Development Of Chronic Kidney Disease Research Articles

Higher oxidative balance score is linearly associated with reduced prevalence of chronic kidney disease in individuals with metabolic syndrome: evidence from NHANES 1999-2018.

Oxidative stress is a key contributor to the development of chronic kidney disease (CKD) in individuals with metabolic syndrome (MetS). The oxidative balance score (OBS) is an emerging composite assessment tool for dietary and lifestyle oxidative balance. We aimed to explore the association of OBS with CKD prevalence in MetS in this national cross-sectional analysis. This was a national cross-sectional analysis. Eligible MetS participants ≥20 years of age from NHANES 1999-2018 were included. OBS was assessed according to previous well-validated methods and consisted of 16 dietary components and 4 lifestyle components. MetS was diagnosed by NCEP-ATP III criteria, while CKD was diagnosed by KDIGO 2021 Clinical Practice Guideline. Multivariate logistic regression models were used to explore the association of OBS with CKD in MetS in this national cross-sectional analysis. A total of 8,095 MetS participants were included, with a CKD prevalence of 24.8%. In fully adjusted models, each score increases in OBS, dietary OBS, and lifestyle OBS was associated with a 2, 1.7, and 7.3% reduction in the prevalence of CKD, respectively. Higher OBS, dietary OBS, and lifestyle OBS were all associated with significantly lower odds of CKD (p for trend all <0.05). Restricted cubic spline analysis showed that these associations all exhibited inverse dose-response. Interaction analyses indicated that cardiovascular disease (CVD) status significantly influenced the impact of OBS and dietary OBS, and these associations were only present in CVD-free subjects. Defining MetS using the IDF criteria did not significantly change the results. OBS was inversely associated with the prevalence of CKD in MetS, especially in CVD-free settings. These findings emphasize that adherence to an antioxidant diet and lifestyle contributes to the early prevention of CKD in the MetS population and necessitates attention to CVD interactions. Future prospective cohort studies are needed to confirm these results.

Influence of Kidney Diseases on Lipid Profile in Patients Undergoing Conservative Managements and Hemodialysis

Kidney function gradually declines as a result of chronic kidney disease (CKD). The current study was conducted at Princess Iman Hospital in Muadi, Jordan from December to March 2024. It aimed to investigate the association between lipids and chronic renal failure (CRF), which refers to the advanced stages of CKD where kidney function has declined significantly, and to understand how dyslipidemia affects the development of CKD and general health outcomes. The study involved three groups of participants: patients with CRF who were on hemodialysis, those receiving conservative management for CRF, and healthy individuals as controls. According to the findings, CRF patients (hemodialysis and conservative management) had significantly higher lipid levels than the control group besides showing low indicators for kidney function (p&lt;0.001). In addition, triglyceride, cholesterol, low-density lipoprotein (LDL) levels, Cholesterol/high-density lipoprotein (HDL) ratio, and LDL/HDL ratio were also found to be significantly high in the hemodialysis group when compared to the conservative group (p&lt;0.001). In this population with CRFs, it was observed that lipid levels correlated positively with markers for kidney disease progression. Therefore, monitoring of lipids should be done regularly across all stages of CKDs to reduce cardiovascular complications associated with atherosclerosis. Hence, incorporating lipid evaluations into standard CKD care regimens, even during the initial phases, is vital for enhancing patient outcomes and lowering mortality risks. In essence, the results highlight the importance of proactive management of lipid levels in CKD individuals to tackle cardiovascular complications effectively. By understanding dyslipidemia's impact on CKD advancement, healthcare practitioners can customize interventions to enhance patient care and diminish related risks, ultimately improving prognosis and decreasing mortality rates among CKD cohorts.

Association of obesity severity and duration with incidence of chronic kidney disease

IntroductionObesity is a known risk factor for chronic kidney disease (CKD), but the impact of obesity severity and duration on CKD incidence is unclear.MethodsCumulative Excess Weight (CEW) and Cumulative Excess Waist Circumference (CEWC) scores were calculated, which represent the accumulation of deviations from expected body mass index and waist circumference values over time until the development of CKD or the end of the follow-up period. Time-dependent Cox models were used to investigate the sex-stratified association of CEW and CEWC with CKD incidence while controlling for confounding variables.ResultsOut of the 8697 participants who were evaluated in this study, 56% (4865) were women and the mean age was 40 ± 14. During the 15-year follow-up period, 41.7% (3629) of the participants developed CKD. Among the CKD patients, 65.4% (829) of men and 77.9% (1839) of women had a BMI higher than 25, and high WC was found to be 73.7% (934) and 55.3% (1306) for men and women, respectively. We found a significant association between one standard deviation change of CEW and the development of CKD in both sexes (fully adjusted hazard ratios and 95% CI of CEW in men and women were 1.155 [1.081–1.232) and 1.105 (1.047–1.167)]. However, the association between CEWC and CKD development was only significant among men participants [HR = 1.074 (1.006–1.147)].ConclusionOver a 15-year follow-up, the accumulation of general and central obesity was associated with an increased incidence of CKD development.

Assessment of brain-derived neurotrophic factor and irisin concentration in children with chronic kidney disease: a pilot study

Patients suffering from chronic kidney disease (CKD) are particularly placed at risk of multiorgan complications. One of them is malnutrition, which adds up to a higher mortality factor among them. This study was designed to determine the usefulness of brain-derived neurotrophic factor (BDNF) and irisin assays in the assessment of CKD development. The study group included 28 children with CKD at stages 2-5 treated conservatively. The outcome of our study revealed decreased serum BDNF and irisin levels in CKD patients, whereas urine concentrations were increased for BDNF and decreased for irisin, comparing to healthy controls. There was a positive correlation between anthropometric measures and urine BDNF concentration, as well as anthropometric measures and both serum and urine irisin levels in the study group, however no dependence of the tested markers on the stage of CKD was observed. In recent years, a role of myokines was described as vital for maintaining metabolic homeostasis therefore we suspect a potential role of these multifaceted markers in detecting malnutrition in CKD children.

Impact of war on the development and progression of chronic kidney disease among residents of frontline regions (Kharkiv): first results of Save Kidneys Study as part of the ISN Clinical Research Program

Impact of war on the development and progression of chronic kidney disease among residents of frontline regions (Kharkiv): first results of Save Kidneys Study as part of the ISN Clinical Research Program

Nutritional assessment and medical dietary therapy for management of obesity in patients with non-dialysis chronic kidney disease: a practical guide for endocrinologist, nutritionists and nephrologists. A consensus statement from the Italian society of endocrinology (SIE), working group of the club nutrition-hormones and metabolism; the Italian society of nutraceuticals (SINut), club ketodiets and nutraceuticals "KetoNut-SINut"; and the Italian society of nephrology

Chronic kidney disease (CKD) is a serious health concern with an estimated prevalence of about 13.4% worldwide. It is cause and consequence of various comorbidities, including cardiovascular diseases. In parallel, common pathological conditions closely related to ageing and unhealthy dietary habits increase the risk of CKD development and progression, including type 2 diabetes and obesity. Among these, obesity is either independent risk factor for new onset kidney disease or accelerates the rate of decline of kidney function by multiple mechanisms. Therefore, the role of diets aimed at attaining weight loss in patients with obesity is clearly essential to prevent CKD as to slow disease progression. Various dietary approaches have been licensed for the medical dietary therapy in CKD, including low-protein diet and Mediterranean diet. Interestingly, emerging evidence also support the use of low-carbohydrate/ketogenic diet (LCD/KD) in these patients. More specifically, LCD/KDs may efficiently promote weight loss, improve metabolic parameters, and reduce inflammation and oxidative stress, resulting in a dietary strategy that act globally in managing collateral conditions that are directly and indirectly related to the kidney function. This consensus statement from the Italian Society of Endocrinology (SIE), working group of the Club Nutrition - Hormones and Metabolism; the Italian Society of Nutraceuticals (SINut), Club Ketodiets and Nutraceuticals "KetoNut-SINut"; and the Italian Society of Nephrology (SIN) is intended to be a guide for Endocrinologist, Nutritionists and Nephrologist who deal with the management of patients with obesity with non-dialysis CKD providing a practical guidance on assessing nutritional status and prescribing the optimal diet in order to best manage obesity to prevent CKD and its progression to dialysis.

The use of a clinical calculator to determine the rate of development of chronic kidney disease in elderly patients with type 2 diabetes mellitus

Aim – to develop an applied prognostic calculator for the rate of progression of CKD in elderly patients with type 2 diabetes, which makes it possible to identify a group of high rate of GFR reduction in conditions of routine outpatient admission. Material and methods. 69 clinical indicators were studied, the interrelationships and significance of differences in parameters in the groups identified according to the original diagnostic parameter, the glomerular filtration rate reduction index with a threshold value of 3.83 ml/min/1.73 m2 per year, above which the rate of progression of CKD was considered high. Results. By using regression analysis, significant factors for the prognostic calculator were identified: the duration of diabetes and insulin therapy, concomitant diagnosis of obesity, pulse in the ankle artery, severe stage of polyneuropathy, risk group IV of hypertension, treatment with sulfonylureas, the number of antihypertensive drugs taken. When evaluating the information capacity and predictive ability of the calculator, the area under the AUC ROC curve was 0.89 (0.80; 0.99) p 0.001, which characterizes the quality of the diagnostic technique as high. Conclusion. The presented calculator gives the doctor the opportunity to identify a group of patients with the risk of rapid progression of CKD directly on an outpatient basis.

Effects of long-term lithium therapy on kidney functioning in mood disorders: A population-based historical cohort study.

Lithium is Food and Drug Administration-approved for bipolar disorder (BD) and is also used in depressive disorders but is underutilized due to concerns about chronic kidney disease (CKD). We explored clinical and demographic profiles of patients on long-term lithium therapy (LTLT) and assessed kidney function. Our aims were to identify the predictors for CKD stage ≥3 and the impact of lithium discontinuation post-CKD diagnosis. We conducted a population-based historical cohort study of adult patients with mood disorders on LTLT at the Marshfield Clinical Health System from 1990 to 2019. Data on lithium therapy and kidney-related information (estimated glomerular filtration rate and CKD) were extracted from electronic medical records. Among 1603 patients with mood disorders (mean age 42.1 years, 60% females), 15.3% (n = 246) developed CKD stage ≥3. Patients without CKD were on lithium for 4.5 years, compared to 6.6 years for those with CKD. Hypertension, age, and BD were significant CKD risk factors. Kidney function declined linearly with lithium duration, returning to pre-treatment trajectory in patients without CKD but showed no improvement in those with CKD after lithium discontinuation. The findings suggest that CKD occurs in 15% of patients with mood disorder receiving LTLT, with its progression potentially influenced by existing comorbidities rather than lithium alone. These results underscore the importance of monitoring kidney function in patients on LTLT and considering individual risk factors for CKD development. In patients who developed CKD, Li discontinuation did not impact change in kidney function.

Arterial stiffness is associated with new-onset chronic kidney disease.

Background: A potential independent association between arterial stiffness (AS) and the development of new-onset chronic kidney disease (CKD) has not been thoroughly examined. Patients and methods: A total of 6929 participants were collected from the Kailuan study. All participants were free of CKD at the baseline. The participants were divided into four groups based on their brachial-ankle pulse wave velocity (baPWV) values. Cox regression models were used to analyze the relationship between baPWV values and the risk of new-onset CKD. Results: Over the course of a 10.06-year follow-up period, a total of 962 cases of new-onset CKD were documented. Cox proportional hazards analyses showed that a higher baPWV quartile was linked to an increased risk of new-onset CKD. Conclusions: Brachial-ankle pulse wave velocity has a strong correlation with the development of new-onset CKD. Therefore, baPWV can be considered an innovative indicator for predicting the occurrence of new-onset CKD.

Unraveling the Mechanisms of Magnesium Supplementation in Alleviating Chronic Kidney Disease Complications and Progression: Balancing Risks and Benefits.

Chronic kidney disease (CKD) is a major cause of death and disability worldwide. It is usually diagnosed at early levels because of its slow progression. Treatment should consider CKD complications (such as electrolyte level imbalance, vascular calcification, and bone mineral disorders), as well as the development of CKD itself. Large-scale studies have shown that current treatment guidelines are nearly ineffective and fail to achieve treatment goals. Guidelines have not paid as much attention to magnesium (Mg) as the other electrolytes, while Mg has a significant role in the treatment goals of CKD. Hypomagnesemia is the only electrolyte imbalance that is equally prevalent in all stages of CKD. A lower plasma Mg level in each stage of CKD is associated with a higher risk of CKD progression and cardiac events. Magnesium exerts its effects both directly and via other ions. Mg supplementation increases insulin sensitivity while reducing proteinuria and inflammation. It lowers blood pressure and inhibits vascular calcification primarily because of its effects on calcium and phosphate, respectively. Vitamin D supplementation for low-active vitamin D in CKD patients increases vascular calcification and cardiac events, but magnesium supplementation enhances vitamin D levels and activity without increasing the risk of cardiac events. However, careful attention is required due to the potential threats of hypermagnesemia, particularly in advanced CKD stages. Starting magnesium supplementation early in patients' treatment plans will result in fewer side effects and more advantages. More original research is needed to determine its optimal dose and serum levels.

Long-term exposure to NO2 and PM2.5 and the occurrence of chronic kidney disease among patients with type 2 diabetes in Taiwan

BackgroundIndividuals diagnosed with type 2 diabetes (T2D) frequently exhibit chronic kidney disease (CKD) which may be caused by environmental hazards such as exposure to air pollutants. However, limited research has explored the effects of prolonged exposure to air pollutants on CKD development in this population. This study examines the relationship between long-term exposure to air pollutants and CKD incidence in a longitudinal cohort of individuals with type 2 diabetes in Taiwan MethodsBetween 2003 and 2005, we recruited 1316 T2D patients (693 females [52.66 %]; mean age 56.16 ± 8.97 years). Patients were followed until December 31, 2012, with at least two clinical visits. Baseline demographics, medical history, and biomarker levels were collected. The development of CKD was determined by eGFR level < 60 mL/min/1.73 m2. Monthly averages of nitrogen dioxide (NO2) and fine particulate matter [PM ≤ 2.5 μm in aerodynamic diameter (PM2.5)] were acquired from 72 ambient air monitoring stations. The kriging method was employed to estimate the exposure levels to PM2.5, NO2, temperature, and relative humidity in the participants' residential areas. Cox regression with time-dependent covariates regression was applied to assess the impact of long-term exposure to air pollutants and CKD risk. ResultsOf 992 patients with normal renal function at baseline, 411 (41.43 %) experienced CKD occurrence over a median follow-up period of 5.45 years. The incidence of CKD was 93.96 cases per 1000 person-years. In multivariable adjusted models, patients exposed to PM2.5 levels above the third quartile of (>33.44 μg/m3) and NO2 levels above the fourth quartile (>22.55 ppb) were found to have an increased risk of CKD occurrence compared to lower exposure levels. ConclusionsThis longitudinal study highlights the increased risk of CKD in individuals with type 2 diabetes due to prolonged exposure to NO2 and PM2.5, emphasizing the need for tailored air quality management strategies for this high-risk population.

Association of biomarkers of endothelial function, coagulation activation and kidney injury with persistent albuminuria in sickle cell anaemia.

Persistent albuminuria (PA) is common in sickle cell anaemia (SCA). With the association of chronic kidney disease (CKD) with increased mortality, biomarkers that predict its development or progression are needed. We evaluated the association of select biomarkers with PA in adults with SCA using Kruskal-Wallis rank-sum test and logistic regression models, with adjustment for multiple testing. Of 280 subjects, 100 (35.7%) had PA. Median plasma levels of soluble vascular cell adhesion molecule-1 (VCAM-1) (1176.3 vs. 953.4 ng/mL, false discovery rate [FDR] q-value <0.003), thrombin-antithrombin complex (5.5 vs. 4.7 ng/mL, FDR q-value = 0.04), and urinary angiotensinogen (AGT) (12.2 vs. 5.3 ng/mg, FDR q-value <0.003), urinary nephrin (30.6 vs. 27.2 ng/mg, FDR q-value = 0.04), and urinary kidney injury molecule-1 (KIM-1) (0.8 vs. 0.5 ng/mg, FDR q-value <0.003), normalized to urine creatinine, were significantly higher in subjects with PA. In multivariable analysis, only urinary AGT (odds ratio = 1.058, FDR q-value <0.0001) remained a significant predictor of PA. In addition, soluble VCAM-1 (FDR q-value <0.0001), D-dimer (FDR q-value <0.0001), urinary AGT (FDR q-value <0.0001), KIM-1 (FDR q-value <0.0001), and nephrin (FDR q-value <0.0001) were significantly associated with urine albumin-creatinine ratio in multivariable analyses. Longitudinal studies to evaluate the predictive capacity of biomarkers for the development and progression of CKD in SCA are warranted.

Uncovering the mechanisms of diosmin in treating obesity-related kidney injury based on network pharmacology, molecular docking, and in vitro validation.

Obesity increases the risk of kidney injury, involving various pathological events such as inflammation, insulin resistance, lipid metabolism disorders, and hemodynamic changes, making it a significant risk factor for the development and progression of chronic kidney disease. Diosmin, a natural flavonoid glycoside, exhibits anti-inflammatory, antioxidant, anti-lipid, and vasodilatory effects. However, whether diosmin has a protective effect on obesity-related kidney injury remains unclear. The molecular formula of diosmin was obtained, and diosmin and target genes related to obesity-related kidney injury were screened. The interaction between overlapping target genes was analyzed. GO functional enrichment and KEGG pathway enrichment analyses were performed on overlapping target genes. Molecular docking was employed to assess the binding strength between overlapping target genes. Palmitic acid-induced damage to HK-2 cells, which were then treated with diosmin. Subsequently, the expression levels of relevant mRNAs and proteins were measured. Network analysis identified 219 potential diosmin target genes, 6800 potential target genes related to obesity-related kidney injury, and 93 potential overlapping target genes. Protein-protein interaction networks and molecular docking results revealed that AKT1, TNF-α, SRC, EGFR, ESR1, CASP3, MMP9, PPAR-γ, GSK-3β, and MMP2 were identified as key therapeutic targets, and they exhibited stable binding with diosmin. GO analysis indicated that these key targets may participate in inflammation, chemical stress, and protein phosphorylation. KEGG revealed that pathways in cancer, AGE-RAGE signaling pathway, PI3K-AKT signaling pathway, PPAR signaling pathway, and insulin resistance as crucial in treating obesity-related kidney injury. CCK-8 assay showed that diosmin significantly restored the viability of HK-2 cells affected by palmitic acid. Oil Red O staining demonstrated that diosmin significantly improved lipid deposition in HK-2 cells induced by palmitic acid. PCR results showed that diosmin inhibited the mRNA levels of AKT1, TNF-α, EGFR, ESR1, CASP3, MMP9, GSK-3β, and MMP2 while promoting the mRNA level of PPAR-γ. Western blot analysis revealed that diosmin restored PPAR-γ protein expression, inhibited NF-kB p-p65 protein expression, and reduced TNF-α protein expression. Diosmin demonstrated multi-target and multi-pathway effects in the treatment of obesity-associated renal injury, with key targets including AKT1, TNF-α, EGFR, ESR1, CASP3, MMP9, PPAR-γ, GSK-3β, and MMP2. The mechanism may be through the modulation of the PPAR-γ/NF-κB signaling pathway, which can attenuate inflammatory responses and protect the kidney.

Obesity is associated with incident chronic kidney disease in individuals with normal renal function.

Obesity has known to be a modifiable risk factor associated with worse outcomes in chronic kidney disease (CKD), but few studies have examined the impact of obesity on CKD incidence in the general population. The purpose of this study was to investigate the role of body mass index (BMI) and waist-to-hip ratio (WHR) as predictors of incident CKD and to evaluate the impact of weight reduction on CKD prevention. A total of 2,711 participants from a community-based cohort with normal renal function were prospectively analyzed. Among participants with obesity, we analyzed the change in WHR to evaluate the association of obesity reduction with CKD development. During a mean follow-up of 11.03 ± 4.22 years, incident CKD occurred in 190 (7.0%) participants. In the fully adjusted multivariable Cox proportional hazard models, the risk of incident CKD increased with higher BMI (hazard ratio, 1.06; 95% confidence interval, 1.00-1.11; p = 0.033) and higher WHR (hazard ratio, 1.33; 95% confidence interval, 1.07-1.66; p = 0.009). In the Kaplan-Meier analysis, cumulative adverse renal events were significantly more common in the maintained obesity group than in the reduced obesity group (p = 0.001). Both higher BMI and WHR were associated with development of CKD, but the magnitude of the effect of WHR was higher than that of BMI. Moreover, reducing obesity would be beneficial for renal prognosis.

Nephrology rapid response team in the intensive care unit

Acute kidney injury (AKI) is a frequent complication in patients admitted to the intensive care unit (ICU), and it is known as an independent factor for adverse outcomes like increased length of hospital stay, the development of chronic kidney disease (CKD), and increased mortality with the associated high cost to healthcare systems. The use of AKI biomarkers and new tools such as point-of-care ultrasonography (POCUS) to perform a hemodynamic and volume status assessment has made it more feasible to detect or predict kidney damage in a very accurate way, thereby avoiding the progression of AKI. The design and implementation of a nephrology rapid response team (NRRT) should be considered to improve patient outcomes and healthcare costs. In this paper, we provide an overview of the implementation of an NRRT.

MiRNA and mRNA Signatures in Human Acute Kidney Injury Tissue

Acute kidney injury (AKI) is an important contributor to the development of chronic kidney disease (CKD). There is a need to understand molecular mediators that drive recovery and progression to CKD. In particular, the regulatory role of miRNAs in AKI is poorly understood. miRNA and mRNA sequencing were performed on biobanked human kidney tissues obtained in the routine care of subjects with a diagnosis of AKI, minimal change disease (MCD), or without known kidney disease in nephrectomy (Ref) tissue. mRNA analysis revealed that Ref tissues exhibited an injury signature similar to AKI, and not identified in MCD samples. The transcriptomic signature of human AKI was enriched in pathways involved in cell adhesion, epithelial-to-mesenchymal transition, and cell cycle arrest (e.g., CDH6, ITGB6, CDKN1A). In AKI, upregulation of miR-146a, miR-155, miR-142, miR-122 was associated with pathways involved in immune cell recruitment, inflammation, and epithelial-to-mesenchymal transition. miR-122 and miR-146 are associated with downregulation of DDR2 and IGFBP6, genes involved in recovery and progression of kidney disease. These data provide integrated miRNA signatures that complement mRNA and other epigenetic data available in kidney atlases.

A Possible Role of P-Cresyl Sulfate and Indoxyl Sulfate as Biomarkers in the Prediction of Renal Function According to the GFR (G) Categories

Background: Gut dysbiosis has been implicated in the development and progression of chronic kidney disease (CKD) by the generation of uremic toxins, such as the protein-bound solutes p-cresyl sulfate (pCS) and indoxyl sulfate (IXS). In this study, we evaluate the associations of total (t) and free fractions (f) of pCS and IXS with the Kidney Disease: Improving Global Outcomes (KDIGO) glomerular filtration rate (GFR; G) categories using contemporary GFR estimation equations. Methods: Liquid chromatography/tandem mass spectrometry has been applied for the identification and quantification of pCS and IXS. Results: We evaluated 80 patients (55 ± 13 years); 41 male. We found a statistically significant increase of pCSt, pCSf, IXSt and IXSf across the CKD spectrum as defined by GFR categories (P &lt; 0.001). A significant negative correlation was observed between estimated glomerular filtration rate (eGFR, any equations) and plasma concentrations of pCS and IXS (all P values &lt; 0.001). For example we reported correlation between eGFR 2021 Chronic Kidney Disease Epidemiology Collaboration, CKD-EPI and pCSt (Spearman’s coefficient Rho [r] = -0.690), pCSf (r = -0.744), IXSt (r = -0.754) and IXSf (r = -0.819). Conclusion: We found that the free fraction as well as total concentrations of pCS and IXS were negatively correlated with estimated GFR (all equations) in CKD patients. The significant increase of pCS and of IXS across the CKD spectrum suggests that both protein-bound solutes may be used as surrogate markers of renal function.

Impact of diabetes mellitus and hypertension on renal function during first-line targeted therapy for metastatic renal cell carcinoma: a retrospective multicenter study.

Renal function deterioration during systemic therapy in patients with metastatic renal cell carcinoma (mRCC) is a long-term concern in treatment planning. Although hypertension (HTN) and diabetes mellitus (DM) are the most common factors that affect chronic kidney disease (CKD) development and progression, their impact on renal function during targeted therapy is unclear. This study investigated whether DM and HTN were associated with a decline in renal function during first-line targeted therapy for mRCC. This retrospective multicenter study analyzed patients receiving first-line targeted therapy for mRCC. They were classified as follows: group 1: HTN-, DM-; group 2: HTN+, DM-; group 3: HTN-, DM+; and group 4: HTN+, DM+. Changes in renal function and factors affecting progression to stage 4 CKD after targeted therapy were analyzed. Among the 424 enrolled patients, 303 (71.5%) and 121 (28.5%) were treated with sunitinib and pazopanib, respectively [median duration: 10.3 months, interquartile range (IQR), 3.1-37.0 months]. Although all groups showed a decreased mean estimated glomerular filtration rate (eGFR) after treatment (P<0.001 for group 1, group 2, and group 4, P=0.02 for group 3, respectively), there were no significant differences in changes in eGFR (∆eGFR) between groups (P=0.10). However, actual renal function change calculated using percent ∆eGFR (%∆eGFR) showed differences between groups (P=0.02); the %∆eGFR of group 4 was significantly lower compared with group 1 (P=0.008). The mean progression time to stage 4 CKD in group 4 (38.6 months) was significantly shorter compared to the other groups (P<0.001). Multivariate analysis identified increased age (P=0.008), increased number of metastatic sites (P=0.047), and DM and HTN coexistence (P<0.001) as predictors of progression to stage 4 CKD. Patients with DM and HTN experienced further decline in renal function and had a higher risk of progression to stage 4 CKD after targeted therapy compared to patients without these risk factors. Recognition and proactive management of DM and HTN are necessary to facilitate the proper administration of life-prolonging oncological treatments.

Causality of Genetically Determined Metabolites on Chronic Kidney Disease: A Two-Sample Mendelian Randomization Study In Silico.

Introduction: Chronic kidney disease (CKD) is associated with metabolic disorders. However, the evidence for the causality of circulating metabolites to promote or prevent CKD is still lacking. Methods: The two-sample Mendelian randomization (MR) analysis was conducted to evaluate the latent causal relationship between the genetically proxied 486 blood metabolites and CKD. Genome-wide association study (GWAS) data for exposures were derived from 7824 European GWAS on metabolite levels, which have been extensively utilized in the medical field to elucidate the mechanisms underlying disease onset and progression. The random inverse variance weighted (IVW) is the primary analysis for causality analysis while MR-Egger and weighted median as complementary analyses. For the further identification of metabolites, reverse MR and linkage disequilibrium score regression were performed for further evaluation. The drug target for N-acetylornithine was subsequently supplemented into the analysis, with MR and colocalization analysis being utilized. Key metabolic pathways were identified via MetaboAnalyst 4.0 (https://www.metaboanalyst.ca/) online website. Results: N-acetylornithine was identified as a reliable metabolite that increases the susceptibility to estimated glomerular filtration rate (eGFR) decrease (β = 0.047; 95% confidence interval: -0.068 to -0.026; PIVW = 1.5E-5). The "glyoxylate and dicarboxylate metabolism" pathway showed significant relevance to CKD development (P = 6E-4), whereas the "glycine, serine, and threonine metabolism" pathway was also recognized as associated with CKD by general practitioners (P = 7E-4). Colocalization analysis revealed a robust genetic link between N-acetylornithine and both CKD and eGFR, with 85.1% and 99.4% colocalization rates, respectively. IVW-MR analysis substantiated these findings with a significant positive association for CKD (odds ratio = 1.43, P = 4.7E-5) and a negative correlation with eGFR (b = -0.04, P = 1.13E-31). Conclusions: MR was utilized to explore the potential causal links between 61 genetic serum metabolites and CKD. N-acetylornithine and NAT8 were further explored as a potential therapeutic target for CKD treatment.

Six months of physical inactivity is insufficient to cause chronic kidney disease in C57BL/6J mice.

Chronic kidney disease (CKD) is a progressive disorder marked by a decline in kidney function. Obesity and sedentary behavior contribute to the development of CKD, though mechanisms by which this occurs are poorly understood. This knowledge gap is worsened by the lack of a reliable murine CKD model that does not rely on injury, toxin, or gene deletion to induce a reduction in kidney function. High-fat diet (HFD) feeding alone is insufficient to cause reduced kidney function until later in life. Here, we employed a small mouse cage (SMC), a recently developed mouse model of sedentariness, to study its effect on kidney function. Wildtype C57BL/6J male mice were housed in sham or SMC housing for six months with HFD in room (22°C) or thermoneutral (30°C) conditions. Despite hyperinsulinemia induced by the SMC+HFD intervention, kidneys from these mice displayed normal glomerular filtration rate (GFR). However, the kidneys showed early signs of kidney injury, including increases in Col1a1 and NGAL transcripts, as well as fibrosis by histology, primarily in the inner medullary/papilla region. High-resolution respirometry and fluorometry experiments showed no statistically significant changes in the capacities for respiration, ATP synthesis, or electron leak. These data confirm the technical challenge in modeling human CKD. They further support the notion that obesity and a sedentary lifestyle make the kidneys more vulnerable, but additional insults are likely required for the pathogenesis of CKD.