Assessment of Thrombotic and Bleeding Tendency in Two Mouse Models of Chronic Kidney Disease: Adenine-Diet and 5/6th Nephrectomy

AbstractThe coexistence of bleeding and thrombosis in patients with chronic kidney disease (CKD) is frequent and poorly understood. Mouse models are essential to understand complications of CKD and to develop new therapeutic approaches improving the health of patients. We evaluated the hemostasis in two models of renal insufficiency: adenine-diet and 5/6th nephrectomy (5/6Nx). Compared with 5/6Nx mice, mice fed with 0.25% adenine had more severe renal insufficiency and so higher levels of prothrombotic uremic toxins like indoxyl sulfate. More severe renal inflammation and fibrosis were observed in the adenine group, as demonstrated by histological and reverse transcription quantitative polymerase chain reaction experiments. Liver fibrinogen γ chain expression and level of plasma fibrinogen were increased only in adenine mice. In both CKD mouse models, tissue factor (TF) expression was increased in kidney and aorta extracts. Immunochemistry analysis of kidney sections showed that TF is localized in the vascular walls. Thrombin–antithrombin complexes were significantly increased in plasma from both adenine and 5/6Nx mice. Tail bleeding time increased significantly only in adenine mice, whereas platelet count was not significant altered. Finally, results obtained by intravital microscopy after laser-induced endothelial injury showed impaired platelet function in adenine mice and an increase in fibrin generation in 5/6Nx mice. To summarize, adenine diet causes a more severe renal insufficiency compared with 5/6Nx. The TF upregulation and the hypercoagulable state were observed in both CKD models. Bleeding tendency was observed only in the adenine model of CKD that recapitulates the whole spectrum of hemostasis abnormalities observed in advanced human CKD.

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Targeting inflammation: New therapeutic approaches in chronic kidney disease (CKD)

Pharmacological Research ◽

10.1016/j.phrs.2014.02.007 ◽

2014 ◽

Vol 81 ◽

pp. 91-102 ◽

Cited By ~ 69

Author(s):

Daniela Impellizzeri ◽

Emanuela Esposito ◽

James Attley ◽

Salvatore Cuzzocrea

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Therapeutic Approaches ◽

New Therapeutic Approaches

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New Therapeutic Approaches to Chronic Kidney Disease

Journal of Comparative Pathology ◽

10.1016/j.jcpa.2017.10.098 ◽

2018 ◽

Vol 158 ◽

pp. 127

Author(s):

A. Nogueira ◽

H. Vala ◽

C. Nóbrega ◽

C.A. Pires ◽

B. Colaço ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Therapeutic Approaches ◽

New Therapeutic Approaches

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P2Y12 Antiplatelet Choice for Patients with Chronic Kidney Disease and Acute Coronary Syndrome: A Systematic Review and Meta-Analysis

Journal of Personalized Medicine ◽

10.3390/jpm11030222 ◽

2021 ◽

Vol 11 (3) ◽

pp. 222

Author(s):

Sohyun Park ◽

Yeo Jin Choi ◽

Ji Eun Kang ◽

Myeong Gyu Kim ◽

Min Jung Geum ◽

...

Keyword(s):

Myocardial Infarction ◽

Chronic Kidney Disease ◽

Kidney Disease ◽

Renal Insufficiency ◽

Clinical Outcomes ◽

Antiplatelet Therapy ◽

Major Bleeding ◽

Standard Dose ◽

Cardiac Outcomes ◽

Severe Renal Insufficiency

This study aims to evaluate potentially appropriate antiplatelet therapy in patients with chronic kidney disease. A systematic analysis was conducted to identify the clinical outcomes of available antiplatelet therapy regimens with enhanced platelet inhibition activity (intervention of 5 regimens) over the standard dose of clopidogrel-based dual antiplatelet therapy in patients with renal insufficiency. An electronic keyword search was performed on Pubmed, Embase, and Cochrane Library per PRISMA guidelines. We performed a prespecified net clinical benefit analysis (a composite of the rates of all-cause or cardiac-related death, myocardial infarction, major adverse cardiac outcomes, and minor and major bleeding), and included 12 studies. The intervention substantially lowered the incidence of all-cause mortality (RR 0.67; p = 0.003), major adverse cardiac outcomes (RR 0.79; p < 0.00001), and myocardial infarction (RR 0.28; p = 0.00007) without major bleeding (RR 1.14; p = 0.33) in patients with renal insufficiency, but no significant differences were noticed with cardiac-related mortality and stent thrombosis. The subgroup analysis revealed substantially elevated bleeding risk in patients with severe renal insufficiency or on hemodialysis (RR 1.68; p = 0.002). Our study confirmed that the intervention considerably enhances clinical outcomes in patients with renal insufficiency, however, a standard dose of clopidogrel-based antiplatelet therapy is favorable in patients with severe renal insufficiency.

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Avaliação da Resiliência em Pacientes com Insuficiência Renal Crônica Submetidos à Hemodiálise / Assessment of Resilience in Patients With Chronic Kidney Disease Undergoing Hemodialysis

REVISTA CIÊNCIAS EM SAÚDE ◽

10.21876/rcsfmit.v6i1.461 ◽

1970 ◽

Vol 6 (1) ◽

pp. 5-13

Author(s):

Renata Izabel dos Santos ◽

Otávia Regina Souza Costa

Keyword(s):

Chronic Kidney Disease ◽

Renal Failure ◽

Health Status ◽

Chronic Renal Failure ◽

Kidney Disease ◽

Renal Insufficiency ◽

Social Economic ◽

Descriptive Study ◽

Psychological Resilience ◽

Resilience Scale

RESUMOObjetivo: Avaliar o nível de resiliência dos portadores de insuficiência renal crônica em tratamento de hemodiálise. Materiais e Métodos: Estudo prospectivo, quantitativo e de abordagem descritiva. A amostra foi constituída por 61 pacientes em tratamento dialítico. Para obtenção dos resultados, foi utilizada a escala de resiliência, desenvolvida por Wagnild e Young (1993) e adaptada por Pesce et al., (2005). Foi aplicado, também, um questionário para caracterização pessoal, familiar, social, econômica e de saúde do grupo. Resultados: Foi constatado que 61% dos pacientes apresentaram tendência à resiliência. O gênero masculino obteve maior pontuação, sugerindo maior tendência à resiliência, bem como os pacientes que são praticantes de uma religião. Conclusão: Os resultados assinalam que os pacientes em tratamento dialítico no hospital apresentam capacidade à resiliência, o que sugere melhor adaptação ao tratamento.Palavras-chave: Avaliação, Resiliência psicológica, Insuficiência renal crônica.ABSTRACTObjective: To evaluate de the level of resilience in patients with chronic renal failure undergoing dialysis. Materials and Methods: Prospective, quantitative and descriptive study. The sample consisted of 61 patients on dialysis. To obtain the results we used Resilience Scale developed by Wagnild and Young (1993) and adapted by Pesce et al., (2005). A questionnaire to characterize personal, familiar, social, economic and health status was applied. Results: It was found that 61% of patients showed trend to resilience. Males had higher scores, suggesting more likelihood to resilience, as well as patients who were practitioners of a religion. Conclusion: The results indicate that the majority of patients on dialysis have capability of resilience, which suggests better adaptation to treatment.Keywords: Evaluation, Psychological resilience, Chronic renal insufficiency.

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Relation of Aortic Valve Calcium to Chronic Kidney Disease (from the Chronic Renal Insufficiency Cohort Study)

The American Journal of Cardiology ◽

10.1016/j.amjcard.2015.02.011 ◽

2015 ◽

Vol 115 (9) ◽

pp. 1281-1286 ◽

Cited By ~ 26

Author(s):

Marie A. Guerraty ◽

Boyang Chai ◽

Jesse Y. Hsu ◽

Akinlolu O. Ojo ◽

Yanlin Gao ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Cohort Study ◽

Kidney Disease ◽

Aortic Valve ◽

Renal Insufficiency ◽

Chronic Renal Insufficiency

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The uremic solute-AHR-tissue factor axis in vascular cells, mouse models and thrombosis in chronic kidney disease patients

Annals of Translational Medicine ◽

10.21037/atm.2018.04.27 ◽

2018 ◽

Vol 6 (11) ◽

pp. 225-225 ◽

Cited By ~ 1

Author(s):

Nigel Mackman ◽

Jonathan H. Erlich

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Tissue Factor ◽

Mouse Models ◽

Vascular Cells

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The kidney in sarcoidosis

Oxford Textbook of Medicine ◽

10.1093/med/9780198746690.003.0494 ◽

2020 ◽

pp. 5012-5015

Author(s):

Ingeborg Hilderson ◽

Jan Donck

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Renal Insufficiency ◽

Calcium Metabolism ◽

Histological Finding ◽

Common Cause ◽

Calcium Deposits ◽

Important Disease ◽

Tubulointerstitial Inflammation ◽

Steroid Sparing

Sarcoidosis is associated with a broad spectrum of renal manifestations, but clinically important disease occurs in few patients. The most common cause of renal dysfunction is abnormal calcium metabolism: untreated chronic hypercalcaemia and hypercalciuria causes progressive tubulointerstitial inflammation with associated calcium deposits, leading to nephrocalcinosis, which is the leading cause of chronic kidney disease. Interstitial granulomatous nephritis is the most typical histological finding, but development of renal insufficiency is unusual. A range of glomerulopathies can be associated with sarcoidosis. When treatment is required, steroids are the first line, with various steroid-sparing agents used in cases that are refractory.

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Combinational Use of Antiplatelet Medication Sarpogrelate with Therapeutic Drug Rosuvastatin in Treating High-Cholesterol Diet-Induced Chronic Kidney Disease in ApoE-Deficient Mice

BioMed Research International ◽

10.1155/2020/1809326 ◽

2020 ◽

Vol 2020 ◽

pp. 1-8

Author(s):

Jingyi Xu ◽

Zuowei Pei ◽

Meng Yu ◽

Xiang Li ◽

Lu Wang ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Kidney Disease ◽

Metabolic Disorders ◽

Expression Profiles ◽

Quantitative Polymerase Chain Reaction ◽

Antiplatelet Agent ◽

Histological Evaluation ◽

Therapeutic Drug ◽

Tubular Damage ◽

Antiplatelet Medication

A number of metabolic disorders, including hyperlipidemia, potentially cause chronic kidney disease (CKD), one of their major chronic complications and comorbidities. Rosuvastatin is one of the widely used antiatherogenic drugs among hyperlipidemic patients. Meanwhile, sarpogrelate is not only a 5-hydroxytryptamine receptor antagonist but also an antiplatelet agent, inhibiting platelet-stimulated blood coagulation and improving peripheral circulation. In this study, a combination of sarpogrelate and/or rosuvastatin was used on CKD mice induced by a high-fat diet for 8 weeks. The mice were tested for pathological changes using histological evaluation. Tremendous alterations were found, including a remarked increase in total cholesterol and low-density lipoprotein cholesterol levels, glomerular endothelial proliferation, and mesangial expansion. Also, tubular damage and extracellular matrix accumulation occurred, namely, a marked increase in the macula densa, scattered and apoptotic loss of the apical brush border with vacuolated basophilic cytoplasm and heavily stained nuclei, and expanded Bowman’s space, which were at least partially ameliorated by sarpogrelate and/or rosuvastatin treatment. The analysis of expression profiles at both the RNA and protein levels, using real-time quantitative polymerase chain reaction and Western blot analysis, indicated that LDL-R/CD68/LOX-1-positive monocyte/macrophage-mediated enhanced proinflammatory activation, including the significant upregulation of tumor necrosis factor-α and interleukin-6, was actually attenuated by sarpogrelate and/or rosuvastatin treatment. The findings indicated that sarpogrelate and/or rosuvastatin treatment potentially ameliorates CKD progression in patients with the aforementioned comorbid metabolic disorders.

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Incidence of Acute Kidney Injury in Patients with Chronic Renal Insufficiency: Transcatheter versus Surgical Aortic Valve Replacement

Journal of Interventional Cardiology ◽

10.1155/2019/9780415 ◽

2019 ◽

Vol 2019 ◽

pp. 1-6 ◽

Cited By ~ 1

Author(s):

Michael Catalano ◽

Dishen Lin ◽

Hugh Cassiere ◽

Nina Kohn ◽

Bruce Rutkin ◽

...

Keyword(s):

Chronic Kidney Disease ◽

Acute Kidney Injury ◽

Kidney Disease ◽

Aortic Valve ◽

Renal Insufficiency ◽

Aortic Valve Replacement ◽

Valve Replacement ◽

Kidney Injury ◽

Surgical Aortic Valve Replacement ◽

Postoperative Aki

Objectives. The objective of this study is to determine incidence of acute kidney injury (AKI) associated with transcatheter aortic valve replacement (TAVR) versus surgical aortic valve replacement (SAVR) in patients with preexisting chronic kidney disease. Background. The incidence of AKI in patients with preexisting renal insufficiency undergoing TAVR versus SAVR is not well described. Methods. All patients with preexisting chronic kidney disease who underwent SAVR for aortic stenosis with or without concomitant coronary artery bypass grafting or TAVR from 5/2008 to 6/2017. Patients requiring preoperative hemodialysis were excluded. Chronic kidney disease was defined as an estimated glomerular filtrate rate (eGFR) of < 60 mL/min/1.73 m2. The incidence of postoperative AKI was compared using the RIFLE classification system for acute kidney injury. Results. A total of 406 SAVR patients and 407 TAVR patients were included in this study. TAVR patients were older and had lower preoperative eGFR as compared to SAVR patients. Covariate adjustment using propensity score between the two groups showed that SAVR patients were more likely to have a more severe degree of postoperative AKI as compared to TAVR patients (OR = 4.75; 95% CI: 3.15, 7.17; p <.001). SAVR patients were more likely to require dialysis postoperatively as compared to TAVR patients (OR = 4.55; 95% CI: 1.29, 15.99; p <.018). Conclusion. In patients with preexisting chronic kidney disease, TAVR was associated with significantly less AKI as compared to SAVR.

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