Renal pathology of polycystic kidney disease and concurrent hereditary nephritis in Bull Terriers

Objective To describe the renal lesions in Bull Terrier polycystic kidney disease (BTPKD), to confirm that the renal cysts in BTPKD arise from the nephron or collecting tubule, an to identify lesions consistent with concurrent BTPKD and Bull Terrier hereditary nephritis (BTHN). Design Renal tissue from five Bull Terriers with BTPKD and eight control dogs was examined by light and transmission electron microscopy. Clinical data were collected from all dogs, and family history of BTPKD and BTHN for all Bull Terriers. Results In BTPKD the renal cysts were lined by epithelial cells of nephron or collecting duct origin that were usually squamous or cuboidal, with few organelles. They had normal junctional complexes, and basal laminae of varying thicknesses. Glomeruli with small, atrophic tufts and dilated Bowman's capsules, tubular loss and dilation, and interstitial inflammation and fibrosis were common. Whereas the lesions seen in BTHN by light microscope were nonspecific, the presence of characteristic ultrastructural glomerular basement membrane (GMB) lesions and a family history of this disease indicated concurrent BTHN was likely in three of five cases of BTPKD. Conclusion This paper provides evidence that renal cysts in BTPKD are of nephron or collecting duct origin. In addition, GBM lesions are described that strongly suggest that BTPKD and BTHN may occur simultaneously.

Associations between human liver and kidney cadmium content and immunochemically detected CYP4A11 apoprotein

This present study was undertaken to assess potential effects of cadmium on CYP4A11 apoprotein in human liver and kidney as detected by Western blotting using a highly specific anti-peptide antibody. Liver and kidney cortex samples were autopsy specimens of 37 individuals (26 mates and I I females) whose ages ranged from 3 to 89 years. All were Caucasians who had not been exposed to cadmium in the workplace. Reduced CYP4A11 apoprotein levels were found in chronic hepatitis samples and in liver samples showing fatty changes. In contrast, increased CYP4A11 apoprotein levels were found in liver samples having higher cadmium content compared to the lower cadmium content samples. Increased CYP4A11 levels were also found in liver samples from female donors, compared to male donors; the difference being attributable to higher female liver cadmium burden. In distinction to liver, lowered CYP4A11 levels were seen in the kidney cortex samples which have high cadmium content, It is proposed here that the difference between the absolute cadmium burden of the liver and kidney samples may be responsible for the different patterns of expression of CYP4A11 in these two tissues. Further, since cadmium exposure may be associated with derangement in blood pressure control, it is interesting to note the possible relationship between altered CYP4A11-dependent production of arachidonic acid hydroxy and epoxy metabolites in kidney cortex and altered control of blood pressure. Our findings provide a possible link between these observations. (C) 2002 Elsevier Science Inc. All rights reserved.

Population pharmacokinetics of tacrolimus in adult kidney transplant recipients

Objectives: The aims of this study were to investigate the population pharmacokinetics of tacrolimus in adult kidney transplant recipients and to identify factors that explain variability. Methods: Population analysis was performed on retrospective data from 70 patients who received oral tacrolimus twice daily. Morning blood trough concentrations were measured by liquid chromatography-tandem mass spectrometry. Maximum likelihood estimates were sought for apparent clearance (CL/F) and apparent volume of distribution (V/F), with the use of NONMEM (GloboMax LLC, Hanover, Md). Factors screened for influence on these parameters were weight, age, gender, postoperative day, days of tacrolimus therapy, liver function tests, creatinine clearance, hematocrit fraction, corticosteroid dose, and potential interacting drugs. Results. CL/F was greater in patients with abnormally low hematocrit fraction (data from 21 patients only), and it decreased with increasing days of therapy and AST concentrations (P

Exogenous Slit2 does not affect ureteric branching or nephron formation during kidney development

In an attempt to elucidate the role of Slit2 invertebrate kidney development, the effect of adding exogenous human Slit2 protein (hSlit2) to developing murine metanephric kidney explants was examined. To confirm the activity of the recombinant Slit2 protein, neurons from 8 day old chick sympathetic nerve chain dorsal root ganglia were cultured with hSlit2 protein, which induced significant neurite branching and outgrowth. Using kidney explants as a model system, metanephric development in the presence of hSlit2 protein was examined. Addition of hSlit2 up to a final concentration of 1 mug/ml had no detectable effect on the formation of nephrons or on branching morphogenesis of the ureteric tree after 2 or 4 days in culture, as assessed via immunofluorescence for the markers WT1 and calbindin 28K respectively. Similarly, maturation of the nephrogenic mesenchyme occurred in a phenotypically normal fashion. In situ analysis of the Slit receptors, Robot and Robot, the vasculogenic markers VEGFA and Flk-1, and the stromal cell marker BF2 displayed no difference in comparison to controls.

Repetitive brief ischemia: Intermittent reperfusion during ischemia ameliorates the extent of injury in the perfused kidney

Acute renal failure commonly follows reduced renal perfusion or ischemia. Reperfusion is essential for recovery but can itself cause functional and structural injury to the kidney. The separate contributions of ischemia and of reperfusion were examined in the isolated perfused rat kidney. Three groups were studied: brief (5 min) ischemia, 20 min ischemia, and repetitive brief ischemia (4 periods of 5 min) with repetitive intervening reperfusion of 5 min. A control group had no intervention, the three ischemia groups were given a baseline perfusion of 30 min before intervention and all groups were perfused for a total of 80 min. In addition, the effects of exogenous (NO)-N-. from sodium nitroprusside and xanthine oxidase inhibition by allopurinol were assessed in the repetitive brief ischemia-reperfusion model. Brief ischemia produced minimal morphological injury with near normal functional recovery. Repetitive brief ischemia reperfusion caused less functional and morphological injury than an equivalent single period of ischemia (20 min) suggesting that intermittent reperfusion is less injurious than ischemia alone over the time course of study. Pretreatment with allopurinol improved renal function after repetitive brief ischemia-reperfusion compared with the allopurinol-untreated repetitive brief ischemia-reperfusion group. Similarly, sodium nitroprusside reduced renal vascular resistance but did not improve the glomerular filtration rate or sodium reabsorption in the repetitive brief ischemia-reperfusion model. Thus, these studies show that the duration of uninterrupted ischemia is more critical than reperfusion in determining the extent of renal ischemia-reperfusion injury and that allopurinol, in particular, counteracts the oxidative stress of reperfusion.

The receptor tyrosine kinase regulator sprouty1 is a target of the tumor suppressor WT1 and important for kidney development

WT1 encodes a transcription factor involved in kidney development and tumorigenesis. Using representational difference analysis, we identified a new set of WT1 targets, including a homologue of the Drosophila receptor tyrosine kinase regulator, sprouty. Sprouty1 was up-regulated in cell lines expressing wild-type but not mutant WT1. WT1 bound to the endogenous sprouty1 promoter in vivo and directly regulated sprouty1 through an early growth response gene-1 binding site. Expression of Sprouty1 and WT1 overlapped in the developing metanephric mesenchyme, and Sprouty1, like WT1, plays a key role in the early steps of glomerulus formation. Disruption of Sprouty1 expression in embryonic kidney explants by antisense oligonucleotides reduced condensation of the metanephric mesenchyme, leading to a decreased number of glomeruli. In addition, sprouty1 was expressed in the ureteric tree and antisense-treated ureteric trees had cystic lumens. Therefore, sprouty1 represents a physiologically relevant target gene of WT1 during kidney development.

ClC-5 chloride channel and kidney stones : what is the link?

Nephrolithiasis is one of the most common diseases in the Western world. The disease manifests itself with intensive pain, sporadic infections, and, sometimes, renal failure. The symptoms are due to the appearance of urinary stones (calculi) which are formed mainly by calcium salts. These calcium salts precipitate in the renal papillae and/or within the collecting ducts. Inherited forms of nephrolithiasis related to chromosome X (X-linked hypercalciuric nephrolithiasis or XLN) have been recently described. Hypercalciuria, nephrocalcinosis, and male predominance are the major characteristics of these diseases. The gene responsible for the XLN forms of kidney stones was cloned and characterized as a chloride channel called ClC-5. The ClC-5 chloride channel belongs to a superfamily of voltage-gated chloride channels, whose physiological roles are not completely understood. The objective of the present review is to identify recent advances in the molecular pathology of nephrolithiasis, with emphasis on XLN. We also try to establish a link between a chloride channel like ClC-5, hypercalciuria, failure in urine acidification and protein endocytosis, which could explain the symptoms exhibited by XLN patients.

Kidney targeting and puncturing during percutaneous nephrolithotomy: recent advances and future perspectives

Background and Purpose: Precise needle puncture of the kidney is a challenging and essential step for successful percutaneous nephrolithotomy (PCNL). Many devices and surgical techniques have been developed to easily achieve suitable renal access. This article presents a critical review to address the methodologies and techniques for conducting kidney targeting and the puncture step during PCNL. Based on this study, research paths are also provided for PCNL procedure improvement. Methods: Most relevant works concerning PCNL puncture were identified by a search of Medline/PubMed, ISI Web of Science, and Scopus databases from 2007 to December 2012. Two authors independently reviewed the studies. Results: A total of 911 abstracts and 346 full-text articles were assessed and discussed; 52 were included in this review as a summary of the main contributions to kidney targeting and puncturing. Conclusions: Multiple paths and technologic advances have been proposed in the field of urology and minimally invasive surgery to improve PCNL puncture. The most relevant contributions, however, have been provided by the applicationofmedical imaging guidance, newsurgical tools,motion tracking systems, robotics, andimage processing and computer graphics. Despite the multiple research paths for PCNL puncture guidance, no widely acceptable solution has yet been reached, and it remains an active and challenging research field. Future developments should focus on real-time methods, robust and accurate algorithms, and radiation free imaging techniques

Kidney targeting and puncturing during percutaneous nephrolithotomy:recent advances and future perspectives

Precise needle puncture of the kidney is a challenging and essential step for successful percutaneous nephrolithotomy (PCNL). Many devices and surgical techniques have been developed to easily achieve suitable renal access. This article presents a critical review to address the methodologies and techniques for conducting kidney targeting and the puncture step during PCNL. Based on this study, research paths are also provided for PCNL procedure improvement. Methods: Most relevant works concerning PCNL puncture were identified by a search of Medline/PubMed, ISI Web of Science, and Scopus databases from 2007 to December 2012. Two authors independently reviewed the studies.

Preliminary clinical trial in percutaneous nephrolithotomy using a real-time navigation system for percutaneous kidney access

Background: Precise needle puncture of renal calyces is a challenging and essential step for successful percutaneous nephrolithotomy. This work tests and evaluates, through a clinical trial, a real-time navigation system to plan and guide percutaneous kidney puncture. Methods: A novel system, entitled i3DPuncture, was developed to aid surgeons in establishing the desired puncture site and the best virtual puncture trajectory, by gathering and processing data from a tracked needle with optical passive markers. In order to navigate and superimpose the needle to a preoperative volume, the patient, 3D image data and tracker system were previously registered intraoperatively using seven points that were strategically chosen based on rigid bone structures and nearby kidney area. In addition, relevant anatomical structures for surgical navigation were automatically segmented using a multi-organ segmentation algorithm that clusters volumes based on statistical properties and minimum description length criterion. For each cluster, a rendering transfer function enhanced the visualization of different organs and surrounding tissues. Results: One puncture attempt was sufficient to achieve a successful kidney puncture. The puncture took 265 seconds, and 32 seconds were necessary to plan the puncture trajectory. The virtual puncture path was followed correctively until the needle tip reached the desired kidney calyceal. Conclusions: This new solution provided spatial information regarding the needle inside the body and the possibility to visualize surrounding organs. It may offer a promising and innovative solution for percutaneous punctures.

10 kVp rule – An anthropomorphic pelvis phantom imaging study using a CR system: impact on image quality and effective dose using AEC and manual mode

Purpose - This study aims to investigate the influence of tube potential (kVp) variation in relation to perceptual image quality and effective dose (E) for pelvis using automatic exposure control (AEC) and non-AEC in a Computed Radiography (CR) system. Methods and materials - To determine the effects of using AEC and non-AEC by applying the 10 kVp rule in two experiments using an anthropomorphic pelvis phantom. Images were acquired using 10 kVp increments (60–120 kVp) for both experiments. The first experiment, based on seven AEC combinations, produced 49 images. The mean mAs from each kVp increment were used as a baseline for the second experiment producing 35 images. A total of 84 images were produced and a panel of 5 experienced observers participated for the image scoring using the two alternative forced choice (2AFC) visual grading software. PCXMC software was used to estimate E. Results - A decrease in perceptual image quality as the kVp increases was observed both in non-AEC and AEC experiments, however no significant statistical differences (p > 0.05) were found. Image quality scores from all observers at 10 kVp increments for all mAs values using non-AEC mode demonstrates a better score up to 90 kVp. E results show a statistically significant decrease (p = 0.000) on the 75th quartile from 0.37 mSv at 60 kVp to 0.13 mSv at 120 kVp when applying the 10 kVp rule in non-AEC mode. Conclusion - Using the 10 kVp rule, no significant reduction in perceptual image quality is observed when increasing kVp whilst a marked and significant E reduction is observed.

Increasing source to image distance for AP pelvis imaging: impact on radiation dose and image quality

Aim - A quantative primary study to determine whether increasing source to image distance (SID), with and without the use of automatic exposure control (AEC) for antero-posterior (AP) pelvis imaging, reduces dose whilst still producing an image of diagnostic quality. Methods - Using a computed radiography (CR) system, an anthropomorphic pelvic phantom was positioned for an AP examination using the table bucky. SID was initially set at 110 cm, with tube potential set at a constant 75 kVp, with two outer chambers selected and a fine focal spot of 0.6 mm. SID was then varied from 90 cm to 140 cm with two exposures made at each 5 cm interval, one using the AEC and another with a constant 16 mAs derived from the initial exposure. Effective dose (E) and entrance surface dose (ESD) were calculated for each acquisition. Seven experienced observers blindly graded image quality using a 5-point Likert scale and 2 Alternative Forced Choice software. Signal-to-Noise Ratio (SNR) was calculated for comparison. For each acquisition, femoral head diameter was also measured for magnification indication. Results - Results demonstrated that when increasing SID from 110 cm to 140 cm, both E and ESD reduced by 3.7% and 17.3% respectively when using AEC and 50.13% and 41.79% respectively, when the constant mAs was used. No significant statistical (T-test) difference (p = 0.967) between image quality was detected when increasing SID, with an intra-observer correlation of 0.77 (95% confidence level). SNR reduced slightly for both AEC (38%) and no AEC (36%) with increasing SID. Conclusion - For CR, increasing SID significantly reduces both E and ESD for AP pelvis imaging without adversely affecting image quality.

10 kVp rule – An anthropomorphic pelvis phantom imaging study using a CR system: impact on image quality and effective dose using AEC and manual mode

Background - Pelvis and hip radiography are consistently found to be amongst the highest contributors to the collective effective dose (E) in all ten DOSE DATAMED countries in Europe, representing 2.8 to 9.4% of total collective dose (S) in the TOP 20 exams list. The level of image quality should provide all the diagnostic information in order not to jeopardise the diagnosis, but being able to provide the needed clinical information with the minimum dose. A recent study suggests further research to determine whether the “10 kVp rule” would have value for a range of examinations using Computed Radiography (CR) systems. As a “rule of thumb” increasing the kVp by 10 whilst halving the mAs is suggested to give a similar perceptual image quality when compared to the original exposure factors. Aims - In light of the 10kVp rule, this study aims to investigate the influence of tube potential (kVp) variation in relation to perceptual image quality and E for pelvis imaging using automatic exposure control (AEC) and non-AEC in a Computed Radiography (CR) system. Research questions - Does the 10kVp rule works for the pelvis in relation to image quality in a CR system? Does the image quality differs when the AEC is used instead of manual mode using the 10kVp rule and how this impacts on E?

New insights on integer-programming models for the kidney exchange problem

In recent years several countries have set up policies that allow exchange of kidneys between two or more incompatible patient–donor pairs. These policies lead to what is commonly known as kidney exchange programs. The underlying optimization problems can be formulated as integer programming models. Previously proposed models for kidney exchange programs have exponential numbers of constraints or variables, which makes them fairly difficult to solve when the problem size is large. In this work we propose two compact formulations for the problem, explain how these formulations can be adapted to address some problem variants, and provide results on the dominance of some models over others. Finally we present a systematic comparison between our models and two previously proposed ones via thorough computational analysis. Results show that compact formulations have advantages over non-compact ones when the problem size is large.

Gender in the allocation of organs in kidney transplants: meta-analysis

OBJECTIVE To analyze whether gender influence survival results of kidney transplant grafts and patients.METHODS Systematic review with meta-analysis of cohort studies available on Medline (PubMed), LILACS, CENTRAL, and Embase databases, including manual searching and in the grey literature. The selection of studies and the collection of data were conducted twice by independent reviewers, and disagreements were settled by a third reviewer. Graft and patient survival rates were evaluated as effectiveness measurements. Meta-analysis was conducted with the Review Manager® 5.2 software, through the application of a random effects model. Recipient, donor, and donor-recipient gender comparisons were evaluated.RESULTS : Twenty-nine studies involving 765,753 patients were included. Regarding graft survival, those from male donors were observed to have longer survival rates as compared to the ones from female donors, only regarding a 10-year follow-up period. Comparison between recipient genders was not found to have significant differences on any evaluated follow-up periods. In the evaluation between donor-recipient genders, male donor-male recipient transplants were favored in a statistically significant way. No statistically significant differences were observed in regards to patient survival for gender comparisons in all follow-up periods evaluated.CONCLUSIONS The quantitative analysis of the studies suggests that donor or recipient genders, when evaluated isolatedly, do not influence patient or graft survival rates. However, the combination between donor-recipient genders may be a determining factor for graft survival.