Disclosures: Yanagita reports receiving research grants from Astellas, Chugai, Daiichi Sankyo, Fujiyakuhin, Kyowa Hakko Kirin, Mitsubishi Tanabe, MSD, Nippon Boehringer Ingelheim and Torii.

January 10, 2022
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Tertiary lymphoid tissues ‘strongly’ associated with late graft dysfunction

Disclosures: Yanagita reports receiving research grants from Astellas, Chugai, Daiichi Sankyo, Fujiyakuhin, Kyowa Hakko Kirin, Mitsubishi Tanabe, MSD, Nippon Boehringer Ingelheim and Torii.

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The presence of advanced tertiary lymphoid tissues in protocol biopsies correlated with decline in graft function among kidney transplant recipients, according to data published in the Journal of the American Society of Nephrology.

“The presence of tertiary lymphoid tissues (TLTs) in transplanted kidneys is well documented. Nevertheless, their clinical relevance remains controversial. The main reasons for these conflicting results include that TLTs were not separated from concurrent rejection, and the definition of TLTs has been inconsistent across studies. The facts that TLTs were frequently observed both in rejected and tolerated murine allografts further complicate their functional identity in transplanted kidneys,” Motoko Yanagita, MD, PhD, a professor in the department of nephrology at Kyoto University in Kyoto, Japan, and colleagues wrote. “To overcome these issues and clarify the effects of TLTs on graft functions, we utilized two major strategies.”

Researchers screened 241 patients who experienced their first living donor kidney transplantation between July 2004 and December 2016 at Akita University in Japan.

Using serial protocol biopsies from 0 hours, 1 month, 2 months and 12 months without evidence of rejection, researchers explored the relationship between TLTs and graft function.

Researchers then identified TLTs as lymphocyte aggregates with indicators of proliferation and used the absence (stage I) or presence (stage II) of follicular dendritic cells to measure the stages of TLTs.

The primary outcome of this study was incidence of death-censored renal function decline.

Among the 241 patients, 214 (mean age was 48.8±12.5 years; 65% were men) were included in the final analysis. Researchers reported that 4% of patients showed TLTs at the 0-hour biopsy, and 50% showed TLTs at the 1-month biopsy. Similarly, prevalence of stage II TLTs reached 19% at the 12-month biopsy. Compared with patients with no TLTs or stage I TLTs, analyses revealed a correlation between stage II TLTs and higher risk of renal function decline after transplant.

“We found that TLTs were frequent in rejection-free protocol biopsies and their cellular and molecular phenotypes were similar to those found in aged patients. By contrast to stage I TLTs that appeared as early as 1 month after kidney transplantation, stage II TLTs developed gradually over time and were independently associated with progressive graft dysfunction,” Yanagita and colleagues wrote. “Prospective studies are needed to confirm whether our novel TLT staging strategy has the potential to serve not only as a valuable tool for systematic classification, but also as a predictor of transplant functional decline. Further investigations are also needed to determine whether therapeutic strategies to prevent the development and maturation of TLTs could lead to better long-term graft outcomes in kidney transplant recipients.”