Urinary cathepsin L is predictive of changes in albuminuria and correlates with glucosepane in patients with type 2 diabetes in a closed-cohort study

• Verfasst von: Brings, Sebastian [VerfasserIn]
• Verfasst von: Fleming, Thomas [VerfasserIn]
• Verfasst von: Herzig, Stephan [VerfasserIn]
• Verfasst von: Nawroth, Peter Paul [VerfasserIn]
• Verfasst von: Kopf, Stefan [VerfasserIn]
• Titel: Urinary cathepsin L is predictive of changes in albuminuria and correlates with glucosepane in patients with type 2 diabetes in a closed-cohort study
• Verf.angabe: Sebastian Brings, Thomas Fleming, Stephan Herzig, Peter P. Nawroth, Stefan Kopf
• E-Jahr: 2020
• Jahr: 2 June 2020
• Umfang: 7 S.
• Fussnoten: Gesehen am 23.09.2020
• Titel Quelle: Enthalten in: Journal of diabetes and its complications
• Ort Quelle: Amsterdam [u.a.] : Elsevier Science, 1992
• Jahr Quelle: 2020
• Band/Heft Quelle: 34(2020,9) Artikel-Nummer 107648, 7 Seiten
• ISSN Quelle: 1873-460X
• DOI: doi:10.1016/j.jdiacomp.2020.107648
• Datenträger: Online-Ressource
• Sprache: eng
• Sach-SW: Advanced glycation end-products
• Sach-SW: Cathepsin D
• Sach-SW: Cathepsin L
• Sach-SW: Diabetic nephropathy
• Sach-SW: Kidney function
• Sach-SW: Lysosomal proteases
• K10plus-PPN: 1733608737

Abstract

Aims - Cathepsin D (CTSD) and L (CTSL) are lysosomal proteases which degrade and detoxify advanced glycation end product (AGE)-modified proteins which are predictive of the development of diabetic nephropathy. We aimed to quantify cathepsin levels in urine from patients with type 2 diabetes and to relate these to the amount of urinary free AGEs at baseline and with kidney function after four years of follow-up in this closed cohort study. - Methods - We established and validated a LC MS/MS method for the quantification of CTSD and CTSL in urine. Patients with type 2 diabetes were screened for diabetic kidney disease and 141 patients were seen at baseline and after four years. CTSD and CTSL and free AGEs were quantified in urine by LC MS/MS at baseline in these patients. - Results - The detection limit of CTSD and CTSL in urine was 2.4ng/l and 19.1ng/l, respectively. CTSD (p<0.0001, r=0.555) and CTSL (p<0.0001, r=0.608) correlated positively with albuminuria at time of recruitment. In addition levels of the proteases but not albuminuria correlated with urinary levels of the major cross-linking AGE glucosepane (CTSD: p=0.012, r=0.225; CTSL: p<0.001, r=0.376). A strong non-linear association between CTSD (r=0.568), CTSL (r=0.588) and change in albuminuria over four years was present. High levels of CTSL (p=0.007, beta=−0.366) were associated with an improvement of albuminuria after four years. - Conclusions - A sensitive LC MS/MS assay for the quantification of CTSD and CTSL in urine was established. High CTSL baseline levels were associated with an improvement in albuminuria at follow-up. An increased excretion and thus detoxification of the free form of the pathogenic cross-linking AGE glucosepane could explain the positive predictive value of high CTSL levels on albuminuria.