Sufferers can spend as much as six years ready for a kidney transplant. Even once they do obtain a transplant, as much as 20 p.c of sufferers will expertise rejection. Transplant rejection happens when a recipient’s immune cells acknowledge the newly obtained kidney as a overseas organ and refuse to simply accept the donor’s antigens. Present strategies for testing for kidney rejection embody invasive biopsy procedures, inflicting sufferers to remain within the hospital for a number of days. A examine by investigators from Brigham and Girls’s Hospital and Exosome Diagnostics proposes a brand new, noninvasive approach to take a look at for transplant rejection utilizing exosomes — tiny vesicles containing mRNA — from urine samples. Their findings are printed within the Journal of the American Society of Nephrology.
“Our objective is to develop higher instruments to watch sufferers with out performing pointless biopsies. We attempt to detect rejection early, so we will deal with it earlier than scarring develops,” mentioned Jamil Azzi, MD, affiliate doctor within the Division of Renal Transplant on the Brigham and an affiliate professor of Drugs at Harvard Medical College. “If rejection isn’t handled, it will possibly result in scarring and full kidney failure. Due to these issues, recipients can face life-long challenges.”
Earlier than this examine, physicians ordered biopsies or blood exams once they suspected that a transplant recipient was rejecting the donor organ. Biopsy procedures pose dangers of problems, and 70-80 p.c of biopsies find yourself being regular. Moreover, creatinine blood exams don’t all the time yield definitive outcomes. Due to the restrictions surrounding present exams, researchers sought alternate and simpler methods to evaluate transplant efficacy.
On this examine, researchers took urine samples from 175 sufferers who have been already present process kidney biopsies suggested by physicians. From these samples, investigators remoted urinary exosomes from the immune cells of the newly transplanted kidneys. From these vesicles, researchers remoted protein and mRNA and recognized a rejection signature — a gaggle of 15 genes — that might distinguish between regular kidney perform and rejection. Notably, researchers additionally recognized 5 genes that might differentiate between two varieties of rejection: mobile rejection and antibody-mediated rejection.
“These findings display that exosomes remoted from urine samples could also be a viable biomarker for kidney transplant rejection,” mentioned Azzi.
This analysis differs from prior makes an attempt to characterize urinary mRNA as a result of clinicians remoted exosomes quite than unusual urine cells. The exosomal vesicle protects mRNA from degrading, permitting for the genes throughout the mRNA to be examined for the match rejection signature. In earlier analysis, mRNA was remoted from cells that shed from the kidney into urine. Nonetheless, with out the extracellular vesicles to guard the mRNA, the mRNA decayed in a short time, making this take a look at tough to do in a scientific setting.
“Our paper reveals that should you take urine from a affected person at totally different closing dates and measure mRNA from inside microvesicles, you get the identical signature over time, permitting you to evaluate whether or not or not the transplant is being rejected,” mentioned Azzi. “With out these vesicles, you lose the genetic materials after a couple of hours.”
One limitation to this analysis is that these exams have been finished on sufferers present process a biopsy ordered by their doctor, who already suspected that one thing was improper. Sooner or later, Azzi and his colleagues purpose to know whether or not a take a look at reminiscent of this one can be utilized on kidney transplant recipients with regular kidney exercise as measured within the blood to detect hidden rejection (subclinical rejection). They’re at the moment doing a second examine on sufferers with secure kidney perform, seeking to see if the identical signature they recognized on this present examine may very well be used on sufferers with out beforehand recognized points however nonetheless detect subclinical rejection.
“What’s most enjoyable about this examine is having the ability to inform sufferers who participated that their effort allowed us to develop one thing that may assist extra individuals sooner or later,” mentioned Azzi. “As a physician-scientist, seeing an concept that began as a frustration within the clinic, and having the ability to use the lab bench to develop this concept right into a scientific trial, that may be very fulfilling to me.”