Atypical histological abnormalities in an adult patient with nephronophthisis harboring NPHP1 deletion: a case report.

BACKGROUND: Nephronophthisis (NPHP) is a chronic tubular interstitial disorder that exhibits an autosomal recessive genetic form and causes progressive renal failure in children. Patients with NPHP rarely show urinary abnormalities, edema, or hypertension. Thus, NPHP is often detected only when renal failure becomes advanced. NPHP can be divided into three types based on the age of end-stage renal failure, i.e., infant type (approximately 5 years old), juvenile type (approximately 13-14 years old), and adolescent type (approximately 19 years old). Here, we report a case of NPHP diagnosed by genetic analysis at 26 years of age with atypical histological abnormalities. CASE PRESENTATION: A 26-year-old woman showed no growth disorders or urinary abnormalities in annual school physical examinations. However, at a check-up at 26 years old, she exhibited renal dysfunction (eGFR 26 mL/min/1.73 m2). Urine tests indicated low specific gravity of urine, but not proteinuria or microscopic hematuria. Urinary ß2-microglobulin was high (805 µg/L), and renal biopsy was performed for definitive diagnosis. Histological findings showed no significant findings in glomeruli. However, moderate fibrosis was observed in the interstitial area, and moderate atrophy was observed in the tubules. There were no significant findings in immunofluorescence analysis, and no electron dense deposits were detected by electron microscopy. Although cyst-like expansion of the tubules was unclear, tubular atrophy was dominantly found in the distal tubule by cytokeratin 7 staining. Genetic analysis of the NPHP1 gene showed complete deletion of this gene, leading to a definitive diagnosis of NPHP. CONCLUSIONS: NPHP is not merely a pediatric disease and is relatively high incidence in patients with adult onset end-stage of renal disease. In this case, typical histological abnormalities, such as cyst-like expansion of the tubular lesion, were not observed, and diagnosis was achieved by genetic analysis of the NPHP1 gene, which is responsible for the onset of NPHP. In patients with renal failure with tubular interstitial disease dominantly in the distal tubules, it is necessary to discriminate NPHP, even in adult cases.

Renal tubular dilation and fibrosis after unilateral ureter obstruction revealed by relaxometry and spin-lock exchange MRI.

We evaluated the use of quantitative MRI relaxometry, including the dispersion of spin-lock relaxation with different locking fields, for detecting and assessing tubular dilation and fibrosis in a mouse model of unilateral ureter obstruction (UUO). C57BL/6 J and BALB/c mice that exhibit different levels of tubular dilation and renal fibrosis after UUO were subjected to MR imaging at 7 T. Mice were imaged before UUO surgery, and at 5, 10 and 15 days after surgery. We acquired maps of relaxation rates and fit the dispersion of spin-lock relaxation rates R1ρ at different locking fields (frequencies) to a model of exchanging water pools, and assessed the sensitivity of the derived quantities for detecting tubular dilation and fibrosis in kidney. Histological scores for tubular dilation and fibrosis, based on luminal space and positive fibrotic areas in sections, were obtained for comparison. Histology detected extensive tubular dilation and mild to moderate fibrosis in the UUO kidneys, in which enlargement of luminal space, deposition of collagen, and reductions in capillary density were observed in the cortex and outer stripe of the outer medulla. Relaxation rates R1 , R2 and R1ρ clearly decreased in these regions of UUO kidneys longitudinally. While R1 showed the highest detectability to tubular dilation and overall changes in UUO kidneys, Sρ , a parameter derived from R1ρ dispersion data, showed the highest correlation with renal fibrosis in UUO. While relaxation parameters are sensitive to tubular dilation in UUO kidneys, Sρ depends primarily on the average exchange rate between water and other chemically shifted resonances such as hydroxyls and amides, and provides additional specific information for evaluating fibrosis in kidney disease.

Kidney Allograft Fibrosis: Diagnostic and Therapeutic Strategies.

Interstitial fibrosis with tubule atrophy (IF/TA) is the response to virtually any sustained kidney injury and correlates inversely with kidney function and allograft survival. IF/TA is driven by various pathways that include hypoxia, renin-angiotensin-aldosterone system, transforming growth factor-ß signaling, cellular rejection, inflammation, and others. In this review, we will focus on key pathways in the progress of renal fibrosis, diagnosis and therapy of allograft fibrosis. This review discusses the role and origin of myofibroblasts as matrix producing cells and therapeutic targets in renal fibrosis with a particular focus on renal allografts. We summarize current trends to use multiomic approaches to identify new biomarkers for IF/TA detection and to predict allograft survival. Furthermore, we review current imaging strategies that might help to identify and follow-up IF/TA complementary or as alternative to invasive biopsies. We further discuss current clinical trials and therapeutic strategies to treat kidney fibrosis.

Weight-gain induced changes in renal perfusion assessed by contrast-enhanced ultrasound precede increases in urinary protein excretion suggestive of glomerular and tubular injury and normalize after weight-loss in dogs.

Early detection of obesity-related glomerulopathy in humans is challenging as it might not be detected by routine biomarkers of kidney function. This study's aim was to use novel kidney biomarkers and contrast-enhanced ultrasound (CEUS) to evaluate the effect of obesity development and weight-loss on kidney function, perfusion, and injury in dogs. Sixteen healthy lean adult beagles were assigned randomly but age-matched to a control group (CG) (n = 8) fed to maintain a lean body weight (BW) for 83 weeks; or to a weight-change group (WCG) (n = 8) fed the same diet to induce obesity (week 0-47), to maintain stable obese weight (week 47-56) and to lose BW (week 56-83). At 8 time points, values of systolic blood pressure (sBP); serum creatinine (sCr); blood urea nitrogen (BUN); serum cystatin C (sCysC); urine protein-to-creatinine ratio (UPC); and urinary biomarkers of glomerular and tubular injury were measured. Glomerular filtration rate (GFR) and renal perfusion using CEUS were assayed (except for week 68). For CEUS, intensity- and time-related parameters representing blood volume and velocity were derived from imaging data, respectively. At 12-22% weight-gain, cortical time-to-peak, representing blood velocity, was shorter in the WCG vs. the CG. After 37% weight-gain, sCysC, UPC, glomerular and tubular biomarkers of injury, urinary immunoglobulin G and urinary neutrophil gelatinase-associated lipocalin, respectively, were higher in the WCG. sBP, sCr, BUN and GFR were not significantly different. After 23% weight-loss, all alterations were attenuated. Early weight-gain in dogs induced renal perfusion changes measured with CEUS, without hyperfiltration, preceding increased urinary protein excretion with potential glomerular and tubular injury. The combined use of routine biomarkers of kidney function, CEUS and site-specific urinary biomarkers might be valuable in assessing kidney health of individuals at risk for obesity-related glomerulopathy in a non-invasive manner.

MRI for diagnosis of post-renal transplant complications: current state-of-the-art and future perspectives.

Kidney transplantation has developed into a widespread procedure to treat end stage renal failure, with transplantation results improving over the years. Postoperative complications have decreased over the past decades, but are still an important cause of morbidity and mortality. Early accurate diagnosis and treatment is the key to prevent renal allograft impairment or even graft loss. Ideally, a diagnostic tool should be able to detect post-transplant renal dysfunction, differentiate between the different causes and monitor renal function during and after therapeutic interventions. Non-invasive imaging modalities for diagnostic purposes show promising results. Magnetic resonance imaging (MRI) techniques have a number of advantages, such as the lack of ionizing radiation and the possibility to obtain relevant tissue information without contrast, reducing the risk of contrast-induced nephrotoxicity. However, most techniques still lack the specificity to distinguish different types of parenchymal diseases. Despite some promising outcomes, MRI is still barely used in the post-transplantation diagnostic process. The aim of this review is to survey the current literature on the relevance and clinical applicability of diagnostic MRI modalities for the detection of various types of complications after kidney transplantation.

Renal tubular markers as screening tools for severe vesicoureteral reflux.

Severe (grades IV and V) vesicoureteral reflux (VUR) is a risk factor for acute pyelonephritis, renal scars, and renal failure. This study evaluates albumin and N-acetylglucosaminidase (NAG) urinary excretion, and renal concentrating ability as screening tools to select patients for voiding cystourethrogram (VCUG). Children (111 M, 52 F) aged 10.97 ± 21.17 months (mean + SD), diagnosed with UTI, and who had undergone renal ultrasound and a VCUG, underwent a desmopressin test and had albumin/creatinine and NAG/creatinine urinary excretion measured. Urine osmolality was significantly lower in 27 children with severe VUR (375.3 ± 171.8 mOsm/kg; mean + SD) compared to 100 patients with normal VCUG (611.5 ± 175.8 mOsm/kg), p < 0.001, and to 36 patients with VUR grades I to III (636.2 ± 180.2 mOsm/kg), p < 0.001. NAG/creatinine ratio was significantly elevated in 20 children with severe VUR (26.4 (28.3) U/g); median and interquartile range compared to 67 children with normal VCUG (10.8 (17.9) U/g), p = 0.003, and to 20 patients with VUR grades I to III (7.6 (21.1) U/g), p = 0.009.Conclusions: Urinary osmolality is significantly decreased and urinary excretion of NAG is significantly increased in patients with severe VUR. These tests could select patients for VCUG to assess for severe VUR. What is Known: • Severe vesicoureteral reflux (SVUR) may contribute to renal damage. Severe vesicoureteral reflux is diagnosed by voiding cystourethrogram and represents about 10% of all patients with VUR. Currently, there are no reliable tests used prior to VCUG to help on the decision of obtaining a VCUG to diagnose SVUR. What is New: • This study shows that renal tubular markers (concentrating ability and N-acetylglucosaminidase (NAG) excretion) are useful tests prior to voiding cystourethrogram to screen for severe vesicoureteral reflux. • This study suggests the use of renal concentrating ability and urinary N-acetylglucosaminidase (NAG) excretion to screen for severe vesicoureteral reflux before requesting a voiding cystourethrogram.

Prediction of Tubulointerstitial Injury in Chronic Kidney Disease Using a Non-Invasive Model: Combination of Renal Sonography and Laboratory Biomarkers.

The goal of the study described here was to evaluate the degree of tubulointerstitial injury in patients with chronic kidney disease (CKD) using a more accurate model that combines renal sonographic parameters and laboratory biomarkers. A total of 308 patients were enrolled. The study protocol included conventional ultrasound, contrast-enhanced ultrasonography and renal biopsy. CKD patients were divided into normal and mild (≤25%), moderate (26%-50%) and severe (>50%) tubulointerstitial injury groups. We created a model comprising peak intensity, time to peak, urinary retinol-binding protein and ß2-microglobulin that could discriminate severe (>50%) tubulointerstitial injury. The area under the receiver operating characteristic curve of this model was 0.832, which had better accuracy than other individual indexes, and the sensitivity and specificity were 74.2% and 82.8%, respectively. Therefore, this model may be used to evaluate the severity of tubulointerstitial injury and may have the potential to serve as an effective auxiliary method to help nephrologists evaluate patients with CKD.

Linking imaging to omics utilizing image-guided tissue extraction.

Phenotypic heterogeneity is commonly observed in diseased tissue, specifically in tumors. Multimodal imaging technologies can reveal tissue heterogeneity noninvasively in vivo, enabling imaging-based profiling of receptors, metabolism, morphology, or function on a macroscopic scale. In contrast, in vitro multiomics, immunohistochemistry, or histology techniques accurately characterize these heterogeneities in the cellular and subcellular scales in a more comprehensive but ex vivo manner. The complementary in vivo and ex vivo information would provide an enormous potential to better characterize a disease. However, this requires spatially accurate coregistration of these data by image-driven sampling as well as fast sample-preparation methods. Here, a unique image-guided milling machine and workflow for precise extraction of tissue samples from small laboratory animals or excised organs has been developed and evaluated. The samples can be delineated on tomographic images as volumes of interest and can be extracted with a spatial accuracy better than 0.25 mm. The samples remain cooled throughout the procedure to ensure metabolic stability, a precondition for accurate in vitro analysis.

All That Glitters Yellow Is Not Gold: Presentation and Pathophysiology of Bile Cast Nephropathy.

BACKGROUND: Acute kidney injury (AKI) often manifests in patients with liver disease because of a prerenal cause and presents as acute tubular necrosis or hepatorenal syndrome. Distinguishing between these entities is important for prognosis and treatment. Some patients may develop AKI related to their underlying liver disease: for example, membranoproliferative glomerulonephritis or IgA nephropathy. Bile cast nephropathy is an often ignored differential diagnosis of AKI in the setting of obstructive jaundice. It is characterized by the presence of bile casts in renal tubules, which can possibly cause tubular injury through obstructive and direct toxic effects. Thus, AKI in patients with liver disease may have a structural component in addition to a functional one. METHODS: In this study, we describe 2 patients with severe hyperbilirubinemia who developed AKI and underwent a kidney biopsy that revealed bile casts in tubular lumens, consistent with bile cast nephropathy. RESULTS: One patient was treated aggressively for alcoholic hepatitis and required hemodialysis for AKI. The second patient was treated conservatively for drug-induced liver injury and did not require dialysis. Both patients saw a reduction in their bilirubin and creatinine toward baseline. CONCLUSION: Bile cast nephropathy is an important pathological entity that may account for the renal dysfunction in some patients with liver disease. It requires kidney biopsy for diagnosis and may often be overlooked given the scarcity of kidney biopsy in this particular clinical setting. The etiology is multifactorial, and it is often difficult to predict without the aid of a renal biopsy.

Bilateral obstruction of bilaterally duplicated collecting systems requiring upper and lower moiety drainage.

A 60-year-old woman with a history of breast cancer presented with bilateral obstruction of bilaterally duplicated renal collecting systems secondary to extrinsic compression from metastatic pelvic lymphadenopathy. Bilateral JJ ureteric stents were inserted, resulting in some improvement of renal function but a failure to normalise completely. Repeat computed tomography demonstrated bilateral duplex collecting systems with persisting obstruction of the undrained moieties. Selective puncture was performed to decompress the obstructed renal moieties for bilateral nephrostomy catheter insertion. This allowed renal function to improve sufficiently for the patient to be discharged and commence chemotherapy. This is the first reported case of bilaterally obstructed partially duplicated collecting systems and it illustrates the importance of recognising anatomical variants to tailor treatment appropriately. It also highlights the important relationship between urology and interventional radiology in the management of such complex patients.

Preclinical development of small-molecular-weight folate-based radioconjugates: a pharmacological perspective.

The folate receptor (FR) has attracted attention as a target structure because of its frequent expression in cancer cells (FR-α) and activated macrophages (FR-ß). The vitamin folic acid has served as a promising targeting ligand allowing selective delivery of attached radionuclides suitable for imaging of the diseased sites and for therapeutic application. A large number of folate radioconjugates with variable chemical structures have been developed over the last 25 years. Accumulation of radioactivity in healthy organs and tissues was always seen in the kidneys due to the expression of the FR in the proximal tubule cells. In some cases unspecific uptake of radiofolates was also seen in the liver and the intestinal tract. To address this situation and improve the target-to-off-target ratios of accumulated radioactivity several strategies were undertaken, including chemical modifications of the folate conjugates, selection of appropriate radionuclides and application of drug combinations. Depending on the radionuclide which was employed various chelators and linker entities were investigated and additional functionalities with albumin-binding properties were tested with the aim to increase the serum half-life of the radioconjugates. A number of diagnostic radionuclides ((99m)Tc, (111)In, (67)Ga, (155)Tb, (125)I) emitting γ-radiation were employed for single photon emission computed tomography (SPECT) and, ß(+)-emitting radionuclides ((68)Ga, 44Sc, (152)Tb, (18)F) were used for positron emission tomography (PET). Moreover, therapeutic radionuclides emitting ß(-)-particles ((177)Lu, (161)Tb, (47)Sc, (131)I) and α-particles ((149)Tb) were also used with folate conjugates. The present review focuses on the development of radiofolates and their in vivo properties and on strategies which were employed to modify their pharmacokinetic and pharmacodynamic properties.

A minimally invasive, lentiviral based method for the rapid and sustained genetic manipulation of renal tubules.

The accelerated discovery of disease-related genes emerging from genomic studies has strained the capacity of traditional genetically engineered mouse models (GEMMs) to provide in-vivo validation. Direct, somatic, genetic engineering approaches allow for accelerated and flexible genetic manipulation and represent an attractive alternative to GEMMs. In this study we investigated the feasibility, safety and efficiency of a minimally invasive, lentiviral based approach for the sustained in-vivo modification of renal tubular epithelial cells. Using ultrasound guidance, reporter vectors were directly injected into the mouse renal parenchyma. We observed transgene expression confined to the renal cortex (specifically proximal and distal tubules) and sustained beyond 2 months post injection. Furthermore, we demonstrate the ability of this methodology to induce long-term, in-vivo knockdown of candidate genes either through somatic recombination of floxed alleles or by direct delivery of specific shRNA sequences. This study demonstrates that ultrasound-guided injection of lentiviral vectors provides a safe and efficient method for the genetic manipulation of renal tubules, representing a quick and versatile alternative to GEMMs for the functional characterisation of disease-related genes.

Renal resistive index correlates with peritubular capillary loss and arteriosclerosis in biopsy tissues from patients with chronic kidney disease.

BACKGROUND: The renal resistive index (RI) is a Doppler-derived measure that reportedly correlates with renal histological changes and renal disease severity and outcome. The aim of this study was to investigate the factors related to the RI elevation in chronic kidney disease (CKD). METHODS: Using Doppler ultrasonography, RIs were determined in 30 patients with CKD, after which they were correlated with interstitial fibrosis, arteriosclerosis, arteriolosclerosis and peritubular capillary (PTC) density. PTC-positive areas were determined based on CD34 immunostaining. Interstitial fibrosis was detected with Masson trichrome staining. All histological markers were assessed using quantitative and semi-quantitative analyses and evaluated statistically using Pearson correlation tests, unpaired t tests and stepwise multiple regression analysis. RESULTS: RI correlated positively with age (r = 0.603, p = 0.0004), systolic blood pressure (r = 0.775, p < 0.0001), diastolic blood pressure (r = 0.575, p = 0.001), interstitial fibrosis (r = 0.381, p = 0.038) and arteriosclerosis (r = 0.520, p = 0.003), and negatively with creatinine clearance (r = -0.471, p = 0.009) and CD34+ (PTC) areas (r = -0.437, p = 0.016). Patients with hypertension or diabetes mellitus showed higher RIs (p < 0.05) than those without the ailments. Multivariate analysis showed PTC and arteriosclerosis to be independent variables correlating with RI (r (2) = 0.321, p < 0.05). CONCLUSIONS: To our knowledge, this is the first report of using RI measurements to evaluate peritubular capillary loss. Our findings indicate that increases in RI are associated with both arteriosclerosis and loss of PTCs.

Renalase: Another puzzle piece between hypertension and simple renal cysts?

BACKGROUND AND AIM: Since renalase is mostly expressed in kidney tubules, simple renal cyst (SRC) originates from the kidney tubules, and both conditions are related to hypertension, it may be possible that SRC is associated with increased renalase levels. Therefore, in the current study we aimed to confirm the relation between renalase and epinephrine levels, the association between SRC and renalase levels and the association between renalase, blood pressure levels and endothelial dysfunction. MATERIALS AND METHODS: We made a cross-sectional study including 75 patients with SRC, and 51 controls were included to the study. Flow-mediated dilatation (FMD) was assessed, and serum renalase and epinephrine levels were determined. RESULTS: Patient with SRC had lower renalase, higher epinephrine and lower FMD levels when compared to patients without SRC (p < 0.05). Log renalase was correlated with log epinephrine (r = -0.302, p = 0.001) and log FMD (r = 0.642, p < 0.0001). There was no correlation between renalase and urine albumin/creatinine ratio and glomerular filtration rate. In univariate analysis, age, glomerular filtration rate, renalase and FMD were associated with the presence of SRC. Multivariate regression analysis of factors which are statistically significant in univariate analysis showed that age and renalase was associated with the presence of SRC. CONCLUSION: We have demonstrated that renalase levels were associated with the presence of SRC and endothelial dysfunction. Further research is necessary to highlight underlying mechanisms.

Mucinous tubular and spindle cell carcinoma of the kidney: the contrast-enhanced ultrasonography and CT features of six cases and review of the literature.

PURPOSE: To report the features of contrast-enhanced ultrasonography (CEUS) and computer tomography (CECT) of mucinous tubular and spindle cell carcinoma (MTSCC) of the kidney. METHODS: Six cases of MTSCC of the kidney were studied, and the literature was reviewed. Ultrasonography, CEUS, and CECT examinations were routinely performed before the operation. Histological analysis, including HE staining and immunohistochemistry, was performed with the envision method. RESULTS: The age of the patients ranged from 48 to 75 years (mean 55.5 years). One patient was male, and five were females. All six tumours exhibited an admixture of tubules, spindle cells, and mucinous stroma in variable proportions. CEUS and CECT showed enhancement of the lesions, but the enhancement was less than the adjacent renal parenchyma, leading to the diagnosis of hypovascular renal tumours. All patients were alive and well at the follow-up time of 17-73 months (mean 39.5 months) with CEUS and/or CECT at 3 months, 6 months, and 1 year and then annually thereafter following surgery. No metastases were detected. CONCLUSIONS: The CEUS and CECT findings of MTSCC were generally hypovascular and needed to be distinguished from other hypovascular renal tumours.

Spontaneously resolving lower polar ATN in a transplant kidney with dual vascular supply demonstrated on 99mTc EC renography.

We report the presence of a differential acute tubular necrosis pattern on renography in a renal transplant recipient who had received a donor kidney with dual renal arterial supply. The proximal accessory renal artery was supplying the lower pole which had been demonstrated on CT angiography. This possibility should be kept in mind while reporting renography with tubular agents like 99mTc EC in transplant patients. Follow-up renography effectively demonstrated spontaneous resolution of the differential retention pattern and acute tubular necrosis. This case reiterates the usefulness of retention of tubular tracers like 99mTc EC for detection of tubular necrosis.

Molecular imaging of the kidneys.

Radionuclide imaging of the kidneys with gamma cameras involves the use of labeled molecules seeking functionally critical molecular mechanisms to detect the pathophysiology of the diseased kidneys and achieve an early, sensitive, and accurate diagnosis. The most recent imaging technology, positron emission tomography, permits quantitative imaging of the kidney at a spatial resolution appropriate for the organ. H(2)(15)O, (82)RbCl, and [(64)Cu] ETS are the most important radiopharmaceuticals for measuring renal blood flow. The renin angiotensin system is the most important regulator of renal blood flow; this role is being interrogated by detecting angiotensin receptor subtype angiotensin subtype 1 receptor by the use of in vivo positron emission tomography. Membrane organic anion transporters are important for the function of the tubular epithelium; therefore, Tc99m MAG3 as well as some novel radiopharmaceuticals, such as copper-64 labeled mono oxo-tetraazamacrocyclic ligands, have been used for molecular renal imaging. In addition, other radioligands that interact with the organic cation transporters or peptide transporters have been developed. Focusing on early detection of kidney injury at the molecular level is an evolving field of great significance. Potential imaging targets are the kidney injury molecule 1, which is highly expressed in kidney injury and renal cancer but not in normal kidneys. Although pelvic clearance, in addition to parenchymal transport, is an important measure in obstructive nephropathy, techniques that focus on up-regulated molecules in response to tissue stress resulting from obstruction will be of great implication. Monocyte chemoattractant protein-1 is a well-suited molecule here. The greatest advances in molecular imaging of the kidneys have been recently achieved in detecting renal cancer. In addition to the ubiquitous [(18)F] fluorodeoxyglucose, other radioligands, such as [(11)C] acetate and anti-1-amino-3-[18F]fluorocyclobutane-1-carboxylic acid, have emerged. Radioimmunoimaging with [(124)I] G250 could lead to radioimmunotherapy for renal cancer. Considering the increasing age of general population, the incidence of kidney diseases, such as atherosclerosis, diabetic nephropathy, and cancer, is expected to increase. Successful management of these diseases offers an opportunity and a challenge for development of novel molecular imaging technologies.

Amifostine use in radiation-induced kidney damage. Preclinical evaluation with scintigraphic and histopathologic parameters.

PURPOSE: To assess the degree of protective effects of amifostine on kidney functions via semiquantitative static renal scintigraphy and histopathologic analysis. MATERIAL AND METHODS: 30 female albino rats were divided into three equal groups as control (CL), radiotherapy alone (RT), and radiotherapy + amifostine (RT+AMI). The animals in the CL and RT groups were given phosphate-buffered saline, whereas the animals in the RT+AMI group received amifostine (200 mg/kg) by intraperitoneal injection 30 min before irradiation. RT and RT+AMI groups were irradiated with a single dose of 6 Gy using a (60)Co unit at a source-skin distance of 80 cm to the whole right kidney. They were followed up for 6 months. CL, RT, and RT+AMI groups underwent static kidney scintigraphy at the beginning of the experiment and, again, on the day before sacrificing. Histopathologically, tubular atrophy and fibrosis of the kidney damage were evaluated. RESULTS: After irradiation, the median value of right kidney function was 48% (44-49%) and 50.5% (49%-52%) in RT and RT+AMI groups, respectively (p = 0.0002). Grade 1 kidney fibrosis was observed to be 60% in the RT group, while it was only 30% in the RT+AMI group. Grade 2 kidney fibrosis was 30% and 0% in the RT and RT+AMI group, respectively. Grade 1 tubular atrophy was 70% and 50% in the RT and RT+AMI group, respectively. Grade 2 tubular atrophy effect was the same in both groups (10%). CONCLUSION: Static kidney scintigraphy represents an objective and reproducible method to noninvasively investigate kidney function following irradiation. Amifostine produced a significant reduction in radiation-induced loss of renal function.

Anatomical and clinical study on effects of sonography with pulse inversion and microbubble contrast in rabbit kidney.

Aim of the present study was to evaluate by transmission electron microscope (TEM) modifications in rabbit kidney-parenchyma after submission to ultrasound contrast agent (UCA) with Pulse Inversion Harmonic Imaging (PIHI). Seven inbred male albino rabbits were divided into three groups: 1) control group (n = 1 animal); 2) sonicated group (n = 3 animals); 3) sonicated group with UCA injection (CEUS) (n = 3 animals). The first group was not exposed to ultrasonography (US) and/or UCA. The second and third groups underwent baseline US and later to US with PIHI with a high mechanical index; in the third group UCA was simultaneously administered. Ultrastructural studies and image analysis were blindly performed on 50 samples (2mm3), including cortex and medulla, by two experienced pathologists with TEM. By TEM observations of the first and second groups showed no structural modifications of renal cortex and medulla. TEM observations of the third group showed ultrastructural changes of renal corpuscle, proximal and distal convoluted tubules and collecting tubules; further in the most of observed sections the filtration membrane had an alteration of typical trilaminar pattern and vacuolisation of glomerular endothelial cells with irregular edges. Therefore in rabbit kidney submitted to CEUS some ultrastructural modifications were observed.