Low White Blood Cell Counts After Kidney Transplant Linked to Higher Costs and CMV Timing

For most people, a routine blood test showing low white cell counts would trigger little more than a repeat test and a watchful wait. For kidney transplant recipients, however, the picture is far more consequential. A new retrospective study from Finland, drawing on nearly a decade of national registry data and covering 966 kidney transplant recipients, has quantified just how common post-transplant leukopenia and neutropenia really are, how their timing intertwines with cytomegalovirus infection, and how much they cost the healthcare system. The findings, published in Transplant International, offer one of the most comprehensive real-world pictures to date of a complication that has long been recognized clinically but rarely characterized at this scale.

The research team, led by investigators from Helsinki University Hospital, Turku University Hospital, Tampere University Hospital, and the data analytics firm Medaffcon, leveraged a uniquely Finnish advantage: near-complete longitudinal health records. By linking the Finnish Kidney Transplant Registry with regional hospital data lakes, the national inpatient and outpatient register (HILMO), pharmacy purchase records from the Social Insurance Institute, and mortality data from Statistics Finland, the researchers assembled a dataset covering approximately half of the Finnish population. All transplantations occurred between 2013 and 2022, and patients were followed for clinical outcomes during the first 18 months and for healthcare resource utilization up to four years after surgery.

The cohort was stratified by cytomegalovirus serostatus, a critical distinction in transplant medicine. Roughly 73 percent of recipients were CMV-seropositive before transplantation (the R+ group), about 21 percent received a kidney from a seropositive donor while being seronegative themselves (the high-risk D+/R− group), and just over 6 percent were seronegative with seronegative donors (D−/R−). This distribution reflects Finland’s CMV seroprevalence of approximately 70 percent, meaning roughly one in five Finnish transplant recipients falls into the highest-risk category for primary CMV infection after surgery.

The headline finding is stark: post-transplant leukopenia or neutropenia, abbreviated PTLN in the study, occurred in 34.5 percent of all recipients within the first year. But the risk was far from evenly distributed. Among D+/R− recipients, 51.5 percent developed PTLN by 12 months, compared with 31.7 percent of R+ recipients and only 10 percent of D−/R− recipients, a difference that remained highly significant after statistical adjustment. In a multivariable logistic regression model, D+/R− serostatus carried 2.42-fold higher odds of PTLN within 18 months, while D−/R− status was actually protective relative to the R+ reference group.

Beyond serostatus, several other risk factors emerged. Female sex was independently associated with PTLN, a finding the authors attribute in part to sex differences in drug pharmacokinetics that may lead to higher plasma drug exposures in women receiving standard doses. Polycystic kidney disease as the primary diagnosis also increased risk, consistent with prior reports that patients with autosomal dominant polycystic kidney disease frequently have leukopenia even before transplantation, possibly related to splenic sequestration or intrinsic immune dysregulation. Delayed graft function, meaning the transplanted kidney did not immediately work, was another independent risk factor. Perhaps most strikingly, induction therapy with anti-thymocyte globulin (ATG) was associated with a seven-fold increase in PTLN risk, a finding the authors note was unsurprising given ATG’s well-known myelosuppressive effects but clinically important given its increasing use in solid organ transplantation.

The relationship between PTLN and CMV infection proved more nuanced than a simple cause-and-effect story. CMV DNAemia, detectable viral DNA in the blood, occurred at broadly similar frequencies in R+ and D+/R− recipients, roughly half of each group. But the timing differed dramatically. In R+ recipients, the median time to first CMV DNAemia was 66 days, with most episodes occurring within the first six months after transplantation. In D+/R− recipients, the median time was 239 days, with most episodes occurring after the six-month mark, coinciding with the end of their standard six-month valganciclovir prophylaxis. This temporal pattern reflects the different prophylactic strategies: 95 percent of D+/R− patients started valganciclovir prophylaxis at transplantation, compared with only 28 percent of R+ patients, who were instead monitored for CMV DNAemia and treated if it appeared.

Using a multistate model that tracked the sequence of events over time, the researchers uncovered a striking asymmetry. In D+/R− recipients, PTLN tended to precede CMV DNAemia, whereas in R+ recipients, CMV DNAemia was more often detected first. By six months post-transplant, 34.5 percent of D+/R− patients had developed PTLN, only 6 percent had CMV DNAemia, and 7.5 percent had experienced both. Among R+ patients, the pattern was nearly reversed: 14.4 percent had PTLN, 31.3 percent had CMV DNAemia, and 11.9 percent had both. The authors caution that these observational findings do not establish causality, and that in R+ patients it was impossible to reliably distinguish CMV-driven cytopenia from valganciclovir-induced myelosuppression because the registry data lacked complete information on drug dosing and indications. Nevertheless, the temporal patterns are clinically plausible given the different prophylactic regimens each group receives.

The economic dimension of the study may prove to be its most consequential contribution. Patients who developed PTLN had substantially higher healthcare resource utilization across virtually every metric measured. Hospital readmission rates at 12 months were 75.3 percent among R+ patients with PTLN versus 64.6 percent among those without, and 78.9 percent versus 72.9 percent in the D+/R− group. ICU admission rates were also elevated, particularly among R+ patients with PTLN, at 13.8 percent versus 6 percent. The cost differences were even more pronounced: during the first year after transplantation, excluding the initial 30 days, inpatient costs averaged 14,028 euros per patient among those with PTLN compared with 5,716 euros among those without, while outpatient costs were 11,695 euros versus 9,045 euros respectively. These differences persisted into the second year of follow-up.

In a multivariable gamma regression model adjusting for demographics, comorbidities, and transplant characteristics, both D+/R− serostatus and PTLN remained independently associated with higher total healthcare costs over four years. The authors emphasize that these cost estimates should be interpreted conservatively, since PTLN may function as a marker of overall clinical complexity rather than a direct cause of increased spending. Many PTLN episodes are managed in outpatient settings through intensified laboratory monitoring and medication adjustments that do not generate inpatient costs, and the exclusion of the first 30 days after transplantation means early PTLN-related events were not captured in the primary cost model.

Notably, the study did not find statistically significant associations between PTLN and graft loss or mortality, though the authors attribute this partly to the limited number of events and note that prior studies have yielded conflicting results on this question. The five-year patient survival rate for the entire cohort was 87.7 percent, and five-year graft survival was 84.7 percent, with no significant differences by CMV serostatus or PTLN status. Advanced recipient age and diabetes as the primary kidney disease were associated with higher mortality and graft loss risk, while female sex and polycystic kidney disease were associated with better graft survival.

The proportion of patients experiencing PTLN also increased over the study period, from 3.6 percent of those transplanted in 2014–2015 to 8.6 percent of those transplanted in 2020–2022. The authors suggest this trend may reflect changes in clinical practice during the decade, including increasing use of ATG induction, greater reliance on tacrolimus-based immunosuppression, and a moderate expansion of valganciclovir prophylaxis, partly driven by more ABO-incompatible transplants and ATG induction protocols. As transplant populations grow older and frailer, the cumulative immunosuppressive burden from multiple concomitant therapies may further elevate PTLN risk, reinforcing the importance of strategies aimed at mitigating both its clinical and economic consequences.

Subject of Research: Post-transplant leukopenia, neutropenia, and cytomegalovirus infection in kidney transplant recipients

Article Title: The frequency and timing of leukopenia and CMV infections in kidney transplant recipients in Finland – a retrospective observational study

Article References: Helanterä, I., Ortiz, F., Havula, E., Tuominen, S., Hakamäki, M., Hellman, T., Mäkelä, S., & Korhonen, R. (2026). The frequency and timing of leukopenia and CMV infections in kidney transplant recipients in Finland – a retrospective observational study. Transplant International, 39, Article 16893. https://doi.org/10.3389/ti.2026.16893

Image Credits: AI Generated

DOI: 10.3389/ti.2026.16893

Keywords: kidney transplantation, leukopenia, neutropenia, cytomegalovirus, valganciclovir, CMV DNAemia, healthcare resource utilization, transplant immunosuppression, Finland, registry study, donor-recipient serostatus, myelosuppression