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Volume: 12 Issue: 6 December 2014

FULL TEXT

ARTICLE
The Effect of Donor-Recipient Body Surface Area Ratio on Donor Age and Donor Glomerular Filtration Rate in Chinese Patients Undergoing a Living-Donor Kidney Transplant

Objectives: The purpose of this study was to evaluate the effect of donor-recipient body surface area ratio on donor age and donor glomerular filtration rate in living-donor kidney transplant.

Materials and Methods: This retrospective study included 254 rejection-free patients who underwent their first living-donor kidney transplant at our center between April 2007 and April 2011. We performed multivariate linear regression and receiver operating characteristic curve analyses to determine independent associations and the cumulative effects on posttransplant graft function and outcomes in persons in China who had a living-donor kidney transplant.

Results: In multivariate linear regression, donor age, donor estimated glomerular filtration rate, and donor-recipient body surface area ratio were inde-pendent predictors of 1-year graft function. Linear regression showed that correcting donor age by donor-recipient body surface area ratio increased the strength of the correlation between donor age and 1-year graft function. In the older group (donor age ≥ 45 y), the effect of donor-recipient body surface area ratio on graft function was stronger. By considering the 1-year donor estimated glomerular filtration rate in 2 groups (< 60 or ≥ 60 mL/min/1.73 m2), the cutoff values for corrected donor age was 55 years and donor estimated glomerular filtration rate before surgery was 113 mL/min/1.73 m2.

Conclusions: By correcting for donor-recipient body surface area ratio, donor age accurately predicted and correlated better with 1 year graft function. During preoperative evaluation donor and recipient body surface area matching may be useful.


Key words : End-stage renal disease, Treatment, Rejection, Survival

Introduction

Kidney transplant is the treatment of choice for end-stage renal disease (ESRD) with regard to the quality of life and patient survival. However, the high demand for organs and limited supply is a problem in China. China has the second largest population of ESRD in the world.1 The prevalence of ESRD in China is approximately 300 per million.2 With help from family members, the annual number of living-donor kidney transplants in China has increased during the last decade.

With the developments in transplant technology and new immunosuppressive agents, the frequency of acute rejection has decreased after kidney transplant. However, long-term graft survival has not improved.3 Patients who have graft failure may resume dialysis, increasing the organ wait list and the gap between supply and demand.

Immunologic risk factors may contribute to chronic allograft dysfunction. In addition, many nonimmunologic risk factors have a detrimental effect on long-term graft survival.4 These risk factors include donor age, sex, body mass index, kidney size, race difference, and sex disparity.5-9 However, few studies have longitudinally correlated graft function with descriptive models of donor and recipient characteristics in the Chinese population.

The purpose of this study was to analyze donor and recipient demographic and laboratory characteristics and identify possible independent associations and cumulative effects on posttransplant graft function and outcomes in Chinese living-donor kidney transplants.

Materials and Methods

Patient population
Between April 2007 and April 2011, there were 310 living-donor kidney transplants performed at the Kidney Disease Center, First Affiliated Hospital, Medical College of Zhejiang University, Zhejiang, China, and 254 of these transplants were included in this study. Included recipients were Chinese adults (age > 18 y) with a minimum 1-year follow-up with functioning allografts and no episodes of rejection. The other 56 patients were excluded because they had ≥ 1 episode of acute rejection in the first year (35 patients [11%]), incomplete data (9 patients), multiple organ transplants (5 patients), age < 18 years (4 patients), or revision kidney transplant (3 patients). Study entry was defined by the day of transplant. Duration of follow-up was 14 to 63 months (range, 35 ± 14 mo). Data were obtained from the transplant database at our center. All patients received triple immunosuppressive therapy con-sisting of cortico-steroids, mycophenolate mofetil, and cyclosporine or tacrolimus.

This retrospective study was approved by the Ethics Committee on Organ Transplantation of First Affiliated Hospital of Zhejiang University and was performed in accordance with the Declaration of Helsinki. Before transplant, the identities of the donors and recipients were validated, and written informed consent was obtained. According to Chinese law for transplants, all living kidney transplants at our center were performed only between spouses, lineal blood relatives, or collateral blood relatives up to the third degree of kinship of the recipient.

Variables and definitions
The following preoperative variables were collected at the time of transplant: donor demographics (age, sex, body mass index [BMI], and body surface area [BSA]) and fasting laboratory variables (serum creatinine, estimated glomerular filtration rate [eGFR], and glucose); recipient demographics, laboratory and clinical history data (including cause of ESRD, hemoglobin, albumin, pretransplant dialysis modality, panel reactive antibody [PRA], and serum hepatitis B virus [HBV] surface antigen); donor-recipient matching variables (donor-recipient BSA ratio, BMI ratio, human leukocyte antigen [HLA] mismatches, and donor-recipient relationship). Serum creatinine was measured in all patients at months 1, 3, 6, 9, and 12 after transplant and annually thereafter until the recipient had graft failure or was lost to follow-up. The eGFR at all data collection points was calculated according to the abbreviated Modification of Diet in Renal Disease study equation.10 The BSA was calculated for all recipients and donors using height and weight values obtained at the time of transplant, according to the Mosteller formula: BSA (m2) = ([height (cm) × weight (kg)]/3600)1/2; the donor-recipient BSA ratio (D/R BSA ratio) was calculated for each transplant.11

We performed continuous linear correlation analysis of all variables. To facilitate analyses and interpretation of the results, data were divided into subgroups. Patients were stratified into 2 groups according to the mean (± SD) donor age: < 45 years and ≥ 45 years. The transplants were divided into 3 groups based on the D/R BSA ratio ≤ 0.9 (group 1), 0.91 to 1.09 (group 2), and ≥ 1.1 (group 3). In group 2, donor and recipient BSA were approximately equal. In group 3, the donor BSA was ≥ 10% compared with the recipient BSA. According to 1-year eGFR, posttransplant patients were classified into 2 groups: < 60 mL/min/1.73 m2 and ≥60 mL/min/1.73 m2.

The corrected donor GFR was calculated accor-ding to the equation: corrected donor eGFR = donor eGFR × D/R BSA ratio. In addition, donor age was corrected according to the equation: corrected donor age = donor age/(D/R BSA ratio).

Statistical analyses
Statistical analyses were performed with software (SPSS, version 17.0, SPSS Inc., Chicago, IL, USA). Data were reported as mean ± SD (minimum-maximum) for continuous variables and number (%) for categorical variables, unless otherwise stated. Numeric differences between the 2 groups were assessed with the t test. According to Kolmogorov-Smirnov test, numeric variables were normally distributed. Analysis of variance was used to compare data between several groups. Post hoc tests were used when appropriate.

For statistical evaluation, the Pearson product moment correlation was used. The multiple linear regression model was applied to study independent associations of donor and recipient variables with eGFR at 1 year after transplant. We performed a receiver operating characteristic (ROC) curve analysis to define the cutoff value. Statistical significance was defined by P < .05.

Results

Donor and recipient characteristics
In the 254 pairs of living donors and recipients, most donors were women and most recipients were men (Table 1). Many recipients (8.7%) were serum HBV positive (Table 1). Regarding pretransplant immu-nologic factors, 2.4% recipients were PRA positive and 20.5% were all HLA matches. Most recipients had hemodialysis before transplant (Table 1). The living donors were blood relatives (91.3%) or spouses (8.7%), and 123 donors (48.4%) were mothers of recipients. The mean eGFR at 1 year after transplant was 75 ± 18 mL/min/1.73 m2.

Donor age, donor estimated glomerular filtration rate, and donor/recipient body surface area ratio as independent correlates of posttransplant graft function
Univariate analyses showed that donor age was significantly inversely correlated with 1-year eGFR after transplant (Table 2). Donor variables associated with size or function of the donor kidney were positively correlated with 1-year eGFR including male sex, donor BSA, and donor eGFR. The D/R BSA ratio was significantly correlated with 1-year eGFR after transplant (Table 2). An association was observed between preemptive transplant and 1-year eGFR (Table 2). However, no correlation was present between pretransplant immunologic factors (PRA positive or HLA mismatches) and 1-year eGFR after transplant. Multivariate linear regression showed that donor age, donor eGFR, and D/R BSA ratio were independent predictors of graft function (Table 2).

Corrected donor estimated glomerular filtration rate and age
Donor pretransplant eGFR (uncorrected) was significantly correlated with posttransplant 1-year eGFR (r = 0.306; P < .001) (Figure 1). Linear correlation analysis showed that the correlation was stronger between corrected donor eGFR (r = 0.395; P < .001) than uncorrected eGFR and 1-year graft function.

Donor age (uncorrected) was significantly inversely correlated with posttransplant 1-year eGFR (r = -0.382; P < .001). The correlation was stronger between corrected donor age (r= -0.421; P < .001) and 1-year posttransplant eGFR than with uncorrected donor age (Figure 2).

By stratified analysis, the effect of the D/R BSA ratio on graft function in the older group was shown as donor age ≥ 45 years (Figure 3). In the subgroup of donor age ≥ 45 years, 1-year posttransplant eGFR was significantly better with D/R BSA ratio ≥ 1.1 (79 ± 18 mL/min/1.73 m2) than D/R BSA ratio ≤ 0.9 (64 ± 10 mL/min/1.73 m2; P < .001).

In multivariate linear regression, the corrected donor age (r = -0.552; P ≤ .001) and corrected donor eGFR (r = 0.219; P ≤ .001) were independent predictors of 1-year posttransplant eGFR.

Receiver operating characteristic curve analysis of correcting donor age and donor estimated glomerular filtration rate
Patients were divided into 2 groups according to 1-year posttransplant eGFR (< 60 or ≥ 60 mL/min/1.73 m2). We performed a ROC curve analysis of corrected donor age and corrected donor eGFR to screen the cutoff value. The ROC curve analysis (Figure 4) showed that cutoff value for corrected donor age was 55 years and corrected donor eGFR was 113 mL/min/1.73 m2. Area under the ROC curve of corrected donor age was 0.704 (sensitivity, 53%; specificity, 78%); area under the ROC curve of corrected donor eGFR was 0.648 (sensitivity, 55%; specificity, 70%).

Discussion

The present study confirmed and extended our previous work about donor age, donor eGFR, and D/R BSA ratio that showed that these variables are independent correlates of recipient kidney allograft function at 1 year after transplant. In addition, D/R BSA ratio had a consistent effect on early graft function after surgery. Although organs were obtained from living donors with large BSA, recipients who had small BSA had better graft function.

Kidney function within the first year after transplant is an important parameter that affects long-term graft survival.12,13 Previous studies suggested that changing eGFR during the first year is critically important for long-term survival.14 A better understanding of the effect of clinical factors on early graft function may lead to better outcomes after kidney transplant.

In addition, the D/R BSA ratio was an important factor associated with graft function. By correcting for the D/R BSA ratio, donor age and donor eGFR had stronger correlations with 1-year graft function. In older patients (donor age ≥ 45 y), the effect of the D/R BSA ratio on graft function was stronger. When we divided the 1-year eGFR into 2 groups (< 60 or ≥ 60 mL/min/1.73 m2), the cutoff value for corrected donor age was 55 years and corrected donor eGFR 113 mL/min/1.73 m2.

The hyperfiltration hypothesis states that insufficient nephron mass may not meet the metabolic demands of kidney recipients and may cause hyperfiltration injuries.15 A small donor kidney in a large recipient maybe a major risk factor for allograft failure. A larger nephron reserve may tolerate ischemic, toxic, or early immune injury and may provide enough filtration to sustain graft function. Measuring the graft kidney weight as a measure of nephron mass may be done during transplant but cannot be done before surgery to match donor kidney to recipient body size. Previous studies have provided some evidence of an effect of relative donor/recipient size on graft and patient outcomes, but few studies have investigated the longitudinal association between graft function and donor/recipient size with descriptive models.8,16 The present results show that 1-year graft function without rejection may be estimated before transplant by combining donor age, donor eGFR, and the correcting effect of the D/R BSA ratio. Routine assessment of these characteristics before living-donor transplant may better predict allograft success.

Current evidence shows that donor age is a strong determinant of graft function and graft survival in living-donor kidney transplant.17 However, because of the increased shortage of donors and the aging population, numerous centers have begun to use older living-donor kidneys. Many studies have shown that older living-donor kidneys may be transplanted with low perioperative risk without compromising recipient short-term and long-term graft survival or donor renal function.18,19 The question of how to improve graft function from older donors is poorly understood. The present data show that the effect of the D/R BSA ratio on graft function is important in the older group (donor age ≥ 45 y). With older donors, a larger D/R BSA ratio may improve graft function. The early graft function predicted by using uncorrected donor age and D/R BSA ratio also may be useful in the evaluation of donors before transplant.

To reduce the gap between supply and demand for kidney transplant, the Chinese Ministry of Health and the Chinese Red Cross Society announced the start of a system for organ donation in 11 provinces in August 2009 and extended this system over the entire country in 2010.20 The program of donation after cardiac death may help solve the organ shortage in China. Until September 2012, there have been > 400 kidney transplants from donors after cardiac death. In the process of donation after cardiac death, we have encountered some problems including marginal kidneys from older donors. Some studies have described that dual transplant of marginal kidneys may provide improved filtration.21

Limitations of the present study include the retrospective study design from a single center with short follow-up. We could not state with certainty that improving the D/R BSA matching predicts long-term graft function and outcome in living-donor kidney transplants. Donor GFR before donation and graft function were assessed by estimation equations. However, in kidney transplants, the Modification of Diet in Renal Disease equation has been validated as an accurate indicator of estimated kidney function and is better than other formulas.22 In addition, the older living donors were 45 to 66 years, and we do not know whether this result is consistent for older donors than donors in this cohort and in the donation after cardiac death cohort.

In summary, the present study showed that preoperative independent predictors of graft function after living-donor kidney transplant include donor age, donor eGFR, and the D/R BSA ratio. When donor age is correcting with the D/R BSA ratio, donor age may correlate better and more accurately predict 1-year graft function. During preoperative evaluation, the D/R BSA ratio may be useful in selecting older donors.


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Volume : 12
Issue : 6
Pages : 515 - 521
DOI : 10.6002/ect.2013.0258


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From the Kidney Disease Center, The First Affiliated Hospital, College of Medicine, Zhejiang University; Key Laboratory of Multiple Organ Transplantation, Ministry of Health, Hangzhou, Zhejiang, China
Acknowledgements: The authors have no conflicts of interest to disclose, and there was no funding for this study.
Corresponding author: Jianyong Wu, The First Affiliated Hospital, College of Medicine, Zhejiang University, Kidney Disease Center, 79 Qingchun Rd, Hangzhou, Zhejiang 310003 China
Phone: +86 13 48 618 3516
Fax: +86 0571 8723 6189
E-mail: wujianyong@medmail.com.cn