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

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

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.

Publication types

  • Observational Study

MeSH terms

  • Adult
  • Biomarkers / blood
  • C-Reactive Protein / metabolism
  • Cathepsin L / blood*
  • Cholesterol, LDL / blood
  • Cross-Sectional Studies
  • Female
  • HMGB1 Protein / blood
  • Hospitalization / statistics & numerical data
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / therapeutic use
  • Kidney Transplantation
  • Leukocyte Count
  • Male
  • Middle Aged
  • Natriuretic Peptide, Brain / blood
  • Neutrophils
  • Nitrites / blood
  • Proteinuria / blood*
  • Proteinuria / diagnosis
  • ROC Curve
  • Renal Insufficiency, Chronic / blood*
  • Retrospective Studies
  • Severity of Illness Index

Substances

  • Biomarkers
  • Cholesterol, LDL
  • HMGB1 Protein
  • HMGB1 protein, human
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Nitrites
  • Natriuretic Peptide, Brain
  • C-Reactive Protein
  • Cathepsin L