The conundrum of high-grade hydronephrosis with non-obstructive drainage on diuretic renography.

BACKGROUND: Patients with high grade hydronephrosis (HN) and non-obstructive drainage on mercaptoacetyltriglycine (MAG-3) diuretic renography (renal scans) can pose a dilemma for clinicians. Some patients may progress and require pyeloplasty; however, more clarity is needed on outcomes among these patients. OBJECTIVE: Our primary objective was to predict which patients with high-grade HN and non-obstructive renal scan, (defined as T ½ time <20 min) would experience resolution of HN. Our secondary objective was to determine predictors for surgical intervention. STUDY DESIGN: Patients with prenatally detected HN were prospectively enrolled from 7 centers from 2007 to 2022. Included patients had a renal scan with T ½<20 min and Society for Fetal Urology (SFU) grade 3 or 4 at last ultrasound (RBUS) prior to renal scan. Primary outcome was resolution of HN defined as SFU grade 1 and anterior posterior diameter of the renal pelvis (APD) < 10 mm on follow-up RBUS. Secondary outcome was pyeloplasty, comparing patients undergoing pyeloplasty with patients followed with serial imaging without resolution. Multivariable logistic regression was used for analysis. RESULTS: Of the total 2228 patients, 1311 had isolated HN, 338 patients had a renal scan and 129 met inclusion criteria. Median age at renal scan was 3.1 months, 77% were male and median follow-up was 35 months (IQR 20-49). We found that 22% (29/129) resolved, 42% of patients had pyeloplasty (54/129) and 36% had persistent HN that required follow-up (46/129). Univariate predictors of resolution were age≥3 months at time of renal scan (p = 0.05), T ½ time≤5 min (p = 0.09), SFU grade 3 (p = 0.0009), and APD<20 mm (p = 0.005). Upon multivariable analysis, SFU grade 3 (OR = 4.14, 95% CI: 1.30-13.4, p = 0.02) and APD<20 mm (OR = 6.62, 95% CI: 1.41-31.0, p = 0.02) were significant predictors of resolution. In the analysis of decision for pyeloplasty, SFU grade 4 (OR = 2.40, 95% CI: 1.01-5.71, p = 0.04) and T ½ time on subsequent renal scan of ≥20 min (OR = 5.14, 95% CI: 1.54-17.1, p = 0.008) were the significant predictors. CONCLUSIONS: Patients with high grade HN and reassuring renal scan can pose a significant challenge to clinical management. Our results help identify a specific candidate for observation with little risk for progression: the patient with SFU grade 3, APD under 20 mm, T ½ of 5 min or less who was 3 months or older at the time of renal scan. However, many patients may progress to surgery or do not fully resolve and require continued follow-up.

Kidney dynamic SPECT acquisition on a CZT swiveling-detector ring camera: an in vivo pilot study.

BACKGROUND: Large field of view CZT SPECT cameras with a ring geometry are available for some years now. Thanks to their good sensitivity and high temporal resolution, general dynamic SPECT imaging may be performed more easily, without resorting to dedicated systems. To evaluate the dynamic SPECT imaging by such cameras, we have performed an in vivo pilot study to analyze the kidney function of a pig and compare the results to standard dynamic planar imaging by a conventional gamma camera. METHODS: A 7-week-old (12 kg) female Landrace pig was injected with [99mTc]Tc-MAG3 and a 30 min dynamic SPECT acquisition of the kidneys was performed on a CZT ring camera. A fast SPECT/CT was acquired with the same camera immediately after the dynamic SPECT, without moving the pig, and used for attenuation correction and drawing regions of interest. The next day the same pig underwent a dynamic planar imaging of the kidneys by a conventional 2-head gamma camera. The dynamic SPECT acquisition was reconstructed using a MLEM algorithm with up to 20 iterations, with and without attenuation correction. Time-activity curves of the total counts of each kidney were extracted from 2D and 3D dynamic images. An adapted 2-compartment model was derived to fit the data points and extract physiological parameters. Comparison of these parameters was performed between the different reconstructions and acquisitions. RESULTS: Time-activity curves were nicely fitted with the 2-compartment model taking into account the anesthesia and bladder filling. Kidney physiological parameters were found in agreement with literature values. Good agreement of these parameters was obtained for the right kidney between dynamic SPECT and planar imaging. Regional analysis of the kidneys can be performed in the case of the dynamic SPECT imaging and provided good agreement with the whole kidney results. CONCLUSIONS: Dynamic SPECT imaging is feasible with CZT swiveling-detector ring cameras and provides results in agreement with dynamic planar imaging by conventional gamma cameras. Regional analysis of organs uptake and clearance becomes possible. Further studies are required regarding the optimization of acquisition and reconstruction parameters to improve image quality and enable absolute quantification.

A Comparison of 68Ga-PSMA PET/CT-Based Split Renal Function with 99mTc-MAG3 Renography in Patients with Metastatic Castration-Resistant Prostate Carcinoma Treated with 177Lu-PSMA.

BACKGROUND: Physiological PSMA expression in the cells of the proximal renal tubules and consecutive radiopharmaceutical binding and retention could potentially lead to radioligand-therapy-induced nephrotoxicity. Thus, patients with metastatic castration-resistant prostate cancer undergo 99mTc-Mercaptoacetyltriglycine (MAG3) renal scintigraphy to assess kidney function and to exclude renal obstruction as part of their workup for PSMA-targeted radioligand therapy (RLT). 99mTc-MAG-3 renal scintigraphy often requires an additional visit to the nuclear medicine department and patients spend 30-90 min in the department, which is inconvenient and takes up camera time. In addition, the patients are subjected to a baseline 68Ga-PSMA PET/CT to assess for PSMA-positive disease prior to targeted radioligand therapy. The aim of this retrospective cross-sectional study was to compare 99mTc-MAG-3-based split renal function (SRF) with 68Ga-PSMA-derived SRF. METHODS: This retrospective cross-sectional study included 28 patients with histologically proven metastatic castration-resistant prostate cancer (mCRPC) who received 177Lu-PSMA617. A comparison between the split renal function using 68Ga-PSMA PET/CT and the 99mTc-MAG-3-derived split renal function was carried out in 56 kidneys (n = 56). The SRF on 68Ga-PSMA was calculated using the volume and the average standard uptake value (SUVmean) within each VOI calculated as previously described by Roser et al.: SRF = (VOLUMEright) ∗ SUVmeanright/(VOLUMEright ∗ SUVmeanright + VOLUMEleft ∗ SUVmeanleft). Paired tests and correlation coefficients were used to compare 68Ga-PSMA and 99mTc-MAG-3. A visual comparison of kidney morphology on both studies was also performed. RESULTS: The median SRF of the right kidney was 49.9% (range: 3-91%) using 68Ga-PSMA PET/CT and 50.5% (range: 0-94%) with 99mTc-MAG3 scintigraphy. Notably, there was a strong correlation between SRF measurements obtained from PSMA and 99mTcMAG3, with a Pearson correlation coefficient of 0.957 (p < 0.001). Both 99mTc-MAG3 and 68Ga-PSMA PET/CT studies identified morphological renal abnormalities; there were nine hydronephrotic kidneys, four shrunken kidneys and one obstructed kidney, and there was a strong positive correlation between 68Ga-PSMA kidney morphology and 99mTcMAG3 renal scintigraphy kidney morphology, with a correlation coefficient of 0.93. CONCLUSIONS: PSMA-derived split function demonstrated a high correlation with renal function assessed on diuretic 99mTc-MAG3 renograms. PET-derived split renal function may, therefore, be considered an alternative to diuretic renogram-based split function. Furthermore, both 99mTc-MAG3 and 68Ga-PSMA PET/CT studies identified morphological renal abnormalities such as hydronephrosis, shrunken and obstructed kidneys. This correlation underscores the potential utility of 68Ga-PSMA imaging as a valuable tool for assessing kidney morphology as an alternative to renogram split function in clinical practice.

Effects of isoflurane anaesthesia depth and duration on renal function measured with [99mTc]Tc-mercaptoacetyltriglycine SPECT in mice.

BACKGROUND: The influence of anaesthetic depth and the potential influence of different anaesthetic beds and thus different handling procedures were investigated in 86 severe combined immunodeficient (SCID) mice using semi-stationary dynamic single photon emission computed tomography (SPECT) for kidney scintigraphy. Therefore, isoflurane concentrations were adjusted using respiratory rate for low (80-90 breath/min) and deep anaesthesia (40-45 breath/min). At low anaesthesia, we additionally tested the influence of single bed versus 3-mouse bed hotel; the hotel mice were anaesthetized consecutively at ~ 30, 20, and 10 min before tracer injections for positions 1, 2, and 3, respectively. Intravenous [99mTc]Tc-MAG3 injection of ~ 28 MBq was performed after SPECT start. Time-activity curves were used to calculate time-to-peak (Tmax), T50 (50% clearance) and T25 (75% clearance). RESULTS: Low and deep anaesthesia corresponded to median isoflurane concentrations of 1.3% and 1.5%, respectively, with no significant differences in heart rate (p = 0.74). Low anaesthesia resulted in shorter aortic blood clearance half-life (p = 0.091) and increased relative renal tracer influx rate (p = 0.018). A tendency toward earlier Tmax occurred under low anaesthesia (p = 0.063) with no differences in T50 (p = 0.40) and T25 (p = 0.24). Variance increased with deep anaesthesia. Compared to single mouse scans, hotel mice in position 1 showed a delayed Tmax, T50, and T25 (p < 0.05 each). Furthermore, hotel mice in position 1 showed delayed Tmax versus position 3, and delayed T50 and T25 versus position 2 and 3 (p < 0.05 each). No difference occurred between single bed and positions 2 (p = 1.0) and 3 (p = 1.0). CONCLUSIONS: Deep anaesthesia and prolonged low anaesthesia should be avoided during renal scintigraphy because they result in prolonged blood clearance half-life, delayed renal influx and/or later Tmax. Vice versa, low anaesthesia with high respiratory rates of 80-90 rpm and short duration (≤ 20 min) should be preferred to obtain representative data with low variance.

Deep learning of renal scans in children with antenatal hydronephrosis.

INTRODUCTION: Antenatal hydronephrosis (ANH) is one of the most common anomalies identified on prenatal ultrasound, found in up to 4.5% of all pregnancies. Children with ANH are surveilled with repeated renal ultrasound and when there is high suspicion for a ureteropelvic junction obstruction on renal ultrasound, a mercaptuacetyltriglycerine (MAG3) Lasix renal scan is performed to evaluate for obstruction. However, the challenging interpretation of MAG3 renal scans places patients at risk of misdiagnosis. OBJECTIVE: Our objective was to analyze MAG3 renal scans using machine learning to predict renal complications. We hypothesized that our deep learning model would extract features from MAG3 renal scans that can predict renal complications in children with ANH. STUDY DESIGN: We performed a case-control study of MAG3 studies drawn from a population of children with ANH concerning for ureteropelvic junction obstruction evaluated at our institution from January 2009 until June of 2021. The outcome was renal complications that occur ≥6 months after an equivocal MAG-3 renal scan. We created two machine learning models: a deep learning model using the radiotracer concentration versus time data from the kidney of interest and a random forest model created using clinical data. The performance of the models was assessed using measures of diagnostic accuracy. RESULTS: We identified 152 eligible patients with available images of which 62 were cases and 90 were controls. The deep learning model predicted future renal complications with an overall accuracy of 73% (95% confidence inteveral [CI] 68-76%) and an AUC of 0.78 (95% CI 0.7, 0.84). The random forest model had an accuracy of 62% (95% CI 60-66%) and an AUC of 0.67 (95% CI. 0 64, 0.72) DISCUSSION: Our deep learning model predicted patients at high risk of developing renal complications following an equivocal renal scan and discriminate those at low risk with moderately high accuracy (73%). The deep learning model outperformed the clinical model built from clinical features classically used by urologists for surgical decision making. CONCLUSION: Our models have the potential to influence clinical decision making by providing supplemental analytical data from MAG3 scans that would not otherwise be available to urologists. Future multi-institutional retrospective and prospective trials are needed to validate our model.

Outcomes of Robot-Assisted Laparoscopic Pyeloplasty Based on Degree of Obstruction on Preoperative Tc-99 MAG-3 Renal Scintigraphy.

Objective: Management of symptomatic ureteropelvic junction (UPJ) obstruction with hydronephrosis and discordant Tc-99 mercaptoacetyltriglycine (MAG-3) renal scintigraphy is challenging. In this study we describe long-term outcomes of patients who underwent robot-assisted laparoscopic pyeloplasty for the correction of symptomatic UPJ obstruction with discordant preoperative Tc-99m MAG-3 renal scintigraphy. Methods: Patients undergoing robot-assisted laparoscopic pyeloplasty for symptomatic UPJ obstruction at a single academic center from 2009 to 2021 were retrospectively reviewed. Patients were categorized into three groups with varying degrees of obstruction based on preoperative MAG-3 imaging: Group 1: no obstruction (Lasix T1/2 clearance <10 minutes), Group 2: equivocal obstruction (Lasix T1/2 clearance 10-20 minutes), and Group 3: obstruction (Lasix T1/2 clearance >20 minutes. Pyeloplasty success was defined as resolution of symptoms and improvement/stable computed tomography (CT) imaging or MAG-3 scintigraphy. Failure was defined as persistence of symptoms with either obstruction on functional imaging, worsening hydronephrosis, or subsequent intervention. Results: A total of 125 cases were identified, with a median patient age of 35 years. Dismembered pyeloplasty technique was performed in 98.4% of cases. Median preoperative split renal function on MAG-3 scintigraphy was the only statistically significant (p = 0.003) difference in preoperative characteristics between the three groups. There were 15 postoperative complications, with a rate of Clavien-Dindo grade 3 or higher complications of 4.8%. Overall pyeloplasty success was 92.8%, with success rates of 100% (15/15) and 97% (32/33) in the no obstruction and equivocal obstruction groups, respectively. Median time to pyeloplasty failure was 20.4 months. Conclusion: Robot-assisted laparoscopic pyeloplasty is a safe and effective surgical intervention for correcting UPJ obstruction. Patients with symptoms of UPJ obstruction and discordant functional imaging studies demonstrate similar or improved success rates after pyeloplasty compared with patients with documented high-grade obstruction. Based on these findings preoperative renal scan may not be reliable in appropriate selection of candidacy for pyeloplasty.

Clinical application of normalized residual activity as a semiquantitative adjunct in assessing renal emptying in pediatric diuretic scans

Background@#The most recent pediatric diuretic imaging guidelines recommend the use of normalized residual activity (NORA) as a semiquantitative index of renal tracer drainage. It is defined as the ratio of post-void renal counts to 1-2 minute post-injection renal counts, with values less than 1 indicative of good drainage. We present two instances where NORA calculation was adjunctive in the evaluation of obstructive uropathy. @*Case Presentation@#The first patient was a 3-month-old male with left-sided congenital hydronephrosis. On dynamic imaging, the diseased kidney showed adequate perfusion and parenchymal extraction; moderate to severe pelvicalyceal tracer retention exhibited good response to diuretic. The pre-diuretic NORA of 1.62 declined to 0.28 after furosemide challenge, concordant with imaging findings that were negative for obstruction. The second patient was a 7-week-old male, also with congenital hydronephrosis of the left kidney. Dynamic images showed the diseased kidney with diminished perfusion and function, as well as pelvicalyceal tracer retention which became more severe after the diuretic was given. The pre-diuretic NORA was 1.81, which became 1.18 post-diuretic. This inadequate decline supplemented imaging findings pointing to significant obstruction. Other semiquantitative parameters have preceded NORA; however, clearance half-time is not validated as a marker of obstructive uropathy in infants and children, and output efficiency requires specialized software to calculate. Standardization of NORA determination is largely provided for by the guidelines recommending a perirenal background region of interest, as well as minimizing the interval between starting camera acquisition and injecting the tracer. @*Conclusion@#Semiquantitative analysis through NORA calculation gives relevant supporting information in the reporting of renal tracer drainage among pediatric patients. Further studies are needed to ascertain its applicability among adults and its diagnostic value in a larger sample of affected Filipino children.

Initial observational management of hydronephrosis in infants with reduced differential renal function and non-obstructive drainage parameters.

INTRODUCTION: Hydronephrosis secondary to ureteropelvic junction (UPJ) obstruction is a common finding in infants with prenatally-diagnosed hydronephrosis and often results in pyeloplasty due to obstructive drainage parameters and/or renal function compromise. However, little is known regarding the natural history of hydronephrosis with reduced differential renal function (DRF) but non-obstructive drainage. OBJECTIVE: We sought to explore our experience with initial observational management of these patients. STUDY DESIGN: A retrospective review of our institutional database of all diuretic MAG-3 renal scans obtained between 2000 and 2016 was performed. We included patients with antenatally-detected unilateral hydronephrosis ≥ SFU grade 2, first MAG-3 scan prior to 18months of age, DRF <40% and post-furosemide half-time (T1/2) <20 min. Exclusion criteria were: hydroureter, VUR, solitary kidney, duplication anomalies. Outcomes of interest were a progression of T1/2 ≥ 20 min and/or further decline in DRF >5%. RESULTS: Of 704 patients with unilateral hydronephrosis, 91 had DRF≤40%, of which 29 (18 boys, 11 girls) met our inclusion criteria and were followed for a mean of 2.8 years (1.4 months-6.6 years). Mean age at first sonogram was 2.3 months. 2 patients had SFU grade 2, 16 had grade 3, and 9 had grade 4 hydronephrosis, and 2 unknown grade. Median half-time on initial MAG-3 scan across all patients was 10 min (3-20 min). Initial MAG3 scan was performed at a median of 2.3 months of age (0.3-17 months). 22/29 patients had >1 MAG3 scan. Of the 7 remaining, 5 were lost to follow-up and 2 demonstrated improvement in hydronephrosis. Worsening drainage occurred in 10/22(45%), median final T1/2 was 45.5 min 8 of these underwent pyeloplasty and 2 were lost to follow up. 4/22 patients (18%) had progressive decline in DRF (mean 8.3%, range 6-10%). 3/4 maintained non-obstructive drainage patterns and stable/improved hydronephrosis, and 1 underwent pyeloplasty. 13/18 remaining patients had stable DRF and 5 had improvement in DRF. 7(39%) of these underwent surgery for worsening drainage (Summary Figure). Overall, 7/29(24%) patients had sufficient resolution of hydronephrosis to be discharged from our care, 8(28%) are under continued observation, 9(31%) underwent pyeloplasty, and 5(17%) were lost to follow-up. In the observational group [median follow-up 4.5 years (3.7-6.6 years)], all 8 demonstrated improved non-obstructive drainage (T1/2 <20 minutes) and/or improvement in hydronephrosis. 4/10(40%) with DRF <35% underwent pyeloplasty versus 5/19(26%) with DRF 35-40%(p=0.67). CONCLUSION: Initial observational management of unilateral hydronephrosis with reduced DRF and nonobstructive drainage is recommended as most kidneys maintain nonobstructive drainage and do not demonstrate further decline in DRF. Even when DRF decreases, the majority remain non-obstructive. Worsening drainage over time more often leads to the decision for pyeloplasty rather than change in DRF.

Deconvolution of Tc-99m-Mercaptoacetyltriglycine Renograms with the Concomitant Use of a Sparse Legendre Polynomial Representation and the Moore-Penrose Pseudo-inverse.

OBJECTIVES: This study aimed to introduce an improved deconvolution technique for Tc-99m-mercaptoacetyltriglycine renograms based on the combination of a sparse Legendre polynomial representation and the Moore-Penrose inversion matrix (LG). This method reduces the effect of noise on the measurement of renal retention function transit time (TT). METHODS: The stability and accuracy of the proposed method were tested using a renal database containing Monte Carlo-simulated studies and real adult patient data. Two clinical parameters, namely, split function (SF) and mean TT (meanTT), obtained with LG were compared with values calculated with the established method that combines matrix deconvolution and a three-point linear smoothing (F121) as recommended by the 2008 International Scientific Committee of Radionuclides in Nephrourology consensus on renal TT measurements. RESULTS: For simulated data, the root mean square error (RMSE) between the theoretical non-noisy renal retention curve (RRC) and the results of the deconvolution methods applied to the noisy RRC were up to two times lower with LG (p<0.001). The RMSE of the reconvoluted renogram and the theoretical one was also lower for LG (p<0.001) and showed better preservation of the original signal. The SF was neither improved nor degraded by the proposed method. For patient data, no statistically significant difference was found between the SF for the LG method compared with the database values, and the meanTT better agreed with the physician's diagnosis than the matrix or clinical software (Hermes) outputs. A visual improvement of the RRC was also observed. CONCLUSION: By combining the sparse Legendre representation of the renogram curves and the Moore-Penrose matrix inverse techniques, we obtained improved noise reduction in the deconvoluted data, leading to better elimination of non-physiological signals -as negative values- and the avoidance of the smear effect of conventional smoothing on the vascular peak, which both influenced the meanTT measurement.

Assessment of Individual Renal Function Using 99mTc-MAG3 Renography.

BACKGROUND/AIM: This study performed 99mTc-MAG3 renal scintigraphy on rabbit kidneys and evaluated its ability to identify obstructive or non-obstructive kidneys. MATERIALS AND METHODS: Renal function was assessed during a four-week post-obstruction period by obtaining planar images of 99mTc-MAG3 activity following an ear vein injection. The individual renal function was evaluated by renal scintigraphy in conjunction with histopathological and morphological examinations. RESULTS: The renal perfusion of 99mTc-MAG3 in the right kidney with a ureteral obstruction decreased with time. The width, height, and cortical thickness of the obstructed right kidney were significantly larger than those of the left kidney. A histopathological examination four weeks after the ureteral obstruction revealed a typical pattern of urinary tract obstruction, including multiple tubules, enlargement of the interstitial area, and cytoplasmic vacuoles. CONCLUSION: 99mTc-MAG3 renal scintigraphy provides the kidney shape and size and can identify potential obstructive and non-obstructive kidneys in rabbits.

Development and autoregulation of kidney function in children: a retrospective study using 99mTc-MAG3 renography.

BACKGROUND: Both the development of kidney function in healthy children and autoregulation ability of kidney function in patients with asymmetric kidneys are important in clinical diagnosis and treatment of kidney-related diseases, but there are however only limited studies. This study aimed to investigate development of kidney function in normal children with healthy symmetric kidneys and autoregulation of the healthy kidney compensating the functional loss of a diseased one in children with asymmetric kidneys. METHODS: Two hundred thirty-seven children (156 male, 81 female) from 0 to 20y (average 4.6y ± 5.1) undergoing 99mTc-MAG3 renography were included, comprising 134 with healthy symmetrically functioning kidneys and 103 with asymmetric kidneys. Clearance was calculated from kidney uptakes at 1-2 min. A developmental model between MAG3 clearance (CL) and patient age in normal group was identified (CL = 84.39Age0.395 ml/min, r = 0.957, p < 0.001). The clearance autoregulation rate in abnormal group with asymmetric kidneys was defined as the ratio of the measured MAG3 clearance and the normal value predicted from the renal developmental model of normal group. RESULTS: No significant difference of MAG3 clearance (p = 0.723) was found between independent abnormal group and normal group. The autoregulation rate of kidney clearance in abnormal group was 94.2% on average, and no significant differences were found between two age groups (p = 0.49), male and female (p = 0.39), and left kidney and right kidney (p = 0.92) but two different grades of asymmetric kidneys (p = 0.02). CONCLUSIONS: The healthy kidney of two asymmetric kidneys can automatically regulate total kidney function up to 94% of two symmetric kidneys in normal children.

Pretherapeutic estimated glomerular filtration rate predicts development of chronic kidney disease in patients receiving PSMA-targeted radioligand therapy.

BACKGROUND: Prostate-specific membrane antigen (PSMA)-targeted radioligand therapy (RLT) may be associated with renal toxicity. We aimed to identify predictive parameters for the development of chronic kidney disease (CKD) in patients with metastatic castration resistant prostate cancer (mCRPC) undergoing RLT. METHODS: In 46 mCRPC patients scheduled for Lu-177-PSMA-RLT, pretherapeutic estimated glomerular filtration rate (eGFR [ml/min/1.73 m2 ]), Tc-99m-mercaptoacetyltriglycine (Tc-99m-MAG3) clearance and baseline Ga-68-PSMA-ligand positron emission tomography (PET)-derived renal cortical uptake and PSMA-tumor volume (TV) were determined. We tested the predictive capability of these parameters and clinical risk factors for the occurrence of CKD (defined as CTCAE vers. 5.0 grade 2 or higher) during follow-up. RESULTS: After 4 ± 3 cycles of RLT average eGFR declined from 76 ± 17 to 72 ± 20 ml/min/1.73 m2 (p = 0.003). Increased estimated renal radiation dose (eRRD) was significantly associated with renal functional decline (p = 0.008). During follow-up, 16/46 (30.4%) developed CKD grade 2 (no grade 3 or higher). In receiver operating characteristic (ROC) analysis, pretherapeutic eGFR was highly accurate in identifying the occurrence of CKD vs no CKD with an area under the curve (AUC) of 0.945 (p < 0.001; best threshold, 77 ml/min/1.73 m2 ), followed by Tc-99m-MAG3-derived tubular extraction rate (TER; AUC, 0.831, p < 0.001; best threshold, 200 ml/min/1.73 m2 ). Renal PET signal (p = 0.751) and PSMA-TV (p = 0.942), however, were not predictive. Kaplan-Meier analyses revealed adverse renal outcome for patients with lower eGFR (p = 0.001) and lower scintigraphy-derived TER (p = 0.009), with pretherapeutic eGFR emerging as the sole predictive parameter in multivariate analysis (p = 0.007). CONCLUSION: Serious adverse renal events are not a frequent phenomenon after PSMA-targeted RLT. However, in patients developing moderate CKD after RLT, pretherapeutic eGFR is an independent predictor for renal impairment during follow-up.

Implementation of a clinical guideline for nonoperative management of isolated blunt renal injury in children.

BACKGROUND: The aim was to evaluate the impact of a standardized nonoperative management protocol by comparing patients with isolated blunt renal injury before and after implementation. METHODS: We retrospectively reviewed the trauma registry at our Level 1 pediatric trauma center. We compared consecutive patients (≤ 18 years) managed nonoperatively for blunt renal injury Pre (1/2010-9/2014) and Post (10/2014-3/2020) implementation of a clinical guideline. Outcomes included length of stay, intensive care unit admission, urinary catheter use, and imaging studies. RESULTS: We included 48 patients with isolated blunt renal injuries (29 Pre, 19 Post). There were no differences in age, sex, injury grade, or mechanism (P > .05). Postprotocol had decreased length of stay (P = .040), intensive care unit admissions (P = .015), urinary catheter use (P = .031), and ionizing radiation imaging (P < .001). CONCLUSION: These data suggest improved outcomes and resource utilization following implementation of a nonoperative management protocol of pediatric isolated blunt renal injuries.

Potential benefits of functional magnetic resonance urography (fMRU) over MAG3 renal scan in children with obstructive uropathy.

INTRODUCTION: Functional renal imaging, most commonly with MAG3 nuclear medicine renal scan, is recommended in the evaluation of children with urinary tract dilation (UTD) suspected of obstructive uropathy. Alternatively, renal function can be evaluated with functional Magnetic Resonance Urography (fMRU), which has superior anatomic detail. However, there are not enough data comparing both methods' equivalency. In this study, we compare the functional and obstruction parameters of fMRU and MAG3 in a pediatric cohort presenting with obstructive uropathy. STUDY DESIGN: This is an IRB-approved retrospective review of all children undergoing fMRU at a single, free-standing children's hospital between May 2008 and September 2017. Patients who also underwent a MAG3 renal scan within 6 months and who had no interval surgical intervention were included in the study. Bladder catheterization was performed prior to both imaging studies. RESULTS: 735 children had 988 fMRU studies performed during the study period. 37 unique patients (13 girls and 24 boys) with median age of 6 months (range: 2 mo-19 y) were included in the final sample. Median time interval between studies was 70 days (range 6-179 days). The majority of participants (26/37, 70.3%) presented with UTD P3 and had diagnosis of uretero-pelvic junction obstruction (UPJO) in 21/37. Differential renal function (DRF) was used to group 10 fMRU and 9 MAG3 patients as normal; 9 fMRU and 11 MAG3 as mild; 11 fMRU and 6 MAG3 as moderate; and 7 fMRU and 6 MAG3 as severe; Wilcoxon signed-rank test (p = 0.5106). Results were similar for DRF among patients with and without duplex kidneys. In the analysis of obstruction, using reference standard T½ MAG3 ≥ 20 min, a greater or equal than 6 min renal transit time (RTT) from fMRU showed a specificity of 94%, a sensitivity of 62%, and an AUC of 0.827. DISCUSSION AND CONCLUSIONS: The differential renal function determined by MAG3 and fMRU in children was not statistically different, therefore we concluded that it was similar and potentially equivalent. Better correlation was shown in patients who had normal split kidney function. While the tests are clinically equivalent, the variability of DRF within each clinical category (i.e., normal, mild, moderate, severe) is not surprising, because MAG3 does not clearly differentiate the dilated collecting system from the functional parenchymal tissue, while fMRU does. Using MAG3 as the gold standard, fMRU was 94.74% specific and 5% more sensitive in detecting UPJO with a RTT of 6min vs. 8min.

Does relative renal function improve after intervention for chronic ureteric obstruction?

INTRODUCTION: Unilateral renal function often deteriorates with chronic ureteric obstruction. Our objectives were to determine the change in relative renal function (RRF) by MAG3 renography after intervention for ureteric obstruction, and to identify clinical/epidemiological factors which influence long-term outcomes. MATERIAL AND METHODS: We identified 228 patients from 2006 to 2017 who underwent MAG3 renography before and after intervention for unilateral ureteric obstruction. Patients were grouped into categories preoperatively - with normal RRF (43-57%) through mild (29-42%), moderate (15-28%) and severe (<15%) impairment of RRF. Patient demographics, types of obstructive uropathy and intervention employed were analysed. Each group was assessed for the absolute change in RRF and change in RRF category postoperatively. RESULTS: The mean patient age was 50.4 years (SD 16.7), and 62.3% were female. Overall, the mean pre- and post-intervention RRF of the obstructed kidney did not differ significantly (32.30% vs. 32.20%, P = 0.835). Most patients remained in their preoperative RRF group: 85.9% of normal, 67.4% of mild, 64.4% of moderate and 73.3% of patients with severe RRF impairment did not change category.Patients with mildly impaired preoperative RRF showed a significant worsening postoperatively (36.37% vs. 34.58%, P = 0.024). The other three groups showed no significant change in RRF following intervention.Multivariate logistic regression analysis showed no statistically significant association between type of intervention, age, gender or diagnosis and improvement in postoperative RRF category. CONCLUSIONS: Our results show that RRF does not improve significantly after intervention for ureteric obstruction. The aim should therefore be to maintain existing renal function and relieve symptoms.

Head to head comparison of [99mTc]Tc(CO)3(NTA) and [99mTc]Tc-MAG3 in patients with suspected obstruction.

PURPOSE: 99mTc-tricarbonyl-nitrilotriacetic acid, [99mTc]Tc(CO)3(NTA), is a new 99mTc-renal radiopharmaceutical with a clearance equal to that of 131I-ortho-iodohippuran, [131I]I-OIH. Our purpose was to compare the performance of [99mTc]Tc(CO)3(NTA) and [99mTc]Tc-MAG3 in patients with suspected obstruction. METHODS: [99mTc]Tc(CO)3(NTA) was prepared with commercially available NTA ligand and CRS Isolink kit, and isolated by HPLC. Eighteen adult patients referred for diuretic renography received an intravenous injection of approximately 40 mg of furosemide 15 min prior to either [99mTc]Tc(CO)3(NTA) or [99mTc]Tc-MAG3 (mean activity of 47 ± 4.4 MBq). Data were acquired for 24 min followed by an anterior image of the liver and gall bladder and a measure of voided volume. Patients received a second furosemide injection equal to one third of the original dose followed fifteen minutes later by administration of the alternate tracer, mean activity of 320 ± 34 MBq. Clearances were measured using a camera-based technique. RESULTS: The clearance of NTA was greater than that of MAG3, 331 ± 146 versus 271 ± 105 mL/min/1.73 m2, respectively, p < 0.0001. The kidney to background ratio for NTA was greater than that of MAG3 for both left and right kidneys, p < 0.001; the 20 min/maximum count ratio was significantly less, p < 0.0001. There was no significant difference in the voiding volumes following NTA and MAG3 administration, 598 ± 237 mL versus 498 ± 170 mL, respectively, p = 0.07. Gall bladder activity was not observed with NTA but was present in 6/17 MAG3 studies. Images and renogram curves were comparable except for two patients where the NTA study excluded obstruction but the MAG3 study suggested an indeterminate or obstructed kidney. CONCLUSIONS: Unlike MAG3, NTA is not eliminated via the hepatobiliary track. Moreover, NTA has a higher kidney to background ratio and more rapid clearance than MAG3. These advantages should allow more robust camera-based clearance measurements and may lead to better discrimination between obstructed and non-obstructed kidneys.

U.S. Diagnostic Reference Levels and Achievable Administered Activities for Adult Renal Scintigraphy: An Analysis of the Intersocietal Accreditation Committee Nuclear Laboratories.

The goal of this work was to determine U.S. diagnostic reference levels (DRLs) and achievable administered activities (AAAs) for adult renal scintigraphy. Methods: Under an Institutional Review Board-approved protocol, data were collected from the Intersocietal Accreditation Commission during one 3-y accreditation cycle encompassing 110 facilities. Elements included radiopharmaceutical, administered activity, practice type, and examination volume. DRLs and AAAs were calculated and compared with non-U.S. values and societal recommendations as available. Results: Ninety-three facilities provided data on 99mTc-mercaptoacetyltriglycine (99mTc-MAG3), and 15 provided data on 99mTc-diethylenetriaminepentaacetic acid (99mTc-DTPA) for adult renal scintigraphy exams. Analysis demonstrated a DRL of 392.2 MBq (10.6 mCi) for 99mTc-MAG3 and 531.7 MBq (14.4 mCi) for 99mTc-DTPA, with an AAA of 370 MBq (10 mCi) for 99mTc-MAG3 and 445.9 MBq (12.1 mCi) for 99mTc-DTPA. Conclusion: The resultant calculated novel U.S. DRLs and AAAs may serve as benchmarks that nuclear medicine facilities may use to refine renal scintigraphy protocols, reduce patient doses, and potentially guide future societal guideline recommendations.

177Lu-PSMA-617 Therapy in Mice, with or without the Antioxidant α1-Microglobulin (A1M), Including Kidney Damage Assessment Using 99mTc-MAG3 Imaging.

Anti-prostate specific membrane antigen (PSMA) radioligand therapy is promising but not curative in castration resistant prostate cancer. One way to broaden the therapeutic index could be to administer higher doses in combination with radioprotectors, since administered radioactivity is kept low today in order to avoid side-effects from a high absorbed dose to healthy tissue. Here, we investigated the human radical scavenger α1-microglobulin (A1M) together with 177-Lutetium (177Lu) labeled PSMA-617 in preclinical models with respect to therapeutic efficacy and kidney toxicity. Nude mice with subcutaneous LNCaP xenografts were injected with 50 or 100 MBq of [177Lu]Lu-PSMA-617, with or without injections of recombinant A1M (rA1M) (at T = 0 and T = 24 h). Kidney absorbed dose was calculated to 7.36 Gy at 4 days post a 100 MBq injection. Activity distribution was imaged with Single-Photon Emission Computed Tomography (SPECT) at 24 h. Tumor volumes were measured continuously, and kidneys and blood were collected at termination (3-4 days and 3-4 weeks after injections). In a parallel set of experiments, mice were given [177Lu]Lu-PSMA-617 and rA1M as above and dynamic technetium-99m mercaptoacetyltriglycine ([99mTc]Tc-MAG3) SPECT imaging was performed prior to injection, and 3- and 6-months post injection. Blood and urine were continuously sampled. At termination (6 months) the kidneys were resected. Biomarkers of kidney function, expression of stress genes and kidney histopathology were analyzed. [177Lu]Lu-PSMA-617 uptake, in tumors and kidneys, as well as treatment efficacy did not differ between rA1M and vehicle groups. In mice given rA1M, [99mTc]Tc-MAG3 imaging revealed a significantly higher slope of initial uptake at three months compared to mice co-injected with [177Lu]Lu-PSMA-617 and vehicle. Little or no change compared to control was seen in urine albumin, serum/plasma urea levels, RT-qPCR analysis of stress response genes and in the kidney histopathological evaluation. In conclusion, [99mTc]Tc-MAG3 imaging presented itself as a sensitive tool to detect changes in kidney function revealing that administration of rA1M has a potentially positive effect on kidney perfusion and tubular function when combined with [177Lu]Lu-PSMA-617 therapy. Furthermore, we could show that rA1M did not affect anti-PSMA radioligand therapy efficacy.