Industry Frontier | The impact of urinary tract infection on ddcfDNA detection values

Urinary tract infection is one of the most common infections after kidney transplantation, with an incidence rate of 20%-80% after transplantation. Studies have suggested that urinary tract infection may affect blood ddcfDNA detection values. This article summarizes the following research results by reviewing multiple relevant research documents and conference reports, hoping to provide help in interpreting the clinical significance of blood ddcfDNA detection values.

1 Urinary tract infection may cause an increase in the relative value of ddcfDNA

Els M Gielis et.al (2019) tested the relative value of ddcfDNA in the blood of 107 patients after kidney transplantation and found that the increase in ddcfDNA% was related to pyelonephritis (6 out of 13 patients with upper urinary tract infection had an increase in the relative value of ddcfDNA, P = 0.032).

In a retrospective study, it was found that 392 patients with both BK virus nephropathy (BKVN) and urinary tract infection (UTI) were tested for blood ddcfDNA, and the relative value of ddcfDNA also increased: in two cases of bacterial infection, the ddcfDNA value increased to 2.8% and 2% respectively. After receiving treatment for urinary tract infection, the ddcfDNA dropped to the normal range (<1%). From this, the authors believe that BK virus and urinary tract infection can cause graft damage, resulting in an increase in the relative value of blood ddcfDNA. A similar phenomenon was also reflected in a single-center study by Jingyu Wen et.al (2020). By testing ddcfDNA in the blood of 183 kidney transplant patients on the 1st, 7th, 14th and 21st day after surgery, it was found that the relative value of ddcfDNA in the transplanted kidney infection group (including urinary tract infection and CMV infection, etc.) increased significantly (P<0.05).

In a literature survey that failed to clearly obtain data on blood ddcfDNA detection values in patients with urinary tract infection, a retrospective study by Lihong Bu et.al (2022) mentioned that the relative value of ddcfDNA in the kidney injury group was significantly higher than that in the control group: the median ddcfDNA value in the control group was 0.21% (n=467, 95% CI: 0.19%-0.34%), the injury mixed group (DSA positive, BK virus, urinary tract infection, urine protein, etc.) was 0.51% (n=180, 95% CI: 0.48%-1.2%), P < 0.0001.

2 Urinary tract infection may cause an increase in total cfDNA in the blood

In addition to affecting the relative value, some studies have shown that when urinary tract infection occurs, it may cause an increase in the total amount of cfDNA in the blood (donor cfDNA + recipient cfDNA). Filippone EJ, et al. (2021) tested the extraction amount of total cfDNA from plasma in 100 patients after kidney transplantation. The results showed that the average extraction amount of cfDNA in the urinary tract infection group (19.43ng/ml) was higher than the clinically stable group (8.45ng/ml, P<0.01). Vanessa Garcı´a Moreira et.al (2009) found that the total cfDNA value in the blood of 21 patients with post-kidney transplant infection (including 4 cases of urinary tract infection) showed an upward trend (P=0.001). It is worth noting that when the total cfDNA value is elevated, it may lead to false negatives when diagnosing rejection. Osmanodja, Bilgin MD et.al (2021) found that total cfDNA increased due to urinary tract infection in 2 rejection patients, causing the patients' relative values ​​to be lower than the normal critical value (0.15% and 0.46% respectively).

3 other factors

In addition, attention should also be paid to the impact of other types of urinary tract injuries on blood ddcfDNA detection values. Els M Gielis et.al (2019) found that the blood ddcfDNA% in patients with acute tubular necrosis was significantly increased (p = 0.011). At this year's American Organ Transplantation Annual Conference (2023ATC), H. I. Shakoor et.al of Baylor University School of Medicine studied heart transplant patients and found that the median blood ddcfDNA% (0.14%) in patients with Active viral infections was significantly higher than that in the control group (<0.12%), P=0.03.

Therefore, in the clinical practice of detecting ddcfDNA, the detection of pathogenic bacteria in urine is very important. It is necessary to combine the content of pathogenic bacteria in urine to comprehensively judge the clinical significance of the blood ddcfDNA detection value.

【Reference】

[1] Goussous N, Xie W, Dawany N, Scalea JR, Bartosic A, Haririan A, Kalil R, Drachenberg C, Costa N, Weir MR, Bromberg JS. Donor-derived Cell-free DNA in Infections in Kidney Transplant Recipients: Case Series. Transplant Direct. 2020 Jun 11;6(7):e568. doi: 10.1097/TXD.0000000000001019. PMID: 32766423; PMCID: PMC7339327.

[2] Bu L, Gupta G, Pai A, Anand S, Stites E, Moinuddin I, Bowers V, Jain P, Axelrod DA, Weir MR, Wolf-Doty TK, Zeng J, Tian W, Qu K, Woodward R, Dholakia S, De Golovine A, Bromberg JS, Murad H, Alhamad T. Clinical outcomes from the Assessing Donor-derived cell-free DNA Monitoring Insights of kidney Allografts with Longitudinal surveillance (ADMIRAL) study. Kidney Int. 2022 Apr;101(4):793-803. doi: 10.1016/j.kint.2021.11.034. Epub 2021 Dec 22. PMID: 34953773.

[3] Filippone EJ, Farber JL. The Monitoring of Donor-derived Cell-free DNA in Kidney Transplantation. Transplantation. 2021;105(3):509-516. doi:10.1097/TP.0000000000003393

[4] García Moreira V, Prieto García B, Baltar Martín JM, Ortega Suárez F, Alvarez FV. Cell-free DNA as a noninvasive acute rejection marker in renal transplantation. Clin Chem. 2009;55(11):1958-1966. doi:10.1373/clinchem.2009.129072

[5] Osmanodja B, Akifova A, Budde K, et al. Absolute or Relative Quantification of Donor-derived Cell-free DNA in Kidney Transplant Recipients: Case Series. Transplant Direct. 2021;7(11):e778. Published 2021 Oct 22. doi:10.1097/TXD.0000000000001237