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Differential impact of glomerular and tubule-interstitial histological changes on kidney outcome between non-proteinuric and proteinuric diabetic nephropathy

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Abstract

Background

Studies on kidney function and histological findings in diabetic nephropathy (DN) with low urinary protein (UP) are few. We examined the differential impact of histological changes on kidney outcomes between non-proteinuric and proteinuric DN.

Methods

Patients diagnosed with DN by renal biopsy during 1981–2014 were divided into non-proteinuric (UP ≤ 0.5 g/day) and proteinuric (UP > 0.5 g/day) DN. The Cox proportional hazard model was used to examine the association of glomerular lesions (GLs) and interstitial fibrosis and tubular atrophy (IFTA) with end-stage kidney disease (ESKD) development after adjusting for relevant confounders.

Results

The non-proteinuric and proteinuric DN groups included 197 and 199 patients, respectively. During the 10.7-year median follow-up period, 16 and 83 patients developed ESKD in the non-proteinuric and proteinuric DN groups, respectively. In the multivariable Cox hazard model, hazard ratios (HRs) [95% confidence intervals (CIs)] of GL and IFTA for ESKD in proteinuric DN were 2.94 [1.67–5.36] and 3.82 [2.06–7.53], respectively. Meanwhile, HRs [95% CIs] of GL and IFTA in non-proteinuric DN were < 0.01 [0–2.48] and 4.98 [1.33–18.0], respectively. IFTA was consistently associated with higher incidences of ESKD regardless of proteinuria levels (P for interaction = 0.49). The prognostic impact of GLs on ESKD was significantly decreased as proteinuria levels decreased (P for interaction < 0.01).

Conclusions

IFTA is consistently a useful predictor of kidney prognosis in both non-proteinuric and proteinuric DN, while GLs are a significant predictor of kidney prognosis only in proteinuric DN.

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Acknowledgements

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Funding

This work was supported by grants from the Japan Society for the Promotion of Science (Grant-in-Aid for Scientific Research 18K15984) to KS.

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Authors and Affiliations

  1. Department of Nephrology, Nara Medical University, 840 Shijo–cho, Kashihara, Nara, 634-8521, Japan

    Fumihiro Fukata, Masahiro Eriguchi, Hiroyuki Tamaki, Takayuki Uemura, Hikari Tasaki, Riri Furuyama, Masatoshi Nishimoto, Takaaki Kosugi, Kaori Tanabe, Keisuke Okamoto, Ken-ichi Samejima & Kazuhiko Tsuruya

  2. Department of Nephrology, Nara Prefecture Seiwa Medical Center, Nara, Japan

    Katsuhiko Morimoto

  3. Department of Nephrology, Nara Prefecture General Medical Center, Nara, Japan

    Masaru Matsui

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  1. Fumihiro Fukata
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Contributions

Research idea and study design: FF and ME; Drafting the manuscript: FF; Revising the manuscript: ME, data analysis/interpretation: FF and ME; statistical analysis: FF; supervision or mentorship: HT, TU, HT, RF, MN, TK, KTa, KM, KO, MM, KS, and KTs. Each author contributed important intellectual content during manuscript drafting or revision and accepts accountability for the overall work by ensuring that questions on the accuracy or integrity of any portion of the work are appropriately investigated and resolved.

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Correspondence to Masahiro Eriguchi.

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Fukata, F., Eriguchi, M., Tamaki, H. et al. Differential impact of glomerular and tubule-interstitial histological changes on kidney outcome between non-proteinuric and proteinuric diabetic nephropathy. Clin Exp Nephrol 28, 282–292 (2024). https://doi.org/10.1007/s10157-023-02433-y

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