EXPERIMENTAL AND CLINICAL TRANSPLANTATION

Objectives: Our objective was to evaluate the effect of kidney graft weight-to-recipient body weight ratio as a nonimmune factor that may affect long-term graft function.

Materials and Methods: We retrospectively collected data from 2531 living donor kidney transplant procedures performed between 1994 and 2010 at Shahid Labbafinejad Medical Center; 635 patients were included in this study. Each kidney was weighed after cold wash. The kidney weight-to-recipient body weight ratio was calculated. As an indicator of graft function, we used the Modification of Diet in Renal Disease Study Group equation to estimate glomerular filtration rate. For statistical analyses, we used simple linear regression analysis and the mixed model test using SPSS version 17.0 software (SPSS, Chicago, IL, USA).

Results: Mean age of recipients and median follow-up duration were 37.5 years (range, 6-77 y) and 36 months (range, 25-84 mo). Long-term graft function showed a positive correlation with kidney graft-to-recipient body weight ratio but not with the graft weight alone. The magnitude of this correlation was higher early after surgery (day 7) and decreased with long-term follow-up but was still statistically significant (P < .001).

Conclusions: From our results, we conclude that kidney graft-to-recipient body weight ratio is correlated with the kidney graft function; graft size matching may be considered for kidney donor selection.

Key words : Body mass index, Graft survival, Kidney transplantation

Despite the success of modern transplant, which can produce early acute rejection rates below 15% and 1-year graft survival rates above 90%, long-term graft attrition rates have remained unchanged at 4% graft loss per year.^1,2

Progressive renal transplant dysfunction often leads to graft failure and return to dialysis, accompanied by substantial morbidity and mortality. Kidney allografts are damaged from both immune and non-immune mechanisms. Immune injury from acute or chronic rejection and nonimmune causes such as calcineurin inhibitor nephrotoxicity, ischemia-reperfusion injury, and recurrent glomerular diseases are potential threats that can reduce kidney graft functional mass resulting in chronic graft failure.

The histopathology of a chronically failing allograft usually shows interstitial fibrosis, tubular atrophy, glomerulosclerosis, and vascular abnormalities. These features represent the summated effects of tissue injury from multiple pathogenic insults combined with the kidney’s fibrotic healing response.³ Hyperfiltration injury from inadequate nephron mass may cause progressive injury in transplanted kidneys.⁴ A recent study on functional nephron mass suggested that incompatibility between kidney graft weight and recipient body weight was an independent predictor of long-term renal allograft survival.^5-7

The purpose of this study is to evaluate the effect of kidney graft weight-to-recipient body weight ratio as a nonimmune factor that may affect long-term graft function.

Materials and Methods

We retrospectively collected data from 2531 living-donor kidney transplant procedures performed between 1994 and 2010 in Shahid Labbafinejad Medical Center. We included a total of 635 consecutive patients with living unrelated kidney transplants having graft weight data available for this study. Our exclusion criteria were renal transplant donations from deceased donors, second transplants, major surgical complication such as arterial and venous thrombosis in early postoperative periods (up to 90 days) and episodes of acute or subacute rejections. Each kidney was weighed on the same electronic weighing scale after cold perfusion with 1000 mL solution and back-table surgery. The immunosuppression protocols in all of the patients were either a cyclosporine-based or tacrolimus-based regimens. We used the Modification of Diet in Renal Disease Study Group equation to estimate glomerular filtration rate (eGFR) as an indicator of graft function. The kidney weight-to-recipient body weight ratio was calculated.

Simple linear regression analysis was used to evaluate the correlation between kidney weight and recipient body weight ratio and eGFR. Mixed model was used to evaluate the independent risk factors for long-term graft function according to time in a multivariate model. Variables that were statistically significant in univariate analysis were included in the mixed model. We used SPSS version 17.0 software (SPSS, Chicago, IL, USA) to perform the statistical analyses. P values < .05 were considered statistically significant.

A total of 635 patients (413 male and 222 female patients) were analyzed. The mean (range) recipient age, donor age, and body weight results were 37.5 years (6-77 y), 28.2 years (4-62 y), and 62 kg (14.2-107 kg). Donors included 515 male donors (81%) and 120 female donors (19%). The mean (range) graft kidney weight measured before implantation was 192.3 g (118-350 g) (Table 1). Most procedures (93%) were living unrelated kidney transplants, and the main immunosuppression protocol was cyclosporine plus mycophenolate mofetil plus corticosteroids. The eGFR results calculated by the Modification of Diet in Renal Disease Study Group equation at day 7 and at 1, 6, 12, and 36 months after kidney transplant were positively correlated with graft weight-to-recipient body weight ratio.

We used the mixed-effects model to identify factors that affected the eGFR over time. In univariate analysis, age, delayed graft function, recipient body mass index, sex, kidney weight, and graft-to-body weight ratio were associated with eGFR. To identify independent factors that affect the eGFR, multivariate analysis using a mixed model was applied. Age (P < .001) and graft-to-body weight ratio (P < .001) were independent factors that affected the eGFR. According to the mixed-effects model, eGFR values decreased over time.

Long-term graft function showed a positive correlation with graft weight-to-recipient body weight ratio but not with graft weight alone. The magnitude of this correlation was higher early after surgery (day 7) and decreased with long-term follow-up, with the correlation still statistically significant at the end of the study. The coefficient of determination was highest at day 7 (P < .001), decreasing after follow-up examination (P < .001) (Figures l-2-3-4-5).

There are some controversies regarding the use of kidneys from small donors for larger recipients. The association between the functional nephron mass and the graft function in kidney transplant has been analyzed in various ways. This study aimed to show the effect of kidney weight-to-recipient body weight ratio on long-term graft function. Size matching between a donor kidney and recipient body weight is considered to promote short- and long-term graft function. The results of the present study correspond well with those of the investigation from Song and associates in which the kidney weight-to-recipient body weight ratio was correlated with long-term graft function.⁴ They concluded that the kidney graft-to-body weight ratio is an important factor for long-term graft function. However, it did not significantly affect long-term graft survival.

Lee and associates reported that living donor kidney volume may have a significant and independent effect on the 6-month posttransplant graft function.⁵ In addition to this, Hwang and associates reported that the graft weight-to-recipient body weight ratio is an important factor for long-term graft survival and early graft function but it did not significantly affect subsequent renal function.⁶ These findings differ from those that claim that the kidney weight-to-recipient body weight ratio is an independent predictor of long-term graft survival. However, those authors explained that the clinical importance of the aforementioned ratio as an independent factor influencing graft survival is comparable to that of the presence of an acute rejection episode or of a delayed graft function after transplant.^7-9 Therefore, the kidney weight-to-recipient body weight ratio may help to improve late clinical outcome when the early benefit of preventing acute rejection is censored. When we adjusted for time using the mixed-effects model in our series, the independent factors associated with long-term graft function were donor age and graft weight-to-recipient body weight ratio.

Dick and colleagues demonstrated that a low donor-to-recipient body surface area ratio was associated with an increased risk of graft loss. Appropriate size matching conferred better long-term graft survival in adolescents receiving living donor kidney transplants.¹⁰ In another study, donor-to-recipient body weight mismatch may have affected glomerular enlargement and increased proteinuria 1 year after kidney transplant. How these two features affect long-term graft survival and function must be addressed in the future.¹¹ Likewise, in the study of Seo and associates, nephron mass (donor kidney weight-to-recipient body weight ratio) was an independent risk factor for graft failure.¹² Another study indicated that kidney graft weight can be estimated by donor sex and body mass index; results of this study demonstrated that graft weight is an important factor in the prediction of renal function 12 months after transplant, and it can be a useful parameter during the selection process of recipients.¹³ Our findings were nearly similar to the results of the aforementioned study.

In contrast to the findings mentioned above, Akoglu and colleagues revealed that transplant kidney volume-to-recipient body weight ratio is not associated with long-term allograft function in living donor kidney transplant.¹⁴ In a study from Gaston and associates, multivariate analyses of 17 variables showed that donor-to-recipient body surface area did not affect risk allograft loss. These data indicated that including nephron mass as a criterion for allocation of deceased organs is unlikely to improve long-term results in renal transplant.¹⁵

From our results, we conclude that the graft weight-to-recipient body weight ratio is correlated with long-term kidney graft function, and graft size matching may be considered for kidney donor selection.

Volume: 15 Issue: 5 October 2017

FULL TEXT