scholarly journals P0744CLINICAL IMPACT OF SERUM INDOXYL SULPHATE MEASURED BY NEW ENZYMATIC METHOD IN PATIENTS WITH CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 35 (Supplement_3) ◽  
Author(s):  
Yoshinari Yasuda ◽  
Ryosuke Kikuchi ◽  
Kazunori Goto ◽  
Ahmad Baseer Kaihan ◽  
Sawako Kato ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Measurement Method ◽  
Multiple Logistic Regression Analysis ◽  
Rank Test ◽  
Uremic Toxin ◽  
Enzymatic Method ◽  
Renal Outcomes ◽  
Indoxyl Sulphate

Abstract Background and Aims Uremic toxins have been highlighted as serious risk factors for deterioration of renal function and onset/progression of cardiovascular diseases (CVD). Serum level of indoxyl sulphate (IS), a major uremic toxin, was demonstrated its significant association with vascular disease and mortality in a cohort of chronic kidney disease (CKD) patients, however, IS has not been available in clinical setting due to time consuming and expensive measurement cost. Recently epoch-making IS measurement method applicable for general auto analyzer has been developed, which could explore new therapeutic avenue in CKD from the view point of uremic toxin management. In this study, clinical utility of new enzymatic IS measurement method was analyzed in association with renal function and CVD among CKD patients. Method Subjects were consecutive 150 CKD patients in Nagoya University Hospital whose serum samples were collected between 2009 and 2014. Serum IS levels were measured by “NIPRO” reagent and analyzed with eGFR, CVD events and renal outcomes defined by 30% decrease in eGFR. Results Characteristics of patients were 69 ± 10 years old, 29% female, eGFR: 44 ± 20 mL/min/1.73m2 (∼G3a: 43％, G3b: 29％, G4: 24％, Ｇ5: 4％), proteinuria 2.8 ± 3. 5ｇ/ｇCr (A1: 29％, A2: 29％, A3: 42％), HTN: 83％, and DM: 39％. Serum IS levels (μmol/L) were 10.5 ± 7.5 (∼G3a: 1.8 ± 0.6, G3b: 2.1 ± 0.6, G4: 15.8 ± 8.1, Ｇ5: 22.9 ± 13.5), and strongly correlated with eGFR (r =0.518, P<0.001). Among IS low (<6), middle and high (≥12) tertiles, significantly different factors were age, eGFR, Hb, iPTH and LDL-C. In multiple logistic regression analysis, only eGFR was significant associating factor with IS tertiles. IS levels in 2 patients prescribed AST-120 (Kremezin) were 8.1 and 10.3, which seems to be very low in comparison to their eGFR of 13.8 and 13.7. During observation period of 5.1 ± 1.0 years, 59 renal outcomes and 9 CVD events were observed. Kaplan-Meier survival curve analysis free from renal outcomes revealed better tendency in IS low group (p= 0.0617 in log-rank test). According to IS levels adjusted by eGFR, only 1 out of 9 CVD events occurred in low IS/eGFR tertile group. Conclusion Serum IS levels could be measured in new enzymatic method. Strong correlation between IS and eGFR was demonstrated, and AST-120 might be effective to improve IS. In renal and CVD outcome analysis, more sample size is needed for further study.

scholarly journals Uremic Toxins and Frailty in Patients with Chronic Kidney Disease: A Molecular Insight

2021 ◽  
Vol 22 (12) ◽  
pp. 6270
Author(s):  
Chia-Ter Chao ◽  
Shih-Hua Lin
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Uremic Toxins ◽  
Heme Oxygenase 1 ◽  
Signal Pathways ◽  
Uremic Toxin ◽  
Nuclear Factor ◽  
Cognitive Frailty ◽  
Renal Function Decline

The accumulation of uremic toxins (UTs) is a prototypical manifestation of uremic milieu that follows renal function decline (chronic kidney disease, CKD). Frailty as a potential outcome-relevant indicator is also prevalent in CKD. The intertwined relationship between uremic toxins, including small/large solutes (phosphate, asymmetric dimethylarginine) and protein-bound ones like indoxyl sulfate (IS) and p-cresyl sulfate (pCS), and frailty pathogenesis has been documented recently. Uremic toxins were shown in vitro and in vivo to induce noxious effects on many organ systems and likely influenced frailty development through their effects on multiple preceding events and companions of frailty, such as sarcopenia/muscle wasting, cognitive impairment/cognitive frailty, osteoporosis/osteodystrophy, vascular calcification, and cardiopulmonary deconditioning. These organ-specific effects may be mediated through different molecular mechanisms or signal pathways such as peroxisome proliferator-activated receptor γ coactivator 1-α (PGC-1α), mitogen-activated protein kinase (MAPK) signaling, aryl hydrocarbon receptor (AhR)/nuclear factor-κB (NF-κB), nuclear factor erythroid 2-related factor 2 (Nrf2), heme oxygenase-1 (HO-1), Runt-related transcription factor 2 (RUNX2), bone morphogenic protein 2 (BMP2), osterix, Notch signaling, autophagy effectors, microRNAs, and reactive oxygen species induction. Anecdotal clinical studies also suggest that frailty may further accelerate renal function decline, thereby augmenting the accumulation of UTs in affected individuals. Judging from these threads of evidence, management strategies aiming for uremic toxin reduction may be a promising approach for frailty amelioration in patients with CKD. Uremic toxin lowering strategies may bear the potential of improving patients’ outcomes and restoring their quality of life, through frailty attenuation. Pathogenic molecule-targeted therapeutics potentially disconnect the association between uremic toxins and frailty, additionally serving as an outcome-modifying approach in the future.

scholarly journals Indoxyl sulfate has a dominant role regarding the risks during different stages of chronic kidney disease

2020 ◽  
Author(s):  
Cheng-Hsu Chen ◽  
Shih-Chien Huang ◽  
Pei-Chih Lin ◽  
Shang-Feng Tsai ◽  
Yi-Chia Huang
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Dominant Role ◽  
Plasma Homocysteine ◽  
Uremic Toxins ◽  
Indoxyl Sulfate ◽  
Antioxidant Enzyme Activities ◽  
Uremic Toxin ◽  
Ckd Stage

Abstract Background: Increased levels of uremic toxins and decreased antioxidant capacities have a significant impact on the progression of chronic kidney disease (CKD). However, it is unclear whether they interact with each other in order to mediate the damage of renal function. The purpose of this study was to determine whether uremic toxins [i.e., homocysteine and indoxyl sulfate (IS)] and glutathione-dependent antioxidant enzyme activities are dependently or independently associated with each other in affecting renal function during different stages of CKD patients.Methods: One hundred thirty-two patients diagnosed with CKD stage 1 to 5 participated in this cross-sectional study.Results: Patients who had reached an advanced CKD stage experienced a gradual increase in plasma uremic toxin levels, along with decreased glutathione peroxidase (GSH-Px) activities. Plasma homocysteine, cysteine and IS concentrations were positively associated with each other, but negatively correlated to GSH-Px activity levels after adjusting potential confounders in all CKD patients. Although plasma homocysteine, cysteine, IS and GSH-Px levels were significantly associated with renal function, only plasma IS levels still had a significant association with renal function after these parameters were simultaneously adjusted.Conclusions: IS plays a more dominant role than other factors in affecting renal function, where a higher IS concentration needs to be controlled in order to defer the progressive loss of renal function.

scholarly journals Therapeutic Targeting of Aristolochic Acid Induced Uremic Toxin Retention, SMAD 2/3 and JNK/ERK Pathways in Tubulointerstitial Fibrosis: Nephroprotective Role of Propolis in Chronic Kidney Disease

Toxins ◽  
2020 ◽  
Vol 12 (6) ◽  
pp. 364
Author(s):  
Jia-Feng Chang ◽  
Chih-Yu Hsieh ◽  
Kuo-Cheng Lu ◽  
Yue-Wen Chen ◽  
Shih-Shin Liang ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Transforming Growth Factor ◽  
Epithelial Mesenchymal Transition ◽  
Plasma Concentrations ◽  
Tubulointerstitial Fibrosis ◽  
Uremic Toxin ◽  
Mesenchymal Transition ◽  
Propolis Extract

The nephrotoxicity of aristolochic acids (AAs), p-cresyl sulfate (PCS) and indoxyl sulfate (IS) were well-documented, culminating in tubulointerstitial fibrosis (TIF), advanced chronic kidney disease (CKD) and fatal urothelial cancer. Nonetheless, information regarding the attenuation of AAs-induced nephropathy (AAN) and uremic toxin retention is scarce. Propolis is a versatile natural product, exerting anti-oxidant, anti-cancer and anti-fibrotic properties. We aimed to evaluate nephroprotective effects of propolis extract (PE) in a murine model. AAN was developed to retain circulating PCS and IS using C57BL/6 mice, mimicking human CKD. The kidney sizes/masses, renal function indicators, plasma concentrations of PCS/IS, tissue expressions of TIF, α-SMA, collagen IaI, collagen IV and signaling pathways in transforming growth factor-β (TGF-β) family were analyzed among the control, PE, AAN, and AAN-PE groups. PE ameliorated AAN-induced renal atrophy, renal function deterioration, TIF, plasma retention of PCS and IS. PE also suppressed α-SMA expression and deposition of collagen IaI and IV in the fibrotic epithelial-mesenchymal transition. Notably, PE treatment in AAN model inhibited not only SMAD 2/3-dependent pathways but also SMAD-independent JNK/ERK activation in the signaling cascades of TGF-β family. Through disrupting fibrotic epithelial-mesenchymal transition and TGF-β signaling transduction pathways, PE improves TIF and thereby facilitates renal excretion of PCS and IS in AAN. In light of multi-faced toxicity of AAs, PE may be capable of developing a new potential drug to treat CKD patients exposed to AAs.

P11 The difference in the serial change of indoxyl sulfate after catheter ablation among atrial fibrillation patients with or without chronic kidney disease

2020 ◽  
Vol 41 (Supplement_1) ◽  
Author(s):  
H Koike ◽  
I Watanabe ◽  
KATSUYA Akitsu ◽  
MASAYA Shinohara ◽  
TOSHIO Kinoshita ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Chronic Kidney Disease ◽  
Renal Function ◽  
Catheter Ablation ◽  
Kidney Disease ◽  
Indoxyl Sulfate ◽  
Uremic Toxin ◽  
Ckd Stage ◽  
Serial Change ◽  
The Difference

Abstract Introduction It is well known that catheter ablation (CA) for patients with atrial fibrillation (AF) improves their renal function. However, the precise mechanism of improving a renal function, such as a transition of the uremic toxin is unclear. Purpose Indoxyl sulfate (IS), a protein-bound uremic toxin, induces chronic kidney disease (CKD) and AF. This study aimed to investigate the transition of serum IS level in the AF patients with and without CKD after CA. Methods A total of 138 consecutive AF patients who underwent CA and maintained sinus rhythm were prospectively enrolled (age 65.5 ± 10.7 years, paroxysmal AF 67.4%). Patients were divided into 4 groups (non-CKD/low-IS:68, non-CKD/high-IS:28, CKD/low-IS:13, CKD/high-IS:29). CKD was defined as CKD stage III (estimated glomerular filtration rate (eGFR) 30-60 ml/min/1.73m2), and high-IS was defined according to the mean of IS (IS≥1.1 μg/ml) before CA. Plasma IS levels and eGFR were determined before and at 1 year after CA. We evaluated the relationship between the IS and eGFR after CA among the 4 groups. Results CA significantly improved the eGFR in patients with CKD (from 50.2 ± 5.7 to 55.4 ± 10.8 ml/min/1.73m2, p < 0.001). The serum IS level in the patients with non-CKD/high-IS was significantly decreased (from 1.7 ± 0.7 to 1.1 ± 0.6 μg/ml, p < 0.001). However, the serum IS level in the patients with CKD/high-IS was not improved (from 1.9 ± 0.9 to 1.7 ± 0.7 μg/ml, p = 0.22) and significantly higher than that in the others (p < 0.001), regardless of improving their eGFR (Figure). Furthermore, the multiple regression analysis revealed that the ΔIS, between before and after CA, was independent of eGFR. Conclusion The change of IS in the patients with CKD was significantly different from that in those without CKD. In the patients with CKD, CA improved their eGFR, however, the serum level of IS, a protein-bound uremic toxin, was not improved after CA. Abstract P11 Figure. Serial Change of eGFR and IS

scholarly journals Variability in Estimated Glomerular Filtration Rate by Area under the Curve Predicts Renal Outcomes in Chronic Kidney Disease

2014 ◽  
Vol 2014 ◽  
pp. 1-8 ◽  
Author(s):  
Szu-Chia Chen ◽  
Ming-Yen Lin ◽  
Teng-Hui Huang ◽  
Chi-Chih Hung ◽  
Yi-Wen Chiu ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Glomerular Filtration Rate ◽  
Kidney Disease ◽  
Glomerular Filtration ◽  
Filtration Rate ◽  
Estimated Glomerular Filtration Rate ◽  
Cox Model ◽  
Renal Outcomes ◽  
End Point

Greater variability in renal function is associated with mortality in patients with chronic kidney disease (CKD). However, few studies have demonstrated the predictive value of renal function variability in relation to renal outcomes. This study investigates the predictive ability of different methods of determining estimated glomerular filtration rate (eGFR) variability for progression to renal replacement therapy (RRT) in CKD patients. This was a prospective observational study, which enrolled 1,862 CKD patients. The renal end point was defined as commencement of RRT. The variability in eGFR was measured by the area under the eGFR curve (AUC)%. A significant improvement in model prediction was based on the −2 log likelihood ratio statistic. During a median 28.7-month follow-up, there were 564 (30.3%) patients receiving RRT. In an adjusted Cox model, a smaller initial eGFR AUC%_12M (P<0.001), a smaller peak eGFR AUC%_12M (P<0.001), and a larger negative eGFR slope_12M (P<0.001) were associated with a higher risk of renal end point. Two calculated formulas: initial eGFR AUC%_12M and eGFR slope_12M were the best predictors. Our results demonstrate that the greater eGFR variability by AUC% is associated with the higher risk of progression to RRT.

EFFECTIVENESS OF ANTIAGGREGANT THERAPY ON KIDNEY ACTIVITY IN THE PREDIALYSIS STAGE OF CHRONIC KIDNEY DISEASE

2020 ◽  
Vol 6 (1) ◽  
pp. 55-60
Author(s):  
Khabib Barnoev ◽  
◽  
Sherali Toshpulatov ◽  
Nozima Babajanova ◽  
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Function ◽  
Kidney Disease ◽  
Comparative Study ◽  
Functional Status ◽  
Stage Ii ◽  
Term Administration ◽  
Antiaggregant Therapy

The article presents the results of a study to evaluate the effectiveness of antiaggregant therapy on the functional status of the kidneys in 115 patients with stage II and III chronic kidney disease on the basis of a comparative study of dipyridamole and allthrombosepin. Studies have shown that long-term administration of allthrombosepin to patients has led to improved renal function.

scholarly journals Renal Function as a Predictor of Reamputation After Initial Transmetatarsal Amputation in the Perioperative Period

2018 ◽  
Vol 3 (3) ◽  
pp. 2473011418S0001
Author(s):  
Junho Ahn ◽  
Katherine Raspovic ◽  
Dane Wukich ◽  
George Liu
Keyword(s):  
Chronic Kidney Disease ◽  
Renal Failure ◽  
Renal Function ◽  
Kidney Disease ◽  
Lower Extremity ◽  
Perioperative Period ◽  
Improvement Program ◽  
Acs Nsqip ◽  
Cell Counts ◽  
Insulin Dependent

Category: Midfoot/Forefoot Introduction/Purpose: With increasing rates of patients being newly diagnosed with diabetes mellitus, foot complications are becoming more common, which often lead to amputation. Compared to major lower extremity amputations, transmetatarsal amputations (TMA) are associated with lower cost, better function, and more aesthetically satisfactory results for patients. Renal failure has been shown to be a significant predictor of morbidity and mortality in lower extremity amputations at various levels. However, previous reports examining the effect of renal function on reamputation rates after TMA have been mixed. As a result, the purpose of this study was to evaluate renal dysfunction as a risk factor for reamputation after initial TMA during the 30-day perioperative period in a large population database. Methods: Patients under 90 years of age who underwent a TMA between 2012 and 2015 were retrospectively identified in the prospectively collected American College of Surgeons-National Surgical Quality Improvement Program® (ACS-NSQIP®) database using the Current Procedure Terminology (CPT) code 28805. Failure of the initial TMA was defined as reamputation in the 30-day perioperative period through corresponding CPT codes. From these criteria, a total of 1,775 patients were identified. More than 150 unique patient factors were included in the study, but glycated hemoglobin (HbA1C) was not reported by the ACS-NSQIP® database. Diabetes status was categorized into four groups: “Insulin” dependent, “Non-Insulin” dependent, or “None.” Filtration rate was estimated using the Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) equation, and patients were categorized into stages of chronic kidney disease (CKD). Results: Over the 30-day perioperative period, the rate of reamputation after TMA was 6.5%. No statistical differences in age, gender, race, body-mass index, or level of pre-operative functional status were found between groups. Reamputation rates after TMA was significantly correlated with higher white blood cell counts (p<.00001), greater serum creatinine (p=.021), higher blood urea nitrogen (p=.021), type of glycemic control (p=.002), stage of CKD (p=.003), dialysis (p=.001), and pre-operative blood transfusion (p=.042). Stage IV-V CKD was associated with 75% increased odds of reamputation (OR=1.75, 95% CI=1.12-2.73), and higher stage of CKD was associated with greater reamputation rates (p=.003) where stage II CKD had the lowest reamputation rate (3.6%) and stage V with the highest reamputation rate (10.9%). A similar trend was seen with 30-day mortality (p<.00001). Conclusion: In the current study, CKD was significantly correlated with reamputation rates after TMA as well as 30-day mortality. In contrast to a previous report, dialysis was also associated with TMA failure and need for reamputation. Our findings corroborate previous findings correlating dialysis-dependent renal failure and mortality. Whether patients in certain stages of CKD would achieve better outcomes with higher-level amputation rather than a TMA should be investigated in future studies.

scholarly journals Uremic toxin indoxyl sulfate promotes proinflammatory macrophage activation by regulation of β-catenin and YAP pathways

2021 ◽  
Author(s):  
Ying Li ◽  
Jing Yan ◽  
Minjia Wang ◽  
Jing Lv ◽  
Fei Yan ◽  
...  
Keyword(s):  
Cardiovascular Disease ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Inflammatory Response ◽  
Macrophage Polarization ◽  
Indoxyl Sulfate ◽  
Uremic Toxin ◽  
Lps Challenge ◽  
Hla Dr ◽  
M1 Macrophage

AbstractEvidence has been shown that indoxyl sulfate (IS) could impair kidney and cardiac functions. Moreover, macrophage polarization played important roles in chronic kidney disease and cardiovascular disease. IS acts as a nephron-vascular toxin, whereas its effect on macrophage polarization during inflammation is still not fully elucidated. In this study, we aimed to investigate the effect of IS on macrophage polarization during lipopolysaccharide (LPS) challenge. THP-1 monocytes were incubated with phorbol 12-myristate-13-acetate (PMA) to differentiate into macrophages, and then incubated with LPS and IS for 24 h. ELISA was used to detect the levels of TNFα, IL-6, IL-1β in THP-1-derived macrophages. Western blot assay was used to detect the levels of arginase1 and iNOS in THP-1-derived macrophages. Percentages of HLA-DR-positive cells (M1 macrophages) and CD206-positive cells (M2 macrophages) were detected by flow cytometry. IS markedly increased the production of the pro-inflammatory factors TNFα, IL-6, IL-1β in LPS-stimulated THP-1-derived macrophages. In addition, IS induced M1 macrophage polarization in response to LPS, as evidenced by the increased expression of iNOS and the increased proportion of HLA-DR+ macrophages. Moreover, IS downregulated the level of β-catenin, and upregulated the level of YAP in LPS-stimulated macrophages. Activating β-catenin signaling or inhibiting YAP signaling suppressed the IS-induced inflammatory response in LPS-stimulated macrophages by inhibiting M1 polarization. IS induced M1 macrophage polarization in LPS-stimulated macrophages via inhibiting β-catenin and activating YAP signaling. In addition, this study provided evidences that activation of β-catenin or inhibition of YAP could alleviate IS-induced inflammatory response in LPS-stimulated macrophages. This finding may contribute to the understanding of immune dysfunction observed in chronic kidney disease and cardiovascular disease.

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