bluuebunny/crossref_metadata_2025 huggingface dataset:
FC002: Humoral and Cellular Immune Responses After a Three-Dose Course of Mrna-1273 Covid-19 Vaccine in Kidney Transplant Recipients: A Prospective Cohort Study
Authors: Cucchiari David , Egri Natalia , Rodríguez Diana , Montagud-Marrahi Enrique , Casals Joaquim , Del Risco Zevallos Jimena , Ventura Aguiar Pedro , Cofan Pujol Federico , Rovira Jordi , Jose Ramirez Maria , Banon Elisenda , Revuelta Ignacio , Oppenheimer Federico , Enriqueta Bayes Genis Beatriu , Diekmann Fritz
Published: May 2022

BACKGROUND AND AIMS

Seroconversion after a two-dose course of mRNA COVID-19 vaccination in kidney transplant recipients ranges between 30% and 50% in different series. We previously demonstrated that a substantial proportion of patients (35%) without a humoral response, develop a cellular response after the second dose assessed by the ELISpot technique. We aim to study the evolution of both humoral and cellular responses in the same cohort before and 1 month after the administration of the third dose of 100 mcg of mRNA-1273 COVID-19 vaccine.

METHOD

Final population included 129 KTRs studied at four time-points: at baseline before the first dose, after the second dose (median 42 days) and before (203 days) and after (232 days) the third dose. At all the time-points, IgG and IgM were assessed as well as N- and S-protein specific ELISpot. The main outcome was seroconversion after the third dose.

RESULTS

After the second dose, 26.7% of naïve cases experienced seroconversion. Before the third dose and in the absence of clinically evident COVID-19, this percentage increased to 61.9%. After the third dose, seroconversion was observed in 80.0% of patients. S-ELISpot positivity after the second dose was significantly associated with final seroconversion [OR (95% CI) 3.14 (1.10–8.96); P = .032], while transplantation < 1 year and previous kidney transplant were negatively associated with [OR (95% CI) 0.23 (0.07–0.80); P = .021 and OR (95% CI) 0.22 (0.06–0.78); P = .020, respectively). IgG after third dose were significantly higher (P < .001) in patients who maintained S-ELISpot positivity throughout the study (34.3%) and were correlated with S-spots after the second dose (r = 0.344, P < .001).

CONCLUSION

A substantial proportion of KTRs vaccinated with mRNA-1273 develops a late seroconversion after two doses and only a fifth remained seronegative after a third. Cellular immunity seems to play a major role in the development of a final strong humoral response.
FC007: The Impact of Sex on the Risk Of Major Adverse Cardiovascular Events in Older Adults with Advanced Chronic Kidney Disease: Results from the Equal Study
Authors: Astley Megan , W. Dekker Friedo , Evans Marie , Caskey Fergus , Torino Claudia , Porto Gaetana , Szymczak Maciej , Drechsler Christiane , Wanner Christoph , Jager Kitty J , Chesnaye Nicholas
Published: May 2022

BACKGROUND AND AIMS

In the general population, men have a higher risk of major adverse cardiovascular events (MACE) compared with women, with this risk difference between men and women decreasing with increasing age. Patients with chronic kidney disease (CKD) are at a higher risk of MACE compared with the general population, but sex differences in this group, especially older adults, are not fully known. We aim to identify differences in the risk of (recurrent) MACE by sex in CKD patients over 65 years old from Europe and explore factors that may explain these differences.

METHOD

The European Quality study (EQUAL study) is a prospective study on stage 4–5 CKD patients not on dialysis from Germany, Italy, Poland, Sweden, the UK and the Netherlands who were ≥ 65 years old. Cox regression and cumulative incidence competing risk curves were used to calculate MACE risks. Mediation analysis was used to identify variables that may explain risk differences between men and women.

RESULTS

In 1136 men and 607 women, over a follow-up period of 5 years, 417 (37%) men and 185 (31%) women experienced at least one MACE, and there was a total of 1247 MACE. Men and women had 123 (14% of total MACE in men) and 54 (14% of total MACE in women) fatal MACE, respectively. The most common type of first MACE was peripheral vascular disease for men and congestive heart failure for women (Fig. 1). Accounting for the competing risk of non-MACE death, the probability of having a first MACE was 43% (95% CI: 40–47%) for men and 39% (95% CI: 34–44%) for women (Fig. 2), corresponding with a 18% lower relative risk of first MACE in women (HR: 0.82; 95% CI: 0.69–0.97; P = 0.02 ). There was no significant difference in the risk of recurrent MACE (HR: 0.91; 95% CI: 0.80–1.03; P = 0.14 ) or fatal MACE (HR: 0.84; 95% CI: 0.61–1.16; P = 0.30) between men and women. Adjusting for pre-existing comorbidities attenuated the MACE risk difference between men and women. MACE risk differences between men and women changed according to age group but not according to diabetes status. In those ≤ 75 years, women had a 25% lower risk of first MACE (HR: 0.75; 95% CI: 0.57–0.99; P = 0.04), which was 15% in those > 75 years old (HR: 0.85; 95% CI: 0.68–1.06; P = 0.14 ). The risk difference of fatal MACE between men and women differed greatly between those ≤ 75 years old (HR: 1.38; 95% CI: 0.82–2.33; P = 0.22 ) and those > 75 years (HR: 0.61; 95% CI: 0.41–0.93; P = 0.02).

CONCLUSION

Men had a higher probability of having a MACE over a 5-year period. Overall, women had lower risks of MACE compared with men, but risk differences between men and women changed with increasing age. Pre-existing comorbidities explained part of this risk difference.
FC015: High Salt Environment Disrupts the Regulatory Effect of Podocin on the Nephrin-Nephrin Distance
Authors: Antal-Kónya Violetta , Pap Domonkos , Schay Gusztáv , Kétszeri Máté , Ungvári-Veres Anita , Tulassay Tivadar , Kellermayer Miklós , Karancsiné Menyhárd Dóra , Tory Kálmán
Published: May 2022

BACKGROUND AND AIMS

The podocin encoding NPHS2 is the most frequently mutated gene in steroid-resistant nephrotic syndrome. Podocin homooligomerizes through C-terminal helical regions [1] and binds nephrin in the glomerular slit diaphragm [2]. We formerly showed that podocin regulates the distance between two neighbouring nephrin molecules in cis, i.e. the shortest dimension of the glomerular pore (3.5-4nm) [3, 4].

High sodium diet has been shown to promote glomerular injury and proteinuria [5]. We aimed to assess the effect of high salt environment on the nephrin-nephrin distance in the presence and absence of podocin.

METHODS

To generate extracellularly tagged nephrin constructs, cDNA sequences encoding YPet or mCherry were inserted in the human wild type nephrin cDNA (YPet-N1 plasmid) replacing the c.3136-3162 nucleotides. Thus, the p.Glu1046-Pro1054 residues of the fibronectin domain, located in the juxtamembraneous extracellular part of nephrin was replaced with either YPet or mCherry. HEK-293 cells were co-transfected with both nephrin constructs with or without wild type HA-tagged podocin construct (pLEX-MCS plasmid). To measure the effect of salt overload, DMEM was supplemented with either 25 mM NaCl or 50 mM mannitol as osmotic control 24-h prior to the FRET measurements. The fluorescence decay curves measured by time-correlated single photon counting (TCSPC) (Chronos BH, ISS Inc.) were decomposed into lifetime components and the longest lifetime population—most suitable for long-range FRET—was used for further calculations. Nonparametric tests were used for statistical analysis.

RESULTS

High salt environment did not influence the nephrin-nephrin distance in the absence of podocin. In accordance with our previous results, podocin decreased the nephrin-nephrin distance in physiological salt environment, as reflected by an increased FRET efficiency between the extracellular YPet and mCherry tags. High salt environment (+25 mM) completely disrupted this effect. Mannitol of similar osmotic concentration did not modify the effect of podocin (Figure 1).

CONCLUSION

High salt environment increases the distance between the nephrin molecules in cis by disrupting the organizing effect of podocin. The deleterious effect of high salt is not explained by an increased osmotic pressure.
FC094: Frax is Useful Tool for Predicting All-Cause Mortality in Addition to the Risk of Fragile Fracture in Hemodialysis Patients
Authors: Fujii Takayuki , Suzuki Satoshi , Tanaka Hiroaki
Published: May 2022

BACKGROUND AND AIMS

The fracture risk assessment tool (FRAX®) was developed to predict the probability of fragile fractures during the next 10 years for the general population, and it is calculated by inputting risk factors of fractures such as age, gender, height, weight, fracture history, presence or absence of rheumatoid arthritis and steroid therapy. Although contents of FRAX do not include CKD as a risk factor, previous studies have shown that FRAX was useful in predicting fracture risk in maintenance dialysis patients. However, many reports are short-term observational studies targeting fracture risk. In the present study, we examined whether FRAX can be useful to predict the risk of fragile fractures and all-cause mortality in hemodialysis patients through the long-term observation.

METHOD

A retrospective cohort study was conducted in 273 patients aged 40 to under 90 who started hemodialysis at our hospital between March 2004 and the present and who could be followed for at least 3 years or had a fracture within 3 years. In order to assess the association between FRAX score and fragile fracture or all-cause mortality, a multivariate analysis was performed using the Cox proportional hazard model with factors related to fractures and mortality as covariates. The 10-year probability (%) of major osteoporotic fracture without bone mineral density was adopted as the FRAX score.

RESULTS

The average follow-up period was 6.7 years, and the average age of patients was 66 years, with women accounting for 29%. Of all 273 patients, 55 developed fragile fractures and 97 died. FRAX scores were divided into two groups (lower FRAX score and higher FRAX score) in accordance with a cut-off value of 8.2%, determined by ROC curve for fracture. Univariate analysis of factors associated with fractures revealed that higher FRAX score (8.2 or more) was a significant factor [hazard ratio (HR): 4.49 (2.59–7.85)]. Multivariate analysis conducted with significant factors in univariate analysis (mean serum albumin level, serum phosphorus level, magnesium level, C-reactive protein level and use or non-use of phosphate binder during the 3 years) as the covariates revealed that higher FRAX score was significantly associated with fractures [HR: 2.40 (1.27–4.5)]. Regarding the association between FRAX score and all-cause mortality, in univariate analysis, higher FRAX score was a significant predictive factor [HR: 4.34 (2.84–6. 64)]. In multivariate analysis adjusted with mean serum albumin level, creatinine level, magnesium level, C-reactive protein level, hemoglobin level, use or non-use of phosphate binder and calcimimetics as the covariates, higher FRAX score was found to be a significant factor of all-cause mortality [HR: 3.22 (1.97–5.22)].

CONCLUSION

FRAX score was also a useful tool for predicting fractures and all-cause mortality in hemodialysis patients even in long-term analysis.
FC 109: Microvascular Inflammation in Kidney Transplant Biopsies in the Absence of HLA-DSA Displays Intense Cytotoxic T-Cell and NK Cell but not Plasma Cell Infiltration
Authors: Buxeda Anna , Llinàs-Mallol Laura , Gimeno Javier , Redondo Pachon Dolores , Arias-Cabrales Carlos , Burballa Carla , Puche Adrián , José Pérez-Saéz María , Pascual Julio , Crespo Marta
Published: May 2022

BACKGROUND AND AIMS

Microvascular inflammation (MVI) without evidence of HLA-donor-specific antibodies (HLA-DSA) or C4d+ deposition remains an enigmatic phenotype, which cannot be classified as antibody-mediated rejection (ABMR) according to recent Banff classifications. We aimed to compare peripheral blood lymphocyte (PBL) distribution and infiltrating immune cells in kidney transplant (KT) biopsies presenting MVI (g + ptc ≥ 2) without C4d+ and HLA-DSA, ABMR and normal histology to explore the role of immune cells in these entities.

METHODS

A total of 221 allograft biopsies with ABMR (n = 73), MVI (n = 32) and normal (n = 116) diagnoses were analysed.

RESULTS

MVI patients showed a decrease in the absolute number of T-cells compared with ABMR and normal cases (P = 0.020 and P = 0.006) due to a significant decrease of CD4+ T-cells compared to normal cases (P = 0.013) and a reduction of CD8+ T-cells compared with ABMR (P = 0.029). ABMR and MVI presented a lower absolute number of circulating Natural Killer (NK) cells than normal cases. Immunohistochemistry assessment was performed in 22 ABMR, 13 MVI and 16 normal cases. Glomeruli in ABMR and MVI had more T-cells and CD68+ infiltration than normal biopsies, although TIA1+ was only increased in MVI (P < 0.001), suggesting increased T-cell cytotoxic capacity. Peritubular capillaries displayed more circulating T-cells, CD56+ TIA1+ and CD68+ in ABMR and MVI groups. Contrarily, MVI cases showed mild circulating plasma cell infiltration (CD138+) in peritubular capillaries (P = 0.059) and interstitial aggregates (P = 0.024) compared with ABMR (Figure 1).

CONCLUSION

In conclusion, MVI without HLA-DSA and C4d+ displays decreased circulating T-cell and NK cells, and intense T-cell and NK cell cytotoxic infiltration in the allograft, similar to ABMR. However, the deficiency of plasma cell infiltration in MVI suggests a different underlying stimulus from ABMR.
FC 119: Kidney-Specific Silencing of Neat1 Alleviates Diabetic Kidney Injury
Authors: Xue Rui , Han Yiu Wai , Chi Kam Leung Joseph , Yuk Ying Chan Loretta , Neng Lai Kar , Yao Lan Hui , Tang Sydney
Published: May 2022

BACKGROUND AND AIMS

Long noncoding RNA Nuclear Enriched Abundant Transcript 1 (Neat1) not only serves as a key structural component of nuclear paraspeckle, but is also involved in a variety of pathophysiological processes. Our previous study shows that increased Neat1 expression is closely associated with the pathogenesis of acute kidney injury. Here, we investigate whether Neat1 plays a role in chronic kidney disease and diabetes (DKD).

METHOD

Neat1 expression on kidney biopsies of patients with DKD and other nondiabetic kidney disease was measured by in situ hybridization. Normal portions of kidney tissues removed from nephrectomy specimens for the treatment of renal carcinoma was used as control. In vivo, streptozotocin (STZ)-induced DKD was established in uninephrectomized C57BL/6 mice with low-dose STZ (50 mg/kg) injection for five consecutive days. Mice injected with citrate buffer were used as control. Neat 1 gene was subsequently knocked down in the kidney by shRNA gene silencing via ultrasound-mediated microbubble technique every 2 weeks. All mice were sacrificed at 10 weeks after STZ injection for renal histopathological examination, urine albumin-to-creatinine ratio (UACR) measurement and Neat 1 expression analysis.

RESULTS

Kidney Neat 1 expression was increased significantly in DKD patients compared with control and other kidney diseases (Figure 1). Similarly, Neat1 was induced in STZ-induced diabetic kidneys while its expression was markedly suppressed following shRNA knockdown as confirmed by real-time qPCR (Figure 2A, C and E). Compared with nondiabetic control, diabetic mice presented increased UACR with significant tubular dilatation and atrophy, while knockdown of Neat1 attenuated both proteinuria and kidney injury in the diabetic mice (Figure 2B, D and F).

CONCLUSION

Increased Neat 1 expression contributes to the pathogenesis of DKD and targeting Neat 1 may be a novel and potential therapeutic strategy for diabetic kidney injury.
FC 123: Baseline Characteristics of the Flow Trial Population: Kidney Outcomes Trial With Once-Weekly Semaglutide in People With Type 2 Diabetes and Chronic Kidney Disease
Authors: Perkovic Vlado , Baeres Florian , Bakris George , Bosch-Traberg Heidrun , Idorn Thomas , Mahaffey Kenneth , Mann Johannes , Mersebach Henriette , Rossing Peter , Tuttle Katherine , Pratley Richard
Published: May 2022

BACKGROUND AND AIMS

Chronic kidney disease (CKD) in type 2 diabetes (T2D) is the most common cause of kidney failure. Despite treatment advances, there is still a large unmet need to prevent CKD progression, which can increase the risk for cardiovascular (CV) disease and kidney failure. Glucagon-like peptide-1 receptor agonists (GLP-1RAs) have beneficial effects on glycaemic control and body weight. Some agents have also shown CV benefit and can be used in people with T2D regardless of CKD status (except in end-stage renal disease). CV outcomes trials have suggested that GLP-1RAs may have kidney-protective effects, reducing albuminuria and preserving estimated glomerular filtration rate (eGFR). FLOW (NCT03819153) is a dedicated kidney outcomes trial designed to evaluate the effect of the once-weekly (OW) GLP-1RA semaglutide on major kidney outcomes in subjects with T2D and CKD; we report the blinded baseline characteristics of the FLOW trial population.

METHOD

FLOW is an ongoing randomized, double-blinded, multinational, phase 3b trial in which 3535 subjects with T2D with an eGFR ≥25–≤75 mL/min/1.73 m², and urine albumin-to-creatinine ratio (UACR) >100 to <5000 mg/g were randomly assigned 1:1 to OW semaglutide 1.0 mg or placebo, as add-on to standard-of-care (including maximum labelled/tolerated renin–angiotensin–aldosterone system inhibitors). The primary endpoint is the time to first occurrence of kidney failure (as measured by persistent eGFR <15 mL/min/1.73 m² or initiation of chronic dialysis or kidney transplantation); ≥50% persistent eGFR reduction compared with baseline; and kidney or CV death.

RESULTS

Baseline characteristics from FLOW are shown in the Table 1. Overall, mean eGFR at baseline was 47.0 mL/min/1.73 m2 with 79.6% of subjects having an eGFR of <60 mL/min/1.73 m2. Median UACR at baseline was 567 mg/g, and 68.5% of subjects had macroalbuminuria (≥300 mg/g). According to Kidney Disease: Improving Global Outcomes categories, 24.8% of subjects were classified as high risk and 68.2% of subjects were classified as very high risk for CKD progression (Figure 1).

CONCLUSION

The FLOW trial will evaluate the efficacy and safety of semaglutide on kidney outcomes in subjects with T2D and high risk of kidney disease progression, a group for which additional therapies are urgently required.
FC 124: Real-World Use of Once-Weekly Semaglutide by Baseline Estimated Glomerular Filtration Rate—A Post-Hoc Analysis of Pooled Data From the Sure Studies (Canada, Denmark/Sweden, Switzerland and UK)
Authors: Rudofsky Gottfried , Catarig Andrei-Mircea , Erhan Umut , Jain Rashmi , Tang Knudsen Søren , Saravanan Ponnusamy , Yale Jean-François
Published: May 2022

BACKGROUND AND AIMS

The SURE programme of observational real-world studies is investigating once-weekly (OW) subcutaneous semaglutide in routine clinical practice across a diverse type 2 diabetes (T2D) patient population, including those with chronic kidney disease. This pooled post-hoc analysis of SURE Canada, Denmark/Sweden, Switzerland and UK evaluated OW semaglutide use and outcomes according to kidney function at semaglutide initiation.

METHOD

The SURE studies (all ∼30 weeks’ duration) enrolled adults (≥18 years) with T2D who received OW semaglutide and other anti-hyperglycaemic drugs prescribed at physician discretion; pooled data were analysed to determine change from baseline to end of study (EOS) in HbA1c and body weight (BW) by estimated glomerular function rate (eGFR) subgroups (<30, 30 to <45,  45 to <60,  60 to <90,  and ≥90 mL/min/1.73 m2). Safety outcomes were assessed; only serious adverse drug reactions (SADRs) were systematically recorded.

RESULTS

Data from 913 patients with median (interquartile range) age of 61 (54–68) years and T2D duration of 11.0 (6.2–17.2) years were included. Patients with eGFR <45 mL/min/1.73 m2 were more likely to be older with longer T2D duration than those with eGFR ≥45 mL/min/1.73 m2. Patients with low eGFR were more likely to be receiving insulin at baseline than those in higher eGFR subgroups. At EOS, there were significant reductions in HbA1c and BW in all subgroups with eGFR ≥30 mL/min/1.73 m2 (P <0.0001; Figure 1). The rates of SADRs and adverse events leading to treatment discontinuation were low across all eGFR subgroups (≤0.3% and ≤1.8%, respectively). Overall, 50/72 patients who experienced more than or equal to severe or documented hypoglycaemic episode were receiving insulin at baseline.

CONCLUSION

OW semaglutide provided clinically relevant glycaemic control and BW improvements, and was well tolerated, in patients with varying degrees of kidney impairment at treatment initiation in a real-world setting. These findings support semaglutide use in routine clinical practice regardless of patients’ kidney function.
FC 125: Comparative Effectiveness of Dipeptidyl Peptidase-4 Inhibitors versus Sulfonylureas in Addition to Metformin: A Population-Based Cohort Study of Patients With Diabetes
Authors: Wu Hon-Yen , Wang Jui , Chien Kuo-Liong
Published: May 2022

BACKGROUND AND AIMS

Effects of dipeptidyl peptidase-4 inhibitors (DPP4i) versus sulfonylureas (SU) in addition to metformin remain controversial in patients with type 2 diabetes. Some studies have shown that DPP4i provided cardioprotective effects, but some have reported that DPP4i showed neutral effects on cardiovascular outcomes. In addition, randomized clinical trials have reported inconsistent effects on heart failure among different types of DPP4i. This study aimed to clarify the conflicting cardiovascular effects of DPP4i and examine whether class effects exist among different types of DPP4i.

METHOD

We conducted a nationwide cohort study using claims data from the National Health Insurance in Taiwan from 2007 to 2013. We enrolled type 2 diabetes patients who received DPP4i or SU in addition to metformin. Participants who received DPP4i for at least three consecutive months were categorized as DPP4i users, and those who received SU for at least three consecutive months were categorized as SU users. DPP4i users were matched to SU users using propensity scores at a ratio of 1:1. The study outcomes were hospitalization for major adverse cardiovascular events (MACEs), heart failure, acute myocardial infarction, cerebrovascular disease, coronary revascularization and hypoglycemia. Univariate and multivariate Cox proportional hazards models were used to estimate the hazard ratios (HRs) and 95% confidence intervals (95% CIs) for study outcomes comparing DPP4i with SU.

RESULTS

There were 37 317 matched pairs of DPP4i and SU users with a mean follow-up of 2.1 years. Compared with SU users, DPP4i users showed a significantly lower risk of hospitalization for MACE (HR 0.79, 95% CI 0.75–0.82), heart failure (HR 0.86, 95% CI 0.79–0.93), acute myocardial infarction (HR 0.79, 95% CI 0.68–0.92) and cerebrovascular disease (HR 0.72, 95% CI 0.67–0.77) (Table 1). Both sitagliptin and vildagliptin showed significantly lower risks of hospitalization for MACE (sitagliptin: adjusted HR 0.89, 95% CI 0.85–0.94; vildagliptin: adjusted HR 0.77, 95% CI 0.60–0.99) and cerebrovascular disease (sitagliptin: adjusted HR 0.81, 95% CI 0.75–0.88; vildagliptin: adjusted HR 0.64, 95% CI 0.44–0.92) (Figure 1). All three types of DPP4i users showed a significantly lower risk of hospitalization for hypoglycemia (sitagliptin: adjusted HR 0.45, 95% CI 0.39–0.52; vildagliptin: adjusted HR 0.22, 95% CI 0.09–0.52; saxagliptin: adjusted HR 0.38, 95% CI 0.17–0.83), but saxagliptin showed a borderline significantly higher risk of hospitalization for heart failure (HR 1.59, 95% CI 1.00–2.55).

CONCLUSION

DPP4i showed better protective effects than SU in outcomes of MACE, heart failure, acute myocardial infarction, cerebrovascular disease and hypoglycemia. Sitagliptin and vildagliptin showed more prominent protective effects. Compared with SU, all three types of DPP4i lowered the risk of hypoglycemia in patients with type 2 diabetes.
MO085: 10-Year Clinical Events Avoided in Diabetic and Chronic Kidney Disease Hypertension Patients Treated With Radiofrequency Renal Denervation: Projections Based on 3-Year Data From the Global Symplicity Registry
Authors: Schmieder Roland E , Cao Khoa , Esler Murray , Kandzari David , Lobo Melvin , Sharp Andrew , Mancia Giuseppe , Böhm Michael , Pietzch Jan
Published: May 2022

BACKGROUND AND AIMS

Clinical event rates over 3 years have been published for patients with uncontrolled hypertension treated with radiofrequency renal denervation (RDN) in the Global SYMPLICITY Registry (GSR). We estimated 10-year clinical event reductions following RDN versus a simulated control group without RDN, for the type 2 diabetes (T2DM) and chronic kidney disease (CKD) subgroups and the full GSR cohort.

METHOD

A Markov model based on Framingham and other multivariate risk equations [1] was used to compare projected 10-year clinical events [stroke, myocardial infarction (MI), cardiovascular death (CVD), heart failure (HF), all-cause death (ACD) and a composite of major adverse cardiac events (MACE, calculated as sum of stroke, MI and CVD)] for RDN patients versus a hypothetical control for the T2DM subgroup (n = 1007; 64 ± 10 years), the CKD subgroup (n = 630; 65 ± 12 years), and for all GSR patients (n = 2651; 61 ± 12 years). The simulated control assumed maintenance of baseline office systolic blood pressure (oSBP) over time. The model was calibrated to 3-year stroke and MI events reported in the GSR and used published meta-regression data [2] to calculate risk reduction based on cohort-specific changes in oSBP from baseline. Relative risks (RRs), events avoided, and numbers needed to treat (NNTs) were calculated at 3 and 10 years, along with the ratio of 10- versus 3-year projected events avoided.

RESULTS

Ten-year MACE rates were 35.8% versus 48.5% (-12.7%, RR = 0.74) for RDN versus simulated control for all patients, 40.5% versus 54.0% (-13.5%, RR = 0.75) for the T2DM subgroup and 48.4% versus 61.3% (-12.9%, RR = 0.79) for the CKD subgroup. Across the studied subgroups, avoided stroke events contributed the most to overall event reductions. RRs of events were lowest for HF (0.53–0.61) and highest for all-cause death (0.88–0.90) across the three subgroups (Table 1). Ten-year NNTs for MACE were comparable between the three cohorts, estimated between 7 and 8. The ratio of 10- versus 3-year events avoided ranged from 4.44 to 4.87 for stroke, 3.74 to 3.96 for MI and 4.22 to 5.20 for MACE across studied cohorts.

CONCLUSION

Based on 10-year model projections from the GSR, RDN may lead to meaningful clinical event reductions in diabetic and chronic kidney disease patients. Ten-year events avoided can be expected to be 3 to 5 times higher than those recently reported for a 3-year horizon.
MO086: Sex Differences in Ambulatory Blood Pressure Trajectories and Blood Pressure Variability in Hemodialysis Patients
Authors: Theodorakopoulou Marieta , Karagiannidis Artemios , Eleni Alexandrou Maria , Pella Eva , Karpetas Antonios , Baksiova Afroditi , Tsouchnikas Ioannis , Papagianni Aikaterini , Sarafidis Pantelis
Published: May 2022

BACKGROUND AND AIMS

Ambulatory blood pressure (BP) control is worse in men than in women with chronic kidney disease (CKD), and this may partially explain the faster CKD progression in men. The aim of this study is to investigate possible sex-differences in ambulatory BP levels, BP trajectories and BP variability (BPV) in hemodialysis patients.

METHOD

129 male and 91 female hemodialysis patients that underwent 48-h ABPM with Mobil-O-Graph-NG were included in this analysis. Ambulatory BP levels over the 2-day interdialytic interval (including two daytime and two nighttime periods) were recorded. We calculated the standard deviation (SD), weighted SD (wSD), coefficient of variation (CV) and average real variability (ARV) of BP with validated formulas.

RESULTS

Age, dialysis vintage, antihypertensive treatment and history of major comorbidities did not differ between men and women. Pre-dialysis SBP levels did not differ between men and women (145.1 ± 22.7 versus 145.9 ± 25.7 mmHg, P = 0.808), but DBP was marginally higher in men (87.6 ± 14.0 versus 84.0 ± 13.7 mmHg, P =0.055). About 48-h SBP/DBP (137.2 ± 17.4/81.9 ± 12.1 mmHg versus 132.2 ± 19.2/75.9 ± 11.7 mmHg, P = 0.045/<0.001) as well as DBP during the first and SBP/DBP during the second 24-h period were significantly higher in men than in women. Similarly, daytime SBP/DBP was significantly higher in men (138.3 ± 17.5/83.2 ± 12.3 mmHg versus 131.9 ± 19.4/76.4 ± 11.5 mmHg, P = 0.011/<0.001). No significant between-group differences were detected for nighttime SBP. All SBP variability indices were similar between men and women; DBP-SD, DBP-wSD and DBP-ARV were higher in men (44-h DBP-ARV 9.4 ± 1.8 versus 8.6 ± 1.9, P = 0.002). No significant differences were revealed in the dipping pattern between men and women.

CONCLUSION

Ambulatory BP levels and trajectories, as well as DBP variability indices are higher in men than women hemodialysis patients. This worse ambulatory BP profile in male compared to female patients may impact on the incidence of cardiovascular events.
MO089: Comparison of Ambulatory Central Hemodynamics and Arterial Stiffness in Hemodialysis Patients With And Without Intradialytic Hypertension
Authors: Theodorakopoulou Marieta , Eleni Alexandrou Maria , Iatridi Foteini , Faitatzidou Danai , Karpetas Antonios , Bikos Athanasios , Papagianni Aikaterini , Sarafidis Pantelis
Published: May 2022

BACKGROUND AND AIMS

Increased arterial stiffness is suggested to be involved in the pathogenesis of intradialytic hypertension (IDH). Ambulatory pulse wave velocity (PWV) is an independent predictor for all-cause-mortality in hemodialysis patients and its prognostic power is better than office PWV. This is the first study comparing ambulatory central blood pressure (BP) and arterial stiffness parameters between patients with and without IDH.

METHOD

This study examined 45 patients with IDH (defined as: SBP rise ≥ 10 mmHg from pre- to post-dialysis and post-dialysis SBP ≥ 150 mmHg) in comparison 197 without IDH. All participants underwent 48-h ABPM with the Mobil-O-Graph-NG device; parameters of central hemodynamics [central systolic (cSBP) and diastolic BP (cDBP), pulse pressure (PP)], wave reflection [augmentation index (AIx) and pressure (AP)] and PWV were estimated.

RESULTS

Age, dialysis vintage, interdialytic weight gain and prevalence of major comorbidities did not differ between the two study groups. Patients with IDH had higher 44-h cSBP (131.6 ± 16.7 versus 119.3 ± 15.6, P < 0.001), 44-h cDBP (86.4 ± 12.8 versus 79.3 ± 11.7, P < 0.001) and 44-h cPP (45.7 ± 10.7 versus 40.3 ± 10.3, P = 0.002) levels compared with patients without IDH. Similarly, during day- and nighttime periods, cSBP/cDBP and cPP levels were higher in IDH patients compared with non-IDH. 44-h augmentation pressure and index, but not AIx(75) were higher in patients with IDH than those without IDH. 44-h PWV (10.0 ± 2.0 vs. 9.2 ± 2.1 m/s, P = 0.020) was significantly higher in patients with IDH.

CONCLUSION

Patients with IDH have higher ambulatory central BP and increased arterial stiffness, as indicated by higher ambulatory cPP and PWV. Increased arterial stiffness could be a prominent factor associated with the high burden of cardiovascular disease in this population.
MO362: Braunschweig Body Composition, Butterfly Sonography and Drug Dosing in AKI Study (B3 D2 AKI––Study)
Authors: Jasbutis Kim , Drescher Julia , Hansen-Hagge Christian , Borchina Dan N , Diedrich Ulrike , Kielstein Jan T
Published: May 2022

BACKGROUND AND AIMS

In-hospital AKI is associated with increased morbidity and mortality. AKI Alert systems are frequently used to allow time detection of AKI patients based on changes in creatinine. We aimed to examine the hydration status, medication errors and prior existing CKD in a series of AKI 3 patients in a tertiary care hospital.

METHOD

Prospective single centre cohort study. Study was approved by the local IRB. Hydration status was assessed by Bioimpedance using the body composition monitor (Fresenius Medical Care). Renal size and exclusion of postrenal failure were accomplished using a point of care ultrasound system (Butterfly Network Inc.). Pharmacotherapy was entered into the Federal Medication Plan of Germany (Bundesmedikationsplan).

RESULTS

A total of 101 patients with AKI 3 were identified based on changes in creatinine only. The median (IQR) age was 74.0 (64.7–82.0) years with a BMI of 27.8 (23.5–34.2) kg/m2. The baseline creatinine of the patients was 1.53 (0.92–2.85) mg/dL. At the time of AKI 3 diagnosis the median [IQR] 4.1 (1.9–5.9) L. Systolic blood pressure was 116 (100–140) mmHg (Fig. 1). Median (IQR) kidney length was 10.4 (9.2–11.7) cm.

Polypharmacy (> 5 drugs) was seen in 89.7% of all patients. Almost half of the patients (48.3%) received 10 or more drugs. A total of 38% of patients receiving an antibiotic received an inadequately high dose, followed by 7.8% receiving an inadequate dosing of oral antidiabetic drugs.

CONCLUSION

Patients detected by an AKI alert in a tertiary care hospital did mostly neither exhibit low blood pressure nor volume depletion. Postrenal AKI was undetected in 1 out of 101 patients. Medication dosing errors were frequently seen, especially in the dosing of antibiotics. A joined nephron-pharmacological approach seems to be important in patients with hospital acquired AKI 3.
Transitional care models in adolescent kidney transplant recipients—a systematic review
Authors: Wildes Dermot Michael , Costigan Caoimhe S , Kinlough Mairead , Flynn Joan , Dolan Niamh , Riordan Michael , Sweeney Clodagh , Stack Maria , Waldron Mary , Walsh Orla , Gorman Kathleen M , Awan Atif
Published: May 2022

Background

Adolescence is a time of significant change for patients, guardians and clinicians. The paediatrician must ensure patients develop the necessary skills and knowledge required to transition and to function as an independent entity, with autonomy over their own care. The transfer from paediatric to adult care carries an increased risk of graft-related complications attributable to a multitude of reasons, particularly non-adherence to immunosuppressive medicines and poor attendance at scheduled appointments. This systematic review was conducted to ascertain the transitional care models available to clinicians caring for kidney transplant recipients and to compare the approach in each respective case.

Methods

A systematic review was performed, in a methodology outlined by the PRISMA guidelines. OVID MEDLINE and EMBASE databases were searched for studies that outlined valid, replicable models pertaining to transitional care of paediatric kidney transplant recipients between 1946 and Quarter 3 of 2021. The reference lists of selected articles were also perused for further eligible studies and experts in the field were consulted for further eligible articles. Two investigators assessed all studies for eligibility and independently performed data extraction. Any discrepancies were settled by consensus.

Results

A total of 1121 abstracts were identified, which was reduced to 1029 upon removal of duplicates. A total of 51 articles were deemed appropriate for full-text review and critical appraisal. A total of 12 articles that described models for transition pertaining to kidney transplant patients were included in qualitative synthesis. Every paper utilized a different transition model. All but one model included a physician and nurse at minimum in the transition process. The involvement of adult nephrologists, medical social work, psychology and psychiatry was variable. The mean age for the initiation of transition was 13.4 years (range: 10–17.5 years). The mean age at transfer to adult services was 18.3 years (range: 16–20.5 years).

Conclusions

Despite the well-established need for good transitional care for paediatric solid-organ transplant recipients, models tailored specifically for kidney transplant recipients are lacking. Further research and validation studies are required to ascertain the best method of providing effective transitional care to these patients. Transitional care should become a standardized process for adolescents and young adults with kidney transplants.
Abnormalities of structural brain connectivity in pediatric brain tumor survivors
Authors: Oyefiade Adeoye , Moxon-Emre Iska , Beera Kiran , Bouffet Eric , Taylor Michael , Ramaswamy Vijay , Laughlin Suzanne , Skocic Jovanka , Mabbott Donald J
Published: May 2022

Background

Pediatric brain tumor survivors are at an increased risk for white matter (WM) injury. However, damage to whole-brain structural connectivity is unelucidated. The impact of treatment on WM connectivity was investigated.

Methods

Whole-brain WM networks were derived from diffusion tensor imaging data acquired for 28 irradiated patients (radiotherapy, RT) (mean age = 13.74 ± 3.32 years), 13 patients not irradiated (No RT) (mean age = 12.57 ± 2.87), and 41 typically developing children (TDC) (mean age = 13.32 ± 2.92 years). Differences in network properties were analyzed using robust regressions.

Results

Participation coefficient was lower in both patient groups (RT: adj. P = .015; No RT: adj. P = .042). Compared to TDC, RT had greater clustering (adj. P = .015), local efficiency (adj. P = .003), and modularity (adj. P = .000003). WM traced from hubs was damaged in patients: left hemisphere pericallosal sulcus (FA [F = 4.97; q < 0.01]; MD [F = 11.02; q < 0.0001]; AD [F = 10.00; q < 0.0001]; RD [F = 8.53; q < 0.0001]), right hemisphere pericallosal sulcus (FA [F = 8.87; q < 0.0001]; RD [F = 8.27; q < 0.001]), and right hemisphere parietooccipital sulcus (MD [F = 5.78; q < 0.05]; RD [F = 5.12; q < 0.05]).

Conclusions

Findings indicate greater segregation of WM networks after RT. Intermodular connectivity was lower after treatment with and without RT. No significant network differences were observed between patient groups. Our results are discussed in the context of a network approach that emphasizes interactions between brain regions.
Clinical outcomes of dose-escalated re-irradiation in patients with recurrent high-grade glioma
Authors: Helis Corbin A , Prim Shih-Ni , Cramer Christina K , Strowd Roy , Lesser Glenn J , White Jaclyn J , Tatter Stephen B , Laxton Adrian W , Whitlow Christopher , Lo Hui-Wen , Debinski Waldemar , Ververs James D , Black Paul J , Chan Michael D
Published: May 2022

Background

Re-irradiation for recurrent gliomas is a controversial treatment option with no clear standard dose or concurrent systemic therapy.

Methods

This series represents a single-institution retrospective review of patients treated with re-irradiation for recurrent high-grade glioma. After 2012, patients were commonly offered concurrent bevacizumab as a cytoprotective agent against radiation necrosis. Kaplan-Meier method was used to estimate overall survival and progression-free survival. Cox proportional hazards regression was used to identify factors associated with overall survival and progression-free survival.

Results

Between 2001 and 2021, 52 patients underwent re-irradiation for a diagnosis of recurrent high-grade glioma. 36 patients (69.2%) had a histologic diagnosis of glioblastoma at the time of re-irradiation. The median BED10 (biological equivalent dose 10 Gy) of re-irradiation was 53.1 Gy. Twenty-one patients (40.4%) received concurrent bevacizumab with re-irradiation. Median survival for the entire cohort and for glioblastoma at the time of recurrence patients was 6.7 months and 6.0 months, respectively. For patients with glioblastoma at the time of recurrence, completing re-irradiation (HR 0.03, P < .001), use of concurrent bevacizumab (HR 0.3, P = .009), and the BED10 (HR 0.9, P = .005) were predictive of overall survival. Nine patients developed grade 3-5 toxicity; of these, 2 received concurrent bevacizumab and 7 did not (P = .15).

Conclusion

High dose re-irradiation with concurrent bevacizumab is feasible in patients with recurrent gliomas. Concurrent bevacizumab and increasing radiation dose may improve survival in patients with recurrent glioblastoma.
Evaluation of an online tool about the expected course of disease for glioblastoma patients—A qualitative study
Authors: van Diest Eva , Oldenmenger Wendy H , Eland Marit , Taal Walter
Published: May 2022

Background

Patients with glioblastoma have a short life-expectancy, with median survival rates of 9 to 12 months. Providing information about the expected course of the disease can be complicated. Therefore, an online tool has been developed. The objective of this tool is to better inform patients and proxies, and decrease their uncertainties and improve their quality of life. This study aims to gather experiences of an initial cohort of patient-proxy dyads, to identify if the tool meets the previously mentioned objectives.

Methods

This is a qualitative study based on thematic analysis. Interviews were conducted with 15 patient-proxy dyads. For these interviews, a combined method of think-aloud sessions and semi-structured interviews were used. Audiotapes of these interviews were transcribed verbatim and thematically analyzed.

Results

The analysis revealed four major themes, namely, unmet information needs, improvement possibilities, effects of the tool and clinical implementation. Participants indicated that this tool could decrease uncertainties and increase their perceived quality of life. Also, they often mentioned that it could have a positive effect on the efficiency and quality of consultations.

Conclusion

Participants considered this tool to be useful and effective in decreasing uncertainties for both patients with glioblastoma and their proxies. Moreover, participants brought up that this tool could positively influence the efficiency and quality of consultations. This could lead to more patient participation and empowerment, and could therefore enhance shared decision making and timely advanced care planning.
Reconfiguration from emergency to urgent elective neurosurgery for glioblastoma patients improves length of stay, surgical adjunct use, and extent of resective surgery
Authors: Sun Rosa , Sharma Shivam , Benghiat Helen , Meade Sara , Sanghera Paul , Bramwell Gregory , Nagaraju Santhosh , Pohl Ute , Dawson Camilla , Petrik Vladimir , Ughratdar Ismail , White Anwen , Zisakis Athanasios , Ramalingam Satheesh , Sawlani Vijay , Watts Colin , Wykes Victoria
Published: May 2022

Background

Glioblastoma (GB) is the most common intrinsic brain cancer and is notorious for its aggressive nature. Despite widespread research and optimization of clinical management, the improvement in overall survival has been limited. The aim of this study was to characterize the impact of service reconfiguration on GB outcomes in a single centre.

Methods

Patients with a histopathological confirmation of a diagnosis of GB between 01/01/2014 and 31/12/2019 were retrospectively identified. Demographic and tumour characteristics, survival, treatment (surgical and oncological), admission status, use of surgical adjunct (5-aminolevulinic acid, intra-operative neuro-monitoring), the length of stay, extent of resection, and surgical complications were recorded from the hospital databases.

Results

From August 2018 the neurosurgical oncology service was reconfigured to manage high-grade tumours on an urgent outpatient basis by surgeons specializing in oncology. We demonstrate that these changes resulted in an increase in elective admissions, greater use of intra-operative adjuncts resulting in the improved extent of tumour resection, and a reduction in median length of stay and associated cost-savings.

Conclusions

Optimizing neuro-oncology patient management through service reconfiguration resulted in increased use of intra-operative adjuncts, improved surgical outcomes, and reduced hospital costs. These changes also have the potential to improve survival and disease-free progression for patients with GB.
Antibiotic Prescribing for Acute Respiratory Illnesses in Persons With HIV Compared With Persons Without HIV
Authors: Keintz Mackenzie R , Abbas Anum , Lyden Elizabeth , Ma Jihyun , Bares Sara H , Van Schooneveld Trevor C , Marcelin Jasmine R
Published: May 2022

Background

Antibiotic overuse increases health care cost and promotes antimicrobial resistance. People with HIV (PWH) who develop acute respiratory infections (ARIs) may be assumed to be “higher risk,” compared with non-PWH, but comparative antibiotic use evaluations have not been performed.

Methods

This observational, single-center study compared antibiotic prescribing in independent clinical encounters for PWH and non-PWH diagnosed with ARI in outpatient clinical practices using International Classification of Diseases, 10th Revision, codes between January 1, 2014, and April 30, 2018. The Fisher exact test compared categorical variables with antibiotic prescribing patterns.

Results

There were 209 patients in the PWH cohort vs 398 patients in the non-PWH cohort. PWH had a median CD4+ count of 610 cells/mm3, with 91% on antiretroviral therapy and 78% virally suppressed. Thirty-seven percent of all visits resulted in an antibiotic prescription, and 89% were inappropriate. Antibiotics were prescribed more frequently in non-PWH (35% PWH vs 40% non-PWH; P = .172) and managed according to guidelines more often in PWH (37% PWH vs 30% non-PWH; P = .039). Antibiotics were prescribed appropriately most frequently in PWH managed by HIV clinicians (29% PWH managed by HIV clinician vs 12% PWH managed by non-HIV clinician vs 8% non-PWH; P = .010). HIV clinicians prescribed antibiotics for a mean duration of 5.9 days vs PWH managed by a non-HIV clinician for 9.1 days vs non-PWH for 7.6 days (P < .0001).

Conclusions

Outpatient antibiotic overuse remains prevalent among patients evaluated for ARI. We found less frequent inappropriate antibiotic use in PWH. Prescriber specialty, rather than HIV diagnosis, was related to appropriateness of antimicrobial prescribing.
Serotonin facilitates late-associative plasticity via synaptic tagging/cross-tagging and capture at hippocampal CA2 synapses in male rats
Authors: Benoy Amrita , Wong Lik-Wei , Ather Niha , Sajikumar Sreedharan
Published: May 2022

Synaptic plasticity in the hippocampal Cornu Ammonis (CA) subfield, CA2, is tightly regulated. However, CA2 receives projections from several extra-hippocampal modulatory nuclei that release modulators that could serve to fine-tune plasticity at CA2 synapses. Considering that there are afferent projections from the serotonergic median raphe to hippocampal CA2, we hypothesized that the neuromodulator serotonin (5-hydroxytryptamine; 5-HT) could modulate CA2 synaptic plasticity. Here, we show that bath-application of serotonin facilitates the persistence of long-term depression (LTD) at the CA3 Schaffer collateral inputs to CA2 neurons (SC-CA2) when coupled to a weak low frequency electrical stimulation, in acute rat hippocampal slices. The observed late-LTD at SC-CA2 synapses was protein synthesis- and N-methyl-D-aspartate receptor (NMDAR)-dependent. Moreover, this late-LTD at SC-CA2 synapses paves way for the associative persistence of transient forms of LTD as well as long-term potentiation to long-lasting late forms of plasticity through synaptic tagging and cross-tagging respectively, at the entorhinal cortical synapses of CA2. We further observe that the 5-HT-mediated persistence of activity-dependent LTD at SC-CA2 synapses is blocked in the presence of the brain-derived neurotrophic factor scavenger, TrkB/Fc.