Detection of Acute Tubular Necrosis Using Blood Oxygenation Level-Dependent (BOLD) MRI.

BACKGROUND/AIMS: To date, there is no imaging technique to assess tubular function in vivo. Blood oxygen level-dependent magnetic resonance imaging (BOLD MRI) measures tissue oxygenation based on the transverse relaxation rate (R2*). The present study investigates whether BOLD MRI can assess tubular function using a tubule-specific pharmacological maneuver. METHODS: Cross sectional study with 28 participants including 9 subjects with ATN-induced acute kidney injury (AKI), 9 healthy controls, and 10 subjects with nephron sparing tumor resection (NSS) with clamping of the renal artery serving as a model of ischemia/reperfusion (I/R)-induced subclinical ATN (median clamping time 15 min, no significant decrease of eGFR, p=0.14). BOLD MRI was performed before and 5, 7, and 10 min after intravenous administration of 40 mg furosemide. RESULTS: Urinary neutrophil gelatinase-associated lipocalin was significantly higher in ATN-induced AKI and NSS subjects than in healthy controls (p=0.03 and p=0.01, respectively). Before administration of furosemide, absolute medullary R2*, cortical R2*, and medullary/cortical R2* ratio did not significantly differ between ATN-induced AKI vs. healthy controls and between NSS-I/R vs. contralateral healthy kidneys (p>0.05 each). Furosemide led to a significant decrease in the medullary and cortical R2* of healthy subjects and NSS contralateral kidneys (p<0.05 each), whereas there was no significant change of R2* in ATN-induced AKI and the NSS-I/R kidneys (p>0.05 each). CONCLUSION: BOLD-MRI is able to detect even mild tubular injury but necessitates a tubule-specific pharmacological maneuver, e.g. blocking the Na+-K+-2Cl- transporter by furosemide.

Clinical Scenarios in Chronic Kidney Disease: Chronic Tubulointerstitial Diseases.

Chronic tubulointerstitial diseases are a common final pathway toward chronic renal failure regardless the primary damage (glomerular, vascular or directly the tubulointerstitium). Chronic tubulointerstitial nephritis (CTN) is characterized by interstitial scarring, fibrosis and tubule atrophy, resulting in progressive chronic kidney disease. Most frequent causes of CTN are drugs, heavy metals, obstructive uropathy, nephrolithiasis, reflux disease, immunologic diseases, neoplasia, ischemia, metabolic diseases, genetics and miscellaneous. At ultrasound (US), kidneys' morphological aspect is similar in all forms of chronic interstitial nephropathy and only chronic pyelonephritis with or without reflux shows distinguishing characteristics. In interstitial nephropathy, kidneys' profiles are finely irregular and corticomedullary differentiation is altered because of a diffused hyperechogenicity. The only indirect sign of chronic interstitial damage can be derived from the value of intrarenal resistive indexes that hardly overcome 0.75. US is mandatory in clinical chronic pyelonephritis work-up because it provides information on kidney's diameter and on growth nomogram in children. Renal profiles can be more or less altered depending on the number of cortical scars and the presence of pseudonodular areas of segmental compensatory hypertrophy. In the early stages, US diagnosis of renal tuberculosis is difficult because parenchymal lesions are non-specific. US sensitivity in the diagnosis of hydronephrosis is very high, close to 100% and, finally, US is the first choice imaging technique in the diagnosis of urinary lithiasis.

Resistance index measured by Doppler ultrasound as a predictor of graft function after kidney transplantation.

INTRODUCTION: Doppler ultrasound (US) has become the primary imaging technique for the evaluation of renal transplants. It provides information about the intrarenal resistance index (RI). A high RI is seen in every form of graft dysfunction. In this article, we review the utility of sonography, particularly the intrarenal RI measured early after renal transplant, as a predictor of acute and chronic clinical outcome in patients. RESULTS: RI is a valuable marker to determine graft function and related vascular complications. It reveals a strong correlation with serum creatinine levels measured days after transplant. Its elevation is typical for acute tubular necrosis and can be used to predict its duration. An RI >1 (absent end-diastolic flow) seen in the first weeks after transplant is associated with impaired renal graft recovery. In addition, it is an early predictor of chronic allograft nephropathy (even correlated with biopsy results), which will allow a change in therapy. CONCLUSIONS: RI measured serially in the early period after kidney transplantation is a valuable marker for determining renal graft function. It is also useful for demonstrating various types of graft dysfunction; however, it cannot differentiate between them. In recent studies, extrarenal factors in kidney transplantation (eg, recipient's age) may significantly influence RI in the recipient, demonstrating that RI depends on the vascular characteristics of the recipient and not on the graft itself.

Power doppler sonography in early renal transplantation: does it differentiate acute graft rejection from acute tubular necrosis?

To evaluate the role of power Doppler in the identification and differentiation between acute renal transplant rejection and acute tubular necrosis (ATN), we studied 67 live donor renal transplant recipients. All patients were examined by spectral and power Doppler sonography. Assessment of cortical perfusion (CP) by power Doppler was subjective, using our grading score system: P0 (normal CP); homogenous cortical blush extending to the capsule, P1 (reduced CP); cortical vascular cut-off at interlobular level, P2 (markedly reduced CP); scattered cortical color flow at the interlobar level. Renal biopsies were performed during acute graft dysfunction. Pathological diagnoses were based on Banff classification 1997. The Mann- Whitney test was used to test the difference between CP grades with respect to serum creatinine (SCr), and resistive index (RI). For 38 episodes of acute graft rejection grade I, power Doppler showed that CP was P1 and RI ranging from 0.78 to 0.89. For 21 episodes of acute graft rejection grade II, power Doppler showed that CP was P1, with RI ranging from 0.88 to >1. Only one case of grade III rejection had a CP of P2. Twelve biopsies of ATN had CP of P0 and RI ranging from 0.80 to 0.89 There was a statistically significant correlation between CP grading and SCr (P <0.01) as well as between CP grading and RI (P <0.05). CP grading had a higher sensitivity in the detection of early acute rejection compared with RI and cross-sectional area measurements. We conclude that power Doppler is a non-invasive sensitive technique that may help in the detection and differentiation between acute renal transplant rejection and ATN, particularly in the early post-transplantation period.

Disturbances of kidney graft perfusion as indicators of acute renal vein thrombosis in contrast-enhanced ultrasonography.

INTRODUCTION: The aim of this study was to evaluate the usefulness of contrast-enhanced ultrasound (US-CE) to diagnose acute renal vein thrombosis (ARVT), acute rejection episodes (ARE), or acute tubular necrosis (ATN) in kidney grafts. MATERIALS AND METHODS: We analyzed 171 US-CE among kidney transplantation patients in the early postoperative period. Patients underwent US-CE following a standard diagnostic protocol including real-time ultrasound (B-mode) and color Doppler ultrasound with spectral flow analysis. Tissue perfusion was analyzed based upon time-intensity curves for two regions: the renal cortex and the renal pyramids. RESULTS: Of 14 patients, in whom standard ultrasound showed high resistance parameters in the renal artery, three showed ARVT and 11 had ATN or ARE, which were confirmed by biopsy. Among patients with ARVT, the US-CE showed a lack of contrast perfusion into the cortex and renal pyramids. Patients with ARE/ATN showed slower contrast inflow into the parenchyma with reduced but still present perfusion. The differences in mean signal intensity values were significant for both the cortex and the renal pyramids: cortex: -53.8±5.4 dB versus -35.0±3.5 dB (P<.05) and pyramids: -54.8±5.4 dB versus -37.0±3.5 dB (P<.05). CONCLUSION: US-CE is a noninvasive method that provides easy, reliable differentiation of ARVT from ARE/ATN.

Perfusion of kidney graft pyramids and cortex in contrast-enhanced ultrasonography in the determination of the cause of delayed graft function.

BACKGROUND: The aim of this study was to assess the usefulness of a new ultrasound technique - contrast-enhanced ultrasound examination (US-CE) - using sulphur hexafluoride in the early post-transplant assessment of graft perfusion. Time-intensity curves (TIC) were compared with hemodynamic flow parameters (resistive index: RI) in patients with good early graft function (EGF) and acute rejection (AR) or acute tubular necrosis (ATN) as a cause of delayed graft function (DGF). MATERIAL/METHODS: US-CE was conducted in order to assess graft perfusion in the early period after kidney transplantation (72-120 hours) in 63 kidney allograft recipients: 35 with EGF and 28 with DGF. The DGF patients were later diagnosed based on graft biopsy as AR (n = 10) or ATN (n = 18). Time-intensity curves were compared with hemodynamic flow parameters typically assessed in post-operative graft diagnostics (e.g., RI). RESULTS: In the examination with US-CE in EGF patients, the regular inflow of contrast medium was demonstrated in all regions of the graft. In patients with DGF, a delay in the inflow of the contrast medium was observed, as well as significant differences in the time of inflow to the regions of interest between those 2 groups. There was a significantly longer inflow time of the contrast medium to the cortex and renal pyramids in patients with AR than in ATN recipients. CONCLUSIONS: US-CE may be a valuable diagnostic tool in the determination of the cause of DGF.

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.

Functional study of the transplanted kidney with power Doppler US and time/intensity curves.

PURPOSE: Power Doppler ultrasound (US) with time-intensity curves was used to study renal graft function both in the absence of disease and with complications (acute tubular necrosis and chronic rejection) in an attempt to identify pathognomonic patterns. Time-intensity curves allow representation of the kidneys' wash-in and wash-out phases after intravenous administration of sonographic contrast material. MATERIALS AND METHODS: Fifty-six asymptomatic renal transplant patients (36 men and 20 women), 19 of whom had altered creatinine clearance levels, were studied by power Doppler US with time-intensity curves followed by biopsy. Ten asymptomatic patients with normal creatinine clearance levels were used as controls. RESULTS: Time-intensity curve analysis enabled identification of three groups of patients: group A, consisting of 27 patients showing peak enhancement between 50 and 65 s from intravenous administration of contrast material; group B, consisting of 16 patients with peak enhancement between 135 and 235 s; group C, consisting of three patients with peak enhancement between 100 and 130 s. CONCLUSIONS: Data showed significant variations according to renal graft function (no abnormality, acute tubular necrosis or chronic rejection). Although confirmation by a larger series is required, our findings appear to indicate pathognomonic patterns in patients with chronic rejection and acute tubular necrosis.

The role of ultrasound in renal insufficiency: the essentials.

Sonography is the best screening modality to evaluate patients presenting with renal insufficiency. Ultrasound findings can be normal in patients with renal disease, especially in prerenal azotemia and acute parenchymal renal disease. Echogenic kidneys indicate the presence of parenchymal renal disease; the kidneys may be of a normal size or enlarged. Small kidneys suggest advanced stage chronic kidney disease. Uncommonly, cystic disease of the kidney, especially adult type polycystic kidney disease may be the cause of the patient's renal insufficiency with bilaterally enlarged kidneys containing multiple cysts of various sizes. If hydronephrosis is present, the level and cause of the obstruction should be sought. When ultrasound cannot diagnose the level and cause of obstruction, other imaging modalities, including CT and MRI may be useful. When renovascular disease (arterial stenosis or venous thrombosis) is suspected, spectral and color Doppler can be useful in detecting abnormalities.

Evaluation of the resistive index (RI) for the diagnosis of acute renal rejection in renal allografts from the same donor.

PURPOSE: To investigate the importance of the resistive index (RI) in the diagnosis of acute renal rejection, compared with the RI of the twin kidney from the same donor, transplanted in two different patients. MATERIAL AND METHODS: From January to December 2000, we studied retrospectively 25 pairs (50 patients) of renal allografts from the same donor considering the RI obtained with by eco color-Doppler ultrasound, daily diuresis and renal function (serum creatinine level) in the first six days following surgery. Improvement of diuresis and renal function after corticosteroid therapy was considered the gold standard for the diagnosis of acute rejection. RESULTS: Medical complications (acute renal rejection) in the first six days were occurred in three cases, two in the first transplanted kidney as first and one in the second; all three cases showed disappearance of the diastolic waveform component. Considering a RI variation >0.15 with respect to the initial value, the sensitivity, specificity and diagnostic accuracy in the Doppler diagnosis of acute rejection were 100%, 97.1% and 97.3% respectively, with a prevalence of 7.8%. There were no statistically significant correlations between the RI variation of the renal transplant and the twin kidney from the same donor. DISCUSSION AND CONCLUSIONS: Doppler ultrasound is an important diagnostic tool in the detection of medical complications in the immediate postoperative period and during renal transplant follow-up. RI analysis, when studied serially and in the right clinical settings, allows an early diagnosis of renal rejection with high sensibility and specificity.

Transureteroureterostomy obstruction mimicking acute tubular necrosis.

A patient receiving nephrotoxic chemotherapy for metastatic cervical cancer was examined for acute renal failure. A Tc-99m MAG3 scan showed symmetric function, bilateral increasing parenchymal activity, and no tracer excretion in either collecting system. The differential diagnosis included cisplatin-induced nephrotoxicity, dose infiltration, and obstruction of the common ureter. Analysis of the scan, an image over the injection site, and a delayed image of the urinary tract indicated obstruction of the common ureter at the anastomotic site of the transureteroureterostomy. In patients with a transureteroureterostomy, symmetric renal dysfunction, and no bladder activity, a delayed image of the urinary tract should be obtained to distinguish obstruction from acute tubular necrosis.

[Comparison of 2 methods of diagnosis of changes in transplanted kidneys in the early postoperative period: biopsy vs dynamic scintigraphy of the graft]. / Srovnání dvou metod v diagnostice zmen transplantované ledviny v casném pooperacním období: biopsie versus dynamická scintigrafie stepu.

Renal transplantation is at present a standard therapeutic method in chronic renal insufficiency. For a favourable development of the graft some investigated criteria are of basic importance: basic diagnosis which led to renal failure, period of dialyzation treatment, high standard collection and perfusion and early diagnosis of the rejection episode. Non-invasive diagnostic methods of the rejection episode are always indirect and correlate with histologically confirmed rejection, depending on the period of transplantation in 10-90% patients. Indirect diagnosis is based in particular on a rise of the creatinemia, decline of glomerular filtration, fluid retention variations of blood pressure and increase of the Doppler assessed index of resistance (IR) in the peripheral veins of the graft [1]. For many years the role of nuclear diagnostics are tested. The disadvantage of direct diagnosis--biopsy--is increased haemorrhage and loss of the graft [1, 2, 3, 4]. The greatest problem is the differentiation of acute (cellular) rejection as compared with acute tubular necrosis during the initial days after transplantation. The authors describe their experience with 81 biopsies in the course of 3 years in patients during the first 10 days after transplantation, comparison with dynamic scintigraphy of the graft. Their attention is focused on the technique and risks of renal biopsy.

Incidental recognition of left subclavian vein obstruction on renal scintigraphy.

In a renal transplant recipient with persistently poor graft function, the flow phase of a renal scan incidentally revealed multiple venous collaterals with focally increased vascular activity near the left lobe of the liver (quadrate lobe). This was initially assumed to represent superior vena cava (SVC) obstruction. A renal biopsy was contemplated to exclude acute rejection because of a nondiagnostic flow phase (loss of a bolus effect). However, because the possibility of venous obstruction at the level of the subclavian and/or brachiocephalic veins (without involving the SVC) also existed, another renal scan was performed, with injection of radiotracer into the contralateral arm. This showed a patent SVC and reasonably preserved renal perfusion consistent with acute tubular necrosis. Subsequently, left subclavian vein obstruction was identified. The graft function improved with conservative management for acute tubular necrosis. These findings illustrate the danger of considering only SVC obstruction when collateral flow patterns and focal hot spots in the liver are present.

Color Doppler sonography in early renal transplantation follow-up: resistive index measurements versus power Doppler sonography.

OBJECTIVE: This study was designed to compare power Doppler images of perfusion with interlobar resistive index measurements obtained during the early monitoring of renal graft transplant to diagnose cortical perfusion abnormalities and assess prognosis. SUBJECTS AND METHODS: Thirty-one patients underwent color Doppler sonography (4-7 MHz and 7-10 MHz) on day 6+/-2 after renal transplantation. Cortical vessel density was assessed visually and classified as either normal or decreased. Twelve months after transplantation, the results of power Doppler imaging and the levels of resistive index were reviewed in light of clinical and laboratory findings, graft biopsy results, and functional outcome. RESULTS: No significant relationship was observed among power Doppler grades, levels of resistive index, and renal function. Power Doppler grades and resistive index levels failed to allow us to distinguish between tubulopathy and rejection. However, we found a statistically significant relationship between renal function at 12 months after transplantation and power Doppler grade (p = .04). CONCLUSION: This study suggests that color Doppler sonography is insensitive in revealing and in allowing radiologists to differentiate the causes of graft dysfunction. However, power Doppler sonography allows a prediction of the functional recovery of the graft at 12 months after transplantation not provided by resistive index levels.

Evaluation of complications of kidney transplantation using artificial neural networks.

The aim of this study was to develop an artificial neural network (ANN) to differentiate between rejection, acute tubular necrosis (ATN) and normally functioning kidneys in a group of patients with renal transplants. The performance of ANN was compared with that of an experienced observer using a database of 35 patients' records, each of which included 12 quantitative parameters derived from renograms and clinical data as well as a clinical evaluation. These findings were encoded as features for a three-layered neural network to predict the outcome of biopsy or clinical diagnosis. The network was trained and tested using the jackknife method and its performance was then compared to that of a radiologist. The network was able to correctly classify 31 of the 35 original cases and gave a better diagnostic accuracy (88%) than the radiologist (83%), by showing an association between the quantitative data and the corresponding pathological results (r = 0.78, P < 0.001). We conclude that an ANN can be trained to differentiate rejection from acute tubular necrosis, as well as normally functioning transplants, with a reasonable degree of accuracy.

Evaluation of renographic and metabolic parameters in human kidney transplantation.

BACKGROUND: The aim of this work is to demonstrate that the value of the mean transit time (MTT) obtained from the 99mTc-MAG3 renogram deconvolution is related to the levels of adenine nucleotides determined in cortical biopsies from transplanted kidneys. METHODS: The functional state was estimated by means of the MTT and the initial height (H0) of the renal retention function obtained from the 99mTc-MAG3 renogram deconvolution and by the measure of adenine nucleotides obtained from biopsies. We studied 30 kidney graft recipients, 25 normal functioning grafts (NFG) and 5 with acute tubular necrosis (ATN). RESULTS: The MTT is significantly longer for ATN (p < 0.001). The initial uptake values (H0) are significantly lower for ATN (p < 0.001). The sum of adenine nucleotides (SAN) is significantly greater for NFG than for ATN (p < 0.001). The values of the MTT seem to reflect the energy state of the cells in transplanted kidney. CONCLUSION: The analysis of MTT may be indicative of the functional metabolic recovery and thus it may be predictive of the renal graft function at least in the same extent than the biochemical analysis of a cortical renal biopsy immediately after blood reperfusion of the tissue.

Gray-scale sonographic characterization of aminoglycoside-induced nephrotoxicosis in a canine model.

RATIONALE AND OBJECTIVES: The diagnostic usefulness of gray-scale sonography was evaluated in a canine model of aminoglycoside-induced nephrotoxicosis. METHODS: Sonography was performed before and during the onset and progression of nephrotoxicosis induced by administration of a toxic dosage of gentamicin. Subjective visualization of increased renal cortex echogenicity (IRCE) was objectified with digital image analysis methods. Results of both subjective and objective evaluation were correlated with clinicopathologic tests and renal cortex biopsy obtained concurrently. RESULTS: Subjective visualization of IRCE was associated with significant nephrotoxicosis and was superior to serum creatinine elevation in nephrotoxicity detection. Objective detection of IRCE improved nephrotoxicity detection sensitivity to that of increased urine enzymuria. CONCLUSIONS: Based on the above results, subjective visualization of IRCE in patients with aminoglycoside-induced nephrotoxicity may occur before azotemia and is suggestive of significant renal dysfunction; application of digital image analysis methods may lead to earlier sonographic recognition of nephrotoxicity.