Advertisement

Effect of pemafibrate, a novel selective peroxisome proliferator-activated receptor-alpha modulator (SPPARMα), on urinary protein excretion in IgA nephropathy with hypertriglyceridemia

  • 4 Accesses

Abstract

Lipid abnormalities, including hypertriglyceridemia, are one of the most common comorbidities in patients with chronic kidney disease (CKD) and are independently associated with disease progression. However, it remains uncertain whether treatment for hypertriglyceridemia has favorable effects on the clinical course of IgA nephropathy (IgAN). Pemafibrate is a novel selective peroxisome proliferator-activated receptor-alpha modulator and may be distinct from conventional fibrates in terms of its pharmacological activity and hepatic and renal safety. A recent clinical study demonstrated that pemafibrate was safe and effective for correcting pro-atherogenic lipid abnormalities in CKD patients with a wide range of renal insufficiency. However, the effect of pemafibrate on renal function in patients with IgAN and hypertriglyceridemia has not been verified. This paper is the first to show that 12 months of pemafibrate (0.1 mg daily) administration in three drug-naïve and mild IgAN patients with variable renal dysfunction and histopathology proven IgAN decreased serum triglyceride level and excretion of urinary protein and liver-type fatty acid-binding protein with no change in estimated glomerular filtration rate (eGFR). These findings suggest that pemafibrate is safe and effective for correcting hypertriglyceridemia and decreasing urinary protein excretion without changing eGFR and blood pressure levels in mild IgAN patients with hypertriglyceridemia.

This is a preview of subscription content, log in to check access.

Access options

Buy single article

Instant unlimited access to the full article PDF.

US$ 39.95

Price includes VAT for USA

Subscribe to journal

Immediate online access to all issues from 2019. Subscription will auto renew annually.

US$ 99

This is the net price. Taxes to be calculated in checkout.

Fig. 1
Fig. 2

References

  1. 1.

    Tsuruya K, Yoshida H, Nagata M, Kitazono T, Iseki K, Iseki C, Fujimoto S, Konta T, Moriyama T, Yamagata K, Narita I, Kimura K, Kondo M, Asahi K, Kurahashi I, et al. Impact of the triglycerides to high-density lipoprotein cholesterol ratio on the incidence and progression of CKD: a longitudinal study in a large Japanese population. Am J Kidney Dis. 2015;66:972–83.

  2. 2.

    Davis TM, Ting R, Best JD, Donoghoe MW, Drury PL, Sullivan DR, Jenkins AJ, O'Connell RL, Whiting MJ, Glasziou PP, Simes RJ, Kesäniemi YA, Gebski VJ, Scott RS, Keech AC, et al. Effects of fenofibrate on renal function in patients with type 2 diabetes mellitus: the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) Study. Diabetologia. 2011;54:280–90.

  3. 3.

    Yamashita S, Masuda D, Matsuzawa Y. Clinical applications of a novel selective PPARalpha modulator, pemafibrate, in dyslipidemia and metabolic diseases. J Atheroscler Thromb. 2019;26:389–402.

  4. 4.

    Yokote K, Yamashita S, Arai H, Araki E, Suganami H, Ishibashi S, Of The KSGOB. Long-term efficacy and safety of pemafibrate, a novel selective peroxisome proliferator-activated receptor-alpha modulator (SPPARMalpha), in dyslipidemic patients with renal impairment. Int J Mol Sci. 2019;20:706.

  5. 5.

    Maki T, Maeda Y, Sonoda N, Makimura H, Kimura S, Maeno S, Takayanagi R, Inoguchi T. Renoprotective effect of a novel selective PPARalpha modulator K-877 in db/db mice: a role of diacylglycerol-protein kinase C-NAD(P)H oxidase pathway. Metabolism. 2017;71:33–45.

  6. 6.

    Kawamura T, Joh K, Okonogi H, Koike K, Utsunomiya Y, Miyazaki Y, Matsushima M, Yoshimura M, Horikoshi S, Suzuki Y, Furusu A, Yasuda T, Shirai S, Shibata T, Endoh M, et al. A histologic classification of IgA nephropathy for predicting long-term prognosis: emphasis on end-stage renal disease. J Nephrol. 2013;26:350–7.

  7. 7.

    Trimarchi H, Barratt J, Cattran DC, Cook HT, Coppo R, Haas M, Liu ZH, Roberts IS, Yuzawa Y, Zhang H, Feehally J, IgAN Classification Working Group of the International IgA Nephropathy Network, and the Renal Pathology Society; Conference Participants. Oxford classification of IgA nephropathy 2016: an update from the IgA nephropathy classification working group. Kidney Int. 2017;91:1014–21.

  8. 8.

    Manno C, Torres DD, Rossini M, Pesce F, Schena FP. Randomized controlled clinical trial of corticosteroids plus ACE-inhibitors with long-term follow-up in proteinuric IgA nephropathy. Nephrol Dial Transpl. 2009;24:3694–701.

  9. 9.

    Pozzi C, Andrulli S, Del Vecchio L, Melis P, Fogazzi GB, Altieri P, Ponticelli C, Locatelli F. Corticosteroid effectiveness in IgA nephropathy: long-term results of a randomized, controlled trial. J Am Soc Nephrol. 2004;15:157–63.

  10. 10.

    Tonelli M, Collins D, Robins S, Bloomfield H, Curhan GC. Effect of gemfibrozil on change in renal function in men with moderate chronic renal insufficiency and coronary disease. Am J Kidney Dis. 2004;44:832–9.

  11. 11.

    Sato K, Sugawara A, Kudo M, Uruno A, Ito S, Takeuchi K. Expression of peroxisome proliferator-activated receptor isoform proteins in the rat kidney. Hypertens Res. 2004;27:417–25.

  12. 12.

    Hennuyer N, Duplan I, Paquet C, Vanhoutte J, Woitrain E, Touche V, Colin S, Vallez E, Lestavel S, Lefebvre P, Staels B. The novel selective PPARalpha modulator (SPPARMalpha) pemafibrate improves dyslipidemia, enhances reverse cholesterol transport and decreases inflammation and atherosclerosis. Atherosclerosis. 2016;249:200–8.

Download references

Acknowledgements

The authors wish to thank Aya Yamada for her excellent secretarial assistance.

Funding

This case report was not supported by any funding bodies.

Author information

Correspondence to Atsushi Tanaka.

Ethics declarations

Conflict of interest

AT has received a research grant from GlaxoSmithKline. KN has received honoraria from Ono, Takeda, Daiichi Sankyo, Astellas, MSD, Boehringer Ingelheim, and Mitsubishi Tanabe; research grants from Asahi Kasei, Astellas, Boehringer Ingelheim, Mitsubishi Tanabe, Teijin, and Terumo; scholarship from Bayer, Takeda, Astellas, Daiichi Sankyo, Teijin, and Bristol-Myers Squibb. The remaining authors declare no conflict of interest.

Ethical approval

This article does not contain any studies with human participants performed by any of the authors.

Informed consent

Informed consent was obtained from the participant included in the article.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

Tanaka, A., Nakamura, T., Sato, E. et al. Effect of pemafibrate, a novel selective peroxisome proliferator-activated receptor-alpha modulator (SPPARMα), on urinary protein excretion in IgA nephropathy with hypertriglyceridemia. CEN Case Rep (2020) doi:10.1007/s13730-020-00444-2

Download citation

Keywords

  • Pemafibrate
  • Selective peroxisome proliferator-activated receptor-alpha modulator (SPPARMα)
  • IgA nephropathy
  • Urinary protein excretion