Candidiasis
Kidney Transplant Recipients
The estimated frequency of donor-derived candidiasis is 1:1000 in kidney transplantation. Most infections are considered to result from contamination of the preservation fluid which can occur prior to or at the time of organ procurement. Isolates in donor-derived candidiasis were genotypically identical to those recovered from the preservation fluid in the respective cases. Rupture of an abdominal viscus as possible source of contamination was identified in 58% of the donors in one report.Candida species have been isolated from ~3.7% of the preservation fluids. When preservation fluid cultures did not yield Candida, infections appear to be unusual; however, the precise risk of infection when the preservation fluid cultures are positive is unknown (Supporting Table S5). Transmissions from donors with candidemia have also been documented. Donor-derived candidiasis may manifest as candidemia, infected urinoma, perirenal hematoma, abscess or a fungus ball. However, vascular complications such as mycotic aneurysm and anastomotic rupture are the most serious manifestations of these infections.
Management
Cultures from blood, urine and other clinically relevant sites should be obtained and antifungal therapy initiated in the recipient when Candida is visualized on stains or grown in preservation fluid or in cases of documented intestinal perforation in the donor. Doppler ultrasound should be performed at baseline and day 7. CT or MR angiography should be considered if Doppler ultrasound is unremarkable but there is a strong clinical suspicion for pathology. Detection of aneurysm should prompt evaluation for the need for nephrectomy. If renal abscesses or perinephric collections are detected, drainage by surgical or interventional approaches should be considered.
Fluconazole is the preferred antifungal therapy. The urinary levels of fluconazole exceed the MIC for susceptible and most dose dependently susceptible species such as C. glabrata (Table 1). The urinary excretion of the triazoles on the other hand is minimal (itraconazole 1%, voriconazole 5%, posaconazole 1%). Although, the triazoles have been used to treat renal parenchymal infections, they are not recommended for urinary tract candidiasis. All azoles have the potential to increase calcineurin-inhibitor agent levels (Table 1) which should be monitored with dosage adjustments as necessary. The echinocandins are extensively metabolized with very little active drug recovered in the urine. Eradication of infection with these drugs in the renal parenchyma is more likely than in the collecting system. Thus, echinocandins should be considered as an alternative only if the Candida species is unknown or if there is a high likelihood of non-albicans Candida in the absence of lower urinary tract infection. Polyenes are active against most Candida (Supporting Table S6). Amphotericin B deoxycholate achieves high urinary levels. However, nephrotoxicity is a limiting factor with its use. The lipid formulations of amphotericin B do not achieve appreciable levels in either the renal parenchyma or urine.
In the absence of documented infection, empiric antifungal therapy may be discontinued after 2 weeks. In patients who develop clinical or microbiologic evidence of infection, imaging studies should be repeated and therapy should be extended to 4–6 weeks depending upon repeat imaging, cultures and clinical data. If vascular involvement is documented, a minimum of 6 weeks of antifungal therapy is recommended. Although existing data do not show a higher rate of invasive candidiasis with the use of depleting antibody induction, its precise impact on the risk of donor-derived candidiasis remains unknown.
Donor candiduria does not contraindicate acceptance of the organ. Such recipients should be managed in a manner similar to those with positive preservation fluid. Use of organs from donors with untreated candidemia is not recommended. The risk of transmission from donors with appropriately treated candidemia and documented mycologic eradication is assumed to be low, but this is not known.
Key Recommendations
Definitive and larger studies are needed to identify the factors that predict the likelihood of transmission of Candida and the costeffectiveness of routinely culturing the preservation fluid. Limited existing data are instructive but insufficient to mandate routine preservation fluid cultures in all cases.
Prophylactic antifungal therapy should be initiated when yeast is visualized on stain or Candida species are isolated from the preservation fluid or in recovery of organs from donors with intestinal perforation.
Fluconazole should be considered as the preferred drug for the treatment or prevention of donorderived candidiasis.