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      Investigation and identification of etiologies involved in the development of acquired hydronephrosis in aged laboratory mice with the use of high-frequency ultrasound imaging

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          Abstract

          Laboratory mice develop naturally occurring lesions that affect biomedical research. Hydronephrosis is a recognized pathologic abnormality of the mouse kidney. Acquired hydronephrosis can affect any mouse, as it is caused by any naturally occurring disease that impairs free urine flow. Many etiologies leading to this condition are of particular significance to aging mice. Non-invasive ultrasound imaging detects renal pelvic dilation, renal enlargement, and parenchymal loss for pre-mortem identification of this condition. High-frequency ultrasound transducers produce high-resolution images of small structures, ideal for detecting organ pathology in mice. Using a 40 MHz linear array transducer, we obtained high-resolution images of a diversity of pathologic lesions occurring within the abdomen of seven geriatric mice with acquired hydronephrosis that enabled a determination of the underlying etiology. Etiologies diagnosed from the imaging results include pyelonephritis, neoplasia, urolithiasis, mouse urologic syndrome, and spontaneous hydronephrosis, and were confirmed at necropsy. A retrospective review of abdominal scans from an additional 149 aging mice shows that the most common etiologies associated with acquired hydronephrosis are mouse urologic syndrome and abdominal neoplasia. This report highlights the utility of high-frequency ultrasound for surveying research mice for age-related pathology, and is the first comprehensive report of multiple cases of acquired hydronephrosis in mice.

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          Most cited references50

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          Pyelonephritis: radiologic-pathologic review.

          Urinary tract infections are the most common urologic disease in the United States and annually account for over 7 million office and 1 million emergency department visits. In adults, diagnosis of urinary tract infection is typically based on characteristic clinical features and abnormal laboratory values. Imaging is usually reserved for patients who do not respond to therapy and for those whose clinical presentation is either atypical or potentially life threatening. Urinary tract infection typically originates in the urinary bladder; when it migrates to the kidney or is seeded there hematogenously, a tubulointerstitial inflammatory reaction ensues, involving the renal pelvis and parenchyma. The condition is characterized as pyelonephritis. Complicated and uncomplicated pyelonephritis, xanthogranulomatous pyelonephritis, and tuberculosis are all urinary tract infections for which imaging evaluation adds diagnostic information important for patient care. Computed tomography (CT), when performed before, immediately after, and at delayed intervals from contrast material injection, is the preferred modality for evaluating acute bacterial pyelonephritis. CT is also preferred over conventional radiography and ultrasonography (US) for assessing emphysematous pyelonephritis. Xanthogranulomatous pyelonephritis is a chronic granulomatous process, induced by recurrent bacterial urinary tract infection. Although US is useful in the diagnosis of this condition, CT is the main imaging tool, as it provides highly specific findings and accurate assessment of the extrarenal extent of disease, which is essential for surgical planning. The increasing prevalence of tuberculosis and continued emergence of antibiotic-resistant strains have significance for genitourinary radiologists, as the urinary tract is the most common extrapulmonary site of tuberculosis. Familiarity with the renal manifestations of the disease--pelvoinfundibular strictures, papillary necrosis, cortical low-attenuation masses, scarring, and calcification--will help in the diagnosis, even in the absence of documented pulmonary disease.
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            Guide for the Care and Use of Laboratory Animals

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              Uncompensated polyuria in a mouse model of Bartter's syndrome.

              We have used homologous recombination to disrupt the mouse gene coding for the NaK2Cl cotransporter (NKCC2) expressed in kidney epithelial cells of the thick ascending limb and macula densa. This gene is one of several that when mutated causes Bartter's syndrome in humans, a syndrome characterized by severe polyuria and electrolyte imbalance. Homozygous NKCC2-/- pups were born in expected numbers and appeared normal. However, by day 1 they showed signs of extracellular volume depletion (hematocrit 51%; wild type 37%). They subsequently failed to thrive. By day 7, they were small and markedly dehydrated and exhibited renal insufficiency, high plasma potassium, metabolic acidosis, hydronephrosis of varying severity, and high plasma renin concentrations. None survived to weaning. Treatment of -/- pups with indomethacin from day 1 prevented growth retardation and 10% treated for 3 weeks survived, although as adults they exhibited severe polyuria (10 ml/day), extreme hydronephrosis, low plasma potassium, high blood pH, hypercalciuria, and proteinuria. Wild-type mice treated with furosemide, an inhibitor of NaK2Cl cotransporters, have a phenotype similar to the indomethacin-rescued -/- adults except that hydronephrosis was mild. The polyuria, hypercalciuria, and proteinuria of the -/- adults and furosemide-treated wild-type mice were unresponsive to inhibitors of the renin angiotensin system, vasopressin, and further indomethacin. Thus absence of NKCC2 in the mouse causes polyuria that is not compensated elsewhere in the nephron. The NKCC2 mutant animals should be valuable for uncovering new pathophysiologic and therapeutic aspects of genetic disturbances in water and electrolyte recovery by the kidney.
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                Author and article information

                Journal
                Pathobiol Aging Age Relat Dis
                Pathobiol Aging Age Relat Dis
                PBA
                Pathobiology of Aging & Age Related Diseases
                Co-Action Publishing
                2001-0001
                01 August 2014
                2014
                : 4
                : 10.3402/pba.v4.24932
                Affiliations
                [1 ]Murine Phenotyping Core, National Heart, Lung, and Blood Institute, National Institutes of Health, Bethesda, MD, USA
                [2 ]Office of Research Services, Division of Veterinary Resources, National Institutes of Health, Bethesda, MD, USA
                Author notes
                [* ]Correspondence to: Danielle A. Springer, National Institutes of Health, Building 14E, Room 105F, Service Road West, Bethesda, MD, USA 20893, Email: ds628k@ 123456nih.gov
                Article
                24932
                10.3402/pba.v4.24932
                4119937
                477b4f03-a737-44cb-87e5-d439638d22d7
                © 2014 Danielle A. Springer et al.

                This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 3.0 Unported License, permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 14 May 2014
                : 16 June 2014
                Categories
                Research Paper

                Geriatric medicine
                ultrasound,hydronephrosis,renal pelvic dilation,mice,abdominal imaging,kidney,pathology,mouse urologic syndrome,abdominal neoplasia

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