- Email: [email protected]
Is the Graft Function of Living Donor Renal Transplants Associated With Renal Mass Matching by Computed Tomography Angiographic Volumetry?
Is the Graft Function of Living Donor Renal Transplants Associated With Renal Mass Matching by Computed Tomography Angiographic Volumetry? J.Y. Choi and O.J. Kwon ABSTRACT Background. Donor renal volume, which can be easily measured by computerized tomographic angiography with 3-dimensional reconstruction, may influence graft outcomes. Low functional renal mass and donor kidneyerecipient body size mismatch can lead to progressive renal injury and poor graft function. Materials and methods. This singleecenter retrospective analysis of 51 consecutive living donor renal transplantations performed between January 2005 and December 2011 defined transplant renal volume per unit recipient body surface area (BSA; mL/m2). The patients were divided into 2 groups: group I (n ¼ 31, donorerecipient BSA ratio 1) and group II (n ¼ 20, BSA ratio >1). We analyzed the clinical characteristics and laboratory data of donors and recipients to ascertain correlations with, renal volumes and graft outcomes. Results. The renal volumes of living donors correlated with estimated glomerular filtration ratios (eGFR; r ¼ .314, P ¼ .025). Serum creatinine after renal transplantation correlated with transplanted renal volume at 1, 3, and 12 months (r ¼ .319, P ¼ .048; r ¼ .407, P ¼ .010; r ¼ .472, P ¼ .002). Serum eGFR also correlated with transplanted renal volume at 3 and 12 months after renal transplantation (r ¼ .318, P ¼ .049 and r ¼ .388, P ¼ .015). There were no significant differences between groups for acute or chronic rejection, infection or delayed graft function. However, serum creatinine levels were higher (P ¼ .011, P ¼ .022, and P ¼ .007) and serum eGFR significantly lower in group I at 1, 3, 6, and 12 months after renal transplantation (P ¼ .036, P ¼ .042, P ¼ .042, and P ¼ .049, respectively). There was no significant difference in graft survival. Conclusions. Renal volume of living donors may reflect renal function and have a significant impact on graft outcomes. Renal volume matching should be considered to select donorerecipient pairs for living donor renal transplantation.
R
ENAL TRANSPLANTATION is considered the treatment of choice for end-stage renal disease (ESRD), because of better survival and improved quality of life compared with dialysis treatment.1 Short-term allograft outcomes have been significantly improved during the past decade due to advances in the use of immunosuppressants.2 Long-term allograft outcomes have also improved somewhat as a result of efforts to identify donorerecipient factors that affect graft function, although many questions remain unanswered.1,3,4 The numbers of ESRD patients awaiting renal transplantation are increasing, while the donor pool remains small.2 The increasing disparity between supply and demand
for organs, had led to increased living donor renal transplantations using extended criteria or exchange programs.2 In addition, ensuring the quality of donated organs and improving their function are of critical importance.3 Some studies have identified donorerecipient factors that contribute to grafts quality,3,5,6 including the volume and
From the Department of Surgery, College of Medicine, Hanyang University, Seoul, Korea. Address reprint requests to Oh Jung Kwon, MD, 17 Haengdang-dong, Seongdong-ku, Seoul 133-792, Korea. E-mail: [email protected]
ª 2013 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/13/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2013.08.045
Transplantation Proceedings, 45, 2919e2924 (2013)
2919
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CHOI AND KWON Table 1. Baseline Characteristics of Donor and Recipients According to Donor-to-Recipient BSA Ratio
Recipient age (ys) Donor age (ys) Recipient BSA (m2) Donor BSA (m2) BSA ratio (donor-to-recipient) Preoperative dialysis duration (ms) Absolute donor renal volume (mL) Transplanted renal volume (mL/ m2) Donor serum creatinine (mg/dL) Donor serum eGFR (mL/min) Recipient sex Male Female Donor sex Male Female HLA-AB matching 0 1 2 3 4 HLA-DR matching 0 1 2 Underlying disease HTN DM Acute rejection Present Absent Chronic rejection Present Absent Viral or fungal infection Present Absent Delayed graft function Present Absent
Total, n ¼ 51 (%)
Group I (BSA ratio 1), n ¼ 30 (%)
Group II (BSA ratio > 1), n ¼ 21 (%)
P value
41.87 10.22 41.23 10.68 1.69 0.16 1.67 0.19 1.38 0.16 15.31 22.20 164.03 26.69 98.03 18.71 0.84 0.13 94.54 10.57
39.53 10.52 44.23 10.25 1.74 0.15 1.57 0.12 0.90 0.08 13.47 21.38 154.48 17.98 88.90 10.20 0.80 0.11 92.96 10.14
45.78 8.61 36.22 9.67 1.59 0.12 1.85 0.14 1.16 0.11 18.39 23.82 179.96 31.45 113.23 19.97 0.91 0.13 97.18 11.05
.039 .010 .001 <.001 <.001 .463 .001 <.001 .003 .183
35 (68.6) 16 (31.4)
24 (80.8) 6 (20.2)
11 (52.4) 10 (47.6)
.036
20 (39.2) 31 (60.8)
7 (23.3) 23 (76.7)
13 (61.9) 8 (38.1)
.005
4 (13.3) 4 (13.3) 10 (33.3) 8 (26.7) 4(13.3) 2.13 1.22
1 (4.8) 2 (9.5) 16 (76.2) 2 (9.5) 0 (0) 1.89 0.68
.038
2 (6.7) 26 (86.7) 2 (6.7) 1.00 0.37
2 (9.5) 18 (85.7) 1 (4.8) 1.06 0.24
.902
40 (89.4) 8 (15.7)
21 (70) 6 (20.0)
19 (50.5) 2 (9.5)
.080 .311
2 (3.9) 49 (96.1)
1 (3.3) 29 (96.7)
1 (4.8) 20 (95.2)
.462
2 (3.9) 49 (96.1)
1 (3.3) 29 (96.7)
1 (4.8) 20 (95.2)
.796
8 (15.7) 43 (84.3)
3 (10.0) 27 (90.0)
5 (23.8) 16 (76.2)
.182
1 (2.0) 50 (98.0)
0 (0) 30 (100)
1 (4.8) 20 (95.2)
.227
5 6 26 10 4
(9.8) (11.8) (51.0) (19.6) (7.8)
4 (7.8) 44 (86.3) 3 (5.9)
.378
.573
BSA, body surface area; eGFR, estimated glomerular filtration rate; HTN, hypertension; DM, diabetes mellitus.
function of the donor kidneys. Mai et al suggested that low renal mass was associated with poor graft outcomes because smaller kidneys imply less nephron mass and lower glomerular filtration rates (GFR)din other words, inferior filtering capacity.6 Also, lower nephron mass can result in hyperfiltration as a consequence of immunologic and nonimmunologic injuries, which can lead to graft failure.7 Since preoperative radiologic evaluation computed tomography by (CT) angiography has became routine, donor renal volume can be calculated easily by 3-dimensional reconstruction.8,9 Therefore, we compared donor and recipient characteristics to analyze graft function retrospectively according to renal volume matching, a possible clinical indicator of outcome.
MATERIALS AND METHODS Between January 2005 and December 2011, we performed 56 living donor renal transplantations. We retrospectively reviewed 51 living donors and their recipients, excluding 5 pairs who were lost to followup. All recipients underwent induction therapy with basiliximab followed by immunosuppressive therapy based on a calcineurin inhibitor (cyclosporine or tacrolimus), mycophenolate mofetil, and prednisolone. Baseline characteristics of donor and recipient were collected such as gender, age, body surface area (BSA), donor serum creatinine and estimated GFR (eGFR) HLA antigen mismatch, recipient serum creatinine and eGFR, acute and chronic rejection, viral and fungal infection, as well as delayed graft function. Acute rejection episodes were suggested by an unexplained rise in serum creatinine. Percutaneous renal biopsy and renal duplex scan were
RENAL MASS MATCHING performed to confirm the diagnosis before starting antirejection therapy. Delayed graft function was defined as a need for dialysis within the first week of after transplantation, graft failure, as a return to dialysis, nephrectomy, or retransplantation. All patients underwent CT angiography to evaluate anatomy and volume before transplantation. Preoperative renal volumes were measured from preoperative CT scans obtained with a 64channel helical CT scanner (Brilliance scanner, Philips Healthcare) using 120 kVp and 230 mA. The scan parameters included a 64 0.625-mm collimation, and 1-mm thickness reconstruction. The CT protocol included an unenhanced scan, followed by 2 enhanced scans in the arterial and renal parenchymal phases after injection of contrast medium. The arterial scan was started when bolus-triggering scans showed an aortic attenuation of 150 HU. The scan for the renal parenchymal phase was started about 90 seconds after the initial injection. The examinations were interpreted by an experienced abdominal radiologist. The 3dimensional reconstruction traced the renal parenchyma of each kidney manually. The region of interest (ROI) was drawn around the edges of each kidney, excluding to the collecting system and any renal cyst.10,11 Renal volume was extrapolated by summation of all measured ROIs on Rapido 2.8 (Seoul, Korea, INFINITT Health Care). To compare the effect of renal volume on graft function and control for the size of the recipient, the volume of each transplanted kidney was adjusted for the BSA of corresponding recipient. donated renal volume ðmLÞ Transplanted renal volume mL=m2 ¼ recipient BSA ðm2 Þ The Modification of Diet in Renal Disease (MDRD) formula was used to calculate the eGFR of donor and recipient. eGFR (mL/min) ¼ 170 Serum creatinine0.999 Age0.176 (0.762 if female) (1.180 if black) Blood urea nitrogen0.170 Albumin0.318 BSA was calculated from the Dubois formula. BSA (m2) ¼ 0.20247 height (m)0.725 weight (kg)0.425 The BSA ratio was calculated as donor BSA/recipient BSA. All data were analyzed according to the donorerecipient BSA ratio and compared the characteristics and outcomes between two groups. Analyses were performed using SPSS 18.0 with Student t test for continuous variables and the chi-square test to compare categorical factors. Pearson correlation coefficient was used to determine correlations between quantitative data. Statistical significance was defined as a P value <.05.
RESULTS
Baseline donor and recipient characteristics are shown in Table 1. The mean recipient age was 74.87 10.22 (range, 16e68) years and the mean donor age, 21.23 10.68 (range 20e68) years; 68.6% (n ¼ 35) of the recipients were males, females outnumbered male donors (n ¼ 31, 60.8%). The mean follow-up period was 49.96 22.28 (range, 10e85) months. The acute and chronic rejection as well as delayed graft function rates were 3.9%, 3.9%, and 2.0%, respectively. The frequency of viral and fungal infections was 15.7%. We evaluated whether the transplanted volume reflected donor renal function. Mean absolute donor renal volume
2921
Fig 1. Correlation between transplanted renal volume (absolute donor volume-to-recipient, body surface area; mL/m2) and estimated glomerular filtration rate (eGFR; mL/min) of living donor after renal transplantation.
calculated by CT angiography was 164.03 26.69 (122.30e275.20) mL and mean transplanted renal volume was 98.03 18.71 (69.88e176.41) mL/m2. Transplanted renal volume showed a significant positive correlation (r ¼ .314, P ¼.025) with donor eGFR (Fig 1). To evaluate the correlation between transplanted renal volume and post-transplant recipient graft function, we examined serum creatinine levels and eGFR using the modified MDRD equation at 1, 3, 6, 12, and 36 months. Transplanted renal volume showed a negative correlation with recipient serum creatinine levels at 1, 3, and 12 months (r ¼ .319 [P ¼ 0.48]; r ¼ .407, [P ¼ .010] and r ¼ .472 [P ¼ .002]; Fig 2). eGFR positively correlated with transplanted renal volume at 3 and 12 months (r ¼ .318 [P ¼ .049] and r ¼ .388, [P ¼ .015]; Fig 3). Since there was a relatively large body size disparity between donor and recipients due to there being more female than male donors, we calculated donor-to-recipient BSA ratios to evaluate the impact of this factor. Mean BSA of recipients and donors were 1.69 0.16 (1.39e2.03) m2 and 1.67 0.19 (1.32e2.10) m2 respectively and mean donor-torecipient BSA ratio was 1.38 0.16 (0.73e1.38) m2. Table 1 shows outcomes according to donor-to-recipient BSA ratio group. There were no differences in the rates of acute and chronic rejection, viral or fungal infection, and delayed graft function. However, recipient age was younger and donor age was older in group I (P ¼ .039 and P ¼ .010). Male recipients and female donors were more frequent (80.8% vs 52.4% [P ¼ .036], and 76.7% vs 38.1% [P ¼ .005]) in group I (donor BSA-to-recipients BSA 1) than group II (donor BSAto-recipient BSA > 1). Serum creatinine levels at 3, 6, and 12 months were higher in group I (P ¼ .011, P ¼ .022, and
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CHOI AND KWON
Fig 2. Correlation between transplanted renal volume (absolute donor volume-to-recipient body surface area; mL/m2) and serum creatinine level (mg/dL) after renal transplantation.
P ¼ .007) and serum eGFR at 1, 3, 6, and 12 months after renal transplantation significantly lower in group I (P ¼ .036, P ¼ .042, P ¼ .042, and P ¼ .049; Table 2). There was no significant difference in graft survival between the 2 groups (P ¼ .780). DISCUSSIONS
Many donor and recipient factors influence allograft outcomes. Transplanted renal volume is one of the factors. Renal volume is proportional to nephron number and total number of functioning glomerulae.1,12 Nephron numbers in adults vary even in the absence of renal disease and tend to be lower in females.12,13 Renal development is complete at approximately 34 to 36 weeks of gestation; the number of nephrons does not increase thereafter.14
Transplanted renal volume affects renal function and allograft outcomes.12e14 Larger measured transplanted renal volumes lead to higher GFR.15,16 Hence, BSA or body mass index is considered an important predictor of renal volume and GFR.17 Many studies have demonstrated an effect of renal mass on long-term graft outcomes; smaller renal mass tends to aggravate injury and exacerbate progression of graft failure.3,17 Graft failure is more common when a kidney is transplanted from a small donor into a large recipient compared with size-matched donore recipient pairs.2,4,5 A small renal transplant volume and an insufficient number of functioning nephrons may have too little capacity to respond to the metabolic demands of the recipient.4,18 In addition, immunologic and nonimmunologic events,
Fig 3. Correlation between transplanted renal volume (absolute donor volume-to-recipient body surface area; mL/m2) and estimated glomerular filtration rate (eGFR; mL/min) after renal transplantation.
RENAL MASS MATCHING
2923
Table 2. Comparison of Renal Function of Recipients According to Donor-to-recipient BSA Ratio Total
Recipient serum creatinine (mg/dL) Preoperative 1 mo 3 mo 6 mo 12 mo 36 mo Recipient serum eGFR (mL/min) Preoperative 1 mo 3 mo 6 mo 12 mo 36 mo
8.25 1.47 1.44 1.40 1.30 1.28 8.36 57.49 55.50 58.11 61.07 60.62
BSA ratio 1 (donor-to-recipient)
3.23 0.87 0.37 0.34 0.35 0.36
3.30 15.89 14.86 15.22 15.55 15.78
8.79 1.70 1.58 1.51 1.42 1.38 8.33 52.60 50.79 53.55 56.62 58.14
BSA ratio > 1 (donor-to-recipient)
P value
4.00 1.09 0.29 0.25 0.29 0.36
7.63 1.20 1.28 1.27 1.13 1.16
1.95 0.40 0.40 0.39 0.35 0.34
.248 .074 .011 .022 .007 .054
3.57 10.80 9.13 10.60 12.77 13.38
8.47 63.19 60.99 63.43 66.26 63.50
3.06 19.06 18.33 18.17 17.19 18.16
.935 .036 .042 .042 .049 .297
BSA, body surface area; eGFR, estimated glomerular filtration rate.
such as ischemia-reperfusion injury, HLA mismatch, and donor age, may reduce the initial functioning nephron mass.1,19 To maintain graft function, the remaining nephrons may undertake maladaptive hyperfiltration. Hence, urinary protein excretion by the transplanted kidney is higher early after renal transplantation.17 As a result, glomerular hypertrophy, glomerulosclerosis, interstitial fibrosis, and tubular atrophy develop leading to reduced graft function and poor long-term graft outcomes.1,5,7 Giral et al showed that incompatibility between graft and recipient weight was an independent predictor of long-term outcome. A low ratio of kidney to recipient weight conferred greater risk of proteinuria and glomerulosclerosis and an increased risk of transplant failure within 2 years. In a study by Poggio et al,4 larger transplanted kidney volume adjusted for recipient BSA (cc/1.73 m2) was associated with better 2-year graft function (P < .001) and a lower acute cellular rejection rate (P ¼ .046). However, Tent et al17 supposed that body size disparity impacts gain in graft function after renal transplantation, independent of donor and recipient gender. In their study, a smaller kidney than the recipient adapted with perfusion and filtration to gain more renal function, meeting the new metabolic demands. There were no differences in absolute renal function between donorerecipient BSA ratio < 1 and 1. We used BSA to adjust absolute renal volume of the donor, because it is easily calculated and is the most important factor affecting renal mass and function.1,17 Also, renal volume calculated by reconstruction of CT angiography has been successfully used to approximate renal mass.8,9 When we analyzed the correlation between transplanted renal volume and graft function, we observed that donor serum creatinine level was not related to transplanted renal volume (r ¼ .139, P ¼ .330), but donor renal volume was correlated (r ¼ .314, P ¼ .025). Therefore we inferred that donor renal volume reflects pretransplant graft function. Also, serum creatinine levels at 1, 3, and 12 months (r ¼ .319 [P ¼ .048]; r ¼ .407,
[P ¼ .010]; and r ¼ .472, [P ¼ .002]) and serum eGFR at 3 and 12 months (r ¼ .318, [P ¼ .049] and r ¼ .388, [P ¼ .015]) significantly correlated with transplanted renal volume. These results mean that larger transplanted kidney volumes result in better graft function in the short-term. To demonstrate a positive association between a larger donated kidney and better recipient outcomes, we evaluated factors that influence graft function according to donor-to-recipient BSA ratio. Our data showed that graft function was influenced by age, gender, and the BSA values of donor and recipient; however, these factors did not impact the rate of acute and chronic rejection, viral or fungal infection, or delayed graft function. Patients receiving grafts from donor-to-recipient BSA 1 displayed significantly higher post-transplant serum creatinine levels and eGFR values at 3 and 12 months compared with donor-to-recipient BSA ratio > l. Our study had some limitations. It was a retrospective analysis of a relatively small number of cases. Also serum creatinine and eGFR are not perfect measures of renal function. How accurately calculated renal volumes represent absolute donor renal volumes is uncertain, because they do not completely reflect physiologic factors such as renal blood flow. In addition, the follow-up period was too short to accurately predict long-term graft outcomes though other studies have shown graft function at 6 or 12 months to strongly correlate with long-term graft survival.20e22 In conclusion, recipients of kidneys from donors with large renal volumes show better graft function and longterm outcomes. It is therefore important to consider renal volume, size, and BSA disparity when choosing donore recipient pairs. Matching donorerecipient renal volumes should improve allograft outcomes.
REFERENCES 1. Saxena AB, Busque S, Arjane P, et al. Preoperative renal volumes as a predictor of graft function in living donor transplantation. Am J Kidney Dis. 2004;44:877.
2924 2. Wang HH, Lin KJ, Liu KL, et al. Size does matter-donor-torecipient body mass index difference may affect renal graft outcome. Transplant Proc. 2012;44:267. 3. Hugen CM, Polcari AJ, Farooq AV, et al. Size does matter: donor renal volume predicts recipient functioning following live donor renal transplantation. J Urol. 2011;185:605. 4. Poggio ED, Hila S, Stephany B, et al. Donor kidney volume and outcomes following live donor kidney transplantation. Am J Transplant. 2006;6:616. 5. Jacobs SC, Nogueira JM, Phelan MW, et al. Transplant recipient renal function is donor renal mass and recipient gender dependent. Transpl Int. 2008;21:340. 6. Ots M, Troy JL, Rennke HG, Brenner BM. Impact of the supplementation of kidney mass on blood pressure and progression of kidney disease. Nephrol Dial Transplant. 2004;19:337. 7. Giral M, Foucher Y, Karam G, et al. Kidney and recipient weight incompatibility reduces long-term graft survival. J Am Soc Nephrol. 2010;21:1022. 8. Chen CH, Shu KH, Cheng CH, et al. Imaging evaluation of kidney using multidetector computerized tomography in livingrelated renal transplantation. Transplant Proc. 2012;44:7. 9. Kato F, Kamishima T, Morita K, et al. Rapid estimation of split renal function in kidney donors using software developed for computed tomographic renal volumetry. Eur J Radiol. 2011;79:15. 10. Hazirolan T, Oz M, Turkbey B, et al. CT angiography of the renal arteries and veins: normal anatomy and variants. Diagn Interv Radiol. 2011;17:67. 11. Summerlin AL, Lockhart ME, Strang AM, et al. Determination of split renal function by 3D reconstruction of CT angiograms: a comparion with gamma camera renography. AJR Am J Roentgenol. 2008;191:1552.
CHOI AND KWON 12. Luyckx VA, Brenner BM. The clinical importance of nephron mass. J Am Soc Nephrol. 2010;21:898. 13. Shapiro R. Size matters in renal allograft survival. J Am Soc Nephrol. 2010;21:890. 14. Abitbol CL, Ingelfinger JR. Nephron mass and cardiovascular and renal disease risks. Semin Nephrol. 2009;29:445. 15. Hidas G, Sosna J, Neeman V, et al. Estimating relative renal function from relative parenchymal volumeda feasibility study. J Endourol. 2008;22:2527. 16. Herts BR, Sharma N, Leiber M, et al. Estimating glomerular filtration rate in kidney donors: a model constructed with renal volme measurements from donor CT scans. Radiology. 2009;252: 109. 17. Tent H, Lely AT, Toering TJ, et al. Donor kidney adapt to body dimensions of recipient: no influence of donor gender on renal function after transplantation. A J Transplant. 2011;11:2173. 18. Oh CK, Lee BM, Jeon KO, et al. Gender-related differences of renal mass supply and metabolic demand after living donor kidney transplantation. Clin Transplant. 2006;20:163. 19. Kwon OJ, Kwak JY. The impact of sex and age matching for long-term graft survival in living donor renal transplantation. Transplant Proc. 2004;36:2040. 20. Lenihan CR, O’kelly P, Mohan P, et al. MDRD-estimated GFR at one year post-renal transplant is a predictor of long-term graft function. Ren Fail. 2008;30:345. 21. Pascual J, Marcen R, Zamora J, et al. Very early serum creatinine as a surrogate marker for graft survival beyond 10 years. J Nephrol. 2009;22:90. 22. First MR. Renal function as a predictor of long-term graft survival in renal transplant patients. Nephrol Dial Transplant. 2003;18:3.
R
ENAL TRANSPLANTATION is considered the treatment of choice for end-stage renal disease (ESRD), because of better survival and improved quality of life compared with dialysis treatment.1 Short-term allograft outcomes have been significantly improved during the past decade due to advances in the use of immunosuppressants.2 Long-term allograft outcomes have also improved somewhat as a result of efforts to identify donorerecipient factors that affect graft function, although many questions remain unanswered.1,3,4 The numbers of ESRD patients awaiting renal transplantation are increasing, while the donor pool remains small.2 The increasing disparity between supply and demand
for organs, had led to increased living donor renal transplantations using extended criteria or exchange programs.2 In addition, ensuring the quality of donated organs and improving their function are of critical importance.3 Some studies have identified donorerecipient factors that contribute to grafts quality,3,5,6 including the volume and
From the Department of Surgery, College of Medicine, Hanyang University, Seoul, Korea. Address reprint requests to Oh Jung Kwon, MD, 17 Haengdang-dong, Seongdong-ku, Seoul 133-792, Korea. E-mail: [email protected]
ª 2013 by Elsevier Inc. All rights reserved. 360 Park Avenue South, New York, NY 10010-1710
0041-1345/13/$esee front matter http://dx.doi.org/10.1016/j.transproceed.2013.08.045
Transplantation Proceedings, 45, 2919e2924 (2013)
2919
2920
CHOI AND KWON Table 1. Baseline Characteristics of Donor and Recipients According to Donor-to-Recipient BSA Ratio
Recipient age (ys) Donor age (ys) Recipient BSA (m2) Donor BSA (m2) BSA ratio (donor-to-recipient) Preoperative dialysis duration (ms) Absolute donor renal volume (mL) Transplanted renal volume (mL/ m2) Donor serum creatinine (mg/dL) Donor serum eGFR (mL/min) Recipient sex Male Female Donor sex Male Female HLA-AB matching 0 1 2 3 4 HLA-DR matching 0 1 2 Underlying disease HTN DM Acute rejection Present Absent Chronic rejection Present Absent Viral or fungal infection Present Absent Delayed graft function Present Absent
Total, n ¼ 51 (%)
Group I (BSA ratio 1), n ¼ 30 (%)
Group II (BSA ratio > 1), n ¼ 21 (%)
P value
41.87 10.22 41.23 10.68 1.69 0.16 1.67 0.19 1.38 0.16 15.31 22.20 164.03 26.69 98.03 18.71 0.84 0.13 94.54 10.57
39.53 10.52 44.23 10.25 1.74 0.15 1.57 0.12 0.90 0.08 13.47 21.38 154.48 17.98 88.90 10.20 0.80 0.11 92.96 10.14
45.78 8.61 36.22 9.67 1.59 0.12 1.85 0.14 1.16 0.11 18.39 23.82 179.96 31.45 113.23 19.97 0.91 0.13 97.18 11.05
.039 .010 .001 <.001 <.001 .463 .001 <.001 .003 .183
35 (68.6) 16 (31.4)
24 (80.8) 6 (20.2)
11 (52.4) 10 (47.6)
.036
20 (39.2) 31 (60.8)
7 (23.3) 23 (76.7)
13 (61.9) 8 (38.1)
.005
4 (13.3) 4 (13.3) 10 (33.3) 8 (26.7) 4(13.3) 2.13 1.22
1 (4.8) 2 (9.5) 16 (76.2) 2 (9.5) 0 (0) 1.89 0.68
.038
2 (6.7) 26 (86.7) 2 (6.7) 1.00 0.37
2 (9.5) 18 (85.7) 1 (4.8) 1.06 0.24
.902
40 (89.4) 8 (15.7)
21 (70) 6 (20.0)
19 (50.5) 2 (9.5)
.080 .311
2 (3.9) 49 (96.1)
1 (3.3) 29 (96.7)
1 (4.8) 20 (95.2)
.462
2 (3.9) 49 (96.1)
1 (3.3) 29 (96.7)
1 (4.8) 20 (95.2)
.796
8 (15.7) 43 (84.3)
3 (10.0) 27 (90.0)
5 (23.8) 16 (76.2)
.182
1 (2.0) 50 (98.0)
0 (0) 30 (100)
1 (4.8) 20 (95.2)
.227
5 6 26 10 4
(9.8) (11.8) (51.0) (19.6) (7.8)
4 (7.8) 44 (86.3) 3 (5.9)
.378
.573
BSA, body surface area; eGFR, estimated glomerular filtration rate; HTN, hypertension; DM, diabetes mellitus.
function of the donor kidneys. Mai et al suggested that low renal mass was associated with poor graft outcomes because smaller kidneys imply less nephron mass and lower glomerular filtration rates (GFR)din other words, inferior filtering capacity.6 Also, lower nephron mass can result in hyperfiltration as a consequence of immunologic and nonimmunologic injuries, which can lead to graft failure.7 Since preoperative radiologic evaluation computed tomography by (CT) angiography has became routine, donor renal volume can be calculated easily by 3-dimensional reconstruction.8,9 Therefore, we compared donor and recipient characteristics to analyze graft function retrospectively according to renal volume matching, a possible clinical indicator of outcome.
MATERIALS AND METHODS Between January 2005 and December 2011, we performed 56 living donor renal transplantations. We retrospectively reviewed 51 living donors and their recipients, excluding 5 pairs who were lost to followup. All recipients underwent induction therapy with basiliximab followed by immunosuppressive therapy based on a calcineurin inhibitor (cyclosporine or tacrolimus), mycophenolate mofetil, and prednisolone. Baseline characteristics of donor and recipient were collected such as gender, age, body surface area (BSA), donor serum creatinine and estimated GFR (eGFR) HLA antigen mismatch, recipient serum creatinine and eGFR, acute and chronic rejection, viral and fungal infection, as well as delayed graft function. Acute rejection episodes were suggested by an unexplained rise in serum creatinine. Percutaneous renal biopsy and renal duplex scan were
RENAL MASS MATCHING performed to confirm the diagnosis before starting antirejection therapy. Delayed graft function was defined as a need for dialysis within the first week of after transplantation, graft failure, as a return to dialysis, nephrectomy, or retransplantation. All patients underwent CT angiography to evaluate anatomy and volume before transplantation. Preoperative renal volumes were measured from preoperative CT scans obtained with a 64channel helical CT scanner (Brilliance scanner, Philips Healthcare) using 120 kVp and 230 mA. The scan parameters included a 64 0.625-mm collimation, and 1-mm thickness reconstruction. The CT protocol included an unenhanced scan, followed by 2 enhanced scans in the arterial and renal parenchymal phases after injection of contrast medium. The arterial scan was started when bolus-triggering scans showed an aortic attenuation of 150 HU. The scan for the renal parenchymal phase was started about 90 seconds after the initial injection. The examinations were interpreted by an experienced abdominal radiologist. The 3dimensional reconstruction traced the renal parenchyma of each kidney manually. The region of interest (ROI) was drawn around the edges of each kidney, excluding to the collecting system and any renal cyst.10,11 Renal volume was extrapolated by summation of all measured ROIs on Rapido 2.8 (Seoul, Korea, INFINITT Health Care). To compare the effect of renal volume on graft function and control for the size of the recipient, the volume of each transplanted kidney was adjusted for the BSA of corresponding recipient. donated renal volume ðmLÞ Transplanted renal volume mL=m2 ¼ recipient BSA ðm2 Þ The Modification of Diet in Renal Disease (MDRD) formula was used to calculate the eGFR of donor and recipient. eGFR (mL/min) ¼ 170 Serum creatinine0.999 Age0.176 (0.762 if female) (1.180 if black) Blood urea nitrogen0.170 Albumin0.318 BSA was calculated from the Dubois formula. BSA (m2) ¼ 0.20247 height (m)0.725 weight (kg)0.425 The BSA ratio was calculated as donor BSA/recipient BSA. All data were analyzed according to the donorerecipient BSA ratio and compared the characteristics and outcomes between two groups. Analyses were performed using SPSS 18.0 with Student t test for continuous variables and the chi-square test to compare categorical factors. Pearson correlation coefficient was used to determine correlations between quantitative data. Statistical significance was defined as a P value <.05.
RESULTS
Baseline donor and recipient characteristics are shown in Table 1. The mean recipient age was 74.87 10.22 (range, 16e68) years and the mean donor age, 21.23 10.68 (range 20e68) years; 68.6% (n ¼ 35) of the recipients were males, females outnumbered male donors (n ¼ 31, 60.8%). The mean follow-up period was 49.96 22.28 (range, 10e85) months. The acute and chronic rejection as well as delayed graft function rates were 3.9%, 3.9%, and 2.0%, respectively. The frequency of viral and fungal infections was 15.7%. We evaluated whether the transplanted volume reflected donor renal function. Mean absolute donor renal volume
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Fig 1. Correlation between transplanted renal volume (absolute donor volume-to-recipient, body surface area; mL/m2) and estimated glomerular filtration rate (eGFR; mL/min) of living donor after renal transplantation.
calculated by CT angiography was 164.03 26.69 (122.30e275.20) mL and mean transplanted renal volume was 98.03 18.71 (69.88e176.41) mL/m2. Transplanted renal volume showed a significant positive correlation (r ¼ .314, P ¼.025) with donor eGFR (Fig 1). To evaluate the correlation between transplanted renal volume and post-transplant recipient graft function, we examined serum creatinine levels and eGFR using the modified MDRD equation at 1, 3, 6, 12, and 36 months. Transplanted renal volume showed a negative correlation with recipient serum creatinine levels at 1, 3, and 12 months (r ¼ .319 [P ¼ 0.48]; r ¼ .407, [P ¼ .010] and r ¼ .472 [P ¼ .002]; Fig 2). eGFR positively correlated with transplanted renal volume at 3 and 12 months (r ¼ .318 [P ¼ .049] and r ¼ .388, [P ¼ .015]; Fig 3). Since there was a relatively large body size disparity between donor and recipients due to there being more female than male donors, we calculated donor-to-recipient BSA ratios to evaluate the impact of this factor. Mean BSA of recipients and donors were 1.69 0.16 (1.39e2.03) m2 and 1.67 0.19 (1.32e2.10) m2 respectively and mean donor-torecipient BSA ratio was 1.38 0.16 (0.73e1.38) m2. Table 1 shows outcomes according to donor-to-recipient BSA ratio group. There were no differences in the rates of acute and chronic rejection, viral or fungal infection, and delayed graft function. However, recipient age was younger and donor age was older in group I (P ¼ .039 and P ¼ .010). Male recipients and female donors were more frequent (80.8% vs 52.4% [P ¼ .036], and 76.7% vs 38.1% [P ¼ .005]) in group I (donor BSA-to-recipients BSA 1) than group II (donor BSAto-recipient BSA > 1). Serum creatinine levels at 3, 6, and 12 months were higher in group I (P ¼ .011, P ¼ .022, and
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CHOI AND KWON
Fig 2. Correlation between transplanted renal volume (absolute donor volume-to-recipient body surface area; mL/m2) and serum creatinine level (mg/dL) after renal transplantation.
P ¼ .007) and serum eGFR at 1, 3, 6, and 12 months after renal transplantation significantly lower in group I (P ¼ .036, P ¼ .042, P ¼ .042, and P ¼ .049; Table 2). There was no significant difference in graft survival between the 2 groups (P ¼ .780). DISCUSSIONS
Many donor and recipient factors influence allograft outcomes. Transplanted renal volume is one of the factors. Renal volume is proportional to nephron number and total number of functioning glomerulae.1,12 Nephron numbers in adults vary even in the absence of renal disease and tend to be lower in females.12,13 Renal development is complete at approximately 34 to 36 weeks of gestation; the number of nephrons does not increase thereafter.14
Transplanted renal volume affects renal function and allograft outcomes.12e14 Larger measured transplanted renal volumes lead to higher GFR.15,16 Hence, BSA or body mass index is considered an important predictor of renal volume and GFR.17 Many studies have demonstrated an effect of renal mass on long-term graft outcomes; smaller renal mass tends to aggravate injury and exacerbate progression of graft failure.3,17 Graft failure is more common when a kidney is transplanted from a small donor into a large recipient compared with size-matched donore recipient pairs.2,4,5 A small renal transplant volume and an insufficient number of functioning nephrons may have too little capacity to respond to the metabolic demands of the recipient.4,18 In addition, immunologic and nonimmunologic events,
Fig 3. Correlation between transplanted renal volume (absolute donor volume-to-recipient body surface area; mL/m2) and estimated glomerular filtration rate (eGFR; mL/min) after renal transplantation.
RENAL MASS MATCHING
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Table 2. Comparison of Renal Function of Recipients According to Donor-to-recipient BSA Ratio Total
Recipient serum creatinine (mg/dL) Preoperative 1 mo 3 mo 6 mo 12 mo 36 mo Recipient serum eGFR (mL/min) Preoperative 1 mo 3 mo 6 mo 12 mo 36 mo
8.25 1.47 1.44 1.40 1.30 1.28 8.36 57.49 55.50 58.11 61.07 60.62
BSA ratio 1 (donor-to-recipient)
3.23 0.87 0.37 0.34 0.35 0.36
3.30 15.89 14.86 15.22 15.55 15.78
8.79 1.70 1.58 1.51 1.42 1.38 8.33 52.60 50.79 53.55 56.62 58.14
BSA ratio > 1 (donor-to-recipient)
P value
4.00 1.09 0.29 0.25 0.29 0.36
7.63 1.20 1.28 1.27 1.13 1.16
1.95 0.40 0.40 0.39 0.35 0.34
.248 .074 .011 .022 .007 .054
3.57 10.80 9.13 10.60 12.77 13.38
8.47 63.19 60.99 63.43 66.26 63.50
3.06 19.06 18.33 18.17 17.19 18.16
.935 .036 .042 .042 .049 .297
BSA, body surface area; eGFR, estimated glomerular filtration rate.
such as ischemia-reperfusion injury, HLA mismatch, and donor age, may reduce the initial functioning nephron mass.1,19 To maintain graft function, the remaining nephrons may undertake maladaptive hyperfiltration. Hence, urinary protein excretion by the transplanted kidney is higher early after renal transplantation.17 As a result, glomerular hypertrophy, glomerulosclerosis, interstitial fibrosis, and tubular atrophy develop leading to reduced graft function and poor long-term graft outcomes.1,5,7 Giral et al showed that incompatibility between graft and recipient weight was an independent predictor of long-term outcome. A low ratio of kidney to recipient weight conferred greater risk of proteinuria and glomerulosclerosis and an increased risk of transplant failure within 2 years. In a study by Poggio et al,4 larger transplanted kidney volume adjusted for recipient BSA (cc/1.73 m2) was associated with better 2-year graft function (P < .001) and a lower acute cellular rejection rate (P ¼ .046). However, Tent et al17 supposed that body size disparity impacts gain in graft function after renal transplantation, independent of donor and recipient gender. In their study, a smaller kidney than the recipient adapted with perfusion and filtration to gain more renal function, meeting the new metabolic demands. There were no differences in absolute renal function between donorerecipient BSA ratio < 1 and 1. We used BSA to adjust absolute renal volume of the donor, because it is easily calculated and is the most important factor affecting renal mass and function.1,17 Also, renal volume calculated by reconstruction of CT angiography has been successfully used to approximate renal mass.8,9 When we analyzed the correlation between transplanted renal volume and graft function, we observed that donor serum creatinine level was not related to transplanted renal volume (r ¼ .139, P ¼ .330), but donor renal volume was correlated (r ¼ .314, P ¼ .025). Therefore we inferred that donor renal volume reflects pretransplant graft function. Also, serum creatinine levels at 1, 3, and 12 months (r ¼ .319 [P ¼ .048]; r ¼ .407,
[P ¼ .010]; and r ¼ .472, [P ¼ .002]) and serum eGFR at 3 and 12 months (r ¼ .318, [P ¼ .049] and r ¼ .388, [P ¼ .015]) significantly correlated with transplanted renal volume. These results mean that larger transplanted kidney volumes result in better graft function in the short-term. To demonstrate a positive association between a larger donated kidney and better recipient outcomes, we evaluated factors that influence graft function according to donor-to-recipient BSA ratio. Our data showed that graft function was influenced by age, gender, and the BSA values of donor and recipient; however, these factors did not impact the rate of acute and chronic rejection, viral or fungal infection, or delayed graft function. Patients receiving grafts from donor-to-recipient BSA 1 displayed significantly higher post-transplant serum creatinine levels and eGFR values at 3 and 12 months compared with donor-to-recipient BSA ratio > l. Our study had some limitations. It was a retrospective analysis of a relatively small number of cases. Also serum creatinine and eGFR are not perfect measures of renal function. How accurately calculated renal volumes represent absolute donor renal volumes is uncertain, because they do not completely reflect physiologic factors such as renal blood flow. In addition, the follow-up period was too short to accurately predict long-term graft outcomes though other studies have shown graft function at 6 or 12 months to strongly correlate with long-term graft survival.20e22 In conclusion, recipients of kidneys from donors with large renal volumes show better graft function and longterm outcomes. It is therefore important to consider renal volume, size, and BSA disparity when choosing donore recipient pairs. Matching donorerecipient renal volumes should improve allograft outcomes.
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2924 2. Wang HH, Lin KJ, Liu KL, et al. Size does matter-donor-torecipient body mass index difference may affect renal graft outcome. Transplant Proc. 2012;44:267. 3. Hugen CM, Polcari AJ, Farooq AV, et al. Size does matter: donor renal volume predicts recipient functioning following live donor renal transplantation. J Urol. 2011;185:605. 4. Poggio ED, Hila S, Stephany B, et al. Donor kidney volume and outcomes following live donor kidney transplantation. Am J Transplant. 2006;6:616. 5. Jacobs SC, Nogueira JM, Phelan MW, et al. Transplant recipient renal function is donor renal mass and recipient gender dependent. Transpl Int. 2008;21:340. 6. Ots M, Troy JL, Rennke HG, Brenner BM. Impact of the supplementation of kidney mass on blood pressure and progression of kidney disease. Nephrol Dial Transplant. 2004;19:337. 7. Giral M, Foucher Y, Karam G, et al. Kidney and recipient weight incompatibility reduces long-term graft survival. J Am Soc Nephrol. 2010;21:1022. 8. Chen CH, Shu KH, Cheng CH, et al. Imaging evaluation of kidney using multidetector computerized tomography in livingrelated renal transplantation. Transplant Proc. 2012;44:7. 9. Kato F, Kamishima T, Morita K, et al. Rapid estimation of split renal function in kidney donors using software developed for computed tomographic renal volumetry. Eur J Radiol. 2011;79:15. 10. Hazirolan T, Oz M, Turkbey B, et al. CT angiography of the renal arteries and veins: normal anatomy and variants. Diagn Interv Radiol. 2011;17:67. 11. Summerlin AL, Lockhart ME, Strang AM, et al. Determination of split renal function by 3D reconstruction of CT angiograms: a comparion with gamma camera renography. AJR Am J Roentgenol. 2008;191:1552.
CHOI AND KWON 12. Luyckx VA, Brenner BM. The clinical importance of nephron mass. J Am Soc Nephrol. 2010;21:898. 13. Shapiro R. Size matters in renal allograft survival. J Am Soc Nephrol. 2010;21:890. 14. Abitbol CL, Ingelfinger JR. Nephron mass and cardiovascular and renal disease risks. Semin Nephrol. 2009;29:445. 15. Hidas G, Sosna J, Neeman V, et al. Estimating relative renal function from relative parenchymal volumeda feasibility study. J Endourol. 2008;22:2527. 16. Herts BR, Sharma N, Leiber M, et al. Estimating glomerular filtration rate in kidney donors: a model constructed with renal volme measurements from donor CT scans. Radiology. 2009;252: 109. 17. Tent H, Lely AT, Toering TJ, et al. Donor kidney adapt to body dimensions of recipient: no influence of donor gender on renal function after transplantation. A J Transplant. 2011;11:2173. 18. Oh CK, Lee BM, Jeon KO, et al. Gender-related differences of renal mass supply and metabolic demand after living donor kidney transplantation. Clin Transplant. 2006;20:163. 19. Kwon OJ, Kwak JY. The impact of sex and age matching for long-term graft survival in living donor renal transplantation. Transplant Proc. 2004;36:2040. 20. Lenihan CR, O’kelly P, Mohan P, et al. MDRD-estimated GFR at one year post-renal transplant is a predictor of long-term graft function. Ren Fail. 2008;30:345. 21. Pascual J, Marcen R, Zamora J, et al. Very early serum creatinine as a surrogate marker for graft survival beyond 10 years. J Nephrol. 2009;22:90. 22. First MR. Renal function as a predictor of long-term graft survival in renal transplant patients. Nephrol Dial Transplant. 2003;18:3.