Ex Vivo Normothermic Perfusion of Declined Human Kidneys After Inadequate In Situ Perfusion

Authors

  • S. A. Hosgood,

    1. Department of Infection, Immunity and Inflammation, Transplant Group, Leicester General Hospital, University of Leicester, Leicester, UK
    Search for more papers by this author
  • M. L. Nicholson

    Corresponding author
    1. Department of Infection, Immunity and Inflammation, Transplant Group, Leicester General Hospital, University of Leicester, Leicester, UK
    Search for more papers by this author

To the Editor:

Twelve to eighteen percent of kidneys are discarded due to concerns about their suitability for transplantation [1]. A system that allows an accurate assessment of a kidney prior to transplantation may help to increase transplant numbers. Herein, we report a case of a pair of kidneys declined for transplantation due to inadequate in situ perfusion and the use of ex vivo normothermic perfusion (EVNP) to restore function and assess viability.

Both kidneys were retrieved from a 42-year-old donation after circulatory death donor (Category 3). The donor had no previous medical history and death was caused by an intracranial hemorrhage. The warm ischemic time was 15 min, defined as the time from circulatory arrest to the start of the in situ flush. The kidneys were retrieved using a standard technique of in situ cooling via an aortic cannula and flush-out with cold University of Wisconsin solution. After the in situ flush, both kidneys appeared inadequately perfused. An attempt was made to flush the kidneys on the back table but both failed to flush properly and they were deemed unsuitable for transplantation. Consent for research and ethical approval was granted for the study.

The kidneys appeared uniformly purple and mottled in color on arrival at the laboratory (Figure 1A and B). Following static cold storage (right 8 h 19 min, left 9 h 39 min), kidneys were flushed with hyperosmolar citrate (Soltran®; Baxter Healthcare, Thetford, UK) 4°C (1 L). They appeared patchy but a significant amount of blood was cleared from each kidney. Kidneys were then perfused ex vivo with 1 U of O positive oxygenated packed red blood cells mixed with a priming solution at 36.0 ± 0.9°C for 60 min as previously described [2].

Figure 1.

(A) Right kidney on arrival. (B) Left kidney on arrival. (C) Right kidney after 5 min EVNP. (D) Left kidney after 5 min EVNP. (E) Right kidney after 60 min EVNP. (F) Left kidney after 60 min EVNP. (G) Histology after EVNP. (H) Histology after EVNP. (A: Interstitial fibrosis, B: flattened epithelium). EVNP, ex vivo normothermic perfusion.

The right kidney had better function than the left. It produced more urine (200 mL vs. 150 mL) and the mean renal blood flow was higher (right 67.3, left 33.4 mL/min/100 g). Both kidneys appeared pink and evenly perfused and the blood flow improved throughout perfusion (Figure 1C–F). However, two small dark purple areas remained on the surface of the left kidney throughout perfusion. The level of creatinine clearance was low in both kidneys (right 3.7, left 2 mL/min/100 g) and tubular injury more severe in the left compared to the right (fractional excretion of sodium; right 27.3, left 48.3%). A biopsy taken after 60 min of EVNP showed significant donor-related changes and there was also some evidence of acute tubular injury, but the nuclei appeared normal and there was no evidence of cortical necrosis in either kidney (Figure 1G and H).

Hypothermic techniques offer limited opportunity to rescue or accurately assess the level of injury in kidneys that have been inadequately perfused [3]. EVNP is designed to provide metabolic support to reduce ischemic injury [4]. In this present report, both kidneys appeared pink and healthy throughout EVNP. Furthermore, the level of renal blood flow and urine output were within range of EVNP parameters in kidneys from our clinical series, suggesting their suitability for transplantation [3].

The true value of EVNP as a quality assurance system can only be established by transplanting these kidneys. Nonetheless, this preliminary report demonstrates that EVNP can be used to assess the functional capacity of a kidney prior to transplantation.

Acknowledgment

This study was supported by funding from Kidney Research UK (Registered Charity No. 25289).

  • S. A. Hosgood and M. L. Nicholson*

  • Department of Infection, Immunity and Inflammation, Transplant Group, Leicester General Hospital, University of Leicester, Leicester, UK

  • *Corresponding author: Michael L. Nicholson, mln2@le.ac.uk

Disclosure

The authors of this manuscript have no conflicts of interest to disclose as described by the American Journal of Transplantation.

Ancillary