Effect of clofibrate on fatty acid metabolism in the kidney of puromycin-induced nephrotic rats

Muroya, Yoshikazu; Itoh, Osamu

doi:10.1007/s10157-016-1253-0

Cited by 9 publications

(10 citation statements)

References 31 publications

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“…Urinary TGF-β1 and 8-OHdG, the biomarkers of renal scaring and oxidative stress, respectively, have also been used in other studies of kidney injury. 17,18 Despite being statistically insignificant, the trend toward the reduction of TGF-β1 in our study suggests possible attenuation of renal fibrosis after mTORIs conversion. A possible link between NGAL and interstitial fibrosis in CKD was also described in a previous study.…”

Section: Discussioncontrasting

confidence: 54%

“…These novel biomarkers might enable the identification of unknown mechanisms of action associated with mTORI conversion on renal protection. [16][17][18] Despite the potential differences between sirolimus and everolimus, head-to-head randomized comparisons between these two mTORIs in liver transplant recipients are lacking. This study was designed to evaluate the differences in renal outcome between sirolimus and everolimus conversion and explore possible mechanisms of renoprotection by using novel renal biomarkers of glomerular or tubular injury, renal fibrosis, and oxidative stress in liver transplant recipients.…”

mentioning

confidence: 99%

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Effects of Conversion From Calcineurin Inhibitors to Sirolimus or Everolimus on Renal Function and Possible Mechanisms in Liver Transplant Recipients

Tsai

Hsu

et al. 2018

The Journal of Clinical Pharma

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Mammalian targets of rapamycin inhibitors (mTORIs), including sirolimus and everolimus, are used for minimizing calcineurin inhibitors after liver transplantation. However, head-to-head randomized comparisons of these 2 mTORIs are lacking. We assessed the differences in renoprotection and possible mechanisms between sirolimus and everolimus in liver transplant recipients. For this prospective cohort study, we recruited liver transplant recipients whose regimens were switched from tacrolimus to sirolimus or everolimus at a Taiwan medical center. Serial changes in estimated glomerular filtration rate (eGFR), urinary N-acetyl-β-D-glucosaminidase, neutrophil gelatinase-associated lipocalin, 8-hydroxy-2 -deoxyguanosine, and transforming growth factor-β1 during 1 year after mTORI conversion were compared within and between groups. In the 61 patients analyzed, no significant change in eGFR occurred within 12 months after conversion in both mTORI groups. Among patients with baseline eGFR <60 mL/min/ 1.73 m 2 , eGFR improved at 6 months and 1 year after conversion (+12.3 and +12.0 mL/min/1.73 m 2 , both P < .05). Urinary N-acetyl-β-Dglucosaminidase decreased in both sirolimus and everolimus groups at 6 months (-68.7 ± 137.6 and -62.0 ± 92.4 U/g creatinine, both P < .05), and the reduction of urinary neutrophil gelatinase-associated lipocalin was significant in the sirolimus group (-4345.1 ± 7763.5 ng/g creatinine; P < .05). Neither transforming growth factor-β1 nor 8-hydroxy-2´-deoxyguanosine changed significantly. In conclusion, the renoprotective effect of mTORI conversion was significant in liver transplant recipients with renal insufficiency, which was similar for sirolimus and everolimus, in the first year and may be associated with ameliorated tubular injury. Available evidence remains insufficient to determine which mTORI conversion therapy is more effective in renoprotection in the long run.

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Section: Discussioncontrasting

confidence: 54%

mentioning

confidence: 99%

Effects of Conversion From Calcineurin Inhibitors to Sirolimus or Everolimus on Renal Function and Possible Mechanisms in Liver Transplant Recipients

Tsai

Hsu

et al. 2018

The Journal of Clinical Pharma

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“…The protective role of peroxisome proliferator-activated receptor α (PPARα) activation in nephrosis induced by fatty acids [1,2] and chronic kidney disease (CKD) [3] recently has been drawing great attention. The nephrosis and CKD can also be identified in neonates with an epigenetic origin [4], and physiological aAlterations in the bioactive lipids pattern [5] and oxidative status have been observed in the abnormal lipid metabolism [6].…”

Section: Introductionmentioning

confidence: 99%

“…Therefore, understanding renal development and adaptation of energy metabolism is very important for human infant health. Fatty acids are the preferred renal energy substrate, and it is believed that maintaining an active fatty acid metabolism is significant for the renal protective effects afforded by PPARα activation [2,7].…”

Section: Introductionmentioning

confidence: 99%

Effects of Dietary Anaplerotic and Ketogenic Energy Sources on Renal Fatty Acid Oxidation Induced by Clofibrate in Suckling Neonatal Pigs

Lin¹,

Pike²,

Zhao³

et al. 2020

IJMS

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Maintaining an active fatty acid metabolism is important for renal growth, development, and health. We evaluated the effects of anaplerotic and ketogenic energy sources on fatty acid oxidation during stimulation with clofibrate, a pharmacologic peroxisome proliferator-activated receptor α (PPARα) agonist. Suckling newborn pigs (n = 72) were assigned into 8 dietary treatments following a 2 × 4 factorial design: ± clofibrate (0.35%) and diets containing 5% of either (1) glycerol-succinate (GlySuc), (2) tri-valerate (TriC5), (3) tri-hexanoate (TriC6), or (4) tri-2-methylpentanoate (Tri2MPA). Pigs were housed individually and fed the iso-caloric milk replacer diets for 5 d. Renal fatty acid oxidation was measured in vitro in fresh tissue homogenates using [1-14C]-labeled palmitic acid. The oxidation was 30% greater in pig received clofibrate and 25% greater (p < 0.05) in pigs fed the TriC6 diet compared to those fed diets with GlySuc, TriC5, and Tri2MPA. Addition of carnitine also stimulated the oxidation by twofold (p < 0.05). The effects of TriC6 and carnitine on palmitic acid oxidation were not altered by clofibrate stimulation. However, renal fatty acid composition was altered by clofibrate and Tri2MPA. In conclusion, modification of anaplerosis or ketogenesis via dietary substrates had no influence on in vitro renal palmitic acid oxidation induced by PPARα activation.

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“…Dose-finding studies to determine whether lower concentrations of amiloride provides glomerular protective effects with reduced risks of complications attributed to doses used in the setting of resistant edema may be appropriate.METHODS AND MATERIALSAnimal Studies. PAN nephropathy was induced as per established protocol 71,72. Briefly, 6-8 weeks old male Wistar rats were intravenously injected either with either PAN (n=7; single IV 100 mg/kg) or PAN + amiloride (n=8; PAN + 0.5mmol/L amiloride).…”

mentioning

confidence: 99%

Plasminogenuria is associated with podocyte injury, edema, and kidney dysfunction in incident glomerular disease

Egerman

Wong

Tian

et al. 2019

Preprint

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Urinary plasminogen/plasmin, or plasmin(ogen)uria, has been demonstrated in proteinuric patients and exposure of cultured podocytes to plasminogen results in injury via oxidative stress pathways. A causative role for plasmin(ogen) as a “second hit” in kidney disease progression has yet to be demonstrated in vivo, and the association between plasmin(ogen)uria and kidney function in glomerular diseases remains unclear. We performed comparative studies in a puromycin aminonucleoside (PAN) nephropathy rat model treated with amiloride, an inhibitor of plasminogen activation, and measured changes in plasmin(ogen)uria and urinary endothelin-1 (ET1). In a glomerular disease biorepository cohort (n=128), we measured time-of- biopsy albuminuria, proteinuria, and plasmin(ogen)uria for correlations with renal outcomes. Increased glomerular plasmin(ogen) was found in PAN rats and FSGS patients. PAN nephropathy was associated with increases in plasmin(ogen)uria, proteinuria, and urinary ET1. Amiloride was protective against PAN- induced glomerular injury, reducing urinary ET1 and oxidative stress. In patients, we found associations between plasmin(ogen)uria and edema status as well as eGFR. Our study demonstrates a role for plasmin(ogen)-induced podocyte injury in the PAN nephropathy model, with amiloride having podocyte- protective properties. In one of largest glomerular disease cohorts to study plasminogen, we validated previous findings while suggesting a potentially novel relationship between plasmin(ogen)uria and eGFR. Together, these findings suggest a role for plasmin(ogen) in mediating glomerular injury and as a viable targetable biomarker for podocyte-sparing treatments.

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Effect of clofibrate on fatty acid metabolism in the kidney of puromycin-induced nephrotic rats

Abstract: Clofibrate is protective against renal lipotoxicity in PAN nephrosis. This study indicates that clofibrate has renoprotective effects through maintaining fatty acid metabolism in the kidney of PAN-induced nephrotic rats.

Cited by 9 publications

References 31 publications

Effects of Conversion From Calcineurin Inhibitors to Sirolimus or Everolimus on Renal Function and Possible Mechanisms in Liver Transplant Recipients

Effects of Conversion From Calcineurin Inhibitors to Sirolimus or Everolimus on Renal Function and Possible Mechanisms in Liver Transplant Recipients

Effects of Dietary Anaplerotic and Ketogenic Energy Sources on Renal Fatty Acid Oxidation Induced by Clofibrate in Suckling Neonatal Pigs

Plasminogenuria is associated with podocyte injury, edema, and kidney dysfunction in incident glomerular disease

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