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Diabetic Nephropathy

Diabetic Nephropathy - DiaPat® DN-PROteom Test

Diabetic nephropathy (DN) is a chronic kidney disease that develops as a result of diabetes mellitus. DN is often characterized by a slow, progressive loss of renal function, with a loss of glomerular filtration over a period of months or years that eventually leads to end-stage renal disease requiring renal replacement therapy (dialysis or kidney transplantation). About 25% to 40% of the patients with diabetes will develop diabetic nephropathy.

Diabetic nephropathy is generally detected by measurements of albumin in urine or changes in serum creatinine concentration in blood. However, these methods are late manifestations of renal damage.

Analysing the urine proteome, the DiaPat® DN-PROteom Test allows the detection of diabetic nephropathy 3-5 years prior to the occurrence of clinical symptoms. An accuracy of >85% was revealed in clinical trials.

Patients can highly benefit from this early detection as appropriate therapy enables preventing or delaying onset of diabetic nephropathy and subsequently end-stage renal disease and dialysis.

 

 

Advantages of the DiaPat® DN-PROteom Test

  • Painless (from urine)
  • Riskless sampling
  • Reliable (highly reliable detection of DN)
  • Long-term monitoring (therapy success and individually adapted treatment)

Risk factors for diabetic nephropathy:

  • diabetes
  • high blood pressure (arterial hypertension)
  • aging
  • family history

 

Figure: Adoption of the DiaPat® DN-PROteom Test (diabetic nephropathy) (Zoom in)

 

References:

Roscioni SS, de Zeeuw D, Hellemons ME, Mischak H, Zürbig P, Bakker SJ, Gansevoort RT, Reinhard H, Persson F, Lajer M, Rossing P, Heerspink HJ.
A urinary peptide biomarker set predicts worsening of albuminuria in type 2 diabetes mellitus.
Diabetologia. 2013 Feb;56(2):259-67. doi: 10.1007/s00125-012-2755-2. Epub 2012 Oct 20.


Zürbig P, Jerums G, Hovind P, MacIsaac R, Mischak H, Nielsen SE, Panagiotopoulos S, Persson F, Rossing P.
Urinary Proteomics for Early Diagnosis in Diabetic Nephropathy.

Diabetes. 2012 Dec;61(12):3304-13. doi: 10.2337/db12-0348. Epub 2012 Aug 7.

 

Andersen S, Mischak H, Zuerbig P, Parving HH, Rossing P
Urinary proteome analysis enables assessment of renoprotective treatment in type 2 diabetic patients with microalbuminuria
BMC Nephrology 2010, 11:29

Alkhalaf A, Zuerbig P, Bakker SJL, Bilo HJG, Cerna M, Fischer C, Fuchs S, Janssen B, Medek K, Mischak H, Roob JM, Rossing K, Rossing P, Rychlík I, Sourij H, Tiran B, Winklhofer-Roob BM, Navis GJ
Multicentric Validation of Proteomic Biomarkers in Urine Specific for Diabetic Nephropathy
PLoS ONE 2010 Oct; 5(10): e13421

Mischak H, Rossing P. 
Proteomic biomarkers in diabetic nephropathy - reality or future promise?
The Journal of biological chemistry 2010 March

Zürbig P, Mischak H, Conrads S
Urinary proteome analysis for early diagnosis of diabetes and its complications
Diabetes, Stoffwechsel und Herz, Band 18, 6/2009

Snell-Bergeon JK, Maahs DM, Ogden LG, Kinney GL, Hokanson JE, Schiffer E, Mischak H, Rewers M
Evaluation of urinary biomarkers for coronary artery disease, diabetes, and diabetic kidney disease
Diabetes, Technology and Therapeutics 2009, 11(1): 1-9

Rossing K, Mischak H, Rossing P, Schanstra JP, Wiseman A, Maahs DM
The urinary proteome in diabetes and diabetes-associated complications: new ways to assess disease progression and evaluate therapy
PROTEOMICS - Clinical Applications 2008, 2(7-8): 997-1007

Rossing K, Mischak H, Dakna M, Zürbig P, Novak J, Julian BA, Good DM, Coon JJ, Tarnow L, Rossing P
Proteomic Discovery and Evaluation of Urinary Biomarkers for Diabetes and Chronic Renal Disease
J Am Soc Nephrol. 2008, 19(7): 1283-1290

Mischak H, Pantke U, Fliser D
Proteomanalyse zur Erkennung, Früherkennung und Therapieevaluierung der diabetischen Nephropathie
journal of preventive medicine 2007, 3(1): 28-35

Meier M, Kaiser T, Herrmann A, Knueppel S, Hillmann M, Koester P, Danne T, Haller H, Fliser D, Mischak H
Identification of urinary protein pattern in type 1 diabetic adolescents with early diabetic nephropathy by a novel combined proteome analysis
J Diabetes Complications. 2005, 19(4): 223-232

Rossing K, Mischak H, Parving HH, Christensen PK, Walden M, Hillmann M, Kaiser T
Impact of diabetic nephropathy and angiotensin II receptor blockade on urinary polypeptide patterns
Kidney Int. 2005, 68(1): 193-205

Mischak H, Kaiser T, Walden M, Hillmann M, Wittke S, Herrmann A, Knueppel S, Haller H, Fliser D
Proteomic analysis for the assessment of diabetic renal damage in humans
Clin Sci (Lond). 2004, 107(5): 485-495
 

In the meantime researches provided evidence that an earlier intensive therapy leads to significant therapeutic success, if early diagnosis is made. Studies featured that the early diagnosis of diabetic nephropathy combined with intensive therapy retards progression of the disease significantly. Furthermore scientists pointed out that the DiaPat® DN-PROteom Test detects DN much more early and precise than the conventional measurement of albumin in urine:

Andresdottir,G., Jensen,M.L., Carstensen,B., Parving,H.H., Rossing,K., Hansen,T.W., and Rossing,P. (2014). Improved survival and renal prognosis of patients with type 2 diabetes and nephropathy with improved control of risk factors. Diabetes Care 37, 1660-1667.

Farmer,A.J., Stevens,R., Hirst,J., Lung,T., Oke,J., Clarke,P., Glasziou,P., Neil,A., Dunger,D., Colhoun,M., Pugh,C., Wong,G., Perera,R., and Shine,B. (2014). Optimal strategies for identifying kidney disease in diabetes: properties of screening tests, progression of renal dysfunction and impact of treatment - systematic review and modelling of progression and cost-effectiveness. Health Technol. Assess. 18, 1-128.

Good,D.M., Zürbig,P., Argiles,A., Bauer,H.W., Behrens,G., Coon,J.J., Dakna,M., Decramer,S., Delles,C., Dominiczak,A.F., Ehrich,J.H., Eitner,F., Fliser,D., Frommberger,M., Ganser,A., Girolami,M.A., Golovko,I., Gwinner,W., Haubitz,M., Herget-Rosenthal,S., Jankowski,J., Jahn,H., Jerums,G., Julian,B.A., Kellmann,M., Kliem,V., Kolch,W., Krolewski,A.S., Luppi,M., Massy,Z., Melter,M., Neususs,C., Novak,J., Peter,K., Rossing,K., Rupprecht,H., Schanstra,J.P., Schiffer,E., Stolzenburg,J.U., Tarnow,L., Theodorescu,D., Thongboonkerd,V., Vanholder,R., Weissinger,E.M., Mischak,H., and Schmitt-Kopplin,P. (2010). Naturally occurring human urinary peptides for use in diagnosis of chronic kidney disease. Mol. Cell Proteomics 9, 2424-2437.

Roscioni,S.S., de,Z.D., Hellemons,M.E., Mischak,H., Zurbig,P., Bakker,S.J., Gansevoort,R.T., Reinhard,H., Persson,F., Lajer,M., Rossing,P., and Heerspink,H.J. (2012). A urinary peptide biomarker set predicts worsening of albuminuria in type 2 diabetes mellitus. Diabetologia 56, 259-267.

Argiles,A., Siwy,J., Duranton,F., Gayrard,N., Dakna,M., Lundin,U., Osaba,L., Delles,C., Mourad,G., Weinberger,K.M., and Mischak,H. (2013). CKD273, a New Proteomics Classifier Assessing CKD and Its Prognosis. PLoS One 8, e62837.

Schanstra, J. P., Zürbig, P., Alkhalaf, A., Argiles, A., Bakker , S. J. L., Beige, J., Bilo, H. J. G., Chatzikyrkou, C, Dakna, M., Dawson, J., Delles, C., Haller, H., Haubitz, M., Husi, H., Jankowski, J., Jerums, G., Kleefstra, N., Kuznetsova, T., Maahs, D., Menne, J., Mullen, W., Ortiz, A., Persson, F., Rossing, P., Ruggenenti, P., Rychlik, I., Serra, A. L., Siwy, J., Snell-Bergeon, J., Spasovski, G., Staessen, J. A., Vlahou, A., Mischak, H., and Vanholder, R. Diagnosis and Prediction of CKD Progression by Assessment of Urinary Peptides. J Am.Soc.Nephrol. in press. 2014.

Zürbig,P., Jerums,G., Hovind,P., MacIsaac,R., Mischak,H., Nielsen,S.E., Panagiotopoulos,S., Persson,F., and Rossing,P. (2012). Urinary Proteomics for Early Diagnosis in Diabetic Nephropathy. Diabetes 61, 3304-3313.

 

Background information

Diabetic nephropathy (DN) is a serious and common complication of diabetes and an important cause of mortality in diabetics.

The most common causes of chronic kidney disease (CKD) in North America, Europe, and Japan are diabetic nephropathy, hypertension, and glomerulonephritis (inflammation of the glomeruli, or small blood vessels in the kidneys). Approximately 75% of all adult cases of end-stage renal disease suffer from one of these three diseases.

At present about 250 million people worldwide have diabetes and the number is expected to double within the next 20 years mainly due to an epidemic increase in the prevalence of type 2 diabetes. Since 25% to 40% of all diabetic patients will develop diabetic nephropathy, it has become the leading cause of end-stage renal disease in the Western world. Therefore, the early identification and subsequent end-organ protective treatment of all patients at risk for end-stage renal disease is of outmost importance.

 

 

 


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