Lower Serum Creatinine Levels Research Articles

#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.

#2209 Hypoglycemia induced by hemodialysis in diabetic and non-diabetic patients, how to prevent it? A prospective study

Abstract Background and Aims Hemodialysis-induced hypoglycemia, a documented complication associated with adverse clinical outcomes, including mortality, is linked to factors such as impaired gluconeogenesis, inadequate nutritional status, reduced insulin clearance, glucose loss to the dialysate, and autonomic neuropathy. Glycemic variability is recognized as an independent risk factor for morbidity and mortality. This study aims to investigate the incidence of hypoglycemia during hemodialysis (HD) by exploring protocol-related factors and their impact, such as in-nutrition during HD. Additionally, the study seeks to examine the relationship between nutritional and inflammatory statuses and variations in intradialytic glycemia in both diabetic and non-diabetic patients. Method This prospective study, conducted between September and December 2023, examined the glycemic profiles of HD patients at a hospital HD program. All patients undergo hemodialysis with a dialysate containing 100 mg/dL of glucose. Plasma glucose levels were assessed at the start, 2:30 hours post-initiation, and the end of sessions. Following the 2:30-hour mark, patients received a meal (523 Kcal). Glycose variability was computed by averaging blood glucose differences across all sessions. Data collected included demographics, hemodialysis specifics, and lab results. Inflammatory and nutritional statuses were evaluated using lab tests at the study's beginning and conclusion [ferritin, protein C reactive (PCR), interleukin 6 (IL-6) and albuminemia, urea, creatinemia, cholesterol, respectively]. Anthropometric measurements and bioimpedance assessments were performed, with values averaged for better representation. Categorical variables are shown with frequencies/percentages, and continuous variables with means/standard deviations or medians/interquartile ranges for skewed distributions. The study used repeated measures ANOVA for glycemic profiles, correlation analyses for outcome influences on glycemia, and parametric/non-parametric tests for relations in diabetic and non-diabetic groups. Significance was set at p<0.05, analyzed with SPSS version 29 for Mac OS 13. Results 63 patients, 67.2% (n=43) were males, the medium age was 72.0±11.8 and 50.8% (n=32) had diabetes. Among 9072 measurements, hypoglycemia was observed in 0.07% (n=6) of diabetic patients and 0.01% (n=1) in non-diabetic individual. The initial blood glucose measurement was 139.5±260.0 mg/dL, the second was 117.05±35 mg/dL, and the third was 132.8±21.3 mg/dL. Significant differences were observed in all measurements [F (1.17, 73.58)=23.62; p<0.001]. The mean glycemic variation between the first and second measurements was 23.8±46.0 mg/dL, and for the third measurement was 5.5±71.5 mg/dL. There was no significant correlation found between glycemic and nutritional parameters neither between inflammatory parameters. In the subgroup analysis comparing diabetic and non-diabetic patients, the diabetic group demonstrated lower serum creatinine levels (6.8±2.7 mg/dL) and total cholesterol (137.4±35.6 mg/dL), coupled with a higher Charlson Index (8.2±1.7). These differences were statistically significant (p=0.055, p=0.035, p<0.001). In the subsequent analysis, no other statistically significant associations were observed. Conclusion Contrary to what is described in the literature, the studied population exhibited a very low incidence of hypoglycemic events. This underscores the importance of nutrition during HD, along with the use of a glucose-containing dialysate, as an effective preventive measure against intradialytic hypoglycemia. Careful consideration of these factors is warranted to prevent adverse health consequences for our patients. It is plausible that diabetic patients may face an elevated risk of malnutrition, necessitating heightened concern and a more proactive preventive approach.

Low serum creatinine levels are associated with major post-operative complications in patients undergoing surgery with gynecologic oncologists

ObjectiveSerum creatinine is a byproduct of muscle metabolism, and low creatinine is postulated to be associated with diminished muscle mass. This study examined the association between low pre-operative serum creatinine...

IJCM_318A: Risk Factors for Anaemia among Type 2 Diabetes Mellitus Patients in Mangalore- A Case Control Study.

Background: Anaemia, a common haematological abnormality, currently stands at a prevalence rate of 24.8% worldwide and 39.86% in India, affecting 1.62 billion individuals overall. Studies have shown that patients with Diabetes are twice as likely to be prone to anaemia. Objective: To study the risk factors for anaemia among patients with type 2 Diabetes Mellitus. Methodology: This is a record-based case-control study of 50 cases (diabetic with anaemia) and 100 controls (diabetic without anaemia) in Government Wenlock Hospital, Mangalore. Patients with haemoglobin concentration below the normal level (as defined by WHO as <13 g/dl for men and <12 g/dl for women) were considered anaemic. Data was entered and analyzed using the statistical software SPSS Version 17.0. Univariate analyses and a Chi-Square test were conducted to identify risk factors. Results: The median age of cases as well as controls was 60 years. The duration of diabetes was 8 years in cases and 7 years in controls. Among 50 cases, there were 39 (78%) males and 11(22%) females and among 100 controls, 68(68%) males and 32(32%) females. On univariate analysis, it was found that the low serum urea, creatinine, albumin, total protein and calcium levels were significantly associated with the presence of anaemia (P <0.05). Conclusion: The above parameters implicate impairment in renal function and hence we can conclude that impaired renal function is a risk factor for developing anaemia in type 2 Diabetes Mellitus patients.

High Serum Galectin-3 Level as a Potential Biomarker of Peripheral Artery Disease in Patients Undergoing Hemodialysis.

Galectin-3 is implicated in the pathogenesis of inflammation and atherosclerosis. Peripheral arterial disease (PAD), characterized by a reduced ankle-brachial index (ABI), is a prognostic marker for mortality in patients on hemodialysis. We investigated the relationship between serum galectin-3 levels and PAD in patients undergoing regular hemodialysis. We carried out a cross-sectional study at a medical center, involving 92 participants. Serum galectin-3 levels were assessed by a commercially available enzyme-linked immunosorbent assay. ABI measurement was done with an automatic device based on oscillometry. Participants were categorized into two groups, normal and low ABI, based on a 0.9 cut-off point. Eighteen patients (19.6%) exhibited a low ABI. In individuals with low ABIs, we observed a greater prevalence of diabetes mellitus, elevated serum C-reactive protein (CRP) levels, increased galectin-3 levels, and lower serum creatinine levels. Furthermore, serum galectin-3 levels (odds ratio [OR]: 1.056, 95% confidence interval [CI]: 1.003-1.112, p = 0.037) and CRP (per 0.1 mg/dL increment, OR: 1.195, 95% CI: 1.032-1.383, p = 0.017) were identified as independent predictors of PAD. Serum galectin-3 and log-transformed CRP levels were also independently and significantly negatively correlated with the left and right ABI values. Serum galectin-3 levels correlate with PAD in patients undergoing maintenance hemodialysis.

Glomerular Exostosin-Positivity is Associated With Disease Activity and Outcomes in Patients With Membranous Lupus Nephritis

IntroductionThe relationship of Exostosin 1 and Exostosin 2 (EXT1/EXT2) expression and outcomes in membranous lupus nephritis (MLN) was controversial. MethodsEXT1/EXT2 was performed by immunohistochemistry in 283 consecutive MLN patients. Clinicopathological characteristics and outcomes of EXT1/EXT2-positive patients were compared with EXT1/EXT2-negative patients.The primary endpoints were adverse renal events include death, dialysis and renal transplantation. Results29.3% MLN patients were positive for EXT1/EXT2. The prevalence of EXT1/2 positive MLN was significantly higher in pure class V MLN than those for mixed class V MLN (44.2% vs. 19.4%, P<0.001). For EXT1/EXT2-positive patients, For EXT1/EXT2-positive patients, the median time between onset of lupus and renal biopsy, and lupus nephritis and renal biopsy is shorter [6 (IQR, 2-25) months vs. 12 (IQR, 3-49) months, P=0.008 and 3 (IQR, 2-18) months vs. 6 (IQR, 2-23) months, P=0.039].) and they had significantly lower Systemic Lupus Erythematosus Disease Activity Index scores (P=0.015) and lower serum creatinine levels (P<0.001), higher hemoglobin (P=0.006) as well as lower blood pressure. The EXT1/EXT2-positive patients had significantly fewer chronicity features (glomerulosclerosis, P<0.001, interstitial fibrosis, P=0.006, and tubular atrophy, P=0.002) and fewer activity indicators (endocapillary hypercellularity, P=0.012, fibrocellular crescents, P=0.007 and cellular crescents, P<0.001) on renal biopsy. After a Median follow-up of 65 (28-126) months, EXT1/EXT2-positive patients were less likely to experience adverse renal events (2.4% vs. 16.0%, P=0.001). ConclusionCompared with EXT1/EXT2-negative patients, the EXT1/EXT2-positive patients presented with lower disease activity and were less likely to experience adverse renal events in relationship with the chronicity index.

Muscle-Derived Stem/Progenitor Cells Ameliorate Acute Kidney Injury in Rats through the Anti-Apoptotic Pathway and Demonstrate Comparable Effects to Bone Marrow Mesenchymal Stem Cells.

Background and Objectives: To date, the therapeutic potential of skeletal muscle-derived stem/progenitor cells (MDSPCs) for acute kidney injury (AKI) has only been evaluated by our research group. We aimed to compare MDSPCs with bone marrow mesenchymal stem cells (BM-MSCs) and evaluate their feasibility for the treatment of AKI. Materials and Methods: Rats were randomly assigned to four study groups: control, GM (gentamicin) group, GM+MDSPCs, and GM+BM-MSCs. AKI was induced by gentamicin (80 mg/kg/day; i.p.) for 7 consecutive days. MDSPCs and BM-MSCs were injected 24 h after the last gentamicin injection. Kidney parameters were determined on days 0, 8, 14, 21, and 35. Results: MDSPCs and BM-MSCs accelerated functional kidney recovery, as reflected by significantly lower serum creatinine levels and renal injury score, higher urinary creatinine and creatinine clearance levels (p < 0.05), lower TUNEL-positive cell number, and decreased KIM-1 and NGAL secretion in comparison to the non-treated AKI group. There was no significant difference in any parameters between the MDSPCs and BM-MSCs groups (p > 0.05). Conclusions: MDSPCs and BM-MSCs can migrate and incorporate into injured renal tissue, resulting in a beneficial impact on functional and morphological kidney recovery, which is likely mediated by the secretion of paracrine factors and an anti-apoptotic effect. MDSPCs were found to be non-inferior to BM-MSCs and therefore can be considered as a potential candidate strategy for the treatment of AKI.

Anti–Phospholipase A2 Receptor 1 and Anti–Cysteine Rich Antibodies, Domain Recognition and Rituximab Efficacy in Membranous Nephropathy: A Prospective Cohort Study

Rationale & ObjectiveProteinuria and anti-phospholipase A2 receptor 1 (anti-PLA2R1) antibody titers are associated with primary membranous nephropathy (MN) outcomes. We evaluated the association of antibodies against the cysteine-rich (CysR) and C-type lectin 1, 7, and 8 (CTLD1, CTLD7, and CTLD8) domains of PLA2R1 with MN outcomes. Study DesignProspective cohort study. Setting & ParticipantsOne-hundred-thirteen consecutive, consenting patients referred to the Nephology Unit of the Azienda-Socio-Sanitaria-Territoriale (ASST) Papa Giovanni XXIII (Bergamo, Italy) with PLA2R1-related, biopsy-proven MN whose persistent nephrotic syndrome (NS) was managed conservatively for >6 months and were monitored with serial evaluations of proteinuria, autoantibodies (by ELISA), and clinical outcomes. ExposureRituximab. OutcomesComplete (proteinuria <0.3 g/24h) or partial (proteinuria >0.3 g/24h and <3.0 g/24h with >50% reduction vs. basal) NS remission. Analytical ApproachUnivariable and multivariable Cox regression analyses. ResultsAll patients had anti-CysR antibodies; 62 (54.9%) were multi-domain recognizers. Anti-PLA2R1 and anti-CysR antibody titers were strongly correlated at baseline (p<0.001, r=0.934), 6 months (p<0.001, r=0.964), and 12 months (p<0.001, r=0.944). During a median (IQR) follow-up of 37.1 (20.3-56.9) months, 71 patients (62.8%) achieved either complete or partial remission of their NS. Lower baseline anti-PLA2R1 [HR (95% CI): 0.997 (0.996-0.999), p=0.002) and anti-CysR [HR (95% CI): 0.996 (0.993-0.998), p=0.001) titers were associated with a higher probability of remission, along with female sex, lower proteinuria, and lower serum creatinine levels (p<0.05 for all comparisons). Anti-CTLD antibodies were not associated with outcomes. At 6 and 12 months, compared to baseline, anti-PLA2R1 and anti-CysR antibody titers decreased more in patients progressing to partial or complete remission than in those without remission (p<0.05 for all comparisons). LimitationsObservational design. ConclusionsIn PLA2R1-related MN, anti-PLA2R1 and anti-CysR antibodies similarly predict rituximab efficacy, independent of PLA2R1 domain recognition. The choice between these tests should be dictated by feasibility and costs. Evaluating anti-CTLD antibodies appears unnecessary.

Overall Survival Prediction by Tumor Microenvironment Lymphocyte Distribution in Hepatocellular Carcinoma After Liver Transplantation

IntroductionOur previous research demonstrated that CD8+ cell density profiling using a hexagonal grid-based digital image analysis method provides predictors of patient outcomes after liver resection due to hepatocellular carcinoma (HCC). Continuing our study, we have further investigated the applicability of the methodology to patients receiving a liver transplant for HCC. MethodsThe retrospective study enrolled patients with HCC who underwent liver transplantation (LT) at the Vilnius University Hospital Santaros Clinics between 2007 and 2020. We determined the density profiles of CD8+ lymphocytes at the interface between HCC and stroma and the interface between the perineoplastic liver parenchyma and stroma. Both digital image analysis and the hexagonal grid-based immunogradient method were applied to CD8+ immunohistochemistry images. Survival statistics based on clinicopathological, peripheral blood analysis, and surgical data determined the prognostic value of these indicators. ResultsUnivariate clinicopathological predictors of worse OS after LT included: patient's age at the time of the transplantation, a higher number of HCC nodules, lower platelet count, longer activated thromboplastin time, lower serum albumin, higher serum total bilirubin, and lower serum creatinine levels. The two independent predictors of overall survival were mean CD8+ cell density at the epithelial edge of the explanted liver parenchyma-stroma interface and peripheral blood platelet count. ConclusionsOur model discloses that preoperative peripheral blood platelet count and mean CD8+ cell density at the epithelial edge of nonmalignant interface in the explanted liver parenchyma are independent predictors of OS for HCC after LT.

Sulfide:quinone oxidoreductase alleviates ferroptosis in acute kidney injury via ameliorating mitochondrial dysfunction of renal tubular epithelial cells

Ferroptosis is iron-dependent and regulates necrosis caused by lipid peroxidation and mitochondrial damage. Recent evidence has revealed an emerging role for ferroptosis in the pathophysiology of acute kidney injury (AKI). Sulfide:quinone oxidoreductase (SQOR) is a mitochondrial inner membrane protein highly expressed in the renal cortex. However, the effects of SQOR on ferroptosis and AKI have not been elucidated. In this study, we evaluated the effects of SQOR in several AKI models. We observed a rapid decrease in SQOR expression after cisplatin stimulation in both in vivo and in vitro models. SQOR-deletion mice exhibit exacerbated kidney impairment and ferroptosis in renal tubular epithelial cells following cisplatin injury. Additionally, our results showed that the overexpression of SQOR or ADT-OH (the slow-releasing H2S donor) preserved renal function in the three AKI mouse models. These effects were evidenced by lower levels of serum creatinine (SCr), blood urea nitrogen (BUN), renal neutrophil gelatinase-associated lipocalin (NGAL), and kidney injury molecule 1 (KIM-1). Importantly, SQOR knockout significantly aggravates cisplatin-induced ferroptosis by promoting mitochondrial dysfunction in renal tubular epithelial cells (RTECs). Moreover, online database analysis combined with our study revealed that SYVN1, an upregulated E3 ubiquitin ligase, may mediate the ubiquitin-mediated degradation of SQOR in AKI. Consequently, our results suggest that SYVN1-mediated ubiquitination degradation of SQOR may induce mitochondrial dysfunction in RTECs, exacerbating ferroptosis and thereby promoting the occurrence and development of AKI. Hence, targeting the SYVN1-SQOR axis could be a potential therapeutic strategy for AKI treatment.

Acute interstitial nephritis caused by ANCA-associated vasculitis: a case based review.

Antineutrophil cytoplasmic antibodies (ANCA)-associated vasculitis (AAV) typically manifests as rapidly progressive glomerulonephritis with crescent formation. In this report, we present a local case of myeloperoxidase (MPO)-AAV-associated acute interstitial nephritis (AIN), showing slight pauci-immune glomerulonephritis and positive MPO-ANCA. This case is characterized by foot process effacement of podocytes in the glomerulus, a favorable prognosis, and an absence of crescentic formation. To further understand this condition, we conducted a comprehensive literature search on Google Scholar and PubMed, employing both free text words and MeSH terms related to "AAV and AIN." This search yielded 24 cases, which we analyzed for their clinical features, laboratory findings, renal pathological characteristics, and therapeutic outcomes. AAV-associated interstitial nephritis predominantly affects elderly patients and is often associated with anemia, proteinuria, hematuria, and nonspecific manifestations, including fever, anorexia, fatigue, edema, and weight loss. Most of the cases in our review were MPO-ANCA-positive and exhibited isolated interstitial inflammation. These patients typically presented with relatively lower levels of serum creatinine, 24-h urine protein levels, and MPO-ANCA titers. All patients in our study received immunosuppressive therapy, including glucocorticoids, immunosuppressants, and rituximab, with the majority achieving clinical remission. Isolated AIN in the context of AAV is a rare occurrence, but it displays distinct clinical, laboratory, and pathological features. Patients with this presentation show a positive response to immunosuppressive treatment. Nevertheless, the establishment of definitive therapy guidelines for AAV-associated AIN remains uncertain and necessitates further investigation to develop comprehensive treatment guidelines. AIN, particularly when lacking typical glomerulus lesions, may represent a novel subgroup within MPO-AAV warranting additional research and clinical attention. Key Points • This study contributes valuable scientific insights by highlighting that MPO-AAV-associated interstitial nephritis, even without crescentic formation, can exhibit podocyte foot process effacement and respond well to treatment. • The presence of AIN, independent of crescentic glomerulonephritis, suggests the potential emergence of a new subclass within MPA-AAV. • Notably, some cases of MPO-AAV-associated AIN may present with normal levels of Scr (Table 5, cases 5, 6, and 17). • This observation highlights the importance of considering renal biopsy, diagnosis, and therapy in a timely manner to prevent the development of chronic kidney disease (CKD).

The frequency of peripheral PD-1+ TCD4+ cells is reversely associated with serum creatinine levels in recipients of kidney allografts

The long-term survival of solid organ allografts remains a challenge for organ transplantation systems worldwide. T-cell exhaustion has been supposed to be associated with immunologic tolerance in transplantation and might reflect the immunologic status in recipients. The aim of the present study was to compare the TCD4+ cells of kidney transplant recipients with high and low serum creatinine levels for their expressions of PD-1 and TIGIT as two well-known exhaustion markers.Blood samples were taken from 20 kidney allograft recipients with serum creatinine levels above 2 mg/dL and 20 recipients with creatinine levels below 2 mg/dL. The percentages of PD-1+ CD4+ and TIGIT+ CD4+ cells were analyzed along with the evaluation of TNF-α, IFN-γ, and IL-10 release from peripheral blood mononuclear cells (PBMCs).The patients with serum creatinine levels below 2 mg/dL demonstrated a higher frequency of PD-1+ CD4+ T-cells (p = 0.003) along with lower TNF-α secretion from PBMCs (p = 0.028). The frequency of PD-1 + CD4+ T-cells was reversely correlated with the serum creatinine levels in recipients of kidney allografts (r = 0.59, p < 0.001). Besides, the MFI of TIGIT on TCD4+ cells demonstrated a trend for higher expression in patients with serum creatinine levels below 2 mg/dL (p = 0.070).The expression of PD-1+ on CD4+ T-cells demonstrated a potential for estimation of the immunologic status of the host in interaction with alloantigens. The exhaustion markers could be regarded as potential diagnostic indicators for the evaluation of immunologic tolerance in renal transplantation.

Acute kidney injury after living‐related liver transplantation in infants with biliary atresia: A retrospective study

AbstractAlthough acute kidney injury (AKI) is a frequent postoperative complication after liver transplantation, renal function following living‐related liver transplantation (LRLT) in infants remains understudied. The aim of this study was to identify the prevalence of AKI and the impact of AKI on outcomes in infant recipients with biliary atresia. We retrospectively reviewed infants who underwent LRLT surgery between January 2018 and January 2021. The primary outcome was the risk of postoperative AKI occurrence in the first 7 postoperative days. A multivariate regression analysis model was used to investigate risk factors for AKI, and the incidence and impacts of AKI on outcomes were analyzed. A total of 98 patients were included in the analysis. AKI occurred in 59 patients (60.2%) within 7 days after surgery. Logistic regression analysis revealed that preoperative transfusion (p &lt; 0.05) and lower serum creatinine (SCr) (p &lt; 0.05) were independent risk factors for AKI. The incidence of serious complications was significantly higher in the AKI group than in the non‐AKI group (p &lt; 0.05). The postoperative mechanical ventilation time (p &lt; 0.05) and hospital stay (p = 0.019) were significantly longer in the AKI group. There was no evidence of chronic kidney disease (CKD) in any surviving infants within 1 year after surgery. In conclusion, AKI is common in infant LRLT (60.2%), and preoperative transfusion and lower SCr levels were independently associated with AKI. AKI may be associated with the incidence of serious complications, prolonged use of ventilators, and hospital stays. No CKD occurred within 1 year.

Low Serum Creatinine as Well as High Serum Creatinine Is Associated with Prognosis of Patients with Cancer in End-of-Life.

The prognosis of end-of-life patients is challenging, and clinicians have attempted to predict survival more accurately. High serum creatinine (sCr) levels are associated with lower survival rates in patients with various cancers; however, low sCr levels are commonly expected in patients with terminal cancer because of muscle wasting and malnutrition. Therefore, we investigated the prevalence of low and high sCr levels and their association with survival duration in patients with terminal cancer in a palliative care unit. We analyzed the medical records of 280 patients admitted to a palliative care unit. Patients were divided into low (<0.5 mg/dL), normal (0.5-1.2 mg/dL), and high (>1.2 mg/dL) sCr groups. Kaplan-Meier survival curves using sCr levels were plotted and compared using the log-rank test. Using stepwise selection, a multivariable Cox proportional hazards model was used to identify the significant prognostic factors. The median survival durations in the high-, low-, and normal-sCr groups were 9.57 days, 22.26 days, and 27.51 days, respectively. Multivariable Cox proportional hazard model identified that males (hazard ratio [HR], 1.81; 95% confidence interval [CI], 1.16-2.85), poor performance status (HR, 3.43; 95% CI, 1.12-10.54), total parenteral nutrition use (HR, 1.84; 95% CI, 1.09-3.1), high sCr (HR, 2.74; 95% CI, 1.52-4.94), and low sCr (HR, 1.22; 95% CI, 1.07-1.43) were significantly associated with a shorter survival time. Low and high serum creatinine levels were significantly associated with poor survival in patients with cancer at the end-of-life stage. Therefore, readily available and simple biomarkers may help plan advanced care in palliative care settings.

Comparative efficacy and safety of sodium–glucose cotransporter 2 inhibitors for renal outcomes in patients with type 2 diabetes mellitus: a systematic review and network meta-analysis

In this study, the summarized WMDs and RRs were calculated using a pairwise analysis and a network meta-analysis with a random effects model, to compare and rank the efficacy and safety of SGLT-2i for renal outcomes in patients with T2DM. Among 1894 identified articles, 30 trials including 50,244 patients with T2DM were evaluated. Network analysis revealed that the administration of canagliflozin was associated with a reduced risk of renal impairment (surface under the cumulative ranking: 90.8%). Further, although the administration of SGLT-2i was not associated with the risk of renal impairment (RR = 0.88, 95%CI = 0.68–1.15, p = 0.354), the administration of empagliflozin was associated with a reduced risk of renal impairment compared to that with the administration of placebo (RR = 0.74, 95%CI = 0.62–0.90, p = 0.002). Moreover, compared with the administration of a placebo, the administration of 50, 100, and 200 mg of canagliflozin was associated with lower serum creatinine levels. Furthermore, compared with the administration of a placebo, the administration of 100 mg canagliflozin, 2.5 mg dapagliflozin, and 25 mg empagliflozin was associated with a lower reduction in the estimated glomerular filtration rate. Except for 300 mg canagliflozin, all SGLT-2i were associated with greater increases in blood urea nitrogen levels (WMD = 1.39, 95%CI = 1.20–1.59, p < 0.001). Finally, the administration of all SGLT-2i significantly increased the ratio of urinary glucose to creatinine compared with the ratio upon administration of placebo (WMD = 36.21, 95%CI = 31.50–40.92, p < 0.001). Briefly, canagliflozin exerts the greatest therapeutic effect in terms of reducing the risk of renal impairment. Empagliflozin and canagliflozin may be more effective than other SGLT-2i in preventing renal impairment.

The impact of pretransplant suspected HLA antibody on the long-term outcome of the graft kidney: A retrospective cohort study

IntroductionThe preoperative examination of kidney transplantation includes HLA antibody screening to initially determine the presence of preexisting donor-specific antibody (DSA) that mediates hyperacute rejection. Recipients with positive HLA antibodies require further HLA specificity analysis to type the antigen and determine the antigen mismatches between the donor and recipient. However, recipients with suspected antibodies would have no further HLA specificity analysis. It is unclear whether suspected HLA antibodies would affect renal graft function. This study aimed to explore the impact of pretransplant suspected HLA antibody on the long-term outcome of the graft kidney and thus determine the necessity of routinely performing the HLA specificity analysis in recipients with suspected HLA antibodies preoperatively. MethodsThis is a single-center retrospective cohort study. 179 kidney transplant recipients (KTRs) were included and further divided into HLA antibody-negative group (Group 1) and HLA antibody-suspected groups (Group 2) based on the result of the pretransplant HLA antibody screen test. And the antibody-suspected group was further divided into a low-mismatched group (Group A) and a high-mismatched group (Group B) according to the HLA specificity analysis. We tracked the renal function indexes, biochemical indexes, and posttransplant adverse events within 5 years after transplantation and explored the necessity of further HLA specificity analysis in recipients with pretransplant suspected HLA antibodies. ResultsThere was no statistically significant difference in demographics between HLA antibody-negative group and HLA antibody-suspected groups. At 5 years of follow-up, the KTRs in HLA antibody-negative group had significantly higher eGFR levels, lower serum creatinine levels, and less urinary protein compared to those in antibody-suspected group. Meanwhile, the KTRs in low-mismatched group also had significantly higher eGFR levels, lower serum creatinine levels, and less proteinuria compared to those in high-mismatched group. Correlation analysis showed that the age of KTRs, urinary protein levels and the load capacity of HLA mismatches were associated with eGFR levels of KTRs at 5 year posttransplant. ConclusionKTRs with suspected HLA antibodies before kidney transplantation have worse graft function than the preoperative HLA antibody-negative recipients in the long-term posttransplant follow-up. The specific load capacity of HLA mismatches, the age of the recipient and the urinary protein was found to be negatively correlated with long-term posttransplant renal outcomes. It is necessary to undergo further HLA specificity analysis for recipients with suspected HLA antibodies in HLA antibody screen test to explicit HLA mismatches and improve long-term posttransplant outcomes.

11-OR: Fetal Renal Hypoxia Response to Maternal Overnutrition

Currently, 50% of women of reproductive age are obese, and one in seven live births is affected by hyperglycemia in mothers with gestational diabetes. To examine the impact of intrauterine overnutrition on the kidneys of the offspring, we generated a novel mouse model by feeding female C57BL6J mice with either control diet (CD) or high-fat diet (HFD, 60% Lipid) during gestation and feeding the male offspring with CD after weaning, allocated to two groups of male offspring, CD and HFD. CD and HFD had similar body weights, blood pressure and urinary albumin levels, but lower serum creatinine levels in HFD (CD; n=17, HFD; n=11, p&amp;lt;0.001), which might be due to renal hyperfiltration. Histologically, HFD presented renal tubular vacuolation at 4 weeks of age and glomerulosclerosis and intrarenal arteriosclerotic lesions at 15 weeks of age. Moreover, perirenal beige fat phenotype was lost in HFD at 4 week of age, presenting white adipose cells unlike the small adipose cells in CD, suggesting that maternal overnutrition induced systemic metabolic abnormality in offspring. Synchrotron phase-contrast micro-CT showed that HFD at 14.5 dpc showed asignificant increase in total kidney volume (CD; n=4, HFD; n=6, p&amp;lt;0.001). On the contrary, no significant difference in renal artery diameter was observed (p=0.52). Blood flow is determined by the supplying vascular diameter due to Murrays’ minimum energy hypothesis. Therefore, we studied the ratio of blood flow as the 3rd power of the diameter of fetal renal artery per renal volume, indicating no significant difference between CD and HFD (p=0.42). Despite of preserved blood supply, the protein expression of HIF-1α, the key hypoxic transcription factor, was higher in HFD than that in CD, suggesting increased oxygen demand due to maternal overnutrition-induced renal metabolism. Maternal overnutrition induces supply-demand mismatch leading to renal hypoxia in the fetus, which persists into adulthood in the offspring, which might promote susceptibility to diabetic nephropathy. Disclosure T.Takiyama: None. Y.Takiyama: None. R.Bessho: None. H.Kitsunai: None. Y.Takiyama: Research Support; Boehringer Ingelheim Japan, Inc., Taisho Pharmaceutical Holdings Co., Ltd., Ono Pharmaceutical Co., Ltd., Abbott Japan Co., Ltd., Roche Diabetes Care, MSD Life Science Foundation, Japan Society for the Promotion of Science, Teijin Pharma Limited, Kyowa Kirin Co., Ltd., Sumitomo Dainippon Pharma Co., Ltd., Eli Lilly Japan K.K.

#5963 THE ASSOCIATION OF FRAILTY, DENTAL STATUS, İNFLAMMATION AND MALNUTRITION İN HEMODIALYSIS PATIENTS

Abstract Background and Aims Persistent low-grade inflammation and malnutrition in chronic kidney disease (CKD) are associated with so many CKD complications. Frailty, the state of increased vulnerability often associated with aging, had a higher incidence in CKD patients regardless of age. In this study, we aimed to investigate the frequency of frailty among hemodialysis patients and volunteers with normal kidney function to define its relationship with inflammatory markers, biochemical parameters and dental status. Method A cohort of 86 CKD patients with hemodialysis (HD) and 74 volunteers with normal kidney function (similar in terms of age and gender distribution) were included in this study. Both groups were evaluated by the Clinical Frailty Scale in three groups as non-brittle, pre-frail and frail. Demographic characteristics, biochemical parameters and dental status were recorded. Results 21 of 86 patients (24.4%) were frail in CKD patients with HD, and 4 of 76 patients (5.4%) in the control group were frail (p&amp;lt;0.001). The frail individuals in the HD group were older (p&amp;lt;0.001), had more systemic diseases (p&amp;lt;0.001), had higher serum C-Reactive Protein (CRP) levels (p&amp;lt;0.001), lower serum albumin levels (P = .001), lower serum creatinine levels (p&amp;lt;0.003). When the number of teeth is evaluated; the number of patients with more than 20 teeth was significantly lower in the frail group than in the non-frail group (p&amp;lt;0.001). Conclusion In our study, the frequency of fraility in hemodialysis patients was found to be significantly higher than in the control group. The lower albumin and serum creatinine levels, the higher CRP levels and the lower number of teeth suggest the relationship between frailty with dental status, malnutrition and inflammation in hemodialysis patients. It can be concluded that improvements in oral health and/or inflammation status can contribute to the improvement of frailty in this patient group.

Haikun Shenxi Capsule for Improving Renal Function in Patients with Chronic Kidney Diseases: A Systematic Review and Meta-analysis

ABSTRACT Haikun Shenxi capsule was widely used for patients with chronic kidney disease (CKD) stages 3–5. This study aimed to systematically evaluate the efficacy and adverse effects of the Haikun Shenxi capsule in the treatment of patients with CKD stages 3–5 (nondialysis-dependent) and provide a reference for clinical application. The Cochrane Library, PubMed, EMBASE, Web of Science, Chinese National Knowledge Infrastructure (CNKI), Wanfang Database, Chongqing VIP Database, and SinoMed Database were searched for randomized-controlled trials applying Haikun Shenxi capsule to treat CKD from their inception date to February 2022. Data extraction and quality assessment were assigned to two researchers, respectively. The risk of bias was assessed by the Cochrane handbook, and Revman5.3 was used for data statistics and analysis. Heterogeneity tests were conducted, and the mean difference (MD) or relative risk (RR) with a 95% confidence interval (95% CI) of the outcomes was presented. Eight randomized controlled trials with 522 patients diagnosed with CKD stages 3–5 (nondialysis-dependent) treated with Haikun Shenxi capsules were included. Compared with the control group, the Haikun Shenxi capsule group showed lower levels of serum creatinine (Scr; MD = −61.14, 95% CI = −68.13 to −54.16, P &lt; 0.00001) and blood urea nitrogen (BUN; MD = −4.21, 95% CI = −5.59 to −2.84, P &lt; 0.00001) and higher creatinine clearance (Ccr; MD = 3.94, 95% CI = 1.47 to 6.42, P = 0.002). No drug-related adverse effects of Haikun Shenxi were found in these studies. The Haikun Shenxi capsule could reduce Scr and BUN levels and increase the Ccr level, thereby improving renal functions of CKD stages 3–5 (nondialysis-dependent) patients without drug-related adverse effects based on conventional therapy.

Correlation between 25-hydroxyvitamin D and nephroblastoma in children and its value in assessing disease prognosis

To study the correlation between 25-hydroxyvitamin D [25-(OH)D] and nephroblastoma in children and its value in assessing the prognosis of the disease. A total of 50 children with nephroblastoma who were admitted from January 2018 to December 2022 were included as the nephroblastoma group, and according to the postoperative pathological type, they were divided into a good prognosis group with 38 children and a poor prognosis group with 12 children. A total of 50 healthy children who underwent physical examination during the same period of time served as the healthy control group. The above groups were compared in terms of serum creatinine and 25-(OH)D level. A Spearman correlation analysis was used to investigate the correlation between serum 25-(OH)D level and therapeutic effect reaction. A multivariate logistic regression analysis was used to identify the risk factors affecting the prognosis of nephroblastoma in children. The nephroblastoma group had significantly lower levels of serum creatinine and 25-(OH)D than the healthy control group (P<0.05). Compared with the good prognosis group, the poor prognosis group had a significantly larger tumor diameter, a significantly higher proportion of children with stage III-IV tumors, a significantly higher rate of tumor metastasis, and significantly lower serum levels of creatinine and 25-(OH)D (P<0.05). The Spearman correlation analysis showed that serum 25-(OH)D level was negatively correlated with therapeutic effect reaction (rs=-0.685, P<0.001). The multivariate logistic regression analysis showed that tumor diameter ≥10 cm, stage III-IV tumors, presence of tumor metastasis, and 25-(OH)D <19 ng/mL were closely associated with the poor prognosis of nephroblastoma in children (P<0.05). Serum 25-(OH)D level had an area under the curve of 0.805 (95%CI: 0.706-0.903, P<0.001) in evaluating the prognosis of nephroblastoma in children, with a Youden index of 0.512, a sensitivity of 0.938, and a specificity of 0.575 at the optimal cut-off value of 1.764 ng/mL. There is a significant correlation between 25-(OH)D level and the prognosis of nephroblastoma in children, and 25-(OH)D can be used for prognosis prediction.