Quantitative and qualitative urinary cellular patterns correlate with progression of murine glomerulonephritis

The kidney is a nonregenerative organ composed of numerous functional nephrons and collecting ducts (CDs). Glomerular and tubulointerstitial damages decrease the number of functional nephrons and cause anatomical and physiological alterations resulting in renal dysfunction. It has recently been repo...

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Veröffentlicht in:PloS one 2011-01, Vol.6 (1), p.e16472-e16472
Hauptverfasser: Kimura, Junpei, Ichii, Osamu, Otsuka, Saori, Kanazawa, Tomonori, Namiki, Yuka, Hashimoto, Yoshiharu, Kon, Yasuhiro
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Ichii, Osamu
Otsuka, Saori
Kanazawa, Tomonori
Namiki, Yuka
Hashimoto, Yoshiharu
Kon, Yasuhiro
description The kidney is a nonregenerative organ composed of numerous functional nephrons and collecting ducts (CDs). Glomerular and tubulointerstitial damages decrease the number of functional nephrons and cause anatomical and physiological alterations resulting in renal dysfunction. It has recently been reported that nephron constituent cells are dropped into the urine in several pathological conditions associated with renal functional deterioration. We investigated the quantitative and qualitative urinary cellular patterns in a murine glomerulonephritis model and elucidated the correlation between cellular patterns and renal pathology.Urinary cytology and renal histopathology were analyzed in BXSB/MpJ (BXSB; glomerulonephritis model) and C57BL/6 (B6; control) mice. Urinary cytology revealed that the number of urinary cells in BXSB mice changed according to the histometric score of glomerulonephritis and urinary albumin; however, no correlation was detected for the levels of blood urea nitrogen and creatinine. The expression of specific markers for podocytes, distal tubules (DTs), and CDs was detected in BXSB urine. Cells immunopositive for Wilms tumor 1 (podocyte marker) and interleukin-1 family, member 6 (damaged DT and CD marker) in the kidney significantly decreased and increased in BXSB versus B6, respectively. In the PCR array analysis of inflammatory cytokines and chemokines, Il10, Cxcl2, C3, and Il1rn showed relatively higher expression in BXSB kidneys than in B6 kidneys. In particular, the highest expression of C3 mRNA was detected in the urine from BXSB mice. Furthermore, C3 protein and mRNA were localized in the epithelia of damaged nephrons.These findings suggest that epithelial cells of the glomerulus, DT, and CD are dropped into the urine, and that these patterns are associated with renal pathology progression. We conclude that evaluation of urinary cellular patterns plays a key role in the early, noninvasive diagnosis of renal disease.
doi_str_mv 10.1371/journal.pone.0016472
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Glomerular and tubulointerstitial damages decrease the number of functional nephrons and cause anatomical and physiological alterations resulting in renal dysfunction. It has recently been reported that nephron constituent cells are dropped into the urine in several pathological conditions associated with renal functional deterioration. We investigated the quantitative and qualitative urinary cellular patterns in a murine glomerulonephritis model and elucidated the correlation between cellular patterns and renal pathology.Urinary cytology and renal histopathology were analyzed in BXSB/MpJ (BXSB; glomerulonephritis model) and C57BL/6 (B6; control) mice. Urinary cytology revealed that the number of urinary cells in BXSB mice changed according to the histometric score of glomerulonephritis and urinary albumin; however, no correlation was detected for the levels of blood urea nitrogen and creatinine. The expression of specific markers for podocytes, distal tubules (DTs), and CDs was detected in BXSB urine. Cells immunopositive for Wilms tumor 1 (podocyte marker) and interleukin-1 family, member 6 (damaged DT and CD marker) in the kidney significantly decreased and increased in BXSB versus B6, respectively. In the PCR array analysis of inflammatory cytokines and chemokines, Il10, Cxcl2, C3, and Il1rn showed relatively higher expression in BXSB kidneys than in B6 kidneys. In particular, the highest expression of C3 mRNA was detected in the urine from BXSB mice. Furthermore, C3 protein and mRNA were localized in the epithelia of damaged nephrons.These findings suggest that epithelial cells of the glomerulus, DT, and CD are dropped into the urine, and that these patterns are associated with renal pathology progression. 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Glomerular and tubulointerstitial damages decrease the number of functional nephrons and cause anatomical and physiological alterations resulting in renal dysfunction. It has recently been reported that nephron constituent cells are dropped into the urine in several pathological conditions associated with renal functional deterioration. We investigated the quantitative and qualitative urinary cellular patterns in a murine glomerulonephritis model and elucidated the correlation between cellular patterns and renal pathology.Urinary cytology and renal histopathology were analyzed in BXSB/MpJ (BXSB; glomerulonephritis model) and C57BL/6 (B6; control) mice. Urinary cytology revealed that the number of urinary cells in BXSB mice changed according to the histometric score of glomerulonephritis and urinary albumin; however, no correlation was detected for the levels of blood urea nitrogen and creatinine. The expression of specific markers for podocytes, distal tubules (DTs), and CDs was detected in BXSB urine. Cells immunopositive for Wilms tumor 1 (podocyte marker) and interleukin-1 family, member 6 (damaged DT and CD marker) in the kidney significantly decreased and increased in BXSB versus B6, respectively. In the PCR array analysis of inflammatory cytokines and chemokines, Il10, Cxcl2, C3, and Il1rn showed relatively higher expression in BXSB kidneys than in B6 kidneys. In particular, the highest expression of C3 mRNA was detected in the urine from BXSB mice. Furthermore, C3 protein and mRNA were localized in the epithelia of damaged nephrons.These findings suggest that epithelial cells of the glomerulus, DT, and CD are dropped into the urine, and that these patterns are associated with renal pathology progression. 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diagnosis</subject><subject>Kidney Tubules, Distal - pathology</subject><subject>Kidneys</subject><subject>Laboratory animals</subject><subject>Medicine</subject><subject>Mice</subject><subject>Mice, Inbred C57BL</subject><subject>mRNA</subject><subject>Nephrons</subject><subject>Pathology</subject><subject>Physiological aspects</subject><subject>Podocytes - pathology</subject><subject>Proteins</subject><subject>Qualitative analysis</subject><subject>Renal function</subject><subject>RNA</subject><subject>Rodents</subject><subject>Urea</subject><subject>Urine</subject><subject>Urine - cytology</subject><subject>Veterinary colleges</subject><subject>Veterinary medicine</subject><subject>WT1 protein</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2011</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><sourceid>DOA</sourceid><recordid>eNqNk1uL1DAUx4so7rr6DUQLguLDjLn1kpeFZfEysLB4fQ1petrJkEm6SbrqtzfjdJap7IPkoWny-__PyUlOlj3HaIlphd9t3OitNMvBWVgihEtWkQfZKeaULEqC6MOj-Un2JIQNQgWty_JxdkIwRYxzcprZz6O0UUcZ9S3k0rb5zSjN4X_02kr_O1dgzGikzwcZI3gbcuW8ByMj5D91XOeDd72HELSzuevy7U4IeW_cFvxoUobD2uuow9PsUSdNgGfT9yz7_uH9t8tPi6vrj6vLi6uFqmgRF0RhVNRNXbCqwUXNcFfhlH1Jq4ZLpAhiFS3rmjcSAW1wXSAiSacazjBI2Rb0LHu59x2MC2IqVRCYJILzCpeJWO2J1smNGLzepoMKJ7X4u-B8L6SPWhkQHanrFrqSYVywFJOrluICYV63GABY8jqfoo3NFloFNnppZqbzHavXone3gqJkxHEyeDMZeHczQohiq8Ou6NKCG4OoC0xIhQhJ5Kt_yPsPN1G9TPlr27kUVu08xQWrSo7KkqFELe-h0mhhq1W6tE6n9Zng7UyQmAi_Yi_HEMTq65f_Z69_zNnXR-wapInr4MwY03MKc5DtQeVdCB66uxpjJHZdcaiG2HWFmLoiyV4c38-d6NAG9A9wiwkz</recordid><startdate>20110131</startdate><enddate>20110131</enddate><creator>Kimura, Junpei</creator><creator>Ichii, Osamu</creator><creator>Otsuka, Saori</creator><creator>Kanazawa, Tomonori</creator><creator>Namiki, Yuka</creator><creator>Hashimoto, Yoshiharu</creator><creator>Kon, Yasuhiro</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>7X8</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20110131</creationdate><title>Quantitative and qualitative urinary cellular patterns correlate with progression of murine glomerulonephritis</title><author>Kimura, Junpei ; Ichii, Osamu ; Otsuka, Saori ; Kanazawa, Tomonori ; Namiki, Yuka ; Hashimoto, Yoshiharu ; Kon, Yasuhiro</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c735t-2c1058b8547b15841f71005637b9a0c204736889ba0e3b18502a2fcb941eaad53</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2011</creationdate><topic>Albumin</topic><topic>Analysis</topic><topic>Animals</topic><topic>Autoimmune diseases</topic><topic>Biomarkers - 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Glomerular and tubulointerstitial damages decrease the number of functional nephrons and cause anatomical and physiological alterations resulting in renal dysfunction. It has recently been reported that nephron constituent cells are dropped into the urine in several pathological conditions associated with renal functional deterioration. We investigated the quantitative and qualitative urinary cellular patterns in a murine glomerulonephritis model and elucidated the correlation between cellular patterns and renal pathology.Urinary cytology and renal histopathology were analyzed in BXSB/MpJ (BXSB; glomerulonephritis model) and C57BL/6 (B6; control) mice. Urinary cytology revealed that the number of urinary cells in BXSB mice changed according to the histometric score of glomerulonephritis and urinary albumin; however, no correlation was detected for the levels of blood urea nitrogen and creatinine. The expression of specific markers for podocytes, distal tubules (DTs), and CDs was detected in BXSB urine. Cells immunopositive for Wilms tumor 1 (podocyte marker) and interleukin-1 family, member 6 (damaged DT and CD marker) in the kidney significantly decreased and increased in BXSB versus B6, respectively. In the PCR array analysis of inflammatory cytokines and chemokines, Il10, Cxcl2, C3, and Il1rn showed relatively higher expression in BXSB kidneys than in B6 kidneys. In particular, the highest expression of C3 mRNA was detected in the urine from BXSB mice. Furthermore, C3 protein and mRNA were localized in the epithelia of damaged nephrons.These findings suggest that epithelial cells of the glomerulus, DT, and CD are dropped into the urine, and that these patterns are associated with renal pathology progression. We conclude that evaluation of urinary cellular patterns plays a key role in the early, noninvasive diagnosis of renal disease.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>21304992</pmid><doi>10.1371/journal.pone.0016472</doi><tpages>e16472</tpages><oa>free_for_read</oa></addata></record>
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subjects Albumin
Analysis
Animals
Autoimmune diseases
Biomarkers - urine
Biosynthesis
C3 protein
Cell Count
Chemokines
Correlation
Creatinine
Cytokines
Cytology
Damage localization
Distal tubules
Epithelial cells
Epithelial Cells - pathology
Fibroblasts
Gene expression
Glomerulonephritis
Glomerulonephritis - diagnosis
Glomerulonephritis - urine
Glomerulus
Histochemistry
Histopathology
House mouse
Inflammation
Inflammatory diseases
Interleukin 1
Interleukin 10
Kidney diseases
Kidney Diseases - diagnosis
Kidney Tubules, Distal - pathology
Kidneys
Laboratory animals
Medicine
Mice
Mice, Inbred C57BL
mRNA
Nephrons
Pathology
Physiological aspects
Podocytes - pathology
Proteins
Qualitative analysis
Renal function
RNA
Rodents
Urea
Urine
Urine - cytology
Veterinary colleges
Veterinary medicine
WT1 protein
title Quantitative and qualitative urinary cellular patterns correlate with progression of murine glomerulonephritis
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