bluuebunny/crossref_metadata_2025_split huggingface dataset:
#2892 CRITICAL ROLE OF SERUM RESPONSE FACTOR IN PODOCYTE EPITHELIAL–MESENCHYMAL TRANSITION OF DIABETIC NEPHROPATHY
Authors: Zhao Long , Xu Yan 
Published: June 2023

Abstract

Background and Aims
To investigate the expression and function of serum response factor (SRF) in podocyte epithelial–mesenchymal transition (EMT) of diabetic nephropathy (DN).

Method
Expression of SRF, pSRF, synaptopodin, P-cadherin, ZO-1, α-SMA, FSP-1, fibronectin and collagen-1 were examined in podocytes or renal cortex following high glucose. SRF was upregulated by SRF plasmids and downregulated by CCG-1423 to investigate how SRF influence podocyte EMT in DN. Streptozocin was used to generate DM in rats.

Results
① High glucose induced EMT and SRF upregulation in podocytes (Figure 1). High glucose suppressed synaptopodin and ZO-1 expression, and induced SRF, pSRF collagen-1, FSP-1 and α-SMA expression. SRF transferred from cytoplasm to nuclei obviously and the level of SRF was also increased in podocytes after high glucose treatment. ② SRF overexpression mediated EMT, migration and barrier dysfunction of podocytes (Figure 2). Overexpression of exogenous SRF reduced epithelial synaptopodin expression, and increased collagen-1, FSP-1, α-SMA and Snail expression in podocytes. Transwell chamber migration assay showed that overexpression of SRF significantly upregulated the migration of podocytes across the pores of transwell filters. Albumin filtration assay showed that albumin easily diffused across the monolayer of podocytes transfected with SRF cDNA. ③ Inhibition of SRF preserved phenotypes of podocytes in vitro (Figure 3). CCG-1423 selectively suppressed the expression of pSRF and SRF in podocytes after high glucose stimulation. Besides, simultaneous treatment of podocytes with CCG-1423 also significantly abolished the reduction of synaptopodin expression and the induction of collagen-1, FSP-1, α-SMA and Snail expression. CCG-1423 also reduced the transfer of SRF from cytoplasm to nucleus in podocytes treated with high glucose. ④ The effect of CCG-1423 in diabetic rats (Figure 4–-5). CCG-1423 significantly abrogated the reduction of synaptopodin expression and the induction of SRF, collagen-1, α-SMA and FSP-1 expression in renal cortex tissues. Masson and PAS staining demonstrated that renal glomerular fibrosis was present in DM group, and after 8 weeks treatment with CCG-1423, renal glomerular fibrosis was dramatically ameliorated. In addition, CCG-1423 significantly preserved P-cadherin expression and suppressed α-SMA and FN expression in DN rats. More importantly, CCG-1423 dramatically decreased 24-h urine protein excretion by about 50%, and increased serum albumin, compared with DM group.

Conclusion
Together, increased SRF activity provokes podocytes EMT and dysfunction in DN. Targeting SRF by small molecule inhibitor may be an attractive therapeutic strategy for DN.
#2912 HYDRATION STATUS IN PATIENTS ON STANDARD HEMODIALYSIS OR ONLINE HEMODIAFILTRATION: ITS RELATIONSHIP WITH PARAMETERS MEASURED OR ESTIMATED BY BIVA
Authors: Vega Nicanor , Alman Francisco Alonso , López Yanet Parodis , Ortega Sebastian Hillebrand , Anton-Perez Gloria 
Published: June 2023

Abstract

Background and Aims
Altered fluid status and inadequate fluid management, independently and concurrently with depletion of lean mass adversely affect patients’ quality of life, outcomes and prognosis of hemodialysis (HD) patients, both standard (HD) and Hemodiafiltration on-line (HDFOL).

Method
We conducted a population-based on 470 patients, retrospective longitudinal cohort study, to determine the physical characteristics of bioimpedance measurements and indexes obtained by BIVA on maintenance HD and HDFOL patients, and to analyze the hydration status of the extra and intracellular compartments. The Propensity Score Matching (PSM) procedure, matches case records with similar control records. It first runs a logistic regression with the case/control group variable as the dependent variable. Then it selects a match for each case from the control group based on the PSM from the logistic regression. Euhydrated and Overhydrated groups were macheted separately.

Results
see Table 1, Figure 1 and 2.

Conclusion
1) Compared to standard HD, the HDFOL technique maintains a better water balance between the intracellular and extracellular spaces, especially when the patient is euhydrated. In overhydrated patients, although the ECW/ICW ratio is high, it is lower in patients on HDFOL. 2) The stability of cell membranes in HDFOL is better than in HD. 3) For an adequate assessment of any of the parameters measured directly or derived from the BIA, it must be a “sine qua non” condition that the patient is in a state of euhydration. 4) In hemodialysis patients, the phase angle, must first be considered as a marker of hydration status, and then as a marker of nutritional status.
#2920 MAGNESIUM DEFICIENCY ABROGATES THE RENOPROTECTIVE EFFECT OF DPP-4 INHIBITOR ON CISPLATIN-INDUCED KIDNEY INJURY
Authors: Iwakura Takamasa , Ema Chiemi , Fujikura Tomoyuki , Fukasawa Hirotaka , Yasuda Hideo 
Published: June 2023

Abstract

Background and Aims
Cisplatin is an effective chemotherapeutic agent, but often induces acute kidney injury (AKI). Magnesium (Mg) deficiency is often found in cancer patients, and the nephrotoxicity of cisplatin is exacerbated under Mg deficiency [1]. We previously reported the potential of Dipeptidyl peptidase-4 (DPP-4) inhibitor to attenuate cisplatin nephrotoxicity in rats and diabetic cancer patients [2, 3]. However, it remains to be investigated whether DPP-4 inhibitor can preserve its renoprotective effect under Mg deficiency. The purpose of this study was to examine whether DPP-4 inhibitor can prevent cisplatin-induced AKI even under Mg deficiency.

Method
Sprague Dawley rats received Mg-deficient diet for 7days to induce Mg deficiency. AKI was induced in rats by injecting cisplatin intravenously. Oral administration of a DPP-4 inhibitor, once a day, was started 1day before injecting cisplatin. Mg sulfate was once injected intraperitoneally just before injecting cisplatin to correct Mg deficiency (Fig. 1A). By using our previous cohort data [3], we divided diabetic cancer patients treated with high-dose cisplatin (&gt;50 mg/m2)-containing regimens into 4 groups according to the use/unused of Mg sulfate or DPP-4 inhibitor. The change of estimated glomerular filtration rate (eGFR) within 2 weeks after cisplatin treatment was compared between the groups.

Results
At the peak of AKI (day 5), Mg sulfate supplementation significantly attenuated the increase of blood urea nitrogen (BUN), and combination of Mg sulfate and DPP-4 inhibitor further suppressed the increase of BUN as compared to rats received only cisplatin. However, DPP-4 inhibitor alone did not attenuate the increase of BUN under Mg deficiency (Fig. 1B). The result of serum creatinine (sCr) was consistent with that of BUN (Fig. 1C). This effect was associated with a reduced renal cell death as evaluated with the terminal uridine nick-end labeling (TUNEL)+ cells (Fig. 1D).The change of eGFR was significantly less in the patients treated with both of DPP-4 inhibitors/Mg supplementation, compared to those without DPP-4 inhibitors/Mg supplementation. The effect was not found in patients with either DPP-4 inhibitor alone or Mg supplementation alone as compared to those without DPP-4 inhibitor/Mg supplementation (Fig. 2).

Conclusion
Our results suggested that Mg deficiency must be corrected to exert the renoprotective effect of DPP-4 inhibitor on cisplatin nephrotoxicity. The molecular mechanisms underlying this phenomenon remain to be defined.
#2934 SGLT-2 INHIBITORS DELAY KIDNEY FAILURE PROGRESSION AND REDUCE NEED OF DIALYSIS IN CHRONIC KIDNEY DISEASE PATIENTS: A META-ANALYSIS
Authors: Mahendra Aditya Indra , Samsu Nur , Gunawan Atma , Rifai Achmad 
Published: June 2023

Abstract

Background and Aims
chronic kidney disease (CKD) is the main complication of type 2 diabetes mellitus (type 2 DM) with up to 7 million cases requiring dialysis therapy. The newest type 2 DM therapy, sodium-glucose co-transporter-2 inhibitor (SGLT-2 inhibitor), has developed into an attractive option for patients with comorbid CKD because of its effect on blood pressure and albuminuria, in addition to its effect on lowering blood sugar. Therefore, we conducted a systematic review and meta-analysis aimed at assessing the effect of SGLT-2 inhibitors in preventing the progression of renal failure and the need for dialysis in CKD patients with and without type 2 DM.

Method
We performed an analysis of randomized controlled trials of SGLT-2 inhibitors reporting renal outcomes in patients with and without type 2 DM. We searched the PUBMED, MEDLINE, and CENTRAL databases from baseline to August 2022 to identify suitable studies. The major outcome evaluated was the combination of a persistent increase in serum creatinine two times from baseline and the need for dialysis.

Results
Of the 2890 identified articles, ten studies were included in the inclusion criteria assessing the effect of using SGLT-2 inhibitors. Out of 76,312 participants, 1716 participants experienced a 2-fold increase in serum creatinine, and 647 participants required dialysis. The use of SGLT-2 inhibitors significantly reduced progressive renal failure and the need for dialysis in both patients with type 2 DM (RR: 0.65, 95% CI 0.60–0.71, p = 0.000) and patients without type 2 DM (RR: 0.59, 95% CI 0.46–0.77, p = 0.000). Subgroup analysis also showed that SGLT-2 inhibitors showed a significant effect in the group with eGFR &gt; 60 ml/min (RR: 0.53, 95% CI 0.45-0.62, p = 0.000) and the group with eGFR 30- 60 ml/min (RR:0.66, 95% CI, 0.57-0.75, p = 0.000).

Conclusion
SGLT-2 inhibitors can significantly inhibit the progression of CKD and reduce the risk of needing dialysis in patients with and without type 2 DM. These effects were shown consistently across groups with varying baseline eGFR values.
#2938 DE NOVO DSA IS ASSOCIATED WITH HUMAN PERIPHERAL BLOOD CXCR5+PD-1+CD8+ T CELLS AND PD-1 PD-L1 MRNA EXPRESSION IN KIDNEY TRANSPLANT PATIENTS
Authors: Ekinci Nurten Sayin , Kocak Huseyin , Ucar Fahri , Yilmaz Vural Taner , Darbas Sule , Kisaoglu Abdullah , Kilinc Yahya , Aydinli Bulent , Uzuner Sezin Yakut 
Published: June 2023

Abstract

Background and Aims
Donor-specific antibody (DSA) development is mainly responsible for chronic antibody-mediated rejection. The immunological events that cause the development of DSA is not fully elucidated. The relationship between the Follicular Cytotoxic T cell subgroup and the development of DSA is unknown. In this study we aimed to examine CD8+CXCR5+PD-1+ follicular cytotoxic T cell levels and expression levels of PD1/PD-L1 genes in peripheral blood lymphocytes in recipients who de-novo DSA positive or negative after kidney transplantation (KTX).

Method
In this study, the expression levels of PD-1, PD-L1 genes were determined using the Real-Time Quantitative PCR method from peripheral blood samples of 22 KTX patients with de-novo DSA positive, 20 KTX patients with DSA negative and 21 healthy control (Table 1). Our patient groups were PRA negative before transplantation. Expression (%) levels of target cells were evaluated by flow cytometry method. IBM SPSS Statistics for Windows Version 22 and R.3.3.2 software were used to evaluate the data.

Results
PD-1 expression level was higher in the KTX patients with de-novo DSA positive compared to the KTX patients with DSA negative group (p:0.006 CT: 0,84±0,23). According to the results of flow cytometry, CD8+CXCR5+PD-1+ cell expression (%) levels were found to be significantly higher in patients (3,06±1,98) compared to the transplant control group (0,52±0,40) (p: 0.001) (Figure 1).

Conclusion
It shows that there may be a direct correlation between DSA and PD-1 / PDL-1 mRNA level and CXCR5+PD1+CD8+ follicular cytotoxic T cell in transplant patients after kidney transplantation.
#2948 β-2-MICROGLOBULIN AND β-TRACE-PROTEIN DO NOT IMPROVE ESTIMATION OF GFR IN KIDNEY TRANSPLANT RECIPIENTS COMPARED TO CREATININE AND CYSTATIN C
Authors: Kure Nathalie , Krogstrup Nicoline , Oltean Mihai , Jespersen Bente , Birn Henrik , Nielsen Marie Bodilsen 
Published: June 2023

Abstract

Background and Aims
Precise estimates of glomerular filtration rate (eGFR) are important in kidney transplant recipients (KTRs). Current eGFR formulas based on plasma creatinine and/or cystatin C are associated with significant bias. We investigated whether race free formulas based on plasma values of β-trace-protein and β-2-microglobulin performed better than formulas based on creatinine and cystatin C in a Scandinavian cohort of KTRs.

Method
We included samples and data from the randomised, controlled trial CONTEXT. GFR was measured by plasma clearance of 51Cr-EDTA or iodothalamate. eGFR was calculated using the new race-free CKD-EPI eGFR-creatinine and/or cystatin C(2021) formulas as well as the CKD-EPI eGFR-β-trace-protein and/or eGFR-β-2-microglobulin formulas. GFR estimates were evaluated at 3 (n = 82) and 12 (n = 64) months post-transplant using mean bias, precision, and accuracy. Also, formulas were analysed for their ability to correctly classify changes in measured GFR from 3 to 12 months.

Results
At 12 months eGFR-creatinine-cystatin C performed best according to mean bias (−4.54 ml/min/1.73 m2), precision (SD = 8.18 ml/min/1.73 m2) and accuracy (P10 = 47%) among creatinine and cystatin C based formulas (Table 1). Among the β-trace-protein and β-2-microglobulin based formulas, eGFR-β-trace-protein-β-2-microglobulin performed best according to precision (SD = 7.64 ml/min/1.73 m2) and accuracy (P10 = 36%) (Table 1). eGFR-β-trace-protein-β-2-microglobulin and eGFR-creatinine-cystatin C performed similar when comparing residuals (p = 0.481). eGFR-β-trace-protein, eGFR-β-trace-protein-β-2-microglobulin and eGFR-creatinine-cystatin C performed best in correctly classifying changes in mGFR from 3 to 12 months.

Conclusion
β-trace-protein and β-2-microglobulin do not improve the measurement of GFR compared to creatinine and cystatin C based formulas in KTRs.
#2964 THE ROLE OF RENAL DYSFUNCTION DURING ANTICOAGULANT USE IN COPD PATIENTS WITH ATRIAL FIBRILLATION
Authors: Karimdjanova Guzal 
Published: June 2023

Abstract

Background and Aims
Renal dysfunction is known to be the most important predictor of outcome in patients with atrial fibrillation (AF). Purpose of the study was to evaluate the prognostic role of kidney dysfunction in terms of possible cardiovascular events and bleeding in patients with COPD and AF treated with oral anticoagulants.

Method
We examined 56 COPD patients with CHF and AF who received oral anticoagulants. Renal function (creatinine level and estimated glomerular filtration rate - eGFR) was assessed at baseline and at follow-up. The functional state of the kidneys was calculated using the CKD-EPI-2011 formula. Initially, the risk of bleeding was assessed using the HAS-BLED score. The deterioration of the functional state of the kidneys was noted with an increase in the level of creatinine or a decrease in eGFR by at least 20%.

Results
In addition to the standard treatment for COPD in the presence of AF, patients received oral anticoagulants during a six-month follow-up. The deterioration of the functional state of the kidneys was observed in 18.3% of patients. In patients with kidney dysfunction, the frequency of episodes of CHF decompensation and non-massive bleeding (MB) was significantly higher. When reduced glomerular filtration rate did not affect the frequency of bleeding and stroke. The oral anticoagulants used did not significantly affect the observed renal dysfunction and did not affect the occurrence of new cardiovascular events in patients with COPD. It turned out that the predictors of renal dysfunction in patients with COPD are age, female gender, and lower hemoglobin levels. In multivariate analysis, renal dysfunction was identified as an independent predictor of non-massive bleeding (OR 2.04, 95%, p&lt;0.05).

Conclusion
In patients with COPD and atrial fibrillation, the presence of kidney dysfunction was an additional aggravating factor associated with adverse cardiovascular prognosis in the medium term and the risk of bleeding. However, oral anticoagulants did not affect the degree of deterioration in renal function or the incidence of cardiovascular events.
#2965 DYNAMICS OF THE FUNCTIONAL STATE OF THE KIDNEYS IN PATIENTS WITH DIABETES MELLITUS AND A HIGH RISK OF CI-AKI AND THE USE OF PREVENTIVE MEASURES
Authors: Nigmonov Baxodir , Muminov Shavkat , Saipova Durdona 
Published: June 2023

Abstract

Background and Aims
Analysis of the pathogenetic mechanisms of the development of contrast nephropathy in patients with coronary artery disease on the background of type 2 diabetes mellitus and the effectiveness of the proposed preventive measures.

Method
The study included 56 patients with type 2 diabetes, the average age of the patients was 58 years, the CG consisted of 20 healthy persons. In most patients, the reason for which the endovascular radiopaque procedure (EVRCP) was performed was associated with atherosclerotic lesions: coronary artery disease, chronic lower limb ischemia (CLLI), atherosclerosis of the brachiocephalic arteries (BCA). EVRCP was performed on the vessels of the coronary basin, BCA, abdominal aorta and its branches, lower extremities. A retrospective analysis included a comparative analysis of two groups of patients with type 2 diabetes who underwent (EVRCP): 29 patients who developed CI-AKI (CI-AKI+ group) and 27 patients in whom the post-procedure period was uneventful. CI-AKI was defined as an increase in venous creatinine concentration of more than 25% by the end of 48 hours after EVRCP. During this phase of the study, the patient's medical history was analyzed - their anamnestic data, glycemic status, general urinalysis, kidneys, estimated glomerular filtration rate (eGFR) initially, 2,4,6,8 and 10 days after the procedure.

Results
The CI-AKI+ and CI-AKI- groups were compared in terms of clinical and anamnestic, hematological, urological data and the results of echocardiography and renal ultrasound with each other and with representatives of the CG. The CI-AKI+ and CI-AKI- groups did not differ in nosological distribution (Fig. 1): in both groups, half of the patients with EVRCP were performed due to the presence of coronary pathology (51.72% and 48.15%, respectively), the rest in patients it was comparable for CCI and CVD (27.59% and 20.69% in the CI-AKI+ group and 25.93% each in the CI-AKI- group).

Conclusion
Taking into account the OR of CI-AKI in patients with DM in the presence of identified predictors, a risk scale was developed. A risk score of 28 points or more demonstrates a predictive sensitivity in terms of the development of CI-AKI of 96.55% (p&lt;0.001).
#2971 LONG-TERM EFFECTS OF THE NEW NORDIC RENAL DIET ON PHOSPHOROUS HOMEOSTASIS IN PATIENTS WITH CHRONIC KIDNEY DISEASE STAGE 3 AND 4
Authors: Hansen Nikita Misella , Kamper Anne Lise , Rix Marianne , Feldt-Rasmussen Bo , Pareek Manan , Sørensen Mads Vaarby , Berg Peder , Leipziger Jens , Astrup Arne , Salomo Louise 
Published: June 2023

Abstract

Background and Aims
Chronic kidney disease (CKD) causes severe disturbances in phosphate metabolism. The New Nordic Renal Diet (NNRD) is a whole food approach designed by our group, with low dietary phosphorus content (850 mg/day). In a 1-week study, NNRD had positive effects on phosphorus homeostasis in patients with CKD stage 3-4 [1]. The aim of the present study was to examine the long-term health effects of a dietary intervention with NNRD in patients with CKD stage 3-4 [2].

Method
A 26-week randomized, controlled, non-blinded trial comparing the effect of NNRD vs. non-restricted habitual diet. Patients in the NNRD group received weekly home delivery of fresh food items (free of charge) and recipes for five days of the week, and on the remaining two days they were instructed to prepare meals according to the NNRD food principles. The study was designed with seven follow-up visits in the outpatient clinic where fasting blood samples and 24-hour urine collection were delivered. Linear mixed-effects models were used to assess the effects of the intervention, time, and the potential interaction between intervention and time. The primary endpoint was the difference in 24-hour urine phosphorus excretion between the two study groups. Secondary endpoints included fractional phosphorus excretion and plasma fibroblast growth factor 23 (p-FGF23).

Results
Sixty patients (mean age 54 years, 31 women) with mean eGFR of 34 ml/min/1.73 m2 were included. Two patients were withdrawn due to dialysis initiation. In the NNRD-group (n = 29), mean 24-hour urine phosphorus excretion during the intervention period was 651 mg (SD, 35 mg) vs. 930 mg (SD, 84 mg) in the control group (n = 29), between-group difference 279 (95% CI; -372, -91; P &lt; 0.001) (Figure 1). Mean fractional phosphorus excretion was 11% (SD, 5%) in the NNRD-group and 14% (SD, 7%) in the control group, between-group difference 3% (95% CI; -6.4, -0.8; P = 0.01). Mean p-FGF23 was 162 pg/ml (SD, 130 pg/ml) in the NNRD-group and 215 pg/ml (SD, 230 pg/ml) in the control group, between-group difference 52 pg/ml (95% CI; -100, 73; P = 0.03). P-urea was 3.4 mmol/L lower in the NNRD group (95% CI; -5.3, -0.2, P = 0.03). P-albumin was 1.1 g/L higher in the NNRD group (95% CI; 0.02, 2.4; P = 0.04) and 24-h urine bicarbonate excretion was 4.1 mmol higher in the NNRD group (95% CI; 0.7, 7.5, P = 0.01). There was no difference between study groups in p-phosphorous, p-creatinine, p-potassium, p-calcium, p-lipids, or proteinuria.

Conclusion
NNRD intervention in the context of fresh food delivery and recipes was feasible and had a major beneficial effect on phosphorous parameters in patients with CKD 3-4.