To Perfuse or Not to Perfuse Kidneys Donated after Cardiac Death

To the Editor: Watson et al. reported no superiority of machine perfusion (MP) over cold storage (CS) for kidneys donated after cardiac death (DCD) (1Watson CJE Wells AC Roberts RJ et al.Cold machine perfusion versus static cold storage of kidneys donated after cardiac death: A UK multicenter randomized controlled trial.Am J Transplant. 2010; 10: 1991-1999Abstract Full Text Full Text PDF PubMed Scopus (172) Google Scholar). This finding intrigues us because it contradicts the European randomized controlled trial results (2Moers C Smits JM Maathuis MH et al.Machine perfusion or cold storage in deceased-donor kidney transplantation.N Engl J Med. 2009; 360: 7-19Crossref PubMed Scopus (757) Google Scholar), and particularly those of our recently reported European DCD trial (3Jochmans I Moers C Smits JM et al.Machine perfusion versus cold storage for the preservation of kidneys donated after cardiac death: A multicenter randomized controlled trial.Ann Surg. 2010; 252: 756-764Crossref PubMed Scopus (213) Google Scholar). Futility-stopping rules led to termination of the UK trial when analysis of data on the first 80 recipients showed no effect of MP on delayed graft function (DGF). In contrast, in our DCD trial, including 164 recipients, MP did reduce DGF (3Jochmans I Moers C Smits JM et al.Machine perfusion versus cold storage for the preservation of kidneys donated after cardiac death: A multicenter randomized controlled trial.Ann Surg. 2010; 252: 756-764Crossref PubMed Scopus (213) Google Scholar). Differences between these two DCD trials might explain the discrepancy. Of 25 centers, only five participated in the UK trial and kidneys were mostly transplanted locally. In contrast, our DCD trial was fully integrated in the everyday practice of an international organ sharing organization (Eurotransplant). Kidneys were allocated according to standard rules to 1 of 18 centers where DCD donation/transplantation is authorized. Centers were blinded at organ offer, which might not have been the case in the UK trial since the same unit often performed retrieval and transplantation. Importantly, we started MP immediately after retrieval whereas it was frequently delayed in the UK trial. It may be that pumping kidneys throughout the entire preservation period is necessary to benefit from MP. Another noticeable difference is the higher DGF rate in the CS arm of our trial. Increased ischemic injury, and perhaps other factors inherent to large international studies, may account for this. Indeed, DCD kidneys were exposed to increased mean warm (2.6 min) and cold (3 h) ischemia times compared with the UK trial (Table 1). It may be that MP has greater benefit when kidneys are more vulnerable to DGF to start with. Unlike the UK trial, we did not standardize preservation solution since center-specific protocols were left unchanged. Accordingly, histidine-tryptophan-ketoglutarate (76%) and University of Wisconsin solution (22%) were used, but this did not influence DGF (p = 0.83). This is consistent with previous observations that histidine-tryptophan-ketoglutarate does not affect DGF (4Stewart ZA Lonze BE Warren DS et al.Histidine-tryptophan-ketoglutarate (HTK) is associated with reduced graft survival of deceased donor kidney transplants.Am J Transplant. 2009; 9: 1048-1054Crossref PubMed Scopus (52) Google Scholar), particularly for short cold ischemia times. Immunosuppression was left at the discretion of participating centers but no difference between the study arms possibly affecting DGF was noted. Finally, DGF in its standard acceptation (dialysis the first week post-transplant) represents a subjective and poor surrogate of graft function. Therefore, we also studied the effect of MP on functional DGF defined as the absence of a creatinine decrease ≥10%/day during 3 consecutive days in the first postoperative week (5Boom H Mallat MJ de Fijter JW Zwinderman AH Paul LC Delayed graft function influences renal function, but not survival.Kidney Int. 2000; 58: 859-866Abstract Full Text Full Text PDF PubMed Scopus (277) Google Scholar). Contrary to Watson et al. who reported no effect of MP on creatinine reduction ratios, we found that MP reduced functional DGF even more than standard DGF. This finding is significant because functional DGF has greater predictive value for long-term function compared to creatinine reduction ratios (6Moore J Ramakrishna S Tan K et al.Identification of the optimal donor quality scoring system and measure of early renal function in kidney transplantation.Transplantation. 2009; 87: 578-586Crossref PubMed Scopus (31) Google Scholar).Table 1:Comparison of graft ischemia times in two randomized controlled trialsWarm ischemia timeCold ischemia timeMachine perfusionCold storageUK trial (1)Mean (range)15 min (4–35)13.9 h (6.7–24.2)14.3 h (7.0–30.1)European DCD trial (3)Median (range)16 min (6–38)15.0 h (4.3–28.9)15.9 h (8.6–46.6)Mean (range)17.6 min (6–38)16.6 h (4.3–28.9)17.3 h (8.6–46.6) Open table in a new tab We believe that the European main and DCD trials reflect the beneficial effect of pumping kidneys from retrieval until transplantation in an international sharing organization where diverse center-specific practices unavoidably influence DGF. The need for immediate versus delayed MP warrants further investigation since it may have important logistical consequences. The authors of this manuscript have conflicts of interest to disclose as described by the American Journal of Transplantation. I.J. is a PhD fellow associated with the Research Foundation-Flanders, Belgium. C.M. receives grant support from the Dutch Kidney Foundation. R.J.P. receives consultancy fees from Bristol-Myers Squibb and grant support from the Dutch Kidney Foundation and the Eurotrans-Bio pro-donor project. R.J.P. is listed as inventor in a patent on a portable preservation apparatus for donor organs. J.P. received grant support from the government of Flanders, Belgium, in cooperation with Organ Recovery Systems to study machine perfusion of liver grafts, for which he received no salary. I.J., C.M. and J.P. received congress travel grants from Organ Recovery Systems.