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A case of idiopathic nodular glomerulosclerosis successfully treated by intensive blockade of the renin–angiotensin–aldosterone system

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Abstract

Idiopathic nodular glomerulosclerosis has a poor renal prognosis and is characterized by diffuse nodular glomerulosclerotic lesions in the absence of diabetic mellitus. Here, we report the case of a 69-year-old woman with no smoking history who developed renal dysfunction and proteinuria in the absence of overt diabetes or obesity. A biopsy specimen showed nodular mesangial sclerosis with arteriolar hyalinosis and severe large-vessel arteriosclerosis, leading to a diagnosis of idiopathic nodular glomerulosclerosis. Addition of esaxerenone to her existing renin–angiotensin–aldosterone inhibitor therapy led to a rapid decrease in the proteinuria levels and the maintenance of renal function without any complications for more than a year. The results suggest that intensive renin–angiotensin–aldosterone blockade might be an effective treatment for idiopathic nodular glomerulosclerosis.

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All data generated or analyzed during this study have been included in this article and its supplementary material. Further inquiries can be directed to the corresponding author.

References

  1. Herzenberg AM, Holden JK, Singh S, Magil AB. Idiopathic nodular glomerulosclerosis. Am J Kidney Dis. 1999;34:560–4.

    Article  CAS  PubMed  Google Scholar 

  2. Markowitz GS, Lin J, Valeri AM, Avila C, Nasr SH, D’Agati VD. Idiopathic nodular glomerulosclerosis is a distinct clinicopathologic entity linked to hypertension and smoking. Hum Pathol. 2002;33:826–35.

    Article  PubMed  Google Scholar 

  3. Kimmelstiel P, Wilson C. Intercapillary Lesions in the Glomeruli of the Kidney. Am J Pathol. 1936;12:83–98.

    CAS  PubMed  PubMed Central  Google Scholar 

  4. Alsaad KO, Herzenberg AM. Distinguishing diabetic nephropathy from other causes of glomerulosclerosis: an update. J Clin Pathol. 2007;60:18.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Yoshida A, Morozumi K, Oikawa T, et al. Nodular glomerulosclerosis in a patient showing impaired glucose tolerance. Jpn J Nephrol. 1990;32:877–84.

    CAS  Google Scholar 

  6. Liew ZH, Tan PH, Foo M, Kee T, Ho QY. Nodular glomerulosclerosis in a kidney transplant recipient with impaired glucose tolerance: diabetic or idiopathic? A case report and literature review. CEN Case Rep. 2021;10:273–80.

    Article  PubMed  PubMed Central  Google Scholar 

  7. Li W, Verani RR. Idiopathic nodular glomerulosclerosis: a clinicopathologic study of 15 cases. Hum Pathol. 2008;39:1771–6.

    Article  PubMed  Google Scholar 

  8. Wu J, Yu S, Tejwani V, et al. Idiopathic nodular glomerulosclerosis in Chinese patients: a clinicopathologic study of 20 cases. Clin Exp Nephrol. 2014;18:865–75.

    Article  PubMed  Google Scholar 

  9. Salvatore SP, Troxell ML, Hecox D, Sperling KR, Seshan SV. Smoking-related glomerulopathy: expanding the morphologic spectrum. Am J Nephrol. 2015;41:66–72.

    Article  PubMed  Google Scholar 

  10. Hamrahian M, Mollaee M, Anand M, Fülöp T. Impaired glucose metabolism—a potential risk factor for idiopathic nodular glomerulosclerosis: a single center study. Med Hypotheses. 2018;121:95–8.

    Article  CAS  PubMed  Google Scholar 

  11. Eadon MT, Lampe S, Baig MM, et al. Clinical, histopathologic and molecular features of idiopathic and diabetic nodular mesangial sclerosis in humans. Nephrol Dial Transplant. 2021;37:72–84.

    Article  PubMed  PubMed Central  Google Scholar 

  12. Qian Y, Feldman E, Pennathur S, Kretzler M, Brosius FC. Mechanisms of glomerulosclerosis in diabetic nephropathy. Diabetes. 2008;57:1439–45.

    Article  CAS  PubMed  Google Scholar 

  13. Nasr SH, D’Agati VD. Nodular glomerulosclerosis in the nondiabetic smoker. J Am Soc Nephrol. 2007;18:2032–6.

    Article  PubMed  Google Scholar 

  14. Ito S, Kashihara N, Shikata K, et al. Esaxerenone (CS-3150) in patients with type 2 diabetes and microalbuminuria (ESAX-DN): phase 3 randomized controlled clinical trial. Clin J Am Soc Nephrol. 2020;15:1715–27.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Bakris GL, Agarwal R, Anker SD, et al. Effect of finerenone on chronic kidney disease outcomes in type 2 diabetes. N Engl J Med. 2020;383(23):2219–29.

    Article  CAS  PubMed  Google Scholar 

  16. Nakamura N, Taguchi K, Miyazono Y, et al. AGEs–RAGE overexpression in a patient with smoking-related idiopathic nodular glomerulosclerosis. CEN Case Rep. 2018;7:48–54.

    Article  PubMed  Google Scholar 

  17. Fukami K, Yamagishi S, Kaifu K, et al. Telmisartan inhibits AGE-induced podocyte damage and detachment. Microvasc Res. 2013;88:79–83.

    Article  CAS  PubMed  Google Scholar 

  18. Wang CC, Lee AS, Liu SH, Chang KC, Shen MY, Chang CT. Spironolactone ameliorates endothelial dysfunction through inhibition of the AGE/RAGE axis in a chronic renal failure rat model. BMC Nephrol. 2019;20(1):351.

    Article  PubMed  PubMed Central  Google Scholar 

  19. Zhang Y, Zheng W, Liu Y, et al. Eplerenone restores 24-h blood pressure circadian rhythm and reduces advanced glycation end-products in rhesus macaques with spontaneous hypertensive metabolic syndrome. Sci Rep. 2016;6(1):23957.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  20. Nishi S, Ueno M, Hisaki S, et al. Ultrastructural characteristics of diabetic nephropathy. Med Electron Microsc. 2000;33:65–73.

    Article  CAS  PubMed  Google Scholar 

  21. Matsumae T, Fukusaki M, Sakata N, Takebayashi S, Naito S. Thin glomerular basement membrane in diabetic patients with urinary abnormalities. Clin Nephrol. 1994;42:221–6.

    CAS  PubMed  Google Scholar 

  22. Hayashi H, Karasawa R, Inn H, et al. An electron microscopic study of glomeruli in Japanese patients with non-insulin dependent diabetes mellitus. Kidney Int. 1992;41:749–57.

    Article  CAS  PubMed  Google Scholar 

  23. Ito S, Itoh H, Rakugi H, Okuda Y, Yoshimura M, Yamakawa S. Double-blind randomized phase 3 study comparing esaxerenone (CS-3150) and eplerenone in patients with essential hypertension (ESAX-HTN study). Hypertension. 2019;75:51–8.

    Article  PubMed  Google Scholar 

  24. Phelps KR, Lieberman RL, Oh MS, Carroll HJ. Pathophysiology of the syndrome of hyporeninemic hypoaldosteronism. Metabolism. 1980;29:186–99.

    Article  CAS  PubMed  Google Scholar 

  25. Price DA, Porter LE, Gordon M, et al. The paradox of the low-renin state in diabetic nephropathy. J Am Soc Nephrol. 1999;10:2382–91.

    Article  CAS  PubMed  Google Scholar 

  26. Sousa AGP, Cabral JVDS, El-Feghaly WB, de Sousa LS, Nunes AB. Hyporeninemic hypoaldosteronism and diabetes mellitus: pathophysiology assumptions, clinical aspects and implications for management. World J Diabetes. 2016;7:101.

    Article  PubMed  PubMed Central  Google Scholar 

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Acknowledgements

We thank Dr. Kensuke Joh of the Department of Pathology, Jikei University School of Medicine, for the pathological diagnosis in this case. The authors acknowledge the technical assistance of Naofumi Imai and Kaori Takahashi. A summary of this case was presented in an oral session at the 58th Kanto Koshinetsu Regional Meeting of the Japanese Diabetes Society, Tokyo, Japan in 2020 and at the 32nd Meeting of the Japanese Diabetic Nephropathy Study Group, Tokyo, Japan in 2020.

Funding

The authors declare that this study received no funding.

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Authors and Affiliations

  1. Division of Clinical Nephrology and Rheumatology, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan

    Hiroki Yamaguchi, Yumi Ito, Yoshiki Suzuki & Ichiei Narita

  2. Department of Pediatrics, Child Health Research Center, University of Virginia School of Medicine, 409 Lane Road, MR4 Building, Room 2001, Charlottesville, VA, 22908, USA

    Hiroki Yamaguchi

  3. Department of Clinical Nutrition Science, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan

    Michihiro Hosojima & Hideyuki Kabasawa

  4. Department of Applied Molecular Medicine, Kidney Research Center, Niigata University Graduate School of Medical and Dental Sciences, 1-757 Asahimachi-Dori, Chuo-ku, Niigata City, Niigata, 951-8510, Japan

    Akihiko Saito

  5. General Internal Medicine, Niigata Health Promotion and Sports Medical Science Center, 67-12 Seigoro, Chuo-ku, Niigata City, Niigata, 950-0933, Japan

    Masaaki Arakawa

Authors
  1. Hiroki Yamaguchi
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  2. Michihiro Hosojima
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  3. Hideyuki Kabasawa
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  4. Yumi Ito
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  5. Yoshiki Suzuki
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  6. Akihiko Saito
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  7. Masaaki Arakawa
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  8. Ichiei Narita
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Corresponding author

Correspondence to Michihiro Hosojima.

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Yamaguchi, H., Hosojima, M., Kabasawa, H. et al. A case of idiopathic nodular glomerulosclerosis successfully treated by intensive blockade of the renin–angiotensin–aldosterone system. CEN Case Rep 12, 311–317 (2023). https://doi.org/10.1007/s13730-022-00766-3

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  • DOI: https://doi.org/10.1007/s13730-022-00766-3

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