Skip to main content
Top
Published in: International Urology and Nephrology 2/2014

01-02-2014 | Urology - Original Paper

Urine kidney injury molecule-1: a potential non-invasive biomarker for patients with renal cell carcinoma

Authors: Ping L. Zhang, Joseph W. Mashni, Venkata S. Sabbisetti, Charles M. Schworer, George D. Wilson, Stacy C. Wolforth, Kenneth M. Kernen, Brian D. Seifman, Mitual B. Amin, Timothy J. Geddes, Fan Lin, Joseph V. Bonventre, Jason M. Hafron

Published in: International Urology and Nephrology | Issue 2/2014

Login to get access

Abstract

Background

KIM-1 staining is upregulated in proximal tubule-derived renal cell carcinoma (RCC) including clear renal cell carcinoma and papillary renal cell carcinoma, but not in chromophobe RCC (distal tubular tumor). This study was designed to prospectively examine urine KIM-1 level before and 1 month after removal of renal tumors.

Patients and design

A total of 19 patients were eventually enrolled in the study based on pre-operative imaging studies. Pre-operative and follow-up (1 month) urine KIM-1 levels were measured. The urine KIM-1 levels (uKIM-1) were then normalized to urine creatinine levels (uCr). Renal tumors were also stained for KIM-1 using immunohistochemical techniques.

Results

The KIM-1-negative staining group included 7 cases, and the KIM-1-positive group consisted of 12 cases. The percentage of KIM-1-positive staining RCC cells ranged from 10 to 100 %, and the staining intensity ranged from 1+ to 3+. In both groups, serum creatinine levels were both significantly elevated after nephrectomy. In the KIM-1-negative group, uKIM-1/uCr remained at a similar level before (0.37 ± 0.1 ng/mg Cr) and after nephrectomy (0.32 ± 0.01 ng/mg Cr). However, in the KIM-1-positive group, elevated uKIM-1/uCr at 1.20 ± 0.31 ng/mg Cr was significantly reduced to 0.36 ± 0.1 ng/mg Cr, which was similar to the pre-operative uKIM-1/uCr (0.37 ± 0.1 ng/mg Cr) in the KIM-1-negative group.

Conclusion

Our small but prospective study showed significant reduction in uKIM-1/uCr after nephrectomy in the KIM-1 positive group, suggesting that urine KIM-1 may serve as a surrogate biomarker for kidney cancer and a non-invasive pre-operative measure to evaluate the malignant potential of renal masses.
Literature
1.
go back to reference Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 59(4):225–249PubMedCrossRef Jemal A, Siegel R, Ward E, Hao Y, Xu J, Thun MJ (2009) Cancer statistics, 2009. CA Cancer J Clin 59(4):225–249PubMedCrossRef
2.
go back to reference Ichimura T, Bonventre JV, Bailly V, Wei H, Hession CA, Cate RL et al (1998) Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J Biol Chem 273(7):4135–4142PubMedCrossRef Ichimura T, Bonventre JV, Bailly V, Wei H, Hession CA, Cate RL et al (1998) Kidney injury molecule-1 (KIM-1), a putative epithelial cell adhesion molecule containing a novel immunoglobulin domain, is up-regulated in renal cells after injury. J Biol Chem 273(7):4135–4142PubMedCrossRef
3.
go back to reference Ichimura T, Hung CC, Yang SA, Stevens JL, Bonventre JV (2004) Kidney injury molecule-1: a tissue and urinary biomarker for nephrotoxicant-induced renal injury. Am J Physiol Renal Physiol 286(3):F552–F563PubMedCrossRef Ichimura T, Hung CC, Yang SA, Stevens JL, Bonventre JV (2004) Kidney injury molecule-1: a tissue and urinary biomarker for nephrotoxicant-induced renal injury. Am J Physiol Renal Physiol 286(3):F552–F563PubMedCrossRef
4.
go back to reference Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV (2002) Kidney injury molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int 62(1):237–244PubMedCrossRef Han WK, Bailly V, Abichandani R, Thadhani R, Bonventre JV (2002) Kidney injury molecule-1 (KIM-1): a novel biomarker for human renal proximal tubule injury. Kidney Int 62(1):237–244PubMedCrossRef
5.
go back to reference van Timmeren MM, van den Heuvel MC, Bailly V, Bakker SJ, van Goor H, Stegeman CA (2007) Tubular kidney injury molecule-1 (KIM-1) in human renal disease. J Pathol 212(2):209–217PubMedCrossRef van Timmeren MM, van den Heuvel MC, Bailly V, Bakker SJ, van Goor H, Stegeman CA (2007) Tubular kidney injury molecule-1 (KIM-1) in human renal disease. J Pathol 212(2):209–217PubMedCrossRef
6.
go back to reference Zhang PL, Rothblum LI, Han WK, Blasick TM, Potdar S, Bonventre JV (2008) Kidney injury molecule-1 expression in transplant biopsies is a sensitive measure of cell injury. Kidney Int 73(5):608–614PubMedCentralPubMedCrossRef Zhang PL, Rothblum LI, Han WK, Blasick TM, Potdar S, Bonventre JV (2008) Kidney injury molecule-1 expression in transplant biopsies is a sensitive measure of cell injury. Kidney Int 73(5):608–614PubMedCentralPubMedCrossRef
7.
go back to reference Ichimura T, Asseldonk EJ, Humphreys BD, Gunaratnam L, Duffield JS, Bonventre JV (2008) Kidney injury molecule-1 is a phosphatidylserine receptor that confers a phagocytic phenotype on epithelial cells. J Clin Invest 118(5):1657–1668PubMedCentralPubMedCrossRef Ichimura T, Asseldonk EJ, Humphreys BD, Gunaratnam L, Duffield JS, Bonventre JV (2008) Kidney injury molecule-1 is a phosphatidylserine receptor that confers a phagocytic phenotype on epithelial cells. J Clin Invest 118(5):1657–1668PubMedCentralPubMedCrossRef
8.
go back to reference de Borst MH, van Timmeren MM, Vaidya VS, de Boer RA, van Dalen MB, Kramer AB et al (2007) 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 292(1):F313–F320PubMedCrossRef de Borst MH, van Timmeren MM, Vaidya VS, de Boer RA, van Dalen MB, Kramer AB et al (2007) 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 292(1):F313–F320PubMedCrossRef
9.
go back to reference Kramer AB, van Timmeren MM, Schuurs TA, Vaidya VS, Bonventre JV, van Goor H et al (2009) 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 296(5):F1136–F1145PubMedCrossRef Kramer AB, van Timmeren MM, Schuurs TA, Vaidya VS, Bonventre JV, van Goor H et al (2009) 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 296(5):F1136–F1145PubMedCrossRef
10.
go back to reference Vaidya VS, Ramirez V, Ichimura T, Bobadilla NA, Bonventre JV (2006) Urinary kidney injury molecule-1: a sensitive quantitative biomarker for early detection of kidney tubular injury. Am J Physiol Renal Physiol 290(2):F517–F529PubMedCrossRef Vaidya VS, Ramirez V, Ichimura T, Bobadilla NA, Bonventre JV (2006) Urinary kidney injury molecule-1: a sensitive quantitative biomarker for early detection of kidney tubular injury. Am J Physiol Renal Physiol 290(2):F517–F529PubMedCrossRef
11.
go back to reference Han WK, Waikar SS, Johnson A, Betensky RA, Dent CL, Devarajan P et al (2008) Urinary biomarkers in the early diagnosis of acute kidney injury. Kidney Int 73(7):863–869PubMedCentralPubMedCrossRef Han WK, Waikar SS, Johnson A, Betensky RA, Dent CL, Devarajan P et al (2008) Urinary biomarkers in the early diagnosis of acute kidney injury. Kidney Int 73(7):863–869PubMedCentralPubMedCrossRef
12.
go back to reference Han WK, Alinani A, Wu CL, Michaelson D, Loda M, McGovern FJ et al (2005) Human kidney injury molecule-1 is a tissue and urinary tumor marker of renal cell carcinoma. J Am Soc Nephrol 16(4):1126–1134PubMedCentralPubMedCrossRef Han WK, Alinani A, Wu CL, Michaelson D, Loda M, McGovern FJ et al (2005) Human kidney injury molecule-1 is a tissue and urinary tumor marker of renal cell carcinoma. J Am Soc Nephrol 16(4):1126–1134PubMedCentralPubMedCrossRef
13.
go back to reference Lin F, Zhang PL, Yang XJ, Shi J, Blasick T, Han WK et al (2007) Human kidney injury molecule-1 (hKIM-1): a useful immunohistochemical marker for diagnosing renal cell carcinoma and ovarian clear cell carcinoma. Am J Surg Pathol 31(3):371–381PubMedCrossRef Lin F, Zhang PL, Yang XJ, Shi J, Blasick T, Han WK et al (2007) Human kidney injury molecule-1 (hKIM-1): a useful immunohistochemical marker for diagnosing renal cell carcinoma and ovarian clear cell carcinoma. Am J Surg Pathol 31(3):371–381PubMedCrossRef
14.
go back to reference Morrissey JJ, London AN, Lambert MC, Kharasch ED (2011) Sensitivity and specificity of urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 for the diagnosis of renal cell carcinoma. Am J Nephrol 34(5):391–398PubMedCrossRef Morrissey JJ, London AN, Lambert MC, Kharasch ED (2011) Sensitivity and specificity of urinary neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 for the diagnosis of renal cell carcinoma. Am J Nephrol 34(5):391–398PubMedCrossRef
15.
go back to reference Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612PubMedCentralPubMedCrossRef Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612PubMedCentralPubMedCrossRef
16.
go back to reference Endre ZH, Pickering JW, Walker RJ, Devarajan P, Edelstein CL, Bonventre JV et al (2011) Improved performance of urinary biomarkers of acute kidney injury in the critically ill by stratification for injury duration and baseline renal function. Kidney Int 79(10):1119–1130PubMedCrossRef Endre ZH, Pickering JW, Walker RJ, Devarajan P, Edelstein CL, Bonventre JV et al (2011) Improved performance of urinary biomarkers of acute kidney injury in the critically ill by stratification for injury duration and baseline renal function. Kidney Int 79(10):1119–1130PubMedCrossRef
17.
go back to reference Holness CL, Simmons DL (1993) Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins. Blood 81(6):1607–1613PubMed Holness CL, Simmons DL (1993) Molecular cloning of CD68, a human macrophage marker related to lysosomal glycoproteins. Blood 81(6):1607–1613PubMed
18.
go back to reference Saito N, Pulford KA, Breton-Gorius J, Masse JM, Mason DY, Cramer EM (1991) Ultrastructural localization of the CD68 macrophage-associated antigen in human blood neutrophils and monocytes. Am J Pathol 139(5):1053–1059PubMed Saito N, Pulford KA, Breton-Gorius J, Masse JM, Mason DY, Cramer EM (1991) Ultrastructural localization of the CD68 macrophage-associated antigen in human blood neutrophils and monocytes. Am J Pathol 139(5):1053–1059PubMed
19.
go back to reference Vaidya VS, Ozer JS, Dieterle F, Collings FB, Ramirez V, Troth S et al (2010) Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nat Biotechnol 28(5):478–485PubMedCentralPubMedCrossRef Vaidya VS, Ozer JS, Dieterle F, Collings FB, Ramirez V, Troth S et al (2010) Kidney injury molecule-1 outperforms traditional biomarkers of kidney injury in preclinical biomarker qualification studies. Nat Biotechnol 28(5):478–485PubMedCentralPubMedCrossRef
20.
go back to reference Liangos O, Perianayagam MC, Vaidya VS, Han WK, Wald R, Tighiouart H et al (2007) Urinary N-acetyl-beta-(D)-glucosaminidase activity and kidney injury molecule-1 level are associated with adverse outcomes in acute renal failure. J Am Soc Nephrol 18(3):904–912PubMedCrossRef Liangos O, Perianayagam MC, Vaidya VS, Han WK, Wald R, Tighiouart H et al (2007) Urinary N-acetyl-beta-(D)-glucosaminidase activity and kidney injury molecule-1 level are associated with adverse outcomes in acute renal failure. J Am Soc Nephrol 18(3):904–912PubMedCrossRef
21.
go back to reference Schworer CM, Zhang PL, Gerhard GS, Lin F (2009) Mutations in the mucin binding domain of the human kidney injury molecule-1 (KIM-1) gene are present in renal epithelial neoplasms. Mod Pathol 22(Suppl 1):192A Schworer CM, Zhang PL, Gerhard GS, Lin F (2009) Mutations in the mucin binding domain of the human kidney injury molecule-1 (KIM-1) gene are present in renal epithelial neoplasms. Mod Pathol 22(Suppl 1):192A
23.
go back to reference Tanaka M, Suzuki Y, Shirato I, Takahara H, Shibata T, Sugaya T et al (2008) Tubular epithelial cells have the capacity to transdifferentiate into CD68-positive macrophage-like cells by oxidative stress. Inflamm Res 57(12):593–600PubMedCrossRef Tanaka M, Suzuki Y, Shirato I, Takahara H, Shibata T, Sugaya T et al (2008) Tubular epithelial cells have the capacity to transdifferentiate into CD68-positive macrophage-like cells by oxidative stress. Inflamm Res 57(12):593–600PubMedCrossRef
24.
go back to reference Zhu L, Yang X, Ji Y, Chen W, Guan W, Zhou SF et al (2009) Up-regulated renal expression of TNF-alpha signalling adapter proteins in lupus glomerulonephritis. Lupus 18(2):116–127PubMedCrossRef Zhu L, Yang X, Ji Y, Chen W, Guan W, Zhou SF et al (2009) Up-regulated renal expression of TNF-alpha signalling adapter proteins in lupus glomerulonephritis. Lupus 18(2):116–127PubMedCrossRef
25.
go back to reference Gloghini A, Rizzo A, Zanette I, Canal B, Rupolo G, Bassi P et al (1995) KP1/CD68 expression in malignant neoplasms including lymphomas, sarcomas, and carcinomas. Am J Clin Pathol 103(4):425–431PubMed Gloghini A, Rizzo A, Zanette I, Canal B, Rupolo G, Bassi P et al (1995) KP1/CD68 expression in malignant neoplasms including lymphomas, sarcomas, and carcinomas. Am J Clin Pathol 103(4):425–431PubMed
26.
go back to reference Sridhar S, Botbol Y, Macian F, Cuervo AM (2012) Autophagy and disease: always two sides to a problem. J Pathol 226(2):255–273PubMedCrossRef Sridhar S, Botbol Y, Macian F, Cuervo AM (2012) Autophagy and disease: always two sides to a problem. J Pathol 226(2):255–273PubMedCrossRef
27.
go back to reference Cox TM, Cachon-Gonzalez MB (2012) The cellular pathology of lysosomal diseases. J Pathol 226(2):241–254PubMedCrossRef Cox TM, Cachon-Gonzalez MB (2012) The cellular pathology of lysosomal diseases. J Pathol 226(2):241–254PubMedCrossRef
Metadata
Title
Urine kidney injury molecule-1: a potential non-invasive biomarker for patients with renal cell carcinoma
Authors
Ping L. Zhang
Joseph W. Mashni
Venkata S. Sabbisetti
Charles M. Schworer
George D. Wilson
Stacy C. Wolforth
Kenneth M. Kernen
Brian D. Seifman
Mitual B. Amin
Timothy J. Geddes
Fan Lin
Joseph V. Bonventre
Jason M. Hafron
Publication date
01-02-2014
Publisher
Springer Netherlands
Published in
International Urology and Nephrology / Issue 2/2014
Print ISSN: 0301-1623
Electronic ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-013-0522-z

Other articles of this Issue 2/2014

International Urology and Nephrology 2/2014 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.