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Early warning blood-marker identified for chronic kidney disease.

Chronic kidney disease causes approximately 47,000 deaths a year and is known as a silent killer, due to the fact most people don’t realize they have it until the disease is well advanced. Chronic kidney disease often causes severe organ damage before symptoms, such as blood in the urine, swollen hands and feet, and excessive thirst, develop.  In the advanced phases, patients develop serious complications, including high blood pressure, and eventually the kidneys may fail. However, because the heart works very intimately with the kidneys, most people with kidney disease die of heart problems before their kidneys give out.

Currently, there is no test to catch kidney disease in it’s earlier stages or even predict who is at risk of developing the disease.  Now, a new study from researchers led by Rush University shows that suPAR, a circulating protein measured by a simple blood test, can reliably predict a person’s chances of developing chronic kidney disease as much as five years before this common killer starts causing damage.  The team state that in the near future, high suPAR levels will probably inform physician-patient conversations about preventing kidney disease.  The study is published in The New England Journal of Medicine.

Previous studies show that physicians rely on two markers to detect and manage chronic kidney disease, which are estimated Glomerular filtration rate (eGFR), based on measuring creatinine in the blood, indicating how well the kidneys filter waste and proteinuria, and the other, which is high protein levels in urine.  While these disease indicators are very helpful in monitoring existing kidney disease, they are not sensitive enough to catch the disease in its early stages or to predict a person’s risk of developing the disease.

Earlier studies from the lab suggested a role for suPAR in causing the kidney disease known as Focal and Segmental Glomerulosclerosis (kidney scarring). While additional research is needed, the new results indicate a bigger role for suPAR across all of chronic kidney disease, with the current study showing that a high suPAR level was an excellent predictor of future kidney disease.

The current study researchers measured suPAR levels and kidney function (based on eGFR rates) in 2,292 people at baseline and again at follow up. The patients are from the Emory Cardiovascular Biobank, a massive collection of blood samples taken from patients who underwent cardiac catheterization between 2003 and 2009.  Results show that of these subjects, 40% of subjects with high suPAR levels greater than 3,040 ng/mL with no known kidney disease and healthy eGFR levels went on to develop chronic kidney disease over the course of five years. In contrast, data findings show that only 10% of those with low suPAR levels at baseline developed the disease.

Results show that suPAR predicts eGFR decline in patients with already established earlier stage kidney disease as well.  The group state that patients can now be classified according to their risk of developing kidney disease using suPAR levels.  They go on to add that the study divides suPAR levels into four quartiles; the first, Normal suPAR, which is less than 2,373 picograms per milliliter (pg/mL); Above Normal, which stands at 2,373-3030 pg/mL; High, which is measured at 3,040-4,020 pg/mL; and Very High, which is above 4,020 pg/mL.

The researchers hypothesize that blocking suPAR may prove to be comparable in its application to the use of angiotensin converting enzyme inhibitors and angiotensin receptor blockers which are among the few drugs approved for treatment of chronic kidney disease.  The lab go on to conclude that high suPAR levels predict the future development of chronic kidney disease in different populations and suggest this molecule may be a target for treatment to improve clinical outcomes in the majority of patients at risk for future kidney disease.

The team surmise that once physicians know which patients have high suPAR levels, they can counsel them on ways to lower their risk of chronic kidney disease and be more aggressive in terms of giving medications to control high blood pressure and diabetes, which contribute to chronic kidney disease.  For the future, the researchers state that early work is under way by a biopharmaceutical company to develop novel drug therapies that would neutralize suPAR.  They go on to add that they are also studying an aggressive form of kidney disease, focal segmental glomerulosclerosis (FSGS), having linked levels of suPAR to it.

Source: Rush University Medical Center

Human Kidney Anatomy. Credit: digitallab3d. © TurboSquid 2015.
Human Kidney Anatomy. Credit: digitallab3d. © TurboSquid 2015.





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