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

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.