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Sci Rep
Sci Rep
Scientific Reports
2045-2322
Nature Publishing Group UK London

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72185
10.1038/s41598-024-72185-6
Article
The impact of JC viruria on renal transplant recovery and prognosis
Zhang Zehua
Wang Yuxiong
Gao Baoshan
Liu Bin
Yu Jinyu
Zhou Honglan hlzhou@jlu.edu.cn

https://ror.org/034haf133 grid.430605.4 0000 0004 1758 4110 Department of Urology II, The First Hospital of Jilin University, Changchun, 130011 China
18 9 2024
18 9 2024
2024
14 217727 6 2024
4 9 2024
© The Author(s) 2024
2024
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Postoperative JC viruria is common in kidney transplant recipients, however there remains a dearth of research on perioperative JCV infection in this population. The clinical significance of JCV monitoring in kidney transplant recipients remains unclear. Based on JCV urine monitoring during the perioperative phase, renal transplant recipients who underwent perioperative and postoperative monitoring at our center were categorized into two groups: the perioperative JC virus infection group and the control group consisting of recipients without detectable JCV DNA in plasma or urine during the two-year follow-up period. A comparative analysis of baseline data was initially performed, followed by a 1:1 propensity score matching of 80 cases from each group. Within the first month after transplantation, the JC viruria group exhibited a significant decrease in the incidence of delayed graft function compared to the control group (P = 0.031).Over the two-year postoperative period, the JC viruria group displayed a significantly lower rate of acute rejection (P = 0.027). Notably, the JC viruria group demonstrated higher estimated glomerular filtration rate levels compared to the control group, particularly within the first year post-transplantation. Moreover, recipient and transplant kidney survival rates did not significantly differ between the two groups (P = 0.642). Perioperative JC viruria in kidney transplant recipients may persist beyond the initial two postoperative years. The presence of JCV is associated with lower rates of DGF and acute rejection, indicating a favorable post-transplant recovery. These findings provide novel insights into the importance of postoperative JCV monitoring.

Keywords

JC virus
Kidney transplantation
JC viruria
Acute rejection
Subject terms

Immunology
End-stage renal disease
Virology
grants from the National Natural Science Foundation of ChinaNo. 82270785 Special Fund for medical and health Talents of Jilin Provinceno. JLSWSRCZX2023-27 issue-copyright-statement© Springer Nature Limited 2024
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pmcIntroduction

JC virus (JCV) is commonly found in the general population and typically infects individuals during childhood, leading to asymptomatic or mild respiratory symptoms. After the initial infection, JCV enters a dormant phase and remains inactive in tissues. Seropositivity for JCV is observed in approximately 70% of adults1 However, individuals with compromised immune function, such as those receiving kidney transplants and undergoing immunosuppression, may experience JCV reactivation. The incidence of asymptomatic JC viruria after kidney transplantation ranges from 16 to 27%, whereas JCV viremia is rarely detected2. Despite being an uncommon cause of post-transplant kidney dysfunction, there is limited research conducted on the subject. The reactivation of JCV is generally believed to be associated with the degree of immunosuppression, particularly suppression of cellular immunity3,4. Nonetheless, consensus regarding monitoring protocols and the necessity of detecting JCV infection after kidney transplantation is currently lacking. Furthermore, the median time for JCV infection after kidney transplantation (11 days post-transplantation) is earlier compared to other infections5; however, no studies presently demonstrate the presence of JCV viruria during the perioperative period in recipients.

In this study, we analyzed follow-up data of kidney transplant recipients who developed JCV infection during the perioperative period (defined as the detection of JCV DNA in urine within one week after surgery) at the First Hospital of Jilin University. Our objective was to investigate the impact of early postoperative JC viruria on the recovery and prognosis of transplanted kidneys.

Patients and methods

Patients group

This study comprises 328 cases of allogeneic kidney transplantation using organ donations at the First Hospital of Jilin University from January 2018 to December 2019. The patients underwent a 2 year follow-up period. Exclusion criteria were established, including: (1) recipients who did not receive regular follow-up and JCV infection monitoring at our center; (2) recipients who initially tested negative for JCV during the perioperative period but later developed JC viruria during the follow-up period; and (3) recipients experiencing delayed graft function (DGF) lasting over two weeks. Based on viral monitoring results, patients were classified into two groups: the early postoperative JC viruria group, including recipients who tested positive for JCV virus within one week after surgery and the control group, comprising recipients who consistently tested negative for JCV in urine during both the perioperative and postoperative regular follow-up.

The study was approved by Ethics Committee of the First Hospital of Jilin University, and this committee waived the need for informed consent (Study no: 2022–091, Date of approval: 2022–02-10). All study procedures were performed in accordance with relevant guidelines and regulations.

Immunosuppression regimen

The immunosuppressive induction regimen consisted of a daily dose of 100 mg of rabbit anti-thymocyte globulin (ATG), initiated on the day of surgery and administered for a total of four days. Methylprednisolone was administered continuously via intravenous infusion at a dose of 500 mg/day from the day of surgery to the second postoperative day, followed by a switch to oral intake (20mg/d) on the third day. The postoperative immunosuppressive maintenance regimen included tacrolimus/cyclosporine A, mycophenolate mofetil, and glucocorticoids. The target concentrations of tacrolimus and cyclosporine in kidney transplant recipients at our center are shown in (Table 1).Table 1 Target concentrations of tacrolimus and cyclosporine for renal transplant recipients at our center postoperatively.

Time after surgery	Tacrolimus (ng/ml)	CsA 0 h (ng/ml)	CsA 2 h (ng/ml)	
1 month	10–15	250–400	1000–1200	
1–3 months	8–10	200–350	1000–1200	
3–6 months	5–8	180–300	900–1000	
6–12 months	5–8	100–200	800–1000	
1–2 years	4–6	100–160	600–800	
After 2 years	4–6	80–150	600–800	

Monitoring protocols

During the perioperative hospitalization, recipients underwent weekly testing for JCV DNA in both blood and urine samples. Within the first three months post-surgery, urine JCV DNA levels were tested monthly. Subsequently, from three months to two years after kidney transplantation, JCV DNA levels in both urine and blood samples were assessed every three months. The quantification of JCV DNA in the samples was conducted using a nucleic acid detection kit (PCR-fluorescent probe method, Beijing Xinuo MediGene Testing Technology Co., Ltd.). The assay kit had a lower limit of detection of 1.0 × 10^3 copies/ml.

Data collection

Data pertaining to the recovery of transplant kidney function, incidence of acute rejection, infection rates, and survival of the transplanted kidney were collected throughout both the perioperative and early postoperative periods of the recipients. Following surgery, recipients requiring dialysis within the first week or experiencing a decrease in daily serum creatinine (Scr) of less than 10% over three consecutive days, or whose Scr does not decrease below 400 μmol/L by the end of the first postoperative week, are classified as having Delayed Graft Function (DGF).To mitigate the risk of false-negative results in JCV monitoring due to anuria in postoperative recipients, the grouping was based on urinary and blood viral test results obtained during the diuretic phase of DGF recipients. Recipients with a postoperative anuria period exceeding two weeks were excluded from the analysis. During follow-up, renal allograft biopsies were performed for recipients with unexplained elevations in serum creatinine levels at any time after transplantation. The confirmation of acute rejection and chronic allograft nephropathy in this investigation relied upon pathological biopsy. For the diagnosis of bacterial urinary tract infection, the criteria included the presence of localized or systemic symptoms concomitant with positive findings in urine routine or urine bacterial culture.

Statistical analysis

The data analysis was performed using SPSS 27.0 software, adhering to standard academic practices. To mitigate group discrepancies and minimize confounding factors, propensity scores were calculated through logistic regression modeling. Subsequently, a 1:1 propensity score matching (PSM) was conducted utilizing the nearest-neighbor approach. The matching variables encompassed baseline data that could impact patient prognosis, including donor history of cardiopulmonary resuscitation (DCD and DBCD), the last pre-procurement serum creatinine level, cold ischemia time of the donor kidney, recipient age, and number of HLA mismatches, with a caliper value of 0.02. Following the matching procedure, the study included 80 patients in each group. For matched categorical variables, the McNemar test was employed, while paired-sample t-tests were conducted for continuous variables. Effect size for categorical and continuous variables were expressed as odds ratio (OR) and standardized mean difference (SMD), respectively. Cumulative survival rates were determined using the Kaplan–Meier method, and statistical significance was defined as P values less than 0.05.

Results

Patient characteristics and matching

A total of 82 patients with JC viruria were identified during the perioperative monitoring, while 151 recipients without JCV detection were followed up. After 1:1 propensity score matching, a final analysis was conducted on 80 cases in both the JC viruria group and the control group, with a follow-up period of two years. There were no statistically significant differences between the two groups in terms of gender, age, receipt of immunosuppressive induction, HLA mismatch, donor age, pre-procurement serum creatinine level, cold ischemia time of the donor kidney, and last pre-procurement serum creatinine level (Table 2). Then we compared the prognosis of two groups of patients after PSM (Table 3).Table 2 Patient characteristics at baseline.

Characteristic	Original cohort (n = 233)	P	Matched cohort (n = 160)	P	
JC viruria group	JC negative group		JC viruria group	JC negative group		
Donor	
 Age, year	45.99 ± 11.79	47.78 ± 10.05	0.245	47.39 ± 9.86	47.88 ± 9.70	0.753	
 Sex, Male, n(%)	68 (82.9%)	113 (74.8%)	0.157	66 (82.5%)	65 (81.3%)	0.837	
 D(B)CD, n(%)	28 (18.5%)	12 (14.6%)	0.450	12 (15%)	15 (18.8%)	0.527	
 Pre-donor creatinine	93.10 ± 42.06	94.49 ± 46.91	0.816	94.93 ± 47.34	94.48 ± 39.74	0.713	
 Cold ischemia time	6.67 ± 2.82	7.17 ± 3.04	0.208	7.06 ± 2.99	6.86 ± 3.01	0.674	
Recipient	
 Age, year	43.83 ± 11.39	44.95 ± 9.56	0.425	44.61 ± 9.39	46.15 ± 11.11	0.346	
 Sex, Male, n(%)	54 (65.9%)	97 (64.2%)	0.805	52 (65%)	47 (58.8%)	0.416	
 HLA mismatch	1.94 ± 0.95	1.70 ± 0.81	0.050	1.71 ± 0.814	1.79 ± 0.924	0.587	
 Initial transplantation, n(%)	82 (100%)	149 (98.7%)	0.542	80 (100%)	80 (100%)	1.000	
 Diabetes, n(%)	28 (34.1%)	50 (33.1%)	0.873	28 (35%)	30 (37.5%)	0.742	
 Dialysis, n(%)	69 (84.1%)	132 (87.4%)	0.488	69 (86.2%)	65 (81.3%)	0.391	

Table 3 Comparison of outcomes between the two groups.

Group	JC viruria positive	JC viruria negative	P value	Effect size (95% CI)	
DGF (n,%)	5 (6.25%)	15 (18.75%)	0.031	OR = 0.289 (0.100–0.838)	
AR within 30 days after surgery (n, %)	3 (3.75%)	4 (5%)	1.000	OR = 0.740 (0.160–3.419)	
AR within 2 years after surgery (n, %)	7 (8.75%)	18 (22.5%)	0.027	OR = 0.330 (0.129–0.842)	
BK viruria within 30 days after surgery (n, %)	12 (15%)	11 (13.75%)	1.000	OR = 1.107 (0.457–2.680)	
BK viruria within 2 years after surgery (n, %)	25 (31.25%)	31 (38.75%)	0.392	OR = 0.718 (0.374–1.380)	
BK viremia within 2 years after surgery (n, %)	7 (8.75%)	10 (12.5%)	0.607	OR = 0.671 (0.242–1.861)	
UTI within 30 days after surgery (n, %)	3 (3.75%)	6 (7.5%)	0.508	OR = 0.481 (0.116–1.992)	
UTI within 2 years after surgery (n, %)	7 (8.75%)	15 (18.75%)	0.134	OR = 0.416 (0.160–1.082)	
Pulmonary infection within 30 days after surgery (n,%)	0	0	1.000		
Pulmonary infection within 2 years after surgery (n,%)	5 (6.25%)	5 (6.25%)	1.000	OR = 1.000 (0.278–3.598)	
Chronic allograft nephropathy (n, %)	1 (1.25%)	4 (5%)	0.375	OR = 0.241 (0.026–2.201)	
eGFR [ml/(min/1.73m2)]	
 1 week eGFR	69.93 ± 30.79	52.34 ± 33.04	0.002	SMD = 0.358 (0.131–0.583)	
 1 month eGFR	73.26 ± 24.14	64.59 ± 30.83	0.059	SMD = 0.215 (0.008–0.436)	
 6 months eGFR	68.18 ± 22.08	61.30 ± 19.20	0.050	SMD = 0.226 (0–0.450)	
 1 year eGFR	69.13 ± 24.06	61.42 ± 19.40	0.023	SMD = 0.265 (0.037–0.491)	
 2 years eGFR	75.58 ± 22.76	69.39 ± 23.20	0.136	SMD = 0.170 (0.054–0.393)	
 3 years eGFR	73.21 ± 22.81	67.72 ± 23.58	0.190	SMD = 0.153 (0.076–0.380)	

Comparison of early complications between the two groups of recipients

1. Delayed graft function (DGF): The incidence of DGF was significantly lower in the JC viruria group (6.25%) compared to the control group (18.75%), OR = 0.289(95% CI 0.100–0.838;P = 0.031).

2. Acute rejection: There was no significant difference in the incidence of acute rejection within one month after surgery between the JC viruria group (3.75%) and the control group (5.00%) (P = 1.000).

3. BKV reactivation: There was no statistically significant difference in the incidence of BKV viruria during the perioperative period between the JC viruria group (15%) and the control group (13.75%) (P = 1.000).

4. Urinary tract infection: The incidence of urinary tract infection was lower in the JC viruria group (3.75%) compared to the control group (7.5%), but the difference was not statistically significant (P = 0.508).

5. Early pulmonary infection did not occur in the matched recipients.

6. CD4 + /CD8 + ratio in the viruria group was lower than that in the control group, SMD = 0.258, 95% CI 0.036–0.479; P = 0.023). No statistically significant differences were observed in other parameters (Table 4).

Table 4 Perioperative data of lymphocyte subsets in two groups of renal transplant recipients.

Group	JC viruria positive	JC viruria negative	P value	
CD3 + (%)	41.3 (24.3,62.5)	44.6 (15.3,69.8)	0.333	
CD3 + CD4 + (%)	20.5 (8.0,36.0)	23.9 (6.3,42.0)	0.238	
CD3 + CD8 + (%)	20.7 (14.0,19.0)	19.6 (10.0,27.0)	0.458	
CD4 + /CD8 + ratio	1.0 (0.6,1.2)	1.3 (0.65,1.65)	0.023	
CD19 + (%)	48.3 (26.5,67.0)	44.8 (20.0,70.6)	0.357	
CD16 + CD56 + (%)	6.6 (3.0,7.8)	7.0 (3.0,10.0)	0.257	
CD3 + count (cells/uL)	376.9 (58.3,557.8)	444.8 (49.8,746.8)	0.123	
CD3 + CD4 + count (cells/uL)	204.5 (18.5,274.0)	270.2 (18.0,443.3)	0.081	
CD3 + CD8 + count (cells/uL)	162.1 (33.3,211.3)	171.8 (28.5,296.5)	0.388	
CD19 + count (cells/uL)	231.0 (126.5,275.3)	247.5 (125.5,302.8)	0.827	
CD16 + CD56 + count ( cells/uL)	62.4 (9.25,54.25)	60.0 (10.0,71.5)	0.124	

Comparison of long-term postoperative complications in two groups of recipients

1. Acute rejection: During the follow-up period of this study (up to 2 years postoperatively), the JC viruria group demonstrated a significantly lower incidence of acute rejection (8.75%) compared to the control group (22.5%), OR = 0.330 (95% CI 0.129–0.842 P = 0.027). A survival curve depicting the occurrence of acute rejection as the outcome was plotted (Fig. 1).

2. Within 2 years after surgery, the incidence of urinary tract infection in the JC viruria group (8.75%) was lower than that in the control group (18.75%), but the difference was not statistically significant, OR = 0.416 (95% CI 0.160–1.082; P = 0.134).

3. The incidence of pulmonary infection was the same in both groups (6.25%).

4. BKV reactivation: The incidence of BKV viruria and BKV viremia in the JC viruria group was lower than that in the control group, but the differences were not statistically significant (31.25 versus 38.75%, OR = 0.718, 95% 0.374–1.380; P = 0.392; 8.75% versus 12.5%, OR = 0.671,95% 0.242–1.861; P = 0.607) respectively.

5. The incidence of chronic allograft nephropathy in recipients with JC viruria (1.25%) was lower than that in the control group (5%), OR = 0.241(95% 0.026–2.201; P = 0.375).

Fig. 1 The incidence of postoperative acute rejection was significantly reduced in patients with JC viruria.

Comparison of renal function between the two groups

The recovery of eGFR in the two recipient groups was compared using paired sample t-tests. At 1 week postoperatively, the eGFR in the JC viruria group was (69.93 ± 30.79) ml/(min·1.73m^2), which was higher than that in the control group, (52.34 ± 33.04) ml/(min·1.73m^2). At 1 month postoperatively, the eGFR in the JC viruria group was (73.26 ± 24.14) ml/(min·1.73m^2), higher than that in the control group, (64.59 ± 30.83) ml/(min·1.73m^2). At 6 months postoperatively, the eGFR in the JC viruria group was (68.18 ± 22.08) ml/(min·1.73m^2), higher than that in the control group, (61.30 ± 19.20) ml/(min·1.73m^2). At 1 year postoperatively, the eGFR in the JC viruria group was (69.13 ± 24.06) ml/(min·1.73m^2), higher than that in the control group, (61.42 ± 19.34) ml/(min·1.73m^2). At 2 years postoperatively, the eGFR in the JC viruria group was (75.58 ± 22.76) ml/(min·1.73m^2), higher than that in the control group, (69.39 ± 23.20) ml/(min·1.73m^2). At 3 years postoperatively, the eGFR in the infection group was (73.21 ± 22.81) ml/(min·1.73m^2), higher than that in the control group, (67.72 ± 23.58) ml/(min·1.73m^2). The effect size with 95% confidence interval and P-values for intergroup comparisons were 0.358(95% CI 0.131–0.583; P = 0.002),0.215(95% CI 0.008–0.436; P = 0.059), 0.226(95% CI 0–0.450; P = 0.050), 0.265(95% CI 0.037–0.491, P = 0.023), 0.170(95% CI 0.054–0.393; P = 0.136), and 0.153(0.076–0.380; P = 0.190), respectively. Statistically significant differences between the groups were observed at 1 week and 1 year postoperatively (Fig. 2).Fig. 2 Postoperative recovery of eGFR in the two groups.

Comparison of postoperative survival rates between two groups of recipients

The postoperative survival rates of recipients in the JCV urine symptoms group were 97.5, 97.5, and 96.25% at 1 year, 2 years, and 3 years after transplantation, respectively, which were slightly lower than those in the control group, 98.75, 98.75, and 97.5%. The difference was not statistically significant (P = 0.642), and no recipients experienced renal graft failure during the follow-up period.

Outcomes of JC viruria

All recipients were subjected to a close monitoring protocol. Among the infection group, 65 recipients (81.25%) tested positive for urinary JCV DNA during the regular follow-up period of two years. Three recipients (3.75%) showed transient negative results for urinary JCV DNA, but later exhibited persistent JCV urine symptoms during subsequent follow-ups. The time points when these recipients had negative results were at 1 month, 3 months, and 6 months postoperatively, respectively. In addition, 12 recipients (15%) experienced a conversion from positive to negative urinary JCV DNA within two years, with an average conversion time of (5.67 ± 4.71) months after transplantation. Throughout the follow-up process, no recipients were found to have JC viremia or JCVN.

Discussion

In post-transplant patients, long-term immunosuppression has been linked to JCV infection or reactivation. Unlike BKV nephropathy, JC viruria rarely progresses to JC viremia and JCVN. During a two-year follow-up period, a study observed that 80 recipients infected with JCV exhibited only JC viruria. One possible initial site of infection could be the stromal cells of the tonsils3, as JCV can invade the body through the respiratory or fecal–oral route. Subsequently, JCV enters the bone marrow and kidneys via infected lymphocytes. In immunocompetent individuals, JCV persists as a low-level latent infection in the kidneys without impacting renal function6–8.

Current research suggests that the transplanted kidney from the donor may be the source of JCV infection in recipients9, with a correlation between the incidence and titers of JCV-specific antibodies in the donor5. However, due to the lack of pre-transplant viral infection-related assays in this study, it is not possible to determine the source of JCV in the included recipients.

During the one-week post-surgery period, JCV DNA was detected in the urine of some kidney transplant recipients, and the majority of them (81.7%, 67/82) exhibited persistent JC viruria over the next two years. Although current domestic and international studies have not found any impact of isolated JC viruria on the transplanted kidney, there is a lack of research on the effect of perioperative JC viruria on the recovery of the transplanted kidney. Therefore, this study aims to compare recipients with perioperative JC viruria to a control group and observe the recovery and prognosis of the transplanted kidney. Surprisingly, the presence of JCV detected in the urine of recipients during the perioperative period appears to be associated with a better prognosis.

JC viruria and delayed graft function (DGF)

The traditional belief suggests that acute kidney injury (AKI) in transplanted kidneys is a risk factor for polyomavirus infections. However, this study found that recipients diagnosed with JC viruria early after surgery had a lower incidence of delayed graft function (DGF). To further explore this, data from 266 recipients who underwent kidney transplantation at our center between 2018 and 2019 were analyzed. Each recipient was monitored for JCV DNA in their urine at least twice a year after surgery. Among the 40 recipients who experienced DGF, 17 of them (42.5%) had at least one episode of JC viruria within two years, with a median time of 32 days. In contrast, among the 226 recipients who did not experience DGF, the proportion was 56.6%, with a median time of 7 days. Overall, recipients with DGF had a lower postoperative JCV infection rate and a later onset of JC viruria.

It is worth noting that a recent multicenter study involving 1025 kidney transplant recipients found that AKI in the donor kidney is a protective factor against BKV viremia, although the study did not investigate the donor's BKV infection status10. Additionally, previous research has shown an association between immediate graft function (IGF) and higher rates of BKV viremia11. Exploring whether AKI leads to a higher selective apoptosis of infected tubular epithelial cells compared to uninfected ones could be an intriguing research target. The selective destruction of infected tubular cells and subsequent regeneration of uninfected cells may help explain the protective effect of donor AKI against polyomavirus infections.

The relationship between JC virus and immunity

The association between JC virus (JCV) and immunity represents a significant area of focus in clinical research. Progressive multifocal leukoencephalopathy (PML), an outcome of JCV infection, is now prevalent in 3 to 5% of individuals with human immunodeficiency virus (HIV), which is a stark contrast to its rarity prior to the HIV epidemic. The prevailing consensus among scholars is that diminished CD4 + T cell count resulting from HIV infection compromises immune control over JCV replication3,12. Previous studies have also reported a lower incidence of acute rejection in recipients with JC viruria5. In our study, we observed a statistically significant lower rate of acute rejection in the JC viruria group compared to the control group, both during the perioperative period and within two years postoperatively. These findings suggest a potential relationship between JC viruria and reduced early acute rejection. Additionally, the control group exhibited four cases of chronic allograft nephropathy, whereas the JC viruria group had only one case, and both groups presented with mesangial proliferative IgA nephropathy as the pathological type. Although the result of chronic allograft nephropathy is not significant (P = 0.375), an odds ratio of 0.241 suggested a moderate to strong protective effect of JC viruria against chronic allograft nephropathy. Unfortunately, due to unavailable pathological results from the native kidneys, we were unable to determine whether the chronic allograft nephropathy was newly developed or recurrent. Interestingly, a separate study involving 500 African Americans demonstrated a 63% decrease in the incidence of nondiabetic nephropathy among JC viruria-positive patients compared to those who tested negative for JC viruria13. Subsequent research has expanded the protective role of JCV to include diabetic nephropathy14.We hypothesize that JCV replication in a healthy individual may indicate a downregulation of systemic immune response, thus preventing the development of chronic allograft nephropathy. Similarly, the persistent presence of JC viruria in kidney transplant recipients appears to be an indicator of adequate immunosuppression, resulting in a lower incidence of acute rejection and reduced risk of new or recurrent chronic allograft nephropathy, a phenomenon that has not been previously reported. To validate this hypothesis, we further collected and analyzed lymphocyte subgroups of two groups of patients one week after surgery. The results revealed that the CD4 + /CD8 + ratio in the viruria group was lower than that in the control group, SMD = 0.258, 95% CI 0.036–0.479; P = 0.023). No statistically significant differences were observed in other parameters (Table 4).Due to the lack of lymphocyte test results for recipients beyond the perioperative period and the variations in immunosuppressive agents used among recipients, we were unable to further demonstrate a causal relationship between JC viruria and the degree of immunosuppression in this study.

JC viruria and other infections

The relationship between JCV and BKV in kidney transplant recipients has been a subject of debate. Some researchers propose a synergistic interaction between JCV and BKV, supported by reports of JCV and BKV recombinant fragments detected in the urine of these recipients15.Conversely, another study suggests mutual inhibition between the two polyomaviruses5. In our study, we found no statistically significant differences in the infection rates of BKV (bacteremia and viruria) between the two groups during the perioperative and early postoperative periods.

Interestingly, besides BKV, the incidence of bacterial urinary tract infections was unexpectedly lower in the infection group during the early postoperative period. From an immunological standpoint, activation of polyomaviruses usually signifies a higher level of immune suppression. However, contrary to expectations, the JC viruria shedding group did not exhibit a higher infection rate compared to the control group, either in the urogenital tract or lungs. We speculate that the higher incidence of urinary tract infections in the control group may be attributed to increased rates of delayed graft function and early acute rejection during the perioperative period, which are known risk factors for urinary tract infections16.

JC viruria and transplanted kidney eGFR and recipient survival rate

This study aims to investigate the impact of perioperative JCV viruria on graft recovery and early recipient prognosis in kidney transplant recipients. Estimated glomerular filtration rate (eGFR) was estimated for transplanted kidneys in both groups at 1 week, 1 month, 6 months, 1, 2, and 3 years postoperatively. The JC viruria shedding group exhibited higher eGFR than the control group at all time points, with statistically significant differences observed at 1 week postoperatively (P = 0.002) and 1 year postoperatively (P = 0.021). The effect size of the 1-week eGFR difference was 0.358, indicating a significant hallmark role of perioperative JC viruria in the early recovery of renal function. Over a period of 3 years, three individuals in the JC viruria shedding group died, with two deaths caused by cardiovascular accidents occurring at 3 months postoperatively and one death caused by severe pulmonary infection at 2 years postoperatively. In the control group, two individuals died, one due to severe pulmonary infection at 8 months postoperatively and the other due to a cardiovascular accident at 2 years postoperatively. The difference in recipient survival rates between the two groups was minimal. The presence of JCV in urine during the early postoperative period appears to be a favorable indicator of good graft recovery. This study did not observe any detrimental effects of persistent JC viruria shedding on transplanted kidney function or recipient survival rates up to 3 years postoperatively. In previous studies, Baljit17 et al. observed that JC viruria frequently manifests early and investigated the short-term prognosis of recipients. While not all recipients developed viruria starting from the perioperative period, no decline in transplant kidney function was noted in individuals carrying JCV. Similarly, a study on high viral load JC viruria, which included histopathological results of transplant kidney, did not reveal any significant differences18.In contrast to Rossi’s findings, we did not observe an impact on survival rates. We report for the first time its protective effect on renal function, and we are the first to apply propensity score matching (PSM) to eliminate bias19.

According to the early manifestations of JCV in renal transplant recipients, this study observed the impact of perioperative JC viruria on the recovery of transplanted kidneys and the early prognosis of recipients, thus initially addressing a gap in this field. However, there are certain limitations. In this single-center retrospective study, the recommended postoperative monitoring of JCV infection within two years by our center resulted in insufficient follow-up time, which is one of the factors limiting the quality of the research. The long-term impact of JC viruria on the function and survival rate of transplanted kidneys was not observed. Furthermore, due to the diverse usage of immunosuppressive agents and the lack of postoperative lymphocyte subset results, the causative relationship between immunosuppressants and JC viruria was not further validated. Given the predictive value of JC viruria for JCV viremia and JCVN, and the absence of reports on JC viruria leading to deterioration of transplanted kidney function, current European guidelines do not recommend continuous JCV screening for all kidney transplant recipients20.

Conclusion

The presence of JCV DNA in urine during the initial week after kidney transplantation has been found to be associated with a decreased occurrence of DGF and acute rejection, along with improved graft function, without an elevated risk of infection. These findings provide novel insights into the monitoring of JCV infection in this particular setting. Importantly, the occurrence of JC viruria, particularly the identification of JCV DNA in urine within the first week following transplantation, holds promise as a prognostic marker for favorable graft outcomes among recipients of kidney transplants.

Acknowledgements

Zehua Zhang performed the study design, wrote the review, created the figures and tables.Yuxiong Wang helped with study design. Baoshan Gao and Bin Liu revised the manuscript, The pathological analysis of the puncture specimens was performed by Jinyu Yu. Honglan Zhou conceptualized, and supervised the study, provided ideas, and acquired funding. All authors agreed with the published version of the manuscript.

Author contributions

Zhang wrote the main manuscript text, Liu and Wang conceived the study. Gao and Zhou revised the manuscript text, some raw data were provided by Yu and all authors reviewed the manuscript.

Funding

This work was supported by grants from the National Natural Science Foundation of China (No. 82270785) and Special Fund for medical and health Talents of Jilin Province (Project No. JLSWSRCZX2023-27).

Data availability

The data that support the findings of this study are not openly available due to reasons of sensitivity and are available from the corresponding author upon reasonable request. Data are located in controlled access data storage at Department of Urology II, The First Hospital of Jilin University.

Competing interests

The authors declare no competing interests.

Publisher's note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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