Chronic kidney diseases

  1. DiaPat® RenOM test
  2. Chronic kidney diseases
  3. Risk factors for chronic kidney diseases
  4. Advantages and benefits of the DiaPat® RenOM test
  5. What physicians say about the DiaPat® RenOM test
  6. Sampling for the DiaPat® RenOM test
  7. Validation of the DiaPat® RenOM test
  8. Studies and publications

DiaPat® RenOM test

By analyzing disease-specific proteins in the urine, the DiaPat® RenOM test enables the early detection of chronic kidney diseases. The urine test has been validated in clinical studies. It reliably detects kidney damage - often before permanent organ damage has occurred. Timely therapy can delay or avoid the complete loss of kidney function and renal replacement therapy (dialysis or kidney transplant) that is then required. The DiaPat® RenOM test can differentiate between the following chronic kidney diseases:

  • Minimal Change Disease (MCD)
  • Membranous Glomerulonephritis (MNGN)
  • Focal Segmental Glomerulosclerosis(FSGS)
  • Immunoglobulin-A Nephropathy (IgA Nephropathy)
  • Lupus Nephritis
  • Vasculitis

Chronic kidney diseases

The kidneys are located on both sides of the spine, are about 12 cm long, and weigh approximately 150 g. Their main tasks include purifying the blood and excreting water. Metabolic products are transported to the kidneys via the blood: toxic products, so-called urinary substances, are excreted via the urine, and substances important for the body are transported back into the body via the blood. The kidneys consist mainly of filter units (nephrons). More than 1,500 liters of blood are filtered there every day. If the kidneys are damaged, toxic substances can no longer leave the body and remain in the blood. In high concentrations, they are very harmful. In addition, the kidneys are responsible for the formation of various hormones that regulate blood pressure and bone metabolism, among other things.

 

 

Damage to the kidneys progresses over a long period without symptoms. However, the destruction of kidney tissue is irreversible, and early diagnosis is therefore crucial. Only when kidney damage is advanced do symptoms such as fluid retention, foamy urine due to increased excretion of protein, itching, high blood pressure and general weakness appear. Pain in the kidney area does not occur in chronic kidney disease.

If the kidneys can no longer perform their function as filters, there is a need for artificial blood washing (dialysis). For this purpose, the patient is connected to a dialysis machine that pumps and filters the blood from the body via a tube system. The purified blood then flows back into the body. Dialysis treatment is necessary several times a week. This can be done over a few years, but kidney function cannot completely replace dialysis either. In the long term, a kidney transplant is necessary.

Risk factors for chronic kidney diseases

  • High blood pressure (Hypertonie)
  • Diabetes mellitus
  • Nephrotoxic drugs
  • Smoking
  • Age 50+
  • Genetic predisposition

Advantages and benefits of the DiaPat® RenOM test

Chronic kidney disease (CKD) is currently diagnosed solely by measuring the function of the kidneys. The focus is on how well the kidney filters (glomeruli) are still working. With albuminuria, the amount of the excreted protein "albumin" is measured. Normally, albumin is retained by the kidney's filters due to its size. The massive damage to the kidney filters that occurs in CKD (shown in the picture by the enlargement of the pores in the membrane) initially causes the albumin to leak into the primary urine, where it is first reabsorbed into the tubule. Only when this system is "flooded" does the albumin leak out with the urine to be excreted and can it be measured. From this, renal dysfunction in CKD can be deduced.

 

 

The reduction in the glomerular filtration rate (GFR) can only be measured with a marker obtained from the blood if the function of the kidney filters is only limited.

The determination of CKD is therefore only possible with the two common functional parameters when massive damage to the kidneys has already occurred. Only this massive kidney damage of at least 50% of the organ causes the conventionally measurable restriction of kidney function. But at least the organ reserve of the kidney has been lost.

This also means: With the beginning of the destruction of the vital organ function beyond the organ reserve, there is only a very limited corridor left to delay the dynamic course of the disease. Significant treatment successes are almost impossible at this point.

The DiaPat® RenOM test, on the other hand, enables early CKD detection and thus successful treatment management for the patient. For the attending physician, there is a long therapeutic period of time to use the approved medication and to determine the efficient dosage in order to halt or even stop the initially only slow progressive disease process.

This is because the development of the disease occurs well before the kidneys' organ reserves are used up. As a rule, the disease-related disorders always appear first at the molecular level. Only then do these disease-specific molecular structures manifest in the tissue or in the organ, the kidneys.

This pathogenesis, a definitive disease state, is only indicated by DiaPat® molecular diagnostics at this early stage. With this revolutionary technology, proteome analysis detects the early disease-related changes in proteins in the body from a urine sample.

With the detection of the onset of the disease at the molecular level, more efficient and successful drug treatment of the patient is ensured. This is derived from the principle of action of the approved drugs: Almost all drugs work on and with proteins. If a drug is to act successfully on the disease in good time, it will no longer be able to do so effectively when the cells of the organ or the glomeruli have died. A damaged or dead kidney filter can no longer be regenerated and therefore cannot be treated. Only the molecular mechanism that leads to kidney damage can be treated. This is to be controlled with medication in such a way that the damage to the kidney filters or their functional deterioration is inhibited or stopped. From this alone, the success of the treatment through the use of the proteome analysis results.

What physicians say about the DiaPat® RenOM test

Professor Dr. Raymond Vanholder, Ghent University Hospital

"Chronic kidney disease usually shows up very late on the basis of symptoms. The DiaPat® RenOM test enables the reliable diagnosis of kidney damage 3 to 5 years before the first symptoms appear."


Professor Hermann Haller, Clinic for Kidney and hypertension diseases, Hannover Medical School

"The results of the therapy can also be optimally monitored with the DiaPat® RenOM test. In addition, it enables the differentiation between six different kidney diseases without the need for intervening measures."

Sampling for the DiaPat® RenOM test

The DiaPat® RenOM test analyzes the midstream urine. For the test, the central stream of the second-morning urine is collected in a urine cup. The urine is then transferred to the enclosed urine monovette* (sample syringe) and cooled. The urine monovette is put into protective packaging* for transport. The dispatch to the laboratory takes place via overnight express.

*will be provided.

Validation of the DiaPat® RenOM test

The DiaPat® RenOM test analyzes specific proteins in the urine that indicate kidney damage at a very early stage. The differential diagnosis can be carried out using further protein analyzes. The diagnostic method is very reliable* and has been validated in clinical studies.

* Sensitivity >85%, specificity >85%. Please ask your doctor for more information.

Studies and publications

Schanstra JP, Zürbig P, Alkhalaf A, Argiles A, Bakker SJ, Beige J, Bilo HJ, Chatzikyrkou C, Dakna M, Dawson J, Delles C, Haller H, Haubitz M, Husi H, Jankowski J, Jerums G, Kleefstra N, Kuznetsova T, Maahs DM, Menne J, Mullen W, Ortiz A, Persson F, Rossing P, Ruggenenti P, Rychlik I, Serra AL, Siwy J, Snell-Bergeon J, Spasovski G, Staessen JA, Vlahou A, Mischak H, Vanholder R.
Diagnosis and Prediction of CKD Progression by Assessment of Urinary Peptides.
J Am Soc Nephrol. 2015 Jan 14. pii: ASN.2014050423. [Epub ahead of print]

Gu YM, Thijs L, Liu YP, Zhang Z, Jacobs L, Koeck T, Zürbig P, Lichtinghagen R, Brand K, Kuznetsova T, Olivi L, Verhamme P, Delles C, Mischak H, Staessen JA.
The urinary proteome as correlate and predictor of renal function in a population study.
Nephrol Dial Transplant. 2014 Dec;29(12):2260-8. doi: 10.1093/ndt/gfu234. Epub 2014 Jun 30.

Argilés A, Siwy J, Duranton F, Gayrard N, Dakna M, Lundin U, Osaba L, Delles C, Mourad G, Weinberger KM, Mischak H.
CKD273, a New Proteomics Classifier Assessing CKD and Its Prognosis.
PLoS One. 2013 May 14;8(5):e62837. doi: 10.1371/journal.pone.0062837. Print 2013.

Kistler AD, Serra AL, Siwy J, Poster D, Krauer F, Torres VE, Mrug M, Grantham JJ, Bae KT, Bost JE, Mullen W, Wüthrich RP, Mischak H, Chapman AB.
Urinary proteomic biomarkers for diagnosis and risk stratification of autosomal dominant polycystic kidney disease: a multicentric study.
PLoS One. 2013;8(1):e53016. doi: 10.1371/journal.pone.0053016. Epub 2013 Jan 10.

Herget-Rosenthal S, Metzger J, Albalat A, Bitsika V, Mischak H.
Proteomic biomarkers for the early detection of acute kidney injury.
Prilozi. 2012 Jul;33(1):27-48.

Duranton F, Cohen G, De Smet R, Rodriguez M, Jankowski J, Vanholder R, Argiles A; European Uremic Toxin Work Group.
Normal and pathologic concentrations of uremic toxins.
J Am Soc Nephrol. 2012 Jul;23(7):1258-70. Epub 2012 May 24.

Mullen W, Delles C, Mischak H; members of EuroKUP COST action.
Urinary proteomics in the assessment of chronic kidney disease.
Curr Opin Nephrol Hypertens. 2011 Nov;20(6):654-61.

Mischak H, Thongboonkerd V, Schanstra JP, Vlahou A
Renal and urinary proteomics.
Proteomics Clin Appl. 2011 Jun;5(5-6):211-3. doi: 10.1002/prca.201190031.

Zürbig P, Dihazi H, Metzger J, Thongboonkerd V, Vlahou A
Urine proteomics in kidney and urogenital diseases: Moving towards clinical applications.
Proteomics Clin Appl. 2011 Jun;5(5-6):256-68. doi: 10.1002/prca.201000133. Epub 2011 May 18.

Foucher C, Schiffer E, Mischak H, Ansquer JC, Wilbraham D
Effect of fenofibrate treatment on the low molecular weight urinary proteome of healthy volunteers
Proteomics Clinical Applications 2011

Good DM, Zürbig P, Argilés A, Bauer HW, Behrens G, Coon JJ, Dakna M, Decramer S, Delles C, Dominiczak AF, Ehrich JHH, Eitner F, Fliser D, Frommberger M, Ganser A, Girolami MA, Golovko I, Gwinner W, Haubitz M, Herget-Rosenthal S, Jankowski J, Jahn H, Jerums G, Julian BA, Kellmann M, Kliem V, Kolch W, Krolewski AS, Luppi M, Massy Z, Melter M, Neusüss C, Novak J, Peter K, Rossing K, Rupprecht H , Schanstra JP, Schiffer E, Stolzenburg JU, Tarnow L, Theodorescu D, Thongboonkerd V, Vanholder R, Weissinger EM, Mischak H, Schmitt-Kopplin P
Naturally occurring human urinary peptides for use in diagnosis of chronic kidney disease.
Mol Cell Proteomics. 2010 Nov;9(11):2424-37. Epub 2010 Jul 8.

Kistler A, Mischak H, Poster D, Dakna M, Wuthrich R, Serra A
Identification of a unique urinary biomarker profile in autosomal dominant polycystic kidney disease
Kidney Int. 2009 Jul;76(1):89-96

Mischak H, Massy ZA, Jankowski J
Proteomics and uremia and renal disease
Semin Dial. 2009 Jul-Aug;22(4):409-16.

Zürbig P, Decramer S, Dakna M, Jantos J, Good DM, Coon JJ, Bandin F, Mischak H, Bascands JL, Schanstra JP.
The human urinary proteome reveals high similarity between kidney aging and chronic kidney disease.
Proteomics. 2009 Apr;9(8):2108-17

Haubitz M, Good DM, Woywodt A, Haller H, Rupprecht H, Theodorescu D, Dakna M, Coon J, Mischak H
Identification and Validation of Urinary Biomarkers for Differential Diagnosis and Evaluation of Therapeutic Intervention in ANCA associated Vasculitis
Mol Cell Proteomics. 2009 Oct;8(10):2296-307. Epub 2009 Jun 28.

Haubitz M, Mischak H, Julian BA, Novak J
Urinary Protein Patterns as a Diagnostic Tool for Patients with Immunoglobulin A Nephropathy
European Renal Disease - Touch Briefings 2008

Schiffer E, Mischak H, Vanholder RC
Exploring the uremic toxins using proteomic technologies
Contrib Nephrol. 2008, 160: 159-171

Zürbig P, Mischak H
Capillary electrophoresis coupled to mass spectrometry for biomarker discovery and diagnosis of kidney diseases
Contrib Nephrol. 2008, 160: 107-126

Raedler T, Wittke S, Jahn H, Kössler A, Mischak H, Wiedemann K
Capillary electrophoresis mass spectrometry as a potential tool to detect lithium-induced nephropathy: Preliminary results
Prog Neuropsychopharmacol Biol Psychiatry 2008, 32(3): 673-678

Julian BA, Wittke S, Novak J, Good D, Coon JJ, Kellmann M, Zurbig P, Schiffer E, Haubitz M, Moldoveanu Z, Calcatera S, Wyatt R, Sykora J, Sladkova E, Hes O, Mischak H, Mc Guire B
Electrophoretic methods for analysis of urinary polypeptides in IgA-associated renal diseases
Electrophoresis 2007, 28(23): 4469-4483

Julian BA, Wittke S, Haubitz M, Zurbig P, Schiffer E, McGuire BM, Wyatt RJ, Novak J
Urinary biomarkers of IgA nephropathy and other IgA-associated renal diseases
World Journal of Urology 2007, 35(5): 467-476

Fliser D, Novak J, Thongboonkerd V, Argiles A, Jankowski V, Girolami MA, Jankowski J, Mischak H
Advances in urinary proteome analysis and biomarker discovery
J Am Soc Nephrol. 2007, 18(4): 1057-1071

Walden M, Wittke S, Mischak H, Vanholder RC
Proteomics of human dialysate and ultrafiltrate fluids yielded by renal replacement therapy
Thongboonkerd V (Ed.) 2006, Proteomics of Human Body Fluids: Principles, Methods, and Applications

Haubitz M, Wittke S, Weissinger EM, Walden M, Rupprecht HD, Floege J, Haller H, Mischak H
Urine protein patterns can serve as diagnostic tools in patients with IgA nephropathy
Kidney Int. 2005, 67(6): 2313-2320

Hillman M, Mischak H
CE-MS as a Tool for Renal Disease Analysis and Biomarker Discovery Pace Setter
The worldwide newsletter for capillary electrophoresis (Beckman Coulter) 2005, 9(2): 1-5

Weissinger EM, Kaiser T, Meert N, De Smet R, Walden M, Mischak H, Vanholder RC
Proteomics: a novel tool to unravel the patho-physiology of uraemia
Nephrol Dial Transplant. 2004, 19(12): 3068-3077

Weissinger EM, Wittke S, Kaiser T, Haller H, Bartel S, Krebs R, Golovko I, Rupprecht HD, Haubitz M, Hecker H, Mischak H, Fliser D
Proteomic patterns established with capillary electrophoresis and mass spectrometry for diagnostic purposes
Kidney Int. 2004, 65(6): 2426-2434

Haubitz M, Fliser D, Haller H
Proteomanalyse – eine neue Perspektive für die klinische Diagnostik
Deutsches Ärzteblatt 2004, 101(21): A-1514 / B-1255 / C-1207

Weissinger EM, Mischak H
Proteom analysis applied towards early diagnosis of renal diseases and transplant-monitoring
Transplantationsmedizin 2004, 16: 2-9