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Unlabelled: One of the potential limitations in the usefulness of both renal output efficiency (ROE) and normalized residual activity (NORA) is their residual dependence on total renal function. The purpose of this study was to present and examine a new quantitative method whereby the effects of this dependence may be removed., Methods: The analytic method involves the determination of a retention function using an unconstrained matrix algorithm deconvolution technique followed by reconvolution with a chosen standard input function to yield a new secondary renal activity time (A/T) curve from which normalized values of ROE and NORA, denoted as N&#95;ROE and N&#95;NORA, respectively, can then be obtained using conventional definitions. The method has been applied in a series of 50 patient studies, which had been acquired using (99m)Tc-mercaptoacetyltriglycine (99(m)Tc-MAG3) and a standard F+18 furosemide protocol, with values of the ratio of plasma clearance to plasma volume (C/V) in the range 0.013-0.242 min(-1)., Results: Pre- and postnormalization values of NORA, calculated at 30 min after injection, showed a significant difference in mean values (paired t test; P < 0.001), with a maximum observed difference, DeltaNORA(30), of -4.82 (-482%) and with a SD on the paired differences, DeltaNORA(30), of 0.56 (56%) or 0.63 (63%) if background subtraction on the input function (BSIF) had been performed. In contrast, corresponding values of ROE showed a nonsignificant difference in means (P > 0.05) and a SD on the paired differences, DeltaROE(30), of 3.7% or 3.2% with and without BSIF, respectively. The normalized parameters N&#95;ROE and N&#95;NORA were found to be strongly linearly correlated (r = -0.99; P < 0.001), in agreement with theoretical predictions., Conclusion: These results suggest that renal function affects NORA significantly more than ROE. The effects can be corrected by our normalization technique, resulting in equivalent values of normalized ROE and normalized NORA.

Technetium-99m diaminocyclohexane (DACH) is a new tubular agent excreted via a cationic transport mechanism, like cyclosporine-A (CsA). It is expected that 99mTc-DACH will permit effective assessment of tubular function in CsA-treated patients. To establish the pharmacokinetic characteristics of 99mTc-DACH and to ascertain whether this new agent is useful in CsA-treated patients, 11 healthy volunteers and 15 CsA-treated patients underwent renal imaging and clearance studies using 99mTc-DACH and chromium-51 ethylene diamine tetra-acetic acid (EDTA). 99mTc-DACH yielded satisfactory dynamic renal images in all participants. The mean plasma clearance of 99mTc-DACH was significantly greater than that of 51Cr-EDTA in volunteers (109.4¿19.7 ml/min versus 86.6 +/- 13.7 ml/min, P<0.05). However, the urinary excretion of 99mTc-DACH at 90 min was significantly lower than that of 51Cr-EDTA (46.1% +/- 9.3% versus 53.1% +/- 8.6%, P<0.05), most probably due to its partial parenchymal retention. The elimination half-life of 99mTc-DACH was significantly increased in CsA-treated patients in comparison to volunteers, and consequently the plasma clearance values were significantly suppressed in these patients, in contrast to 51Cr-EDTA and endogenous creatinine clearance values. In conclusion, our findings indicate that 99mTc-DACH, as a sensitive marker of cationic tubular function, could be used to monitor renal haemodynamics in patients receiving CsA treatment.

The aim of the study was a quantitative comparison of relative renal uptake and both the whole-kidney and the parenchymal transit time derived from factor analysis of image sequences and provided by standard clinical procedues. In order to extract the stable, well-interpretable factors, factor analysis was performed locally in the problem-specific time and spatial windows and the resulting factor images either evaluated directly as functional images or used as fuzzy regions of interest (ROIs) for the subsequent extraction of time-activity curves from the analysed data. The values of relative renal uptake of the left kidney measured in the functional factor images, which demonstrate the initial accumulation of activity in renal parenchyma (mean 51.0%), did not differ significantly from the values obtained by a standard method (mean 51.5%, r = 0.98, P<0.001). Whole-kidney transit time calculated using fuzzy ROI curves correlated well with the reference values (r = 0.84, P<0.001); however, both its mean value (336.5 s) and the standard deviation (151.5 s) were substantially greater than those of the values provided by a standard procedure (262.8+/-86.9 s). Parenchymal transit time calculated using ROI curves correlated better with the transit time through a wider corticomedullary region rather than through a narrow cortical region, which is decisive in a differential diagnosis of renal disorders. In general, values of transit times provided by factor analysis correlated well with those provided by reference methods but with a shift towards the higher numerical values. This may have been a consequence of a greater extent of the automatically extracted fuzzy ROIs, or of occasionally delayed accumulation in the upper calyces. Results of the study provide quantitative evidence that the factor analysis of dynamic data, even without the introduction of prior physiological information, may yield clinically relevant information. However, some basic requirements, such as sufficiently high sampling frequency and count rate, adaption of the method to a specific clinical task, and proper selection of time and spatial windows for locally performed analysis, have to be fullfilled if the method is to be successfully applied clinically.

Complete ureteric occlusion produces various pathophysiological changes that can be monitored externally by technetium 99m diethylenetriamine penta-acetic acid (99mTc-DTPA) diuretic renography (RDR). Being a dynamic imaging study, it reflects the function of the kidneys and the urodynamics of the urinary tract. The aim of this study was to correlate the changes in parameters of RDR with the histological changes before and after the release of complete ureteric occlusion. In 9 sheep, RDR studies were performed serially after various periods of complete ureteric occlusion (up to 7 weeks) and after release of the occlusion (up to 5 weeks). The histological changes were correlated with changes in RDR. The progressive decrease in renal flow seen on renal images and flow time-activity curves (TACs) was explained by the development of endarteritis and thrombosis of small renal arteries. The progressive decrease in the renal uptake as indicated by the percentage renal uptake and the extraction slope of TAC is related to the progressive damage to the renal parenchyma, initially affecting the collecting ducts and tubules, with increasing interstitial fibrosis in the later stages. Obstruction for 3 weeks or less was associated with moderate damage to the parenchyma from which recovery was possible. Obstruction for 7 weeks was associated with marked damage without chance of recovery. The RDR is a non-invasive technique that can be used to monitor kidney damage after various periods of complete ureteric occlusion and to predict the outcome of surgery before the release of occlusion.

Functional significance of renal artery stenosis (RAS) was assessed by 99Tcm-DTPA radionuclide scintigraphy, using the mean parenchymal transit time (MPTT) of the tracer as an index of renovascular disorder. Two groups of subjects were investigated retrospectively: eight normal live kidney donors; and 11 patients with hypertension, six with and five without significant RAS. MPTT was 171 +/- 11 s in the kidney donors, and there was a significantly prolonged MPTT in patients with RAS, 313 +/- 27 s (p less than 0.05). MPTT was also prolonged in three hypertensive patients with intrinsic renal disorders. The advantages and limitations of this technique are discussed. It is concluded that prolongation of MPTT can detect functionally significant renovascular disorder without pharmacological challenge.

The effects of irrigation with sterile and infected saline after acute ureteric dilatation by graded Teflon dilators were evaluated renographically and histologically in minipigs. The minipig ureter was dilated from its normal calibre of 4 F to 10 F, and 100 ml of sterile or infected saline were then introduced from a height of 60 cm under gravity. One week after irrigation and dilatation the ipsilateral kidney was either functioning less than 10% or there was an obstructive nephropathy. Histology at 3 months suggested that extravasation of infected irrigating fluid was the most likely cause of ureteric stricture formation.

A technique is described for measuring an index of cardiac output, total and individual renal plasma flow, cortical and juxtamedullary nephron flow non-invasively in man with a single injection of 123I-o-iodohippurate. Ibopamine, a dopamine analogue, was administered orally, 200 and 600 mg, in a double-blind, placebo-controlled cross-over study in 6 healthy subjects. No change in pulse, blood pressure, cardiac output, urea, creatinine or electrolytes was seen. Ibopamine reduced effective renal plasma flow and cortical nephron flow and increased urine flow significantly. This may be due to differential vasoconstrictor and vasodilator effects on the two populations of nephrons. Indoramin, and alpha-1 postsynaptic adrenoceptor blocker, was administered orally, 50 mg, in a double-blind, placebo-controlled cross-over study in 14 healthy young males. No change in pulse, cardiac output, urea, creatinine or electrolytes was seen. Indoramin significantly reduced upright but not supine blood pressure and significantly increased effective renal plasma flow. Cortical nephron flow and juxtamedullary nephron flow tended to rise. Plasma renin activity was significantly elevated although there was no change in urinary sodium output. The effect of drugs on intrarenal blood flow distribution may be relevant to the management of essential hypertension.

Renal and intrarenal distribution of flow together with an index of cardiac output is measurable using a single injection of 123I-o-iodohippurate. The argument is presented that in the treatment of essential hypertension one should avoid using drugs that reduce renal blood flow, a property of chronic therapy with most beta-blockers or diuretics. Reduction of renal blood flow is a stimulus to salt retention and renin release which tend to maintain hypertension. Drugs which increase renal blood flow, thereby augmenting the renal loss of salt and decreasing renin release, tend to reduce hypertension in the long term.

1. The spectrum of transit times of sodium o-iodohippurate (Hippuran) through the kidney can be derived from an 131I- (or 123I-) labelled Hippuran renogram by deconvolution. In the rabbit and pig, as has previously been shown in man, the frequency distribution curve for the transit times was bimodal. Since the transit time is likely to be proportional to the nephron length, the area of the first mode is likely to represent plasma flow to the shorter outer cortical nephrons whereas the delayed mode represents flow to the long juxtamedullary nephrons. 2. This interpretation was tested by simultaneously comparing renography with the microsphere method of measuring intrarenal plasma flow distribution in 12 rabbits and two pigs with a variety of anaesthetics. A close agreement was found between both methods for the percentage of plasma flow distributed to the outer cortical nephrons, thus supporting the use of "transit renography" to determine the intrarenal distribution of plasma flow.

Sixty-three patients presenting with the clinical problem of renal outflow disorder were studied using 99mTc DTPA. The techniques of frusemide diuresis and parenchymal transit time index analysis were compared and both shown to be successful in aiding the decision as to the presence or absence of significant outflow obstruction.