Urine Biomarker Can Predict Chronic Kidney Disease Progression

MedicalResearch.com Interview with:
Wenjun Ju, Ph.D., M.S.
Research Assistant Professor, Internal Medicine
Matthias Kretzler, M.D.
Professor, Internal Medicine, Nephrology
Research Professor, Computational Medicine and Biology
University of Michigan Health System 

Medical Research: What is the background for this study? What are the main findings?

Response: Chronic kidney disease (CKD) is a global health issue that affects approximately 15% of the global population.. While not all patients with CKD will progress to end-stage kidney disease (ESKD), those that do tend to advance quickly and require dialysis or kidney transplant. They are also at an increased risk of death from cardiovascular disease.

According to the International Society of Nephrology, treatment of CKD, including medical management, dialysis and kidney transplant, is very costly.  In the U.S. alone, therapy for CKD is likely to exceed $48 billion per year, and the ESKD program consumes 6.7 percent of the total Medicare budget to care for less than 1 percent of the covered population. In China, the disease will cost the economy the equivalent of $558 billion in the U.S. over the next decade.

Early identification of patients that are more likely to experience end-stage kidney disease is an urgent, unmet clinical need. Currently, kidney biopsy is required to determine diagnosis and prognosis of kidney disease. This procedure is costly, carries a low, but significant health risk, and has limited ability to predict the future course of kidney disease.

Together with the European Renal cDNA Bank and the Peking University Institute of Nephrology, the University of Michigan team identified epidermal growth factor (EGF) as a promising candidate for prediction of kidney function loss while analyzing transcriptomic data derived from kidney tissue biopsies of CKD patients across Europe and the U.S. We then validated the findings in urine samples from more than 940 patients in North America, Europe and China, and found that a decrease in urinary EGF protein concentration is an early sign of diminishing kidney function and pinpoints the at-risk patient population.

Medical Research: What should clinicians and patients take away from your report?

Response: People with early-stage CKD tend to not notice any symptoms.  Once detected, CKD can be treated with medicines and lifestyle changes, including healthier food and beverage choices. These treatments usually decrease the rate at which CKD worsens, but cannot prevent progression. Understanding which patients are at risk for severe CKD can lead to earlier and more effective treatments, thus preserving kidney function and helping patients lead longer and healthier lives.

Urinary EGF can help patients in two very important ways.

  • First, patients with low urinary EGF are four times more likely to worsen than those who retain EGF function in their kidneys. In clinical practice, this finding could be used to prioritize care for those patients most at risk of losing their kidney function.
  • Second and more immediately, using urinary EGF levels will improve and speed up clinical trials. Enrolling only those patients who are likely to develop specific disease endpoints can reduce the number of people needed in the study and ensure the trial achieves an optimal mix of patients.

Medical Research: What recommendations do you have for future research as a result of this study?

Response: A simple test can identify patients at risk for adverse renal outcome by measuring EGF in a routine urine sample.   Urinary EGF provides significant additive value for CKD progression when combined with current clinical measurements. We anticipate that uEGF will be measured by healthcare providers in the future, which we believe will help to improve patient prognosis and care.

Citation:

Ju, V. Nair, S. Smith, L. Zhu, K. Shedden, P. X. K. Song, L. H. Mariani, F. H. Eichinger, C. C. Berthier, A. Randolph, J. Y.-C. Lai, Y. Zhou, J. J. Hawkins, M. Bitzer, M. G. Sampson, M. Thier, C. Solier, G. C. Duran-Pacheco, G. Duchateau-Nguyen, L. Essioux, B. Schott, I. Formentini, M. C. Magnone, M. Bobadilla, C. D. Cohen, S. M. Bagnasco, L. Barisoni, J. Lv, H. Zhang, H.-Y. Wang, F. C. Brosius, C. A. Gadegbeku, M. Kretzler.
Tissue transcriptome-driven identification of epidermal growth factor as a chronic kidney disease biomarker. Science Translational Medicine, 2015; 7 (316): 316ra193 DOI: 10.1126/scitranslmed.aac7071


Wenjun Ju, Ph.D., M.S., & Matthias Kretzler, M.D (2015). Urine Biomarker Can Predict Chronic Kidney Disease Progression MedicalResearch.com

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