bluuebunny/crossref_metadata_2025_split huggingface dataset:
#3527 NOVEL MODELS FOR THE PREDICTION OF NON-DIABETIC RENAL DISEASE IN TYPE 2 DIABETES MELLITUS
Authors: Gao Qi , Xin Xu , Nie Sheng 
Published: June 2023

Abstract

Background and Aims
Accurately distinguishing non-diabetic renal disease (NDRD) from patients with diabetic kidney disease (DKD) in absence of kidney biopsy remains big challenge. We aimed to develop and validate a prediction model to guide the kidney biopsy among DKD patients in clinical practice.

Method
A total of 3,205 patients with type 2 diabetes mellitus who underwent kidney biopsy between 2000 and 2021 were included. Random sampling approach stratified by predictive outcome was used to acquire the training set (N = 2,244) and testing set (N = 961). The primary outcome was the occurrence of biopsy-proven NDRD. TheLASSO model and XGBoost model using 80 candidate predictors were developed and compared with a Clinical model using currently recommended indicators. The performance of predictive models was evaluated by the areas under receiver operating characteristic (ROC) curves and precision and recall (PR) curves, calibration plot, the categorical net reclassification improvement (NRI) and the integrated discrimination improvement (IDI).

Results
The training set and testing set included 1,456 and 624 patients with NDRD, respectively. In the testing set, the predictive performance of XGBoost model (ROC-AUC, 0.905; 95% CI, 0.886-0.923) and LASSO model (ROC-AUC, 0.845; 95% CI, 0.820-0.871) were significantly better than Clinical model (ROC-AUC, 0.737; 95% CI, 0.705-0.771) (P &lt;2.2e-16 for both). The LASSO model and XGBoost model also had higher PR-AUC values and significant improvement in reclassification as assessed by NRI and IDI. Utilizing the XGBoost mode in the full dataset based on the low- and high- risk thresholds, we could screen out 559 (49.7%) patients with isolated diabetic nephropathy (DN) to avoid kidney biopsy, and identify 1221 (58.7%) patients with NDRD before kidney biopsy.

Conclusion
Our models outperformed recommended indicators for guiding the kidney biopsy among patients with DKD. Physicians could use these models to screen out patients with isolated DN to avoid kidney biopsy, and identify patients with high suspicion of NDRD for recommended kidney biopsy.
#3528 DIALYSATE SODIUM: IS IT STILL MYTH OR NOT?
Authors: Eftimovska-Otovikj Natasha , Poposka Elizabeta , Vrevezoska Bojana , Karakostova Marija , Vuinov Venco 
Published: June 2023

Abstract

Background and Aims
Pre-hemodialysis serum sodium levels can vary among patients, therefore, a single dialysate sodium prescription may not be appropriate for all patients. The aim of the study was to investigate whether dialysis patients will have some beneficial effects of prescription of different models of dialysate sodium.

Method
77 nondiabetic subjects performed 12 months hemodialysis (HD) sessions with dialysate sodium concentration set up at 138 mmol/L, followed by additional 4 models of dialysate sodium (each one 4 months sessions lasted) wherein dialysate sodium was set up: model 1: according to pre-hemodialysis serum sodium concentration, model 2: sodium concentration in UF fluid, model 3: sodium profiling (144-136 mmol/L, every hour decreasing of dialysate sodium during dialysis), model 4: stepwise dialysate sodium (starting dialysis with a dialysate sodium of 138 mmol/L and reducing it every week by 1 mmol/L sodium for the next 4 weeks). Blood pressure (BP), interdialytic weight gain (IDWG), thirst score, sodium gradient were analysed. After the standard dialysate sodium hemodialyses, the subjects were divided into normotensive, hypertensive and hypotensive based on the average pre-hemodialysis systolic BP during the standard dialysate sodium hemodialyses.

Results
Model 1: resulted in significantly lower BP (153.60±14.26 versus 133,61±11.88 mmHg; p = 0.000) and IDWG (2.21±0.93 versus 1.87±0.92 kg; p = 0.018) in hypertensive patients, whereas normotensive patients showed only significant decrease in IDWG (p = 0,004). Hypertensive patients had significant highest sodium gradient compared to other patients (p&lt;0.05), followed by significant increase of 0,6% IDWG confirmed with univariate regression analysis. Thirst score was significantly lower in all patients with individualized-sodium HD and no relationship between the sodium gradient and the subjective feeling of thirst was confirmed (p = 0.368). Model 2: resulted in significantly lower BP in normotensive and hypertensive patients, with no influence on IDWG and thirst score compared to standard dialysate sodium (p = 0.474 and p = 0.212, retrospectively). Patients who were hypotensive, due to frequent collapses and unmeasurable blood pressure values, as well as for ethical reasons, were excluded from analysis with this dialysate sodium model. Model 3: confirmed significantly higher BP and IDWG in all 3 groups (p = 0.006) and significantly higher thirst score in normo and hipotensive patients (p = 0.000), with no influence in hypertensive patients. Model 4: significant decrease in SBP and DBP in hypertensive patients and insignificant increase in IDWG, but with no effects in normotensive and hypotensive patients on BP, IDWG and thirst score.

Conclusion
Model 1 resulted in better clinical outcome in hypertensive and normotensive patients compared to standard dialysate sodium, whereas other 3 models didn't show any clinical benefits.
#3555 LYMPHOCYTE SENESCENCE: A CROSS-SECTIONAL STUDY COMPARING SYSTEMIC LUPUS ERYTHEMATOSUS AND END STAGE RENAL DISEASE
Authors: Moysidou Eleni , Lioulios Georgios , Christodoulou Michalis , Xochelli Aliki , Nikolaidou Vasiliki , Mitsoglou Zoi , Stai Stamatia , Fylaktou Asimina , Papagianni Aikaterini , Stangou Maria 
Published: June 2023

Abstract

Background and Aims
Immunosenescence, as a consequence of ageing or chronic inflammation, encompasses a spectrum of lymphocyte characteristics, including the presence or absence of certain lymphocyte surface molecules. Aim of the present study was to evaluate the immunosenescent effect of two different forms of chronic inflammation, Systemic Lupus Erythematosus (SLE), a chronic autoimmune disease and end stage renal disease (ESRD), a chronic inflammatory disorder.

Method
Certain lymphocyte surface molecules, including CD31, CD45RA, CCR7, CD28, CD57, for T, and IgD, CD27 for B lymphocytes, were analyzed by flow cytometry, and distinct naïve, active and senescent lymphocyte subtypes were determined, in SLE and ESRD patients. Results were compared to healthy controls (HC) of similar age, gender and nationality.

Results
Lymphopenia was significant in both SLE and ESRD patients, compared to HC, affecting B cells 75.4(14.4–520.8), 97(32–341) and 214(84–576)cells/μL, respectively, P &lt; 0.0001, and CD4+ cells 651.2(71.1–1478.2), 713(234–1509) and 986(344–1591)cells/μL, respectively, P &lt; 0.0001. The allocation of B cell subpopulations was remarkably different between SLE and ESRD patients, with the SLE showing a clear shift to senescent (IgD-CD27-) 11.75(2.3–74.2)% vs. 8.1 (1.7–35), and ESRD patients, to naïve subpopulations, compared to HC 69.9(1.1–92)% vs. 62 (4.5–86.9)%, P = 0.019. Instead, senescent subtypes of CD4+ lymphocytes, were reduced in SLE, compared to ESRD and HC, 3.2 (0.1–42.2)%, 6 (0.4–56.4)% and 3.5 (0.3–19.5)% for CD4+CD28null cells and 1.2 (0.1–23.9)%, 2.5 (0–51.9)% and 1.9 (0–17.9)%, for CD4+CD28-CD57+ cells. CD8+ lymphocyte subtypes presented a complete redistribution, in favor of CD8+CD45RA-CCR7+ (central memory), 53(1.8–92.4)%, 52.2(0.1–91.5)% and 23.4(0.1–92)%, respectively, and lowering the terminally differentiated populations (CD45RA+CCR7-), 2.8 (0–58.1)%, 7.8 (0.2–54.4)% and 12.8(0–71.6), respectively. CD8+CD28null cells were significantly reduced in SLE, compared to ESRD and HC, 31.9(1.1–87.2)%, 44.4(14–89.7)% vs. 34.5(6.4–72.3)%, respectively, P = 0.04.

Conclusion
Senescent phenotype of B lymphocytes predominated in SLE patients, while ESRD patients showed a completely different profile, with increased senescence involving mainly CD8+ lymphocytes.
#3572 CLINICAL AND GENETIC CHARACTERISTICS OF CHILDREN WITH BARTTER SYNDROME: A SINGLE CENTER LONG-TERM EXPERIENCE
Authors: Askiti Varvara , Zampetoglou Argyroula , Mila Maria , Mitsioni Andromachi 
Published: June 2023

Abstract

Background and Aims
Bartter syndrome is an autosomal recessive renal tubular disorder. Clinical diagnosis can be challenging due to rarity and phenotypic overlap. Little information is available on a long term follow-up in Bartter syndrome. Our aim was to describe clinical -genetic correlations as well as our experience from the long term follow up of these patients.

Method
Clinical and genetic characteristics of patients with Bartter syndrome at diagnosis and long term follow up are reported in 19 children. Genetic testing (whole exome sequencing, WES) was done in 14/19 patients. The study period was 17 years (January 1, 2006 to December 31, 2022).

Results
16 Caucasian and 3 of gipsy origin (13 boys, 68%) were included. The median age at diagnosis was 0,52 yrs. Median follow up time was 9.8yrs (IQR 6.86-13.8). WES revealed 6 mutations in KCNJ1 genes, 5 in SLC12A1 and 3 in CLCNKB genes. 4 new mutations were identified (3 in KCNJ1 genes and 1 in SLC12A1. 18/19 children were born pre-term (including 2/3 patients with CLCNKB). Nephrocalcinosis was present in 18/19 patients (included the 3 patients with CLCKNB mutations). 4/6 patients with KCNJ1 mutations presented initially with hyperkalemia. Medical treatment in the last follow up included supplementation with potassium in 18, non -steroidal anti-inflammatory agents in 15 and gastroprotective drugs in 13, ramipril in 2. 2/19 received recombinant growth hormone. At last follow up body weight and height were within normal ranges in 16/19 (84%) patients. Hyperparathyroidism (median time of PTH 151.5 pg/ml) have 6/11 (56%) of patients with Bartter I (ΚCNJ1mutation) and Bartter II (SLC12A1 mutation) and only 1/3 with Bartter III (CLCNKB mutation). 2/19 patients have proteinuria. Chronic kidney disease (CKD) occurred in 7/19 (37%) suggesting that the long term prognosis can be unfavorable (4 CKD stage II, 3 CKD stage III). Of note 2 patients with CKD had impaired renal function since diagnosis while the remaining 5 progressed gradually during followup.

Conclusion
WES is useful in dealing with the phenotypic heterogeneity of Bartter syndrome. Our results emphasize the need for early diagnosis, regular followup and appropriate treatment in order to maintain normal renal function and achieve normal final height and weight.
#3594 CHANGES IN ALBUMINURIA AND KIDNEY FUNCTION AFTER 8 WEEK HIGH-INTENSITY INTERVAL TRAINING PROGRAM IN 2ND AND 3RD TRIMESTER OF PHYSIOLOGICAL PREGNANCY
Authors: Wołyniec Wojciech , Kochanowicz Andrzej , Radzimiński Łukasz , Mieszkowski Jan , Renke Marcin , Szumilewicz Anna 
Published: June 2023

Abstract

Background and Aims
Physical exercise is the best prophylaxis of many disorders and should be continued during uncomplicated pregnancy. Several studies suggested that most pregnant women had no contraindications to perform intensive exercises. In recently published studies the beneficial effect of high-intensity interval training (HIIT) on both mental health and reduction of excessive weight gain during pregnancy has been demonstrated. The knowledge regarding kidney function after exercise in pregnancy is very scarce and only few studies concerning this topic were published. The aim of this study was to estimate changes in markers of kidney function in healthy pregnant exercising women. Changes after single intensive exercise and after 8 week training program were analyzed.

Method
The group of 36 women in 2nd and 3rd trimester of pregnancy were recruited to the study. At the beginning of the study all participants had normal kidney function (serum creatinine level below 0.6 mg/dl) and albuminuria (uACR below 30 mg/g) in rest. 19 women participated in 8-week HIIT program and 17 women in 8-week educational program (EDU group). Before and after 8 week training and education programs a progressive maximal exercise test on cyclometer was performed. Several biochemical measurements were performed.

Results
Women from both groups revealed mild changes concerning kidney function in rest, typical for physiological pregnancy (e.g. low sodium, creatinine and uric acid levels). After progressive maximal exercise test some unexpected findings were found: the fractional excretion of urea and uric acid increased (FeUrea from 41.25 to 50.05%; FeUA from 7.18 to 8.04%) and serum uric acid decreased significantly (sUA from 3.35 to 3.28mg/dL). Other changes after short exercise were typical: significant increase of uACR (from 5.12 to 9.43mg/g), serum creatinine (from 0.52 to 0.56mg/dL) and urea (from 16.45 to 21.65 mg/dL), among others. The 8-week HIIT training program did not change kidney function in rest. In both groups a significant increase of eCrCl and sUA were observed. The interesting observation was that uACR increased significantly only in EDU group.

Conclusion
Changes in kidney function after short intensive exercise in pregnancy were typical for healthy subjects, but there was no negative impact on markers of renal hypoperfusion. It was probably related to increased renal blood flow occurring in healthy pregnancy. The supervised 8-week HIIT training program had no negative impact on kidney function. The possible positive impact of this training on albuminuria was suggested.
#3612 STING IS INVOLVED IN THE CELLULAR SENESCENCE PROCESS ASSOCIATED WITH RENAL AGING
Authors: Tejedor Lucia , Marquez-Exposito Laura , Marcela Córdoba David Gina , García-Giménez Jorge , Marchant Vanessa , Basantes Pamela Estefanía , Tejera Antonio , Diez Raul Rodrigues , Rayego-Mateos Sandra , Ortiz Alberto , Ruiz-Ortega Marta , Cortassa Adrián Mario Ramos 
Published: June 2023

Abstract

Background and Aims
Cellular senescence is an adaptative process in response to damage or stress. It consists of a cell-cycle-arrest (CCA) alternatively to the programmed cell death process, which is necessary for the regeneration of damaged tissues. However, permanent senescence promotes an aberrant inflammatory response associated to chronic diseases, fibrosis and aging. One of the mechanisms which triggers cellular senescence is the DNA damage response (DDR) activation, that leads to the emergence of a cellular senescence-associated secretory phenotype (SASP), inflammation and fibrosis. Sting is a detection protein of pathogenic DNA derived from cellular damage and genotoxic and environmental stresses, starting an innate immune response and inflammation. A deregulated DDR response and thus the process of senescence itself, are also able to activate Sting. Nevertheless, the role of Sting in senescence associated to renal aging is an unknown fact. The aim of this study is to evaluate the role of STING in aging-associated pathophysiological changes in the kidney.

Method
Studies were carried out in C57BL76 mice (wild type mice) and in mice with a phenotype deficient in the Sting gene (KO-Sting), of different ages: 3 (young) and 18 (aged) months. Renal function parameters, histology and markers of kidney damage, and activation of cellular senescence in presence or absence of Sting were studied.

Results
C57BL76 mice of 18 month presented renal dysfunction and fibrosis that was not observed in KO-Sting mice of the same age. Interestingly, 18 months wild-type mice showed an activation of the Sting pathway, characterized by increased transcriptional levels of Ifit1, Oasl2, Usp19 and Mx2. Moreover, the activation of STING pathway was associated to activation of cellular senescence mechanisms, including elevated renal gene expression of SASP components, such as Ccl2, Ccn2, Il1β, Il6, Pai1 or Tgf-β. Importantly, in Sting KO mice of 18 months, DNA damage response was not activated (no increase in ɣH2AX) and cell cycle arrest was not induced, as determined by the p21 and p16 markers. In addition, SAPS gene expression remained at basal levels in aged KO-Sting mice. However, Klotho gene expression levels are downregulated in all 18-month-old mice, wild type and KO mice.

Conclusion
In conclusion, these findings suggest that the absence of STING prevents age-related renal cellular senescence in a Klotho independent manner in a murine experimental model.
#3627 PHOSPHATIDYLSERINE EXPOSURE AND SHORTENED LIFE SPAN OF ERYTHROCYTES IN RENAL ANEMIA
Authors: Seki Momoko , Arashiki Nobuto , Hanafusa Norio , Hoshino Junichi , Tsuchiya Ken , Nakamura Fumio 
Published: June 2023

Abstract

Background and Aims
The lifespan of erythrocytes in patients with renal anemia is shortened (∼70 days) compared to that of healthy erythrocytes (120 days), but the pathological mechanisms and causes are unclear. Senescent erythrocytes express phosphatidylserine (PS) on their outer membrane, which is a signal for being removed by macrophages. The PS localization in the cellular membrane is mainly regulated by two transporters: flippases and scramblases. Flippases, type Ⅳ P-type ATPases (P4-ATPases), maintain PS localization in the inner leaflet by transporting PS from the outer leaflet of the cell membrane. When scramblases are activated, they facilitate equal distribution of phospholipids between the inner and outer lipid bilayers, resulting in the exposure of PS on the outer leaflet. Recently, we have revealed that reduced flippase activity contributes to PS exposure in healthy senescent erythrocytes [1]. In this study, we examined the percentage of PS-exposed cells and the transporter activity in erythrocytes from renal anemia to elucidate the mechanism of the shortened lifespan.

Method
This study was approved by the Ethics Committee of Tokyo Women's Medical University (#3835, #4822R2). Erythrocytes from the renal anemic patients undergoing maintenance hemodialysis were separated with the centrifugation using Percoll-density gradient according to our previous report. Resultant heavy and light fractions were used as senescent and young erythrocytes, respectively. We analyzed the percentage of PS-exposed cells (n = 12), flippase/scramblase activities (n = 7), and the factors involved in those enzymatic activities such as intracellular K+ (n = 10) and ATP concentration (n = 9). We also measured protein 4.1a/b and HbA1c as an index of erythrocytes’ age.

Results
The cells from renal anemia were separated to heavy (senescent) and light (young) fractions, which was similar to the distributions previously performed on healthy erythrocytes. The PS-exposed erythrocytes in the heavy fraction were slightly more than those of the light fraction (p &lt; 0.01, Wilcoxon test), and the flippase activity of the heavy fraction decreased more than that of the light fraction (p &lt; 0.01, paired t-test). Intracellular K+ concentration decreased in the heavy fraction more than in the light fraction similar to the healthy senescent erythrocytes, but there was no statistical difference in the intracellular ATP concentration between the heavy and light fractions. The measurement of protein 4.1a/b and HbA1c in these fractions is still in progress.

Conclusion
Similar to healthy erythrocytes, reduced flippase activity contributes to PS exposure in senescent erythrocytes of renal anemia, maybe due to the decreased intracellular K+ concentration. This may occur in an earlier stage of senescence than the healthy ones, which may explain the mechanism of the shortened life span.
#3644 CLINICAL VALUE OF SOLUBLE UROKINASE-TYPE PLASMINOGEN ACTIVATOR RECEPTOR IN DIAGNOSIS AND PROGNOSIS OF SEPSIS-ASSOCIATED ACUTE KIDNEY INJURY
Authors: Gu Yue , Zhang Wenwen , Zhou Jing 
Published: June 2023

Abstract

Background and Aims
Acute kidney injury (AKI) is a common complication of hospitalized adults with increased risk of chronic kidney disease and end-stage kidney disease. Sepsis is the most common reason of AKI in patients admitted in intensive care unit(ICU) with the incidence over 50%. Soluble urokinase-type plasminogen activator receptor (suPAR) is an important immune mediator involved in kidney injury. Numerous studies have shown that the suPAR is associated with a variety of kidney diseases.However, it remains unknown on the diagnosis and prognosis value of suPAR in sepsis-associated acute kidney injury (S-AKI). Hence,this study aimed to explore the diagnostic value for the prediction of S-AKI courses and 28-day death.

Method
In this prospective study, adult patients with sepsis admitted to the ICU of Henan people's Hospital from December 2020 to February 2022 were enrolled. Plasma suPAR levels at 0, 12,24 and 48 hours after admission to ICU were measured by enzyme-linked immunosorbent assay. We assessed the development of S-AKI as the primary outcome and the occurrence of death within 28 days in patients who had S-AKI as a secondary outcome. The prediction of the suPAR level on S-AKI and death was tested using receiver operating characteristic curve (ROC) analysis, by calculating the area under the curve (AUC), and 95% confidence interval (CI).

Results
Of the 182 sepsis patients, 66 (36.3%) developed AKI during hospitalization, of whom 31 (46.9%) died. At 12,24 and 48 hours after admission to ICU, the plasma suPAR level was significantly higher in patients with S-AKI than in patients without AKI (P&lt;0.05). (Figue 1) In sepsis patients dead with 28 days after admission in ICU, the plasma suPAR level was significantly higher at 0 and 48 hours after admission in ICU compared to the survival patients(P&lt;0.05). (Figue 1) Diagnostic performance of plasma suPAR level improved over time with the highest area under the receiver operating characteristic curve of 0.701 (95% CI, 0.623∼0.779) 24 hours after study inclusion. Additionally, plasma suPAR levels at 0h have the highest area under the receiver operating characteristic curve of 0.647 (95% CI, 0.512∼0.782) in predicting 28-day death. The best discrimination ability for the S-AKI was achieved for suPAR 24 hours after inclusion by applying a cutoff value of greater than or equal to 6.31 ng/ml (sensitivity 62.1, specificity 71.6). The suPAR at 0h after inclusion performed best in discriminating 28-day death by using a cutoff value of greater than or equal to 4.57 ng/mL (sensitivity 87.1, specificity 51.4). (Table 1)

Conclusion
Plasma suPAR level can be a potential biomarker for early diagnosis of S-AKI and has a certain clinical value in predicting the short-term death of S-AKI. However, further clinical studies with larger sample size is needed.