99mTc-MAG3 scintigraphy for the longitudinal follow-up of kidney function in a mouse model of renal ischemia-reperfusion injury.

BACKGROUND: Experimental models are essential tools in the development and evaluation of novel treatment options, but the preclinical model of renal ischemia-reperfusion injury is limited to the retrieval of (very) early functional data, leaving the pivotal long-term outcome unknown. The present study applies technetium-99m-mercapto-acetyl-tri-glycine [99mTc-MAG3] scintigraphy for the longitudinal follow-up examination of long-term kidney function after renal ischemia-reperfusion injury. METHODS: Unilateral warm ischemia was induced in scid beige mice by vascular clamping of the kidney hilum for 40 min. 99mTc-MAG3 scintigraphy was performed prior to injury, 8 and 14 days post ischemia. The fractional uptake rate [FUR] was calculated from scintigraphy data as a measure of renal clearance. RESULTS: FUR demonstrated a significant functional impairment of the ischemic kidney 8 and 14 days after injury (P < 0.05 vs. baseline), while contralateral non-ischemic kidneys showed no significant changes. In histological analysis, ischemic kidneys exhibited tubular dilatation and cytoplasmic degeneration as signs of hypoxia without any evidence for necrosis. CONCLUSIONS: FUR enables the detection of renal dysfunction and longitudinal long-term follow-up examination in the same individual. Our model may facilitate preclinical therapy evaluation for the identification of effective renoprotective therapies.

Probable range for whole kidney mean transit time values determined by reexamination of UK audit studies.

OBJECTIVES: Inconsistency in the intercentre measurement of whole kidney mean transit time (MTT) has been reported in a previously published UK audit. The main objectives of this study were to identify a probable value of MTT for each kidney in the UK audit data and to find likely reasons for the reported variations. METHODS: Datasets of MTT values were obtained by an independent review of the audit data by four experienced practitioners of deconvolution techniques. The deconvolution techniques used included the matrix method, a constrained least squares method as well as a residence time technique. The datasets were compared using t-test, linear regression, and mean difference analysis. RESULTS: Twelve of a total of 13 datasets showed nonsignificant differences using a paired t-test (P>0.05). For each kidney (x), a collective mean and standard deviation, Mx and SDx, respectively, were calculated from these 12 datasets and a probable range was defined as Mx+/-3SDx. Average SDx/Mx was 3.6% (range 1.5-7.7%). For five kidneys, Mx exceeded the median of the audit results by 3.5-15.3 SDx (P<0.001). CONCLUSION: Probable ranges for whole kidney MTT have been estimated with good precision. Underestimation of the area under the plateau of the renal retention function as well as overestimation of the plateau height might have contributed to an underestimation of MTT apparent in some audit results. Visual display of both the renal retention function and the reconvolution curve are suggested as simple quality control measures for analysis software.

International Scientific Committee of Radionuclides in Nephrourology (ISCORN) consensus on renal transit time measurements.

This report is the conclusion of the international consensus committee on renal transit time (subcommittee of the International Scientific Committee of Radionuclides in Nephrourology) and provides recommendations on measurement, normal values, and analysis of clinical utility. Transit time is the time that a tracer remains within the kidney or within a part of the kidney (eg, parenchymal transit time). It can be obtained from a dynamic renogram and a vascular input acquired in standardized conditions by a deconvolution process. Alternatively to transit time measurement, simpler indices were proposed, such as time of maximum, normalized residual activity or renal output efficiency. Transit time has been mainly used in urinary obstruction, renal artery stenosis, or renovascular hypertension and renal transplant. Despite a large amount of published data on obstruction, only the value of normal transit is established. The value of delayed transit remains controversial, probably due to lack of a gold standard for obstruction. Transit time measurements are useful to diagnose renovascular hypertension, as are some of the simpler indices. The committee recommends further collaborative trials.

Elimination of the influence of total renal function on renal output efficiency and normalized residual activity.

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_ROE and N_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_ROE and N_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.