CMV DNAemia Linked to Higher Creatinine After Living-Donor Kidney Transplantation

A retrospective cohort study of 112 living-donor kidney transplant recipients with low immunological risk has found that patients in whom cytomegalovirus DNA was detectable in the blood during the first year after surgery had significantly higher serum creatinine at six months than patients without detectable viral DNA. The study, conducted at Gaziantep University Şahinbey Research and Application Hospital between January 2019 and June 2022 and published in BMC Nephrology, monitored CMV DNAemia and renal function longitudinally using quantitative real-time PCR. Because of its observational, single-center design and the absence of multivariable adjustment, the researchers emphasize that the findings show associations rather than causal effects and require confirmation in prospective studies.

The cohort consisted of recipients classified as low immunological risk according to the center’s protocol: negative panel reactive antibodies for both Class I and II, a negative lymphocyte cross-match test, no more than three HLA mismatches at the A, B, and DR loci, and no anti-thymocyte globulin induction. Of 283 live-donor recipients screened during the study period, 123 met these criteria; five patients who died during follow-up and six who continued care at external centers were excluded, leaving 112 recipients with complete clinical and laboratory data. The mean age was 37.07 plus or minus 14.41 years, with a range of six to 73 years, 64.3 percent were male, and 53.6 percent underwent preemptive transplantation without prior dialysis. All living donors were CMV IgG-positive and CMV IgM-negative, with CMV DNA undetectable by PCR at donor evaluation.

Viral monitoring relied on quantitative real-time PCR targeting a 182-base-pair sequence within the UL55 gene, which encodes glycoprotein B, a highly conserved region of the virus. DNA was extracted from plasma on a QIAsymphony robotic system using the DSP Virus/Pathogen Midi Kit, and amplification was performed on a Rotor-Gene Q instrument with 45 thermal cycles. Results were calibrated against World Health Organization International Standards and reported in International Units per milliliter. Although the analytical detection limit of the assay was 78 IU/mL, the investigators defined CMV DNAemia as a plasma CMV DNA level of at least 100 IU/mL to avoid over-interpreting borderline low-level results. All recipients received oral valganciclovir prophylaxis for 100 days after transplantation, with the dose adjusted for renal function, and routine PCR measurements were scheduled at baseline and at three, six, and twelve months.

CMV DNAemia was detected in 29 of the 112 recipients, or 25.9 percent. In every case the first episode occurred within the first two postoperative months, which meant that group assignment was fixed before the renal function comparisons at months six and twelve. All 29 recipients with DNAemia received intravenous ganciclovir until CMV DNA became undetectable, and viral clearance was achieved in all treated patients during follow-up. Oral valganciclovir prophylaxis was interrupted during intravenous treatment and resumed afterward if the 100-day period was incomplete, and mycophenolate mofetil was reduced or temporarily discontinued when clinically indicated while tacrolimus continued under therapeutic drug monitoring. No statistically significant correlation emerged between CMV DNAemia and age, gender, HLA compatibility, or preemptive transplant status.

The central renal function comparison was unadjusted for baseline renal function, age, sex, and preemptive transplantation status. At six months, median serum creatinine with an interquartile range of 1.38 (1.05 to 1.70) mg/dL in recipients with CMV DNAemia versus 1.17 (0.93 to 1.40) mg/dL in those without, a difference the authors report as statistically significant at p = 0.047. Measured GFR was lower in the DNAemia group, 65.34 plus or minus 24.69 versus 74.78 plus or minus 21.64 mL/min/1.73 m², but this difference did not reach statistical significance (p = 0.054). At twelve months the pattern persisted only numerically: creatinine was 1.26 (1.04 to 1.86) versus 1.13 (0.97 to 1.34) mg/dL (p = 0.067) and GFR was 67.12 plus or minus 26.14 versus 74.51 plus or minus 21.26 mL/min/1.73 m² (p = 0.133), with neither comparison statistically significant.

Within the 29 recipients with CMV DNAemia, longitudinal analysis showed that serum creatinine differed significantly across the four time points (Friedman χ² = 13.360, p = 0.004). After Bonferroni correction for six pairwise comparisons, creatinine was higher at month twelve than at baseline (adjusted p = 0.048) and higher at months six and twelve than at month three (adjusted p = 0.012 and 0.025), while the baseline-to-month-six contrast was not significant after correction (adjusted p = 0.090). A repeated-measures ANOVA with Greenhouse-Geisser correction likewise indicated a significant overall effect of time on creatinine (F(1.663, 46.554) = 4.382, p = 0.024, partial η² = 0.135), although none of three successive parametric contrasts survived Bonferroni correction. By contrast, GFR showed no significant overall change over time in either the Friedman test (χ² = 3.851, p = 0.278) or the corrected ANOVA (F = 0.579, p = 0.549, partial η² = 0.020). Mean GFR in this subgroup was 70.71 plus or minus 27.18 mL/min/1.73 m² at baseline, 65.34 at month six, and 67.12 at month twelve.

Other measured parameters shifted during follow-up. The urine protein-to-creatinine ratio differed significantly over time in the DNAemia subgroup (χ² = 20.876, p < 0.001), with lower values at months three, six, and twelve than at baseline (adjusted p = 0.001, 0.002, and 0.010), although the Greenhouse-Geisser-corrected ANOVA did not confirm a significant overall time effect (p = 0.076). White blood cell counts also changed significantly (χ² = 13.262, p = 0.004), with lower values at months three and six than at baseline after correction, and CRP levels showed a significant overall difference (χ² = 10.655, p = 0.014) with no surviving pairwise comparison. CMV DNA levels across the four scheduled time points differed overall (χ² = 8.134, p = 0.043), but no pairwise comparison remained significant after Bonferroni correction; in the full cohort, the mean CMV level at month six was 192.99 plus or minus 870.00 IU/mL, with individual extremes of 6400 and 8419 IU/mL widening the confidence interval.

An exploratory, descriptive analysis compared CMV DNA levels according to preemptive transplantation status. At the six-month scheduled measurement, mean CMV DNA was 1206 IU/mL in recipients with a history of dialysis versus 491 IU/mL in those transplanted preemptively, and by month twelve the preemptive group measured 169 IU/mL while the dialysis group showed higher numerical values. The authors stress that these group comparisons are descriptive and should not be interpreted as evidence of a protective effect of preemptive transplantation; they may instead reflect differences in immune status, since prior work has linked prolonged dialysis to chronic inflammation and immune dysregulation. Similar descriptive patterns were noted by sex, with mean creatinine at month six of 2.16 versus 1.46 mg/dL in female versus male recipients, and by age group, but no inferential tests supported these subgroup differences.

The authors interpret their results cautiously. They note that the higher intensity of immunosuppression in the early post-transplant period may partly explain the temporal overlap between CMV DNAemia and renal function changes, and that inflammatory mechanisms proposed for CMV-related graft dysfunction, such as cytokine responses and endothelial injury, are consistent with the observed CRP and leukocyte changes but are not established as mechanisms by this study. The absence of a statistically significant GFR decline may reflect inter-individual variability and the limited sensitivity of GFR to subtle early changes, and the apparent reduction in proteinuria may reflect improved clinical status after transplantation rather than an effect of the virus. Key limitations include the retrospective, single-center design, the modest sample size, exclusion of patients who died or transferred care, the lack of multivariable adjustment, and unadjusted between-group comparisons. Within those constraints, the study suggests that monitoring CMV DNAemia alongside renal function in the first post-transplant year may help identify changes in renal parameters over time in low immunological risk recipients.

Subject of Research: Longitudinal monitoring of CMV DNAemia and renal function after living-donor kidney transplantation

Article Title: Longitudinal real-time PCR monitoring of CMV DNAemia and renal function in living-donor kidney transplant recipients with low immunological risk

Article References: Gülteki̇n, M., Çakmak, E., & Bulut, A. (2026). Longitudinal real-time PCR monitoring of CMV DNAemia and renal function in living-donor kidney transplant recipients with low immunological risk. BMC Nephrology, 27(1), Article 629. https://doi.org/10.1186/s12882-026-05460-5

Image Credits: AI Generated

DOI: 10.1186/s12882-026-05460-5

Keywords: cytomegalovirus, kidney transplantation, CMV DNAemia, real-time PCR, serum creatinine, glomerular filtration rate, living-donor transplant, retrospective cohort, valganciclovir, graft function, preemptive transplantation, BMC Nephrology