95% CI −0.216 to −0.059), indicating no agreement among the judgments of human doctor, LLM and online medical calculator in critically ill patients for the interpretation of acid-base status. MDCalc showed that all patients had mixed acid-base disorders while nephrologist that 4 patients had simple acid-base disorder and 1 patient had normal acid-base balance. By contrast, ChatGPT reported that 51 patients had only simple acid-base disorder. Furthermore, according to ChatGPT, normal acid-base balance was found in 27 patients, who were all diagnosed as having acid-base disorders by MDCalc or nephrologist.

Conclusion

We found that current ChatGPT does not yet provide better diagnostic performance for interpreting acid-base balance in critically ill patients who with usually have mixed acid-base disorders compared with an existing online medical calculator or nephrologist.