Canine Kidneys Research Articles

Prevalence of canine renal crest hyperattenuation in precontrast computed tomography.

Normal canine kidneys are relatively homogeneous soft tissue attenuating structures on nonenhanced CT images. However, visible differences in attenuation between the renal crest and medulla are occasionally observed. This finding and its potential clinical implications have not been previously investigated. This study aimed to estimate the prevalence of renal crest hyperattenuation (RCH) and investigate possible associations with signalment and laboratory parameters. Abdominal CT studies from 100 dogs, with biochemistry and urinalysis data obtained within 48h before the CT acquisition, were categorized by two radiologists into those with and without visible RCH. The attenuation in Hounsfield units (HU) of the renal crest and renal medulla were measured. Signalment, biochemical, and urinalysis data were analyzed for associations with RCH. Correlation coefficients were calculated for measured HU and associated continuous parameters. Prevalence of RCH was 42.42% (42/99 dogs, 95% CI, 33-52%). Urinary specific gravity (USG) was significantly different between dogs with and without RCH (P=.034). Weak positive correlations were identified between left and right renal crest attenuation and USG (r=0.233 and 0.253, respectively; P=.05). Renal crest hyperattenuation is a common finding in dogs undergoing abdominal CT. Although the correlation between the USG and renal crest HU is weak, the dogs with RCH have significantly higher USG. Renal crest hyperattenuation might, therefore, not be associated with renal insufficiency. No other specific associations of RCH were identified with parameters typically altered in a variety of diseases. Further investigation may be warranted for its relevance to specific diseases or if it indeed represents a physiological variant.

Preliminary Evaluation of Cortical and Medullary Echogenicity in Normal Canine Fetal Kidneys during the Last 10 Days of Pregnancy.

The objective of this study was to assess changes in the echogenicity of the cortex and medulla of canine fetal kidneys in relation to days before parturition (dbp), maternal size and litter size. Monitoring of 10 healthy pregnant bitches (2-8 years old, 8.8-40.3 kg bw) was conducted from -10 to 0 dbp using ultrasound. A single renal sonogram was obtained by scanning in a longitudinal section the three most caudal fetuses. The mean gray level (MGL) and SD of a manually drawn region of interest (ROI) in the renal cortex and medulla were measured using the Fiji Image J software (Image J 1.51h, Java 1.6 0_24 64 bit). A linear mixed model taking into account the maternal size as a fixed effect, dbp and litter size as covariates and the bitch as a random and repeated effect was used. The regression coefficients (b) were estimated. Cortical SD (C-SD) and cortico-medullary SD (C/M-SD) were influenced by dbp, with a significant decrease at the approaching day of parturition (b = 0.23 ± 0.06, p < 0.001 and b = 0.5 ± 0.02, p = 0.038, respectively). Maternal size had a significant impact on C/M-MGL with differences observed in large-sized (1.95 ± 0.13) compared to small- (1.41 ± 0.10, p = 0.027) and medium-sized bitches (1.51 ± 0.09, p = 0.016). The C/M-MGL was influenced by litter size, showing a decrease as the number of pups increased (b = -0.08 ± 0.03, p = 0.018). C-SD and C/M-SD were exclusively affected by dbp, and not by maternal and litter size. This suggests their potential as valuable parameters, warranting further investigations in future studies.

Urinalysis in Great Dane Puppies from Birth to 28 Days of Age.

Simple SummaryStill, nowadays, small animal perinatology is quite an unknown field of veterinary medicine. To help decrease the high mortality rates reported for canine newborns, veterinary practitioners should become more aware of neonatal physiology and pathology, focusing their attention on metabolic balance. It is impossible to discriminate healthy puppies from pathological littermates in the absence of reference ranges for specific parameters, which are obviously different from those of adults. Since blood samples are more difficult and dangerous to collect from newborns, practitioners could rely on urinary samples, easily gathered by the stimulation of the somato-vesical spinal reflex. The present research, based on 624 urine samples, offers results that can be used as references for the first-line evaluation of newborn Great Danes by dipstick rapid urinalysis. In healthy puppies, specific gravity and pH vary from birth to 28 days of age, while glucosuria and proteinuria are never reported. The present results, derived from a sample of single-breed puppies, can represent the starting point for a further multi-breed evaluation.Urinalysis, a common test in infants, could represent a suitable non-invasive clinical tool in puppies. In dog neonates, urine is easily collected by stimulating the somato-vesccal reflex. Information on urine characteristics during the neonatal period is missing. Beside instrumental laboratory analyses, the dipstick was proven useful for rapid urinalysis to evaluate specific gravity (SG), pH, leukocytes, nitrites, glucose, proteins, ketones, urobilinogen, bilirubin, and blood. The present study aimed to describe urinalysis features by the dipstick test and refractometer along the neonatal period. Urine samples (n = 624) were collected by manual stimulation from 48 healthy Great Danes, daily from birth to seven days, then twice a week until 28 days, to assess age-related changes (ANOVA, p < 0.05) and the possible effects of gender and litter (T-test, p < 0.05). The SG and pH significantly changed during the neonatal period. Other parameters did not vary significantly in relation to age. No significant differences were observed either among litters or between genders. The present study confirmed that canine kidneys are able to concentrate urine from the second week of age when the urinary SG started to be similar to adults, while pH still increased towards the typical values of adults at 28 days. Significant glucosuria and proteinuria were never detected. Dipstick urinalysis represents a useful first-line complementary tool in newborns clinical examination, providing information about systemic homeostasis.

Methods for glomerular quantification in dogs: a comparative study

ABSTRACT: It was evaluated the different methodologies for glomerular enumeration described in the literature in a quantitative, double-blind study on the number of glomeruli present in kidney biopsy specimens obtained using a Tru-cut-type biopsy needle. Eighteen samples were taken (n=18) from various regions of canine kidneys harvested immediately after euthanasia. Sample collection was carried out using Tru-cut-type, semi-automated, 16 gauge needles. Reading and evaluation of the specimens were performed independently by four researchers by means of eye loupe inspection, light microscopy, light microscopy with a reduced condenser aperture, and dissection microscopy. Samples were also subjected to histopathological evaluation for comparison purposes. There was no inter-researcher variation for any of the tested methods. The glomerular counts obtained using light microscopy with reduced condenser aperture were similar to those reported in the histopathological evaluation (P=0.44);whereas, the other glomerular enumeration methods yielded significantly lower counts when compared to the histopathological analysis (eye loupe inspection: P&lt;0.01; conventional light microscopy: P=0.02; dissection microscopy: P&lt;0.01).Light microscope with lowering of the condenser lens delivers better results than conventional light microscopy and eye loupe inspection. Results obtained using dissection microscopy and eye loupe inspection did not correlate well with those provided by histopathological evaluation; consequently, these two methods should be avoided.

Changes in Renal Peritubular Capillaries in Canine and Feline Chronic Kidney Disease

Renal capillary rarefaction is a crucial event that leads to tubulointerstitial damage during the progression of chronic kidney disease (CKD). In the present study, changes in CD34-positive renal capillaries were investigated in dogs and cats with CKD. A significant decrease in CD34-positive capillaries was observed in canine diseased kidneys, even at the early stage of disease. In cats, CD34-positive capillaries were well preserved in the diseased kidneys, with no link to the severity of CKD. Renal capillary rarefaction might be a trigger event that leads to the progression of CKD in dogs, rather than in cats.

The Flavonoid Quercetin Protects MDCK Cells against Toxicity of CPT by Induction of Autophagy

In chemotherapy, two or more pharmaceuticals targeting different metabolic pathways are often combined in the expectation that they will synergize or function additively against the tumor. Flavonoids, typically polycyclic plant pigments, have many beneficial effects in humans, including being putatively anticancer, inducing apoptosis by undefined means. Camptothecin (CPT), a powerful chemotherapeutic natural product used in Chinese traditional medicine is a topoisomerase inhibitor. In this study, we investigated whether two recommended flavonoids from plants, baicalein and quercetin, affected the capability of CPT to kill cells. We exposed MDCK (Madin Darby Canine Kidneys) cells to each flavonoid in the presence or absence of CPT; the flavonoids themselves were very modestly toxic at 50-100 μg/ml. However, quercetin but not baicalein reduces cell death induced by CPT. The flavonoids induced autophagy, which can protect cells against CPT and other stressors and is likely to be a major factor protecting cells from toxins like CPT. This potential effect indicates that not all putatively pro-apoptotic agents will synergize with others, and they may even restrain the oncolytic toxicity of other chemotherapeutic drugs. Presumptively beneficial natural products used in folk medicine may even antagonize the oncolytic effect of the chemotherapy.

組織培養液 RPMI-1640 を用いたイヌ腎低温灌流保存の研究

組織培養液 RPMI-1640 を用いたイヌ腎低温灌流保存の研究

Aging in the Canine Kidney.

Given the irreversible nature of nephron loss, aging of the kidney is of special interest to diagnostic and toxicologic pathologists. There are many similarities among histologic lesions in aged human and canine kidneys, including increased frequency of glomerulosclerosis, interstitial fibrosis, and tubular atrophy. Unfortunately, there are few studies in which renal tissue from aged healthy dogs was adequately examined with advanced diagnostics-namely, transmission electron microscopy and immunofluorescence-so age-associated changes in canine podocytes and glomerular basement membranes are poorly characterized. An age-associated decrease in the glomerular filtration rate in humans and dogs (specifically small breed dogs) has been documented. Although lesions in aged rats and mice differ somewhat from those of aged dogs and humans, the knowledge gained from rodent models is still vital to elucidating the pathogenesis of age-associated renal disease. Many novel molecules implicated in renal aging have been identified through genetically modified rodent models and transcriptomic and proteomic analysis of human kidneys. These molecules represent intriguing therapeutic targets and diagnostic biomarkers. Likewise, influencing critical pathways of cellular aging, such as telomere shortening, cellular senescence, and autophagy, could improve renal function in the elderly.

Free-breathing, motion-corrected, highly efficient whole heart T2 mapping at 3T with hybrid radial-cartesian trajectory.

To develop and test a time-efficient, free-breathing, whole heart T2 mapping technique at 3.0T. ECG-triggered three-dimensional (3D) images were acquired with different T2 preparations at 3.0T during free breathing. Respiratory motion was corrected with a navigator-guided motion correction framework at near perfect efficiency. Image intensities were fit to a monoexponential function to derive myocardial T2 maps. The proposed 3D, free breathing, motion-corrected (3D-FB-MoCo) approach was studied in ex vivo canine hearts and kidneys, healthy volunteers, and canine subjects with acute myocardial infarction (AMI). Ex vivo T2 values from proposed 3D T2 -prep gradient echo were not different from two-dimensional (2D) spin echo (P = 0.7) and T2 -prep balanced steady-state free precession (bSSFP) (P = 0.7). In healthy volunteers, compared with 3D-FB-MoCo and breath-held 2D T2 -prep bSSFP (2D-BH), non-motion-corrected (3D-FB-Non-MoCo) myocardial T2 was longer, had a larger coefficient of variation (COV), and had a lower image quality (IQ) score (T2 = 40.3 ms, COV = 38%, and IQ = 2.3; all P < 0.05). Conversely, the mean and COV and IQ of 3D-FB-MoCo (T2 = 37.7 ms, COV = 17%, and IQ = 3.5) and 2D-BH (T2 = 38.0 ms, COV = 15%, and IQ = 3.8) were not different (P = 0.99, P = 0.74, and P = 0.14, respectively). In AMI, T2 values and edema volumes from 3D-FB-MoCo and 2D-BH were closely correlated (R(2) = 0.88 and 0.96, respectively). The proposed whole heart T2 mapping approach can be performed within 5 min with similar accuracy to that of the 2D-BH T2 mapping approach.

ULTRASONOGRAPHIC ELASTOGRAPHY OF THE LIVER, SPLEEN, KIDNEYS, AND PROSTATE IN CLINICALLY NOR-MAL BEAGLE DOGS [corrected

Standard ultrasonography is often insensitive for distinguishing normal vs. diseased states for canine abdominal organs. Ultrasonographic elastography is a new technique that is becoming increasingly available and may help to improve sensitivity. This study evaluated the feasibility, repeatability, and reproducibility of strain elastography of the liver, spleen, kidneys, and prostate in healthy dogs and described the elasticity of each organ using strain values and strain ratios. The reproducibility of strain elastography was excellent, and intraobserver repeatability was moderate to excellent. The strain value of each organ was not significantly different among dogs (liver = 143.38 ± 7.41, spleen = 141.04 ± 9.03, left renal cortex = 141.26 ± 7.50, right renal cortex = 145.80 ± 7.79, and prostate = 135.46 ± 5.80), except for the renal medulla (left = 51.19 ± 4.54 and right = 51.93 ± 5.09) (P < 0.05). The strain ratios for the liver, spleen, renal cortex, and prostate were similar with no significant difference (liver = 10.20 ± 1.47, spleen = 8.40 ± 1.53, left renal cortex = 9.62 ± 1.56, right renal cortex = 8.29 ± 1.63, and prostate = 8.20 ± 1.21), except for the renal medulla (left = 3.48 ± 0.68 and right = 2.95 ± 0.63) (P < 0.05). Our results indicated that strain elastography was feasible for estimating tissue stiffness in the canine liver, spleen, kidneys, and prostate. This study provides basic information for strain values and strain ratios for the liver, spleen, kidneys, and prostate in clinically normal dogs.

Concentrations of strontium, barium, cadmium, copper, zinc, manganese, chromium, antimony, selenium, and lead in the liver and kidneys of dogs according to age, gender, and the occurrence of chronic kidney disease

This study was conducted to measure the concentrations of strontium (Sr), barium (Ba), cadmium (Cd), copper (Cu), zinc (Zn), manganese (Mn), chromium (Cr), antimony (Sb), selenium (Se), and lead (Pb) in canine liver, renal cortex, and renal medulla, and the association of these concentrations with age, gender, and occurrence of chronic kidney disease (CKD). Tissues from 50 dogs were analyzed using inductively coupled plasma mass spectrometry. Cu, Zn, and Mn levels were highest in the liver followed by the renal cortex and renal medulla. The highest Sr, Cd, and Se concentrations were measured in the renal cortex while lower levels were found in the renal medulla and liver. Female dogs had higher tissue concentrations of Sr (liver and renal medulla), Cd (liver), Zn (liver and renal cortex), Cr (liver, renal cortex, and renal medulla), and Pb (liver) than male animals. Except for Mn and Sb, age-dependent variations were observed for all element concentrations in the canine tissues. Hepatic Cd and Cr concentrations were higher in dogs with CKD. In conclusion, the present results provide new knowledge about the storage of specific elements in canine liver and kidneys, and can be considered important reference data for diagnostic methods and further investigations.

In vivo irreversible electroporation kidney ablation: experimentally correlated numerical models.

Irreversible electroporation (IRE) ablation uses brief electric pulses to kill a volume of tissue without damaging the structures contraindicated for surgical resection or thermal ablation, including blood vessels and ureters. IRE offers a targeted nephron-sparing approach for treating kidney tumors, but the relevant organ-specific electrical properties and cellular susceptibility to IRE electric pulses remain to be characterized. Here, a pulse protocol of 100 electric pulses, each 100μs long, is delivered at 1pulse/s to canine kidneys at three different voltage-to-distance ratios while measuring intrapulse current, completed 6h before humane euthanasia. Numerical models were correlated with lesions and electrical measurements to determine electrical conductivity behavior and lethal electric field threshold. Three methods for modeling tissue response to the pulses were investigated (static, linear dynamic, and asymmetrical sigmoid dynamic), where the asymmetrical sigmoid dynamic conductivity function most accurately and precisely matched lesion dimensions, with a lethal electric field threshold of 575 ± 67V/cm for the protocols used. The linear dynamic model also attains accurate predictions with a simpler function. These findings can aid renal IRE treatment planning under varying electrode geometries and pulse strengths. Histology showed a wholly necrotic core lesion at the highest electric fields, surrounded by a transitional perimeter of differential tissue viability dependent on renal structure.

Echobiometrics kidney and renal artery triplex doppler of canine fetuses

The aim of this study was to assess the sogographic parameters and biometry of canine fetal kidneys using the B mode, and to determinate the vascular index of the fetal renal arteries using the Doppler Triplex. Twenty four Shi-tzu and Pug, weighting between 4 and 10kg, aging between 4 and 6 years old were evaluated. The B mode, the fetal renal echobiometry and regularity of the renal surface, echotexture and cortex:medular ratio were evaluated during the 5th, 6th, 7th and 8th weeks of pregnancy. At the same time point of the B mode evaluation, the Doppler Triplex was carried out to assess the sistolic peak velocity (SPV), end diastolic velocity (EDV), vascular resistive (RI) and pulsatility index (PI). B mode revealed no fetal renal abnormalities and echobiometry showed important measurements during fetal development (P&lt;0.0001). The values of the fetal renal arteries index (PSV and EDV) increased during the course of the pregancy (P&lt;0.05) and remained constant for PI and RI (P&gt;0.05). B mode and Doppler Triplex were important tools for the assessment of fetal renal development, using echobiometry and renal arterial index in canie fetuses.

Three-Dimensional Subharmonic Ultrasound Imaging In Vitro and In Vivo

Although contrast-enhanced ultrasound imaging techniques such as harmonic imaging (HI) have evolved to reduce tissue signals using the nonlinear properties of the contrast agent, levels of background suppression have been mixed. Subharmonic imaging (SHI) offers near complete tissue suppression by centering the receive bandwidth at half the transmitting frequency. The aims of this study were to demonstrate the feasibility of three-dimensional (3D) SHI and to compare it to 3D HI. Three-dimensional HI and SHI were implemented on a Logiq 9 ultrasound scanner with a 4D10L probe. Four-cycle SHI was implemented to transmit at 5.8 MHz and receive at 2.9 MHz, while two-cycle HI was implemented to transmit at 5 MHz and receive at 10 MHz. The ultrasound contrast agent Definity was imaged within a flow phantom and the lower pole of two canine kidneys in both HI and SHI modes. Contrast-to-tissue ratios and rendered images were compared offline. SHI resulted in significant improvement in contrast-to-tissue ratios relative to HI both in vitro (12.11 ± 0.52 vs 2.67 ± 0.77, P< .001) and in vivo (5.74 ± 1.92 vs 2.40 ± 0.48, P = .04). Rendered 3D subharmonic images provided better tissue suppression and a greater overall view of vessels in a flow phantom and canine renal vasculature. The successful implementation of SHI in 3D allows imaging of vascular networks over a heterogeneous sample volume and should improve future diagnostic accuracy. Additionally, 3D SHI provides improved contrast-to-tissue ratios relative to 3D HI.

Nephron segment identification in the normal canine kidney by using lectin histochemistry

Lectin-binding patterns in normal canine kidneys were histochemically investigated using eight lectins. WGA, ConA, and RCA-I showed positive signals in glomerular capillary walls, with signals for RCA-I being detected heterogeneously. In tubular segments, signals for WGA, s-WGA, ConA, and RCA-I were distributed widely from proximal tubules to collecting ducts, whereas those for SBA, PNA, DBA, and UEA-I were localized in thin limbs of the loop of Henle, thick ascending limbs, distal tubules, or collecting ducts. Apart from PNA and UEA-I, lectins showed heterogeneous bindings in collecting ducts with the heterogeneity. UEA-I-positive reactions were restricted to those parts of the distal tubules in close proximity to the glomeruli, and in these parts, signals in the macula densa were markedly stronger than in other regions. Based on the present findings, lectin probes, singly or in combination, could be utilized to identify the affected nephron segment in canine renal pathology.

Comparison of Radiofrequency Ablation with Saturated Saline Preinjection and Renal Artery Occlusion: In Vivo Study in Canine Kidneys

Radiofrequency ablation (RFA) is a minimally invasive treatment used for renal cell carcinomas that preserves renal function (1, 2). Previous clinical studies on renal RFA reported good results for treatment of small renal tumors (1-6). However, large renal tumors (> 3 cm) were not completely eradicated by RFA using a single electrode in one treatment session (2-6). For complete tumor ablation, RFA should induce an ablation zone large enough to cover the entire tumor with the ideal ablative margin (0.5-1 cm) (7). Monopolar RFA using a single electrode in one treatment session has limitations in regards to its ability to induce an adequately sized ablation zone for large tumor. Sequentially overlapping single electrode ablation can be used for large tumors (8); however, repositioning the electrode into an untreated tumor area is difficult and requires additional Original Article

Percutaneous radiofrequency ablation of virtual tumours in canine kidney using Global Positioning System‐like technology

What's known on the subject? And what does the study add? We have previously shown that percutaneous radiofrequency ablation guided by image-fusion technology allows for precise needle placement with real time ultrasound superimposed with pre-loaded imaging, removing the need for real-time CT or MR guidance. Emerging technology also allows real-time tracking of a treatment needle within an organ in a virtually created 3D format. To our knowledge, this is the first study utilising a sophisticated ultrasound-based navigation system that uses both image-fusion and real-time probe-tracking technologies for in-vivo renal ablative intervention. • To evaluate the feasibility, accuracy and efficacy of ultrasonography (US)-guided percutaneous radiofrequency ablation (RFA) in the canine kidney model using novel Global Positioning System-like probe tracking technology. • Virtual tumours in the canine kidney were ablated in vivo by percutaneous RFA guided exclusively by two-dimensional (2D) US and a virtual navigation system. • Gold fiducial markers were inserted into renal parenchyma to serve as centres of virtual tumours. • After capturing 2D US images, navigation software created a three-dimensional planning model of the kidney, and superimposed it onto the live US image. • Percutaneous RFA was guided by multiplanar navigation, showing real-time probe positions within the superimposed images, to treat each virtual tumour with a single treatment. • Navigator software predicted the percentage of tumour treated; treated kidney specimens were examined to evaluate projection and targeting accuracy. • In total, 32 virtual tumours (median diameter 16 mm, range 10-24 mm) were treated in 16 canine kidneys. • Median (range) error between 'fiducial tumour centre' and 'treated area centre' was 1.8 (0-25) mm. • Targeting accuracy improved with experience: median (range) error decreased from 6.3 (2-25) mm in an initial 12 tumours to 1.3 (0-9.0) mm in the last 20 tumours (P= 0.008). • The percentage (range) of tumour actually treated improved significantly from the initial series at 23% (0-100%) to 100% (51-100%) (P < 0.001). • Overall, navigator-reported and pathologically confirmed treatment percentages were correlated significantly (r= 0.5; P= 0.006). • Percutaneous renal RFA guided exclusively by real-time 2D US with multiplanar Global Positioning System-like probe tracking is feasible and accurate. • Near-future technologies, including elastic fusion overlay and anticipation of soft-tissue deformation, will further augment this guidance system.

Histologic features of harvested canine kidneys preserved in four different crystalloid solutions.

Endless efforts are required in the investigation of the best organ preservative. Normal Saline, 5% dextrose, Darrows and Ringers’ Lactate were used as preservatives with the view to investigate the prospect of kidney survival in these solutions post harvest at the Veterinary Teaching Hospital, Ahmadu Bello University-Zaria. Sixteen normal kidneys were harvested, preserved and evaluated from sixteen adult Nigerian indigenous breed of dogs. The dogs were acclimatized and conditioned for 2 weeks while presurgical evaluations were done. Kidney harvesting was performed under ge neral anaesthesia, asepsis was observed strictly in all cases. The left kidneys were harvested for each dog through an 8 cm cranioventral midline approach under general anaesthesia. Post nephrectomy, the kidneys were flushed/perfused through the renal artery and preserved for 96 hours at 40C in labeled bowls (A, B C and D) containing these solutions: ARingers Lactate, B-Darrows, C-5% Dextroses and D-Normal Saline solutions which was incorporated 15000 iu of heparin, 5mls of 2% xylocaine, 400000 iu penicillin and 75mg streptomycin. Following preservation for 96 hours, histopathology study was undertaken. Mean pre-surgical haematological, serum chemistry and urinalysis values were within normal range. The gross appearances of the harvested kidneys post preservation were normal. The renal parenchyma for all the kidneys preserved for 72 hours were normal. At 96 hours, kidneys preserved in solutions C and D showed no histological changes. The findings revealed that Normal Saline would preserve better followed by 5% Dextrose and then Darrows and Ringers Lactate being the mild preservative. Keywords: Canine kidney, crystalloid, histologic, preserved, transplantation

Pretransplant Kidney-Specific Treatment to Eliminate the Need for Systemic Immunosuppression

Despite significant side effects, chronic systemic immunosuppression remains the backbone of clinical transplantation. We investigated the feasibility of preventing early allorecognition in canine renal allografts using a nonsystemic pretreatment. The renal vasculature was treated with a bioengineered interface consisting of a nano-barrier membrane during 3 hr of ex vivo warm perfusion. Preliminary feasibility of the immunocloaking technology was established by the following criteria: it is possible to achieve approximately 90% coverage of the vasculature with nano-barrier membrane after 3 hr of ex vivo warm perfusion; covering the luminal surfaces prevents allorecognition as determined by mixed lymphocyte-vascular endothelial reaction; covering the luminal surfaces does not negatively affect renal function as determined by autotransplant outcomes; and graft rejection is significantly postponed in canine kidneys treated with the immunocloaking technology. In the absence of systemic immunosuppression, untreated control dogs experienced a mean onset of rejection on day 6, whereas in the treated dogs with modified renal vascular luminal surfaces, the mean onset of rejection was significantly delayed until day 30. The ability to postpone, or eventually eliminate, the allorecognition that occurs immediately on reperfusion could provide a new window of opportunity to introduce adjunct therapies to support tolerance induction. To our knowledge, this is the first time significantly prolonged canine renal allograft survival has been achieved in the absence of systemic immunosuppression or immunologic manipulation of the recipient.

Initial Investigation of Acoustic Droplet Vaporization for Occlusion in Canine Kidney

Acoustic droplet vaporization (ADV) shows promise for spatially and temporally targeted tissue occlusion. In this study, substantial tissue occlusion was achieved in operatively exposed and transcutaneous canine kidneys by generating ADV gas bubbles in the renal arteries or segmental arteries. Fifteen canines were anesthetized, among which 10 underwent laparotomy to externalize the left kidney and five were undisturbed for transcutaneous ADV. The microbubbles were generated by phase conversion of perfluoropentane droplets encapsulated in albumin or lipid shells in the blood. A 3.5-MHz single-element therapy transducer was aligned with an imaging array in a water tank with direct access to the renal artery or a segmental artery. In vivo color flow and spectral Doppler imaging were used to identify the target arteries. Tone bursts of 1 kHz pulse repetition frequency with 0.25% duty cycle vaporized the droplets during bolus passage. Both intracardiac (IC) and intravenous (IV) injections repeatedly produced ADV in chosen arteries in externalized kidneys, as seen by B-mode imaging. Concurrent with this in two cases was the detection by pulse-wave Doppler of blood flow reversal, along with a narrowing of the waveform. Localized cortex occlusion was achieved with 87% regional flow reduction in one case using IC injections. Vaporization from IV injections resulted in a substantial echogenicity increase with an average half-life of 8 min per droplet dose. Gas bubbles sufficient to produce some shadowing were generated by transcutaneous vaporization of intrarenal artery or IV-administered droplets, with a tissue path up to 5.5 cm. (E-mail: maggiez@umich.edu)