Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
*Purpose: Chronic allograft nephropathy is the main cause of kidney graft loss. With the use of potent immunosuppressive treatments, acute rejections are less and less frequent. In native kidney pyelonephritis is reported to represents about 10% of cause of ESRD. However, the role of urinary tract infection is still not well defined in kidney transplant. Objective: To assess urinary tract infection and immunosuppression through T cell response during the course of kidney transplant lifespan.
*Methods: : PBMC were obtained from 38 transplant patients (with kidney transplant aging from 0-20 years) by means of density gradient centrifugation of blood samples. Fifty thousand PBMC per well, were incubated overnight (15-18 hours) in triplicate with 5µg/ml of a mitogen, Phytohemagglutinin (PHA). The Promega CellTiter-Glo Luminescent Cell Viability assay which signals the presence of intracellular ATP by means of the luciferin/luciferase. Turner Biosystem luminometer were used to measure ATP in relative lights units (RLU). Clinical status including urinary tract infection (UTI) and transplant rejection were recorded during a 3-month period. Results were analysed according to the age of the transplant. Using descriptive methods and group comparison using ANOVA or Kruskall Wallis according to normality test. Logistic regression analysis was used to assess association of variables including age, UTI status, rejection.
*Results: As shown in the Table below, T cells from transplant patients were less responsive to PHA stimulation as transplant time increased, p=0.0107. UTI was observed in 26% of patient and mostly in the 6-10-year transplant age group. Acute transplant rejection was less frequent.
|All patients n=38||0-5y transp n=8||6-10y transp n=18||11-15y transp n=7||16-20y transp n=5||P value|
|Mean [ATP] ±SEM (ng/ml)||265.74 ±25.75||386.25 ±79.14||228.72 ±30.44||259.57 ±47.97||214.80 ±48.60||p=0.0107|
|UTI frequency||10 26%||0 0||8 44%||1 14%||1 20%|
*Conclusions: T cell response of our patients decreased with the duration of kidney transplant. This may correspond to a progression toward an immune tolerant state. As most kidney transplants fail during or after the 6-10year period, does UTI (acute or chronic) play a greater role in the loss of kidney transplant than currently recognized? BK virus UTI is now recognized as a cause of graft loss. Other microorganisms may also be responsible. The large role played by interstitial fibrosis in the pathology of transplant kidney biopsies may support this proposal. T cell functional assays may help in monitoring and calibrating the reduction of the immunosuppressive therapy. This observation warrants further studies to evaluate factors involved in T cell suppression such as T regulatory cells.
To cite this abstract in AMA style:Assounga A, Omarjee S. T Cell Hyporesponsiveness in Kidney Transplant Recipients is Associated with Urinary Tract Infections and Age of Kidney Transplant: Implications for Allograft Nephropathy [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/t-cell-hyporesponsiveness-in-kidney-transplant-recipients-is-associated-with-urinary-tract-infections-and-age-of-kidney-transplant-implications-for-allograft-nephropathy/. Accessed August 1, 2021.
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