Double Transplant Doubles Early Infection Risk but Survivors Fare Just as Well

For patients with type 1 or longstanding type 2 diabetes whose kidneys have failed, surgeons can offer two very different paths: a kidney transplant on its own, or a combined operation that replaces both the kidney and the pancreas at once. Simultaneous pancreas-kidney transplantation, known as SPK, is the more ambitious of the two procedures. By grafting a working pancreas, it restores normal blood sugar control and frees patients from insulin injections, and large registry analyses have shown that it improves long-term survival compared with kidney transplantation alone. But the operation is longer, the incisions are more extensive, an extra solid organ is introduced, and the immune suppression needed to protect two grafts is typically more intense. All of that raises an obvious and clinically important question: does the double transplant expose patients to a meaningful excess of infections during the fragile first year after surgery?

A new retrospective cohort study from the Department of Organ Transplantation at The Second Affiliated Hospital of Guangzhou Medical University, published in BMC Infectious Diseases, addresses that question with unusually detailed infection phenotyping. The research team, led by Rongxin Chen and Jialin Wu, with Luhao Liu and Zheng Chen as corresponding authors, followed 228 SPK recipients and 98 diabetic recipients of kidney transplantation alone, or KTA, who underwent surgery between January 2019 and June 2025 at a single center. The primary endpoint was infection-related hospitalization within 12 months of transplant, a measure chosen because it captures infections severe enough to disrupt recovery, not merely laboratory findings. Secondary endpoints included bloodstream infection, infections at specific anatomical sites, reactivation of cytomegalovirus, Pneumocystis jirovecii pneumonia, and one-year patient and graft survival.

The headline finding is a statistically robust increase in infection-related hospitalizations after SPK. Recipients of the combined transplant experienced 0.54 hospitalization episodes for infection per person-year in the first 12 months, compared with 0.31 episodes per person-year among kidney-alone recipients, an incidence rate ratio of 1.76 with a 95 percent confidence interval of 1.22 to 2.57 and a p-value of 0.003. In plain terms, SPK patients were hospitalized for infection roughly three-quarters more often than their kidney-alone counterparts. When the analysis was refined with multivariable Cox regression, accounting for differences in baseline characteristics between the two groups, the association persisted: SPK performed with rabbit anti-thymocyte globulin induction remained significantly more likely to result in infection-related hospitalization than KTA performed with basiliximab induction, with an adjusted hazard ratio of 1.6 and a p-value of 0.04.

The pattern of infections differed strikingly between the two operations, and that pattern is where the biology becomes visible. Surgical-site and intra-abdominal infections dominated after SPK, affecting 18.9 percent of those recipients compared with just 3.1 percent of kidney-alone recipients, an odds ratio of 7.36. This is precisely what one would expect from a procedure that opens the peritoneal cavity, places an additional vascularized organ, and creates two sets of anastomoses where leaks and collections can occur. By contrast, pulmonary infections were more common after kidney transplantation alone, at 25.5 percent versus 7.9 percent after SPK. The authors also documented a dramatic difference in bloodstream infection: bacteremia occurred at a rate of 0.10 episodes per person-year after SPK versus 0.01 after KTA, an incidence rate ratio of 9.4, indicating that the abdominal surgical burden of the double transplant translates directly into a far higher risk of organisms entering the circulation.

Viral complications added a second layer of risk. Cytomegalovirus DNAemia, detected by polymerase chain reaction in the blood, developed in 53.5 percent of SPK recipients, meaning that more than half of the cohort experienced reactivation of this herpesvirus within the first year. Cytomegalovirus is a well-known driver of indirect effects in transplant recipients: it is immunomodulatory, impairing host defenses well beyond its own direct tissue damage, and prior literature has identified it as a dominant risk factor for Pneumocystis jirovecii pneumonia, a fungal infection that can be devastating in immunosuppressed patients. This study provided a striking confirmation of that relationship. In every affected SPK recipient, cytomegalovirus DNAemia preceded the development of Pneumocystis pneumonia, and the authors report that extending prophylaxis with trimethoprim-sulfamethoxazole after documented DNAemia was followed by no subsequent cases of the fungal infection in the cohort.

That final observation deserves emphasis because it points toward a practical intervention. The authors are careful to describe it as preliminary, since a single-center retrospective series cannot establish causation the way a randomized trial could, and the number of patients who progressed to Pneumocystis pneumonia is necessarily small. Even so, the temporal chain they observed, in which cytomegalovirus reactivation consistently preceded Pneumocystis infection and prolonged prophylaxis appeared to interrupt that chain, is exactly the kind of signal that prospective studies should test. If validated, monitoring for cytomegalovirus DNAemia could become a trigger for extending anti-pneumocystis coverage, a low-cost strategy that might spare high-risk patients a life-threatening complication.

The most reassuring part of the study is what the extra infections did not do. One-year patient survival was statistically indistinguishable between the groups, at 96.3 percent for SPK recipients and 95.0 percent for kidney-alone recipients, with a p-value of 0.32. This suggests that although the combined operation generates more infectious complications, those complications were largely treatable and did not, within the first year, claim additional lives. Better still, death-censored kidney graft survival was actually higher after SPK, at 98.8 percent versus 93.0 percent, a difference that reached statistical significance with a p-value of 0.04. Pancreas graft survival at one year was 94.2 percent. The combined transplant, in other words, delivered its expected metabolic and renal benefits while weathering its own infectious storm.

The methodological architecture of the study strengthens confidence in these findings. The investigators used Kaplan-Meier estimation to characterize time-to-event patterns, multivariable Cox regression to adjust for confounders, and, critically, a Fine-Gray competing-risk sensitivity analysis. The latter is a technical detail that matters: when patients die, they can no longer experience infection, and naive analyses can distort infection rates by treating death as ordinary censoring. The Fine-Gray model treats death as a competing event and confirms that the infection signal is not an artifact of different mortality patterns between the groups. The use of infection-related hospitalization as the primary endpoint also avoids the common pitfall of counting asymptomatic viral detections as infections, anchoring the analysis in events that carry real clinical and economic weight.

The study’s limitations follow naturally from its design. It was conducted at a single center in Guangzhou, China, so induction and maintenance immunosuppression regimens, antimicrobial prophylaxis protocols, and local epidemiology of multidrug-resistant organisms may not generalize everywhere. The retrospective design means the two groups were not randomized, and although multivariable adjustment mitigated measurable imbalances, unmeasured differences between patients selected for a major double operation and those receiving a kidney alone may persist. Importantly, the comparison of induction agents, rabbit anti-thymocyte globulin in the SPK group versus basiliximab in the kidney-alone group, means that part of the adjusted hazard ratio reflects differences in induction strategy as well as the operation itself, a confounding that the authors acknowledge implicitly through their phrasing of the adjusted comparison. Rabbit anti-thymocyte globulin is a lymphocyte-depleting agent associated with deeper and more prolonged immunosuppression, which plausibly contributes to the infection excess.

For clinicians and patients weighing these two operations, the message is nuanced rather than alarming. The double transplant carries a real and quantifiable early infectious price, concentrated in surgical-site and intra-abdominal infections, bacteremia, and cytomegalovirus reactivation, roughly 76 percent more infection-related hospitalizations in the first year. But that price did not purchase worse outcomes; survival was equivalent and kidney graft survival was better, while the pancreas graft offered insulin independence for the vast majority of recipients. The practical implications are twofold: centers performing SPK should expect and surveil for the specific infection profile documented here, and the apparent protective effect of extending Pneumocystis prophylaxis after cytomegalovirus DNAemia is a hypothesis worth testing prospectively. As SPK volumes grow worldwide and donor organs remain scarce, studies like this one, which quantify the trade-offs rather than assume them, are what allow patients and their surgeons to make that choice with open eyes.

Subject of Research: Infection outcomes in the first year after simultaneous pancreas-kidney transplantation compared with kidney transplantation alone in diabetic recipients

Article Title: One-year infection outcomes in simultaneous pancreas-kidney versus kidney transplantation alone in diabetic recipients: a retrospective cohort study

Article References: One-year infection outcomes in simultaneous pancreas-kidney versus kidney transplantation alone in diabetic recipients: a retrospective cohort study. (n.d.). https://doi.org/10.1186/s12879-026-14532-8

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14532-8

Keywords: simultaneous pancreas-kidney transplantation, kidney transplantation, diabetes, organ transplantation, infection-related hospitalization, bacteremia, surgical site infection, cytomegalovirus, Pneumocystis jirovecii pneumonia, immunosuppression, graft survival, retrospective cohort study