Article

Implications of Donor Disseminated Intravascular Coagulation on Kidney Allograft Recipients

Connie J. Wang, Shahzad Shafique, Johanna McCullagh, Dennis A. Diederich, Franz T. Winklhofer, and James B. Wetmore

Summary Background and objectives Disseminated intravascular coagulation (DIC) is common in deceased kidney donors and is considered a relative contraindication to donation. The significance of donor DIC on recipient kidney function is poorly understood. Additionally, the significance of thrombocytopenia in recipients of kidneys from DIC-positive donors is understudied. Design, setting, participants, & measurements In a retrospective cohort of 162 kidney transplants, the presence of DIC in donors, the occurrence of thrombocytopenia in recipients, and risk factors for delayed or slow graft function (DGF/SGF) were assessed. The effects of DIC donor status on DGF/SGF in the study sample as a whole, and of thrombocytopenia on DGF/SGF in recipients of DIC-positive kidneys specifically, were examined using multiple logistic regression. Results DIC donor status was not associated with occurrence of DGF/SGF, but thrombocytopenia was significantly associated with DIC-positive donor status (P 0.008). Thrombocytopenia was independently associated with DGF/SGF only in the recipients of DIC-positive kidneys (P 0.005). Patient and graft survival at 1 year were not affected by donor DIC status or by thrombocytopenia status. Conclusions Donor DIC was not associated with short-term suboptimal graft function, defined as DGF/ SGF, nor with long-term patient or graft survival. However, thrombocytopenia appears to portend DGF/ SGF in recipients of DIC-positive kidneys and may be a clinical sign on which the basis of therapeutic decisions could be undertaken. Clin J Am Soc Nephrol 6: 1160 1167, 2011. doi: 10.2215/CJN.07280810

Division of Nephrology and Hypertension, University of Kansas Medical Center, Kansas City, Kansas Correspondence: Dr. Connie J. Wang, MS 3002, 3901 Rainbow Boulevard, Kansas City, KS 66160. Phone: 913588-6074; Fax: 913588-3769; E-mail: cwang@kumc.edu

Introduction
The number of potential recipients of kidney transplants far outstrips the number of organs available for transplantation (1). To narrow this disparity, strategies have been implemented to expand the deceased-donor pool (2), but additional approaches could be considered. One such potential approach is the use of organs from donors with disseminated intravascular coagulation (DIC). Characterized by formation of intravascular fibrin, DIC, which results in thrombotic occlusion of small and midsized vessels (3) and which can prompt multiorgan failure, has traditionally been considered by many to be a strong relative contraindication to kidney donation (4 11), probably because of empirical observations of poor graft outcomes (12). Therefore, utilization of kidneys from DIC-positive (DIC()) donors remains controversial. However, some recent case reports (9,10) and a case series (7) have described favorable outcomes utilizing kidneys from DIC() donors. Because donor DIC is relatively common, being present in as many as 29% of deceased organ donors (13), an understanding of the suitability of organ transplantation from DIC() donors has potentially important implications.
1160 Copyright 2011 by the American Society of Nephrology

An associated question is the clinical significance of thrombocytopenia in individuals receiving DIC() donor kidneys. We have noted a disproportionately high rate of posttransplant thrombocytopenia in recipients of kidneys from DIC() donors, an observation also made by others (9,10). This observation has a plausible mechanistic explanation because the decrease in platelets in the setting of DIC is a result of ongoing thrombosis and consumption of platelets (14,15). Thus, recipient thrombocytopenia could signal processes such as ongoing thrombosis and activation of coagulation attributable to the presence of a focus of DIC (i.e., the donor kidney). Whether recipient thrombocytopenia might be a marker of ongoing thrombosis in the donor kidney that adversely affects graft function has not been systematically studied. Because study of the effects of donor DIC on recipient outcomes is lacking, we assembled a single-center retrospective cohort of 162 kidney transplant recipients. Using strictly specified criteria for the selection of DIC() donors, we sought to determine whether the presence of DIC in kidney donors, independent of traditional risk factors, is associated with delayed or
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slow graft function after transplantation. Additionally, we examined whether the presence of low platelets immediately after organ implantation in recipients of kidneys procured from DIC() donors is associated with poor outcomes.

Materials and Methods

Participants The participants consisted of a retrospective cohort of all 162 consecutive recipients of deceased-donor renal allografts (in the form of kidney transplants alone or simultaneous pancreas-kidney [SPK] transplants) at a single center between May 1, 2007 (the start of the United Network for Organ Sharing electronic donor notification system known as Donornet) and December 31, 2008. We included SPK recipients because our center makes little distinction in allocating kidneys to SPK recipients on the basis of donor DIC. The institutional review board, in accordance with the principles of the Declarations of Helsinki, approved this study. Experimental Design and Associated Definitions Information on recipients (demographics, medical histories, laboratory values, operative characteristics, immunosuppressive regimens [protocols for which are shown in Supplementary Table 1], and outcomes of interest) was collected. Relevant information on the donors was obtained from Donornet. Definitions were established for DIC (in the donor), thrombocytopenia (in the recipient), and the combined outcome of delayed plus slow graft function of the allograft. Diagnostic criteria for DIC required a DIC score at least 4 based on a system proposed by the International Society of Thrombosis and Hemostasis (16), a system commonly used in transplantation (13,17,18). Diagnosis of donor DIC was made if three or more of the following clinical criteria were met: peak protime 15 seconds, peak activated partial prothromboplastin time 50 seconds, platelet count nadir 150,000/ml (the lower limit of normal in our laboratory), fibrinogen nadir 100 mg/dl and/or D-dimer peak 1000 mg/L. Potential DIC() donors were excluded if any of the following criteria were met: age 60 years or 3 years, extended criteria donor (ECD) status, cold ischemia time (CIT) 36 hours, terminal creatinine (Cr) 3.0 mg/dl, glomerular sclerosis 10% (if biopsied), blood flow 90 ml/min, or resistance 0.4 mmHg/ml per minute (if placed on a pulsatile perfusion machine). There was no lower weight limit for adult donors (although 5% of the donors weigh 60 kg), whereas for pediatric donors 3 years, weight had to exceed 10 kg. Kidneys were eligible for machine perfusion if donors had one or more of the following criteria: ECD or donation after cardiac death (DCD) status; CIT 30 hours; Cr 2.0 mg/dl; and/or history of hypertension, diabetes, or kidney disease. Presence of DIC in the donor alone was not an indication for machine perfusion. Thrombocytopenia was defined as (1) onset within 4 days posttransplant if platelet count was 150,000/ml, or (2) a 50% reduction in baseline platelet count within 4 days posttransplant if the pretransplant platelet count was 150,000/ml. The attribution of thrombocytopenia was

made whether or not the patient received thromboglobulin (see below). Delayed graft function (DGF) was defined a need for dialysis (hemodialysis in all patients) within 7 days posttransplant, whereas slow graft function (SGF) was defined as serum Cr 3.0 mg/dl on posttransplant day 5 (19). Hemodialysis, used relatively infrequently at our center, was initiated based on prespecified criteria (listed in Supplementary Table 2). Statistical Analyses Two-sided t tests were used to describe continuous variables and 2 tests for dichotomous variables. Univariate and multivariate logistic regression modeling was undertaken to analyze the potential effect of DGF risk factors, including donor DIC status, on the primary outcome (combined DGF plus SGF). Because the rate of ECDs and DCDs differed between recipients of DIC() and DIC-negative (DIC()) kidneys, a sensitivity analysis was performed in which all recipients of ECD/DCD kidneys were eliminated. To model the independent effect of posttransplant thrombocytopenia on outcome in recipients of DIC() donor kidneys, univariate and multivariate modeling was again used. In recipients of DIC() donor kidneys, a sensitivity analysis was undertaken in which the rate of thrombocytopenia in recipients of DIC() donor kidneys was operationally reduced by subtracting the background rate of thrombocytopenia (determined by an analysis of the rate of thrombocytopenia in the DIC() cohort) to determine the theoretical risk of DGF/SGF associated with thrombocytopenia attributable only to DIC() donor status. A final analysis was undertaken to determine whether thrombocytopenia was associated with DGF/SGF only in the recipients of DIC() donor kidneys. All analyses used SAS version 9.1 (SAS Institute, Cary, NC); a P value of 0.05 was considered as statistically significant.

Results
Baseline characteristics of the recipients are shown in Table 1. The rate of ECD and DCD kidneys varied significantly between groups because the simultaneous presence of donor DIC and either ECD or DCD status is a relative contraindication to transplantation at our center. Donor characteristics were examined by DIC status; platelet count (75,000 67,000/ml versus 174,000 99,000/ml, P 0.0001) and PTT (89 86 seconds versus 34 11 seconds, P 0.0001) were different in DIC() and DIC() donors, respectively. Final Cr was higher (1.2 0.7 mg/dl versus 1.0 0.4 mg/dl, P 0.01) and donor age was younger (24.9 14.2 versus 35.5 17.1, P 0.001) in the DIC() group. As expected, head trauma as a cause of death was significantly higher in the DIC() than in the DIC() donors (70.5% versus 48.3%, P 0.014), whereas no DIC() donor had hypertension or diabetes. Rate of machine perfusion was similar between the DIC() and DIC() groups (18.2% versus 28.0%, P 0.23) and between thrombocytopenia and nonthrombocytopenia recipients of kidneys from DIC() donors (12.5% versus 21.4%, P 0.70). Unadjusted outcomes are shown in Figure 1A through 1D. Recipients of DIC() donor kidneys fared no worse than their DIC() counterparts in the rate of DGF/SGF

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Table 1. Baseline characteristics of kidney transplant recipients, by donor DIC status

Recipient Characteristic (n 162) Age, yearsa 60 years, n (%) Male gender, n ( %) African-American race, n (%) Body mass index (kg/ m2)a 30 kg/m2, n (%) PRA 30%, n (%) History of previous transplant, n (%) CIT, hoursa 24 hours, n (%) ECD or DCD source, n (%) SPK, n (%)
a

From DIC() Donors (n 44) 49.5 13.8 14 (31.8) 27 (61.4) 7 (15.9) 27.2 4.8 16 (36.4) 3 (6.8) 5 (11.4) 15.7 7.0 7 (15.9) 1 (2.3) 8(18.2%)

From DIC() donors (n 118) 53.3 12.9 44 (37.3) 66 (55.9) 29 (24.6) 27.3 5.1 41 (34.8) 16 (13.6) 24 (20.3) 16.5 6.8 24 (20.3) 41 (34.7) 8(6.8%)

P 1.00 0.52 0.53 0.24 0.97 0.85 0.24 0.19 0.55 0.52 0.005 0.04

Data shown as mean standard deviation.

Figure 1. | Graft and patient outcomes by DIC donor status: (A) DGF plus SGF, (B) serum Cr at hospital discharge, (C) hospital length of stay, (D) 1-year patient and graft survival rates, and (E) rate of thrombocytopenia in recipients. Only the rate of thrombocytopenia varied significantly between groups.

(31.8% versus 29.7%, P 0.79), Cr at discharge (1.6 0.7 mg/dl versus 1.8 0.9 mg/dl, P 0.19), or length of hospital stay (10.5 5.4 days versus 12.2 14.6 days, P 0.26). Patient survival rate (100% versus 96.6%, P 0.56) and graft survival rate (97.7% versus 90.7%, P 0.18) at 1 year showed no difference between DIC() and DIC()

groups, respectively. As shown in Table 2, univariate analysis demonstrated that although DIC() donor status was not associated with occurrence of DGF/SGF, CIT 24 hours, male gender, and history of previous transplant were. Multivariate modeling in which DIC() donor status was forced into the model failed to demonstrate an inde-

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Table 2. Logistic regression model of factors associated with poor graft function (DGF SGF) in the entire study sample

Univariate Association Variables OR Age 60 years Male gender African-American race Body mass index 30 kg/m2 PRA 30% History of previous transplant CIT 24 hours ECD or DCD source DIC() donor 0.93 2.08 1.20 0.85 1.41 2.17 3.12 0.76 1.10 95% CI 0.46 to 1.85 1.03 to 4.35 0.53 to 2.63 0.41 to 1.72 0.49 to 3.70 0.86 to 5.00 1.41 to 7.14 0.34 to 1.64 0.51 to 2.33 P 0.846 0.044 0.648 0.657 0.507 0.063 0.005 0.507 0.791 OR 1.95 1.91 3.06 1.22

Multivariate Association 95% CI 0.95 to 4.17 0.80 to 4.16 1.34 to 7.02 0.55 to 2.66 P 0.075 0.144 0.008 0.613

pendent association of DIC status with DGF/SGF; only CIT 24 hours remained significant (P 0.008). Because ECD/DCD donors were differentially distributed among recipients of DIC() and DIC() donor kidneys, a sensitivity analysis was performed in which all recipients of kidneys from ECD/DCD donors were excluded; there was still no evidence of an association of DIC donor status with DGF/SGF (P 0.88, data not shown). The presence of thrombocytopenia by DIC donor status was examined. Individuals who experienced thrombocytopenia showed a decrease in platelets from 196,000 40,000 to 96,000 26,000, a drop of 51.1%. The results are shown in Figure 1E. Thrombocytopenia was significantly more common in recipients of kidneys from DIC() donors (36.4% versus 16.9%, P 0.008). No statistical significant difference was observed in the rate of recipient thymoglobulin use before postoperative day (POD) 4 between the DIC() and DIC() groups (38.6% versus 51.7%, P 0.16). Because three recipients in the DIC() donor group developed thrombocytopenia a mean of 1.8 days after thymoglobulin, they were recoded as having thrombocytopenia for a sensitivity analysis designed to test the robustness of our findings (no recipients in the DIC() donor group developed thrombocytopenia before thymoglobulin was given). A significant difference between rates of thrombo-

cytopenia persisted (36.4% in the DIC() group versus 19.5% in the DIC() group, P 0.02). Additionally, we also specifically investigated whether thymoglobulin or heparin prescribed before POD 4 could confound the association between donor DIC status and thrombocytopenia. Overall, neither thymoglobulin or heparin use before POD 4 differed by donor DIC status: 38.6% of recipients in the DIC() group received thymoglobulin versus 51.7% from the DIC() group (P 0.16), whereas 18.2% of recipients from DIC() donors received heparin versus 11.9% of those from DIC() donors (P 0.31). Also, use of thymoglobulin was not associated with plasmin renin activity (PRA) status (P 0.62 for PRA 30% versus 30%). Examined in another way, thymoglobulin was used in 45.5% of recipients from the DIC() group with thrombocytopenia and 56.3% of those from the DIC() group with thrombocytopenia (P 0.74), whereas heparin was used in 12.5% of recipients from DIC() donors with thrombocytopenia and 10.0% of recipients from DIC() donors with thrombocytopenia (P 1.0). The subset of 44 individuals who received DIC() donor kidneys was stratified according to thrombocytopenia status. Baseline characteristics, including traditional risk factors associated with DGF/SGF, are shown in Table 3. There were no significant differences in any variable examined.

Table 3. Baseline characteristics of kidney transplant recipients from DIC() donors by platelet status

Recipient Characteristics (n 44) Age, yearsa 60 years, n (%) Male gender, n ( %) African-American race, n (%) Body mass index (kg/m2)a 30 kg/m2, n (%) PRA 30%, n (%) History of previous transplant, n (%) CIT, hoursa 24 hours, n (%) ECD or DCD source, n (%) SPK, n (%)

Recipient with 2Plt (n 16) 45.2 14.3 4 (25%) 13 (81.2%) 2 (12.5%) 25.8 4.6 4 (25%) 0 2 (12.5%) 16.3 6.3 2 (12.5%) 0 2 (12.5%)

Recipient without 2Plt (n 28) 52 13 10 (35.7%) 14 (50%) 5 (17.9%) 28.0 4.8 12 (42.9%) 3 (10.7%) 3 (10.7%) 15.4 7.5 5 (17.9%) 1 (3.6%) 6 (21.4%)

P 0.130 0.520 0.057 1.000 0.144 0.333 0.290 1.000 0.688 1.000 1.000 0.690

2Plt represents thrombocytopenia, defined as platelet count 150,000/ml or a 50% decrease from baseline when baseline count was 150,000/ml. Plt, platelets. a Data shown as mean standard deviation.

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Key graft and patient outcomes were examined in the recipients of DIC() donor kidneys, as shown in Figure 2. In unadjusted analysis, recipients who developed thrombocytopenia had significantly higher rates of DGF/SGF than those who did not (56.3% versus 17.9%, P 0.009), higher serum Cr level at discharge (1.9 0.7 mg/dl versus 1.5 0.6 mg/dl; P 0.041), and longer hospital stays (13.3 6.1 days versus 8.9 4.3 days; P 0.017). However, patient survival rate (100% in both groups) and graft survival rate (100% versus 96.4%, P 1.00) at 1 year showed no difference between groups. In the recipients of kidneys from DIC() donors, we determined whether thrombocytopenia or other factors were independently associated with DGF/SGF. As shown in Table 4, univariate analysis demonstrated that

only thrombocytopenia was associated with DGF/SGF (odds ratio [OR] 5.91, 95% confidence interval [CI] 1.48 to 23.56, P 0.012). In multivariate modeling, PRA status was marginally associated with outcome (P 0.05), whereas thrombocytopenia was strongly associated with DGF/SGF (OR 9.43, 95% CI 2.17 to 52.53, P 0.005). Because thrombocytopenia, a common clinical occurrence, had a baseline rate of 16.9% even in recipients of DIC() donor kidneys, all instances of thrombocytopenia in recipients of DIC() donor kidneys might not be appropriately attributed to DIC in donors. We performed a sensitivity analysis in which approximately 19% (the nearest integer percentage to 16.9%) of thrombocytopenic patients were manually reassigned to nonthrombocytopenia

Figure 2. | Short-term graft and patient outcomes of recipients who received kidneys from DIC() donors by thrombocytopenia status: (A) DGF plus SGF, (B) serum Cr at hospital discharge, (C) hospital length of stay, (D) 1-year patient and graft survival rates.

Table 4. Multivariate logistic regression of factors associated with DGF/SGF in recipients of DIC() donor kidneys

Univariate Association Variables OR Age 60 years Male gender African-American race Body mass index 30 kg/m2 PRA 30% History of previous transplant CIT 24 hours ECD or DCD source Thrombocytopenia
a

Multivariate Association P 0.318 0.786 0.498 0.542 0.216 0.553 0.498 0.980 0.012 OR 14.67 9.43 95% CI 1.10 to 382.72 2.17 to 52.53 P 0.050 0.005

95% CI 0.09 to 1.91 0.33 to 4.76 0.31 to 9.09 0.40 to 5.56 0.42 to 111.11 0.02 to 3.82 0.31 to 9.09 1.48 to 23.56

0.47 1.20 1.77 1.49 4.76 0.50 1.79 0.09 5.91

Insufficient variation for reliable estimation of CI.

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status. This conservative reanalysis demonstrated that thrombocytopenia remained independently associated with DGF/SGF (OR 5.37, 95% CI 1.29 to 24.80, P 0.024). We demonstrate that use of a kidney from DIC() a donor does not appear to be associated with an increased risk of DGF/SGF, nor with 1-year patient or graft survival. However, we found that thrombocytopenia in recipients of kidneys from DIC() donors was associated with DGF/ SGF. Our findings were bolstered by several sensitivity analyses designed to test the robustness of our findings by varying clinical assumptions. Previous case reports and series (510,12,13,20 22) have presented an ominous picture: nearly half of transplanted DIC() kidneys did not achieve immediate graft function. Older data from organ procurement organizations revealed that 41% of transplant centers would not even consider organs from donors with DIC (4); these findings are concordant with our anecdotal experiences and those garnered from colleagues at several other centers. These reports may be responsible for the traditional hesitancy among the transplant community to utilize kidneys from DIC() donors. However, two important studies suggest that the association of donor DIC with outcomes may be more complex than initially appreciated. Hefty et al., who utilized clinical criteria to diagnose DIC, reported that DIC donor status was not associated with DGF (13), whereas McCall et al., who utilized rigorous donor biopsy criteria to report the presence of thrombus in donor kidneys, showed that although donor DIC was associated with an increased rate of DGF, it did not affect long-term outcomes (22). This may be because the recipient fibrinolytic system has the potential to rapidly lyse the clot present once the organ is placed (5,6,23,24). Biopsy appears to an imperfect method to guide organ allocation in this setting because of (1) false-negative results (because of the more time-sensitive, but nonspecific, staining techniques generally used in this situation) (20,2527), (2) false-positive presence of fibrin thrombi resulting from foreign particles introduced during organ handling and storage (in which case the thrombi may have no deleterious effects) (28), and (3) the inability of biopsy to predict the reversibility of fibrin by the glomerular fibrinolytic system after transplantation (29 32). As such, biopsy findings have not been validated by clinical outcomes. The paper presented here differs from many of the previous contributions in several ways. This study was undertaken from the perspective of the recipient, rather than from that of the donor, and it was much larger than previous studies; as such, various factors traditionally associated with DGF or SGF could be analyzed. Previous studies in which the donor status was established as the starting point of the investigation (13,22) did not take into account clinical risk factors in recipients, factors that, if concealed, are likely to confound the exposure-outcome relationship. Second, as a single-center study, variation in treatment is unlikely to substantially influence outcomes, unlike in other studies (13). In our study, we did not find that some traditional DGF risk factors (e.g., kidneys from DCD or ECD donors and

Discussion

older recipient age) were associated with poorer graft outcomes. However, some other studies report similar findings. Locke et al. found that DGF rate was comparable between kidneys from DCDs and from SCDs if DCD donor age was 50 years old and CIT was 12 hours (33); the mean age of our DCD donors was only 34.9 years old, whereas CIT was a modest 14.9 hours. In another study, when ECD grafts were carefully allocated to selected recipients with lower immunological risk and functional need, clinical outcomes were no worse than for kidneys from SCDs (34,35). Finally, several studies (36) appeared to demonstrate that age itself was not a risk factor for DGF, as did the prospective Neoral-MOST (Multinational Observational Study in renal Transplantation) of 3655 individuals (37). Collectively, these results may explain why we did not find independent associations of DCD status, ECD status, and recipient age with suboptimal renal function. We also investigated whether thrombocytopenia in the recipients of kidneys from DIC() donors occurs more frequently and if it heralds DGF/SGF. A DIC() kidney presumably contains microthrombi, providing an exogenous source of fibrin. Because an early drop of recipient platelet count was noted to be the only sign suggesting ongoing thrombotic processes during DIC (14,38), recipient thrombocytopenia may be the early signal for intrarenal clotting events, thereby contributing to poorer graft function. We indeed found evidence that thrombocytopenia, which occurs much more frequently in DIC() donor kidneys, is associated with DGF/SGF, a finding that was preserved even when we attenuated the rate of thrombocytopenia in DIC() kidney recipients by subtracting a background rate of thrombocytopenia. We did consider the possibility that drugs such as valgancyclovir, mycophenolate mofetil, heparin, and thymoglobulin (the only lymphocyte-depleting agent used in our study) caused thrombocytopenia. However, we required that thrombocytopenia develop within 4 days of transplantation. Valganciclovir was not given to any patient before day 4, whereas mycophenolate mofetil is unlikely to be responsible for our between-group findings because it is prescribed universally. Heparin and thymoglobulin exposure were not statistically different by DIC or thrombocytopenia status; additionally, in the DIC() group, thrombocytopenia developed before thymoglobulin was given. We acknowledge several limitations to our study. First, our sample size, although larger than that of most reports, was modest. Second, because we rarely utilize DIC() kidneys from donors with other risk factors, our findings cannot be generalized to all donors and may only be applicable in an environment in which the DIC() donors are younger, have a high incidence of head trauma, and have negligible rates of hypertension and diabetes. We also elected to create a combined outcome measure, namely DGF plus SGF. This was done for several reasons. First, any function other than normal (immediate) function is suboptimal, and SGF is associated with poorer long-term outcome in its own right (19). Second, at our institution, clinical criteria for dialysis initiation are relatively stringent; the practical implication of this is that many individuals who might be classified as DGF at other institutions are classified as SGF at ours. Thus, to reduce possible

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misclassification bias, we combined SGF with DGF. Finally, it is conceivable that machine perfusion criteria could have a bearing on graft function. However, the criteria at our organ bank are fairly standard, and because the rate of perfusion was not significantly different between DIC() and DIC() donors, it is unlikely that perfusion practices substantially influenced our findings. In summary, we demonstrate that there is no evidence of an independent association of donor DIC status with graft outcome. If our results are borne out in future long-term prospective studies, the traditional hesitancy of clinicians to use kidneys from DIC() donors might warrant reexamination. We also show that thrombocytopenia in the setting of receipt of a kidney from a DIC() donor appears to be an independent risk factor for suboptimal graft function. Such a clinical event in the absence of other causes of thrombocytopenia may provide an early signal prompting changes in clinical management, such as risk-stratifying individuals at risk for DGF/SGF and perhaps modifying care by administering dialysis in a timely fashion or by delaying the introduction of calcineurin inhibitors. These prospects should be the subject of future studies.
Disclosures None.

References 1. U.S. Renal Data System: USRDS 2006 Annual Data Report: Atlas of Chronic Kidney Disease and End-Stage Renal Disease in the United States, Bethesda, MD, National Institute of Health, National Institute of Diabetes and Digestive and Kidney Disease, 2006, Available at: http://www.usrds.org/ adr.htm. Accessed 2010. 2. Organ Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients (OPTN/SRTR). 2006 3. Levi M, Ten Cate H: Disseminated intravascular coagulation. N Engl J Med 341: 586 592, 1999 4. Karlson CG, Lucier J, Bradley JW, Cho, SI: DIC in cadaver kidney donors [Abstract]. Am Society of Transplant Surgeons 1985 5. Ruers TJ, Bosman F, Kootstra G, van Hooff JP: Intravascular coagulation and kidney donation. Transplantation 42: 307 308, 1986 6. Shamash FS, Oh HK, Lee MW, Dienst SG: Kidney retrieval from cadaver donors with disseminated intravascular coagulopathy. Curr Surg 46: 6 9, 1989 7. Gil-Vernet S, Martinez-Brotons F, Gonzalez C, Domenech P, Carreras M: Disseminated intravascular coagulation in multiorgan donors. Transplant Proc 24: 33, 1992 8. Takeda A, Morozumi K, Uchida K, Haba T, Tominaga Y, Yoshida A, Orihara A, Kobayashi T, Yokoyama I: Case study of paired cadaver renal allografts from the same donor: Influence of local DIC kidney and concomitant acute rejection on early graft outcome. Clin Transplant 13[Suppl 1]: 1316, 1999 9. Pastural M, Barrou B, Delcourt A, Bitker MO, Ourahma S, Richard F: Successful kidney transplantation using organs from a donor with disseminated intravascular coagulation and impaired renal function: Case report and review of the literature. Nephrol Dial Transplant 16: 412 415, 2001 10. Bennett WM, Hansen KS, Houghton DC, McEvoy KM: Disseminated intravascular coagulation (DIC) in a kidney donor associated with transient recipient DIC. Am J Transplant 5: 412 414, 2005 11. Nghiem DD, Olson PR, Sureshkumar KK: Significance of microvascular thrombosis in renal allografts: Role of ex vivo thrombolytic therapy. Clin Transplant 21: 172176, 2007

12. Meyers AM, Lewing J, Disler PB, Milne FJ, Hyde P, Abrahams C, Myburgh JA: Donor disseminated intravascular coagulation (DIC), intraglomerular fibrin deposition, and subsequent graft function. Kidney Int 13: 432, 1978 13. Hefty TR, Cotterell LW, Fraser SC, Goodnight SH, Hatch TR: Disseminated intravascular coagulation in cadaveric organ donors. Incidence and effect on renal transplantation. Transplantation 55: 442 443, 1993 14. Saba HI, Morelli GA: The pathogenesis and management of disseminated intravascular coagulation. Clin Adv Hematol Oncol 4: 919 926, 2006 15. Wolfe RA, Ashby VB, Milford EL, Ojo AO, Ettenger RE, Agodoa LY, Held PJ, Port FK: Comparison of mortality in all patients on dialysis, patients on dialysis awaiting transplantation, and recipients of a first cadaveric transplant. N Engl J Med 341: 17251730, 1999 16. Taylor FB Jr, Toh CH, Hoots WK, Wada H, Levi M: Towards definition, clinical and laboratory criteria, and a scoring system for disseminated intravascular coagulation. Thromb Haemost 86: 13271330, 2001 17. Valdivia M, Chamorro C, Romera MA, Balandin B, Perez M: Effect of posttraumatic donors disseminated intravascular coagulation in intrathoracic organ donation and transplantation. Transplant Proc 39: 24272428, 2007 18. Cheng SS, Pinson CW, Lopez RR, Crass RA, Johnson RS: Effect of donor-disseminated intravascular coagulation in liver transplantation. Arch Surg 126: 12921296, 1991 19. Humar A, Johnson EM, Payne WD, Wrenshall L, Sutherland DE, Najarian JS, Gillingham KJ, Matas AJ: Effect of initial slow graft function on renal allograft rejection and survival. Clin Transplant 11: 623 627, 1997 20. Kaufman HH, Hui KS, Mattson JC, Borit A, Childs TL, Hoots WK, Bernstein DP, Makela ME, Wagner KA, Kahan BD, et al.: Clinicopathological correlations of disseminated intravascular coagulation in patients with head injury. Neurosurgery 15: 34 42, 1984 21. Hull D, Karlson CG, Lucier JS, Bradley JW, Cho SI: DIC in cadaver kidney donors. Transplant Proc 18: 469 470, 1986 22. McCall SJ, Tuttle-Newhall JE, Howell DN, Fields TA: Prognostic significance of microvascular thrombosis in donor kidney allograft biopsies. Transplantation 75: 18471852, 2003 23. Faulk WP, Gargiulo P, McIntyre JA, Bang NU: Hemostasis and fibrinolysis in renal transplantation. Semin Thromb Haemost 15: 88 98, 1989 24. Levin RD, Kwaan HC, Ing TS, Miller AW, Merkel FK: Return of function in the thrombosed kidney after transplantation. Nephron 19: 146 152, 1977 25. Craig JM, Gitlin D, Janeway JA: Studies on the nature of fibrinoid in the collagen diseases. Am J Pathol 33: 5577, 1957 26. Davison AM, Thomson D, Macdonald MK, Rae JK, Uttley WS, Clarkson AR: Identification of intrarenal fibrin deposition. J Clin Pathol 26: 102112, 1973 27. Gitlin D, Craig JM: Variations in the staining characteristics of human fibrin. Am J Pathol 33: 267283, 1957 28. Guarrera JV, Nasr SH, Reverte CM, Samstein B, Brown T, Balachandran V, Samuels MJ, Kelly J, Hardy MA, Markowitz GS, DAgati VD, Ratner LE: Microscopic intrarenal particles after pulsatile machine preservation do not adversely affect outcomes after renal transplantation. Transplant Proc 38: 3384 3387, 2006 29. Bergstein JM: Glomerular fibrin deposition and removal. Pediatr Nephrol 4: 78 87, 1990 30. Kanfer A: Role of coagulation in glomerular injury. Toxicol Lett 46: 8392, 1989 31. Kanfer A: Glomerular coagulation system in renal diseases. Ren Fail 14: 407 412, 1992 32. Wardle EN: Fibrin in renal disease: Functional considerations. Clin Nephrol 2: 8592, 1974 33. Locke JE, Segev DL, Warren DS, Dominici F, Simpkins CE, Montgomery RA: Outcomes of kidneys from donors after cardiac death: Implications for allocation and preservation. Am J Transplant 7: 17971807, 2007 34. Stratta RJ, Rohr MS, Sundberg AK, Armstrong G, Hairston G, Hartmann E, Farney AC, Roskopf J, Iskandar SS, Adams, PL:

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Increased kidney transplantation utilizing expanded criteria deceased organ donors with results comparable to standard criteria donor transplant. Ann Surg 239: 688 695; discussion 695 687, 2004 35. Stratta RJ, Rohr MS, Sundberg AK, Farney AC, Hartmann EL, Moore PS, Rogers J, Iskandar SS, Gautreaux MD, Kiger DF, Doares W, Anderson TK, Hairston G, Adams, PL: Intermediate-term outcomes with expanded criteria deceased donors in kidney transplantation: A spectrum or specter of quality? Ann Surg 243: 594 601; discussion 601593, 2006 36. Moore PS, Farney AC, Hartmann EL, Rogers J, Doares W, Gautreaux MD, Iskandar SS, Hairston G, Adams PL, Stratta, RJ: Experience with deceased donor kidney transplantation in 114 patients over age 60. Surgery 142: 514 523; discussion 523 e511 e512, 2007

37. Lebranchu Y, Halimi JM, Bock A, Chapman J, Dussol B, Fritsche L, Kliem V, Oppenheimer F, Pohanka E, Salvadori M, Soergel M, Tufveson G: Delayed graft function: Risk factors, consequences and parameters affecting outcome-results from MOST, A Multinational Observational Study. Transplant Proc 37: 345347, 2005 38. Vincent JL, De Backer D: Does disseminated intravascular coagulation lead to multiple organ failure? Crit Care Clin 21: 469 477, 2005 Received: August 19, 2010 Accepted: December 16, 2010 Published online ahead of print. Publication date available at www.cjasn.org.