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Cathepsin L activity correlates with proteinuria in chronic kidney disease in humans

  • Nephrology – Original Paper
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Abstract

Background

The presence and severity of proteinuria is considered an important prognostic marker in patients with chronic kidney disease (CKD) and is associated with mortality and morbidity. Cathepsin L is highly expressed in the foot processes of podocytes in the kidney, which serves as an ultrafiltration barrier. Cathepsin L is also up-regulated in the setting of inflammation as a feature of CKD. Therefore, we postulated that proteinuria severity in CKD patients might correlate with increased serum levels of cathepsin L.

Methods and results

In this retrospective observational study, a total of 135 patients diagnosed with CKD, 31 renal transplant patients and 48 healthy controls were included. The demographic characteristics and clinical indicators were analyzed. Serum cathepsin L activity was significantly higher in patients with CKD than in renal transplant recipients and healthy controls (P < 0.01). Patients with severe proteinuria had a higher cathepsin L activity compared to those with moderate or mild proteinuria (P < 0.01). Serum cathepsin L activity positively associated with age, body mass index, nitrite level, neutrophil count, high-sensitivity C-reactive protein (hs-CRP), N-terminal pro-brain natriuretic peptide, high-mobility group box-1 protein (HMGB1) and 24-h proteinuria. In the ROC analysis, the sensitivity of cathepsin L activity in diagnosis of moderate and heavy is 0.86 and the specificity is 0.73. Moreover, CKD patients with higher cathepsin L activity had a significantly higher hospital admission rate. The data also showed patients with statin administration present significantly lower cathepsin L activity (P < 0.01), hs-CRP (P < 0.01), HMGB1 (P < 0.01) and proteinuria (P < 0.01) compared to non-statin treatment group.

Conclusion

This study revealed that serum cathepsin L activity is significantly elevated in CKD patients and its level correlates with the severity of proteinuria as well as prognosis, suggesting that serum cathepsin L may serve as a potential biomarker for CKD. Further prospective study is needed to explore its clinical implications in the future.

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Abbreviations

BMI:

Body mass index

CKD:

Chronic kidney disease

eGFR:

Estimated glomerular filtration rate

ESR:

Erythrocyte sedimentation rate

GBM:

Glomerular basement membrane

GTPase:

Guanosine triphosphatase

HMGB1:

High-mobility group box 1

hs-CRP:

High-sensitivity C-reactive protein

NT-pro-BNP:

N-terminal pro-brain natriuretic peptide

MHC:

Major histocompatibility complex

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Acknowledgements

This work was supported in part by the National Science Foundation of China (NSFC) Project 81570271 (to JJ Cai) and the China National Major Scientific and Technological Special Project for Significant New Drugs Development 2012ZX09303014-001 (to H Yuan).

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Authors and Affiliations

  1. Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, 410013, China

    Yu Cao, Weihong Jiang, Alex F. Chen, Hong Yuan & Jingjing Cai

  2. The Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, China

    Xing Liu, Ying Li, Yao Lu, Hua Zhong, Alex F. Chen, Timothy R. Billiar, Hong Yuan & Jingjing Cai

  3. Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA

    Alex F. Chen, Timothy R. Billiar, Hong Yuan & Jingjing Cai

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  1. Yu Cao
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  2. Xing Liu
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Correspondence to Jingjing Cai.

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All procedures performed in studies involving human participants were in accordance with the ethical standards of the Institutional Ethics Committee of the Third Xiangya Hospital and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

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Cao, Y., Liu, X., Li, Y. et al. Cathepsin L activity correlates with proteinuria in chronic kidney disease in humans. Int Urol Nephrol 49, 1409–1417 (2017). https://doi.org/10.1007/s11255-017-1626-7

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