fter removal of 1 kidney because of disease, cancer,

injury, or transplant donation, functional adaptation andcompensatory hypertrophy of the remaining kidney takeplace. Compensatory renal growth has been shown instudies of animals and humans (1—4).Kidney enlargementhasbeen estimated radiologically by an increase in length orin some indices using the length, width, or volume (1,3,4).Renal volume determination by sonography has shown a20%—100%increase in the remaining kidney volume (3,4).Functional adaptation of the remaining kidney after unilateral nephrectomy has a rapid onset, more so for glomerular

function than for tubular function. The creatinine clearanceincreases to 70%—75%of the preoperative creatinine clearance within several weeks postoperatively (5) and remainsstable for more than 10 y after nephrectomy (6—8).Theserum creatimne level usually increases up to 20% abovebaseline, remaining within the normal range (9,10). Theeffectiverenalplasmaflowincreasesby about30% asearlyas 1 wk after surgery (8) and remains above the prenephrectomy level even after 10 y.

The renal uptake of 99mTc..dimercaptosuccinic acid(DMSA) has been shown to correlate well with effectiverenal plasma flow, glomerular filtration rate, and creatinineclearance(11—13).QuantitativeSPECT of @Tc-DMSA(QDMSA) uptake by the kidneys has been shown to beuseful in separating normal from diseased kidneys (14), tocorrelate well with creatinine clearance and serum creatimne

level in patients with single kidneys (14, 15), and to be areproducible method to monitor serial changes in individualrenal function (16). The aim of this investigation was toevaluate the volume and function of the remaining kidneyafter resection of a functioning kidney by QDMSA studies.

MATERIALS AND METHODS

Patient PopulationForty-five patients with renal tumors were enrolled prospec

tively in the study. Fifteen of these patients were excluded: 5 werelost to follow-up, 2 died after surgery, 2 had diagnoses of benignrenal cysts and did not have surgery, 2 had hypofunctioning of theresectedkidney,1 refusedsurgery,1 hadwidespreaddiseasewith

To determinethe function of the remainingcontralateral kidneyafter the removalof a functioningkidney,30 consecutivepatients(18 men, 12 women; average age, 67 y; age range, 34—87y) whowere undergoingunilateral radical nephrectomywere evaluatedby sequentialquantitative @Tc-dimercaptosuccinicacid (DMSA)SPECT (QDMSA) studies. Methods: The 30 patients wereundergoingradicalnephrectomyfor renaltumors.The first studywas done before surgery.Follow-upstudieswere performed2—23moaftersurgery.Clinicalevaluationsanddeterminationsofserum creatinine level were performedat the same time as theQDMSA studies.Results: The relativecontributionof the resected kidneys to the global renal function before surgery was43.2% ±7.3%.Aftersurgerytheuptakeofthe remainingkidneyincreasedfrom 13.4% ±4.0% to 18.3% ±5.8% (t = 5.7; P =0.0000). The relative function ofthe remaining kidney increasedfrom 56.8% ±7.1% to 79.1% ±23.6% (t = 4.9; P < 0.0001) ofthe global renal function before nephrectomy.Increases in therenal volume (from211 ±62 cm3to 229 ±68 cm3;t = 4.5; P =0.0001) and in the percentage injected dose per cubic centimeter(%lDIcm3)of the remainingkidney(from0.066 ±0.02 %ID/cm3to 0.085 ±0.03 %ID/cm3t = 4.6; P = 0.0001)wereassociatedwiththis change.Ninepatientshad2 follow-upstudiesperformed3—4mo after surgery and 12—14mo after surgery. The volume ofthe remaining kidney (209.22 ±46.20 cm3 versus 217.88 ±58.85 cm3; t = 0.962; P = 0.364), the %lD/cm3(0.09 ±0.016%ID/cm3versus0.093 ±0.025 %lD/cm3;t = 0.362;P = 0.726),and the percentageuptake (19.26% ±4.45% versus 20.11% ±7.01%) did not change significantly between these 2 QDMSAstudies. Conclusion: The results of this study suggest thatadaptivechangescausinghyperfunctionof the remainingkidneymay occur after nephrectomyof a functioning kidney in adults.These changesoccur soon after surgery,persist for at least 1 y,and are evidenton QDMSAstudies.

Key Words: radionuclideimaging;quantitativeSPECT; @TcDMSA;nephrectomy

J NuclMed2000;41:1025—1029

ReceivedJun. 14, 1999; revision accepted Sep. 21, 1999.For correspondence or reprints contact: Simona Ben-Haim, MD, DSc,

Department of Nuclear Medicine, Carmel Medical Center, Haifa, Israel 34362.

KIDNEY FUNCTION AFTER RADICAL NEPHRECTOMY •Ben-Haim et al. 1025

Kidney Function After Radical Nephrectomy:Assessment by Quantitative SPECT of99mTCDMSAUptake by the KidneysSimonaBen-Haim, Vladimir Sopov,Avi Stein,Boar Moskovitz, Avi Front,Yoel Mecz, Levy Las,Alexander Kastin,Ofer Nativ, and David Groshar

Departments ofNuclear Medicine and Urology, Cannel Medical Center and Bnai Zion Medical Center@Faculty of Medicine,Technion—IsraelInstitute ofTechnology, Haifa, Israel

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lung metastases and did not have surgery, 1 had partial infiltrationof the radiopharmaceuticaldose and the study was technicallyinadequate, and 1 did not have follow-up of his serum creatimnelevel at the time of the QDMSA study after surgery. The studypopulation consisted of the remaining 30 patients (18 men, 12women; average age, 67 y; age range, 34—87y). Twelve (40%)patients had hypertension, 2 (6%) had diabetes, and 1 (3%) hadnephrolithiasis of the remaining kidney. All patients underwentradical nephrectomy of a functioning kidney. Twenty-six patientshad malignant tumors: 24 had@ renal cell carcinoma, 1 had atransitional cell carcinoma of the ureter, and 1 had a retroperitonealliposarcoma. Four patients had benign tumors of the kidney: 1 hada cystic nephroma, 1 had a simple cyst, 1 had multilocularrenalcysts, and 1 had perinephric pseudocysts. Each patient had 2 or 3sequential QDMSA studies. A total of 69 QDMSA studies wereevaluated. All patients had a study performed immediately beforesurgery. A second study was performed 2—23mo after surgery. In 9of these patients an early follow-up study was performed 2—6moafter surgery(early follow-up) and anotherstudy wasperformed12—17mo after surgery (late follow-up). At the same time, patientswere evaluatedclinically, and serumcreatininelevels were determined.

QuantitativeSPECTThe techniquehas been reportedin detail (14) and is described

briefly. Quantitative SPECT of@―Tc-DMSAuptake by the kidneyswas measured using the same methodology as in previous studies(14,15,17). The patient was injected with 75—150MBq (2—4mCi)

@Tc-DMSA,and SPECT was performedafter 4-6 h. The exactdose injected was obtained by measurement of the syringe in thedose calibrator before and after the injection. The amount ofradioactivity was corrected for decay from the time of injection tothe time the study was actually performed. The studies wereperformed using a rotating, single-head @ycamera equipped by anall-purpose, low-energy collimator (Apex 415-ECT; Elscint, Ltd.,Haifa, Israel). Data acquisition lasted 20 mm, with 120projections,30 apart. accumulating 3—5 X 10@ counts per study. The raw data

were reconstructed by filtered backprojection using a Hann filterwith a cutoff of 0.5 cycle/cm. After reconstruction, each image wassectioned at 1-pixel (0.68 cm) intervals in the transaxial, coronal,and sagittalplanes using a 64 X 64 byte matrix.Kidney volumesandradioactiveconcentrationmeasurementswerecalculatedon thetransaxial reconstruction data using the threshold method. Afterobtaining a series of phantom measurements using volumes of30—3800cm3 and concentrations between 0.375 and 135 kBq/cm3,a threshold value of43% was found to be optimal for @Tc(15,18).

On the transaxial slices the operator identifies the slice to definethe kidney and draws a region of interest aroundthe organ. Forvolume measurements(in cubic centimeters)the numberof pixelscontaining activity greater than the threshold in all sectionsmultiplied by the slice thickness is calculated. For concentrationmeasurements, the threshold value is subtracted from all pixels inthe regions of interest in all slices. All nonzero pixels with highercounts than the threshold value are used to calculate the concentration. Counts per voxel are converted into concentrationunits (inkBq/cm3)using the regression line obtained previously by phantommeasurements (18). The percentage injected dose per cubic centimeter (%ID/cm3) of renal tissue is calculated using this valuecorrected for radioactivity decay. Kidney uptake is then obtainedby multiplying kidney volume (in cubic centimeters) and %ID/cm3

(14). Excellent correlation (r 0.99) has been found betweenactual concentration in kidney phantoms and SPECT-measuredconcentration (14), and a coefficient of variation for replicatestudies of <2% was also found in phantom studies (19), indicatingthat the method can be used reliably to measure the concentrationof @Tc-DMSAin the kidneys.

Statistical AnalysisThe t test and paired t test were used to compare preoperative

versus postoperative and remaining versus resected kidney valuesofvolume in cubic centimeters, %ID/cm3,and percentage uptake aswell as serum creatinine levels. Values are expressed as mean ±SD. Linearregressionanalysiswas used to evaluatethecorrelationbetween serum creatinine level and renal uptake before and aftersurgery.

RESULTS

Patientcharacteristicsand resultsof QDMSA studiesaresummarized in Table 1 and Table 2. Before surgery theoperated kidneys contributed 43.2% ±7.3% to the globalrenal function (right and left kidneys), and the contralateralkidneys contributed56.8% ±7.3%. The uptake of @TcDMSA before surgery in the contralateral kidney was13.4% ±4.0%. This increased to 18.3% ±5.8% (t = 5.7;P = 0.0000). This increase was associated with an increasein renal volume from 211 ±62 cm3 to 229 ±68 cm3 (t =4.5; P = 0.0001) as well as an increase in %ID/cm3 from0.066 ±0.02 %ID/cm3 to 0.085 ±0.03 %ID/cm3 (t = 4.6;P = 0.0001). In the 9 patients who had early and lateQDMSA studies performed after surgery there was nosignificant change in the contralateral kidney uptake(19.26% ±4.45% versus 20.11% ±7.01%; t = 0.457; P =0.6599), renal volume (209.22 ±46.2 cm3 versus 217.88 ±58.85 cm3; t = 0.962; P = 0.364), and %ID/cm3 (0.09 ±0.016 versus 0.093 ±0.025 %ID/cm3; t = 0.362; P = 0.726)betweenthese2 examinations.After surgerythe functionofthe remaining kidney increased to 79.1% ±23.6% of total(both kidneys) preoperative renal function compared with56.8% ±7.3% preoperatively (t = 4.9; P < 0.001).

Serum creatininelevels before surgerywere within normal limits in all patients, except for 2 (6.6%) with creatiinelevels of 1.7 and 2.0 mg/dL (patients 1 and 27; Table 1). Theaverage preoperative serum creatiine level was 1.04 ±0.28mg/dL. It increased to 1.55 ±0.46 mg/dL after surgery (t =7.695; P = 0.0000). In the 9 patients who had theircreatinine levels determined at early and late follow-up aftersurgery,no significant changewas found between thoselevels (1.433 ±0.40 mg/dL versus 1.45 ±0.40 mg/dL; t =0.80; P = 0.447). Abnormal serum creatimne levels (>1.6mg/dL) were more common after surgery, occurring in 6(20%) of the patients. In the 6 patients with elevatedcreatinine levels after surgery, the uptake of @Tc-DMSAinthe nonoperated kidney before surgery was 11.2% ±3.0%compared with 14.3% ±4.0% in the nonoperated kidneys ofpatients with postoperative serum creatinine levels < 1.6mg/dL (t = 2.007; P = 0.0545). Otherwise, no change in thepatients' clinical status occurred after surgery.

1026 Tim Joui@u. OFNUCLEARMEDICINE•Vol. 41 No. 6 •June 2000

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Creatinine(mg/dL)

Patient AgeQDMSARemoved

kidney, preopContralateral kidney, preopContralateral kidney,postopVolumeUptakeVolumeUptakeVolume

UptakeFollowno. (y) Sex Preop Postop(cm3) %ID/cm3(%)(cm3) %ID/cm3(%)(cm3) %lD/cm3 (%)up(mo)1

71 M 1.7 2.3143 0.0253.55201 0.0367.3197 0.0397.78265 M 1.0 1.6152 0.046.1240 0.05312.7250 0.06215.62377 M 1.1 1.6180 0.0488.8198 0.0489.5226 0.04710.77465 F 1.0 1.1179 0.0814.4191 0.0917.0201 0.12024.72534 F 0.4 0.9229 0.07116.4198 0.08216.4232 0.10123.510671 M 1.0 2.8252 0.037.6328 0.04615.2364 0.04215.411763 M 1.4 1.6220 0.061 3.2220 0.06414.2242 0.07919.23852 M 1.1 1.3291 0.0319.1437 0.03917.4471 0.02913.97944 M 0.8 1.5193 0.0397.7256 0.0379.54277 0.06618.331068 M 1.0 1.6240 0.05613.5250 0.0512.5258 0.045 11.6121170 F 0.9 1.3192 0.06713.1196 0.0713.9208 0.09119.0131253 M 1.0 1.4208 0.05912.4225 0.08118.2260 0.09324.3141387 M 1.2 2.5220 0.04610.3220 0.06213.8210 0.08217.4231466 F 0.8 1.4231 0.0399.2250 0.0399.9259 0.05815.3101573 F 1.0 1.5135 0.0669.0121 0.0799.6137 0.09713.331675 M 1.0 1.4174 0.0569.8169 0.06611 .2204 0.10120.7141755 F 0.9 1.1166 0.0711.7168 0.06811.5211 0.07215.13/12*1852 M 1.1 1.4251 0.038.6229 0.0512.3270 0.09826.63/14*1973 F 1.0 1.4131 0.11414.9159 0.10516.6185 0.16931.232079 M 0.9 1.3165 0.069.4180 0.0610.4180 0.11921.53/12*2174 F 0.9 1.5132 0.1114.5159 0.1117.0174 0.11920.73/13*2269 M 1.2 1.7139 0.034.6196 0.059.2172 0.11720.282380 M 1.1 1.5125 0.1113.9203 0.1224.5197 0.11923.632480 M 1.2 1.9168 0.069.6232 0.06515.0210 0.10020.63/12*2566 M 1.0 1.2204 0.0611.6259 0.0512.2310 0.04616.52/11*2673 F 0.9 1.2124 0.0749.24224 0.08619.3288 0.11934.03/172776 M 2.0 2.3173 0.0417.12144 0.0557.9135 0.08114.36/12*2876 F 0.8 1.0114 0.0637.24172 0.09416.3155 0.11217.362971 F 0.9 1.51 98 0.05711 .3159 0.0528.37159 0.0365.7543046 F 0.8 1.1145 0.0912.4170 0.0915.4184 0.09016.03/12*follow-up.

Preop= preoperative;postop= postoperative.

DISCUSSION stimulation for renal growth. Humoral and neural mecha

After removal of 1 kidney compensatory growth changes msms are also possible causative factors (21,22). Hyperplaoccur in the remaining kidney (20). Increasedrenal blood sia and hypertrophyare characteristicof the compensatoryflow and glomerular pressures may cause a mechanical growth. Several studies have examined the effects of renal

donation on the contralateral kidney. Hypertension, mildproteinuria, and a decrease in creatinine clearance may

TABLE 2Quantitative DMSA SPECT Before and After Nephrectomy develop in long-term follow-up, but theseare no greater than

____________________________________________ those in the normal population. In spite the known functionalResected Contralateral Contralateral and structural changes after nephrectomy, donor renalkidney, kidney, kidney, function remains stable for many years after renal donation

Parameter preop preop postop (8,22—25).

Volume(cm3) 186 ±45 211 ±62 229 ±68* Renal cortical scintigraphy with @Tc-DMSA is being%ID/cm3 0.059±0.02 0.066±0.02 0.085±0.03* used for functional imaging of the proximal renal tubularUptake(%) 10.3±3.2 13.4 ±4.0 18.3±5.8t mass, which is dependent on renal blood flow and on the

proximal tubule cell membrane transport function (13,26).*P = 0.0000. Quantitation of @Tc-DMSAuptake in each kidney sepatP = 0.0001 . rately provides a practical index of absolute renal functionPreop= preoperative;postop= postoperative. (11—15,17,27—30).Absolute quantitation of @Tc-DMSA

TABLE 1PatientCharacteristicsand QDMSA SPECT Data BeforeandAfterNephrectomy

KIDNEY FUNCTIONAFFER R@rnc@u.NEPHRECTOMY•Ben-Haim et al. 1027

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uptake by the kidneys has been used in separating normalfrom diseased kidneys (14). A good correlation (r = 0.76)between QDMSA and creatinine clearance (15) and between

QDMSA and serum creatinine (14,15) has been reported inpatients with a single kidney. QDMSA has also been shownto be a reproduciblemethod that can be used to monitorserial changes in individual renal function with a precisionofl.l%(16).

Patients in this group, after nephrectomy because of renaltumor, showeda compensatoryresponsein the remainingkidney. The compensatory increase in the absolute uptake of

@Tc-DMSAby the remaining kidney was associated withan increasein the renal volume andan increasein %ID/cm3.The functionof the remainingkidney increasedto 79.1% ofthe total preoperative renal function compared with 56.8%beforesurgery.The compensatorychangesseenearly afternephrectomy remain unchanged between the early and late

follow-up studies, probably reaching a plateau at this time.These findings agree with similar observations made indifferent patient groups undergoing nephrectomy. Kidneyenlargement of 20%—l00% was shown by sonographyduring long-term follow up (2—4).Anderson et al. (8)measured renal function on ‘311-labeledo-iodohippuratescans and found an increase in the effective renal plasmaflow of 32.5% by 1 wk and 30.1% within 1 y over thebaselinepreoperativevaluesafter renal donation.The meanpostoperative effective renal plasma flow represented 66%

of the total preoperative effective renal plasma flow. Pabicoet al. (31) found a 55% increase in the effective renal plasmaflow calculated with p-aminohippurate clearance within10—14d after donor nephrectomy. Vincenti et al. (5) found acreatinine clearance of 72% of the preoperative value 1 wkafter nephrectomy.

In 27 patients who were monitored for more than 20 y,Regazzoni et al. (25) found an immediate increase increatinine clearance of about 34%, peaking at 2—6mopostoperatively and then reaching a plateau. Smith et al. (32)monitored 40 patients for 5—30y (mean, 11.8 y) afterunilateral nephrectomy. Serum creatinine levels increased in

these patients by 17% (from 1.1 to 1.29 mg/dL), althoughthis increase was not statistically significant. Measures ofglomerular function (serum creatinine, creatinine clearance,or inulin clearance) are remarkably stable with time afterunilateral nephrectomy. The glomerular filtration rate afterdonor nephrectomy generally stabilizes at 75%—85%of thepredonation values, and serum creatinine increasesbyapproximately 20% (5—8,10,33—35).Our findings agree withthese reports, which also showed an increase in serumcreatinine levels in all patients. However, this increase wasmore pronounced than that in our patients, reaching to 55%abovebaseline.This finding may associatedwith the factthat our patients were older and a significant percentage hadother disordersaffecting renal function, suchas hypertension, diabetes, and nephrolithiasis of the remaining kidney.

This study also assessed the possibility of predicting

long-term follow-up results on the basis of the preoperativeevaluation of the contralateral kidney function, indicated bythe absolute uptake of @Tc-DMSAby that kidney. In the 6patients who had significant increases in creatinine levelsafter surgery, reaching the abnormal range (> 1.6 mg/dL),

thepreoperativeQDMSAdatasuggesta relativelyreducedpreoperative uptake (although not statistically significant) inthe nonoperated kidney. If, indeed, it is possible to predictpreoperatively the postoperative renal function on the basisof QDMSA, thisstudymay be potentiallyusefulin identifying a subset of patients who may need consideration of adifferent surgical intervention (e.g., nephron-sparing surgery), a special diet (e.g., dietary restriction of protein andphosphate), a change in medication to prevent renal functiondeterioration (angiotensin-converting enzyme inhibitors,heparin, or calcium channel blockers), and a closer follow-up for the evaluation of the possibledeteriorationofrenal function after surgery.However, our findingsare notstatistically significant, possibly because of the small number of patients and overall relatively preserved renal function in thispatientgroup.No patientdevelopedrenal failureafter surgery.

CONCLUSION

Compensatory hyperfunction is common after nephrectomy because ofrenal tumor and can be shown on QDMSA.Compensatory hyperfunction is caused by an increase inrenal volume and in %ID/cm3 in the remaining kidney,occurs early after surgery, and remains essentially unchanged for at least 1 y after surgery. The ability to identifypreoperatively a high-risk group of patients with significantpostsurgical deterioration of renal function needs to befurtherevaluated.

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KIDNEY FUNCTIONAFTER RADICALN@mu@croMY •Ben-Haim et a!. 1029

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2000;41:1025-1029.J Nucl Med.   Nativ and David GrosharSimona Ben-Haim, Vladimir Sopov, Avi Stein, Boaz Moskovitz, Avi Front, Yoel Mecz, Levy Las, Alexander Kastin, Ofer 

Tc-DMSA Uptake by the Kidneys99mKidney Function After Radical Nephrectomy: Assessment by Quantitative SPECT of

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