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      Call for Papers: Green Renal Replacement Therapy: Caring for the Environment

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      Advantages and Controversies in the Era of Intrarenal Volumetry

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          Abstract

          Background/Aims: Ultrasound is the preferred imaging modality in nephrology. In many kidney diseases, however, more accurate methods are needed to distinguish between relevant intrarenal structures. MRI could be a solution, although the use of MRI contrast has caused severe complications in some cases, and invasive kidney biopsies may follow, even though such small specimens traditionally provide inaccurate quantitative data. We evaluated the usefulness of MRI volumetry and quantitative kidney biopsies to assess glomerular number and volume as well as cortical volume. Methods: We specifically highlight an experimental study in which different MRI scans were performed in healthy pigs as well as pigs with unilateral ureteral obstruction to assess intrarenal volume. Single-kidney glomerular filtration rate (GFR) was measured using ureteral cannulation and <sup>51</sup>Cr-EDTA. Kidney biopsies were taken and evaluated employing stereological techniques to measure number and volume of glomeruli. Pigs were sacrificed and kidneys were removed for stereological analysis. Non-contrast-based MRI intrarenal volumes were – without significant difference to intrarenal volumes – obtained using contrast-enhanced MRI and ex vivo techniques. Results: Kidney biopsies gave valid estimates regarding quantitative parameters, such as mean number and volume of glomeruli in the cortex. Different structural parameters correlated with kidney GFR with high, although varying, correlation coefficients. Conclusion: Non-contrast MRI is suitable for estimating intrarenal volumes in healthy and diseased kidneys. We advocate further research in diagnostic modalities combining MRI and biopsies. Major challenges are the cortical architecture and heterogeneous distribution of glomeruli within the kidney.

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          The intrarenal renin-angiotensin system: from physiology to the pathobiology of hypertension and kidney disease.

          In recent years, the focus of interest on the role of the renin-angiotensin system (RAS) in the pathophysiology of hypertension and organ injury has changed to a major emphasis on the role of the local RAS in specific tissues. In the kidney, all of the RAS components are present and intrarenal angiotensin II (Ang II) is formed by independent multiple mechanisms. Proximal tubular angiotensinogen, collecting duct renin, and tubular angiotensin II type 1 (AT1) receptors are positively augmented by intrarenal Ang II. In addition to the classic RAS pathways, prorenin receptors and chymase are also involved in local Ang II formation in the kidney. Moreover, circulating Ang II is actively internalized into proximal tubular cells by AT1 receptor-dependent mechanisms. Consequently, Ang II is compartmentalized in the renal interstitial fluid and the proximal tubular compartments with much higher concentrations than those existing in the circulation. Recent evidence has also revealed that inappropriate activation of the intrarenal RAS is an important contributor to the pathogenesis of hypertension and renal injury. Thus, it is necessary to understand the mechanisms responsible for independent regulation of the intrarenal RAS. In this review, we will briefly summarize our current understanding of independent regulation of the intrarenal RAS and discuss how inappropriate activation of this system contributes to the development and maintenance of hypertension and renal injury. We will also discuss the impact of antihypertensive agents in preventing the progressive increases in the intrarenal RAS during the development of hypertension and renal injury.
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            Volume progression in autosomal dominant polycystic kidney disease: the major factor determining clinical outcomes.

            Autosomal dominant polycystic kidney disease (PKD) is a hereditary condition characterized by the progressive enlargement of innumerable renal cysts that contribute to life-altering morbidity early in the course of the disease. Evidence indicates that the rate of increase in kidney volume can be reliably measured by magnetic resonance or computed tomography imaging, thus providing objective means to judge the effectiveness of therapies that are targeted to the aberrant growth of renal tubules. It is now possible, therefore, to monitor the effectiveness of potential therapies on the signature abnormality in autosomal dominant PKD before irreversible damage has been done by the cysts. Evidence accumulated from human cross-sectional and longitudinal studies and longitudinal studies of PKD models in animals provide strong support for the view that reducing the rate of kidney volume enlargement will ameliorate the late-stage development of renal insufficiency.
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              Normal kidney size and its influencing factors - a 64-slice MDCT study of 1.040 asymptomatic patients

              Background Normal ultrasound values for pole-to-pole kidney length (LPP) are well established for children, but very little is known about normal kidney size and its influencing factors in adults. The objectives of this study were thus to establish normal CT values for kidney dimensions from a group of unselected patients, identify potential influencing factors, and to estimate their significance. Methods In multiphase thin-slice MDCTs of 2.068 kidneys in 1.040 adults, the kidney length pole to pole (LPP), parenchymal (PW) and cortical width (CW), position and rotation status of the kidneys, number of renal arteries, pyelon width and possible influencing factors that can be visualized, were recorded from a volume data set. For length measurements, axes were adjusted individually in double oblique planes using a 3D-software. Analyses of distribution, T-tests, ANOVA, correlation and multivariate regression analyses were performed. Results LPP was 108.5 ± 12.2 mm for the right, and 111.3 ± 12.6 mm for the left kidney (p < 0.0001 each). PW on the right side was 15.4 ± 2.8 mm, slightly less than 15.9 ± 2.7 mm on the left side (p < 0.0001), the CW was the same (6.6 ± 1.9 mm). The most significant independent predictors for LPP, CW, and PW were body size, BMI, age, and gender (p < 0.001 each). In men, the LPP increases up to the fifth decade of life (p < 0.01). It is also influenced by the position of the kidneys, stenoses and number of renal arteries (SRA/NRA), infarctions suffered, parapelvic cysts, and absence of the contralateral kidney; CW is influenced by age, position, parapelvic cysts, NRA and SRA, and the PW is influenced in addition by rotation status (p < 0.05 each). Depending on the most important factors, gender-specific normal values were indicated for these dimensions, the length and width in cross section, width of the renal pelvis, and parenchyma-renal pyelon ratio. Conclusions Due to the complex influences on kidney size, assessment should be made individually. The most important influencing factors are BMI, height, gender, age, position of the kidneys, stenoses and number of renal arteries.
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                Author and article information

                Journal
                AJN
                Am J Nephrol
                10.1159/issn.0250-8095
                American Journal of Nephrology
                S. Karger AG
                978-3-8055-9767-8
                978-3-8055-9768-5
                0250-8095
                1421-9670
                2011
                June 2011
                10 June 2011
                : 33
                : Suppl 1
                : 40-45
                Affiliations
                aMR Research Center and bInstitute of Clinical Medicine, cStereology and Electron Microscopy Laboratory and Center for Stochastic Geometry and Advanced Bioimaging, and dDepartment of Nephrology, Aarhus University Hospital, Skejby, Denmark
                Author notes
                *Jens R. Nyengaard, MD, Dr. Med. Sc., Stereology and Electron Microscopy Laboratory, Building 10G, Aarhus University Hospital NBG, Noerrebrogade 44, DK–8000 Aarhus C (Denmark), Tel. +45 8949 9928, E-Mail nyengaard@ki.au.dk
                Article
                327078 Am J Nephrol 2011;33(suppl 1):40–45
                10.1159/000327078
                21659734
                a1d92133-c3e0-4ae3-9e96-a0b76205e3e9
                © 2011 S. Karger AG, Basel

                Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher. Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug. Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

                History
                Page count
                Figures: 3, Pages: 6
                Categories
                In-Depth Topic Review

                Cardiovascular Medicine,Nephrology
                Glomeruli,MRI volumetry,Microscopy,Animal models,Pathology,Kidney biopsy,Contrast-enhanced MRI

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