ARFI-based tissue elasticity quantification and kidney graft dysfunction: first clinical experiences.

BACKGROUND AND PURPOSE: Beyond the medical history, the clinical exam and lab findings, non-invasive ultrasound parameters such as kidney size and Doppler values (e.g. the resistive index) are important tools assisting clinical decision making in the monitoring of renal allografts. The gold standard for the diagnosis of renal allograft dysfunction remains the renal biopsy; while an invasive procedure, the justifiable necessity for this derives from its definitive nature a requirement beyond the synopses of all non-invasive tools. "Acoustic Radiation Force Impulse Imaging"(ARFI)-quantification is a novel ultrasound-based technology measuring tissue elasticity properties. So far experience related to this new method has not been reported in renal transplant follow-up. The purpose of this study was to evaluate changes in ARFI-measurements between clinically stable renal allografts and biopsy-proven transplant dysfunction. METHODS: We employed "Virtual Touch™ tissue quantification" (Siemens Acuson, S2000) for the quantitative measurement of tissue stiffness in the cortex of transplant kidneys. We performed initial baseline and later disease-evaluative ultrasound examinations in 8 renal transplant patients in a prospective study design. Patients were first examined during stable allograft function with a routine post-transplant renal ultrasound protocol. A second follow-up examination was carried out on subsequent presentation with transplant dysfunction prior to allograft biopsy and histological evaluation. All patiens were examined using ARFI-quantification (15 measurements/kidney). Resistive indices (RI) were calculated using pulsed-wave Doppler ultrasound, and transplant kidney size was measured on B-mode ultrasound images. All biopsies were evaluated histologically by a reference nephropathologist unaware of the results of the ultrasound studies. Histopathological diagnoses were based on biopsy results, taking clinical and laboratory findings into account. Finally we calculated the relative changes in ARFI-quantification, resistive indices and the absolute change of kidney size on a percentage basis at these defined assessment times and compared the results with the final pathologic diagnosis. RESULTS: Histological results enumerated five cases of acute T-cell-mediated rejection, one case of calcineurin inhibitor toxicity and two cases of acute tubular necrosis. Calcineurin inhibitor toxicity and acute tubular necrosis were subsumed as "other pathologies". Mean ARFI-values showed an average increase of more than 15% percent in transplants with histologically proven acute rejection whereas no increase was seen in transplants with other pathologies. Mean RI-values showed no increase either in the diagnostic group of acute rejection, nor in the group with other pathologies. Kidney size showed a mean absolute increase of 0.5 centimetres in allografts with acute rejection, whereas a mean decrease of 0.17 centimetres was seen in the group with other pathologies. CONCLUSION: As shown before in other studies, RI values and kidney size are of doubtful utility in the evaluation of kidney allograft dysfunction. ARFI-based elasticity measurement shows promise as a complementary non-invasive parameter in follow-on diagnosis of renal allograft rejection.

ARFI-based tissue elasticity quantification in comparison to histology for the diagnosis of renal transplant fibrosis.

BACKGROUND AND PURPOSE: Until recently clinical diagnosis of chronic renal allograft dysfunction could only be established invasively by renal biopsy. Given the risks of that procedure, a non-invasive, diagnostic test would be very advantageous. Novel ultrasound-based elasticity tools, using "Acoustic Radiation Force Impulse (ARFI)" technology are now available. Previously this technique has been utilised to quantify liver fibrosis. First results of these studies are promising. The purpose of our study was to investigate correlation between stiffness values obtained by ARFI-quantification and histological fibrosis score in renal transplants. METHODS: We employed "Virtual Touch™ tissue quantification" (Siemens Acuson, S2000) to quantitatively measure tissue stiffness in the cortex of transplant kidneys. Eighteen patients were included in this prospective study, recording close temporal ARFI-quantification and fibrosis measurements. All patients undergoing renal transplant biopsy were examined with ARFI-quantification (15 measurements per transplant kidney). Resistive indices were also calculated from pulsed-wave Doppler ultrasound. Transplant biopsies were histologically evaluated by a reference nephropathologist and graded according to the percentage of fibrosis and to the BANFF-score. Due to the non-normal distribution of the data the Spearman-correlation-coefficient (rho) was used to assess the bivariate relationship of ARFI and fibrosis in the transplant kidney. RESULTS: There was a significant positive moderate correlation between mean ARFI-values and the grade of fibrosis (rho = +0.465; p = 0.026). This correlation was also valid for the mean ARFI-values and the BANFF-category (rho = +0.468; p = 0.025). There was no significant correlation between the mean ARFI-values and the resistive indices in the transplant kidney (rho = +0.034; p = 0.904). Nevertheless, a positive correlation between the mean RI-values of the kidney and the grade of fibrosis was established (rho = +0.563; p = 0.015). CONCLUSION: The mean values of ARFI measurements and the resistive indices are potentially independent explanation variables for evaluating the grade of fibrosis in transplant kidneys.

Diagnostic strategies in urinalysis.

The traditional methods in urinalysis (visual microscopy, qualitative test strip screening) were compared with automated microscopy (UA-1000, TOA-medicals, Japan) and quantitative single protein analysis in 562 fresh morning urine samples. Albumin served as "glomerular" and alpha 1-microglobulin as "tubular" markers measured by turbidimetry. The test strip delivered at least one positive result in 60% of the urine for blood (21%), leukocytes (27%), or protein (34%). In only 4% casts or renal cells were found by traditional microscopy, whereas automated microscopy was positive for these findings in 28% of the urine. Quantitative urine protein analysis alone exhibited results outside the reference interval in 52% of the urine. Combination of the test strip procedure for blood and leukocytes with urine protein analysis increased the number of positives to 73%. Thirteen percent of these additional findings were classified as glomerular (64%) and tubular (72%) proteinurias. In 7% of the urine a false positive protein test strip result was confirmed by quantitative albumin determination. Of 157 urine samples, positive in mechanized video recorded screening, 60 (38%) were normal in single protein analysis. The results allow for the conclusion that the advanced techniques are superior to traditional screening procedures in detecting abnormal urine composition. It is suggested that traditional urinalysis should be supported or replaced by quantitative determination of albumin and alpha 1-microglobulin. This recommended strategy is able to exclude or detect tubulo-interstitial nephropathies or microalbuminuria in earlier phases of renal complications, such as in diabetes mellitus, hypertension or in nephrotoxic injury. A fully mechanized version is suggested to meet appropriate quality criteria and economic needs.(ABSTRACT TRUNCATED AT 250 WORDS)