Role of Radioisotope Renal Scans in the Choice of Nephrectomy Side in Live Kidney Donors

0022-5347/03/1702-0373/0 THE JOURNAL OF UROLOGY® Copyright © 2003 by AMERICAN UROLOGICAL ASSOCIATION

Vol. 170, 373–376, August 2003 Printed in U.S.A.

DOI: 10.1097/01.ju.0000074897.48830.58

ROLE OF RADIOISOTOPE RENAL SCANS IN THE CHOICE OF NEPHRECTOMY SIDE IN LIVE KIDNEY DONORS AHMED A. SHOKEIR,* HOSAM M. GAD

AND

TAREK EL-DIASTY

From the Urology and Nephrology Center, Mansoura University, Mansoura, Egypt

ABSTRACT

Purpose: We determined the role of radioisotope renal scans in the choice of nephrectomy side in potential live kidney donors. Materials and Methods: The study included 300 consecutive potential live kidney donors. In addition to routine laboratory and radiological evaluation, a radioisotope renal scan with selective determination of glomerular filtration rate (GFR) of each kidney was performed for all donors. Results of the first 100 potential donors were used to standardize the technique and to show the normal difference in GFR of both kidneys due to technical and normal physiological variations. The subsequent 200 potential donors who underwent nephrectomy were considered the study group. In the study group kidneys with a GFR difference less than or equal to mean normal difference were considered equal in function. Disparity in function was considered if the GFR difference between both kidneys was greater than normal mean difference. Results: Of the 100 control donors there was no difference between mean GFR ⫾ SD of the left and right kidney (57.7 ⫾ 9.09 vs 58.09 ⫾ 8.93 ml per minute, respectively). The disparity in clearance of both kidneys ranged from 0 to 14.25 ml per minute and averaged 6.12 ⫾ 0.42. This average difference represents 5.31% ⫾ 0.27% of average total renographic GFR. Based on control group results a disparity greater than 5.31% of total GFR was considered significant in the study group. Of the 200 study group donors GFR of both kidneys was comparable in 116 cases (58%), the left had better function in 49 (24.5%) and the right had better function in 35 (17.5%). Therefore, a total of 84 donors (42%) had disparity in function between both kidneys. In all these donors the kidney with less function was chosen for nephrectomy regardless of anatomical considerations such as multiplicity of renal arteries. In donors with comparable GFR in both kidneys the harvested kidney was essentially chosen on an anatomical basis. Conclusions: When renal function of 2 kidneys is similar or nearly similar, anatomical factors determine the side of the harvested kidney. When there is a significant difference in clearance value (greater than 6 ml per minute) the kidney with lower clearance is chosen irrespective of anatomical findings. Since this difference is expected in about 40% of healthy individuals, radioisotopic determination of split renal function should be an integral part of the preoperative evaluation of potential kidney donors. KEY WORDS: kidney, living donors, nephrectomy; glomerular filtration rate, kidney function tests

Living donors are still the main source of kidneys for transplantation in many countries because of a lack in organization required for cadaver evaluation and poor legal definitions. The use of living donors has been justified further by the fact that recipient and graft survival rates with living donors have consistently exceeded rates achieved with cadaveric donors.1 Once a suitable living donor has been found it is necessary to ensure that he or she will not suffer as a result of donation. In particular it is necessary to ensure that the donor has 2 well functioning kidneys and that renal function is evenly divided. If the donor has an unusual asymmetry of function, measurement of individual renal function should not deprive the donor of the better kidney. In previous reports2, 3 the decision to use the right or left kidney for transplantation was usually based on morphological studies such as excretory urography and angiography. In this study in addition to these parameters we used a radioisotopic method for selective determination of glomerular filtration rate (GFR) of donors before nephrectomy. The choice of the kidney to be used for donation was founded on a functional basis and not on an anatomical basis alone.

MATERIALS AND METHODS

The study included 300 potential live kidney donors who visited our center between January 2000 and September 2002. In addition to routine evaluation, radioisotope renal scans were performed on all donors. The first 100 consecutive donors were considered the control group to standardize the technique of renal scans. The subsequent 200 potential donors who underwent nephrectomy were considered the study group. Demographic characteristics of study and control donors are given in table 1. Preparation of donors. Potential donors were initially identified on the basis of ABO compatibility. Then a thorough preliminary medical evaluation including a careful history, physical examination and adequate laboratory evaluation was performed. The donor-recipient pair was then assessed for histocompatibility with tissue typing (HLA-A, B and-DR) and crossmatching. Radiological imaging of the kidneys was performed with plain abdominal x-ray (KUB), ultrasonography (US) and magnetic resonance angiography with magnetic resonance urography. If magnetic resonance angiography was inadequate for visualization of renal arteries, donors underwent intraarterial digital subtraction angiography.4 Finally, selective determination of

Accepted for publication February 21, 2003. * Corresponding author: Department of Urology, Mansoura University, Mansoura, Egypt. 373

374

ROLE OF RADIOISOTOPE RENAL SCANS IN CHOICE OF NEPHRECTOMY SIDE TABLE 1. Characteristics of study and control groups Study Group Mean ⫾ SD

Control Group Mean ⫾ SD

Age (yrs) 42 ⫾ 7 44 ⫾ 8 Sex (M/F) 131/69 66/34 Wt (kg) 69 ⫾ 11 72 ⫾ 10 Serum creatinine (mg/dl) 0.9 ⫾ 0.3 0.9 ⫾ 0.4 Creatinine clearance (ml/min) 122 ⫾ 12 124.4 ⫾ 11.9 Blood pressure (mm Hg): Systolic 125 ⫾ 10 123 ⫾ 11 Diastolic 80 ⫾ 8 83 ⫾ 9 Hemoglobin (gm/dl) 13.4 ⫾ 2.6 13.6 ⫾ 2.5 Hematocrit (%) 40 ⫾ 6 41 ⫾ 7 No significant difference was observed among any of the compared parameters.

the function of both kidneys was determined using radioisotope renography. Technique of radioisotope renography. The patient must be well hydrated by taking in 1,500 ml of fluids during the 2 hours before the study. A bolus of 111 MBq (3 mCi) of 99m technetium diethylenetetramine pentaacetic acid is given intravenously. The patient lies supine and a SMV DST XLi ␥ camera (GE Medical Systems, Milwaukee, Wisconsin) with a parallel hole collimator interfaced with a digital computer is underneath. One minute count of the activity to be injected is obtained by placing the syringe 30 cm from the center of the collimator and stirring the count data in 128 ⫻ 128 matrix. The patient posterior view in the upright position is studied. Data acquisition begins at the time of injection as 2 seconds per frame for 1 minute followed by 15 seconds per frame for 19 minutes. Another 1-minute post-injection syringe count is obtained at the end of the study. Subtraction technique is done between pre and post-injection syringes to calculate net activity. Composite images are generated by adding all 8 frames (15 seconds per frame acquired for 2 minutes). A total of 50% of the background count level is subtracted to optimize kidney identification. Regions of interest are taken for both kidneys and background areas are drawn below kidneys. The net count for each kidney is determined in the 2 to 3 minutes following tracer arrival. GFR calculation. Depth correction is done using Tonnesen’s formulas.5 Right kidney (RK) depth in cm ⫽ 13.3 weight/height ⫹ 0.7 and left kidney (LK) depth in cm ⫽ 13.2 weight/height ⫹ 0.7. Depth corrected counts (cts) are then calculated for RK and LK with

RK depth ⫺ corrected cts ⫽

RK cts ⫺ background ⫺␮XR

LK depth ⫺ corrected cts ⫽

LK cts ⫺ background ⫺␮XL

and

where ␮ is the linear attenuation cofficient for 99mTC (0.153 cm), XR is RK depth and XL is LK depth. Renal uptake of the tracer is calculated as a percentage of the administered dose. Renal uptake % ⫽

LK depth corrected cts ⫹ LK depth⫺corrected cts pre-injection cts ⫺ post-injection cts GFR is then calculated using a regression formula generated from data collection on a large number of subjects for which renal uptake during a 2 to 3-minute interval was plotted against creatinine clearance values, GFR ⫽ (% renal uptake) (9.81270) ⫺ (6.82519). The contributions of right and left kidney are easily determined, with right kidney GFR ⫽ (% right uptake) ⫻ (total GFR), and left kidney GFR ⫽ (% left uptake) ⫻ (total GFR). All results are normalized according to body surface area.6

Standardization of radioisotope renography. Results of the first 100 potential healthy donors were used to standardize the technique and to show the normal difference between GFR of both kidneys due to technical and normal physiological variations. In the study group kidneys with a GFR difference less than or equal to mean normal difference were considered equal in function. Disparity in function was considered if the GFR difference between both kidneys was greater than normal mean difference. The recipients of all donations were followed for a minimum of 3 months relative to graft function (serum creatinine and 24-hour creatinine clearance) to establish whether a relation exists between the selective clearance of the donated kidney and the ultimate graft function. RESULTS

Among the 100 potential healthy control donors there was no difference between GFR of the left and right kidney (57.7 ⫾ 9.09 vs 58.09 ⫾ 8.93 ml per minute, respectively). No significant difference between mean combined renographic clearance (115.8 ⫾ 16.4 ml per minute) and mean 24-hour creatinine clearance (124.4 ⫾ 11.9) was found. Moreover, a strong correlation was evident between values obtained using both methods (r ⫽ 0.70, p ⬍0.0001), confirming the validity of the former technique in assessment (fig. 1). The disparity in clearance of both kidneys ranged from 0 to 14.25 ml per minute and averaged 6.12 ⫾ 0.42. This average difference represents 5.31% ⫾ 0.27% of average total renographic GFR. Based on control group results a disparity greater than 5.31% of total GFR was considered significant in the study group. Of the 200 study group donors GFR of both kidneys was comparable in 116 cases (58%), the left had better function in 49 (24.5%) and the right had better function in 35 (17.5%). Therefore, a total of 84 donors (42%) had disparity in function between both kidneys. Figure 2 summarizes the frequency distribution of the difference in GFR between the harvested and contralateral kidney in the 84 donors who exhibited disparity in function. In all these donors the kidney with less function was chosen for nephrectomy regardless of anatomical considerations such as multiplicity of renal arteries. In donors with comparable GFR of both kidneys the harvested kidney was essentially chosen on an anatomical basis. The left kidney was removed in 81 (70%) of these cases because of the advantage offered by the longer vein. The right kidney was removed in 35 cases (30%) in view of the multiplicity of renal arteries in the left side (15 cases), when the donor was a female of childbearing age (13 cases) and for pediatric recipients (7 cases) since it was easier to use the right kidney when the renal vein was anastomosed to the inferior vena cava of the recipient. Table 2 summarizes the nephrectomy side relative to split renographic clearance of both kidneys in the 200 study group donors. The impact of the initial clearance value on the final outcome in terms of graft function was also evaluated. There was no difference among recipients who received a kidney with a clearance comparable to its mate and those who received a kidney with a lower clearance value. DISCUSSION

Assuming that total renal function is evenly divided between both kidneys of healthy donors, the decision to use the right or left kidney for transplantation is usually based on morphological findings such as the anatomy of the collecting system on excretory urography and the number of renal arteries on angiography.2, 3 If both kidneys are anatomically similar the left kidney is preferred since it has a longer vein and is thus easier to implant in the recipient. However, anatomical variations occasionally dictate harvesting the right kidney in view of abnormalities in the collecting system or a multiplicity of renal arteries in the left kidney. The right kidney is preferred for donation from females of childbearing

ROLE OF RADIOISOTOPE RENAL SCANS IN CHOICE OF NEPHRECTOMY SIDE

375

FIG. 1. Regression of combined isotope clearance on 24-hour creatinine clearance (r ⫽ 0.7, p ⬍0.0001)

FIG. 2. Frequency distribution of difference in GFR between harvested and contralateral kidney in 84 donors who had disparity in function between both kidneys.

TABLE 2. Nephrectomy side relative to split renographic clearance of both kidneys in 200 donors Renographic Clearance

No. Pts (%)

Rt ⫽ lt Rt less than lt Rt greater than lt

116 (70) 49 (24.5) 35 (17.5)

No. Nephrectomy Side Rt

Lt

35 49 0

81 0 35

age because the left kidney is somewhat more protected from the back pressure changes noted more frequently on the right side during pregnancy.3 Again, the choice of harvested kidney may be determined by specific situations such as previous in situ renal transplants, ileal conduits, the presence of peritoneal dialysis catheters or arteriosclerotic disease.3 Although the previously mentioned factors are important the evaluation of individual renal function is even more critical. It is logical and ethical to leave the donor with the better functioning side. Using bilateral ureteral catheters Hulet et al observed that differences in function between separate kidneys of normal subjects averaged 7.6% and were as high

as 21% for GFR.7 Using radioisotope renography Britton and Whitfield reported that the normal variation of the percentage contribution of each kidney to total radioisotope GFR was 42.5% to 57.2%.8 An error of measurement in the order of 7% due to variation between the depth of each kidney can partly explain this difference. In this series the validity of the technique was confirmed when total renographic clearance was correlated with 24-hour creatinine clearance. The data showed that the disparity in clearance of both kidneys ranged from 0 to 14.25 ml per minute and averaged 6.12 ⫾ 0.42. This average difference represents 5.31% ⫾ 0.27% of average total renographic GFR. A total of 42% of donors had disparity in function between both kidneys of more than the normal average difference. Under such circumstances the choice of the harvested kidney should be based on functional evaluation irrespective of anatomical variations. Studies are invited to correlate radioisotope renography findings with renal mass as determined by US and/or magnetic resonance imaging. If data indicated that renal mass measurement was a reasonable way of predicting differential renal function in the living donor then radioisotope renography would be unnecessary. However, if differential renal

376

ROLE OF RADIOISOTOPE RENAL SCANS IN CHOICE OF NEPHRECTOMY SIDE

function studies with radioisotope renography provide significantly different results, then a case could be made for including radioisotope renography as a routine part of the kidney transplant procedure. Until these studies prove or disprove the importance of renal mass as a method of predicting renal function it is our routine to include radioisotope renography in the selective determination of renal function in potential live kidney donors. One of the reasons for renal imaging in potential kidney donors is to exclude donors with renal stone disease from the group. Our routine evaluation of potential donors includes initial evaluation of both kidneys by KUB and US. It is established that US can easily visualize stones located at the pelviureteral junction, renal pelvis and calices. In a study by Haddad et al9 combined KUB and US yielded a sensitivity of 94% and a specificity of 90% in the diagnosis of renal and ureteral stones. However, stones located in the middle part of the ureter are difficult to visualize with US and could not be seen by KUB if radiolucent. Nevertheless, patients with ureteral stones are usually symptomatic and US shows some dilatation of the pelvicaliceal system. Dilatation will be also evident by magnetic resonance urography. With these conditions spiral computerized tomography is performed to exclude donors with stone disease from the group. It should be reserved if stone disease is suspected based on history of stone passage or previous attacks of renal colic with no evidence of stones on US and KUB. On the recipient side it also remains to be seen whether a transplanted kidney with initial lower efficiency will be able to provide a function similar to that provided by a kidney with initial higher efficiency. This question may be difficult to answer in view of the numerous factors influencing the function of the transplanted kidney such as the effects of ischemia time, trauma, mechanical obstruction, rejection episodes and compensatory hypertrophy. In this study the final graft function was similar among recipients who received a kidney with a clearance comparable to its mate and those who received a kidney with a lower clearance value. However, longer controlled studies are invited to answer this question. Kumar et al recently performed a study to determine the function and outcome of transplanted kidneys from elderly donors with possible nephrosclerosis, atherosclerosis and low GFR. They concluded that elderly kidneys with lower GFR can be used without increasing risk to donor or compromising graft outcome.10

CONCLUSIONS

When renal function of left and right kidney is similar or nearly similar, anatomical factors determine the side of the kidney to be harvested. When there is a significant difference in clearance value (greater than 6 ml per minute) the kidney with the lower clearance value is chosen irrespective of anatomical findings. Since this difference is expected in about 40% of healthy individuals radioisotopic determination of split renal function should be an integral part of the preoperative evaluation of potential kidney donors. REFERENCES

1. Eggers, P. W.: Effect of transplantation on the Medicare end-stage renal disease program. N Engl J Med, 318: 223, 1988 2. Streem, S. B., Novick, A. C., Steinmuller, D. R. and Graneto, D.: Flank donor nephrectomy: efficacy in the donor and recipient. J Urol, 141: 1099, 1989 3. Riehle, R. A., Jr., Steckler, R., Naslund, E. B., Riggio, R., Cheigh, J. and Stubenbord, W.: Selection criteria for the evaluation of living related renal donors. J Urol, 144: 845, 1990 4. Shokeir, A. A., el-Diasty, T. A., Nabeeh, A., Shaaban, A. A., el-Kenawy, M., Wafa, E. W. et al: Digital subtraction angiography in potential live-kidney donors: a study of 1000 cases. Abdom Imag, 19: 461, 1994 5. Tonnesen, K. H., Munch, O. and Hald, T.: Influence on the renogram of variation in skin to kidney distance and the clinical importance thereof. In: Radionuclides in Nephrology. Edited by K. zum Winkel, M. D. Blaufox and J.-L. Funck-Brentano. New York: Mosby-Year Book, Inc., pp. 79 – 81, 1975 6. Gelfand, M. J. and Thomas, S. R.: Effective Use of Computers in Nuclear Medicine. New York: McGraw-Hill Book Co., pp. 51– 53, 1988 7. Hulet, W. H., Baldwin, D. S. and Biggs, H. W.: Measurement of separate kidney function in normal subjects. J Clin Invest, 39: 389, 1960 8. Britton, K. and Whitfield, H.: The radionuclide measurement of disordered renal function. In: The Scientific Foundations of Urology. Edited by G. D. Chisholm and D. I. Williams. London: Heinemann, pp. 65–75, 1982 9. Haddad, M. C., Sharif, H. S., Shahed, M. S., Mutaiery, M. A., Samihan, A. M., Sammak, B. M. et al: Renal colic: diagnosis and outcome. Radiology, 184: 83, 1992 10. Kumar, A., Verma, B. S., Srivastava, A., Bhandari, M., Gupta, A. and Sharma, R. K.: Long-term followup of elderly donors in a live related renal transplant program. J Urol, 163: 1654, 2000