Prediction of Kidney Transplant Outcome by Donor Quality Scoring Systems: Expanded Criteria Donor and Deceased Donor Score

Prediction of Kidney Transplant Outcome by Donor Quality Scoring Systems: Expanded Criteria Donor and Deceased Donor Score A. Arnau, E. Rodrigo, E. Miñambres, J.C. Ruiz, M.A. Ballesteros, C. Piñera, G. Fernandez-Fresnedo, R. Palomar, and M. Arias ABSTRACT Due to disparity between organ supply and demand, use of kidneys from suboptimal donors has become increasingly common. Several donor quality systems have been developed to identify kidneys with an increased risk for graft dysfunction and loss. The purpose of our study was to compare the utility of Deceased Donor Score (DDS) and expanded criteria donor (ECD) status to predict kidney transplant outcomes in a single center. We analysed 280 deceased donor renal transplantation procedures, collecting data from the prospectively maintained institutional database. Kidney transplant outcome variable included delayed graft function, 1-year glomerular filtration rate (GFR1y), and death-censored graft loss (DCGL). Kidneys were obtained from marginal donors in 45.7% of transplant recipients by DDS and in 24.9% by ECD. DDS-defined marginal donors suffered delayed graft function (DGF) more frequently than nonmarginal donors (40.8% vs 25.0%; P ⫽ .006), whereas ECD did not develop DGF at a greater rate. GFR1Y was significantly worse among patients receiving kidneys from marginal donors: DDS 40.3 ⫾ 12.9 vs 57.7 ⫾ 19.4 mL/min/1.73 m2 (P ⬍ .001) and ECD 39.4 ⫾ 14.1 vs 53.8 ⫾ 19.1 mL/min/1.73 m2 (P ⬍ .0001). The most severe donor category defined by DDS (grade D) showed an independently worse death-censored graft survival hazard rate [HR] 2.661, 95% confidence interval [CI], 1.076 – 6.582; P ⫽ .034). DDS and ECD scoring systems are based on donor information available at the time of transplantation that predict 1-year graft function. Moreover in our center, DDS was better to predict DGF and death-censored graft survival than ECD. HE increased disparity between the demand for kidney transplantation and the availability of suitable organs, has caused the number of patients awaiting renal transplantation to increase progressively in recent years.1 Due to this disparity, the use of kidneys from suboptimal donors has become increasingly common. In the early 2000s, the concept of expanded criteria donors (ECD) was defined to include older individuals with hypertension, diabetes, or renal dysfunction, who were expected to produce allografts at greater risk of graft loss than standard donors, albeit sufficiently adequate for transplantation.2 However, now there are no unequivocal definitions of adequate versus marginal donors. Several donor score systems have been developed to improve the stratification and identification of deceased donor kidneys showing an increased risk for graft dysfunction and loss: the deceased donor score (DDS), the donor risk score, and the kidney donor risk index.2–5 The purpose of our study was to compare the utility of the DDS

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and the ECD status to predict kidney transplant outcomes in a single center. METHODS We analyzed 280 deceased-donor adult renal transplantation that had adequate data and were performed in our hospital from 1996 to 2006. Patients were excluded if they underwent a pre-emptive transplantation and additional organ transplantation other than kidney or if they lost the graft in the first 5 days due to vascular thrombosis. Recipient, donor, and transplantation variables were From the Nephrology Service (A.A., E.R., J.C.R., C.P., G.F.-F., R.P., M.A.), and Intensive Care Unit (E.M., M.A.B.), University Hospital “Marqués de Valdecilla,” University of Cantabria, ISCIII (REDINREN 06/16), Fundación Marqués de Valdecilla-IFIMAV, Santander, Spain. Address reprint requests to Alvaro Arnau, Servicio de Nefrologia, Hospital Universitario Marques de Valdecilla, Avda Valdecilla s/n, 39008, Santander, Spain.

© 2012 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710

0041-1345/–see front matter http://dx.doi.org/10.1016/j.transproceed.2012.09.061

Transplantation Proceedings, 44, 2555–2557 (2012)

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collected from a prospectively maintained database of all renal transplant recipients and brain-dead donors in the intensive care unit (ICU) of our hospital. Both databases were matched anonymously by the hospital donor’s number. Kidney transplant outcome variables included delayed graft function (DGF), which was defined as dialysis requirement during the first week postoperatively, 1-year glomerular filtration rate (GFR1y) estimated by the MDRD-abbreviated equation (Modification of Diet in Renal Disease), chronic kidney disease stage 4 (CKD4) defined by a GFR1y ⬍30 mL/min, and death-censored graft loss (DCGL). DDS and ECD were defined according to previously reported criteria.2,3 Deceased donor kidneys were stratified by cumulative DDS: grade A, 0 –9 points; grade B, 10 –19; grade C, 20 –29; and grade D, 30 –39; marginal donors, according to DDS were those included in C and D grades. The study was conducted according to the guidelines of the Declaration of Helsinki and approved by the ethical committee of our hospital. Continuous variables were analyzed using Student t test; categorical data were analyzed using the chi-square test. Pearson correlation was used to describe the relationship between DDS score and GFR1y. Discrimination ability to predict CKD4 was estimated using receiver operating characteristics (ROC) curve c statistic. Cox model was used to calculate hazard ratios (HR) of DCGL associated with DDS and ECD criteria. P ⬍ .05 was reported to be statistically significant. Statistical analyses were performed with SPSS, version 15.0 (SPSS Inc, Chicago, Ill, United States).

RESULTS

Recipient, donor, and transplantation characteristics are shown in Table 1 Kidneys were obtained from marginal donors in 45.7% of cases in accord with DDS, whereas only 24.9% as defined by ECD. There was substantial agreement (kappa index ⫽ 0.598; P ⬍ .001) between both scores to define marginal donors. All ECD were identified to be marginal donors by DDS score, whereas 54/206 (26.2%) non-ECD were marginal by DDS. DDS-defined marginal Table 1. Recipient, Donor, and Transplantation Characteristics N

Recipient age (y) Recipient gender (male) Diabetes mellitus recipient Peak PRA (%) HLA mismatches Number of transplantations ⬎1 Donor age (y) Last donor creatinine (mg/dL) Donor death cause (stroke) DGF 1-year acute rejection 1-year serum creatinine (mg/dL) 1-year MDRD (mL/min/1.73 m2) CKD4 at 1 y ECD DDS DDS marginal DDS grade D Abbreviation: PRA, panel reactive antibody.

47 ⫾ 13 68.6% 12.9% 10.9 ⫾ 20.4 3.5 ⫾ 1.1 27.8% 44 ⫾ 16 1.1 ⫾ 0.5 55.4% 32.2% 31.4% 1.7 ⫾ 0.9 83 ⫾ 33 12.7% 24.9% 17.1 ⫾ 9.6 45.7% 8.2%

donors suffered DGF more frequently than nonmarginal donors (40.8% vs 25.0%; P ⫽ .006). By contrast, ECD did not develop DGF at a higher rate than standard donors (33.3% vs 31.8%; P ⫽ .814). Moreover, the DGF rate was higher by each grade of DDS (20.8%, 29.2%, 41.8%, and 36.3%; P ⫽ .031). GFR1y was significantly worse among patients receiving kidneys from marginal than standard donors: DDS–marginal donors 40.3 ⫾ 12.9 vs 57.7 ⫾ 19.4 mL/min/1.73 m2 (P ⬍ .001) and ECD–marginal donors 39.4 ⫾ 14.1 vs 53.8 ⫾ 19.1 mL/min/1.73 m2 (P ⬍ .001). GFR1y was worse for each DDS class (64.2 ⫾ 18.9, 51.8 ⫾ 18.1, 40.5 ⫾ 12.6, 39.2 ⫾ 14.3 mL/min/1.73 m2, analysis of variance [ANOVA] P ⬍ .001). DDS value was inversely related to 1-year renal function (r ⫽ ⫺0.517; r2 ⫽ 0.267; P ⬍ .001). Similarly, marginal donors defined by both criteria were related to a GFR1y ⬍ 30 mL/min/1.73 m2 (marginal– DDS 19.2% vs 7.8%; P ⫽ .010; ECD 25.9% vs 8.2% P ⫽ .001). Area under the ROC curve of DDS to predict CKD4 at 1 year was 0.696 (95% confidence interval [CI], 0.593– 0.799; P ⫽ .001). Last, after adjusting by recipient age, DGF, acute rejection episodes, mismatches, and peak panel reactive antibody (PRA) neither ECD. (HR 1.430; 95% CI, 0.845–2.419; P ⫽ .182) nor DDS-defined marginal donors (HR 1.333; 95% CI, 0.723– 2.459; P ⫽ .357) were significantly related to DCGL. By contrast, the most severe donor category defined using DDS (grade D) showed an independently worse death-censored graft survival (5-year graft survival rate, 57% vs 73%; HR 2.661; 95% CI, 1.076 – 6.582; P ⫽ .034). DISCUSSION

Both ECD and DDS-defined marginal donors were related to 1-year graft function in our study. DDS was specifically developed to predict renal function measured as creatinine clearance at 6 months, whereas ECD was designed as a predictor of graft loss.2,3 Moore et al also reported that ECD and DDS were related to 1-year renal function, but, different from us, they observed ECD to perform better than DDS.6 One important advantage of DDS is that it provides a quantitative approach to evaluate marginal kidneys. In this sense, each more severe grade of DDS showed a lower GFR1y and a higher rate of CKD4. The high Pearson correlation value indicated that DDS influenced more than 25% of the variability of GFR1y because 1-year renal function is one of the main determinants of long-term graft outcome. But in our single-center study DDS performed better than ECD to predict short-term and long-term kidney allograft outcomes. On the one hand, DDS was and ECD was not related to DGF development. On the other hand, the most severe grade of DDS was independently related to further graft loss, a finding similar to the original report.3 To conclude, DDS and ECD scoring systems are based on donor information available at the time of transplantation. They show predictive ability to estimate 1-year graft function. Moreover, DDS was better related to DGF and

DONOR QUALITY SCORING SYSTEMS

death-censored graft survival than ECD in our center. DDS provided a quantitative approach to evaluate the impact of marginal donors on graft outcomes and can help to improve renal allocation. REFERENCES 1. Perico N, Ruggenenti P, Scalamogna M, et al: Tackling the shortage of donor kidneys: how to use the best that we have. Am J Nephrol 23:245, 2003 2. Port FK, Bragg-Gresham JL, Metzger RA, et al: Donor characteristics associated with reduced graft survival: an approach

2557 to expanding the pool of kidney donors. Transplantation 74:1281, 2002 3. Nyberg SL, Matas AJ, Kremers WK, et al: Improved scoring system to assess adult donors for cadaver renal transplantation. Am J Transplant 3:715, 2003 4. Schold JD, Kaplan B, Baliga RS, et al: The broad spectrum of quality in deceased donor kidneys. Am J Transplant 5:757, 2005 5. Rao PS, Schaubel DE, Guidinger MK, et al: A comprehensive risk quantification score for deceased donor kidneys: the kidney donor risk index. Transplantation 88:231, 2009 6. Moore 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 87:578, 2009