Eva V. Dubovsky

Rapid Loss of Vertebral Mineral Density after Renal Transplantation

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.

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.

Short-term and long-term changes in renal function after donor nephrectomy

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.

Quantitation of renal function with glomerular and tubular agents

Quantitative methods to measure the glomerular and tubular function of the kidneys with radionuclides have been available for many years. They have not been widely used because the techniques and the calculations exceeded the scope of routine nuclear medicine practice. Validation of simplified methods and the introduction of computer technology have made measurement of the effective renal plasma flow (ERPF) and the glomerular filtration rate (GFR) simple enough so that they can be performed reproducibly in most nuclear medicine departments. The estimation of ERPF with radioiodinated OIH and GFR with 99mTcDTPA can be achieved in many ways, all of which yield clinically useful results. How to get the best results using the simplest methods is still unclear. The required accuracy depends on the intended clinical use. Our preference at the present time is to use a single or double plasma sample to calculate global ERPF or GFR, and to use the 1-2 min OIH or 1-3 min Tc-DTPA uptake to calculate relative function of the two kidneys (split function ERPF or GFR). The choice of method will be influenced by local factors, such as the nature of the patient population, the case volume, and the resources available. A desirable goal for future studies is to document carefully the capabilities and limitations of each alternative method, so that the choice can be rational.

New formulas for the calculation of effective renal plasma flow

Estimation of effective renal plasma flow (ERPF) can be made easily, inexpensively, and accurately by means of a single plasma concentration determination, sampled 44 min after injection of 131I-orthoiodohippurate (OIH). We originally established predictive regression equations based on a series of patients with a wide variety of diseases and a few normal potential kidney donors. The equation best fitting that data was parabolic in form and assumed a negative slope when high ERPF rates were encountered. This problem has been corrected by deriving new equations (parabolic and exponential) based on an expanded series which includes a large number of subjects with high ERPF. Errors of estimation are lower than those of the more classic para-aminohippuric acid (PAH) clearances and well within the exigencies of clinical practice.

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.

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.

On the mechanism by which chloride corrects metabolic alkalosis in man

To determine whether administration of chloride corrects chloride-depletion metabolic alkalosis (CDA) by correction of plasma volume contraction and restoration of glomerular filtration rate or by an independent effect of chloride repletion, CDA was produced in normal men by the administration of furosemide and maintained by restriction of dietary sodium chloride intake. Negative sodium balance (-112 +/- 16 meq) and reduced plasma volume (2.53 versus 2.93 liters, p less than 0.05) developed. The cumulative chloride deficit of 271 +/- 16 meq was then repleted by oral potassium chloride (267 +/- 19 meq) over 36 hours with continued serial measurements of glomerular filtration rate, effective renal plasma flow, plasma volume, body weight, and plasma renin and aldosterone levels. CDA was corrected, even though body weight, plasma volume, glomerular filtration rate, and renal plasma flow all remained reduced and plasma aldosterone was elevated; urinary bicarbonate excretion increased during correction. Administration of an identical potassium chloride load to similarly sodium-depleted but not chloride-depleted normal subjects produced no change in acid-base status. It is concluded that chloride repletion can correct CDA by a renal mechanism without restoring plasma volume or glomerular filtration rate or by altering sodium avidity.

Renal Function after Acute and Chronic Spinal Cord Injury

Computer-assisted renal scintigraphy was performed on 160 acute and 240 chronic spinal cord injury patients, and 287 noninjured controls. Concurrently, measurements of global and individual kidney effective renal plasma flow, time of maximum activity in each kidney, ratio of maximum counts to the counts at 27 minutes after injection over each kidney and number of counts in each kidney at 1 to 2 minutes after injection were made. The time of peak activity over the kidney and differential function at 1 to 2 minutes after injection were not affected significantly by age, sex or spinal cord status. Global and individual effective renal plasma flows were significantly affected by all of these factors. Both plasma flow measures generally were higher for male than for female patients. Effective renal plasma flow decreased steadily after early adulthood and, except for the youngest and oldest patients, values were lower for spinal cord injury patients than for normal controls. The ratio of peak to 27-minute counts was affected significantly by age and spinal cord injury but not by sex. In patients without obvious pathological conditions followup scintigrams 1 to 3 years after injury showed no significant changes owing to interval since injury on any parameter studied. Lower limits of basal scintigraphic parameters are given for evaluation of renal status in neurologically intact or spinal cord injury persons.

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 (Spearmanρ=0.469,n=53,P <0.005) and for the R20/3 (againρ=0.469,n=53,P <0.005) using the whole-kidney ROI and using only the baseline data without captopril. (Spearmansρ 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.