Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy

Justyna Siwy; Joost P Schanstra; Angel Argiles; Stephan J L Bakker; Joachim Beige; Petr Boucek; Korbinian Brand; Christian Delles; Flore Duranton; Beatriz Fernandez-Fernandez; Marie-Luise Jankowski; Mohammad Al Khatib; Thomas Kunt; Maria Lajer; Ralf Lichtinghagen; Morten Lindhardt; David M Maahs; Harald Mischak; William Mullen; Gerjan Navis; Marina Noutsou; Alberto Ortiz; Frederik Persson; John R Petrie; Johannes M Roob; Peter Rossing; Piero Ruggenenti; Ivan Rychlik; Andreas L Serra; Janet Snell-Bergeon; Goce Spasovski; Olivera Stojceva-Taneva; Matias Trillini; Heiko von der Leyen; Brigitte M Winklhofer-Roob; Petra Zürbig; Joachim Jankowski

doi:10.1093/ndt/gfu039

Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy

Justyna Siwy
, Joost P Schanstra
, Angel Argiles
, Stephan J L Bakker
, Joachim Beige
, Petr Boucek
, Korbinian Brand
, Christian Delles
, Flore Duranton
, Beatriz Fernandez-Fernandez
, Marie-Luise Jankowski
, Mohammad Al Khatib
, Thomas Kunt
, Maria Lajer
, Ralf Lichtinghagen
, Morten Lindhardt
, David M Maahs
, Harald Mischak
, William Mullen
, Gerjan Navis

Marina Noutsou, Alberto Ortiz, Frederik Persson, John R Petrie, Johannes M Roob, Peter Rossing, Piero Ruggenenti, Ivan Rychlik, Andreas L Serra, Janet Snell-Bergeon, Goce Spasovski, Olivera Stojceva-Taneva, Matias Trillini, Heiko von der Leyen, Brigitte M Winklhofer-Roob, Petra Zürbig, Joachim Jankowski

Research output: Contribution to journal › Article › Research › peer-review

Abstract

BACKGROUND: Diabetic nephropathy (DN) is one of the major late complications of diabetes. Treatment aimed at slowing down the progression of DN is available but methods for early and definitive detection of DN progression are currently lacking. The 'Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial' (PRIORITY) aims to evaluate the early detection of DN in patients with type 2 diabetes (T2D) using a urinary proteome-based classifier (CKD273).

METHODS: In this ancillary study of the recently initiated PRIORITY trial we aimed to validate for the first time the CKD273 classifier in a multicentre (9 different institutions providing samples from 165 T2D patients) prospective setting. In addition we also investigated the influence of sample containers, age and gender on the CKD273 classifier.

RESULTS: We observed a high consistency of the CKD273 classification scores across the different centres with areas under the curves ranging from 0.95 to 1.00. The classifier was independent of age (range tested 16-89 years) and gender. Furthermore, the use of different urine storage containers did not affect the classification scores. Analysis of the distribution of the individual peptides of the classifier over the nine different centres showed that fragments of blood-derived and extracellular matrix proteins were the most consistently found.

CONCLUSION: We provide for the first time validation of this urinary proteome-based classifier in a multicentre prospective setting and show the suitability of the CKD273 classifier to be used in the PRIORITY trial.

Original language	English
Pages (from-to)	1563-70
Number of pages	8
Journal	Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association
Volume	29
Issue number	8
DOIs	https://doi.org/10.1093/ndt/gfu039
Publication status	Published - Aug 2014

Keywords

Adult
Aged
Diabetes Mellitus, Type 2/complications
Diabetic Nephropathies/diagnosis
Diagnosis, Differential
Disease Progression
Female
Follow-Up Studies
Humans
Male
Middle Aged
Peptidomimetics/urine
Prospective Studies
Proteomics/methods

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10.1093/ndt/gfu039

Cite this

Siwy, J., Schanstra, J. P., Argiles, A., Bakker, S. J. L., Beige, J., Boucek, P., Brand, K., Delles, C., Duranton, F., Fernandez-Fernandez, B., Jankowski, M.-L., Al Khatib, M., Kunt, T., Lajer, M., Lichtinghagen, R., Lindhardt, M., Maahs, D. M., Mischak, H., Mullen, W., ... Jankowski, J. (2014). Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, 29(8), 1563-70. https://doi.org/10.1093/ndt/gfu039

@article{2221830841854794a6823b066b69e480,

title = "Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy",

abstract = "BACKGROUND: Diabetic nephropathy (DN) is one of the major late complications of diabetes. Treatment aimed at slowing down the progression of DN is available but methods for early and definitive detection of DN progression are currently lacking. The 'Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial' (PRIORITY) aims to evaluate the early detection of DN in patients with type 2 diabetes (T2D) using a urinary proteome-based classifier (CKD273).METHODS: In this ancillary study of the recently initiated PRIORITY trial we aimed to validate for the first time the CKD273 classifier in a multicentre (9 different institutions providing samples from 165 T2D patients) prospective setting. In addition we also investigated the influence of sample containers, age and gender on the CKD273 classifier.RESULTS: We observed a high consistency of the CKD273 classification scores across the different centres with areas under the curves ranging from 0.95 to 1.00. The classifier was independent of age (range tested 16-89 years) and gender. Furthermore, the use of different urine storage containers did not affect the classification scores. Analysis of the distribution of the individual peptides of the classifier over the nine different centres showed that fragments of blood-derived and extracellular matrix proteins were the most consistently found.CONCLUSION: We provide for the first time validation of this urinary proteome-based classifier in a multicentre prospective setting and show the suitability of the CKD273 classifier to be used in the PRIORITY trial.",

keywords = "Adult, Aged, Diabetes Mellitus, Type 2/complications, Diabetic Nephropathies/diagnosis, Diagnosis, Differential, Disease Progression, Female, Follow-Up Studies, Humans, Male, Middle Aged, Peptidomimetics/urine, Prospective Studies, Proteomics/methods",

author = "Justyna Siwy and Schanstra, \{Joost P\} and Angel Argiles and Bakker, \{Stephan J L\} and Joachim Beige and Petr Boucek and Korbinian Brand and Christian Delles and Flore Duranton and Beatriz Fernandez-Fernandez and Marie-Luise Jankowski and \{Al Khatib\}, Mohammad and Thomas Kunt and Maria Lajer and Ralf Lichtinghagen and Morten Lindhardt and Maahs, \{David M\} and Harald Mischak and William Mullen and Gerjan Navis and Marina Noutsou and Alberto Ortiz and Frederik Persson and Petrie, \{John R\} and Roob, \{Johannes M\} and Peter Rossing and Piero Ruggenenti and Ivan Rychlik and Serra, \{Andreas L\} and Janet Snell-Bergeon and Goce Spasovski and Olivera Stojceva-Taneva and Matias Trillini and \{von der Leyen\}, Heiko and Winklhofer-Roob, \{Brigitte M\} and Petra Z{\"u}rbig and Joachim Jankowski",

year = "2014",

month = aug,

doi = "10.1093/ndt/gfu039",

language = "English",

volume = "29",

pages = "1563--70",

journal = "Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association",

issn = "0931-0509",

publisher = "Oxford University Press",

number = "8",

}

Siwy, J, Schanstra, JP, Argiles, A, Bakker, SJL, Beige, J, Boucek, P, Brand, K, Delles, C, Duranton, F, Fernandez-Fernandez, B, Jankowski, M-L, Al Khatib, M, Kunt, T, Lajer, M, Lichtinghagen, R, Lindhardt, M, Maahs, DM, Mischak, H, Mullen, W, Navis, G, Noutsou, M, Ortiz, A, Persson, F, Petrie, JR, Roob, JM, Rossing, P, Ruggenenti, P, Rychlik, I, Serra, AL, Snell-Bergeon, J, Spasovski, G, Stojceva-Taneva, O, Trillini, M, von der Leyen, H, Winklhofer-Roob, BM, Zürbig, P & Jankowski, J 2014, 'Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy', Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, vol. 29, no. 8, pp. 1563-70. https://doi.org/10.1093/ndt/gfu039

Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy. / Siwy, Justyna; Schanstra, Joost P; Argiles, Angel et al.
In: Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association, Vol. 29, No. 8, 08.2014, p. 1563-70.

Research output: Contribution to journal › Article › Research › peer-review

TY - JOUR

T1 - Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy

AU - Siwy, Justyna

AU - Schanstra, Joost P

AU - Argiles, Angel

AU - Bakker, Stephan J L

AU - Beige, Joachim

AU - Boucek, Petr

AU - Brand, Korbinian

AU - Delles, Christian

AU - Duranton, Flore

AU - Fernandez-Fernandez, Beatriz

AU - Jankowski, Marie-Luise

AU - Al Khatib, Mohammad

AU - Kunt, Thomas

AU - Lajer, Maria

AU - Lichtinghagen, Ralf

AU - Lindhardt, Morten

AU - Maahs, David M

AU - Mischak, Harald

AU - Mullen, William

AU - Navis, Gerjan

AU - Noutsou, Marina

AU - Ortiz, Alberto

AU - Persson, Frederik

AU - Petrie, John R

AU - Roob, Johannes M

AU - Rossing, Peter

AU - Ruggenenti, Piero

AU - Rychlik, Ivan

AU - Serra, Andreas L

AU - Snell-Bergeon, Janet

AU - Spasovski, Goce

AU - Stojceva-Taneva, Olivera

AU - Trillini, Matias

AU - von der Leyen, Heiko

AU - Winklhofer-Roob, Brigitte M

AU - Zürbig, Petra

AU - Jankowski, Joachim

PY - 2014/8

Y1 - 2014/8

N2 - BACKGROUND: Diabetic nephropathy (DN) is one of the major late complications of diabetes. Treatment aimed at slowing down the progression of DN is available but methods for early and definitive detection of DN progression are currently lacking. The 'Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial' (PRIORITY) aims to evaluate the early detection of DN in patients with type 2 diabetes (T2D) using a urinary proteome-based classifier (CKD273).METHODS: In this ancillary study of the recently initiated PRIORITY trial we aimed to validate for the first time the CKD273 classifier in a multicentre (9 different institutions providing samples from 165 T2D patients) prospective setting. In addition we also investigated the influence of sample containers, age and gender on the CKD273 classifier.RESULTS: We observed a high consistency of the CKD273 classification scores across the different centres with areas under the curves ranging from 0.95 to 1.00. The classifier was independent of age (range tested 16-89 years) and gender. Furthermore, the use of different urine storage containers did not affect the classification scores. Analysis of the distribution of the individual peptides of the classifier over the nine different centres showed that fragments of blood-derived and extracellular matrix proteins were the most consistently found.CONCLUSION: We provide for the first time validation of this urinary proteome-based classifier in a multicentre prospective setting and show the suitability of the CKD273 classifier to be used in the PRIORITY trial.

AB - BACKGROUND: Diabetic nephropathy (DN) is one of the major late complications of diabetes. Treatment aimed at slowing down the progression of DN is available but methods for early and definitive detection of DN progression are currently lacking. The 'Proteomic prediction and Renin angiotensin aldosterone system Inhibition prevention Of early diabetic nephRopathy In TYpe 2 diabetic patients with normoalbuminuria trial' (PRIORITY) aims to evaluate the early detection of DN in patients with type 2 diabetes (T2D) using a urinary proteome-based classifier (CKD273).METHODS: In this ancillary study of the recently initiated PRIORITY trial we aimed to validate for the first time the CKD273 classifier in a multicentre (9 different institutions providing samples from 165 T2D patients) prospective setting. In addition we also investigated the influence of sample containers, age and gender on the CKD273 classifier.RESULTS: We observed a high consistency of the CKD273 classification scores across the different centres with areas under the curves ranging from 0.95 to 1.00. The classifier was independent of age (range tested 16-89 years) and gender. Furthermore, the use of different urine storage containers did not affect the classification scores. Analysis of the distribution of the individual peptides of the classifier over the nine different centres showed that fragments of blood-derived and extracellular matrix proteins were the most consistently found.CONCLUSION: We provide for the first time validation of this urinary proteome-based classifier in a multicentre prospective setting and show the suitability of the CKD273 classifier to be used in the PRIORITY trial.

KW - Adult

KW - Aged

KW - Diabetes Mellitus, Type 2/complications

KW - Diabetic Nephropathies/diagnosis

KW - Diagnosis, Differential

KW - Disease Progression

KW - Female

KW - Follow-Up Studies

KW - Humans

KW - Male

KW - Middle Aged

KW - Peptidomimetics/urine

KW - Prospective Studies

KW - Proteomics/methods

U2 - 10.1093/ndt/gfu039

DO - 10.1093/ndt/gfu039

M3 - Article

C2 - 24589724

SN - 0931-0509

VL - 29

SP - 1563

EP - 1570

JO - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

JF - Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association

IS - 8

ER -

Siwy J, Schanstra JP, Argiles A, Bakker SJL, Beige J, Boucek P et al. Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association. 2014 Aug;29(8):1563-70. doi: 10.1093/ndt/gfu039

Multicentre prospective validation of a urinary peptidome-based classifier for the diagnosis of type 2 diabetic nephropathy

Abstract

Keywords

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