Biomedical subjects
Publications and source records attributed to E V Dubovsky.
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.
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.
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).
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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.
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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.
BACKGROUND: Osteopenia is a major complication of renal transplantation. Immunosuppressive regimens including cyclosporine, which permit the use of lower doses of glucocorticoids, may reduce glucocorticoid-induced osteopenia. METHODS: We prospectively studied the magnitude, distribution, and mechanism of bone loss in 20 adults who received renal allografts from living related donors, who had good renal function, and who were treated with azathioprine, cyclosporine, and low doses of prednisone. We measured serum biochemical markers of bone metabolism, determined the bone mineral density of the second, third, and fourth lumbar vertebrae and the shaft of the radius, and analyzed the histomorphometric features of iliac bone at the time of transplantation and six months later. Measurements of vertebral mineral density were repeated 18 months after transplantation in 17 of the patients. RESULTS: After transplantation, the mean serum concentrations of parathyroid hormone, phosphorus, and alkaline phosphatase decreased and the serum calcitriol concentration increased. The mean (+/- SD) bone mineral density of the vertebrae had decreased 6.8 +/- 5.6 percent 6 months after transplantation (P less than 0.05) and 8.8 +/- 7.0 percent 18 months after transplantation. In contrast, the bone mineral density of the radius had increased six months after transplantation (P less than 0.05). The histomorphometric studies showed that the rate of bone formation decreased from 50.5 +/- 44.8 to 23.1 +/- 13.8 microns3 per square micrometer per year (P less than 0.05), and the formation period lengthened from 70 +/- 42 to 146 +/- 144 days (P less than 0.05). Consequently, the amount of bone replaced during a remodeling cycle diminished. CONCLUSIONS: Osteopenia associated with renal transplantation remains a problem in the cyclosporine era. The loss of vertebral bone in our subjects was due to an imbalance in bone remodeling consistent with a toxic effect of glucocorticoids.
We retrospectively examined the effect of nephrectomy on renal function in 55 living related donors. Renal function was measured with 131iodine-orthoiodohippurate scans. All patients were studied preoperatively, and 1 week and 1 year postoperatively. In 20 patients 10-year followup was available. Compensatory hypertrophy was complete 1 week postoperatively: effective renal plasma flow of the remaining kidney was 32.5% higher than preoperatively. The increase remained stable for at least a year. The degree of compensatory hypertrophy was significantly greater in male patients (46.9% after 1 week) than in female patients (26.7%). Compensatory hypertrophy occurred in all age groups studied and it was most pronounced in patients less than 30 years old. In the patients followed for 10 years effective renal plasma flow decreased from 387.7 ml. per minute 1 week after nephrectomy to 367.4 ml. per minute at 10 years. This result is similar to the decrease seen in the normal population. According to our results, renal donation by living related persons does not lead to long-term decrease in renal function.
It has been proposed that once functioning renal mass has been reduced below a critical level, either as the result of disease, congenital absence of a kidney, or surgical ablation, that hyperfiltration and glomerular hypertension lead to progressive glomerular sclerosis and end-stage renal failure. We report the clinical course and renal function of a human subject followed for 10.8 years after extensive renal ablation. Functioning renal mass was estimated at one fourth to one fifth of normal. During the follow-up period, creatinine clearance increased from 0.27 mL/s (16 mL/min) to 0.88 mL/s (53 mL/min), the total renal plasma flow (all of which was to the left kidney) increased from 62 mL/min to 190 mL/min, and 24-hour urine protein excretion increased from 0.09 g to 0.4 g. Despite probable glomerular hyperfiltration, neither progressive glomerular dysfunction nor end-stage renal failure developed over a period of 10 years.
Hypertension in renal transplant recipients is an important risk factor for graft function and cardiovascular morbidity and mortality. The mechanisms of posttransplant hypertension are not well understood. Most of the time, the nature of this hypertension is multifactorial. Rejection, both acute and chronic, recurrent renal disease, graft renal artery stenosis, native kidney disease and drug therapy with steroids and cyclosporin have all been implicated. Where a single cause can be identified, the therapy can be rational and often very successful. For this reason, the diagnosis of graft renal artery stenosis is important, because percutaneous transluminal angioplasty or surgery can lead to the cure of hypertension and improvement of the graft function. Noninvasive testing, using captopril renography for the diagnosis of hemodynamically significant renal artery stenosis, presently yields encouraging results.
There are a variety of radiopharmaceuticals that can be used to perform captopril renography effectively. We examined a number of technetium and iodine compounds and the circumstances under which each radiopharmaceutical compound is the compound of choice. Considerations of cost, ease of use, reliability, dosage, and the effects of different protocols were all examined.
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Development and validation of simplified renal clearance methods has required a research data base of multiple blood samples drawn over a substantial time interval, which is difficult to obtain for children. While the medical risks entailed in drawing multiple samples may be negligible, the problems of parental and institutional consent make such studies more difficult in the pediatric population. Scaling for patient size permits combining data from patients of different age and limits the number of studies required. A scaling technique is presented and evaluated here. With scaling, adult data can be used successfully to predict pediatric responses and to develop pediatric methods based on adult data alone. Inclusion of pediatric data improves the fit and permits development of generic methods that work with both adults and children.
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Renal parenchymal transit time of the recently introduced radiopharmaceutical 99mTc-MAG3 (mercaptoacetylglycylglycinel) was measured in 37 kidneys, using factor analysis to separate parenchymal activity from that in the collecting system. A new factor algorithm was employed, based on prior interpolative background subtraction and use of the fact that the initial slope of the collecting system factor time-activity curve must be zero. The only operator intervention required was selection of a rectangular region enclosing the kidney (by identifying two points at opposite corners). Transit time was calculated from the factor time-activity curves both by deconvolution of the parenchymal factor curve and also by measuring the appearance time for collecting system activity from the collecting system factor curve. There was substantial agreement between the two methods. Factor analysis led to a narrower range of normal values than a conventional cortical region-of-interest method, presumably by decreasing crosstalk from the collecting system. In preliminary trials, the parenchymal transit time did not well separate four obstructed from seventeen unobstructed kidneys, but it successfully (p less than 0.05) separated six transplanted kidneys with acute rejection or acute tubular necrosis from 10 normal transplants.