| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
Departments of 1Pathology and Laboratory Medicine, 2Internal Medicine, and 5Surgery, University Medical Center Groningen and University of Groningen, Groningen, The Netherlands; 3Renal Division, Brigham and Women's Hospital, Harvard Medical School, Boston; and 4Biogen, Incorporated, Cambridge, Massachusetts
Submitted 13 October 2005 ; accepted in final form 1 February 2006
Kim-1, a recently discovered membrane protein, is undetectable in normal kidneys but markedly induced in proximal tubules after ischemic and toxic injury. The function of Kim-1 is unclear, but it is implicated in damage/repair processes. The Kim-1 ectodomain is cleaved by metalloproteinases and detectable in urine. We studied Kim-1 in a nontoxic, nonischemic, model of tubulointerstitial damage caused by acute proteinuria. Uninephrectomized (NX) rats received daily (ip) injections of 2 g BSA (NX+BSA, n = 12) or saline (NX, n = 6) for 3 wk. Kidneys were stained for various damage markers by immunohistochemistry (IHC). Kim-1 mRNA (RT-PCR, in situ hybridization), protein (IHC, Western blotting), and urinary Kim-1 (Luminex) were determined. Spatial relations between Kim-1 and other damage markers were studied by double labeling IHC. NX+BSA rats developed massive proteinuria (1,217 ± 313 vs. 18 ± 2 mg/day in NX, P < 0.001) and significant renal damage. Kim-1 mRNA was upregulated eightfold in NX+BSA (ratio Kim-1/
-actin, 4.08 ± 2.56 vs. 0.52 ± 0.64 in NX, P < 0.001) and localized to damaged tubules. Kim-1 protein expression was markedly induced in NX+BSA (2.46 ± 1.19 vs. 0.39 ± 0.10% staining/field in NX, P < 0.001). Urinary Kim-1 was significantly elevated in NX+BSA (921 ± 592 vs. 87 ± 164 pg/ml in NX, P < 0.001) and correlated with tissue Kim-1 expression (r = 0.66, P =0.02). Kim-1 protein was found at the apical membrane of dilated nephrons. Kim-1 expression was limited to areas with inflammation (MØ), fibrosis (
-smooth muscle actin), and tubular damage (osteopontin), and only occasionally with tubular dedifferentiation (vimentin). These results implicate involvement of Kim-1 in the pathogenesis of proteinuria-induced renal damage/repair. Urinary Kim-1 levels may serve as a marker of proteinuria-induced renal damage.
tubulointerstitial damage; proximal tubular cell; proteinuria; renal pathology
This article has been cited by other articles:
|
|
 |
|
  A. B. Kramer, M. M. van Timmeren, T. A. Schuurs, V. S. Vaidya, J. V. Bonventre, H. van Goor, and G. Navis Reduction of proteinuria in adriamycin-induced nephropathy is associated with reduction of renal kidney injury molecule (Kim-1) over time Am J Physiol Renal Physiol, May 1, 2009; 296(5): F1136 - F1145. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. V. Bonventre Kidney injury molecule-1 (KIM-1): a urinary biomarker and much more Nephrol. Dial. Transplant., March 23, 2009; (2009) gfp010v1. [Full Text] [PDF]
|
|
|
|
|
|
A. J. Rees and R. Kain Kim-1/Tim-1: from biomarker to therapeutic target? Nephrol. Dial. Transplant., November 1, 2008; 23(11): 3394 - 3396. [Full Text] [PDF]
|
|
|
|
 |
|
 J. Zhang, R. P. Brown, M. Shaw, V. S. Vaidya, Y. Zhou, P. Espandiari, N. Sadrieh, M. Stratmeyer, J. Keenan, C. G. Kilty, et al. Immunolocalization of Kim-1, RPA-1, and RPA-2 in Kidney of Gentamicin-, Mercury-, or Chromium-Treated Rats: Relationship to Renal Distributions of iNOS and Nitrotyrosine Toxicol Pathol, April 1, 2008; 36(3): 397 - 409. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. G. Wong, Y. Suzuki, C. Tanifuji, H. Akiba, K. Okumura, T. Sugaya, T. Yamamoto, S. Horikoshi, S. Y. Tan, C. Pollock, et al. Peritubular Ischemia Contributes More to Tubular Damage than Proteinuria in Immune-Mediated Glomerulonephritis J. Am. Soc. Nephrol., February 1, 2008; 19(2): 290 - 297. [Full Text] [PDF]
|
|
|
|
|
|
D. Bolignano, G. Coppolino, S. Campo, C. Aloisi, G. Nicocia, N. Frisina, and M. Buemi Urinary neutrophil gelatinase-associated lipocalin (NGAL) is associated with severity of renal disease in proteinuric patients Nephrol. Dial. Transplant., January 1, 2008; 23(1): 414 - 416. [Full Text] [PDF]
|
|
|
|
 |
|
 Y. Zhou, V. S. Vaidya, R. P. Brown, J. Zhang, B. A. Rosenzweig, K. L. Thompson, T. J. Miller, J. V. Bonventre, and P. L. Goering Comparison of Kidney Injury Molecule-1 and Other Nephrotoxicity Biomarkers in Urine and Kidney Following Acute Exposure to Gentamicin, Mercury, and Chromium Toxicol. Sci., January 1, 2008; 101(1): 159 - 170. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Z. Zhang, B. D. Humphreys, and J. V. Bonventre Shedding of the Urinary Biomarker Kidney Injury Molecule-1 (KIM-1) Is Regulated by MAP Kinases and Juxtamembrane Region J. Am. Soc. Nephrol., October 1, 2007; 18(10): 2704 - 2714. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. M. Yamaleyeva, K. D. Pendergrass, N. T. Pirro, P. E. Gallagher, L. Groban, and M. C. Chappell Ovariectomy is protective against renal injury in the high-salt-fed older mRen2.Lewis rat Am J Physiol Heart Circ Physiol, October 1, 2007; 293(4): H2064 - H2071. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. Chen, E. A. Bridenbaugh, A. D. Akintola, J. M. Catania, V. S. Vaidya, J. V. Bonventre, A. C. Dearman, H. W. Sampson, D. C. Zawieja, R. C. Burghardt, et al. Increased susceptibility of aging kidney to ischemic injury: identification of candidate genes changed during aging, but corrected by caloric restriction Am J Physiol Renal Physiol, October 1, 2007; 293(4): F1272 - F1281. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 M. Waldman, R. J. Crew, A. Valeri, J. Busch, B. Stokes, G. Markowitz, V. D'Agati, and G. Appel Adult Minimal-Change Disease: Clinical Characteristics, Treatment, and Outcomes Clin. J. Am. Soc. Nephrol., May 1, 2007; 2(3): 445 - 453. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. H. de Borst, M. M. van Timmeren, V. S. Vaidya, R. A. de Boer, M. B. A. van Dalen, A. B. Kramer, T. A. Schuurs, J. V. Bonventre, G. Navis, and H. van Goor Induction of kidney injury molecule-1 in homozygous Ren2 rats is attenuated by blockade of the renin-angiotensin system or p38 MAP kinase Am J Physiol Renal Physiol, January 1, 2007; 292(1): F313 - F320. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Kramer, M. van den Hoven, A. Rops, T. Wijnhoven, L. van den Heuvel, J. Lensen, T. van Kuppevelt, H. van Goor, J. van der Vlag, G. Navis, et al. Induction of Glomerular Heparanase Expression in Rats with Adriamycin Nephropathy Is Regulated by Reactive Oxygen Species and the Renin-Angiotensin System J. Am. Soc. Nephrol., September 1, 2006; 17(9): 2513 - 2520. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
