Accuracy of single-photon emission computed tomography in differentiating frontotemporal dementia from Alzheimer's disease.

BACKGROUND: Alzheimer's disease (AD) and frontotemporal dementia (FTD) are the commonest causes of presenile dementia. In the absence of a biological marker, diagnosis is reliant on clinical evaluation. Confirmation is often sought from neuroimaging, including single-photon emission computed tomography (SPECT). Most previous SPECT studies lack pathological validation. AIM: To examine the accuracy of SPECT in differentiating FTD from AD in patients with subsequent pathological confirmation. METHODS: Technetium-99-labelled hexamethyl propylene amine oxime SPECT images obtained at initial evaluation in 25 pathologically confirmed cases of FTD were examined. These images were visually rated by an experienced blinded nuclear medicine consultant and compared with those of 31 patients with AD, also with pathological validation. RESULTS: A reduction in frontal cerebral blood flow (CBF) was more common in FTD and was of diagnostic value (sensitivity 0.8, specificity 0.65 and likelihood ratio (LR) 2.25; 95% CI 1.35 to 3.77). A pattern of bilateral frontal CBF reduction without the presence of associated bilateral parietal CBF change is diagnostically more accurate (sensitivity 0.80, specificity 0.81 and +LR 4.13, 95% CI 1.96 to 8.71). Diagnostic categorisation (FTD or AD) on the basis of SPECT alone was less accurate than clinical diagnosis (based on neurology and detailed neuropsychological evaluation). One patient with FTD was initially clinically misdiagnosed as AD, owing to the lack of availability of full neuropsychological assessment. However, SPECT correctly diagnosed this patient, providing a diagnostic gain of 4%. CONCLUSION: Technetium-99-labelled hexamethyl propylene amine oxime SPECT CBF patterns provide valuable information in the diagnosis of FTD and AD. These data can be better used as an adjunct to clinical diagnosis if pathology is to be correctly predicted in life.

A reverse perfusion pattern during Technetium-99m stress myocardial perfusion imaging does not predict flow limiting coronary artery disease.

BACKGROUND: A reverse redistribution pattern during myocardial perfusion imaging is most widely described using thallium (Tl-201), when stress images exhibit greater perfusion than rest. Technetium (Tc-99 m) radiopharmaceuticals may also yield a reverse perfusion (RP) pattern, but its significance is uncertain. This study tested the hypothesis that RP correlates with the presence and location of flow limiting coronary stenosis(es). METHOD: We reviewed 842 consecutive Tc-99 m tetrofosmin SPECT stress studies performed at a cardiothoracic centre over a 15 month period. 69 (8.2%) demonstrated RP. Thirty-three patients (age 32-79 mean 56, 17 female) had undergone cardiac catheterisation within 12 months of the scan. Correlation was sought between the presence and location of angiographic stenoses and RP pattern. RESULTS: 10/33 (30.3%) had significant (>60%) coronary stenosis(es); 5 single-vessel, 2 two-vessel and 3 three-vessel disease (3VD). Stenosis location correlated poorly with the RP territory (LAD/Anterior 5/17, RCA/Inferior 1/10, Cx/lateral 0/4 (p = 0.57)). Of the 6 patients with a lesion in the RP territory, 3 had 3VD; 2 of these had a simultaneous reversible defect. All 5 patients with previous myocardial infarction had a simultaneous fixed defect. However only 3/12 with co-existent reversible defects had significant disease. CONCLUSION: The reverse perfusion pattern is a poor predictor of flow limiting coronary disease, and does not correlate with stenosis location in those with significant lesions. Such patients should not undergo invasive investigation purely on the basis of this result.

Diagnostic patterns of regional atrophy on MRI and regional cerebral blood flow change on SPECT in young onset patients with Alzheimer's disease, frontotemporal dementia and vascular dementia.

OBJECTIVES: Alzheimer's disease (AD), frontotemporal dementia (FTD) and vascular dementia (VaD) are the three most common causes of young onset dementias. Most neuroimaging studies of these disorders have involved comparisons with normal controls. The aims of this study were to examine the clinical diagnostic value of magnetic resonance imaging (MRI) and single photon emission computed tomography (SPECT) (in combination and in isolation) in the differentiation of one form of dementia from another from amongst a group of AD, FTD and VaD. METHODS: T1 weighted MRI images and 99mTc-HMPAO SPECT images were obtained from consecutive patients with FTD (n=21), AD (n=23) and VaD (n=20) and rated visually by experienced neuroradiologists and nuclear medicine physicians. RESULTS: Asymmetrical atrophy was seen only in FTD. Frontotemporal dementia patients were the most atrophic whereas severe atrophy was rarely observed in VaD. Severe frontal atrophy (unilaterally or bilaterally) and/or asymmetrical atrophy on MRI is highly diagnostic (sensitivity 0.71, specificity 0.93, LR 10.24) of FTD from within a group of FTD and non-FTD (AD, VaD) patients. Mild or severe parietal atrophy with severe reduction in parietal regional cerebral blood flow on SPECT is diagnostic (sensitivity 0.71, specificity 0.76, LR 3.02) of AD from within a group of AD and non-AD (VaD, FTD) patients. CONCLUSION: Anatomical (MRI) and functional (SPECT) imaging provide different information and a combination of these modalities improves diagnostic specificity.

The effect of diclofenac (voltarol) and pethidine on ureteric peristalsis and the isotope renogram.

Diclofenac (a non-steroidal anti-inflammatory drug) and pethidine (a synthetic opiate) are the two analgesics most commonly used to relieve the pain of ureteric colic. Fast frame renography is a non-invasive means of imaging ureteric peristalsis and renal drainage. The aim of this study was to determine the effects of each of these drugs on the drainage pattern of the upper tracts. Twelve normal male volunteers were studied. All underwent a standard fast frame renogram using 75 MBq of technetium-99m-mercaptoacetyltriglycine, and were then administered either 100 mg pethidine or 75 mg diclofenac by intramuscular injection. Fast frame renography was then repeated. Peristalsis was determined from the condensed image of each ureter and the renogram curves were analysed to obtain standard parameters and deconvolution analysis. Diclofenac caused a profound disruption to both ureteric peristalsis and the renogram curve. This effect was not seen after the administration of pethidine. Deconvolution analysis suggests the effects of diclofenac are mediated via a direct effect on drainage rather than by any alteration of blood flow to the kidney. This study suggests that pethidine is the analgesic of choice prior to renography and that inferences about alterations of drainage in the presence of diclofenac should be interpreted with care.

Idiopathic bile acid malabsorption: qualitative and quantitative clinical features and response to cholestyramine.

BACKGROUND: Idiopathic bile acid malabsorption is a poorly recognized cause of chronic diarrhoea. The SeHCAT (75Selenium HomotauroCholic Acid Test) can accurately diagnose this condition. AIM: To identify patients with idiopathic bile acid malabsorption, to describe their clinical features, both qualitatively and quantitatively, and to assess the response to cholestyramine. METHOD: Idiopathic bile acid malabsorption was considered in all patients complaining of chronic diarrhoea. They were included in the study if their SeHCATs were positive (< 15% retention) and secondary causes of bile acid malabsorption were excluded. The response to therapy with cholestyramine was assessed. RESULTS: Nine patients were diagnosed with idiopathic bile acid malabsorption (median SeHCAT retention 8%, range 3-12.6). Their median daily faecal weight was 285 g (range 85-676) and median faecal fat output was 17 mmol/24 h (range 8.3-38.8). Six patients had an immediate response to cholestyramine. There was a marked reduction in stool frequency (median stool frequency pre-treatment 5/day vs. 2/day post-treatment, P = 0.03). Five patients had large volume diarrhoea (faecal weight > 200 g/day) and three had steatorrhoea. CONCLUSIONS: Idiopathic bile acid malabsorption, once suspected, especially by documenting true 'large volume' watery diarrhoea or steatorrhoea, is easily diagnosed and response to therapy is often very good. There is often a previous history of gastrointestinal infection and this condition should be considered in patients with chronic diarrhoea of undetermined origin, especially before they are labelled as having irritable bowel syndrome.

A clinical role for 99mTc-HMPAO SPECT in the investigation of dementia?

OBJECTIVES: To provide the clinician with a guide to the clinical utility of 99mTc-HMPAO single photon emission computed tomography (SPECT) and to the interpretation of specific test results in the differential diagnosis of dementia. METHODS: Three hundred and sixty three patients with dementia were studied prospectively for a median three (range 1-6) years and classified into disease groups on the basis of established clinical criteria. The degree to which different patterns of cerebral blood flow (CBF) abnormality found on 99mTc-HMPAO SPECT imaging at the time of initial patient presentation modified clinical diagnoses was determined by calculating the likelihood ratios for pairwise disease group comparisons. The optimal clinical usage of 99mTc-HMPAO SPECT was determined by calculating the percentage of significant test results for each pairwise disease group comparison. RESULTS: Bilateral posterior CBF abnormality was found to significantly increase the odds of a patient having Alzheimer's disease as opposed to vascular dementia or frontotemporal dementia. Bilateral anterior CBF abnormality significantly increased the odds of a patient having frontotemporal dementia as opposed to Alzheimer's disease, vascular dementia, or Lewy body disease. "Patchy" CBF changes significantly increased the odds of a patient having vascular dementia as opposed to Alzheimer's disease. Unilateral anterior, unilateral anterior plus unilateral posterior, and generalised CBF abnormality failed to contribute to the differentiation of any of these forms of dementia. CONCLUSIONS: 99mTc-HMPAO SPECT was found to be most useful in distinguishing Alzheimer's disease from vascular dementia and fronto temporal dementia, and least useful in differentiating between Alzheimer's disease and Lewy body disease, and between vascular dementia, frontotemporal dementia, and progressive aphasia. It is suggested that CBF SPECT should be used selectively and as an adjunct to clinical evaluation and CT.

A 99mTc-HMPAO single-photon emission computed tomography study of Lewy body disease.

The purpose of this study was to investigate patterns of 99mTc-HMPAO single-photon emission computed tomography (SPECT) abnormality in Lewy body disease (LBD) and to compare findings with those encountered in Alzheimer's disease (AD). The study group comprised 20 consecutive patient referrals fulfilling clinical criteria for LBD. All patients had fluctuating cognitive impairment and 'subcortical' dysfunction with or without perceptuospatial and/or linguistic impairment. Six patients had asymmetrical signs of parkinsonism (three left-sided and three right-sided), and 14 patients had symmetrical features of extrapyramidal involvement. 99mTc-HMPAO SPECT imaging was performed on LBD patients and findings compared with those of 57 patients with 'probable' AD and 11 normal age-matched controls. Within the LBD and AD groups, patterns of cortical and subcortical blood-flow abnormality were compared with patterns of cognitive and neurological breakdown. LBD was associated with bilateral posterior cortical blood flow abnormality, a pattern strikingly similar to that found in AD. Within the LBD group, cortical blood-flow abnormality was found to reflect patterns of neurological dysfunction (parkinsonism) indicative of subcortical involvement. In contrast, cortical blood-flow changes did not reflect patterns of neuropsychological impairment suggestive of cortical dysfunction. Within the AD group, cortical blood-flow changes were mirrored by the pattern of neuropsychological impairment. Findings support the notion that cortical blood-flow abnormality in LBD might reflect a combination of direct cortical pathology and cortical deafferentation secondary to subcortical Lewy body pathology. It would appear that 99mTc-HMPAO SPECT imaging is of limited value in the clinical differentiation of LBD and AD.

The use of 99Tcm-Technegas in the investigation of patients with pulmonary thromboembolism.

Pulmonary embolism remains a major cause of morbidity and mortality, being responsible for an estimated 200,000 deaths per annum in the USA and 21,000 per annum in the UK. Lung scintigraphy is in many instances the investigation of choice in suspected pulmonary thromboembolism. A normal perfusion lung scan excludes pulmonary embolism. An abnormal perfusion scan, while being sensitive, is of low specificity for the diagnosis of pulmonary embolism and needs to be complemented with a ventilation study. Lung ventilation has been studied using inert gases of radiolabelled aerosols. The new radiopharmaceutical 99Tcm-Technegas is a suspension of 99Tcm-labelled, ultrafine, carbon particles produced in an atmosphere of high-purity argon. The size of the particles is of the order of 0.005-0.2 microns, which assures good peripheral penetration and alveolar deposition. After inhalation, static images in multiple projections may be acquired. The resultant images are of excellent technical quality and several publications have shown the value of Technegas images as an adjunct to perfusion imaging in suspected pulmonary thromboembolism. Studies comparing Technegas images with other ventilatory radiopharmaceuticals have in the majority of instances reported comparable diagnostic qualities.

The contribution of single photon emission tomography to the clinical differentiation of degenerative cortical brain disorders.

The accurate clinical diagnosis of degenerative cortical brain disorders is a necessary prerequisite for patient management and the critical evaluation of new treatments. This study has evaluated the ability of single photon emission tomography (SPET) to differentiate between Alzheimer's disease (AD) and different forms of non-Alzheimer lobar atrophy (LA), using a multi-purpose system in widespread routine clinical use. 99mTc-HMPAO SPET was carried out in patients with AD and three clinical syndromes associated with LA: frontotemporal dementia (FTD), progressive non-fluent aphasia (PA) and semantic dementia (SD). Principal component (PC) analysis was performed on regional cerebral blood flow (rCBF) data and inter-group comparisons were performed for PC scores using multiple t-tests. Three PCs explained 86.5% of the variation in rCBF values between individual patients and normal controls. The first PC reflected the average rCBF value and separated patient groups from normal controls but failed to distinguish between patient groups. The second PC reflected anterior-posterior asymmetry and separated AD from all three forms of LA. This PC also separated FTD and SD from controls but failed to distinguish between FTD, PA and SD. The third PC reflected left-right asymmetry and separated PA from all other groups. 99mTc-HMPAO SPET is able to differentiate between degenerative cortical brain disorders in a simple and physiological meaningful way, thereby showing considerable potential as a routine tool in the clinical evaluation and differentiation of AD and LA.

The value of SPET imaging in dementia.

This review critically evaluates the current role of single photon emission tomography (SPET) imaging in the clinical management of patients with dementia. The classification of the dementias is discussed and the clinical and pathological features of the various dementing illnesses are described. Typical appearances on cerebral blood flow imaging are presented for each of the conditions, together with the findings on D2 dopaminergic receptor and muscarinic receptor imaging where this is relevant. The review concludes with a section on the clinical value of SPET imaging in dementia. SPET imaging can make a valuable contribution to the accurate clinical differentiation of dementia, providing findings are interpreted in the light of neurological evaluation and structural imaging. The possible future role of SPET imaging in the prediction and evaluation of response to future therapeutic agents is discussed.

Inter-relation between "classic" motor neuron disease and frontotemporal dementia: neuropsychological and single photon emission computed tomography study.

The purpose of this study was to examine the possible association between "classic" motor neuron disease (cMND) and frontotemporal dementia (FTD), using neuropsychological evaluation and single photon emission computed tomography (SPECT). Psychological tests assessing language, perceptuospatial, memory, and "frontal lobe" functions were given to patients with cMND and test scores were compared with those of normal control subjects. 99mTc-HMPAO SPECT was performed on patients with cMND, FTD and motor neuron disease (FTD/MND), FTD alone, and normal control subjects. Regional cerebral blood flow indices (rCBFi) were determined in 36 cortical regions, and differences between grouped rCBFi data were investigated by canonical discriminant analysis. There were significant group differences in the scores of picture sequencing and token tests in patients with cMND compared with normal controls. Regional CBFi data showed frontal and anterior temporal reductions in patients with cMND compared with normal controls. A similar pattern of SPECT abnormality was seen in patients with FTD/MND and FTD alone, but to a more pronounced degree than in patients with cMND. Neuropsychological and SPECT findings in cMND, FTD/MND, and FTD showed a common pattern of cerebral involvement, most pronounced in the second two conditions. It is suggested that cMND, FTD/MND, and FTD represent a clinical range of a pathological continuum.

Texture analysis of technegas lung ventilation images.

Technegas lung ventilation images sometimes have 'hot spots', particularly in patients with respiratory disease. A novel technique is presented for quantifying this 'spottiness' using morphological texture analysis. A set of 32 images from patients with various respiratory diseases is studied. Images are filtered at a range of scales using morphological opening, and the slopes of image metrics versus structuring element size are used as texture parameters. The results are compared with the opinions of three experienced nuclear medicine physicians who have classified the images into two groups, 'spotty' and 'non-spotty', and have ranked the former. For the spotty images, the computer and observer ranks are compared; the highest correlation is rs = 0.66 (p = 0.01) for a single parameter, and rs = 0.71 (p < 0.01) for a combination of two parameters. Using a pair of parameters, 83% and 90% correct classification rates are obtained for the spotty and non-spotty classes, respectively. It is concluded that these texture parameters provide a useful measure of image spottiness, and it is demonstrated that this technique is superior to previously published methods. The practical value of the technique is illustrated using two applications.

Imaging techniques in the diagnosis of urinary tract infection.

In terms of future morbidity and mortality, one of the most important considerations in urinary tract infection is the age of the patient. In adults, only those with complications or illnesses that fail to respond to treatment require investigation to exclude underlying pathology. In contrast, the young are at risk of future hypertensive and renal disease; imaging techniques are therefore of paramount importance to identify those with renal parenchymal disease at an early stage and permit appropriate and adequate treatment. 99mTc-dimercaptosuccinic acid scintigraphy is emerging as the method of choice for this purpose, because it combines high specificity and sensitivity with convenience, repeatability, and acceptable radiation doses. Voiding cystourethrography will also be required in many cases to exclude bladder pathology. New developments include the use of color Doppler ultrasonography and the nuclear magnetic resonance technique of rapid acquisition recall echo urography, both of which may become of value for the detection of scarring.

Angiotensin II as a risk factor for cyclosporin nephrotoxicity in patients with psoriasis.

Abnormalities of the renin-angiotensin system after low-dose cyclosporin (5 mg/kg/day or less) have not been adequately defined in patients with normal kidneys. 27 patients with psoriasis were assessed before starting cyclosporin, after three months of cyclosporin (5 mg/kg/day or less) and then finally three months after finishing cyclosporin. On each occasion plasma renin activity (PRA), aldosterone, angiotensin II and atrial natriuretic peptide (ANP) were measured together with total renal blood flow (RBF), GFR and filtration fraction (FF) following an i.v. bolus injection of Tc-99m DTPA. Significant renal hemodynamic toxicity was defined as > 25% fall in RBF or > 20% fall in GFR. Using these criteria we identified 12 patients with hemodynamic toxicity (Group A) and 15 patients whose GFR and RBF did not fall significantly (Group B). In Group A a significant fall in GFR (p < 0.001) and reduction in renal blood flow (p < 0.04) were associated with significant rises in both ambulant and recumbent angiotensin II (p < 0.0005). PRA, aldosterone and ANP did not significantly alter. GFR partially recovered after withdrawal of cyclosporin although RBF remained significantly lower compared to initial values. In Group B there was no significant change in GFR or RBF although there was a reversible fall in FF (p < 0.02). There were no significant differences in angiotensin II, PRA, aldosterone or ANP. Circulating angiotensin II rises in patients who develop cyclosporin nephrotoxicity and may be responsible for mediating the hemodynamic effects.

Choice of reference region in the quantification of single-photon emission tomography in primary degenerative dementia.

This study evaluated the effect of using two different reference regions in the quantification of single-photon emission tomography (SPET). SPET scans of 30 patients with Alzheimer's disease (AD) and 30 patients with frontotemporal dementia were compared with the scans of ten age-matched controls. Regions of interest (ROIs) were defined on transaxial slices by a semi-automatic method. Regional cerebral blood flow indices (rCBFi) in each ROI were determined by normalizing the count densities to both cerebellar and occipital cortex reference regions. Mean rCBFi for each ROI were calculated for the patient and control groups and significant group differences determined. The number and topographical distribution of ROIs with significant group differences varied depending upon the choice of reference region. The magnitude of these differences was greatest when the cerebellum was used as the reference region. The disparity between results obtained with the two reference regions was most apparent in the AD group. The reasons for these differences are discussed and we conclude that the cerebellum is the more appropriate choice of reference region in the quantification of SPET in primary degenerative dementia.

Condylar hyperplasia: correlation of histological and scintigraphic features.

Scintigaphy using 99mTc-MDP is widely advocated as a method of diagnosis and presurgical assessment of patients with condylar hyperplasia. A previous study has demonstrated that hyperplasia of the mandibular condyle is characterized histologically by the presence of an uninterrupted layer of undiffentiated germinative mesenchyme cells, a layer of hypertrophic cartilage and the presence of islands of chondrocytes in the subchondral trabecular bone. This study was undertaken to determine whether there was any association between the degree of 99mTc-MDP uptake and the histological features of condylar hyperplasia. The parameters examined were trabecular bone volume, depth of cartilage islands and the presence of forming and resorbing surfaces. The images were analyzed by three experienced observers, who ranked the images according to degree of asymmetry between sides and the degree of uptake on the affected side. There was a significant correlation between the proportions of resorbing and osteoid covered bone surfaces and scintigraphic appearances. The rank correlations were rs = 0.55 (P = 0.3) between the resorptive surfaces and degree of symmetry and rs = 0.53 (P = 0.04) between the osteoid surfaces and absolute uptake. The correlation was higher for both methods (rs = 0.64 in each case) when the osteoid surface and resorptive surface measurements were combined. The results indicate that visual examination of radioisotope bone scans by experienced observers is a valid form of assessment of bone activity in condylar hyperplasia.

The influence of inhalation technique on Technegas particle deposition and image appearance in normal volunteers.

The aim of this work was to investigate the influence of inhalation technique on Technegas image quality and on fractional particle deposition. This was investigated in six normal volunteers using three different types of breathing pattern. Fractional deposition was determined by analysis of dynamic gamma camera images acquired during Technegas administration. Static lung images were subsequently acquired and assessed independently by three experienced observers. High-quality images were obtained in all cases although slight differences were noted. The images produced using a slow deep inspiration with a breath hold (i.e. the standard method) were of more uniform texture and also had the least gradient in activity from apex to base. The converse was true for a rapid inhalation technique. The average fractional deposition per breath was 55%, but this varied between individuals and with breathing pattern, being most influenced by the total duration of a breath. We conclude that for patient studies the standard inhalation technique is best, although variation to suit individual patients would be acceptable. These results contrast with similar studies using conventional radio-aerosols, which tend to show a greater sensitivity of image appearance to changes in breathing pattern and lower fractional depositions.

Interrelationship between serum concentrations of 1,25-dihydroxyvitamin D, parathyroid hormone and renal haemodynamics after low dose cyclosporin.

It is unclear whether cyclosporin A (CsA) alters the synthesis of 1,25-dihydroxyvitamin D3 [1,25(OH)2D] by the normal human kidney. Serial changes in 1,25(OH)2D, parathyroid hormone (PTH), GFR and renal blood flow were compared in 14 patients with psoriasis who were being treated with less than 5 mg/kg/day of cyclosporin for 3 months. GFR fell significantly although there were no significant changes in serum 1,25(OH)2D, 25-hydroxyvitamin D or PTH. Absolute values for GFR and PTH were negatively correlated (rP = -0.54; p < 0.001) as were the changes in GFR and PTH observed during CsA therapy (rP = -0.73; p < 0.05). The significant fall in serum magnesium was not significantly correlated with changes in PTH. The close relationship between changes in GFR and PTH suggests that a reduction of GFR within the normal range is enough to stimulate production of PTH. CsA does not appear to stimulate the synthesis of 1,25(OH)2D3 in man.

Altered clearance of N-1 methylnicotinamide associated with the use of low doses of cyclosporine.

To improve the monitoring of patients on low doses of cyclosporine there is a need for new tests of tubular function. N-1 methylnicotinamide (NMM) is an endogenous organic cation that is secreted by the proximal tubule and its clearance can be measured. In 27 patients with psoriasis, serial measurements of NMN clearance, plasma aldosterone, plasma chloride, bicarbonate, and magnesium were compared with changes in the radionuclide measurement of glomerular filtration rate and renal blood flow before, during, and after a 3-month course of low-dose cyclosporine (< 5 mg/kg/d). N-1 methylnicotinamide clearance decreased significantly with cyclosporine only (2.5 mg/kg/d, n = 10, P < 0.01). Recovery of NMN clearance lagged behind that of glomerular filtration rate and renal blood flow. Serum magnesium decreased significantly on cyclosporine (2.5 mg/kg, n = 10, P < 0.01; 5 mg/kg, n = 9, P < 0.0001). In the whole group, plasma potassium increased significantly (n = 27, P < 0.02) and plasma aldosterone was inappropriately low. Low doses of cyclosporine in psoriasis cause a reduced clearance of NMN, hypomagnesemia, and a variable hyperchloremic acidosis. Nifedipine may alter these biochemical variables without necessarily improving renal hemodynamics. The delayed recovery of NMN clearance in comparison with renal haemodynamic measurements following cyclosporine therapy suggests that this noninvasive test of tubular function may be a marker of persisting cyclosporine nephrotoxicity and that it should be evaluated further.