Prediction of renal transplant survival from early postoperative radioisotope studies.

UNLABELLED: It has been routine at the University of Alabama Medical Center to obtain a radionuclide renal function study immediately after transplantation (usually within 3 d) that includes estimation of effective renal plasma flow (ERPF) from a single plasma sample in addition to imaging. We present here the correlation between baseline measurements and the 1-y graft survival. METHODS: Two cohort years were reviewed: 1988, when 131I-orthoiodohippurate (OIH) was used; and 1995, when 99mTc-mercaptoacetyltriglycine (MAG3) was used. ERPF was measured concurrently with gamma-camera imaging by previously published single-injection, single-sample methods (converting MAG3 clearance to ERPF by means of a correction factor). RESULTS: Graft survival during the first postoperative year improved significantly in the interval between cohort years, from 74% of 147 cadaver (CD) grafts in 1988 to 91% of 200 CD grafts in 1995 (log rank test, P < 0.05). In contrast, for living related donor (LRD) grafts there was no significant change, from 91% of 66 in 1988 to 91% of 83 in 1995. The baseline ERPF was a significant predictor of graft survival in both 1988 and 1995 (Wilcoxon test, P > 0.05). For LRD grafts the association was not significant in either year. Using MAG3 (1995), the peak time and the ratio of counting rate (R) at 20 min to that at 3 min (R20:3) were also significant predictors for CD graft survival. Using OIH (1988 cohort), the correlation with peak time did not reach significance, and the R20:3 measurement was not available. Although multivariate combinations (Cox proportional hazards model) did not have significantly more predictive value at the 95% confidence level than ERPF or R20:3 alone, some statisticians suggest a 75% confidence level for adding an additional covariate to a multivariate model. Use of this level led to a model including both ERPF and R20:3. CONCLUSION: Single-sample ERPF measured in the immediate post-transplant period, whether from OIH clearance or MAG3 clearance, was a statistical predictor of graft survival for CD transplants. For MAG3, the peak time and R20:3 were also significant predictors. These associations held only for CD transplants and not for LRD transplants.

Effect of arteriovenous difference in measuring renal function by single-injection plasma clearance: role of bolus.

Error estimates for arteriovenous difference were calculated by two models, a lag time model and a compartmental model, using Tc99m-diethylenetriaminepentaacetic acid (DTPA) plasma clearance curves from 40 subjects and Tc99m-MAG3 (mercaptoacetyltriglycine) curves from 18 subjects. It was found that correcting for the effect of the initial bolus largely cancelled the conventional arteriovenous difference, so that the net error was negligible.

Reproducibility of single-sample clearance of 99mTc-mercaptoacetyltriglycine and 131I-orthoiodohippurate.

UNLABELLED: Recent literature has questioned whether 99mTc-mercaptoacetyltriglycine (MAG3) clearance measurements are reproducible enough for routine clinical monitoring of renal function. For many years, we have routinely followed the renal function of patients with spinal cord injuries using a combination of radionuclide imaging and clearance measurement. METHODS: In this study, we retrospectively review 1626 effective renal plasma flow (ERPF) measurements in 197 patients with paraplegia or quadriplegia performed over a 21-y period, using 131I-orthoiodohippurate (OIH) through 1990 and MAG3 since 1991. MAG3 clearance was divided by 0.53 to convert it to ERPF. Reproducibility was measured as pooled SD from the single-patient linear regression lines of ERPF versus time. RESULTS AND CONCLUSION: There was no significant difference between MAG3 (SD = 46 mL/min, n = 907) and OIH (SD = 52 mL/min, n = 719). The data were therefore combined to obtain the SD for a single ERPF measurement, which was 49 mL/min. The corresponding coefficient of variation was 8.5% of the mean value of 581 mL/min. In our experience, this is adequate for monitoring the renal function of these patients.

Report of the Radionuclides in Nephrourology Committee for evaluation of transplanted kidney (review of techniques).

Comprehensive evaluation of renal transplants has been important in differential diagnosis of medical and surgical complications in the early post-transplantation period and in the long-term follow-up. If performed well, it yields excellent functional and good anatomic information about the graft that can be effectively used in the patient. That includes selection of patients for biopsy and for various drug regimens. This is true especially in patients with anuric acute tubular necrosis (ATN) and in patients with developing chronic rejection. Improving indices of renal function (effective renal plasma flow, uptake of tubular tracers) can indicate resolution of tubular injury (ATN) while there is still no improvement in plasma creatinine. In patients with chronic rejection, plasma creatinine increases only after approximately 30% of renal function is lost due to graft fibrosis. Early recognition of this condition could permit treatment and delay of retransplantation. The protocol recommended at the Copenhagen meeting includes a flow study, scintigram of the kidneys, prevoid and postvoid bladder image, injection site image (quality control), time/activity curves of the graft and bladder, and quantitative data of perfusion, function, and tracer transit. The flow study obtained during the initial transit of the bolus through the graft could be performed either with 99mTc mercaptoacetyltriglycine, or 99mTc diethylenetriaminepentaacetate (DTPA). Quantitative analysis of perfusion facilitates interpretation of the study during the early post-transplantation period. ATN, common in cadaver transplants, typically shows adequate perfusion. The function phase should include images and time/activity curves. Images alone are insufficient. Quantitative data such as clearance or other indices of function and indices of tracer transit are essential for correct interpretation of the results. Normal images and normal graft function reliably exclude clinically important complications. A single scintigram demonstrating prolonged tracer transit with decreased function cannot separate acute rejection and ATN. On serial studies, decline in function and poor perfusion are indicative of acute rejection. A normally appearing scintigram without cortical retention, but with low function, is consistent with chronic rejection. Pharmacological intervention to exclude obstruction (diuretic renogram) or hemodynamically significant renal artery stenosis (angiotensin converting enzyme challenge) should be used whenever indicated.

Prediction of urinary excretion of technetium-99m-MAG3.

UNLABELLED: The urinary excretion of 99mTc-mercaptotriacetylglycine (MAG3), like that of 131I-orthoiodohippurate (OIH), can be used to identify acute renal transplant rejection and measure its severity. This parameter is often quantitated as the excretory index (observed excretion/predicted excretion). A new method for predicting the urinary excretion of 99mTc-MAG3 is presented. METHODS: The expected excretion was calculated from multisample plasma time-activity curves in 122 subjects, with correction for the first pass of the initial bolus. The resulting formula was tested prospectively against actual urine measurements in an additional 466 subjects. RESULTS: Least-squares fitting led to the following equation: Predicted excretion = 0.79(1-exp(-0.0066CMAG3), with residual s.d. 0.06, where CMAG3 is MAG3 clearance in ml/min and the predicted excretion is expressed as a fraction of the administered dose. Tested prospectively in the additional 466 subjects, the s.d. was 0.09. CONCLUSION: A new formula to predict the urinary excretion of 99mTc-MAG3 has been developed and prospectively validated. Based on our data, the normal range for the excretory index using MAG3 is the same as that of 131I-OIH, 0.8-1.2.

Use of macroaggregated albumin lung perfusion scan to diagnose hepatopulmonary syndrome: a new approach.

BACKGROUND & AIMS: We have reported that contrast echocardiography is a sensitive screening test for the hepatopulmonary syndrome (HPS). However, contrast echocardiography lacks specificity because many cirrhotic patients have positive study results with normal arterial blood gases and therefore do not fulfill criteria for HPS. The aim of this study was to assess the role of macroaggregated albumin lung perfusion scans (MAA scans) in the diagnosis of HPS. METHODS: MAA scans were performed in 25 patients with HPS, 25 cirrhotic patients without HPS, and 15 hypoxemic subjects with intrinsic lung disease alone. An MAA shunt fraction was calculated from brain and lung counts. RESULTS: MAA scan results were positive in 21 of 25 patients with HPS and negative in all controls. All 21 patients with positive MAA scans had PO2 values of <60 mm Hg. There was a strong inverse correlation between the degree of the MAA shunt fraction and arterial hypoxemia (r = -0.726). CONCLUSIONS: A positive MAA scan result in cirrhosis is specific for the presence of moderate to severe HPS. We speculate that MAA scans may be particularly useful in evaluating the contribution of HPS to the hypoxemia in cirrhotic patients with intrinsic lung disease.

Renal vascular transit time and tubular transit time dispersion for 99Tcm-MAG3.

Renal transit time usually refers to tubular transit time, as introduced by Taplin, but other measures of renal transit have been proposed. Here we examine the vascular transit time (VTT, following Rutland) and the standard deviation of tubular transit time (SDTT, following Britton) in a group of 30 patients having baseline and ACE-inhibitor 99Tcm-MAG3 renography prior to arteriography. A same-day, low-dose/high-dose protocol was used for renography; only the post-captopril dose was high enough to measure VTT. Pre-captopril, the Spearman rank correlation coefficient for SDTT was rho = 0.52 (n = 53 kidneys; P < 0.0002); post-captopril, rho = 0.54 (n = 49 kidneys; P < 0.0002). For VTT, the post-captopril value was rho = 0.24 (n = 30 kidneys; N.S.). For comparison, the same statistics were calculated for Taplin's original measure of transit time: the time from injection to maximum count rate (peak time). Pre-captopril, for peak time, rho was 0.47 (n = 53 kidneys; P < 0.001); post-captopril, rho was 0.39 (n = 50 kidneys, P < 0.01). These findings confirm the diagnostic value of SDTT but not of VTT. SDTT correlated better than peak time with the arteriographic findings.

Comparison of long-term renal function after spinal cord injury using different urinary management methods.

OBJECTIVE: To determine the effect of different bladder management methods on long-term renal function in persons with spinal cord injury (SCI). DESIGN: Cohort study. SETTING: Model SCI care system within a large teaching hospital. PATIENTS: Consecutive sample of 1,114 persons with SCI who were injured between 1969 and 1994. MAIN OUTCOME MEASURE: Total and individual kidney effective renal plasma flow (ERPF). RESULTS: ERPF was generally lower in persons with cervical injuries or kidneys that had a renal stone, older persons, and women. Overall, there was very little change in renal function as time postinjury increased, and there were no clinically meaningful differences in the change in renal function over time among persons using different bladder management methods. CONCLUSION: Renal function was adequately preserved in the great majority of persons and did not appear to be influenced to any great extent by method of bladder management.

Measurement of renal function with technetium-99m-MAG3 in children and adults.

UNLABELLED: A single-injection, single-sample procedure for measuring 99mTc-MAG3 clearance is presented that incorporates scaling for patient size and is valid for both children and adults. METHODS: The procedure is based on an empirical formula in which all measurements are expressed in dimensionless combinations. The formula was obtained by fitting data collected from 122 adults and 80 children at several centers. RESULTS: All results were scaled to standard adult surface area and are presented in units of ml/min/1.73 m2. For adult subjects, the residual standard deviation (r.s.d.) calculated from a single sample at 45 min was found to be 23, using the plasma clearance calculated from a multi-sample clearance curve as a reference. This did not differ significantly from the value of 22 obtained with our previous formula, which was valid for adults only. For pediatric subjects, an r.s.d. of 24 was calculated by the new formula from a single sample at 35 min; a comparable value of 33 was found using a pediatric formula previously published. CONCLUSION: The new clearance formula is recommended as a replacement for the formula we previously published, since it is based on a larger and more diverse subject population, and since it now holds for children as well, with no loss of accuracy for adult subjects.

Techniques for measuring renal transit time.

A variety of techniques have been used for quantitative estimation of renal transit time. We compared different indices of transit time in a group of 30 patients having baseline and ACE inhibitor technetium-99m mercaptoacetyltriglycine (MAG3) renography prior to arteriography: peak time, mean transit time, and the ratio of background-subtracted counts at 20 min to those at 3 min. Each index was calculated from whole-kidney ROI, cortical ROI, and cortical factor (by factor analysis). The strongest correlations between angiographic percent of stenosis and transit time index were observed for the peak time (Spearman p=0.469, n=53, P <0.005) and for the R20/3 (again p=0.469, n=53, P <0.005) using the whole-kidney ROI and using only the baseline data without captopril. (Spearman's p is simply the correlation coefficient calculated from rank in list, which allows for nonlinear correlation.) Thus simple indices of transit time (whole-kidney peak time and R20/3) correlated as well with the observed pathology as did more complicated methods that required deconvolution, factor analysis, or selection of a cortical ROI.

Compliance with annual urologic evaluations and preservation of renal function in persons with spinal cord injury.

We located 59 persons with spinal cord injury (SCI) who had not been examined for 3-15 years and paid them to undergo evaluation and comparison with 101 controls examined on an annual basis. Renal function during the first year post-injury and at follow-up was measured by radioisotopic scanning to determine effective renal plasma flow (ERPF) and information was obtained regarding occurrence of specific secondary complications. Subjects and controls were alike with respect to demographic characteristics, injury-related variables and occurrence of specific secondary complications. Mean initial and follow-up ERPF values adjusted for increasing age were not significantly different for subjects and controls, nor was there significant change within individuals over time. Although serial examination of the urinary tract following SCI is important, after the first few years it may be acceptable to lengthen the periods between examinations or substitute less expensive, noninvasive diagnostic techniques. SCI care centers should carefully evaluate recommendations regarding follow-up urologic examinations in persons with SCI in order to provide the most cost-effective program while maintaining optimum patient care.

Comparison of single-injection multisample renal clearance methods with and without urine collection.

UNLABELLED: Single-injection renal clearance methods based on plasma clearance alone, without urine collection, are sometimes met with skepticism. They require data extrapolation to infinite time, which is hard to justify a priori. It has been asserted that they are less accurate for rapidly cleared tubular agents than for slowly cleared glomerular filtration rate agents. In this study, we compare urine-based and urine-free methods for the tubular agents 99mTc-MAG3 and 131I-OIH. METHODS: In 18 patients, dual-tracer plasma data were obtained from 4 to 90 min after injection (nine samples). Urine was also collected for 90 min (in two voidings). The urine counts wre corrected for residual bladder activity by pre- and postvoid dual-channel gamma camera images. RESULTS: When comparing the two methods of clearance calculations, the difference between urine-based and urine-free measurements 1 +/- 5 ml/min for 99mTc-MAG3 and 23 +/- 8 for 131I-OIH (mean +/- s.e. of the mean). For 99mTc-MAG3, the regression line did not differ significantly from the line of identity. The correlation coefficient was 0.94 for both agents. CONCLUSION: Urine collection is not necessary to measure renal clearance, even for the rapidly cleared tubular agents, except at low clearance levels (when the small absolute error corresponds to a large percentage error).

Radionuclide evaluation of renal transplants.

Chronic renal failure caused by hypertension or by parenchymal kidney disease is a very common global health problem. Patients with chronic renal failure have two therapeutic options, dialysis and transplantation, of which transplantation has become a preferred modality. This review article is an update of a more comprehensive previous review (Semin Nucl Med, 181-198, 1988) and concentrates on the changes that have taken place in this field in recent years. These changes comprise new criteria for the selection of transplant candidates, newer techniques for the diagnosis of medical and surgical complications after transplantation, the use of new tracers (Tc-99m MAG3), and new antirejection regimens.

A single-injection, two-sample method for measuring renal 99mTc-MAG3 clearance in both children and adults.

We present a method for estimating 99mTc-MAG3 clearance from both a single injection and two blood samples that is valid for both adults and children. It was obtained by fitting a scaled two-compartment model (having only two adjustable parameters) to adult and pediatric data from multiple centers.

Quantitation of renal parenchymal retention of technetium-99m-MAG3 in renal transplants.

UNLABELLED: When imaging renal transplants with tubular agents, such as mercaptoacetyltriglycine, marked parenchymal retention is a hallmark of acute rejection (AR) or acute tubular necrosis (ATN). (AR can be distinguished from ATN by the time course on serial studies.) The quantitative relationship of retention to uptake can be measured by dividing the background-corrected renal activity at 20 min by that at 3 min. METHODS: The diagnostic value of this ratio (R20/3) was tested in a series of 555 renograms. Because patients with mild disease have minimal abnormalities, the patients were ranked by their estimated severity of disease (1-4 for abnormal and 0 for normal). RESULTS: R20/3 was found to correlate strongly with severity of ATN (Spearman's rho = 0.879, p < 0.001, n = 168) and also with severity of AR (rho = 0.888, p < 0.001, n = 267). There were two (3%) false-positive results in 64 normal patients. CONCLUSION: If 0.8 is taken as the upper limit of normal for R20/3, then among patients with disease severity 3 or 4, there were no false-negative findings in 104 patients with ATN or in 203 patients with AR. R20/3, despite its simplicity, is an effective diagnostic parameter.

Renal transplant hypertension caused by iliac artery stenosis.

A captopril renal study performed with both radiohippuran and 99mTc-MAG3 demonstrated the typical changes of a hemodynamically significant renal artery stenosis in a hypertensive renal allograft recipient. Arteriography demonstrated high grade stenosis not of the renal artery but of the iliac artery. After successful angioplasty, the patient's hypertension resolved.