Detection of carnosinase-1 in urine of healthy individuals and patients with type 2 diabetes: correlation with albuminuria and renal function

Low serum carnosinase (CN-1) concentrations are associated with low risk for development of diabetic nephropathy (DN) in patients with type 2 diabetes (T2D). Although CN-1 is expressed in the kidney, urinary CN-1 (CNU) excretion and its pathological relevance in patients with T2D have not been inves...

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Main Authors: Rodriguez-Niño, Angelica (Author) , Braun, Jana D. (Author) , Zhang, Shiqi (Author) , Albrecht, Thomas (Author) , Qiu, Jiedong (Author) , Krämer, Bernhard (Author) , Herold, Anna (Author) , Hauske, Sibylle J. (Author) , Yard, Benito A. (Author)
Format: Article (Journal)
Language:English
Published: 2019
In: Amino acids
Year: 2018, Volume: 51, Issue: 1, Pages: 17-25
ISSN:1438-2199
DOI:10.1007/s00726-018-2602-y
Online Access:Verlag, Volltext: https://doi.org/10.1007/s00726-018-2602-y
Verlag: https://link.springer.com/article/10.1007%2Fs00726-018-2602-y
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Author Notes:Angelica Rodriguez-Niño, Christina M. Gant, Jana D. Braun, Xia Li, Shiqi Zhang, Thomas Albrecht, Jiedong Qiu, Stephan J.L. Bakker, Gozewijn D. Laverman, Bernhard K. Krämer, Anna Herold, Sibylle J. Hauske, Benito A. Yard
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Summary:Low serum carnosinase (CN-1) concentrations are associated with low risk for development of diabetic nephropathy (DN) in patients with type 2 diabetes (T2D). Although CN-1 is expressed in the kidney, urinary CN-1 (CNU) excretion and its pathological relevance in patients with T2D have not been investigated to date. The present study therefore assessed the extent of CNU excretion in healthy subjects (n = 243) and in patients with T2D (n = 361) enrolled in the DIAbetes and LifEstyle Cohort Twente-1 (DIALECT-1) in relation to functional renal parameters. CNU was detected in a high proportion of healthy individuals, 180 (74%); median CNU excretion was 0.25 mg/24 h [(IQR 0-0.65 mg/24 h]. In patients with T2D the prevalence and extent of CNU increased in parallel with albuminuria (r = 0.59, p < 0.0001; median CNU 0.1 vs 0.2 vs 1.5 mg/24 h, p < 0.0001; prevalence of CNU 61 vs. 81 vs. 97% p < 0.05 in normo- (n = 241), micro- (n = 80) and macroalbuminuria (n = 40), respectively). Patients with estimated glomerular filtration rate (eGFR) < 30 ml/min/1.73 m2 displayed higher median CNU excretion rates in comparison to patients with preserved eGFR (> 90 ml/min/1.73 m2) (1.36 vs 0.13 mg/24 h, p < 0.05). Backward stepwise multivariate linear regression analysis revealed albuminuria, eGFR and glycosuria to be independent factors of CNU excretion rates, all together explaining 37% of variation of CNU excretion rates (R2 = 0.37, p < 0.0001). These results show for the first time that CN-1 can be detected in urine and warrants prospective studies to assess the relevance of CNU for renal function deterioration in diabetes patients.
Item Description:Published online: 30 June 2018
Gesehen am 09.10.2019
Physical Description:Online Resource
ISSN:1438-2199
DOI:10.1007/s00726-018-2602-y