bluuebunny/crossref_metadata_2025_split huggingface dataset:
#4482 PREGNANCY AND RENAL OUTCOMES IN WOMEN WITH CHRONIC KIDNEY DISEASE: A POPULATION STUDY
Authors: Ralston Elizabeth , Wang Yanzhong , Farmer Chris , Childs Steve , Akolekar Ranjit , Bramham Kate 
Published: June 2023

Abstract

Background and Aims
Women with CKD stages 3-5 are at higher risk of adverse pregnancy outcomes, including preterm delivery and low birthweight and progression of kidney disease. However, data describing outcomes of women with less severe kidney disease are limited, and few compare with women normal renal function. Furthermore, most studies report cohorts recruited from specialist clinics and may not be representative. This study aimed to describe pregnancy outcomes in a UK population cohort according to pre-conception eGFR &lt;90 ml/min/1.73 m2 compared with women with eGFR ≥90 ml/min/1.73 m2.

Method
Routinely collected pregnancy data from three NHS Trust hospitals in Kent (UK) between 2010 and 2020 were extracted with Research Ethics Committee approval (19/LO/1242 and 18/SC/0158). Local laboratory and clinical data were linked to identify women with eGFR measured within two years of conception. Women without preconception creatinine were excluded from analysis. Baseline characteristics were described and comparisons between eGFR and adverse pregnancy and renal outcomes were tested.

Results
A total of 14,243 pregnancies with confirmed pre-pregnancy creatinine were included, of which 1,405/14,243 (9.9%) had CKD stages 1-4 (stage 1: 221/14,243 (1.6%), stage 2: 1,170/14,243 (8.2%), stage 3: 12/14,243 (0.1%), stage 4: 2/14,243 (0.01%) (Table 1). Women with pre-pregnancy eGFR 60-89 ml/min/1.73 m2 (stage 2) were significantly older at conception than women without CKD (eGFR ≥90 ml/min/1.73 m2) but there were no significant differences in live birth rates, small for gestational age, gestation at delivery, and preterm birth. In pregnancies with CKD (1,405, stages 1-4), pre-pregnancy eGFR was weakly correlated with birthweight (rs = 0.05, p = 0.05), and gestational age (rs = 0.06, p = 0.05).

Conclusion
To our knowledge, this is the largest population cohort to describe pregnancy outcomes between women with eGFR 60-89 ml/min/1.73 m2 compared with eGFR ≥90 ml/min/1.73 m2. Women with eGFR 60-89 ml/min/1.73 m2 did not have worse renal or pregnancy outcomes compared to eGFR ≥90 ml/min/1.73 m2. Limitations include lack of proteinuria data and details of structural CKD (Class 1 CKD), and only one eGFR measurement prior to pregnancy may have led to some women with temporary reduction in function being included in the cohort. Overall, the findings suggest that women with eGFR 60-89 ml/min/1.73 m2 should not be discouraged from pregnancy.
#4484 EFFECT OF BROCCOLI SPROUT EXTRACT IN PATIENTS WITH TYPE 2 DIABETES AND CHRONIC KIDNEY DISEASE (INITIATE) - DESIGN AND BASELINE DATA
Authors: Avesani Carla Maria , Swartling Oskar , Svensson Maria Eriksson , Heimbürger Olof , Lundberg Sigrid , Guron Gregor , Jonsson P Andreas , Segelmark Marten , Evans Marie , Stenvinkel Peter 
Published: June 2023

Abstract

Background and Aims
In advanced stages of chronic kidney disease (CKD) some glucose-lowering agents, such as metformin, cannot be prescribed to patients with type 2 diabetes (T2D) due to the risk of accumulation and adverse events. Foods with bioactive components, “functional food”, can be an alternative to mitigate the metabolic disturbances in these patients. Previous research on experimental animals and patients with T2D has shown that sulforaphane, present in broccoli sprouts, improves insulin sensitivity and glucose control. We hypothesize that sulforaphane ingested as a broccoli sprout extract (BSE) can improve glucose control in patients with T2D and CKD.

Method
This is an ongoing multicentre randomized double-blinded controlled trial with glucose control as the primary outcome. Glucose control is evaluated by fasting serum glucose, serum insulin in all patients, and oral glucose tolerance test (OGTT) in patients not on insulin treatment. Moreover, as a secondary aim, we investigate the role of BSE in improving other signs of metabolic alterations, including oxidative stress, proteinuria, inflammation and production of uremic toxins from the gut microbiota. Patients: Adult patients with T2D and CKD (eGFR 15- 45 ml/min/1.73m2) are included and randomized 1:1 to receive BSE or placebo. Both groups are followed for 20 weeks. The first 12 weeks, patients receive BSE or placebo and are then followed for 8 weeks. Patients randomized to BSE receive an increasing dose of sulforaphane administered as BSE (Lantmännen®) starting with 50 µmmol/day in week 0 - 4; 100 µmmol/day in week 5 - 8 and 150 µmmol/day in week 9 - 12. The placebo consists of maltodextrin sprayed with copper-chlorophyllin. Blood and urine laboratory measurements and OGTT is performed at week 0, 12 and 20. Randomization is done using a computer-based block randomization algorithm. The protocol is registered at clinicaltrials.gov (NCT04858854).

Results
98 patients with T2D and CKD from 12 centers in Sweden were included and the recruiting phase has now been finalized but the follow up phase is still ongoing. We here present baseline characteristics of all study participants (Table 1). Median age is 75 years and a minority are women. Mean eGFR corresponds to CKD stage 4 and there are large variations in albumin/creatinine ratios. Most participants are on a combination of oral glucose-lowering agents and insulin. A history of cardiovascular disease is common, and 21% had a previously had myocardial infarction.

Conclusion
We are currently conducting a randomized clinical trial testing if BSE can be used as an alternative or add-on to improve glucose control in patients with T2D and CKD stages 3-4 type and to see if this ‘high risk’ patient group could benefit from treatment with BSE.
#4486 VALIDATION OF A CKD PROGRESSION RISK PREDICTION MODEL IN THE FIDELITY TRIAL POPULATION
Authors: Tangri Navdeep , Ferguson Thomas , Leon-Mantilla Silvia , Anker Stefan D , Pitt Bertram , Rossing Peter , Ruilope Luis , Farjat Alfredo , Farag Youssef , Lawatscheck Robert , Rohwedder Katja , Bakris George 
Published: June 2023

Abstract

Background and Aims
Chronic kidney disease (CKD) is often underrecognised until later stages when most of the kidney function is lost and the therapeutic window for disease-modifying therapy is narrow [1]. We previously developed a lab-based risk prediction model to accurately predict CKD progression in adults at all stages of CKD [2]. Here, we describe a validation of our model in the clinical trial population of FIDELITY, a prespecified pooled analysis of the phase III FIDELIO-DKD (NCT02540993) and FIGARO-DKD (NCT02545049) trials for the nonsteroidal mineralocorticoid receptor antagonist finerenone [3].

Method
We performed a post hoc analysis of all participants from the FIDELITY database, irrespective of estimated glomerular filtration rate (eGFR) or albuminuria stage. Baseline values for the underlying laboratory tests required for the model, Klinrisk, were extracted from the complete blood count, comprehensive metabolic panel and urine albumin-to-creatinine ratio (UACR). The predicted outcome was a ≥40% decline in eGFR or kidney failure. We calculated discrimination ability of the model and calibration using area under the curve (AUC), Brier scores and calibration plots in the overall population, and stratified by treatment assignment. Sensitivity analyses examined the accuracy of the models in predicting ≥57% decline in eGFR, as well as the change in risk score over time. Kidney Disease: Improving Global Outcomes (KDIGO) heat map categories were used as the reference standard.

Results
We included 13,026 participants with a mean age of 64.8 ± 9.5 years, mean eGFR of 57.6 ± 21.7 ml/min/1.73 m2, and median UACR of 58.2 mg/mmol (interquartile range 22.4–129.6). At time horizons of 2 and 4 years, 984 and 1795 patients experienced a primary outcome event, respectively. The Klinrisk model predicted progression accurately, with an AUC of 0.81 (95% confidence interval [CI] 0.79–0.82) at 2 years and 0.86 (95% CI 0.84–0.87) at 4 years, compared with the KDIGO heatmap categories (AUC of 0.59 [95% CI 0.58–0.60] at 2 years and 0.66 [95% CI 0.65–0.68] at 4 years). Calibration was appropriate (Brier score of 0.067 [95% CI 0.064–0.070] at 2 years and 0.115 [95% CI 0.109–0.120] at 4 years). Similar discrimination accuracy was seen for the ≥57% decline outcome (C-statistic 0.88, 95% CI 0.87–0.90) at 3 years.

Conclusion
Based on routinely collected lab data, our machine learning model (Klinrisk) accurately predicts CKD progression events in a well characterized global clinical trial population. Prospective implementation of the model in clinical trial enrolment as well as clinical care pathways is needed.
#4489 EFFECT OF RENAL ARTERY CALCIFICATION ON THE OCCURRENCE OF ACUTE KIDNEY INJURY AND MORTALITY
Authors: Jeon Hae Eun , Kwon Soie , Hwang Jin Ho 
Published: June 2023

Abstract

Background and Aims
Renal artery stenosis not only causes secondary hypertension and drug-resistant hypertension by enhancing renin-angiotensin-aldosterone system (RAAS), but also causes ischemic acute/chronic kidney injury by impeding blood flow to the kidneys. Renal artery calcification (RAC) suggests chronic severe atherosclerotic changes, but the relationship between its severity and clinical prognosis has not been established.

Method
This study was conducted on subjects aged 60 years or older who had serum creatinine measured more than 3 times among patients prescribed and performed abdominal CT at Chung-Ang University Hospital from January 1, 2005 to February 28, 2020. The renal artery calcification score (RACS) was obtained by Agatston score measurement, and the incidence of AKI and mortality were compared between the groups.

Results
Of a total of 29,410 patients, 17,478 had no RAC and 11,932 was RAC (+). The median value of the group in which RACS was measured was 117.8. The prevalence and history of diabetes mellitus (DM), hypertension, dyslipidemia, and history of cardiovascular disease were significantly higher in the RAC (+) group, lower eGFR and higher proteinuria, and higher prescribing rates of ARB or ACEi, spironolactone, and statin. In the group of RAC (+), the incidence of AKI (HR 1.231, CI 1.174-1.292, P&lt;0.001, Figure1) and all-cause mortality (HR 1.265, CI 1.182-1.355, P&lt;0.001) was high. Regardless of DM or RACS, the risk of AKI was higher in those who were prescribed ACEi or ARB (HR 1.786, CI 1.7-1.875, P&lt;0.001). In patients with DM, mortality risk was reduced in those taking ACEi or ARB regardless of the presence of RACS (HR 0.759, CI 0.645-0.892, P&lt;0.001).

Conclusion
RAC(+) was associated with higher AKI and mortality risk than RAC(-). The use of RAAS blockades increased the risk of AKI regardless of the presence of RAC, but reduced mortality in patients with DM regardless of the presence or absence of RACS.
#4516 CLINICAL CHARACTERISTICS OF PATIENTS WITH LUPUS NEPHRITIS CLASS III–V: ANALYSIS OF INTERNATIONAL REAL-WORLD DATA
Authors: Anderson Seth , Delgado Ana , He Xin , Tang Zhiliu , Milligan Jack , Bracher Marguerite 
Published: June 2023

Abstract

Background and Aims
Lupus nephritis (LN) is a severe renal manifestation of systemic lupus erythematosus (SLE) that negatively impacts morbidity and mortality; however, real-world data for LN is scarce. This study describes: the proportion of patients with SLE managed by rheumatologists (rheum-managed) and by nephrologists (neph-managed) with LN class III–V; the proportion of patients with a Safety of Estrogens in Lupus Erythematosus National Assessment - SLE Disease Activity Index (SELENA-SLEDAI) score ≥8 by region; extra-renal organ systems involvement by region; flaring by region; and EQ-5D and EQ-visual analogue scale (VAS) scores by estimated glomerular filtration rate (eGFR).

Method
Data were drawn from the Adelphi Lupus Disease Specific Programme, a cross-sectional, multi-subscriber survey of physicians and their consulting patients conducted April 2021–May 2022 in China, Japan, EU5 (France, Germany, Italy, Spain and the UK) and the USA. Physicians provided demographic and clinical data for 5–6 consecutive adult patients consulting for SLE/LN. LN class III–V was assessed by the physician at data collection. SELENA-SLEDAI scores were derived by physician assessment of patients’ current clinical manifestations. Patients had the opportunity to complete an EQ-5D form. All analyses were descriptive.

Results
Overall, 9% (183/2148) of rheum- and 48% (364/766) of neph-managed patients had LN. Most patients with LN had a SELENA-SLEDAI score ≥8 (70% of rheum- and 76% of neph-managed; Table 1), compared with 48% (1032/2148) of rheum-managed patients with SLE alone. The proportion of neph-managed patients with LN with a SELENA-SLEDAI score ≥8 varied by region, from 58% in the USA to 87% in China. In total, 62% of rheum- and 43% of neph-managed patients with LN had ever flared (any organ system; Table 1). The proportion of rheum-managed patients with LN who had ever flared ranged from 52% in China + Japan to 75% in EU5. The proportion of patients with LN currently experiencing a flare was similar between rheum- (31%) and neph-managed (35%) patients, but varied by region, with the highest proportion for rheum-managed patients in China (59%) and lowest in the USA (18%). In subgroups with ≥15 patients, EQ-5D and EQ-VAS scores generally worsened as eGFR lowered (Figure 1).

Conclusion
Patients with LN class III–V had high disease burden (SELENA-SLEDAI scores ≥8) and flaring that varied by region, suggesting a need for more efficacious treatments for patients with LN.
#4589 HYPOCHLOREMIA AS A MARKER OF ALL-CAUSE MORTALITY AND UNPLANNED DIALYSIS STARTS IN A COHORT OF ACUTE KIDNEY INJURY: A 4-YEAR FOLLOW-UP STUDY
Authors: García Daniela Medina , Amado Ernesto Francisco Valga , Monzon Tania , D'orazio Yuliana Stefania Daruiz , Quintana Cristo Adonay Santana , Perez Patricia 
Published: June 2023

Abstract

Background and Aims
Serum chloride is an emerging marker of mortality in patients with hypertension, heart failure, sepsis, and chronic kidney disease. The relationship between hyperchloremia and acute kidney injury is well known, especially in critically ill patients. However, the role of baseline hypochloremia in the prognosis of hospitalized patients with acute kidney injury (AKI) remains poorly understood.

Method
Retrospective cohort type study. We included n=243 patients with AKI stage 3 from consultations received by the nephrology department of our hospital between January 1, 2017, to December 31, 2017. The sample was divided into two groups considering baseline serum chloride (Cl−) levels. Hypochloremia was considered if Cl−&lt; 98 mEq/L. The primary endpoint was a composite variable for unplanned dialysis starts and all-cause mortality.

Results
The mean age was 68 years. Females accounted for 39.5%. The mean baseline sodium was 137±7.2 mEq/l, and the mean baseline chloride was 98.9±7.05 mEq/l (Table 1). The mean follow-up of the patients was 21±19.61 months. The incidence of the primary endpoint was n=166 (68.3%). 148 (60.9%) died, of whom 78 (32%) died during their hospital stay. The causes of death were: 30.6% cardiovascular, 12.9% tumor, 44.7% infectious, and 11.8% other. Kaplan-Meier estimates showed lower survival rates in patients with chloride levels below 98 mEq/l (p=0.006, log-rank test) (Figure 1).

Conclusion
Patients with AKI stage 3 with lower baseline chloride levels (&lt;98 mEq/L) were more likely to have higher overall mortality and unplanned dialysis starts.
#4645 HISTONE LACTYLATION ENHANCES PERITONEAL FIBROSIS BY INDUCING PERITONEAL MESOTHELIAL CELL SENESCENCE
Authors: Yu Fang , Wang Xiaoyue , Cai Qingli , He Yani , Chen Kehong 
Published: June 2023

Abstract

Background and Aims
Peritoneal fibrosis (PF) is a serious complication limiting the application of peritoneal dialysis (PD). Histone lactylation has recently been found to increase with glycolysis and intracellular lactate levels, thereby mediating chronic organ damage. This study investigated the role and mechanism of histone lactylation in high glucose peritoneal dialysate-induced peritoneal fibrosis in mice.

Method
The PF mouse model induced by high glucose peritoneal dialysate was constructed by daily intraperitoneal injection of 4.25% glucose peritoneal dialysate combined with 40 mM Methylglyoxal for 2 weeks. We also used a lactylation enhancer (rotenone) and a lactylation inhibitor (oxamate) to validate the effects of histone lactylation in vivo and in vitro. The parietal peritoneum samples and cultured peritoneal mesothelial cells in various groups were analyzed for evidence of senescence, fibrosis, glycolysis, and histone lactylation levels. In addition, we generated DcR2 knockout mice to further verify the effects of histone lactylation on peritoneal mesothelial cell (PMCs) senescence by clearing senescent cells.

Results
In the PF group, the results of Masson staining and immunohistochemistry revealed increased peritoneal thickness and expression of fibrosis markers (α-SMA, Collagen I, and Fibronectin) and senescence markers (P16, P21, and DcR2) compared to the control group. We found that lactate and glycolysis levels were significantly higher in the PF group compared to the control group, and further immunoprecipitation results also showed enhanced levels of histone lactylation modifications in the PF group. We further found that the level of lactylation modification of H3K18la site increased significantly, suggesting that H3K18la site may play an important role in promoting PF. Similarly, in vitro, we verified that peritoneal mesothelial cells (PMCs) exhibited enhanced levels of lactate and lactylation in response to stimulation by high glucose, while we found an increasing expression of cell senescence phenotype (P16, P21, and DcR2) and senescence-associated cytokines secretion (IL-1β, IL-6, and TNF-α). By enhancing or inhibiting lactylation, we found that PMCs senescence was significantly enhanced in the lactylation-enhanced group, while the lactylation-inhibited group alleviated PMCs senescence induced by high glucose peritoneal dialysate. In the PF model of DcR2 knockout mice, compared with the wild group, there was no significant difference in the level of histone lactylation, while peritoneal thickness and the expression of markers of fibrosis markers (α-SMA, Collagen I, and Fibronectin) were significantly reduced.

Conclusion
Histone lactylation leads to peritoneal fibrosis induced by high glucose peritoneal dialysate by promoting PMSCs senescence. Histone lactylation may be a vital mechanism of peritoneal dialysis-related peritoneal fibrosis.
#4709 PERSONALISED INDUCTION THERAPY IN ANCA GLOMERULONEPHRITIS
Authors: Hamburger Laura , Leung Wing Yin , Bruce Ian , Brix Silke 
Published: June 2023

Abstract

Background and Aims
Patient and kidney outcome in ANCA glomerulonephritis (GN) remains unsatisfactory. Rituximab use failed to reduce the rate of infectious complications and demonstrates a significant rate of hypogammaglobulinaemia in ANCA vasculitis. Adjusting the rituximab dosage to the individual patient's need promises a reduction in treatment toxicity.

Method
Retrospective analysis of a single centre cohort of ANCA GN patients with disease flares between 2019 – 2022 using a stratified induction immunosuppression with rituximab and cyclophosphamide. Treatment intensity was adjusted to resolution of systemic inflammation and microscopic haematuria, peripheral CD19 cell count depletion and immunoglobulin G (IgG) levels.

Results
45 patients (median age 57 years, 55.7% female, median eGFR 27 mls/min) were treated with a median dose of 1.5 grams Rituximab during induction (interquartile range, IQR 1 – 2 grams). 18 patients received concomitant intravenous cyclophosphamide pulses to control the acute inflammation (median cumulative dose of 2 grams, IQR 1.65 – 3 grams). Peripheral B cell depletion was 91.4% at 3 months and 90.3% at 6 months (&lt;3 CD19 cells/ul). During the initial 12 months treatment, IgG level fell below 7g/l in 20 patients, below 5g/l in nine patients and below 3g/l in one patient. Seven patients required renal replacement therapy at diagnosis (15.6%). Five patients recovered kidney function and three patients developed end stage kidney disease (6.7%). Twelve infections were reported requiring antibiotic treatment (26.7%), seven severe infections were documented requiring hospitalisation (13.3%) and one patient died (2.2%).

Conclusion
An early assessment of treatment response assists adjusting vasculitis therapy. Adjusting management to the patient's individual immunological and treatment response may result in better outcome with less treatment toxicity.
#4740 DIFFERENT ORAL IRON PREPARATIONS IN CHRONIC KIDNEY DISEASE: A COMPARATIVE ANALYSIS
Authors: Sharma Sourabh , Sharma Neha , Varma Prem 
Published: June 2023

Abstract

Background and Aims
Anaemia is common and undertreated morbidity in chronic kidney disease (CKD). Optimal approach to treatment of renal anemia is matter of ongoing debate. This is the first comparative analysis between different oral iron preparations in CKD patients.

Method
This prospective observational multicentre study was performed from March 2019 to May 2021. In total, 214 non-dialysis dependent CKD stage3-5 patients with 3 months follow-up were included. Inclusion & exclusion criteria are mentioned in Table 1. Primary outcome was rise in Haemoglobin at 1 month/3 months & rise in Transferrin saturation (TSAT) at 3 months. Treatment adherence was also evaluated. Figure 1 depicts the study model.

Results
Table 2 depicts demographic data while Table 3 depicts correlation between baseline haemoglobin & different modifiable/non-modifiable variables. Rise in haemoglobin & TSAT with different oral iron preparations has been shown in Table 4 while the ANOVA tables for clinical significance of this rise has been shown in Figures 2 & 3. Rise in haemoglobin and TSAT% was highest with Ferric Pyrophosphate &gt; Ferric Fumarate &gt; Ferric Saccharate. Treatment adherence was highest with Ferric Pyrophosphate (100%) &gt; Heme Iron Polypeptide (91.4%) &gt; Ferrous Ascorbate (88.9%).

Conclusion
Ferric Pyrophosphate is most effective among available oral iron preparations in rising haemoglobin level. It effectively repletes iron stores & has highest treatment adherence.