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Gut microbial products valerate and caproate predict renal outcome among the patients with biopsy-confirmed diabetic nephropathy

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Abstract

Aims

Valerate and caproate are two subtypes of short-chain fatty acids produced by gut microbiota. We aimed to measure the serum valerate and caproate levels and analyze the associations between them and renal prognosis of diabetic nephropathy (DN).

Methods

The serum samples of patients with biopsy-confirmed diagnosis of DN were collected in the First Affiliated Hospital of Zhejiang University, from April 1, 2013, to March 31, 2018. One hundred patients were included and divided into an early DN group (eGFR ≥ 60 ml/min, n = 42) and an advanced DN group (eGFR < 60 ml/min, n = 58). The valerate and caproate were measured using gas chromatography–mass spectrometry. Participants were followed up until the cutoff date of August 31, 2018, or if they met the primary endpoint of end-stage renal disease (ESRD).

Results

There were 71 males and 29 females in this study, and 29 patients developed ESRD. We observed a significant lower concentration of valerate and caproate in the advanced DN group. There were negative correlations between valerate and glomerular classification (r = − 0.20, P = 0.03) and between caproate and interstitial fibrosis and tubular atrophy (IFTA) (r = − 0.24, P = 0.01). And there were positive correlations between valerate or caproate and eGFR (r = 0.22, P = 0.02; r = 0.38, P < 0.01). Multivariate Cox analysis revealed higher levels of valerate and caproate were negatively related to progression to ESRD (HR = 0.024, P = 0.016; HR = 0.543, P = 0.030). The area under the curve values of valerate and caproate levels were 0.66 and 0.63, respectively, in predicting progression to ESRD.

Conclusion

This study showed alterations in serum valerate and caproate in DN and demonstrates lower valerate and caproate levels with progression of DN to ESRD.

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Funding

This study was supported by the funds from Zhejiang Provincial Natural Science Foundation of China (LY20H05005), Medical Scientific Research Foundation of Zhejiang Province, China (2019KY174, 2018KY696), Ningbo Public Service Technology Foundation, China (2019C50084), and Key Medicinal Subjects of Joint Construction Between Provinces and Cites, China (Grant No. 2022-S03).

Author information

Authors and Affiliations

  1. Department of Nephrology, HwaMei Hospital, University of Chinese Academy of Sciences, 41 Xibei Street, Ningbo, 315010, Zhejiang Province, People’s Republic of China

    Chenyu Zhong, Xu Bai, Qinghuo Chen, Qun Luo & Kedan Cai

  2. Department of Endocrinology, HwaMei Hospital, University of Chinese Academy of Sciences, Ningbo, Zhejiang Province, People’s Republic of China

    Jianhui Li & Jie Zhang

  3. The First Affiliated Hospital, College of Medicine, Zhejiang University, Hangzhou, Zhejiang Province, People’s Republic of China

    Yanhong Ma

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  1. Chenyu Zhong
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Contributions

KC, CZ and QL were involved in the study conception and design and data analysis and interpretation. KC and QL contributed to the administrative support. KC, CZ and YM were involved in the patient education and instruction. KC, CZ, XB, QC, JL and JZ collected and assembled the data; KC and CZ took the lead in writing the manuscript with input from all authors. All authors were involved in manuscript writing and final approval of manuscript.

Corresponding author

Correspondence to Kedan Cai.

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Conflict of interest

The authors declare that they have no conflict of interest.

Ethics approval and consent to participate

This study was approved by the Ethics Committee of the First Affiliated Hospital of Medical School of Zhejiang University, and all participants provided written informed consent.

Informed consent

All participants provided written informed consent.

Additional information

This article belongs to the Topical Collection “Diabetic Nephropathy”, managed By Giuseppe Pugliese.

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Zhong, C., Bai, X., Chen, Q. et al. Gut microbial products valerate and caproate predict renal outcome among the patients with biopsy-confirmed diabetic nephropathy. Acta Diabetol 59, 1469–1477 (2022). https://doi.org/10.1007/s00592-022-01948-2

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  • DOI: https://doi.org/10.1007/s00592-022-01948-2

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