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Int Urol Nephrol. 2017 Aug;49(8):1409-1417. doi: 10.1007/s11255-017-1626-7. Epub 2017 May 22.

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

Cao Y1, Liu X2, Li Y2, Lu Y2, Zhong H2, Jiang W1, Chen AF1,2,3, Billiar TR2,3, Yuan H1,2,3, Cai J4,5,6.

Author information

1
Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, 410013, China.
2
The Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, China.
3
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
4
Department of Cardiology, The Third Xiangya Hospital, Central South University, Changsha, 410013, China. caijingjing83@hotmail.com.
5
The Center of Clinical Pharmacology, The Third Xiangya Hospital, Central South University, Changsha, China. caijingjing83@hotmail.com.
6
Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA. caijingjing83@hotmail.com.

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.

KEYWORDS:

Biomarker; Cathepsin L; Chronic kidney disease; Proteinuria

PMID:
28534128
DOI:
10.1007/s11255-017-1626-7
[Indexed for MEDLINE]

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