bluuebunny/crossref_metadata_2025 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

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 <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

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<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

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 < 0.0001, and CD4+ cells 651.2(71.1–1478.2), 713(234–1509) and 986(344–1591)cells/μL, respectively, P < 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

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

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

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

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 < 0.01, Wilcoxon test), and the flippase activity of the heavy fraction decreased more than that of the light fraction (p < 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

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<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<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.
#3679 ANOCTAMIN 1 INHIBITION SUPPRESSES CYSTOGENESIS BY ENHANCING CILIOGENESIS AND THE CILIARY DOSAGE OF POLYCYSTINS
Authors: Xu Tao
Published: June 2023

Background and Aims

Autosomal dominant polycystic kidney disease (ADPKD) is a ciliopathy which is characterized by abnormal tubular epithelial proliferation and fluid secretion. Anoctamin 1 (ANO1) is a calcium-dependent chloride channel, which has recently been shown to be involved in ADPKD progression. However, how ANO1 contributes to ADPKD is largely unexplored.

Method

1. Based on mRNA gene chips, the expression of ANO1 abnormally increased in human ADPKD kidneys. 2. Immunohistochemical staining showed ANO1 location. 3. Real-time PCR and Western blot showed mRNAs and protein of ANO1 in ADPKD patients and animal model-PKD1RC/RC mice. 4. Confocal immunofluorescence showed ANO1 and PC2 location in the cilia. 5. 3D gel culture to verify the function of ANO1 in cysts formation. 6. ANO1 inhibitors and siRNA to discover STAT3 and ERK pathway in ADPKD cell by WB.

Results

We found that ANO1 is consistently upregulated inhuman and mouse PKD kidneys. Intriguingly, ANO1 located in a vesicle-like patten at the ciliary base but not on the ciliary surface. ANO1 deficiency promotes both ciliogenesis and the ciliary dosage of polycystin-2 in human Pkd1-/- cells, and reduced cyst formation in 3D culture models. Moreover, inhibition of ANO1 abolished the activation of STAT3 and ERK pathways in PKD cells.

Conclusion

Our data indicate ANO1 may aggravate ADPKD by regulating the cilia length and PC2 expression. Moreover, ANO1 could support cyst growth by activating STAT3 and ERK pathways. Thus ANO1 is a negative regulator for both cilia formation and cilia trafficking of polycystins and provide mechanistic insights regarding the therapeutic potential of ANO1 pathway in ADPKD treatment.
#3687 KIDNEY TRANSCRIPTOME VARIES BETWEEN DONOR TYPES, WITH A DIFFERENTIAL REPONSE TO ISCHEMIC PRECONDITIONING
Authors: Coelho Tiago Pinto , Erpicum Pauline , Navez Margaux , Zhang Chenyu , Poma Laurence , Detry Olivier , Jouret François
Published: June 2023

Background and Aims

The prevention/attenuation of graft ischemic injury is a challenge in kidney transplantation. We developed two rat models to investigate the impact of mesenchymal stromal cells (MSCs) in the ischemic preconditioning of kidneys from Donors after Circulatory Death (DCD) and Donors after Brain Death (DBD).

Method

Under general anesthesia, rats underwent iv injection of saline (S-groups) or 1.5 106 MSCs (MSC-groups) followed by either DBD (6hr of brain death) or DCD (6hr of anesthesia and 20min warm ischemia) models, resulting in 4 groups (S-DBD, S-DCD, MSC-DBD, MSC-DCD). Kidneys were then procured after IGL1 flush. One kidney was directly fixed and the other one immersed for 14 hours in IGL1 at 4°C. Serum samples were collected before treatment (baseline) and at the time of kidney collection. Urine samples were collected by bladder puncture at the time of kidney collection. Renal function was evaluated. Kidney histology was assessed by PAS staining and KIM1 immunostaining. Total RNA was extracted from S-DCD vs S-DBD kidneys for RNAseq.

Results

BUN was increased after 6h of anesthesia (DCD) or brain death (DBD) (p<0.01). SCr increased in both S-DBD and MSC-DBD but was lower in MSC-treated rats (MSC-DBD 0.5±0.2mg/dL vs S-DBD 0.7±0.1mg/dL; p = 0.037). Urinary KIM1 was lower in MSC-treated DBD (S-DBD 10.9±4.5 vs MSC-DBD 7.1±1.7; p = 0.03). Acute Tubular Injury (ATI) and KIM1 expression were higher in S-DBD (ATI: S-DBD 65±24% of surface vs S-DCD 39±27% of surface (p = 0.03) and KIM1: S-DBD 0.39±0.24% of surface vs S-DCD 0.10±0.09% of surface (p = 0.0002)). In MSC groups, there was no difference in both ATI extension and KIM1 expression. RNAseq showed that proinflammatory and proapoptotic pathways were upregulated in DBD, whereas transmembrane transport and metabolic pathways were downregulated, compared to DCD.

Conclusion

The RNA profiles of the kidneys are different upon donor types, which may impact the response to MSC-based ischemic preconditioning.
#3712 INTRAVASCULAR VOLUMES AND THE INFLUENCE ON ANAEMIA IN PATIENTS UNDERGOING MAINTENANCE HAEMODIALYSIS
Authors: Vinje Vårin , Bomholt Tobias , Hornum Mads , Oturai Peter , Rix Marianne , Lundby Carsten , Lindhard Kristine
Published: June 2023

Background and Aims

Fluid overload is a major challenge in haemodialysis (HD) patients and might cause hypervolaemia. We speculated that HD patients reaching dry weight could have undetected hypervolaemia and low haemoglobin concentration (Hb) due to haemodilution.

Method

The study included HD patients (n = 22) and matched healthy controls (n = 22). Blood volume, plasma volume, red blood cell volume, and total haemoglobin mass (Hb mass) were determined using a carbon monoxide (CO)-rebreathing method in HD patients reaching dry weight and controls. Blood volume measurements were also obtained by a dual-isotope labelling technique in a subgroup for validation purposes.

Results

Blood volume was higher in 16 out of the 22 HD patients compared to controls. In the HD group, the median blood volume was 89.3 mL/kg (interquartile range (IQR) 76.7–95.4 mL/kg) and was higher than in the control group (79.9 mL/kg (IQR 70.4–88.0 mL/kg); P < 0.037) (Table 1). The median plasma volume was 54.7 mL/kg (IQR 47.1–61.0 mL/kg) and 44.0 mL/kg (IQR 38.7–49.5 mL/kg) in the HD and control groups, respectively (P < 0.001). Hb was lower in HD patients (P<0.001), whereas no difference in total Hb mass was observed between groups (P = 0.11). Changes in Hb levels during and after dialysis were observed in the HD group and is shown in Fig. 1. A correlation was found between blood volume measured by the CO-rebreathing test and the dual-isotope labelling technique in the control group (r = 0.83, P = 0.015), but not the HD group (r = 0.25, P = 0.60).

Conclusion

The HD group had increased blood volume at dry weight due to high plasma volume, indicating a hypervolaemic state. The total Hb mass was similar between HD patients and controls, unlike Hb, which emphasizes that Hb is an inaccurate marker of anaemia among HD patients.
#3719 INCIDENCE, OUTCOMES AND RISK FACTORS OF ACUTE KIDNEY INJURY IN PATIENTS THAT UNDERWENT TRANSCATHETER AORTIC VALVE REPLACEMENT
Authors: Isaranuwatchai Suramath , Triwatana Wutipong , Jitpreeda Amaraluk , Srirattana Netnapis , Sukitpunyaroj Damrong
Published: June 2023

Background and Aims

The incidence of acute kidney injury (AKI) in transcatheter aortic valve replacement (TAVR) varied among different centers and populations. The studies about the AKI in TAVR in Asian population were relatively scarce. Here, we reported the first descriptive study of AKI in patients underwent TAVR in Thailand. We also analyzed the risk factors of AKI in patients underwent TAVR.

Method

We reviewed the medical records of patients underwent TAVR in Chulabhorn hospital from August 2019 to September 2022. Baseline characteristics, serum creatinine and estimated glomerular filtration rate (eGFR) at baseline, day 2, day 7 and at discharge were recorded. Patients who did not have serum creatinine measured at day 2 or day 7 were excluded from our study. Patients who already underwent hemodialysis or peritoneal dialysis before TAVR also excluded from our study. We used the definition of AKI by KDIGO guideline. Outcome of AKI including 30-day mortality, 1-year mortality and renal replacement therapy were also recorded.

Results

We included 113 patients who underwent TAVR, all of which had the diagnosis of severe symptomatic aortic stenosis. 56 patients (49.6%) were male patients. The mean age was 80.2 +/- 5.6 years. The average length of stay was 9.9 days. 54 patients (47.8%) had pre-existing chronic kidney disease (CKD) before underwent TAVR. Other co-morbidities were hypertension (81/113 = 71.7%), dyslipidemia (71/113 = 62.8%), prior myocardial infarction (53/113 = 46.9%), diabetes (36/113 = 31.9%), and prior stroke or transient ischemic attack (5/113 = 4.4%). AKI occurred in seven patients (6.2%). Four patients (4/7 = 57.1%) underwent acute dialysis after TAVR. 30-day mortality rate was 0% and 1-year mortality rate was 1.8%. The 1-year mortality rate in patient with AKI was 14.3% compared with 0.9% in patient without AKI. The univariate analysis revealed that age, prior myocardial infarction, pre-existing CKD and pre-TAVR serum creatinine were risk factors for developing AKI after TAVR.

Conclusion

This is the first study exploring incidence, outcomes and risk factors of AKI in patients underwent TAVR in Thailand. The incidence of AKI was 6.2%, relatively low compared with previous study.
#3720 ON THE DEVELOPMENT OF SOME PAIN SYNDROMES IN PATIENTS ON DIALYSIS
Authors: Khalmukhamedov Javokhir
Published: June 2023

Background and Aims

To study the incidence and intensity of cramps in patients with end-stage CKD during dialysis.

Method

In a cross-sectional study in 2021, 160 male and female patients on program dialysis (PD), aged 22 to 77 (53.3±7.11) receiving for 7.7 ± 1.83 (1 to 25) lasting 12 ± 0.24 hours per week (average KT / V 1.4 ± 0.03) on Fresenius and B. Braun devices. The intensity of cramps was assessed according to a numeric rating scale (NRS) from 0 to 10, as well as its impact on quality of life. To identify patients with intradialytic hypotension (IDH), we used the KDOQI guidelines, which define IDH as a 20 mm Hg decrease in systolic blood pressure (BP) from the origin, assessed over 3 consecutive sessions. All patients' blood serum was checked for phosphorus (P), calcium (Ca), parathyroid hormone (PTH).

Results

Patients were divided into 2 groups, presence 81 (51.0%) or absence 79 (49.0%) of cramps (Table 1). Among patients with diabetes, the frequency of absence of cramps is 2 times higher than among patients with diabetes (6% vs. 94%, respectively) (Table 2). Among patients with hypotension, only in 15% there were no cramps, while without hypotension 85% (Table 3). No statistically significant difference was found between the groups for any of the 3 parameters (PTH, P, Ca).

Conclusion

Painful muscle spasms have been insufficiently studied, although their impact on the quality life of dialysis patients is clinically significant. The first steps should be on correcting for potentially modifying risk factors, development of hypotension during a procedure and correction of phosphorus levels.
#3738 KIDNEY TRANSPLANT RECIPIENTS BECOME LESS ADHERENT TO PREVENTIVE MEASURES AFTER SARS‑COV‑2 VACCINATION AND AFTER AWARENESS OF ANTIBODY RESPONSE
Authors: Frölke Sophie , Bouwmans Pim , Messchendorp Lianne , Vervoort Hanneke , Nieuwkerk Pythia , Abrahams Alferso C , De Vries Aiko , Hemmelder Marc , Gansevoort Ronald , Hilbrands Luuk , Reinders Marlies , Sanders Jan-Stephan , Bemelman Frederike , Geerlings Suzanne
Published: June 2023

Background and Aims

Kidney transplant recipients (KTRs) were advised to tightly adhere to government recommendations to curb the spread of SARS-CoV-2 because of a high risk of morbidity and mortality and decreased immunogenicity after vaccination. The aim of this study was to analyze the change in adherence to preventive measures after vaccination and awareness of antibody response, and to evaluate the effectiveness of these measures.

Method

Questionnaires were sent to 3531 KTRs enrolled in the Dutch RECOVAC studies, retrospectively asking for adherence to nine preventive measures on a 5-point Likert scale before and after SARS-CoV-2 vaccination and after awareness of antibody response. Blood samples were collected 28 days after the second vaccination. Antibody response was categorized as non-responder (≤50 BAU/mL), low-responder (>50 ≤300 BAU/mL) or high-responder (>300 BAU/mL), and shared with participants as a correlate of protection. Adherence before and after vaccination were compared by the Wilcoxon signed rank sum test. Logistic regression analysis was performed to estimate the association between antibody response and adherence, and adherence on acquiring SARS-CoV-2 infection.

Results

In 2939 KTRs (83%) who completed the first questionnaire on adherence to preventive measures, adherence was higher before than after SARS-CoV-2 vaccination (4.56, IQR 4.11-4.78 and 4.22, IQR 3.67-4.67, p < .001) (Figure 1). Adherence after awareness of antibody response was analyzed in 2399 KTRs (82%) of whom also blood samples were available, containing 949 non-responders, 500 low-responders and 950 high-responders. Compared to non-responders, low- and high-responders reported lower adherence (Figure 2). Higher adherence was associated with lower infection rates before and after vaccination (OR 0.67 [0.51-0.91], p = 0.008 and OR 0.48 [0.28–0.86], p = 0.010).

Conclusion

To the best of our knowledge, we are the first to show that KTRs became less adherent to social isolation and other preventive measures after vaccination against COVID-19. Adherence decreased in KTRs who were aware of a subsequent antibody response compared to those without. Moreover, preventive measures in this vulnerable group are effective, regardless of vaccination status.
#3763 RELATIONSHIP BETWEEN INITIAL EGFR DIP AND CHANGES IN LABORATORY PARAMETERS WITH DAPAGLIFLOZIN TREATMENT IN NON-DIABETIC CKD PATIENTS
Authors: Kokubu Maiko , Okanishi Go , Tansho Kosuke , Matsui Masaru
Published: June 2023

Background and Aims

Treatment with sodium-glucose co-transporter-2 inhibitors (SGLT2i) induces an initial decline in estimated glomerular filtration rate, also termed the ‘eGFR dip’ and remains beneficial effects for cardiovascular and kidney outcomes, even after modified by eGFR dip in diabetic CKD. However, the difference of eGFR dip after SGLT2i between diabetic and non-diabetic CKD patients and the effects of eGFR dip on changes of laboratory parameters is not fully understood. In this study, we aimed to investigate the eGFR dip after Dapagliflozin and its relationship with clinical and laboratory data in non-diabetic CKD patients.

Method

We conducted a cohort study on 127 non-diabetic CKD patients receiving Dapagliflozin in whom at least two measurements of eGFR levels at three months were confirmed. eGFR dip was defined by percent eGFR change from baseline. eGFR was calculated using Japanese equation. Correlation analyses between initial eGFR dip and clinical value were conducted using the Pearson correlation coefficient.

Results

The mean age of study participants was 60±13 years and 69 (54%) were male. The underlying kidney diseases included glomerulonephritis in 59 (46%) patients and hypertensive nephrosclerosis in 57 (45%). The mean levels of baseline eGFR were 43±13 mL/min/1.73 m2 and the mean proteinuria was 0.58±0.83 g/gCre. The mean eGFR change from baseline was −0.33±4.3 mL/min/1.73 m2 with eGFR dip of 0.8±9.4%. Factors including age, sex, body mass index, baseline eGFR and urinary protein were not significantly associated with the eGFR dip. Dapagliflozin increased hemoglobin levels by 0.5g/dL and decreased uric acid levels by 0.9 mg/dL. We found indirect and direct correlation of the eGFR dip with changes in proteinuria (r = 0.30, p = 0.001) and uric acid levels (r = 0.21, p = .015) after Dapagliflozin, respectively.

Conclusion

Our results suggest that the eGFR dip following SGLT2i initiation may be associated with the changes of proteinuria and uric acid levels in non-diabetic CKD patients.
#3770 EBV-NEGATIVE KIDNEY TRANSPLANT RECIPIENTS AND PTLD: THE IMPACT OF INDUCTION THERAPY
Authors: Attieh Rose Mary , Mao Shennen , Mao Michael , Pungpapong Surakit , Cheungpasitporn Wisit , Jarmi Tambi , Wadei Hani , Taner Burcin , Leeaphorn Napat
Published: June 2023

Background and Aims

Individuals who are most susceptible to developing PTLD are those who are EBV-negative and receive organs from EBV-positive donors (EBV R-/D+). The evidence regarding the connection between ATG induction therapy and PTLD is inconsistent. No studies have specifically examined the relationship between ATG use and PTLD in subgroups of EBV-negative transplant recipients (EBV R-). Using the UNOS database, we studied the association between the use of induction agents and PTLD in EBV R- patients.

Method

We analyzed data from 2007 to 2022 of EBV R- patients who underwent their first kidney-only transplant and excluded those who received induction agents other than ATG, basiliximab, or alemtuzumab. We used logistic regression to evaluate the association between induction agents and PTLD.

Results

Of 20,531 recipients, 50.7% received ATG, 19.13% received basiliximab, 13.42% received alemtuzumab, and 16.75% received no induction. The overall PTLD incidence was 2.14%. ATG recipients had higher rates of deceased donor transplants, higher degree of HLA mismatch, longer dialysis vintage, and were less likely to be white, compared to non-ATG recipients. Multivariate analysis showed ATG recipients had a higher risk of PTLD compared to non-ATG (odds ratio = 1.47, p<0.001). After excluding recipients who did not receive induction, ATG remained a significant independent risk factor for PTLD when compared to recipients who received either basiliximab or alemtuzumab (odds ratio = 1.35, p = 0.007). There was no statistically significant difference in PTLD risk among patients treated with basiliximab, alemtuzumab, or no induction (refer to Table 1).

Conclusion

The use of ATG induction in EBV-negative kidney transplant recipients is associated with a higher risk of PTLD compared to basiliximab, alemtuzumab, and no induction. The risk of PTLD should be considered when choosing induction therapy for this patient population.
#3781 INSULIN RESISTANCE IS ASSOCIATED WITH INCIDENT CHRONIC KIDNEY DISEASE IN POPULATION WITH NORMAL RENAL FUNCTION
Authors: Bae Eun Hui , Song Su Hyun , Kim Su In , Cho Da Hae , Lim Sang Yoeb , Kim Soo Wan , MA Seong Kwon
Published: June 2023

Background and Aims

Insulin resistance is prevalent in chronic kidney disease (CKD) and may accelerate its progression. This study aimed to investigate whether insulin resistance was associated with the development of incident CKD in a population with normal renal function.

Method

A total of 3,331 individuals with normal renal function from a community-based cohort formed the study population. We determined the relationship between insulin resistance indices and incident CKD using Cox proportional hazard model and Kaplan-Meier survival analysis.

Results

During a mean follow-up of 11.03 ± 4.22 years, incident CKD occurred in 414 (12.4%) participants. The high homeostasis model assessment-insulin resistance (HOMA-IR) level group had an increased risk of incident CKD (HR, 1.40; 95% CI, 1.13-1.74; p = 0.002) compared to the normal group after adjusting for confounding factors The risk of incident CKD also increased with lower quantitative insulin sensitivity check index (QUICKI) levels (HR, 0.62; 95% CI, 0.41-0.92; p = 0.018) and higher leptin-adiponectin ratio (LAR) levels (HR, 1.23; 95% CI, 1.06-1.42; p = 0.006).

Conclusion

Higher insulin resistance indices were associated with the incidence of CKD. Our data suggests that increased insulin resistance may be involved in the development of incident CKD in individuals with normal renal function.
#3783 INCIDENCE AND PREDICTORS OF MAJOR ADVERSE KIDNEY EVENTS IN ICU PATIENTS WITH SEPSIS: A PROSPECTIVE COHORT STUDY FROM A DEVELOPING COUNTRY
Authors: Rao Indu Ramachandra , Thanekar Saurabh , Nagaraju Shankar Prasad , Prabhu Ravindra Attur
Published: June 2023

Background and Aims

Acute kidney injury (AKI) occurs in 15-60% of intensive care unit (ICU) admissions and is associated with higher mortality, morbidity and increased healthcare costs. Major adverse kidney events (MAKE) is a clinically meaningful patient-centred outcome for AKI which includes mortality, need for renal replacement (RRT) and persistent kidney dysfunction. There is a paucity of data on the incidence and risk factors of MAKE, particularly from developing countries. We sought to examine the incidence of MAKE at day 30 (MAKE30) and its predictors in a cohort of critically ill patients with sepsis.

Method

This was a prospective cohort study conducted in the medical ICUs of a tertiary-care hospital in India. Ethical clearance was obtained from the Institutional Ethics Committee. Adult patients (≥ 18 years) admitted in the medical ICUs between 1st September, 2022 and 31st December, 2022 with sepsis (as defined by Sepsis-3 criteria) were included. Those with chronic kidney disease stage 5/5D, those requiring dialysis within 72 hours of admission and with an ICU stay of <72 hours were excluded. Baseline clinical and demographic data were recorded on the day of admission. AKI was defined as per KDIGO 2012 guidelines. Patients were followed up till hospital discharge or day 30 (whichever was earlier) and clinical outcomes were noted. The primary outcome measure was MAKE30 (defined as a composite of death, provision of RRT, or sustained loss of kidney function i.e., a final inpatient creatinine ≥200% of the baseline value, at hospital discharge or at 30 days, whichever comes first).

Results

A total of 250 patients admitted in the medical ICUs during the study period were included for analysis. The baseline characteristics are tabulated below (Table 1). Over the 30-day follow-up period, AKI was noted in 185 (74%) patients, with stage 1 AKI in 38 (15.2%), stage 2 AKI in 29 (11.6%) and stage 3 AKI in 118 (47.2%). Renal replacement therapy was initiated in 86 (34.4%) patients. Mortality occurred in 58 (23.2%). Overall, MAKE30 was seen in 102 (40.8%) patients. Serum lactate (OR 1.04, 95% CI:1.01-1.06; P = 0.010) and SOFA score (OR 1.38, 95% CI:1.27-1.56; P <0.001) at admission were independently associated with MAKE30 (Table 2). There was no association with age, gender, diabetes, type of resuscitation fluid or cumulative fluid balance (at 72 hours) with MAKE30.

Conclusion

In this cohort of critically ill patients with sepsis, MAKE30 was observed in 40.8%. Serum lactate and SOFA score at admission were independent predictors of MAKE30.
#3786 CORONARY ARTERY CALCIFICATION IN AN SLE PATIENT WITH RENAL:
IS IT PATIENT OR DISEASE RELATED?
Authors: Mohamed Nourelsabah , Refaie Ayman , Zayed Kareem , Sobh Mohamed
Published: June 2023

Background and Aims

Cardiovascular disease is one of the leading causes of death in SLE patients (Fors Nieves CE, et al. 2016). Coronary artery calcium scores can be used as a predictor CVD events, independent of traditional risk factors. CAC scores quantify the presence and extent of calcified plaque in the coronary arteries. A CAC>0 in the general population is an independent predictor of CVD mortality (PatKiani AN, et al. 2015) patients with SLE, especially those aged >45 years, have an increased prevalence of CAC and the presence of renal affection obviously increases this risk. Patients with SLE aged ≤45 years have an increased prevalence of detectable CAC compared with the general population (Yevgeniya Gartshteyn, et al. 2019). We evaluated CAC in SLE with predominantly renal affection.

Method

in this observational study We identified 86 patients with SLE and documented lupus nephritis by renal biopsy ISN/RPS classification 2004, without known coronary artery disease and who had a non-contrast chest CT performed as part of their clinical care, with images retrievable for calculation of CAC scores. Demographics, disease characteristics and comorbidities were ascertained and adjusted for.

Results

15.1% of patients with SLE, LN (mean age 43±11 years, 84%female,) had CAC>0, 53.8% for age ≤45 years and 46.2% for age >45. Patients with SLE with CAC>0 were older and had longer disease duration and higher disease activity than patients with normal CAC (p.value 0.004, 0.004 and 0.02 respectively) Furthermore, DM was at higher incidence in normal CAC patient and all patients with CAC>0 were hypertensive.

Conclusion

Patients with SLE and LN have an increased prevalence of detectable CAC Our data suggest that subclinical atherosclerosis in SLE may develop early and it is directly related to disease factors as its duration and pathological activity. although, patient age is an important risk factor for developing coronary artery calcification. and this need a close monitoring and even some cardioprotective interventions.