Kidney Disease Research Articles

The Protective Effects of Acteoside and Total Glycosides of the Leaves of Rehmannia on Three Types of Glomerular Structural Cells Under High Glucose and Inflammatory Stimulation

ABSTRACT Background: The challenge of chronic glomerulonephritis necessitates innovative strategies for preventing renal function deterioration. Acteoside (ACT), the primary bioactive compound of total glycosides of the leaves of Rehmannia (DHYZG), has been demonstrated availability and safety in reducing proteinuria, showing promising prospects in the treatment of kidney disease. This study aimed to elucidate the impact of ACT and DHYZG on glomerular structural cells and key proteins of rat glomeruli under several injury states. Methods: Employing 3-(4,5)-dimethylthiazolyl(-Z-Y1)-3,5-diphenyltetrazolium bromide (MTT) and Western blot methodologies, the investigation assessed varying concentrations of ACT and clinical concentration of DHYZG on cell viability and intracellular biomarkers. Specifically, the study explored the influence of ACT on connective tissue growth factor (CTGF), transforming growth factor-β (TGF-β), matrix metalloproteinase-2 (MMP-2), and MPP in rat mesangial cells, endothelial cells, and podocytes stimulated by lipopolysaccharide (LPS), high glucose, and interleukin-1β (IL-1β). Additionally, the impact of high glucose on angiotensin II (Ang II) expression in endothelial cells was investigated. Results: ACT and DHYZG demonstrated a protective effect on all cell types, and ACT administration shows a significant dose-dependent response. These compounds attenuated the expression of CTGF and TGF-β in LPS-stimulated mesangial cells and reduced the expression of MMP-2 and MMP-9 in all three cell types following IL-1β stimulation. Moreover, the high glucose-induced expression of Ang II in endothelial cells was mitigated. Conclusion: ACT and DHYZG exhibit a pronounced protective effect on glomerular cells, with ACT being the primary contributor to the therapeutic efficacy of DHYZG. Notably, ACT demonstrates a significant superiority over DHYZG in terms of both proliferation and cytokine expression in glomerular endothelial cells.

Potential Role of Bone Metabolism Markers in Kidney Transplant Recipients.

The impact of treatments, suppressing the immune system, persistent hyperparathyroidism, and other risk factors on mineral and bone disorder (MBD) after kidney transplantation is well-known. However, there is limited knowledge about their effect on bone metabolism biomarkers. This study aimed to investigate the influence of kidney transplant on these markers, comparing them to patients undergoing hemodialysis and healthy individuals. In this cross-sectional study, three groups were included: kidney transplant patients (n = 57), hemodialysis patients (n = 26), and healthy controls (n = 31). Plasma concentrations of various bone metabolism biomarkers, including Dickkopf-related protein 1, osteoprotegerin, osteocalcin, osteopontin, sclerostin, and fibroblast growth factor 23, were measured. Associations between these biomarkers and clinical and laboratory data were evaluated. A total of 114 patients participated. Transplant recipients had significantly lower levels of Dickkopf-related protein 1, osteoprotegerin, osteocalcin, osteopontin, sclerostin, and fibroblast growth factor 23 compared to hemodialysis patients. Alkaline phosphatase levels positively correlated with osteopontin (r = 0.572, p < 0.001), while fibroblast growth factor 23 negatively correlated with 25-hydroxyvitamin D (r = -0.531, p = 0.019). The panel of bone biomarkers successfully predicted hypercalcemia (area under the curve [AUC] = 0.852, 95% confidence interval [CI] = 0.679-1.000) and dyslipidemia (AUC = 0.811, 95% CI 0.640-0.982) in transplant recipients. Kidney transplantation significantly improves mineral and bone disorders associated with end-stage kidney disease by modulating MBD markers and reducing bone metabolism markers, such as Dickkopf-related protein 1, osteoprotegerin, osteocalcin, osteopontin, and sclerostin. Moreover, the panel of bone biomarkers effectively predicted hypercalcemia and dyslipidemia in transplant recipients.

Loneliness, social isolation and incident chronic kidney disease among patients with diabetes

BackgroundIndividuals with diabetes have a significantly higher risk of developing chronic kidney disease (CKD) and higher levels of social isolation and loneliness compared with those without diabetes. Recently, the American...

Advanced Care Planning in Chronic Kidney Disease: Qualitative Impact of the MY WAY Intervention

ContextDespite recommendations for shared decision-making and advanced care planning (ACP) for people with chronic kidney disease (CKD), such conversations are infrequent. The MY WAY educational and patient coaching intervention aimed to promote high-quality ACP. ObjectivesThis qualitative substudy sought to gain participant feedback on the MY WAY ACP coaching intervention, and how it impacted their wishes, perceptions of kidney care, and factors that helped them reflect on ACP. MethodsWe conducted semi-structured interviews with participants from the intervention arm of the MY WAY study about their prior experience with ACPs in the context of CKD, impressions of the MY WAY intervention, and outcomes of the MY WAY intervention. We conducted a qualitative thematic analysis of transcribed interviews. ResultsAmong 15 intervention participants, the following major themes emerged: 1) Patients with CKD approach ACP with varied experiences; 2) Patients felt the MY WAY coaching intervention supported ACP by reinforcing values; and 3) Patients found the coaching intervention focused on end of life, but not necessarily on decision making regarding CKD. ConclusionParticipants perceived the coaching intervention to have high utility in facilitating ACP, but had a limited impact on CKD-specific decision-making. These findings suggest that the coach plays a crucial role in comfort with ACP conversations and that ACP readiness and engagement may not correlate with treatment preferences or understanding of CKD treatment decisions.

Kidney transplant outcomes in children with simultaneous versus sequential heart-kidney transplants.

Heart transplant recipients frequently require kidney transplantation for concomitant advanced chronic kidney disease. Data on simultaneous (heart and kidney transplants performed simultaneously) versus sequential (heart transplant performed before kidney) heart-kidney transplants in children are limited. Herein, we compare kidney transplant outcomes between the two groups. We used the Scientific Registry of Transplant Recipients to identify all pediatric (age <21 years) heart transplant recipients who also received a kidney transplant within 10 years of the heart transplant. We divided the study cohort into simultaneous heart-kidney and sequential heart-kidney recipients. We compared patient and death-censored graft survival using the Cox regression, adjusting for age at kidney transplant, sex, race, pre-transplant dialysis, donor type, and prior kidney transplant. We evaluated delayed graft function (defined as dialysis within the first week posttransplant) using logistic regression. Our analysis cohort included 165 recipients (86 simultaneous and 79 sequential). The incidence of delayed graft function was higher in simultaneous recipients (22.4 vs. 7.7%, p=0.017), but the difference lost statistical significance on multivariable analysis. We found no difference in patient survival (aHR 0.97; 95% CI 0.39, 2.41; p=0.95) after kidney transplant but higher death-censored kidney graft survival in sequential heart-kidney recipients compared with simultaneous heart-kidney recipients (aHR 4.26; 95% CI 1.21, 14.9; p=0.02). Sequential heart-kidney transplants are associated with higher death-censored kidney allograft survival in children compared with simultaneous heart-kidney transplants.

Detection of chronic kidney disease using binary whale optimization algorithm

Chronic kidney disease (CKD), a medical illness, is characterized by a steady deterioration in kidney function. A disease's ability to be prevented and effectively significantly treated depends on early diagnosis. The addition of filter feature selection to the machine learning algorithm has been done to detect CKD. However, the quality of its feature subset is not optimal. Wrapper feature selection can improve the quality of these feature subsets. Therefore, we proposed wrapper feature selection and binary whale optimization algorithm (BWOA) to enhance the accuracy of early CKD detection. We also make data improvements to improve accuracy, namely the preprocessing process with the median and modus techniques. We used a public dataset of 250 medical records of kidney sufferers and 150 completely healthy people. There are 24 features in this dataset. The test results showed that adding BWOA feature selection can increase accuracy. The proposed method produced an accuracy of 100%. Further research on these methods can be used to develop expert systems for early detection of CKD.

A practical approach to nutritional intervention for people with chronic kidney disease in Vietnam.

A comprehensive nutritional management is necessary for favourable outcomes in patients with chronic kidney disease (CKD). We aimed to assess the changes in nutritional status and disease progression with nutritional management where renal replacement therapy (RRT) was not in place. A quasi-experiment intervention was conducted on 70 CKD patients at stages 3-5 from July to December 2022. Participants were excluded if they underwent RRT, including dialy-sis (hemodialysis or peritoneal dialysis), or kidney transplantation. The nutritional regimen covered nutrition-al counseling, samples of the dietary menu, and supplement products. We evaluated nutritional status using Subjective Global Assessment (SGA) scale and sub-clinical blood test at T0 (hospital admission) and T1 (two weeks after the admission or 24 hours before the discharge). After the intervention, the number of patients classified as malnutrition or at risk of malnourished reduced significantly (65.7% to 54.3% and 25.7% and 5.7%, respectively). The serum concentration of urea, creatinine and parathyroid hormone decreased remarkably, especially in patients receiving nutritional management. In the intervention group, the dietary pattern provided increased intakes of calcium and iron at T1, while phosphorus, sodium and potassium decreased after follow-up. Nausea/vomiting, loss of appetite, tiredness and sleep disorders were improved in the intervention compared to the control group. Nutritional therapy enhanced the nutritional sta-tus, and quality of dietary and renal function in CKD patients without RRT. Applying nutrition education and treatment at an early stage can slow CKD progression, which should be applicable elsewhere in Vietnam.

Unveiling the influence of hyponatremia on morbidity, mortality, and resource utilization in colorectal carcinoma: Insights from a 5-year nationwide study.

e15657 Background: Historically, Hyponatremia has been associated with higher mortality rates and longer hospital stays in patients with solid tumors. The existing literature contains limited information on the connection between hyponatremia and Colorectal cancer (CRC). Thus, our study aimed to assess the impact of hyponatremia on mortality, morbidity, and resource usage in patients with CRC. Methods: A retrospective analysis using the National Inpatient Sample database and International Classification of Diseases, Tenth Revision codes was conducted to examine the impact of hyponatremia on mortality, morbidity, and resource utilization in patients with CRC. Categorical variables were compared using chi-square tests, while continuous variables were compared using t-tests. Multivariable regression analyses were performed, adjusting for demographics, hospital-level characteristics, and relevant comorbidities. Confounding variables were adjusted using multivariate logistic and linear regression analyses. These included gender, race, Charlson Comorbidity Index, chronic kidney disease, congestive heart failure, cirrhosis, nephrotic syndrome, hypothyroidism, adrenal insufficiency, alcohol use disorder, and admission for hypovolemia or psychogenic polydipsia and various patient and hospital characteristics. Results: A total of 337,190 patients with a primary diagnosis of colon cancer were included in the study, of which 12.6% (3,369) presented with hyponatremia (Table 1). The in-hospital mortality rate was 7.8% for patients with hyponatremia, compared to 4.1% for patients without hyponatremia. After adjusting for confounding factors, hyponatremia was found to significantly increase the odds of mortality (adjusted odds ratio [aOR] for mortality 1.85, 95% confidence interval [CI]: 1.68–2.03, P &lt; 0.01). Patients with colon cancer and hyponatremia also had higher odds of developing sepsis (OR = 2.60), acute kidney injury (OR = 2.63), peritonitis (OR = 2.25), and ICU admission (OR = 2.12) (Table 1). Additionally, hyponatremia was associated with increased resource utilization, as evidenced by a longer mean length of stay and higher mean total hospital charges. Conclusions: This retrospective analysis demonstrated that hyponatremia significantly increases mortality, morbidity, and resource utilization in individuals with CRC. Patients with colorectal cancer and hyponatremia have substantially higher mortality rates, underscoring the importance of monitoring sodium levels and implementing appropriate interventions to prevent and manage this electrolyte imbalance. The high incidence rates of sepsis, acute kidney injury, and peritonitis, along with frequent ICU admissions, provide further evidence of the negative impact of hyponatremia on patient outcomes.

Bridging the Evidence and Practice Gap in Chronic Kidney Disease: A System Thinking Approach to Population Health.

Chronic kidney disease (CKD) is common, costly, and life-limiting, requiring dialysis and transplantation in advanced stages. Although effective guideline-based therapy exists, the asymptomatic nature of CKD together with low health literacy, adverse social determinants of health, unmet behavioral health needs, and primary care providers' (PCP) limited understanding of CKD result in defects in screening and diagnosis. Care is fragmented between PCPs and specialty nephrologists, with limited time, expertise, and resources to address systemic gaps. In this article, the authors define how they classified defects in care and report the current numbers of patients exposed to these defects, both nationally and in their health system Accountable Care Organization. They describe use of the health system's three-pillar leadership model (believing, belonging, and building) to empower providers to transform CKD care. Believing entailed engaging individuals to believe defects in CKD care could be eliminated and were a collective responsibility. Belonging fostered the creation of learning communities that broke down silos and encouraged open communication and collaboration between PCPs and nephrologists. Building involved constructing a fractal management infrastructure with transparent reporting and shared accountability, which would enable success in innovation and transformation. The result is proactive and relational CKD care organized around the patient's needs in University Hospitals Systems of Excellence. Systems of excellence combine multiple domains of expertise to promote best practice guidelines and integrate care throughout the system. The authors further describe a preliminary pilot of the CKD System of Excellence in primary care.

Mitochondrial DNA 13513G>A Mutation Causing Leber Hereditary Optic Neuropathy Associated With Adult-Onset Renal Failure.

Leber hereditary optic neuropathy (LHON) is one of the more common mitochondrial diseases and is rarely associated with mitochondrial renal disease. We report 3 unrelated patients with a background of adult-onset renal failure who presented to us with LHON and were shown to have a heteroplasmic mitochondrial DNA mutation (m.13513G>A). Retrospective chart review. All 3 patients had a background of chronic renal failure and presented to us with bilateral optic neuropathy (sequential in 2) and were found to have heteroplasmic m.13513G>A mutations in the MT-ND5 gene. Two of the patients were females (aged 30 and 45 years) with chronic kidney disease from their 20s, attributed to pre-eclampsia, one of whom also had diabetes and sudden bilateral hearing loss. One patient was a male (aged 54 years) with chronic kidney disease from his 20s attributed to IgA nephropathy. His mother had diabetes and apparently sudden bilateral blindness in her 70s. Renal biopsy findings were variable and included interstitial fibrosis, acute tubular necrosis, focal segmental glomerulosclerosis, and IgA/C3 tubular casts on immunofluorescence. Mild improvements in vision followed treatment with either idebenone or a combination supplement including coenzyme Q10, alpha-lipoic acid, and B vitamins. Our cases expand the clinical syndromes associated with m.13513G>A to include bilateral optic neuropathy and adult-onset renal disease. This highlights that in patients with bilateral, especially sequential, optic neuropathy a broad approach to mitochondrial testing is more useful than a limited LHON panel. Mitochondrial diseases present a diagnostic challenge because of their clinical and genetic variability.

Progression of valve heart disease in a cohort of patients undergoing renal replacement therapy.

Cardiovascular disease is an important cause of death among patients with chronic kidney disease (CKD). Valve calcification is a predictor of cardiovascular mortality and coronary artery disease. To assess heart valve disease frequency, associated factors, and progression in CKD patients. We conducted a retrospective study on 291 CKD patients at Hospital das Clínicas de Pernambuco. Inclusion criteria were age ≥ 18 with CKD and valve disease, while those on conservative management or with missing data were excluded. Clinical and laboratory variables were compared, and patients were categorized by dialysis duration (<5 years; 5-10 years; >10 years). Statistical tests, including chi-square, Fisher's exact, ANOVA, and Kruskal-Wallis, were employed as needed. Simple and multivariate binary regression models were used to analyze valve disease associations with dialysis duration. Significance was defined as p < 0.05. Mitral valve disease was present in 82.5% (240) of patients, followed by aortic valve disease (65.6%; 86). Over time, 106 (36.4%) patients developed valve disease. No significant association was found between aortic, pulmonary, mitral, or tricuspid valve disease and dialysis duration. Secondary hyperparathyroidism was the sole statistically significant factor for mitral valve disease in the regression model (OR 2.59 [95% CI: 1.09-6.18]; p = 0.031). CKD patients on renal replacement therapy exhibit a high frequency of valve disease, particularly mitral and aortic valve disease. However, no link was established between dialysis duration and valve disease occurrence or progression.

Evaluating the Predictive Value of a Cardiac Perfusion Scan for Cardiac Events in Chronic Kidney Disease

Background: Cardiovascular diseases are among the leading causes of morbidity and mortality in chronic kidney disease (CKD) patients. Therefore, predicting cardiac events in CKD patients is essential. Objectives: The present study aims to evaluate the predictive value of single-photon emission computed tomography myocardial perfusion imaging (SPECT-MPI) in patients with different stages of CKD. Methods: Consecutive CKD patients with an estimated glomerular filtration rate (eGFR

High glucose-induced downregulation of PTEN-Long is sufficient for proximal tubular cell injury in diabetic kidney disease

During the progression of diabetic kidney disease, proximal tubular epithelial cells respond to high glucose to induce hypertrophy and matrix expansion leading to renal fibrosis. Recently, a non-canonical PTEN has been shown to be translated from an upstream initiation codon CUG (leucine) to produce a longer protein called PTEN-Long (PTEN-L). Interestingly, the extended sequence present in PTEN-L contains cell secretion/penetration signal. Role of this non-canonical PTEN-L in diabetic renal tubular injury is not known. We show that high glucose decreases expression of PTEN-L. As a mechanism of its function, we find that reduced PTEN-L activates Akt-2, which phosphorylates and inactivate tuberin and PRAS40, resulting in activation of mTORC1 in tubular cells. Antibacterial agent acriflavine and antiviral agent ATA regulate translation from CUG codon. Acriflavine and ATA, respectively, decreased and increased expression of PTEN-L to altering Akt-2 and mTORC1 activation in the absence of change in expression of canonical PTEN. Consequently, acriflavine and ATA modulated high glucose-induced tubular cell hypertrophy and lamininγ1 expression. Importantly, expression of PTEN-L inhibited high glucose-stimulated Akt/mTORC1 activity to abrogate these processes. Since PTEN-L contains secretion/penetration signals, addition of conditioned medium containing PTEN-L blocked Akt-2/mTORC1 activity. Notably, in renal cortex of diabetic mice, we found reduced PTEN-L concomitant with Akt-2/mTORC1 activation, leading to renal hypertrophy and lamininγ1 expression. These results present first evidence for involvement of PTEN-L in diabetic kidney disease.

Intracranial hemorrhage in glioblastoma: Incidence, risk factors, and outcome.

2074 Background: The incidence and clinical implications of intracranial hemorrhage (ICH) in patients with glioblastoma have not been well studied. Risk factors for ICH and associations with therapy and outcome remain unknown. It has been speculated that prior radiotherapy, chemotherapy-associated thrombocytopenia, steroid medications as well as age, other comedications and comorbidities contribute to the risk of ICH in this patient population. Methods: We identified consecutive patients with glioblastoma per WHO 2021 definition from the electronic charts of the University Hospital in Zurich, Switzerland and explored the incidence, putative risk factors, management and outcome of ICH in patients with glioblastoma. ICH was identified on central MRI and imaging report review. The study has been approved by Swissethics (2023-00532). Results: Among 387 patients diagnosed between 2010 and 2019, 6 patients presented with ICH, and 22 patients experienced ICH in the further disease course, after a median time of 153 days (IQR 79-323 days). Of the 6 patients with ICH at diagnosis, 2 patients were on anti-platelet agents and 1 was on anticoagulation. ICH occurred in the tumor region in all these patients. There were no specific features in their history compared with patients that did not present with ICH at diagnosis. Among 22 patients with ICH after diagnosis, 9 patients (41%) experienced ICH prior to first progression. ICH were not restricted to the tumor region, but included subdural hematomas in 7 patients and an epidural hematoma in one patient. Fifteen patients (68%) were hospitalized for ICH, and 5 patients (23%) had a craniotomy. Thirteen patients (59%) had no change in management, 4 patients (18%) started a new intervention, and 5 patients (23%) went to palliative care. Compared with patients without any ICH ever documented, the 28 patients with ICH were more often male, but not older, did not have a history of arterial hypertension, diabetes, chronic kidney disease or smoking, and did not have larger tumors at diagnosis. At the timepoint of intracranial hemorrhage, six patients (27%) had been preexposed to bevacizumab, yet, 188 patients (53%) of the reference cohort received bevacizumab across the disease trajectory without experiencing an ICH. Three patients (14%) had platelet counts below 100,000/µl. Overall survival in the 28 patients who experienced an ICH was not inferior to survival in the population of patients without an ICH. Conclusions: ICH at diagnosis is rare in glioblastoma and its etiology remains to be identified. It may be related to intrinsic features of the tumor and its blood vessels since no other patient-related risk factors were identified. Overall, male sex was the only risk factor associated with ICH in this study, but ICH does not signify a poor outcome overall.

Blood Purification for the Treatment of Chronic Kidney Disease-associated Pruritus

ABSTRACT Chronic kidney diseases-associated pruritus (CKD-aP) is a term that indicates the itching associated to end stage kidney disease without any apparent cause. This symptom leads to decreased quality of life and increased risk of long-term morbidities and mortality. The pathogenesis of uremic pruritus is still unknown, however, different theories have merged: uremic toxins deposition, immune system dysregulation, peripheral neuropathy, and opioid imbalance. While in the last decade, research focused prevalently on pharmaceutical treatment of CKD-aP, extracorporeal therapies have also evolved providing an alternative but efficient treatment option. In this review, we assess the role of different extracorporeal methods on the treatment of CKD-aP.

Characteristics and quality of clinical practice guidelines for diabetic kidney disease: a systematic review.

To assess the quality of Clinical practice guidelines (CPGs) in the context of diabetic kidney disease (DKD) and determine whether any factors affect the quality. We searched eight databases along with five international and national organizations to develop or archive guidelines from their inception to July 2023, with an additional search of medlive.cn. And the authoritative organizations related to nephrology. CPGs and consensus statements created using direct differential diagnosis or therapy for DKD were included without language restrictions. Their quality was evaluated by four reviewers using the Appraisal of Guidelines for Research and Evaluation Ⅱ (AGREE Ⅱ) instrument. Along with the item and domain scores, the guideline was also allocated an overall quality score, which ranged from 1 (lowest possible quality) to 7 (highest possible quality). Moreover, an overall recommendation for use was also assigned ("recommended", "recommended with modifications" or "not recommended"). A total of 16 CPGs were included, of which 14 were from Asia and the remaining two from Europe. These two CPGs were updated in the third version. Six CPGs were recommended for use because their primary domains scored in the medium or high category. Furthermore, five CPGs were recommended with modifications as the stakeholder involvement, applicability, and editorial independence domains were evaluated as low categories. In all domains, the lowest average score was for rigour of development (33%), followed by application (36%), and stakeholder involvement (51%). The highest average score was for scope and purpose (79%), followed by clarity of presentation (75%). None of the CPGs considered the patient's viewpoint, and six of 16 CPGs did not use any grading system to translate the evidence into recommendations. Additionally, only three of 16 CPGs shared search strategy, and eight of 16 CPGs did not declare a funding source. According to the AGREE II evaluation, more than one in four CPGs for DKD had poor methodological quality. Enhanced efforts are needed to advance the rigour of development, application, and editorial independence of DKD guideline panels for most guidelines. Stakeholders, CPG developers, and CPG users should consider methodological quality while choosing CPGs, and interpret and implement their issued suggestions.

Effect of sodium-glucose cotransporter 2 inhibitor dapagliflozin on ejection fraction reduction, myocardial and renal NF-κB expression and systemic pro-inflammatory biomarkers in models of short-term doxorubicin cardiotoxicity.

e24013 Background: Anthracycline-mediated adverse cardiovascular events are among the leading causes of morbidity and mortality in cancer patients. Sodium-glucose cotransporter 2 inhibitors (SGLT2i) exerts multiple cardiometabolic benefits in patients with/without type 2 diabetes, chronic kidney disease and heart failure with reduced and preserved ejection fraction. We hypothesized that the SGLT2i Dapagliflozin administered before and during doxorubicin therapy, could improve cardiac function and reduce pro-inflammatory pathways in preclinical models. Methods: Female C57Bl/6 mice were treated for 10 days with a saline solution or DOXO (2.17 mg/kg), DAPA (10 mg/kg) or DOXO combined to DAPA. Systemic levels of ferroptosis-related biomarkers, galectin-3, hs-CRP and pro-inflammatory chemokines (IL-1α, IL-1β, IL-2, IL-4, IL-6, IL-10, IL-12, IL17-α, IL-18, IFN-γ, TNF-α, G-CSF, and GM-CSF) were quantified. After treatments, immunohistochemical staining of myocardial and renal p65/NF-kB was performed. Results: DAPA prevented the reduction of radial and longitudinal strain and ejection fraction after 10 days of treatment with DOXO. A reduced myocardial expression of NLRP-3 and MyD-88 was seen in DOXO-DAPA group compared to DOXO mice. Systemic levels of IL-1β, IL-6, TNF-α, G-CSF and GM-CSF were significantly reduced after treatment with DAPA. Serum levels of galectine-3 and hs-CRP were strongly enhanced in DOXO group; contrary, their expression were reduced in DAPA-DOXO group. Troponin-T, BNP and NT-pro-BNP were strongly reduced in DOXO-DAPA group, revealing cardioprotective properties of SGLT2-i. Mice treated with DOXO and DAPA exhibited reduced myocardial and renal NF-kB expression. Conclusions: The overall picture of the study encourages the use of DAPA in primary prevention of cardiomyopathies induced by anthracyclines in cancer patients.

Application of improved glomerular filtration rate estimation by a neural network model in patients with neurogenic lower urinary tract dysfunction.

Previous studies have indicated that creatinine (Cr)-based glomerular filtration rate (GFR) estimating equations - including the new Chronic Kidney Disease Epidemiology creatinine (CKD-EPIcr) equation without race and the estimated glomerular filtration rate (eGFR) equation developed for the Chinese population - displayed suboptimal performance in patients with neurogenic lower urinary tract dysfunction (NLUTD), which limited their clinical application for detecting changes in GFR levels in all cohorts. To develop a neural network model based on multilayer perceptron (MLP) for evaluating GFR in Chinese NLUTD patients, and compare the diagnostic performance with Cr-based multiple linear regression equations for Chinese and the CKD-EPIcr equation without race. Single-center, cross-sectional study of GFR estimation from serum Cr, demographic data, and clinical characteristics in Chinese patients with NLUTD. A total of 204 NLUTD patients, from 27 different geographic regions of China, were selected. A random sample of 141 of these subjects was included in the training sample set, and the remaining 63 patients were included in the testing sample set. The reference GFR (rGFR) was assessed by the technetium-99m-labeled diethylenetriaminepentaacetic acid (99mTc-DTPA) double plasma sample method. A neural network model based on MLP was developed to evaluate GFR in the training sample set, which was then validated in the testing sample set and compared with Cr-based GFR equations. The MLP-based model showed significant performance improvement in evaluating the difference, absolute difference, precision, and accuracy of GFR estimation compared with the Cr-based GFR equations. Additionally, compared with the rGFR, we found that the MLP-based model provided an acceptable level of accuracy (greater than 85%, which was within a 30% deviation from the rGFR). The MLP-based model offered significant advantages in estimating GFR in Chinese NLUTD patients, and its application could be suggested in clinical practice.

Association of Serum Bicarbonate Level with Mortality in Patients with Acute Kidney Injury: A Retrospective Cohort Study

ABSTRACT Background: Metabolic acidosis due to a decreased level of serum bicarbonate in patients with chronic kidney disease is associated with increased mortality, but the association of serum bicarbonate with outcomes in patients with acute kidney injury (AKI) is uncertain. We investigated the association of serum bicarbonate level with mortality in patients with AKI. Methods: The study cohort consisted of 4800 patients diagnosed with AKI at multiple hospitals between September 17, 2013, and April 14, 2014. Smooth curve fitting, threshold effect analysis, and multiple regression analysis were used to assess the relationship between serum bicarbonate and 14-day mortality (primary outcome) and with intensive care unit (ICU) admission, length of hospitalization, and total hospital costs (secondary outcomes). Results: Multiple regression analysis, adjusting for confounding factors, demonstrated a U-shaped association between serum bicarbonate levels and AKI mortality. The lowest mortality rate was observed in patients with a bicarbonate level of 26.9 mmol/L, while greater rates were observed in those with lower and higher levels. Additionally, patients with AKI exhibiting high serum bicarbonate levels (&gt; 26.9 mmol/L) had a significantly lower rate of ICU admission and a shorter hospital stay compared to those with low serum bicarbonate levels (&lt; 26.9 mmol/L). Conclusion: A serum bicarbonate level of 26–29 mmol/L in patients with AKI is associated with a lower 14-day mortality rate, with the lowest rate observed at a serum bicarbonate level of 26.9 mmol/L. Prospective clinical studies are needed to determine whether optimizing the serum bicarbonate level can decrease mortality in this population.

Tolvaptan therapy for edema in patients with chronic kidney disease.

Tolvaptan is a vasopressin V2 receptor antagonist that is commonly prescribed to alleviate edema associated with renal diseases. However, the clinical benefits of tolvaptan in chronic kidney disease (CKD) remain unclear. This study aimed to evaluate the effectiveness of tolvaptan in managing edema caused by CKD. The efficacy and treatment regimen of tolvaptan were assessed in a cohort of 96 patients with renal edema and CKD. During the treatment, the patients' creatinine (CR), uric acid (UA), and estimated glomerular filtration rate (eGFR) were monitored as important indicators of kidney function. Coagulation-associated molecules including fibrinogen, D-dimer, and fibrin degradation products (FDPs) were measured. Electrolyte disorders and acute kidney injury were closely monitored. Tolvaptan was administered at a daily dose of 7.5 mg, and 30 mg of edoxaban was administered to manage deep vein thrombosis. During the course of tolvaptan therapy, the eGFR of the patients was not declined. Edema was eliminated in 82.18% of patients. Proteinuria was reduced in the patients (p<0.05). There were no significant changes in serum sodium levels throughout treatment, and no significant difference was observed in blood volume between the end of treatment and baseline levels. Importantly, acute kidney injury did not occur, and renal edema and deep vein thrombosis were successfully treated. As long as a rational treatment regimen is followed, tolvaptan is a safe and effective diuretic for treating edema in CKD, even in the late stages of CKD without reducing residual renal function in the patients.