Tenofovir disoproxil fumarate co-administered with lopinavir/ritonavir is strongly associated with tubular damage and chronic kidney disease

2018 ◽  
Vol 24 (7) ◽  
pp. 549-554 ◽  
Author(s):  
Daisuke Mizushima ◽  
Dung Thi Hoai Nguyen ◽  
Dung Thi Nguyen ◽  
Shoko Matsumoto ◽  
Junko Tanuma ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Tenofovir Disoproxil Fumarate ◽  
Tubular Damage

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

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.

Using the chronic kidney disease guidelines to evaluate the renal safety of tenofovir disoproxil fumarate in hepatitis B patients

2018 ◽  
Vol 47 (12) ◽  
pp. 1673-1681 ◽  
Author(s):  
H. J. Tsai ◽  
Y. W. Chuang ◽  
S. W. Lee ◽  
C. Y. Wu ◽  
H. Z. Yeh ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Hepatitis B ◽  
Tenofovir Disoproxil Fumarate ◽  
Renal Safety

scholarly journals Addition of aliskiren to olmesartan ameliorates tubular injury in chronic kidney disease patients partly by reducing proteinuria

2011 ◽  
Vol 13 (1) ◽  
pp. 122-127 ◽  
Author(s):  
Tsukasa Nakamura ◽  
Eiichi Sato ◽  
Mayuko Amaha ◽  
Yasuhiro Kawagoe ◽  
Sayaka Maeda ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Combination Therapy ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Renin Angiotensin System ◽  
Stage I ◽  
Tubular Damage ◽  
Tubular Injury ◽  
Fatty Acid Binding

Introduction: Tubular injury is more important than glomerulopathy for renal prognosis in chronic kidney disease (CKD) patients. Numerous studies have demonstrated the active participation of the renin–angiotensin system (RAS) in CKD. However, whether addition of aliskiren, a direct renin inhibitor, to olmesartan improves renal tubular injury in CKD patients is unknown. Methods: This study compared the effects of aliskiren (300 mg daily), olmesartan (40 mg daily), and its combination therapy on urinary L-fatty acid binding protein (L-FABP), a marker of tubular injury in stage I or II CKD patients. It also examined which clinical variables were independently correlated with tubular damage. Results: Olmesartan or aliskiren monotherapy for 6 months comparably decreased blood pressure (BP) and proteinuria. BP and proteinuria levels were reduced more by combination therapy than by either monotherapy. Olmesartan or aliskiren decreased urinary L-FABP level, and combination therapy produced more incremental reduction in L-FABP level relative to each monotherapy. Multiple stepwise regression analysis revealed that BMI, low-density lipoprotein (LDL)-cholesterol and proteinuria were independently related to urinary L-FABP level. Conclusions: The present study demonstrated that addition of aliskiren to olmesartan decreased urinary L-FABP level partly via reduction of proteinuria in stage I or II CKD patients.

scholarly journals Monitoring the Effects of Tenofovir Disoproxil Fumarate to Tenofovir Alafenamide Switch for Tubulotoxicity in Highly Treatment-Experienced or in Very Sick Individuals Infected with HIV

2018 ◽  
Vol 2 (2) ◽  
pp. 1-5
Author(s):  
Nicole Lioufas ◽  
Alan Street ◽  
Paul Champion De Crespigny ◽  
Stephen G. Holt
Keyword(s):  
Chronic Kidney Disease ◽  
Human Immunodeficiency Virus ◽  
Kidney Disease ◽  
Tenofovir Disoproxil Fumarate ◽  
Serum Biochemistry ◽  
Lower Serum ◽  
Frequent Monitoring ◽  
Immunodeficiency Virus ◽  
Tubular Toxicity ◽  
Tenofovir Alafenamide

Tenofovir disoproxil fumarate (TDF) is a common antiretroviral utilised in the treatment of human immunodeficiency virus (HIV) and hepatitis B infections. It is associated with the development of tubulotoxicity and tubulopathies, and is not recommended in the treatment of patients with baseline chronic kidney disease. Until now, guidelines have suggested frequent monitoring of serum biochemistry to detect the development of such complications. In recent trials, a new prodrug formulation of tenofovir alafenamide (TAF) has been shown to exhibit less tubular toxicity than its counterpart due to a lower serum concentration of its metabolites. In this article, we share our experience with two patients who developed tubulotoxicity following the commencement of TDF-based regimens in HIV, and its improvement following its change to TAF, and review the available literature regarding tenofovir-based nephrotoxicity.

scholarly journals Indomethacin Reduces Glomerular and Tubular Damage Markers but Not Renal Inflammation in Chronic Kidney Disease Patients: A Post-Hoc Analysis

PLoS ONE ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. e37957 ◽  
Author(s):  
Martin H. de Borst ◽  
Ferdau L. Nauta ◽  
Liffert Vogt ◽  
Gozewijn D. Laverman ◽  
Ron T. Gansevoort ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Tubular Damage ◽  
Renal Inflammation ◽  
Post Hoc Analysis ◽  
Post Hoc

scholarly journals Urinary Biomarkers of Tubular Damage Are Associated with Mortality but Not Cardiovascular Risk among Systolic Blood Pressure Intervention Trial Participants with Chronic Kidney Disease

2019 ◽  
Vol 49 (5) ◽  
pp. 346-355 ◽  
Author(s):  
Vasantha K. Jotwani ◽  
Alexandra K. Lee ◽  
Michelle M. Estrella ◽  
Ronit Katz ◽  
Pranav S. Garimella ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Systolic Blood Pressure ◽  
Strong Predictor ◽  
Urinary Biomarkers ◽  
Tubular Damage ◽  
Intervention Trial ◽  
Cvd Risk ◽  
Trial Participants

Background: Kidney tubulointerstitial fibrosis on biopsy is a strong predictor of chronic kidney disease (CKD) progression, and CKD is associated with elevated risk of cardiovascular disease (CVD). Tubular health is poorly quantified by traditional kidney function measures, including estimated glomerular filtration rate (eGFR) and albuminuria. We hypothesized that urinary biomarkers of tubular injury, inflammation, and repair would be associated with higher risk of CVD and mortality in persons with CKD. Methods: We measured urinary concentrations of interleukin-18 (IL-18), kidney injury molecule-1, neutrophil gelatinase-associated lipocalin, monocyte chemoattractant protein-1, and chitinase-3-like protein-1 (YKL-40) at baseline among 2,377 participants of the Systolic Blood Pressure Intervention Trial who had an eGFR < 60 mL/min/1.73 m2. We used Cox proportional hazards models to evaluate biomarker associations with CVD events and all-cause mortality. Results: At baseline, the mean age of participants was 72 ± 9 years, and eGFR was 48 ± 11 mL/min/1.73 m2. Over a median follow-up of 3.8 years, 305 CVD events (3.6% per year) and 233 all-cause deaths (2.6% per year) occurred. After multivariable adjustment including eGFR, albuminuria, and urinary creatinine, none of the biomarkers showed statistically significant associations with CVD risk. Urinary IL-18 (hazard ratio [HR] per 2-fold higher value, 1.14; 95% CI 1.01–1.29) and YKL-40 (HR per 2-fold higher value, 1.08; 95% CI 1.02–1.14) concentrations were each incrementally associated with higher mortality risk. Associations were similar when stratified by randomized blood pressure arm. Conclusions: Among hypertensive trial participants with CKD, higher urinary IL-18 and YKL-40 were associated with higher risk of mortality, but not CVD.

scholarly journals Oxalate-induced chronic kidney disease with its uremic and cardiovascular complications in C57BL/6 mice

2016 ◽  
Vol 310 (8) ◽  
pp. F785-F795 ◽  
Author(s):  
Shrikant R. Mulay ◽  
Jonathan N. Eberhard ◽  
Victoria Pfann ◽  
Julian A. Marschner ◽  
Murthy N. Darisipudi ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Kidney Disease ◽  
Cardiac Fibrosis ◽  
Control Diet ◽  
Cardiovascular Complications ◽  
Tubular Damage ◽  
Histological Changes ◽  
Renal Histology ◽  
Atubular Glomeruli ◽  
Normochromic Anemia

Chronic kidney disease (CKD) research is limited by the lack of convenient inducible models mimicking human CKD and its complications in experimental animals. We demonstrate that a soluble oxalate-rich diet induces stable stages of CKD in male and female C57BL/6 mice. Renal histology is characterized by tubular damage, remnant atubular glomeruli, interstitial inflammation, and fibrosis, with the extent of tissue involvement depending on the duration of oxalate feeding. Expression profiling of markers and magnetic resonance imaging findings established to reflect inflammation and fibrosis parallel the histological changes. Within 3 wk, the mice reproducibly develop normochromic anemia, metabolic acidosis, hyperkalemia, FGF23 activation, hyperphosphatemia, and hyperparathyroidism. In addition, the model is characterized by profound arterial hypertension as well as cardiac fibrosis that persist following the switch to a control diet. Together, this new model of inducible CKD overcomes a number of previous experimental limitations and should serve useful in research related to CKD and its complications.

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