Median Level Research Articles

Prevalence of iron deficiency and anemia in pediatric heart transplant recipients.

The prevalence of iron deficiency and anemia in the setting of modern-day maintenance immunosuppression in pediatric heart transplant (HTx) recipients is unclear. The primary aim was to determine the prevalence of iron deficiency (serum ferritin<30ng/mL±transferrin saturation<20%) and anemia per World Health Organization diagnostic criteria and associated risk factors. Single-center, cross-sectional analysis of 200 consecutive pediatric HTx recipients(<21 years old) from 2005 to 2021. Data were collected at 1-year post-HTx at the time of annual protocol biopsy. Median age at transplant was 3 years (IQR.5-12.2). The median ferritin level was 32ng/mL with 46% having ferritin<30ng/mL. Median transferrin saturation (TSAT) was 22% with 47% having TSAT<20%. Median hemoglobin was 11g/dL with 54% having anemia. Multivariable analysis revealed lower absolute lymphocyte count, TSAT<20%, and estimated glomerular filtration rate<75mL/min/1.73m2 were independently associated with anemia. Ferritin<30ng/mL in isolation was not associated with anemia. Ferritin<30ng/mL may aid in detecting absolute iron deficiency while TSAT<20% may be useful in identifying patients with functional iron deficiency±anemia in pediatric HTx recipients. Iron deficiency and anemia are highly prevalent in pediatric HTx recipients. Future studies are needed to assess the impact of iron deficiency, whether with or without anemia, on clinical outcomes in pediatric HTx recipients.

Trends in clinical outcomes of older hemodialysis patients: data from the 2023 Korean Renal Data System (KORDS)

With an increasing aging population, the mean age of patients with end-stage kidney disease (ESKD) is globally increasing. However, the current clinical status of elderly patients undergoing hemodialysis (HD) is rarely reported in Korea. The current study analyzed the clinical features and trends of older patients undergoing HD from the Korean Renal Data System (KORDS) database. The patients were divided into three groups according to age: &lt;65 years (the young group), n = 50,591 (35.9%); 65–74 years (the younger-old group), n = 37,525 (26.6%); and ≥75 years (the older-old group), n = 52,856 (37.5%). The proportion of older-old group undergoing HD significantly increased in incidence and decreased in prevalence from 2013 to 2022. The median levels of hemoglobin, serum creatinine, albumin, calcium, phosphorus, and intact parathyroid hormone significantly decreased in the older-old group. The proportions of arteriovenous fistula creation and left forearm placement showed decreased trends with age. Although the utilization of low surface area dialyzers increased with age, the dialysis adequacy, including urea reduction ratio and Kt/V was within acceptable range in the older-old group on HD. Over the past 20 years, the mortality rate in the older-old group has increased, with cardiovascular diseases decreasing and infectious diseases increasing. The incidence of elderly patients undergoing HD has increased over time, but the high mortality of the older-old group needs to be solved. Therefore, it is imperative to develop holistic strategies based on age and individual needs for patients with ESKD.

Exploratory analysis on the association of dietary live microbe and non-dietary prebiotic/probiotic intake with serum cotinine levels in the general adult population

BackgroundPrevious research has indicated the potential involvement of the microbiota in smoking-related processes. The present study seeks to examine the relationship between dietary live microbes, as well as probiotic or prebiotic consumption, and serum cotinine levels.MethodsThis study used data from the National Health and Nutrition Examination Survey 1999–2018. Dietary intake information and probiotic/prebiotic intake data was collected through self-reported questionnaires. Participants were stratified into low, medium, and high intake groups according to their consumption of foods with varying microbial content. Multiple linear models were applied to explore the relationships of dietary live microbes, probiotic or prebiotic use with the serum cotinine level.ResultsA total of 42,000 eligible participants were included in the final analysis. The weighted median serum cotinine level was 0.05 (0.01, 10.90) ng/ml. Participants with low, medium, and high dietary microbe intake represented 35.4, 43.6, and 21.0% of the cohort, respectively. Furthermore, participants were stratified into three groups based on their overall consumption of foods with variable microbe contents. The association between dietary live microbe intake and serum cotinine levels remained robust across all models, with medium intake as the reference (Model 2: β = −0.14, 95% CI: −0.20, −0.07; High: β = −0.31, 95% CI: −0.39, −0.22). Moreover, both prebiotic and probiotic use exhibited an inverse relationship with serum cotinine levels (Prebiotic: β = −0.19, 95% CI: −0.37, −0.01; Probiotic: β = −0.47, 95% CI: −0.64, −0.30). Subgroup analyses revealed no discernible interactions between dietary live microbe, prebiotic, probiotic use, and serum cotinine levels.ConclusionOur findings suggest a negative correlation between dietary live microbe intake, as well as non-dietary prebiotic/probiotic consumption, and serum cotinine levels.

Clinical management of iron deficiency anemia in Japan: iron prescription patterns, treatment effectiveness, and assessments.

Iron deficiency anemia is one of the most common types of anemia, but real-world clinical management practices in Japan are unclear. This study retrospectively explored iron prescription patterns, treatment effectiveness, and assessments. Patients with at least one treatment period between September 2020 and September 2022 were included and classified into three groups (ferric carboxymaltose [FCM]: 7437 patients, saccharated ferric oxide [SFO]: 98,648 patients, and oral iron: 359,547 patients). Iron-related laboratory values over time and testing proportions were evaluated. Median baseline hemoglobin levels were lowest with FCM (FCM: 8.10g/dL, SFO: 8.70g/dL, oral iron: 9.70g/dL), but changes in hemoglobin levels by 12weeks were greatest with FCM (FCM: 3.20g/dL, SFO: 2.60g/dL, oral iron: 1.70g/dL). The median serum ferritin level at 8weeks after FCM treatment was 43.70ng/mL for ≤500mg, versus 123.30ng/mL for >500 to ≤1500mg. All groups had a low proportion of serum ferritin and transferrin saturation (TSAT) testing at diagnosis (<38%), which decreased further for post-treatment assessment (<24%). This study suggests the importance of prescribing an appropriate total iron cumulative dose per the package insert, along with diagnosis and assessments based on serum ferritin/TSAT.

Dietary Survey of Japanese Individuals with Type 2 Diabetes Mellitus on a Low-Carbohydrate Diet: An Observational Study

The nutrient intake of persons with diabetes placed on a low-carbohydrate diet remains unclear. This study aimed to assess nutrient intake in persons with type 2 diabetes mellitus treated with a low-carbohydrate diet. The brief-type self-administered diet history questionnaire was used to collect the dietary information of 335 outpatients at Kitasato Institute Hospital, while their clinical characteristics were collected from their electronic medical records. The median age, HbA1c level, and body mass index of the participants were 68 (60–74) years, 49 (45–55) mmol/mol [6.7 (6.3–7.2)%], and 24.0 (21.8–26.7) kg/m2, respectively; median energy intake was 1457 (1153–1786) kcal/day; and protein–energy, fat–energy, and available carbohydrate–energy ratios were 18.6 (15.7–21.4)%E, 36.8 (31.6–43.2)%E, and 34.6 (26.0–42.4)%E, respectively. As the available carbohydrate–energy ratio decreased, the fat–energy ratio increased significantly. The total dietary fibre and salt intake were 7.1 (5.6–8.4) g/1000 kcal and 6.5 (5.6–7.5) g/1000 kcal, respectively. Japanese individuals with type 2 diabetes mellitus placed on a low-carbohydrate diet had a fat-to-energy ratio exceeding 30%, while the fat–energy ratio increased as the carbohydrate–energy ratio decreased.

Afamelanotide for Treatment of the Protoporphyrias: Impact on Quality of Life and Laboratory Parameters in a US Cohort

Background: Erythropoietic protoporphyria (EPP) and X-linked protoporphyria (XLP) are rare disorders of heme biosynthesis characterized by severe cutaneous phototoxicity. Afamelanotide, an α-melanocyte-stimulating hormone analogue, is the only approved treatment for protoporphyria and leads to increased light tolerance and improved quality of life (QoL). However, published experience with afamelanotide in the US is limited. Methods: Here, we report on all adults who received at least one dose of afamelanotide at the Massachusetts General Hospital Porphyria Center from 2021 to 2022. Changes in the time to phototoxic symptom onset, QoL, and laboratory parameters were assessed before and during treatment with afamelanotide. Results: A total of 29 patients with protoporphyria were included, 26 of whom (72.2%) received ≥2 afamelanotide implants. Among the patients who received ≥2 implants, the median time to symptom onset following sunlight exposure was 12.5 min (IQR, 5–20) prior to the initiation of afamelanotide and 120 min (IQR, 60–240) after treatment (p &lt; 0.001). Improvements in QoL during afamelanotide treatment were measured using two QoL tools, with good correlation observed between these two instruments. Finally, we found no improvements in the median levels of metal-free erythrocyte protoporphyrin, plasma protoporphyrin, or liver biochemistries during versus prior to the initiation of afamelanotide treatment. Conclusions: This study highlights a dramatic clinical benefit of afamelanotide in relation to light tolerance and QoL in protoporphyria, albeit without improvement in protoporphyrin levels or measures of liver function.

Primary brain lymphoma and glioblastoma: evaluation of DCE T1 and DSC T2 MRI perfusion findings.

The accurate differentiation of primary central nervous system lymphoma (PCNSL) from glioblastoma multiforme (GBM) is clinically crucial due to the different treatment strategies between them. To define magnetic resonance imaging (MRI) perfusion findings in PCNSL to make a safe distinction from GBM with dynamic contrast-enhanced (DCE) T1 and DSC T2 MRI perfusion findings. This retrospective analysis included 19 patients with histopathologically diagnosed PCNSL and 21 individuals with GBM. DCE T1 vascular permeability perfusion values including K-trans, Ve, Kep, IAUGC, and DSC T2 perfusion values including cerebral blood volume (CBV) and cerebral blood flow (CBF) in axial sections from the pathological lesion and contralateral normal brain parenchyma were measured quantitatively using region of interest analysis. The study observed no statistically significant difference between patients with PCNSL (T/B cell) and GBM in the median values of DCE T1 perfusion ratios (P > 0.05). Nevertheless, the DSC T2 perfusion ratios showed a substantial distinction between the two groups. In contrast to patients with PCNSL (1.185 vs. 1.224, respectively), those with GBM had higher median levels of r-CBV and r-CBF (2.898 vs. 2.467, respectively; P 0.01). A cutoff value of ≤1.473 for r-CBV (Lesion/N) and ≤1.6005 for r-CBF (Lesion/N) was found to estimate the positivity of PCNSL. DSC T2 MRI perfusion values showed lower r-CBV and r-CBF values in PCNSL patients compared to GBM patients. According to the findings, r-CBV and r-CBF are the most accurate MRI perfusion parameters for distinguishing between PCSNL and GBM.

Coexistence of cardiac sarcoidosis and genetic cardiomyopathies: a conundrum

Abstract Introduction Cardiac sarcoidosis (CS) is a chronic inflammatory disease characterized histologically by the formation of non-caseating granuloma in the myocardium, however, causes remain largely unknown. Genetic arrhythmogenic cardiomyopathy (ACM) is an important differential diagnosis of CS. Until now, few data are available about the coexistence of CS in a patient with genetic ACM harboring a desmoglein-2 (DSG2) variant. Purpose We report a case series of patients who demonstrate coexistence of histologically proven CS and genetic ACM. Methods This is a multicentric study, which included patients from four high-volume cardiology referral centres for heart failure and ACM in Switzerland, Italy, and Austria. Patients with both a biopsy-proven diagnosis of sarcoidosis with cardiac involvement (according to the 2014 HRS criteria) also harboring a pathogenic/likely pathogenic (P/LP) variant for cardiomyopathy-associated genes were 1:1 matched for age, gender and genetic variant with patients with genetic ACM without CS (Gen-only). Clinical and imaging data (echocardiography (TTE), cardiac magnetic resonance (CMR) and positron-emission tomography (18FFDG-PET/CT) were collected. Results Each group included 5 patients (Gen+CS: age 48 ± 11 years, Gen only: age 52 ± 13.7 years, n=3 (60%) female in both groups). For each group, the following genes with P/LP variants were found: PKP2: n=2 (40%), DSG2: n=1 (20%), DSP: n=1 (20%), TTN: n=1 (20%). In patients with Gen+CS, atrio-ventricular block (AVB) I° (80% vs 20%, p=0.05) and paroxysmal atrial fibrillation (80% vs 0%, p=0.004) were more frequent, and median NT-proBNP levels (1346ng/l, IQR:103-4276 vs. 214ng/l, IQR:131-326, p=0.046), as well as high-sensitive C-reactive protein levels were higher (3.1g/dl, IQR:1.1-24.2 vs. 0.7g/dl, IQR:0.3-0.95, p=0.016). On imaging, Gen+CS patients were more likely to have septal involvement (60% vs 0%, p=0.021), as highlighted by positive late-gadolinium enhancement on CMR, metabolic activity on PET, or focal wall motion anomalies on TTE. Conclusions CS and genetic ACM can coexist. Hence, detection of a P/LP genetic variant associated with ACM should not lead to exclusion of CS, which more frequently presents with AVB, septal involvement, heart failure, and metabolic activity on imaging. On the contrary, CS can be associated with genetic variants in cardiomyopathy-associated genes.FDG-PET/CT

Can the pan-immune-inflammation value predict gram negative bloodstream infection-related 30-day mortality in solid organ transplant patients?

BackgroundThe recently used pan-immune-inflammation value (PIV) has not been adequately studied as a predictive marker for mortality in immunosuppressed patients. The aim of this study was to evaluate the usefulness of baseline PIV level as a predictor of 30-day mortality in solid organ transplant (SOT) recipients with gram negative bloodstream infections (GN-BSI).MethodsThis retrospective, cross-sectional study was conducted between January 1, 2019, and December 31, 2022, in 1104 SOT recipients. During the study period, 118 GN-BSI were recorded in 113 patients. Clinical, epidemiological, and laboratory data were collected, and mortality rates (30-day and all-cause) were recorded.ResultsThe 113 recipients had a median age of 50 years [interquartile range (IQR) 37.5–61.5 years] with a male predominance (n = 72, 63.7%). The three most common microorganisms were as follows: 46 isolates (38.9%) of Escherichia coli, 41 (34.7%) of Klebsiella pneumoniae, and 12 (10.2%) of Acinetobacter baumannii. In 44.9% and 35.6% of the isolates, production of extended-spectrum beta-lactamases and carbapenem resistance were detected, respectively. The incidence of carbapenem-resistant GN-BSI was higher in liver recipients than in renal recipients (n = 27, 69.2% vs n = 13, 17.6%, p < 0.001). All-cause and 30-day mortality rates after GN-BSI were 26.5% (n = 30), and 16.8% (n = 19), respectively. In the group with GN-BSI-related 30-day mortality, the median PIV level was significantly lower (327.3, IQR 64.8–795.4 vs. 1049.6, IQR 338.6–2177.1; p = 0.002). The binary logistic regression analysis identified low PIV level [hazard ratio (HR) = 0.93, 95% confidence interval (CI) 0.86–0.99; p = 0.04], and increased age (HR = 1.05, 95% CI 1.01–1.09; p = 0.002) as factors associated with 30-day mortality. The receiver operating characteristic analysis revealed that PIV could determine the GN-BSI-related 30-day mortality with area under curve (AUC): 0.723, 95% CI 0.597–0.848, p = 0.0005.ConclusionsPIV is a simple and inexpensive biomarker that can be used to estimate mortality in immunosuppressed patients, but the results need to be interpreted carefully.

Association of maternal and cord vitamin B12 levels with anthropometry in term neonates born to malnourished mothers in coastal South India

Background Malnourished pregnant women are at increased risk of micronutrient deficiency. We assessed the vitamin B12 status in both malnourished and normally nourished pregnant women and their neonates. Additionally, we studied the association between maternal B12 levels, cord B12 levels and neonatal anthropometry. Methods This cross-sectional study enrolled 63 malnourished and 63 normally nourished mothers and neonates. Maternal and cord blood samples were collected at the time of delivery for estimation of vitamin B12 levels. Maternal and cord vitamin B12 levels were compared using the Mann–Whitney U test. Neonatal anthropometry was correlated with maternal and cord B12 levels using Spearman’s correlation. Data were analyzed using SPSS version 25. Results Mean maternal age was 26.58 yrs. The median cord B12 levels were lower than the maternal B12 levels. Maternal B12 levels showed a strong positive correlation with cord B12 levels (rho = 0.879; p &lt; 0.001). Maternal (p &lt; 0.001) and cord (p &lt; 0.001) vitamin B12 levels were significantly lower in the malnourished group than in the normally nourished group. In malnourished group, 66.8% mothers and 95.2% neonates were Vitamin B12 deficient, whereas 1.5% mothers and 4.7% neonates were vitamin B12 deficient in normally nourished group. In the malnourished group, maternal B12 levels were positively correlated with birth weight (rho 0.363, p = 0.003) and length (rho 0.330, p =0.008), whereas cord B12 levels were positively correlated with birth weight in the normally nourished group. (rho 0.277 p= 0.028) Conclusion High rates of vitamin B12 deficiency were observed in malnourished mothers and neonates. There was a positive correlation between birth weight, length, and maternal vitamin B12 levels in malnourished mothers. These findings emphasize the need to address maternal malnutrition and vitamin B12 deficiency to improve neonatal health.

Long-term proton pump inhibitors therapy and prevalence of hyperprolactinemia. a cross-sectional study in outpatient gastroenterology clinics

Objective: To evaluate serum prolactin and macroprolactin levels in patients on long-term proton pump inhibitors therapy. Method: The cross-sectional study was conducted from January 2018 to November 2019 after approval from the ethics review committee of the Commission on Science and Technology for Sustainable Development in the South University, Abbottabad, Pakistan. And comprised patients from two gastroenterology outpatient clinics in the Khyber Pakhtunkhwa province using proton pump inhibitors for &gt;3 months either alone or in combination with either histamine receptor antagonists or prokinetics. Blood samples were collected from each patient for hormonal screening. Data was analysed using SPSS 25. Results: Of the 166 patients, 101(60.8%) were females and 65(39.2%) were males. The overall mean age was 42.5±14.2 years, and the median serum prolactin level was 23.2ng/ml (interquartile range: 14.0-38.0ng/ml). There were 96(58%) patients with normoprolactinemia and 70(42%) with hypreprolactinemia. There were 19(11.4%) patients using combination therapy, while the rest were on proton pump inhibitors monotherapy. There was a significant increase in serum prolactin level with combination therapy compared to monotherapy (p=0.001). Pateints having treatment duration 11-20 months (p=0.006) and &gt;40 months (p=0.001) were at high risk of developing hyperprolactinemia. Conclusion: Long-term use of proton pump inhibitors could increase serum prolactin levels, and appropriate evaluation is essential for clinical management. Key Words: Proton pump inhibitors, Long-term therapy, Hyperprolactinemia, Omeprazole, Prolactin.

#807 Presepsin and procalcitonin levels are associated with acute kidney injury in sepsis patients

Abstract Background and Aims Acute kidney injury (AKI) is a leading cause of death in patients with sepsis. Presepsin is a novel biomarker which has been used to predict sepsis and the outcomes of sepsis. Presepsin was also demonstrated in a small clinical trial to be associated with AKI in sepsis patients. Procalcitonin is a biomarker which was well-studied in sepsis and AKI patients. We aimed to study the association of presepsin and procalcitonin with AKI and outcomes of AKI in sepsis patients. Method We conducted a multicenter prospective trial in eight tertiary-care hospitals in Thailand. We included suspected sepsis patients aged 18 years or older who entered the emergency room during January 2021 to July 2022. We excluded patients with pregnancy, previous trauma, and postcardiac arrest. We also excluded dialysis patients and patients with estimated glomerular filtration rate (eGFR) less than 30 ml/min/1.73 m2 from our study. We measured blood presepsin and procalcitonin at day 0, 3 and 7 along with other investigation for usual intensive care of sepsis. We calculated the level of presepsin and procalcitonin that could distinguish between sepsis patients with and without AKI. We also analyzed whether presepsin and procalcitonin were associated between severity of AKI determined by Kidney Disease: Improving Global Outcomes (KDIGO) staging of AKI. Results We recruited 621 patients who was diagnosed sepsis at emergency department. AKI was diagnosed in 246 patients (39.6%). Of these AKI patients, maximal KDIGO stage of AKI were stage 1, 2 and 3 in 140 (56.9%), 64 (26.0%) and 42 (17.1%) patients, respectively. The median age was 70.1 years with 54.6% was male patients. The median BMI was 21.9 kg/m2. The median Charlson comorbidity index (CCI) was 5 (IQR 4-7). The median presepsin level in AKI patients was 1012 pg/mL (IQR 528-1719 pg/mL), which was significantly higher (P &amp;lt; 0.001) than the median presepsin level in non-AKI patients, which was 594 pg/mL (IQR 337-1138 pg/mL). The median procalcitonin level in AKI patients was 1.24 ng/mL (IQR 0.22-6.06 ng/mL), which was significantly higher (P &amp;lt; 0.001) than the median presepsin level in non-AKI patients, which was 0.50 ng/mL (IQR 0.09-2.34 ng/mL). The cut-point of presepsin level and the procalcitonin level of ≥795 pg/mL and ≥0.9 ng/mL was associated with AKI in sepsis patients respectively. The higher level of presepsin and procalcitonin also significantly associated with higher KGIDO staging of AKI as shown in Fig. 1. However, the mortality rate in both groups were not significantly different (24.0% in AKI group vs. 21.1% in non-AKI group, P = 0.39) Conclusion To date, this is one of the largest studies to evaluate the association between presepsin level, procalcitonin level and AKI in sepsis patients. The presepsin level and the procalcitonin level of ≥795 pg/mL and ≥0.9 ng/mL was associated with AKI in sepsis patients respectively.

#2315 Impact of iron and erythropoiesis-stimulating agent dose on mortality of hemodialysis patients with cancer

Abstract Background and Aims Anemia and iron deficiencies are frequent in hemodialysis (HD) patients and in patients with cancer. If specific guidelines on the management of erythropoiesis-stimulating agent (ESA) in HD patients with cancer have been published, the association between the iron status and the risk of morbidity and mortality in this population remains elusive. Method This retrospective, observational study include HD patients who had been diagnosed with cancer after the start of HD, between September 2009 and March 2021. Demographics, lab test, iron status and cumulative dose of iron and ESA were collected quarterly, from one year before cancer diagnosis to one year after. Univariate analyses were performed to assess the impact of iron or ESA exposure on mortality, after modelling exposure before and after diagnosis of cancer. Then, each model was adjusted, using the baseline variables that were found to be independently associated with mortality. Cox proportional-hazards modelling was used for all regression analyses. P-value &amp;lt; .05 is considered significant. Results Seventy-nine patients were included, with a median follow-up of 2.2 years (IQR: 0.9–5.3). At baseline, the median age was 72 years (IQR 63–79), 30.4% were women. The median dialysis vintage before the diagnosis of cancer was 3 years (IQR 2-7). The main cancers found were prostate (14%), colorectal (13%), bronchopulmonary (11%), urothelial (10%) and skin (10%). Lymph node involvement were observed in 18% and metastasis in 16% patients. The median hemoglobin level was 10.4 g/dL (IQR 9.9–11.7), the median ferritin level was 412 ng/mL (IQR 213–626). The median cumulative quarterly dose of iron was 600 (215–900) mg and the cumulative dose of ESA was 71 (IQR 40–148) UI/kg/week of darbopoetin alfa or equivalent. The year following the cancer diagnosis, the median dose of iron administered remained stable, but with significant variations between patients. There was an increase in the median dose of ESA, particularly after the 6th month, up to 134 (35–314) UI/kg/week. The median hemoglobin remained between 10 and 12 g/dL. The median ferritin level rises moderately during the first 6 months, then returns to values equivalent to those preceding the diagnosis of cancer. Mortality after 12 months of follow-up was high (mortality rate of 47.4%). Age, the presence of a atrial fibrillation, lymphatic invasion, metastatic invasion, or the need for more than one antitumor treatment were independently associated with mortality. In adjusted analysis (using baseline characteristics associated with death), an association with all-cause mortality was only observed with the cumulative dose of ESA in the year preceding the diagnosis of cancer (HR 1.41 [1.06–1.88], P = .017). In multivariate analysis, an association was observed between all-cause mortality and the cumulative dose of ESA in the year preceding the diagnosis of cancer, with an HR of 1.37 (1.03-1.83, P = .031). This association between all-cause mortality and cumulative dose of ESA was also found in the year following cancer diagnosis, but without reaching significance (HR 1.37 [0.95-1.98], P = .092). However, there was no association between mortality and the cumulative dose of iron administered before or after the diagnosis of cancer in multivariate analyses. Conclusion In HD patients diagnosed with cancer, the amount of iron administered was not associated with an increased risk of mortality, probably making it possible to increase the doses administered, if necessary, without any additional risk. However, it was not possible to guarantee the safety of increasing the dose of ESA in these patients. These findings should be confirmed in a larger population in order to define guideline for iron and ESA supplementation in this population.

#2886 Machine learning-based assessment of serum creatinine and NT-proBNP levels for predicting mortality in patients with heart failure and kidney injury

Abstract Background and Aims In a population hospitalized for acute heart failure, about 20% are affected by acute kidney injury, a significant independent factor linked to increased mortality both during hospitalization and within one year. While existing research offers insights, crafting a precise model to predict mortality in heart failure cases remains a complex task, primarily due to the difficulties in pinpointing critical determinants and achieving high accuracy. The aim of our research was to assess the efficacy of serum creatinine and NT-proBNP levels as predictors for mortality in heart failure patients, using machine learning. Method In our retrospective cross-sectional study, we examined the records of 1,042 patients hospitalized due to acute heart failure at the Institute of Cardiovascular Diseases of Vojvodina, spanning the period from January 1, 2021, to December 31, 2022. The data was initially cleaned, after which we employed a Random Forest model for our analysis. The dataset was partitioned into a training subset, constituting 70% of the data, and a testing subset, comprising the remaining 30%. To achieve optimal precision, we ran the model 100 times. Key performance metrics, including mean sensitivity, specificity, accuracy, F1 score, Matthew's correlation coefficient (MCC), and the area under the Receiver Operating Characteristic (ROC) curve (AUC), were derived from the model to assess its efficacy. Results Following data cleansing, the dataset encompassed a total of 389 patients, of which 58% were male. The median age in this cohort was 71 years, with an interquartile range (IQR) of 63 to 79 years. Key laboratory findings included a median serum creatinine level of 111 µmol/L (IQR: 85-167 µmol/L) and a median NT-proBNP level of 6,589 pg/mL (IQR: 2,822-15,608 pg/mL). After the partition, the median number of patients in the training set was 272 and the testing set comprised 117 patients. The performance of the Random Forest model was characterized by a sensitivity of 0.530, specificity of 0.916, an overall accuracy of 0.856, and an F1 score of 0.516. The MCC stood at 0.439 with the AUC under the ROC curve being 0.713. Conclusion While the relatively low sensitivity observed in our model could be attributed to the generally lower levels of serum creatinine upon admission and the retrospective nature of the study, which may have influenced the model's ability to identify all true positive cases effectively, serum creatinine and NT-proBNP levels hold promise as effective predictors for mortality in heart failure patients.

#2700 Serum C3/C4 levels in renal antineutrophil cytoplasmic antibody-associated vasculitis: predictors of lung disease and worse prognosis

Abstract Background and Aims Complement activation, specially the alternative pathway, has been implicated in the development of antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This was further corroborated with the efficacy of Avacopan, a selective C5a receptor inhibitor used as a corticosteroids reduction strategy in the treatment of AAV [1]. Low complement factor 3 (C3) levels without real hypocomplementemia are predictors of prognosis in AAV [2]. Low C4 levels have not yet been associated with worst outcomes. We aimed to evaluate the association between circulating C3 and C4 levels at diagnosis of AAV with clinical and biochemical features and with relevant outcomes: relapse, dialysis and death. Method This is a retrospective study including 63 patients with AAV with renal involvement followed between 2003-2023, with C3 and C4 levels measurements at diagnosis. Data was recorded from clinical registries. Patients were grouped according to the median C3 and/or C4 levels, as previously performed [2]. Groups were compared using the chi-square test for categorical variables and non-parametric tests for continuous variables. We created a logistic regression model for the outcomes, adjusting for covariates. Results Mean age at diagnosis was 61.1 ± 13.4 years old and most patients had ANCA MPO specificity (69.8%, n = 44). Only 3 patients had low C3 levels (&amp;lt; 83 mg/dL) and C4 hypocomplementemia (&amp;lt;12 mg/dL) was present in other 3 patients. Median C3 levels were 127.5 mg/dL (107.3-139.0) and median C4 levels were 29.5 mg/dL (22.0-35.0). Groups were defined according to these values: low C3 levels (C3 &amp;lt;127.5 mg/dL, n = 31), low C4 levels (C4 &amp;lt;29.5 mg/dL, n = 31) and low C3 and/or C4 levels, when either of these conditions were met (n = 40). There was a positive correlation between C3 and C4 levels (r = 0.57, p &amp;lt; 0.001). Patients with low C3 levels had more frequent lung involvement than patients with higher C3 levels (71% vs 31.3%, p = 002), as well as alveolar hemorrhage (38.7% vs 12.9%, p = 0.020). Regarding the outcomes, there was a tendency for more patients requiring acute dialysis (first month) and progressing to dialysis during follow-up in the low C3 subgroup. Relapse and death rates were similar between the two groups. Low C4 levels were associated with older age (75 ± 11.8 vs 67.5 ± 13.7 years, p = 0.043), higher relapse rates (50% vs 25.8%, p = 0.05) and faster progression to dialysis (1.0 (1.0-5.0) vs 9.5 (1.8-54) months, p = 0.034). When combining low C3 and/or C4 levels, lung involvement was again more frequent in patients with lower complement levels (62.5% vs 30.4%, p = 0.014). Time to dialysis was lower and relapse rates were higher in the subgroup with low complement levels, but not statistically significant. No association with death was found. Interestingly, acute dialysis requirement was more prevalent in the low C3/C4 levels subgroup (32.5% vs 8.7%, p = 0.033). After adjustment for baseline renal function, low C3/C4 levels showed an increase of 7 times the odds of a patient requiring acute dialysis (OR 6.98; 95% CI 1,196-40,839, p = 0.031, Table 1). Low C3/C4 levels independently predicted the odds of lung disease in AAV (OR = 5,069; 95% CI 1,475-17,612 p = 0.010, Table 2). Conclusion Complement activation in AAV has been previously associated to renal outcomes, but our results also highlight a possible role of complement in the pathophysiology of lung disease. Low C4 levels were associated with higher relapse rates and faster progression to dialysis, revealing that C4 activation impacts outcomes in AAV and that both classic and alternative complement pathways are involved. Combining low C3 and/or C4 levels identified patients at higher risk of acute dialysis requirement, independently of renal function at admission. Further insights in the specific effects of C3/C4 are needed to stipulate the value of monitoring and targeting complement factors in AAV.

#1649 Obinutuzumab is effective for the treatment of rituximab-resistant membranous nephropathy

Abstract Background and Aims Membranous nephropathy (MN) is a leading cause of nephrotic syndrome in nondiabetic adults. Rituximab has become the first-line therapy for patients with MN after the recognition of MN as an autoimmune disease. However, 40% of patients with MN do not respond to rituximab. Obinutuzumab is a humanized and glycoengineered type II anti-CD20 monoclonal antibody that has superior in vitro B-cell cytotoxicity compared with rituximab which might provide an attractive option for rituximab-resistant MN. We presented our single-center experience of treating MN with obinutuzumab. Method Fourteen patients with rituximab-resistant PLA2R-associated MN who received obinutuzumab at the First affiliated hospital of Xi'an Jiaotong university between January 2022 and June 2023 were included in this retrospective study. Resistance to rituximab was defined as the failure to achieve complete (urinary protein excretion &amp;lt;0.3 g/d along with normal serum albumin concentration and stable renal function) or partial (urinary protein excretion &amp;lt;3.5 g/d or with ≥50% reduction vs baseline, accompanied by improvement or normalization of serum albumin concentration and stable GFR) remission of NS in 3-6 months after 2 doses of rituximab administration. Clinical and laboratory parameters were evaluated at presentation, before and after obinutuzumab administration. Results Of all patients with an average age of 50.0 ± 13.6 years, 10 (71.4%) patients were men, 8 (57.1%) patients had hypertension and 4 (28.6%) patients had diabetes. The median disease duration was 1.3 (1.0, 4.8) years. At presentation, the proteinuria and albumin levels were 7.94 ± 4.23 g/d and 21.5 ± 3.6 g/L, respectively. The mean serum creatinine level was 70.5 ± 10.7 µmol/L and the patients had a median baseline anti-PLA2R level of 193.5 (104.5,299.2) RU/mL. Six patients had been previously exposed to steroids, alkylating agents, calcineurin inhibitors in different combinations in addition to rituximab. Both patients received 1 g of obinutuzumab on day 0 and day 15. At obinutuzumab administration, the proteinuria and albumin levels were 8.43 ± 3.36 g/d and 22.4 ± 4.0 g/L, respectively. The mean serum creatinine level was 85.1 ± 28.5 µmol/L and median anti-PLA2R level decreased to 32.7 (10.7,178.) RU/mL compared with that at presentation. After a median follow-up of 5.4 (4.0, 9.7) months after obinutuzumab therapy, complete remission was achieved in 4 (28.6%) and partial remission was achieved in 8 (57.1%) of patients. Of the remaining two patients who did not achieve complete or partial remission, 1 patient had a follow-up of 4 months and had a 33% decline in proteinuria accompanied by improvement in serum albumin. The other patient had an anti-PLA2R level higher than 1500 RU/mL (exceeding detection upper limit) at obinutuzumab administration and an inadequate follow-up of 3 months without proteinuria decline. Whereas, anti-PLA2R level decreased to 18.17 RU/ml accompanied by B-lymphocyte depletion (absolute CD19 count &amp;lt;5 cells/ml) at that time. Of the 12 patients who achieved complete or partial remission, the median time from treatment to remission was 4.7 ± 2.3 months. Two patients with longer follow-up maintained complete remission at 1 year. At first complete or partial remission, the proteinuria and albumin levels were 3.47 ± 1.99 g/d and 32.5 ± 3.3 g/L, respectively. The mean serum creatinine level was 74.8 ± 24.1 µmol/L and anti-PLA2R levels of 11 patients had a decline in the titer to &amp;lt;2 RU/ml (negative result for our immunology laboratory). B-lymphocyte depletion was achieved in all these patients. Conclusion Obinutuzumab may represent an attractive alternative therapy in patients with resistance to rituximab. Larger prospective studies are needed to validate these findings.

#933 Serum and kidney complement and severity of ANCA associated vasculitis in the kidney

Abstract Background and Aims Kidney involvement in ANCA associated vasculitis (AAV) is commonly described as pauci-immune based on histological characteristics. However, we now know that the complement system is activated and contributes to the pathogenesis of AAV – with Avacopan (C5a inhibitor) demonstrating superior efficacy in maintenance of remission over Prednisolone in the ADVOCATE trial. Our aim was to evaluate if there is an association between kidney disease severity and the presence of serum and histological complement activation markers. Method Retrospective cohort study of 59 patients with AAV diagnosed between November 2015 and May 2019. Complement activation markers were serum complements (C3 and C4) levels and presence of complement (C3, C1q and C4) in glomerular capillary walls in immunofluorescence with intensity of 2+ and 3+. Kidney disease severity markers were peak serum creatinine value at presentation, anti-MPO or anti-PR3 levels, and number and proportion of glomeruli with crescents on kidney biopsy. Associations were evaluated using Spearman correlation or Mann Whitney U test as appropriate Results Among 59 patients with biopsy-proven AAV in the kidney, the median (25th percentile, 75th percentile) age was 68.8 (60.7, 73.4) years, serum creatinine was 263 (156, 560) µmol/L, and anti-MPO and anti-PR3 levels were 100.0 (81.5, 199.2) and 128.8 (22.9, 200) in 41 and 7 patients, respectively. respectively. The number and proportion of glomeruli with crescents were 6 (3, 12) and 33.3% (12.0%, 42.6%), respectively. Serum C3 and C4 were performed in 41 patients and the median levels were 1.00 (0.83, 1.14) and 0.24 (0.18, 0.31), respectively. Serum C3 level did not correlate with serum creatinine, anti-MPO or anti-PR3 titers, and number and proportion of glomeruli with crescents. Serum C4 level was negatively correlated with anti-MPO titer (34 patients; r = −0.393, p = 0.02) but did not correlate with serum creatinine or number or proportion of crescents. Complement in the glomerular capillary wall was present in 8 patients (13.6%): C3, C1q and C4 were present in 8, 3 and 1 patients, respectively. Serum creatinine [median 299 (IQR 133, 998) µmol/L versus 261 (156, 359) µmol/L, p = 0.39], anti-MPO titer [100 (88.3, 200) IU/ml versus 100 (79.4, 198) IU/ml, p = 0.74], number of crescents [14 (4, 21) versus 5 (3, 12), p = 0.90] and proportion of crescents [38.9% (12.5%, 42.3%) versus 31.3% (11.1%, 44.3%), p = 0.59] were not different in those with and without complement in the kidney biopsy. Conclusion The presence of complement activation markers was not associated with kidney disease severity in AAV. However, the detection of clinically significant associations may have been limited by our cohort size.

#1980 Past peritonitis episodes are linked to decreased peritoneal Immune Cell Function and Associated with Chronic Increased Peritoneal Inflammation

Abstract Background and Aims Chronic peritoneal inflammation and infectious complications occur in a significant proportion of PD patients. A relationship between peritoneal IL-6 levels and local immunocompetence is suspected. To analyse local immunocompetence, an ex-vivo stimulation assay of PD effluent was developed. The aim of this study was to analyse peritoneal inflammation and immunocompetence in a PD cohort in relation to clinical outcomes. Method Prospectively, 245 routinely performed 4-hour PETs (143 patients, 2679 patient-months) of patients exclusively receiving 2. generation PD fluids (two-chamber, pH neutral, low amount of glucose degradation products) were analysed. An ex-vivo cell stimulation protocol of the fresh effluents was performed of all PETs. Peritoneal immune cell function was analysed using ex-vivo Toll-like receptor (LPS/Pam3Cys) stimulated IL-6 release as an index of immunocompetence. The molecular effects of effluent components and the addition of alanyl-glutamine to PD fluid were analysed in heterologous cell stimulation experiments and using an effluent proteomics and metabolomics approach. Results IL-6 in the effluent showed no association with various patient characteristics (incl. RRF, underlying disease, peritonitis episodes, time on PD). A significant association of peritoneal IL-6 with solute transport rates and systemic markers of uremic inflammation was found. IL-6 in effluent (HR 2.54) and stimulated 1 h effluent (HR 0.34) was predictive of subsequent peritonitis episodes. An inverse association was observed with ex-vivo stimulated IL-6 release from peritoneal cells (P = .02), most pronounced in patients with a history of peritonitis (P = .008). Patients with above median elevated IL-6 levels showed reduced peritoneal immune cell function. The results were validated in an independent multi-centre PD cohort (n = 48). A proteomics (n = 17) and targeted metabolomics (patients n = 134, 1004 metabolites) analysis of PD effluents show an overrepresentation of apoptosis and neutrophil degranulation pathways in patients with elevated effluent IL-6 levels and reduced response mechanisms to pathogens when compared to effluents from patients with low effluent IL-6 levels. Heterologous donor-PBMC stimulation (4 Healthy donors) with 4h PET PD-effluents of 20 patients showed reduced immunocompetence with elevated IL-6 (P = .038) and improved immunocompetence when 8 mM alanyl-glutamine were added to the PD fluid during the dwell. These results could also be validated in a post-hoc analysis of a RCT testing alanyl-glutamine addition to PD fluid for 8 weeks in PD patients. Conclusion This is the first longitudinal study to show the relationship between peritoneal inflammation and impaired immune function of peritoneal cells, possibly predisposing to infectious complications. The possible underlying mechanistic link may represent the biological correlate (“immune-paralysis”) for PD patients at increased risk for recurrent episodes of peritonitis.

#3115 Effectiveness of SGLT2 inhibitors in patients with glomerulonephritis: a single center experience

Abstract Background and Aims Sodium-glucose cotransporter 2 (SGLT2) inhibitors have become widely used in recent years because of favorable outcomes on kidney function in people with diabetes mellitus and chronic kidney disease (CKD). The main effect of SGLT2 inhibitors is inhibiting sodium and glucose reabsorption, acting precisely in the early proximal tubule of the renal nephron. Although these drugs developed as glucose-lowering agents for their capability to induce glycosuria, cardiovascular outcome studies found that the reduction in kidney function was significantly delayed, and the incidence of severe decline in kidney function was reduced in patients taking SGLT2 inhibitors. Later on, these outcomes were confirmed by the results of the DAPA-CKD, EMPA-KIDNEY, and CREDENCE studies, which were specific outcome trials in patients with CKD. However, data about the use of SGLT2 inhibitors in patients with glomerulonephritis at routine clinical practice are still limited. The purpose of this study is to investigate the impact of SGLT2 inhibitors use in patients with glomerulonephritis. Method Patients diagnosed with biopsy-proven GN who continued their routine follow-up in Etlik City Hospital nephrology clinic were retrospectively examined. Patients with a steroid treatment history for GN were excluded from this study. We identified 29 patients who were treated with SGLT2 inhibitors for proteinuria. We analyzed the baseline characteristics, comorbidities, GN types, and laboratory parameters (baseline, sixth and twelfth months at the follow-up). Each patient was matched to the control with a similar baseline feature under conservative therapy (n = 29). Both patient groups were treated in line with the KDIGO glomerulonephritis guideline and were received RAAS blockers at the maximum tolerated dose. According to baseline levels, the reduction rate in proteinuria and eGFR of the sixth and twelfth months were calculated as percentages. The study was performed in accordance with the Declaration of Helsinki. The local ethical committee approved the study design. Results Our study involved 58 patients diagnosed with 32 (55%) IgA nephropathy, 16 (28%) with membranous nephropathy, and 10 (17%) with focal segmental glomerulosclerosis. In the treatment group, 23 (79%) patients used dapagliflozin, and 6 (21%) used empagliflozin as SGLT2 inhibitors. Baseline proteinuria levels at [1940 (1780-2700 mg/d) vs. 1890 (1670-2400 mg/d); p = 0.8], eGFRs [60 (44-82) vs. 64 (46-80) ml/min/1.73 m2; p = 0.8] and serum albumin levels (39.6 ± 0.3 vs. 39.1 ± 0.2; p = 0.4) were similar between both groups. The proteinuria reduction rate in the sixth month was 34% (27.3-40.5) for the treatment group and 12% (6.9-20.7) for the control group (&amp;lt;0.0001). Besides, the reduction rate was still higher in the treatment group at the 12th month [50.5% (39-52.6) vs. 26.3% (17.2-35.4); p ≤ 0.0001]. eGFR declining rate at 6th months and 12th months were lower in SGLT2 group than the control group [3.1% (0-6.2) vs. 8.6% (4.1-16.6); p = 0.004 and 0.8% (0-5) vs. 5.9% (3.3-15.2); 0.005, respectively] (Table 1). Proteinuria levels at 6th months were 1170 (970-1890) mg/d and 1730 (1180-2100) mg/d for treatment and control group, respectively. At 12th months, median proteinuria level of SGLT2 group was 940 (840-1480) mg/d and control group was 1250 (1120- 2040) mg/d (Fig. 1). Conclusion In this study with a well-matched control group, we found that SGLT2 inhibitors demonstrate efficacy in mitigating the decline in estimated GFR and reducing albuminuria in patients with GN. However, randomized-controlled trials are still required specific to patients with GN.

#1170 Efficacy and safety of telitacicept in IgA nephropathy: a real-world study

Abstract Background and Aims IgA nephropathy (IgAN) is the most common primary glomerular disease in the world, and the specific therapeutic methods are limited in IgAN. Telitacicept is a humanized fusion protein composed of a transmembrane activator and calcium-modulating cyclophilin ligand interactor receptor and human IgG. This study was designed to evaluate the efficacy and safety of telitacicept in adult patients with IgAN in a real-world study. Method Biopsy-proven IgAN patients with 24-hour proteinuria greater than 0.5 g/day who received telitacicept 240 mg once a week were recruited in this study and 1:1 matched with patients who received supportive treatment only or immunosuppressive treatment by propensity score matching. The primary outcome was the change from baseline in 24-hour proteinuria over the 3-month follow-up. Results Twenty-one patients in each group were enrolled. The mean eGFR was 80.1 ml/min/1.73 m2, and the median 24-hour urine protein level was 1.48 g/day. At the end of the 3-month follow-up period, telitacicept reduced median proteinuria by 0.72 g/d (54.6%) from baseline, compared with a reduction of 0.18 g/d (20%) in the supportive treatment group (P &amp;lt; 0.001), and 1.12 g/d (72.1%) in the immunosuppressive treatment group (P = 0.814). Preserved eGFR levels were observed in the telitacicept group (1.9 ml/min/1.73 m2 [4.3%]), while the eGFR level declined in the supportive treatment group (- 2.9 ml/min/1.73 m2 [- 5.8%]) and immunosuppression group (- 6.1 ml/min/1.73 m2 [- 8.4%]). No serious adverse events were observed in the telitacicept treatment group. Injection site reactions were more prevalent in the telitacicept group (8/21 [38.1%]), meanwhile immunosuppression group had more respiratory tract infections (7/21, [33.3%]). Conclusion Telitacicept can reduce proteinuria in patients with IgAN and showed a favourable safety profile in patients with IgAN.