Incidence and outcomes of fever of unknown origin after kidney transplant in the modern era

Margaret R Jorgenson; Sandesh Parajuli; Hanna L Kleiboeker; Daniel C Felix; Brad C Astor; Christopher M Saddler; Jeannina A Smith; Didier A Mandelbrot

doi:10.1111/ctr.15217

Incidence and outcomes of fever of unknown origin after kidney transplant in the modern era

Clin Transplant. 2024 Jan;38(1):e15217. doi: 10.1111/ctr.15217. Epub 2023 Dec 11.

Authors

Margaret R Jorgenson¹, Sandesh Parajuli², Hanna L Kleiboeker³, Daniel C Felix¹, Brad C Astor⁴, Christopher M Saddler², Jeannina A Smith², Didier A Mandelbrot²

Affiliations

¹ Department of Pharmacy, University of Wisconsin Hospital and Clinics, Madison, Wisconsin, USA.
² Department of Medicine, University of Wisconsin-Madison School of Medicine and Public Health, University of Wisconsin Hospital and Clinics, Madison, Wisconsin, USA.
³ Department of Pharmacy, Northwestern Memorial Hospital, Chicago, Illinois, USA.
⁴ Department of Medicine and Department of Population Health Sciences, University of Wisconsin-Madison School of Medicine and Public Health, University of Wisconsin Hospital and Clinics, Madison, Wisconsin, USA.

PMID: 38078682
DOI: 10.1111/ctr.15217

Abstract

Background: While presumably less common with modern molecular diagnostic and imaging techniques, fever of unknown origin (FUO) remains a challenge in kidney transplant recipients (KTRs). Additionally, the impact of FUO on patient and graft survival is poorly described.

Methods: A cohort of adult KTRs between January 1, 1995 and December 31, 2018 was followed at the University of Wisconsin Hospital. Patients transplanted from January 1, 1995 to December 31, 2005 were included in the "early era"; patients transplanted from January 1, 2006 to December 31, 2018 were included in the "modern era". The primary objective was to describe the epidemiology and etiology of FUO diagnoses over time. Secondary outcomes included rejection, graft and patient survival.

Results: There were 5590 kidney transplants at our center during the study window. FUO was identified in 323 patients with an overall incidence rate of .8/100 person-years. Considering only the first 3 years after transplant, the incidence of FUO was significantly lower in the modern era than in the early era, with an Incidence Rate Ratio (IRR) per 100 person-years of .48; 95% CI: .35-.63; p < .001. A total of 102 (31.9%) of 323 patients had an etiology determined within 90 days after FUO diagnosis: 100 were infectious, and two were malignancies. In the modern era, FUO remained significantly associated with rejection (HR = 44.1; 95% CI: 16.6-102; p < .001) but not graft failure (HR = 1.21; 95% CI: .68-2.18; p = .52) total graft loss (HR = 1.17; 95% CI: .85-1.62; p = .34), or death (HR = 1.17; 95% CI: .79-1.76; p = .43.

Conclusions: FUO is less common in KTRs during the modern era. Our study suggests infection remains the most common etiology. FUO remains associated with significant increases in risk of rejection, warranting further inquiry into the management of immunosuppressive medications in SOT recipients in the setting of FUO.

Keywords: complication; infection and infectious agents; patient survival.

MeSH terms

Adult
Fever of Unknown Origin* / diagnosis
Fever of Unknown Origin* / epidemiology
Fever of Unknown Origin* / etiology
Humans
Incidence
Kidney Transplantation* / adverse effects
Neoplasms*