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Brings, S.* ; Fleming, T.* ; Herzig, S. ; Nawroth, P.P.* ; Kopf, S.*

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

J. Diab. Complic. 34:107648 (2020)
Postprint DOI Order publishers version
Open Access Green
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 2.4 ng/l and 19.1 ng/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 = 0376). 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.
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Publication type Article: Journal article
Document type Scientific Article
Keywords Advanced Glycation End-products ; Cathepsin D ; Cathepsin L ; Diabetic Nephropathy ; Kidney Function ; Lysosomal Proteases; Randomized Controlled-trial; Kidney-disease; Stress-reduction; Statin Use; Protein; Risk; Quantification; Association; Sensitivity; Digestion
ISSN (print) / ISBN 1056-8727
e-ISSN 1056-8727
Quellenangaben Volume: 34, Issue: 9, Pages: , Article Number: 107648 Supplement: ,
Publisher Elsevier
Publishing Place Ste 800, 230 Park Ave, New York, Ny 10169 Usa
Reviewing status Peer reviewed