Urinary cathepsin L is predictive of changes in albuminuria and correlates with glucosepane in patients with type 2 diabetes in a closed-cohort study
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 re...
Ausführliche Beschreibung
Gespeichert in:
| Autor*in: |
Brings, Sebastian [verfasserIn] Fleming, Thomas [verfasserIn] Herzig, Stephan [verfasserIn] Nawroth, Peter P. [verfasserIn] Kopf, Stefan [verfasserIn] |
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| Format: |
E-Artikel |
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| Sprache: |
Englisch |
| Erschienen: |
2020 |
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| Schlagwörter: |
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| Übergeordnetes Werk: |
Enthalten in: Journal of diabetes and its complications - Amsterdam [u.a.] : Elsevier Science, 1992, 34 |
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| Übergeordnetes Werk: |
volume:34 |
| DOI / URN: |
10.1016/j.jdiacomp.2020.107648 |
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ELV004472381 |
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| 024 | 7 | |a 10.1016/j.jdiacomp.2020.107648 |2 doi | |
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| 035 | |a (ELSEVIER)S1056-8727(20)30407-4 | ||
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| 100 | 1 | |a Brings, Sebastian |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Urinary cathepsin L is predictive of changes in albuminuria and correlates with glucosepane in patients with type 2 diabetes in a closed-cohort study |
| 264 | 1 | |c 2020 | |
| 336 | |a nicht spezifiziert |b zzz |2 rdacontent | ||
| 337 | |a Computermedien |b c |2 rdamedia | ||
| 338 | |a Online-Ressource |b cr |2 rdacarrier | ||
| 520 | |a 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 = 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. | ||
| 650 | 4 | |a Advanced glycation end-products | |
| 650 | 4 | |a Cathepsin D | |
| 650 | 4 | |a Cathepsin L | |
| 650 | 4 | |a Diabetic nephropathy | |
| 650 | 4 | |a Kidney function | |
| 650 | 4 | |a Lysosomal proteases | |
| 700 | 1 | |a Fleming, Thomas |e verfasserin |4 aut | |
| 700 | 1 | |a Herzig, Stephan |e verfasserin |4 aut | |
| 700 | 1 | |a Nawroth, Peter P. |e verfasserin |4 aut | |
| 700 | 1 | |a Kopf, Stefan |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Journal of diabetes and its complications |d Amsterdam [u.a.] : Elsevier Science, 1992 |g 34 |h Online-Ressource |w (DE-627)320456773 |w (DE-600)2006763-X |w (DE-576)09523795X |x 1873-460X |7 nnns |
| 773 | 1 | 8 | |g volume:34 |
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| 912 | |a GBV_ILN_20 | ||
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| 912 | |a GBV_ILN_23 | ||
| 912 | |a GBV_ILN_24 | ||
| 912 | |a GBV_ILN_31 | ||
| 912 | |a GBV_ILN_32 | ||
| 912 | |a GBV_ILN_40 | ||
| 912 | |a GBV_ILN_60 | ||
| 912 | |a GBV_ILN_62 | ||
| 912 | |a GBV_ILN_63 | ||
| 912 | |a GBV_ILN_65 | ||
| 912 | |a GBV_ILN_69 | ||
| 912 | |a GBV_ILN_70 | ||
| 912 | |a GBV_ILN_73 | ||
| 912 | |a GBV_ILN_74 | ||
| 912 | |a GBV_ILN_90 | ||
| 912 | |a GBV_ILN_95 | ||
| 912 | |a GBV_ILN_100 | ||
| 912 | |a GBV_ILN_101 | ||
| 912 | |a GBV_ILN_105 | ||
| 912 | |a GBV_ILN_110 | ||
| 912 | |a GBV_ILN_151 | ||
| 912 | |a GBV_ILN_224 | ||
| 912 | |a GBV_ILN_370 | ||
| 912 | |a GBV_ILN_602 | ||
| 912 | |a GBV_ILN_702 | ||
| 912 | |a GBV_ILN_2003 | ||
| 912 | |a GBV_ILN_2004 | ||
| 912 | |a GBV_ILN_2005 | ||
| 912 | |a GBV_ILN_2011 | ||
| 912 | |a GBV_ILN_2014 | ||
| 912 | |a GBV_ILN_2015 | ||
| 912 | |a GBV_ILN_2020 | ||
| 912 | |a GBV_ILN_2021 | ||
| 912 | |a GBV_ILN_2025 | ||
| 912 | |a GBV_ILN_2027 | ||
| 912 | |a GBV_ILN_2034 | ||
| 912 | |a GBV_ILN_2038 | ||
| 912 | |a GBV_ILN_2044 | ||
| 912 | |a GBV_ILN_2048 | ||
| 912 | |a GBV_ILN_2049 | ||
| 912 | |a GBV_ILN_2050 | ||
| 912 | |a GBV_ILN_2056 | ||
| 912 | |a GBV_ILN_2059 | ||
| 912 | |a GBV_ILN_2061 | ||
| 912 | |a GBV_ILN_2064 | ||
| 912 | |a GBV_ILN_2065 | ||
| 912 | |a GBV_ILN_2068 | ||
| 912 | |a GBV_ILN_2111 | ||
| 912 | |a GBV_ILN_2112 | ||
| 912 | |a GBV_ILN_2113 | ||
| 912 | |a GBV_ILN_2118 | ||
| 912 | |a GBV_ILN_2122 | ||
| 912 | |a GBV_ILN_2129 | ||
| 912 | |a GBV_ILN_2143 | ||
| 912 | |a GBV_ILN_2147 | ||
| 912 | |a GBV_ILN_2148 | ||
| 912 | |a GBV_ILN_2152 | ||
| 912 | |a GBV_ILN_2153 | ||
| 912 | |a GBV_ILN_2190 | ||
| 912 | |a GBV_ILN_2336 | ||
| 912 | |a GBV_ILN_2507 | ||
| 912 | |a GBV_ILN_2522 | ||
| 912 | |a GBV_ILN_4035 | ||
| 912 | |a GBV_ILN_4037 | ||
| 912 | |a GBV_ILN_4112 | ||
| 912 | |a GBV_ILN_4125 | ||
| 912 | |a GBV_ILN_4126 | ||
| 912 | |a GBV_ILN_4242 | ||
| 912 | |a GBV_ILN_4251 | ||
| 912 | |a GBV_ILN_4305 | ||
| 912 | |a GBV_ILN_4313 | ||
| 912 | |a GBV_ILN_4323 | ||
| 912 | |a GBV_ILN_4324 | ||
| 912 | |a GBV_ILN_4325 | ||
| 912 | |a GBV_ILN_4326 | ||
| 912 | |a GBV_ILN_4333 | ||
| 912 | |a GBV_ILN_4334 | ||
| 912 | |a GBV_ILN_4335 | ||
| 912 | |a GBV_ILN_4338 | ||
| 912 | |a GBV_ILN_4393 | ||
| 936 | b | k | |a 44.89 |j Endokrinologie |
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| 952 | |d 34 | ||
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2020 |
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2020 |
| allfields |
10.1016/j.jdiacomp.2020.107648 doi (DE-627)ELV004472381 (ELSEVIER)S1056-8727(20)30407-4 DE-627 ger DE-627 rda eng 610 DE-600 44.89 bkl Brings, Sebastian verfasserin aut Urinary cathepsin L is predictive of changes in albuminuria and correlates with glucosepane in patients with type 2 diabetes in a closed-cohort study 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 = 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. Advanced glycation end-products Cathepsin D Cathepsin L Diabetic nephropathy Kidney function Lysosomal proteases Fleming, Thomas verfasserin aut Herzig, Stephan verfasserin aut Nawroth, Peter P. verfasserin aut Kopf, Stefan verfasserin aut Enthalten in Journal of diabetes and its complications Amsterdam [u.a.] : Elsevier Science, 1992 34 Online-Ressource (DE-627)320456773 (DE-600)2006763-X (DE-576)09523795X 1873-460X nnns volume:34 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.89 Endokrinologie AR 34 |
| spelling |
10.1016/j.jdiacomp.2020.107648 doi (DE-627)ELV004472381 (ELSEVIER)S1056-8727(20)30407-4 DE-627 ger DE-627 rda eng 610 DE-600 44.89 bkl Brings, Sebastian verfasserin aut Urinary cathepsin L is predictive of changes in albuminuria and correlates with glucosepane in patients with type 2 diabetes in a closed-cohort study 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 = 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. Advanced glycation end-products Cathepsin D Cathepsin L Diabetic nephropathy Kidney function Lysosomal proteases Fleming, Thomas verfasserin aut Herzig, Stephan verfasserin aut Nawroth, Peter P. verfasserin aut Kopf, Stefan verfasserin aut Enthalten in Journal of diabetes and its complications Amsterdam [u.a.] : Elsevier Science, 1992 34 Online-Ressource (DE-627)320456773 (DE-600)2006763-X (DE-576)09523795X 1873-460X nnns volume:34 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.89 Endokrinologie AR 34 |
| allfields_unstemmed |
10.1016/j.jdiacomp.2020.107648 doi (DE-627)ELV004472381 (ELSEVIER)S1056-8727(20)30407-4 DE-627 ger DE-627 rda eng 610 DE-600 44.89 bkl Brings, Sebastian verfasserin aut Urinary cathepsin L is predictive of changes in albuminuria and correlates with glucosepane in patients with type 2 diabetes in a closed-cohort study 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 = 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. Advanced glycation end-products Cathepsin D Cathepsin L Diabetic nephropathy Kidney function Lysosomal proteases Fleming, Thomas verfasserin aut Herzig, Stephan verfasserin aut Nawroth, Peter P. verfasserin aut Kopf, Stefan verfasserin aut Enthalten in Journal of diabetes and its complications Amsterdam [u.a.] : Elsevier Science, 1992 34 Online-Ressource (DE-627)320456773 (DE-600)2006763-X (DE-576)09523795X 1873-460X nnns volume:34 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.89 Endokrinologie AR 34 |
| allfieldsGer |
10.1016/j.jdiacomp.2020.107648 doi (DE-627)ELV004472381 (ELSEVIER)S1056-8727(20)30407-4 DE-627 ger DE-627 rda eng 610 DE-600 44.89 bkl Brings, Sebastian verfasserin aut Urinary cathepsin L is predictive of changes in albuminuria and correlates with glucosepane in patients with type 2 diabetes in a closed-cohort study 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 = 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. Advanced glycation end-products Cathepsin D Cathepsin L Diabetic nephropathy Kidney function Lysosomal proteases Fleming, Thomas verfasserin aut Herzig, Stephan verfasserin aut Nawroth, Peter P. verfasserin aut Kopf, Stefan verfasserin aut Enthalten in Journal of diabetes and its complications Amsterdam [u.a.] : Elsevier Science, 1992 34 Online-Ressource (DE-627)320456773 (DE-600)2006763-X (DE-576)09523795X 1873-460X nnns volume:34 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.89 Endokrinologie AR 34 |
| allfieldsSound |
10.1016/j.jdiacomp.2020.107648 doi (DE-627)ELV004472381 (ELSEVIER)S1056-8727(20)30407-4 DE-627 ger DE-627 rda eng 610 DE-600 44.89 bkl Brings, Sebastian verfasserin aut Urinary cathepsin L is predictive of changes in albuminuria and correlates with glucosepane in patients with type 2 diabetes in a closed-cohort study 2020 nicht spezifiziert zzz rdacontent Computermedien c rdamedia Online-Ressource cr rdacarrier 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 = 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. Advanced glycation end-products Cathepsin D Cathepsin L Diabetic nephropathy Kidney function Lysosomal proteases Fleming, Thomas verfasserin aut Herzig, Stephan verfasserin aut Nawroth, Peter P. verfasserin aut Kopf, Stefan verfasserin aut Enthalten in Journal of diabetes and its complications Amsterdam [u.a.] : Elsevier Science, 1992 34 Online-Ressource (DE-627)320456773 (DE-600)2006763-X (DE-576)09523795X 1873-460X nnns volume:34 GBV_USEFLAG_U SYSFLAG_U GBV_ELV SSG-OLC-PHA GBV_ILN_20 GBV_ILN_22 GBV_ILN_23 GBV_ILN_24 GBV_ILN_31 GBV_ILN_32 GBV_ILN_40 GBV_ILN_60 GBV_ILN_62 GBV_ILN_63 GBV_ILN_65 GBV_ILN_69 GBV_ILN_70 GBV_ILN_73 GBV_ILN_74 GBV_ILN_90 GBV_ILN_95 GBV_ILN_100 GBV_ILN_101 GBV_ILN_105 GBV_ILN_110 GBV_ILN_151 GBV_ILN_224 GBV_ILN_370 GBV_ILN_602 GBV_ILN_702 GBV_ILN_2003 GBV_ILN_2004 GBV_ILN_2005 GBV_ILN_2011 GBV_ILN_2014 GBV_ILN_2015 GBV_ILN_2020 GBV_ILN_2021 GBV_ILN_2025 GBV_ILN_2027 GBV_ILN_2034 GBV_ILN_2038 GBV_ILN_2044 GBV_ILN_2048 GBV_ILN_2049 GBV_ILN_2050 GBV_ILN_2056 GBV_ILN_2059 GBV_ILN_2061 GBV_ILN_2064 GBV_ILN_2065 GBV_ILN_2068 GBV_ILN_2111 GBV_ILN_2112 GBV_ILN_2113 GBV_ILN_2118 GBV_ILN_2122 GBV_ILN_2129 GBV_ILN_2143 GBV_ILN_2147 GBV_ILN_2148 GBV_ILN_2152 GBV_ILN_2153 GBV_ILN_2190 GBV_ILN_2336 GBV_ILN_2507 GBV_ILN_2522 GBV_ILN_4035 GBV_ILN_4037 GBV_ILN_4112 GBV_ILN_4125 GBV_ILN_4126 GBV_ILN_4242 GBV_ILN_4251 GBV_ILN_4305 GBV_ILN_4313 GBV_ILN_4323 GBV_ILN_4324 GBV_ILN_4325 GBV_ILN_4326 GBV_ILN_4333 GBV_ILN_4334 GBV_ILN_4335 GBV_ILN_4338 GBV_ILN_4393 44.89 Endokrinologie AR 34 |
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Brings, Sebastian @@aut@@ Fleming, Thomas @@aut@@ Herzig, Stephan @@aut@@ Nawroth, Peter P. @@aut@@ Kopf, Stefan @@aut@@ |
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2020-01-01T00:00:00Z |
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Brings, Sebastian |
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Brings, Sebastian ddc 610 bkl 44.89 misc Advanced glycation end-products misc Cathepsin D misc Cathepsin L misc Diabetic nephropathy misc Kidney function misc Lysosomal proteases Urinary cathepsin L is predictive of changes in albuminuria and correlates with glucosepane in patients with type 2 diabetes in a closed-cohort study |
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610 DE-600 44.89 bkl Urinary cathepsin L is predictive of changes in albuminuria and correlates with glucosepane in patients with type 2 diabetes in a closed-cohort study Advanced glycation end-products Cathepsin D Cathepsin L Diabetic nephropathy Kidney function Lysosomal proteases |
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ddc 610 bkl 44.89 misc Advanced glycation end-products misc Cathepsin D misc Cathepsin L misc Diabetic nephropathy misc Kidney function misc Lysosomal proteases |
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ddc 610 bkl 44.89 misc Advanced glycation end-products misc Cathepsin D misc Cathepsin L misc Diabetic nephropathy misc Kidney function misc Lysosomal proteases |
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ddc 610 bkl 44.89 misc Advanced glycation end-products misc Cathepsin D misc Cathepsin L misc Diabetic nephropathy misc Kidney function misc Lysosomal proteases |
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Urinary cathepsin L is predictive of changes in albuminuria and correlates with glucosepane in patients with type 2 diabetes in a closed-cohort study |
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Urinary cathepsin L is predictive of changes in albuminuria and correlates with glucosepane in patients with type 2 diabetes in a closed-cohort study |
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Brings, Sebastian |
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Journal of diabetes and its complications |
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Brings, Sebastian Fleming, Thomas Herzig, Stephan Nawroth, Peter P. Kopf, Stefan |
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Brings, Sebastian |
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10.1016/j.jdiacomp.2020.107648 |
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| title_sort |
urinary cathepsin l is predictive of changes in albuminuria and correlates with glucosepane in patients with type 2 diabetes in a closed-cohort study |
| title_auth |
Urinary cathepsin L is predictive of changes in albuminuria and correlates with glucosepane in patients with type 2 diabetes in a closed-cohort study |
| 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 2.4 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 = 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. |
| abstractGer |
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 = 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. |
| abstract_unstemmed |
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 = 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. |
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Urinary cathepsin L is predictive of changes in albuminuria and correlates with glucosepane in patients with type 2 diabetes in a closed-cohort study |
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|
| score |
7.400137 |