Int Urol Nephrol DOI 10.1007/s11255-013-0592-y
UROLOGY - ORIGINAL ARTICLE
Change in renal parenchymal volume in living kidney transplant donors Turun Song • Lei Fu • Zixing Huang • Shaofeng He • Ruining Zhao • Tao Lin Qiang Wei
•
Received: 3 September 2013 / Accepted: 18 October 2013 Ó Springer Science+Business Media Dordrecht 2013
Abstract Purpose Uninephrectomy would induce compensatory hypertrophy in the remaining kidney. We investigated the relationship between changes in renal parenchymal volume (RPV) and renal function after nephrectomy in living kidney donors. Methods From July 2011 and January 2012, 45 kidney donors were enrolled in this study. Magnetic resonance scanning was performed before surgery, 3 and 7 days postoperatively, and RPV was calculated through disc summarize methods. Participants were followed up for 1 year. Results The RPV of the remaining kidney was 118.06 ± 23.51 cm3 and then increased by 21.23 % to 143.13 ± 25.52 cm3 at 3 days and by 24.17 % to 146.60 ± 25.86 cm3 at 7 days. Multivariate regression analysis showed that preoperative RPV is positively related to its initial function (p = 0.037); the RPV at 7 days is directly related to its initial, preoperative size (p \ 0.001). With respect to change in postoperative RPV, there is bigger gain in size in smaller kidneys (p = 0.005). The kidneys that has C20 % increase RPV after 7 days are more likely to show further increase in GFR at 1 year (p = 0.024). Conclusions Uninephrectomy induced immediately increment in RPV of the remaining kidney. Donors with RPV increase of C20 % at 1 week have a more favourable renal function adaptation at 1 year.
T. Song L. Fu Z. Huang S. He R. Zhao T. Lin Q. Wei (&) Department of Urology, West China Hospital, Sichuan University, Guoxue Xiang #37, Chengdu 610041, Sichuan, People’s Republic of China e-mail: [email protected]
Keywords Living kidney donor Nephrectomy Magnetic resonance image Renal parenchymal volume Renal function
Introduction Renal transplantation is long referred to as the favoured option for patient with end-stage renal disease (ESRD) with better cost-effectiveness and survival. Rising numbers of patients reaching ESRD intensify the demand for expansion of donor pool. Living-related kidney transplantation results in better patient and graft survival and avoids the long wait on dialysis that the number of living donation has increased recently [1–3]. For donor’s safety, precise pre-donation evaluation is necessary when selecting eligible kidney donors. After unilateral nephrectomy, functional adaptation will occur in the remaining kidney. Long-term ([10 years) follow-up have revealed that the glomerular filtration rate (GFR) increases to 60–80 % of the preoperative level within several weeks postoperatively and then stabilizes or increases very slightly [4, 5]. Advanced age, female sex, smoking, hypertension, and proteinuria have been reported as negative factors for functional adaptation [4]. In addition, upon kidney removal, the remnant will work in a compensatory state, and consequently, renal hypertrophy will occur [6]. Prior studies using enhanced CT scan have demonstrated that in patients underwent unilateral nephrectomy, remnant renal parenchymal volume (RPV) increased significantly after surgery, even at 1 week. This morphological change is highly correlated with the function adaptation [7, 8]. However, all the included participants were of pathological conditions, mostly tumours and advanced aged.
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Int Urol Nephrol
With the availability of magnetic resonance imaging (MRI) techniques, more accurate calculations of renal volume have been possible because with this modality, multiple consecutive image sections through the entire kidney are obtained. Cheong et al. [9] concluded from their study that kidney volumes acquired from MRI with contrast using the disc summation methods were within 5 % of true kidney volume as determined by the reference standard water displacement methods. Other studies also found MRI with gadolinium provides excellent tissue contrast [10, 11]. However, gadolinium has important limitations, leading to the development of nephrogenic systemic fibrosis [12]. Recently, Mignani et al. [13] proved MRI without contrast is a reliable, objective, and reproducible method of assessing the total renal volume in autosomaldominant polycystic kidney disease. In this study, we apply MRI without contrast to investigate the increase in RPV of remnant kidney after donation and factors influencing compensatory hypertrophy in living kidney donors.
Materials and methods
Imaging procedures All subjects were designed to undergoing three times of MRI scanning, within 5 days prior to surgery and at the 3rd and 7th day after the surgery. MRI was performed with a 3.0-tesla MR scanner (Siemens Magnetom Trio Tim, Germany). An eight-channel phased-array coil was used for signal reception. A plain scan that covered the entire length of the kidney in craniocaudal direction was acquired using a T1-weighted gradient-echo sequence. The specific acquisition parameters were as follows: TR = 110 ms, TE = 2.5 s, FOV = 380 9 380, flip angle 70 degrees, 7 slices, slice thickness = 6 mm, gap = 1.2 mm, breathhold duration 15 s; a fat saturation pulse was used to suppress the signal from surrounding perirenal adipose tissue and improve delineation of the renal border. The RPV was calculated from the 3D volume images using the voxel-count method applied to coronal MR images as described by Cheong [9]. In this method, the boundaries of the renal parenchyma of each slice of the kidney were manually mapped. The RPV was then calculated as follows: P RPV (ml) = n (i)(parenchymal area 9 slice thickness)i.
Patients Statistical analysis The study was approved by the hospital’s ethics committee. All patients provided informed consent before undergoing the requested MRI examination. We prospectively evaluated 45 living kidney donors (11 male and 34 female) in a consecutive fashion as they presented to transplant clinic for transplantation, between July 2011 and January 2012. Potential participants had to be at least 18 years old, not pregnant and without a contraindication to an MRI examination. In addition, all subjects undergo a thorough preoperative evaluation process to ensure that they are medically fit for donation and their kidney is suitable for transplantation. If there is a more than 15 % difference in renal function between the right and the left kidneys, the less functional kidney is usually removed. A 99 mTc-mercaptoacetyltriglycine renal scintigraphy was performed in all patients, and effective renal plasma flow (ERPF) was calculated using a camera-based technique. Serum creatinine levels were determined preoperatively and at postoperative day 7 in all patients, and 1 year postoperatively in 36 patients. The glomerular filtration rate (GFR) was calculated estimated by Cockcroft–Gault formula [14]. The preoperative single-kidney GFR was calculated as the preoperative total GFR multiplied by the differential ratio of the single-kidney ERPF. In order to rule out the difference in BSA among included patients, pre- and postoperative GFR were adjusted to the standard BSA (1.73 m2). BSA was calculated as described in the literature [15].
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All continuous data are presented as mean ± SD and compared using Student’s t test, chi-square test for categorical data. Univariate and multivariate stepwise regression analysis was used to test the relationship between the increment in remnant RPV and patient characteristics. All tests were two-sided, and p \ 0 0.05 was considered statistically significant. All statistical analyses were performed using Statistical Package for Social Sciences software (SPSS 18.0, Chicago, IL).
Results The characteristics of all included subjects are presented in Table 1. The preoperative serum creatinine level was 65.34 ± 11.41 lmol/L, and it increased to 105.07 ± 22.62 lmol/L at 7 days postoperatively and then stabilized at a slightly lower level of 97.54 ± 19.09 lmol/L at 1 year. The preoperative GFR was 97.62 ± 18.08 mL/min/ 1.73 m2. The GFR of donated kidney is 48.87 ± 10.23 mL/min/1.73 m2. The GFR of remaining kidney increased by 26.38 % from 48.75 ± 8.93 to 61.61 ± 13.41 mL/min/1.73 m2 at 1 week (p \ 0.001) and by 34.15 % to 65.40 ± 11.82 mL/min/1.73 m2 at 1 year (p \ 0.001). The preoperative volume of the donated kidney is 124.45 ± 25.53 cm3 and that of the remaining kidney was
Int Urol Nephrol Table 1 Characteristics of patients included Value
p
Table 2 Correlation between preoperative patient characteristics and RPV Preoperative
7 days postoperative
b
b
Sex Male
11
Female
34
Age (years)
48.24 ± 8.14
Female sex
0.027*
0.017
0.841
58.07 ± 6.69
Age
0.030
0.864
0.067
0.523
1.60 ± 0.06
BSA
0.166
0.302
0.287
0.006*
1.60 ± 0.10
GFR of the resected kidney
0.276
Weight (kg) Height (m) 2
BSA (m ) Serum creatinine (lmol/L) Preoperative
65.34 ± 11.41
7 days postoperative
105.07 ± 22.62
1 year postoperative GFR of the resected kidney (mL/ min/1.73 m2) 3
PRV of the resected kidney (cm )
p \ 0.001
124.45 ± 25.53 48.75 ± 8.93 61.61 ± 13.41
1 year postoperative
3 days postoperative
143.13 ± 25.52 146.60 ± 25.86
0.089
0.477 \0.001*
0.151
0.092
–
0.728 \0.001*
–
Table 3 Correlation between preoperative patient characteristics and increment of RPV 7 days postoperative
RPV of remaining kidney (cm )
7 days postoperative
0.519
0.278
p \ 0.001
65.40 ± 11.82 118.06 ± 23.51
-0.097
0.037*
0.515
* P \ 0.05
3
Preoperative
p
RPV renal parenchymal volume, BSA body surface area, GFR glomerular filtration rate
GFR of the remaining kidney (mL/min/1.73 m2) 7 days postoperative
-0.275
RPV of resected kidney
97.54 ± 19.09 48.87 ± 10.23
Preoperative
-0.294
GFR of remaining kidney (preoperative) RPV of remaining kidney (preoperative)
p
p \ 0.001
BSA body surface area, GFR glomerular filtration rate, RPV renal parenchymal volume
118.06 ± 23.51 cm3. The RPV of the remaining kidney increased by 21.23 % to 143.13 ± 25.52 cm3 at 3 days after kidney donation (p \ 0.001) and by 24.17 % to 146.60 ± 25.86 cm3 at 7 days (p \ 0.001). Multivariate regression analysis showed that preoperative RPV of the remaining kidney was positively associated with its GFR (p = 0.037). In terms of postoperative RPV, it is positively associated with corresponding preoperative RPV (p \ 0.001; Table 2). Univariate and multivariate analysis demonstrated that the increase in RPV at day 7 was negatively associated with preoperative RPV. There is no statistically significant association for gender, age, single-kidney GFR, RPV in the donated kidney (Table 3). To investigate the changes in renal function, the study population was stratified into 2 groups according to the increase in RPV at 1 week. Group 1 included patients with an RPV increase of \20 % and group 2 those with an RPV increase of C20 %. The RPV of the remaining kidney in Group 1 is significantly greater than that of Group 2 (134.29 ± 19.82 vs. 107.01 ± 19.46 cm3, p \ 0.001). The GFR of the remaining kidney increased significantly 7 days after surgery in both groups (Group 1: 47.58 ± 7.72 vs. 61.21 ± 15.28 mL/min/1.73 m2, p \ 0.001; Group 2:
Female sex
Univariate analysis
Multivariate analysis
b
p
b
p
-0.006
0.969
-0.028
Age
0.067
0.660
0.342
0.878 0.113
BSA
0.080
0.602
0.146
0.508
GFR of the resected kidney
0.129
0.397
-0.015
0.956
GFR of remaining kidney (preoperative)
0.222
0.142
0.476
0.072
RPV of resected kidney RPV of remaining kidney (preoperative)
0.122 -0.081
0.425 0.002*
0.185 -0.408
0.362 0.005*
RPV renal parenchymal volume, BSA body surface area, GFR glomerular filtration rate * P \ 0.05
50.63 ± 8.64 vs. 61.84 ± 12.60 mL/min/1.73 m2, p \ 0.001; Table 4). However, 1 year after kidney donation, the GFR of remaining kidney in Group 1 remains stable and comparable to that at 7 days (63.61 ± 12.72 vs. 61.21 ± 15.28 mL/min, p = 0.244); the GFR in Group 2 is significantly higher than that at 7 days (66.42 ± 11.45 vs. 61.84 ± 12.60, p = 0.024).
Discussion The surgical removal of a normal kidney causes dramatic haemodynamic alternation, which induces immediate adaptation in functional and morphologic changes in the
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Int Urol Nephrol Table 4 Patient characteristics stratified by increase in RPV 1 week postoperatively RPV increase
p
\20 %
C20 %
Male
3
4
0.499
Female Age (years)
10 47.46 ± 5.29
19 47.26 ± 9.79
0.946
Weight (kg)
60.31 ± 6.71
50.08 ± 6.01
0.061
Height (m)
1.60 ± 0.08
1.60 ± 0.06
0.984
BSA (m2)
1.64 ± 0.11
1.58 ± 0.09
0.092
Sex
Serum creatinine (lmol/L) Preoperative
69.25 ± 13.63
61.21 ± 9.95
0.078
7 days postoperative
110.49 ± 30.71
101.51 ± 18.74
0.282
1 year postoperative
104.26 ± 24.41
93.75 ± 14.61
0.114
GFR of the resected kidney (mL/min/1.73 m2)
46.87 ± 8.93
51.23 ± 10.67
0.222
PRV of the resected kidney (cm3)
134.10 ± 21.30
115.03 ± 24.58
0.025
GFR of the remaining kidney (mL/min/1.73 m2) Preoperative
47.58 ± 7.72
50.63 ± 8.64
0.299
7 days postoperative
61.21 ± 15.28
61.84 ± 12.60
0.894
1 year postoperative
63.61 ± 12.72
66.42 ± 11.45
0.5
RPV of remaining kidney (cm3) Preoperative
134.29 ± 19.82
107.01 ± 19.46 \0.001
BSA body surface area, GFR glomerular filtration rate, RPV renal parenchymal volume
remaining kidney. Animal model has shown that the effective renal blood flow of the remnant kidney increased by 40 % after uninephrectomy [16]. When compared with the preoperative level, kidney donors presented same phenomenon as that of animal study, with renal blood flow increased by 25–32.5 % at 1 week and 29–30.1 % at 1 year after kidney donation [17, 18]. With respect to GFR, Hosteller et al. [19] reported single-nephron glomerular filtration rate increased from 27.8 to 62.5 mL/min in kidney resected rat model. Similarly, in kidney donors, Bohlouli et al. [20] reported that GFR of the remaining kidney increased by 63 % at 1 week and 91 % at 3 months compared with the baseline preoperative values. Though our study observed 26.38 % increment in GFR of the remnant kidney 1 week after kidney donation, it was much lower. As previous study has indicated that advanced age is a negative factor for functional adaptation [21], this discrepancy may be explained as a result of different demographic data of included subjects with the mean age of Bohlouli’s participants was 25.41 ± 2.67 years and the mean age of our subjects was 48.24 ± 8.14 years.
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Magnetic resonance imaging provides high-resolution images with superb tissue contrast and new MR scanner design helps avoid claustrophobia, which was one concern of this technique. Previous studies have proven MRIderived kidney volume using disc summation is a reliable, objective, and reproducible method of assessing the renal volume [9–11]. Different from them, our study regards the use of MRI without the injection of contrast medium, without subjecting donors at the risk of developing renal fibrosis. Cheung et al. [22] underlined a significant correlation between the RPV calculated using MR images and the single-kidney GFR. It is corroborated by our results that RPV of the remaining kidney is significantly associated with GFR. However, this significance only been detected in baseline. A further analysis revealed that at 7 days after surgery, there is no significant association between the RPV and GFR (p = 0.366), indicating the volume change and functional adaptation are not parallel. Histological examination revealed the primary site of hypertrophy is the cortex, in which proximal tubular cell hypertrophy, collecting tubular cell enlargement, and glomerular mesangial expansion occur within weeks after nephrectomy [23, 24]. These structure modifications are believed induced by dramatic hemodynamic change immediately after kidney removal [18, 25]. However, it is not likely that histological reconstruction is completed within 1 week. Studies have shown that renal plasma flow began to increase at 30 min after contralateral nephrectomy, reached a plateau at 2 h, and decreased thereafter to baseline by 2 days. Funahashi et al. [26] hypothesized that the increase in RPV at early phase after uninephrectomy would be a result of an enlarged vascular bed caused by increased renal blood flow and then follows the histological hypertrophic responses [27]. This speculation is supported by our results, which revealed that the RPV increases 3 days after kidney donation and remains almost unchanged thereafter. Furthermore, our findings are also consistent with other studies reporting the RPV increase immediately after nephrectomy and reach a plateau within 1 week [7, 8]. We found that patients with increment in RPV of remaining kidney greater than 20 % at 7 days have a more favourable renal function adaptation 1 year postoperatively. Thus, we speculated that kidneys with a lesser increase in size after contralateral nephrectomy might have poorer compensatory potential and a poor long-term prognosis. Although long-term follow-up of kidney donors revealed comforting results [1], when taken the RPV into stratification, a prospective trial with larger sample size and longer follow-up might be required to detect long-term outcomes. Conflict of interest
There is no conflict of interests to be disclosed.
Int Urol Nephrol
References 1. Goldfarb DA, Matin SF, Braun WE et al (2001) Renal outcome 25 years after donor nephrectomy. J Urol 166:2043–2047 2. Lima DX, Petroianu A, Hauter HL (2006) Quality of life and surgical complications of kidney donors in the late post-operative period in Brazil. Nephrol Dial Transplant 21:3238–3242 3. Textor SC, Taler SJ, Driscoll N et al (2004) Blood pressure and renal function after kidney donation from hypertensive living donors. Transplantation 78:276–282 4. Johansson M, Moonen M (2001) Prediction of post-operative glomerular filtration rate after nephrectomy for renal malignancy. Clin Physiol 21:688–692 5. Tanaka N, Fujimoto K, Tani M et al (2004) Prediction of the postoperative renal function by the preoperative serum creatinine level and 3-dimensional diagnostic image reconstruction in patients with renal cell carcinoma. Urology 64:904–908 6. Kaufman JM, Siegel NJ, Hayslett JP (1975) Functional and hemodynamic adaptation to progressive renal ablation. Circ Res 36:286–293 7. Funahashi Y, Hattori R, Yamamoto T et al (2011) Relationship between renal parenchymal volume and single kidney glomerular filtration rate before and after unilateral nephrectomy. Urology 77(6):1404–1408 8. Funahashi Y, Hattori R, Yamamoto T et al (2009) Change in contralateral renal parenchymal volume 1 week after unilateral nephrectomy. Urology 74(3):708–712 9. Cheong B, Muthupillai R, Rubin MF et al (2007) Normal values for renal length and volume as measured by magnetic resonance imaging. Clin J Am Soc Nephrol 2:38–45 10. Lee YR, Lee KB (2006) Reliability of magnetic resonance imaging for measuring the volumetric indices in autosomaldominant polycystic kidney disease: correlation with hypertension and renal function. Nephron Clin Pract 103:c173–c180 11. Reichardt W, Romaker D, Becker A et al (2009) Monitoring kidney and renal cyst volumes applying MR approaches on a rapamycin-treated mouse model of ADPKD. MAGMA 22:143– 149 12. Wiginton CD, Kelly B, Oto A et al (2008) Gadolinium-based contrast exposure, nephrogenic systemic fibrosis, and gadolinium detection in tissue. AJR Am J Roentgenol 190(4):1060–1068 13. Mignani R, Corsi C, De Marco M et al (2011) Assessment of kidney volume in polycystic kidney disease using magnetic
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resonance imaging without contrast medium. Am J Nephrol 33(2):176–184 Cockcroft DW, Gault MH (1976) Prediction of creatinine clearance from serum creatinine. Nephron 16:31–41 Mosteller RD (1987) Simplified calculation of body-surface area. N Engl J Med 317:1098 Ziada G, Youseif H, Khalil M (2009) Compensatory changes in the function of the remaining kidney immediately after unilateral nephrectomy in sheep. Tohoku J Exp Med 219(2):165–168 Anderson RG, Bueschen AJ, Lloyd LK et al (1991) Short-term and long-term changes in renal function after donor nephrectomy. J Urol 145:11–13 Indudhara R, Kenney PJ, Bueschen AJ et al (1999) Live donor nephrectomy in patients with fibromuscular dysplasia of the renal arteries. J Urol 162:678–681 Hosteller TH, Olson JL, Rennke HG et al (2001) Hyperfiltration in remnant nephrons: a potentially adverse response to renal ablation. J Am Soc Nephrol 12:1315–1325 Bohlouli A, Tarzamni MK, Zomorodi A et al (2010) Remnant kidney function and size in living unrelated kidney donors after nephrectomy. Saudi J Kidney Dis Transpl 21(2):246–250 Ito K, Nakashima J, Hanawa Y et al (2004) The prediction of renal function 6 years after unilateral nephrectomy using preoperative risk factors. J Urol 171:120–125 Cheung CM, Shurrab AE, Buckley DL et al (2006) MR-derived renal morphology and renal function in patients with atherosclerot renovascular disease. Kidney Int 69(4):715–722 Lee GSL, Nast CC, Peng SC et al (1998) Differential response of glomerular epithelial and mesangial cells after subtotal nephrectomy. Kidney Int 53:1389–1398 Preisig P (1999) What makes cells grow larger and how do they do it? Renal hypertrophy revisited. Exp Nephrol 7:273–283 Shimamura T, Morrison AB (1975) A progressive glomerulosclerosis occurring in partial five-sixths nephrectomized rats. Am J Pathol 79:95–106 Funahashi Y, Hattori R, Yamamoto T et al (2011) Renal parenchymal volume increases after contralateral nephrectomy: assessment using three dimensional ultrasonography. Int J Urol 18(12):857–860 Young LS, Regan MC, Sweeney P et al (1998) Changes in regional renal blood flow after unilateral nephrectomy using the techniques of autoradiography and microautoradiography. J Urol 160:926–931
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UROLOGY - ORIGINAL ARTICLE
Change in renal parenchymal volume in living kidney transplant donors Turun Song • Lei Fu • Zixing Huang • Shaofeng He • Ruining Zhao • Tao Lin Qiang Wei
•
Received: 3 September 2013 / Accepted: 18 October 2013 Ó Springer Science+Business Media Dordrecht 2013
Abstract Purpose Uninephrectomy would induce compensatory hypertrophy in the remaining kidney. We investigated the relationship between changes in renal parenchymal volume (RPV) and renal function after nephrectomy in living kidney donors. Methods From July 2011 and January 2012, 45 kidney donors were enrolled in this study. Magnetic resonance scanning was performed before surgery, 3 and 7 days postoperatively, and RPV was calculated through disc summarize methods. Participants were followed up for 1 year. Results The RPV of the remaining kidney was 118.06 ± 23.51 cm3 and then increased by 21.23 % to 143.13 ± 25.52 cm3 at 3 days and by 24.17 % to 146.60 ± 25.86 cm3 at 7 days. Multivariate regression analysis showed that preoperative RPV is positively related to its initial function (p = 0.037); the RPV at 7 days is directly related to its initial, preoperative size (p \ 0.001). With respect to change in postoperative RPV, there is bigger gain in size in smaller kidneys (p = 0.005). The kidneys that has C20 % increase RPV after 7 days are more likely to show further increase in GFR at 1 year (p = 0.024). Conclusions Uninephrectomy induced immediately increment in RPV of the remaining kidney. Donors with RPV increase of C20 % at 1 week have a more favourable renal function adaptation at 1 year.
T. Song L. Fu Z. Huang S. He R. Zhao T. Lin Q. Wei (&) Department of Urology, West China Hospital, Sichuan University, Guoxue Xiang #37, Chengdu 610041, Sichuan, People’s Republic of China e-mail: [email protected]
Keywords Living kidney donor Nephrectomy Magnetic resonance image Renal parenchymal volume Renal function
Introduction Renal transplantation is long referred to as the favoured option for patient with end-stage renal disease (ESRD) with better cost-effectiveness and survival. Rising numbers of patients reaching ESRD intensify the demand for expansion of donor pool. Living-related kidney transplantation results in better patient and graft survival and avoids the long wait on dialysis that the number of living donation has increased recently [1–3]. For donor’s safety, precise pre-donation evaluation is necessary when selecting eligible kidney donors. After unilateral nephrectomy, functional adaptation will occur in the remaining kidney. Long-term ([10 years) follow-up have revealed that the glomerular filtration rate (GFR) increases to 60–80 % of the preoperative level within several weeks postoperatively and then stabilizes or increases very slightly [4, 5]. Advanced age, female sex, smoking, hypertension, and proteinuria have been reported as negative factors for functional adaptation [4]. In addition, upon kidney removal, the remnant will work in a compensatory state, and consequently, renal hypertrophy will occur [6]. Prior studies using enhanced CT scan have demonstrated that in patients underwent unilateral nephrectomy, remnant renal parenchymal volume (RPV) increased significantly after surgery, even at 1 week. This morphological change is highly correlated with the function adaptation [7, 8]. However, all the included participants were of pathological conditions, mostly tumours and advanced aged.
123
Int Urol Nephrol
With the availability of magnetic resonance imaging (MRI) techniques, more accurate calculations of renal volume have been possible because with this modality, multiple consecutive image sections through the entire kidney are obtained. Cheong et al. [9] concluded from their study that kidney volumes acquired from MRI with contrast using the disc summation methods were within 5 % of true kidney volume as determined by the reference standard water displacement methods. Other studies also found MRI with gadolinium provides excellent tissue contrast [10, 11]. However, gadolinium has important limitations, leading to the development of nephrogenic systemic fibrosis [12]. Recently, Mignani et al. [13] proved MRI without contrast is a reliable, objective, and reproducible method of assessing the total renal volume in autosomaldominant polycystic kidney disease. In this study, we apply MRI without contrast to investigate the increase in RPV of remnant kidney after donation and factors influencing compensatory hypertrophy in living kidney donors.
Materials and methods
Imaging procedures All subjects were designed to undergoing three times of MRI scanning, within 5 days prior to surgery and at the 3rd and 7th day after the surgery. MRI was performed with a 3.0-tesla MR scanner (Siemens Magnetom Trio Tim, Germany). An eight-channel phased-array coil was used for signal reception. A plain scan that covered the entire length of the kidney in craniocaudal direction was acquired using a T1-weighted gradient-echo sequence. The specific acquisition parameters were as follows: TR = 110 ms, TE = 2.5 s, FOV = 380 9 380, flip angle 70 degrees, 7 slices, slice thickness = 6 mm, gap = 1.2 mm, breathhold duration 15 s; a fat saturation pulse was used to suppress the signal from surrounding perirenal adipose tissue and improve delineation of the renal border. The RPV was calculated from the 3D volume images using the voxel-count method applied to coronal MR images as described by Cheong [9]. In this method, the boundaries of the renal parenchyma of each slice of the kidney were manually mapped. The RPV was then calculated as follows: P RPV (ml) = n (i)(parenchymal area 9 slice thickness)i.
Patients Statistical analysis The study was approved by the hospital’s ethics committee. All patients provided informed consent before undergoing the requested MRI examination. We prospectively evaluated 45 living kidney donors (11 male and 34 female) in a consecutive fashion as they presented to transplant clinic for transplantation, between July 2011 and January 2012. Potential participants had to be at least 18 years old, not pregnant and without a contraindication to an MRI examination. In addition, all subjects undergo a thorough preoperative evaluation process to ensure that they are medically fit for donation and their kidney is suitable for transplantation. If there is a more than 15 % difference in renal function between the right and the left kidneys, the less functional kidney is usually removed. A 99 mTc-mercaptoacetyltriglycine renal scintigraphy was performed in all patients, and effective renal plasma flow (ERPF) was calculated using a camera-based technique. Serum creatinine levels were determined preoperatively and at postoperative day 7 in all patients, and 1 year postoperatively in 36 patients. The glomerular filtration rate (GFR) was calculated estimated by Cockcroft–Gault formula [14]. The preoperative single-kidney GFR was calculated as the preoperative total GFR multiplied by the differential ratio of the single-kidney ERPF. In order to rule out the difference in BSA among included patients, pre- and postoperative GFR were adjusted to the standard BSA (1.73 m2). BSA was calculated as described in the literature [15].
123
All continuous data are presented as mean ± SD and compared using Student’s t test, chi-square test for categorical data. Univariate and multivariate stepwise regression analysis was used to test the relationship between the increment in remnant RPV and patient characteristics. All tests were two-sided, and p \ 0 0.05 was considered statistically significant. All statistical analyses were performed using Statistical Package for Social Sciences software (SPSS 18.0, Chicago, IL).
Results The characteristics of all included subjects are presented in Table 1. The preoperative serum creatinine level was 65.34 ± 11.41 lmol/L, and it increased to 105.07 ± 22.62 lmol/L at 7 days postoperatively and then stabilized at a slightly lower level of 97.54 ± 19.09 lmol/L at 1 year. The preoperative GFR was 97.62 ± 18.08 mL/min/ 1.73 m2. The GFR of donated kidney is 48.87 ± 10.23 mL/min/1.73 m2. The GFR of remaining kidney increased by 26.38 % from 48.75 ± 8.93 to 61.61 ± 13.41 mL/min/1.73 m2 at 1 week (p \ 0.001) and by 34.15 % to 65.40 ± 11.82 mL/min/1.73 m2 at 1 year (p \ 0.001). The preoperative volume of the donated kidney is 124.45 ± 25.53 cm3 and that of the remaining kidney was
Int Urol Nephrol Table 1 Characteristics of patients included Value
p
Table 2 Correlation between preoperative patient characteristics and RPV Preoperative
7 days postoperative
b
b
Sex Male
11
Female
34
Age (years)
48.24 ± 8.14
Female sex
0.027*
0.017
0.841
58.07 ± 6.69
Age
0.030
0.864
0.067
0.523
1.60 ± 0.06
BSA
0.166
0.302
0.287
0.006*
1.60 ± 0.10
GFR of the resected kidney
0.276
Weight (kg) Height (m) 2
BSA (m ) Serum creatinine (lmol/L) Preoperative
65.34 ± 11.41
7 days postoperative
105.07 ± 22.62
1 year postoperative GFR of the resected kidney (mL/ min/1.73 m2) 3
PRV of the resected kidney (cm )
p \ 0.001
124.45 ± 25.53 48.75 ± 8.93 61.61 ± 13.41
1 year postoperative
3 days postoperative
143.13 ± 25.52 146.60 ± 25.86
0.089
0.477 \0.001*
0.151
0.092
–
0.728 \0.001*
–
Table 3 Correlation between preoperative patient characteristics and increment of RPV 7 days postoperative
RPV of remaining kidney (cm )
7 days postoperative
0.519
0.278
p \ 0.001
65.40 ± 11.82 118.06 ± 23.51
-0.097
0.037*
0.515
* P \ 0.05
3
Preoperative
p
RPV renal parenchymal volume, BSA body surface area, GFR glomerular filtration rate
GFR of the remaining kidney (mL/min/1.73 m2) 7 days postoperative
-0.275
RPV of resected kidney
97.54 ± 19.09 48.87 ± 10.23
Preoperative
-0.294
GFR of remaining kidney (preoperative) RPV of remaining kidney (preoperative)
p
p \ 0.001
BSA body surface area, GFR glomerular filtration rate, RPV renal parenchymal volume
118.06 ± 23.51 cm3. The RPV of the remaining kidney increased by 21.23 % to 143.13 ± 25.52 cm3 at 3 days after kidney donation (p \ 0.001) and by 24.17 % to 146.60 ± 25.86 cm3 at 7 days (p \ 0.001). Multivariate regression analysis showed that preoperative RPV of the remaining kidney was positively associated with its GFR (p = 0.037). In terms of postoperative RPV, it is positively associated with corresponding preoperative RPV (p \ 0.001; Table 2). Univariate and multivariate analysis demonstrated that the increase in RPV at day 7 was negatively associated with preoperative RPV. There is no statistically significant association for gender, age, single-kidney GFR, RPV in the donated kidney (Table 3). To investigate the changes in renal function, the study population was stratified into 2 groups according to the increase in RPV at 1 week. Group 1 included patients with an RPV increase of \20 % and group 2 those with an RPV increase of C20 %. The RPV of the remaining kidney in Group 1 is significantly greater than that of Group 2 (134.29 ± 19.82 vs. 107.01 ± 19.46 cm3, p \ 0.001). The GFR of the remaining kidney increased significantly 7 days after surgery in both groups (Group 1: 47.58 ± 7.72 vs. 61.21 ± 15.28 mL/min/1.73 m2, p \ 0.001; Group 2:
Female sex
Univariate analysis
Multivariate analysis
b
p
b
p
-0.006
0.969
-0.028
Age
0.067
0.660
0.342
0.878 0.113
BSA
0.080
0.602
0.146
0.508
GFR of the resected kidney
0.129
0.397
-0.015
0.956
GFR of remaining kidney (preoperative)
0.222
0.142
0.476
0.072
RPV of resected kidney RPV of remaining kidney (preoperative)
0.122 -0.081
0.425 0.002*
0.185 -0.408
0.362 0.005*
RPV renal parenchymal volume, BSA body surface area, GFR glomerular filtration rate * P \ 0.05
50.63 ± 8.64 vs. 61.84 ± 12.60 mL/min/1.73 m2, p \ 0.001; Table 4). However, 1 year after kidney donation, the GFR of remaining kidney in Group 1 remains stable and comparable to that at 7 days (63.61 ± 12.72 vs. 61.21 ± 15.28 mL/min, p = 0.244); the GFR in Group 2 is significantly higher than that at 7 days (66.42 ± 11.45 vs. 61.84 ± 12.60, p = 0.024).
Discussion The surgical removal of a normal kidney causes dramatic haemodynamic alternation, which induces immediate adaptation in functional and morphologic changes in the
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Int Urol Nephrol Table 4 Patient characteristics stratified by increase in RPV 1 week postoperatively RPV increase
p
\20 %
C20 %
Male
3
4
0.499
Female Age (years)
10 47.46 ± 5.29
19 47.26 ± 9.79
0.946
Weight (kg)
60.31 ± 6.71
50.08 ± 6.01
0.061
Height (m)
1.60 ± 0.08
1.60 ± 0.06
0.984
BSA (m2)
1.64 ± 0.11
1.58 ± 0.09
0.092
Sex
Serum creatinine (lmol/L) Preoperative
69.25 ± 13.63
61.21 ± 9.95
0.078
7 days postoperative
110.49 ± 30.71
101.51 ± 18.74
0.282
1 year postoperative
104.26 ± 24.41
93.75 ± 14.61
0.114
GFR of the resected kidney (mL/min/1.73 m2)
46.87 ± 8.93
51.23 ± 10.67
0.222
PRV of the resected kidney (cm3)
134.10 ± 21.30
115.03 ± 24.58
0.025
GFR of the remaining kidney (mL/min/1.73 m2) Preoperative
47.58 ± 7.72
50.63 ± 8.64
0.299
7 days postoperative
61.21 ± 15.28
61.84 ± 12.60
0.894
1 year postoperative
63.61 ± 12.72
66.42 ± 11.45
0.5
RPV of remaining kidney (cm3) Preoperative
134.29 ± 19.82
107.01 ± 19.46 \0.001
BSA body surface area, GFR glomerular filtration rate, RPV renal parenchymal volume
remaining kidney. Animal model has shown that the effective renal blood flow of the remnant kidney increased by 40 % after uninephrectomy [16]. When compared with the preoperative level, kidney donors presented same phenomenon as that of animal study, with renal blood flow increased by 25–32.5 % at 1 week and 29–30.1 % at 1 year after kidney donation [17, 18]. With respect to GFR, Hosteller et al. [19] reported single-nephron glomerular filtration rate increased from 27.8 to 62.5 mL/min in kidney resected rat model. Similarly, in kidney donors, Bohlouli et al. [20] reported that GFR of the remaining kidney increased by 63 % at 1 week and 91 % at 3 months compared with the baseline preoperative values. Though our study observed 26.38 % increment in GFR of the remnant kidney 1 week after kidney donation, it was much lower. As previous study has indicated that advanced age is a negative factor for functional adaptation [21], this discrepancy may be explained as a result of different demographic data of included subjects with the mean age of Bohlouli’s participants was 25.41 ± 2.67 years and the mean age of our subjects was 48.24 ± 8.14 years.
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Magnetic resonance imaging provides high-resolution images with superb tissue contrast and new MR scanner design helps avoid claustrophobia, which was one concern of this technique. Previous studies have proven MRIderived kidney volume using disc summation is a reliable, objective, and reproducible method of assessing the renal volume [9–11]. Different from them, our study regards the use of MRI without the injection of contrast medium, without subjecting donors at the risk of developing renal fibrosis. Cheung et al. [22] underlined a significant correlation between the RPV calculated using MR images and the single-kidney GFR. It is corroborated by our results that RPV of the remaining kidney is significantly associated with GFR. However, this significance only been detected in baseline. A further analysis revealed that at 7 days after surgery, there is no significant association between the RPV and GFR (p = 0.366), indicating the volume change and functional adaptation are not parallel. Histological examination revealed the primary site of hypertrophy is the cortex, in which proximal tubular cell hypertrophy, collecting tubular cell enlargement, and glomerular mesangial expansion occur within weeks after nephrectomy [23, 24]. These structure modifications are believed induced by dramatic hemodynamic change immediately after kidney removal [18, 25]. However, it is not likely that histological reconstruction is completed within 1 week. Studies have shown that renal plasma flow began to increase at 30 min after contralateral nephrectomy, reached a plateau at 2 h, and decreased thereafter to baseline by 2 days. Funahashi et al. [26] hypothesized that the increase in RPV at early phase after uninephrectomy would be a result of an enlarged vascular bed caused by increased renal blood flow and then follows the histological hypertrophic responses [27]. This speculation is supported by our results, which revealed that the RPV increases 3 days after kidney donation and remains almost unchanged thereafter. Furthermore, our findings are also consistent with other studies reporting the RPV increase immediately after nephrectomy and reach a plateau within 1 week [7, 8]. We found that patients with increment in RPV of remaining kidney greater than 20 % at 7 days have a more favourable renal function adaptation 1 year postoperatively. Thus, we speculated that kidneys with a lesser increase in size after contralateral nephrectomy might have poorer compensatory potential and a poor long-term prognosis. Although long-term follow-up of kidney donors revealed comforting results [1], when taken the RPV into stratification, a prospective trial with larger sample size and longer follow-up might be required to detect long-term outcomes. Conflict of interest
There is no conflict of interests to be disclosed.
Int Urol Nephrol
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