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Erschienen in: International Urology and Nephrology 8/2019

19.06.2019 | Nephrology - Original Paper

Association of urinary monocyte chemoattractant protein-1 (MCP-1) and kidney injury molecule-1 (KIM-1) with risk factors of diabetic kidney disease in type 2 diabetes patients

verfasst von: Khalid Siddiqui, Salini Scaria Joy, Khalid Al-Rubeaan

Erschienen in: International Urology and Nephrology | Ausgabe 8/2019

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Abstract

Purpose

Urinary kidney injury molecule-1 and monocyte chemoattractant protein-1 are significance factors in the diagnosis and intervention of diabetic kidney diseases. This study determined levels of these proteins in diabetic patients with varying degrees of kidney disease and assessed their relationship with risk factors associated with diabetic kidney diseases.

Methods

A total of 185 patients with type 2 diabetes were divided into three groups [low risk (n = 47), moderate risk (n = 63), and high risk (n = 75)] based on the severity of diabetic kidney disease according to kidney disease: improving global outcomes guidelines. Both urinary kidney injury molecule-1 and monocyte chemoattractant protein-1 levels were measured by enzyme-linked immunosorbent assay. Student`s t test, analysis of variance, and Spearman’s correlation were used for statistical analysis.

Results

The kidney injury molecule-1-to-creatinine ratio (P = 0.035) and monocyte chemoattractant protein-1-to-creatinine ratio (P < 0.001) increased significantly with the increase in kidney disease severity and varied according to different albuminuria statuses and estimated glomerular-filtration rates. The monocyte chemoattractant protein-1-to-creatinine ratio showed a significant correlation with hemoglobin A1c (P = 0.002) and inflammatory marker levels (interleukin-6, P = 0.005; tumor necrosis factor-α, P < 0.001).

Conclusion

Urinary levels of both kidney injury molecule-1 and monocyte chemoattractant protein-1 represent distinguishing markers for the evaluation of diabetic kidney disease progression according to the associated degrees of albuminuria or/and the estimated glomerular-filtration rate. In addition, correlations between urinary monocyte chemoattractant protein-1 and glycemic and inflammatory marker levels revealed the role of hyperglycemia and chronic inflammation in the pathogenesis of diabetic kidney disease.
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Literatur
2.
Zurück zum Zitat SCOT Data (2017) Dialysis in the Kindom of Saudi Arabia. Saudi J Kidney Dis Transpl 28:949–957 SCOT Data (2017) Dialysis in the Kindom of Saudi Arabia. Saudi J Kidney Dis Transpl 28:949–957
3.
Zurück zum Zitat Bhattacharjee N, Barma S, Konwar N, Dewanjee S, Manna P (2016) Mechanistic insight of diabetic nephropathy and its pharmacotherapeutic targets: an update. Eur J Pharmacol 791:8–24CrossRefPubMed Bhattacharjee N, Barma S, Konwar N, Dewanjee S, Manna P (2016) Mechanistic insight of diabetic nephropathy and its pharmacotherapeutic targets: an update. Eur J Pharmacol 791:8–24CrossRefPubMed
4.
Zurück zum Zitat Ichimura T, Bonventre JV, Bailly V, Wei H, Hession CA, Cate RL, Sanicola M (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 273:4135–4142CrossRefPubMed Ichimura T, Bonventre JV, Bailly V, Wei H, Hession CA, Cate RL, Sanicola M (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 273:4135–4142CrossRefPubMed
5.
Zurück zum Zitat 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 212:209–217CrossRefPubMed 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 212:209–217CrossRefPubMed
6.
Zurück zum Zitat Vaidya VS, Waikar SS, Ferguson MA, Collings FB, Sunderland K, Gioules C, Bradwin G, Matsouaka R, Betensky RA, Curhan GC, Bonventre JV (2008) Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans. Clin Transl 1:200–208CrossRef Vaidya VS, Waikar SS, Ferguson MA, Collings FB, Sunderland K, Gioules C, Bradwin G, Matsouaka R, Betensky RA, Curhan GC, Bonventre JV (2008) Urinary biomarkers for sensitive and specific detection of acute kidney injury in humans. Clin Transl 1:200–208CrossRef
7.
Zurück zum Zitat Bangstad HJ, Seljeflot I, Berg TJ, Hanssen KF (2009) Renal tubulointerstitial expansion is associated with endothelial dysfunction and inflammation in type 1 diabetes. Scand J Clin Lab Invest 69:138–144CrossRefPubMed Bangstad HJ, Seljeflot I, Berg TJ, Hanssen KF (2009) Renal tubulointerstitial expansion is associated with endothelial dysfunction and inflammation in type 1 diabetes. Scand J Clin Lab Invest 69:138–144CrossRefPubMed
9.
Zurück zum Zitat Fu WJ, Xiong SL, Fang YG, Wen S, Chen ML, Deng RT, Zheng L, Wang SB, Pen LF, Wang Q (2012) Urinary tubular biomarkers in short-term type 2 diabetes mellitus patients: a cross-sectional study. Endocrine 41:82–88CrossRefPubMed Fu WJ, Xiong SL, Fang YG, Wen S, Chen ML, Deng RT, Zheng L, Wang SB, Pen LF, Wang Q (2012) Urinary tubular biomarkers in short-term type 2 diabetes mellitus patients: a cross-sectional study. Endocrine 41:82–88CrossRefPubMed
10.
Zurück zum Zitat El-Ashmawy NE, El-Zamarany EA, Khedr NF, Abd El-Fattah AI, Eltoukhy SA (2015) Kidney injury molecule-1 (Kim-1): an early biomarker for nephropathy in type II diabetic patients. Into J Diabetes Dev Ctries 35:431–438CrossRef El-Ashmawy NE, El-Zamarany EA, Khedr NF, Abd El-Fattah AI, Eltoukhy SA (2015) Kidney injury molecule-1 (Kim-1): an early biomarker for nephropathy in type II diabetic patients. Into J Diabetes Dev Ctries 35:431–438CrossRef
11.
Zurück zum Zitat Banba N, Nakamura T, Matsumura M, Kuroda H, Hattori Y, Kasai K (2000) Possible relationship of monocyte chemoattractant protein-1 with diabetic nephropathy. Kidney Int 58:684–690CrossRefPubMed Banba N, Nakamura T, Matsumura M, Kuroda H, Hattori Y, Kasai K (2000) Possible relationship of monocyte chemoattractant protein-1 with diabetic nephropathy. Kidney Int 58:684–690CrossRefPubMed
12.
Zurück zum Zitat Wang QY, Chen FQ (2009) Clinical significance and different levels of urinary monocyte chemoattractant protein-1 in type 2 diabetes mellitus. Diabetes Res Clin Pract 83:215–219CrossRefPubMed Wang QY, Chen FQ (2009) Clinical significance and different levels of urinary monocyte chemoattractant protein-1 in type 2 diabetes mellitus. Diabetes Res Clin Pract 83:215–219CrossRefPubMed
13.
Zurück zum Zitat Tashiro K, Koyanagi I, Saitoh A, Shimizu A, Shike T, Ishiguro C, Koizumi M, Funabiki K, Horikoshi S, Shirato I, Tomino Y (2002) Urinary levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 and renal injuries in patients with type 2 diabetic nephropathy. J Clin Lab Anal 16:1–4CrossRefPubMedPubMedCentral Tashiro K, Koyanagi I, Saitoh A, Shimizu A, Shike T, Ishiguro C, Koizumi M, Funabiki K, Horikoshi S, Shirato I, Tomino Y (2002) Urinary levels of monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 and renal injuries in patients with type 2 diabetic nephropathy. J Clin Lab Anal 16:1–4CrossRefPubMedPubMedCentral
14.
Zurück zum Zitat Ibrahim S, Rashed L (2008) Correlation of urinary monocyte chemoattractant protein- 1 with other parameters of renal injury in type 2 diabetes mellitus. Saudi J Kid Dis Transpl 19:911–917 Ibrahim S, Rashed L (2008) Correlation of urinary monocyte chemoattractant protein- 1 with other parameters of renal injury in type 2 diabetes mellitus. Saudi J Kid Dis Transpl 19:911–917
15.
Zurück zum Zitat Tilak P, Khashim Z, Kumpatla S, Babu M, Viswanathan V (2010) Clinical significance of urinary Monocyte Chemoattractant Protein-1 (uMCP-1) in Indian type 2 diabetic patients at different stages of diabetic nephropathy. Int J Diabetes Mellit 2:15–19CrossRef Tilak P, Khashim Z, Kumpatla S, Babu M, Viswanathan V (2010) Clinical significance of urinary Monocyte Chemoattractant Protein-1 (uMCP-1) in Indian type 2 diabetic patients at different stages of diabetic nephropathy. Int J Diabetes Mellit 2:15–19CrossRef
16.
Zurück zum Zitat World Medical Association (2013) World Medical Association Declaration of Helsinki: ethical principles for medical research involving human patients. JAMA 310:2191–2194CrossRef World Medical Association (2013) World Medical Association Declaration of Helsinki: ethical principles for medical research involving human patients. JAMA 310:2191–2194CrossRef
17.
Zurück zum Zitat Al-Rubeaan K, Siddiqui K, Alghonaim M, Youssef AM, AlNaqeb D (2018) The Saudi Diabetic Kidney Disease study (Saudi-DKD): clinical characteristics and biochemical parameters. Ann Saudi Med 38:46–56CrossRefPubMedPubMedCentral Al-Rubeaan K, Siddiqui K, Alghonaim M, Youssef AM, AlNaqeb D (2018) The Saudi Diabetic Kidney Disease study (Saudi-DKD): clinical characteristics and biochemical parameters. Ann Saudi Med 38:46–56CrossRefPubMedPubMedCentral
18.
Zurück zum Zitat National Kidney Foundation (2012) KDOQI clinical practice guideline for diabetes and CKD: 2012 update. Am J Kidney Dis 60:850–886CrossRef National Kidney Foundation (2012) KDOQI clinical practice guideline for diabetes and CKD: 2012 update. Am J Kidney Dis 60:850–886CrossRef
19.
Zurück zum Zitat Kidney Disease: Improving Global Outcomes (KDIGO) (2013) Chapter 1: definition and classification of CKD. Kidney Int Suppl 3:19–62CrossRef Kidney Disease: Improving Global Outcomes (KDIGO) (2013) Chapter 1: definition and classification of CKD. Kidney Int Suppl 3:19–62CrossRef
20.
Zurück zum Zitat Ketteler M, Block GA, Evenepoel P, Fukagawa M, Herzog CA, McCann L, Moe SM, Shroff R, Tonelli MA, Toussaint ND, Vervloet MG, Leonard MB, (2018) Diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder: synopsis of the kidney disease: improving global outcomes 2017 clinical practice guideline update. Ann Intern Med 168:422–430CrossRefPubMed Ketteler M, Block GA, Evenepoel P, Fukagawa M, Herzog CA, McCann L, Moe SM, Shroff R, Tonelli MA, Toussaint ND, Vervloet MG, Leonard MB, (2018) Diagnosis, evaluation, prevention, and treatment of chronic kidney disease-mineral and bone disorder: synopsis of the kidney disease: improving global outcomes 2017 clinical practice guideline update. Ann Intern Med 168:422–430CrossRefPubMed
21.
Zurück zum Zitat Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612CrossRefPubMedPubMedCentral Levey AS, Stevens LA, Schmid CH, Zhang YL, Castro AF 3rd, Feldman HI, Kusek JW, Eggers P, Van Lente F, Greene T, Coresh J, CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150:604–612CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Harjutsalo V, Groop PH (2014) Epidemiology and risk factors for diabetic kidney disease. Adv Chronic Kidney Dis 21:260–266CrossRefPubMed Harjutsalo V, Groop PH (2014) Epidemiology and risk factors for diabetic kidney disease. Adv Chronic Kidney Dis 21:260–266CrossRefPubMed
24.
Zurück zum Zitat Bonventre JV (2009) Kidney injury molecule-1 (KIM-1): a urinary biomarker and much more. Nephrol Dial Transplant 24:3265–3268CrossRefPubMed Bonventre JV (2009) Kidney injury molecule-1 (KIM-1): a urinary biomarker and much more. Nephrol Dial Transplant 24:3265–3268CrossRefPubMed
25.
Zurück zum Zitat 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 62:237–244CrossRefPubMed 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 62:237–244CrossRefPubMed
26.
Zurück zum Zitat van Timmeren MM, Bakker SJ, Vaidya VS, Bailly V, Schuurs TA, Damman J, Stegeman CA, Bonventre JV, van Goor H (2006) Tubular kidney injury molecule-1 in protein-overload nephropathy. Am J Physiol Renal Physiol 29:F456–F464CrossRef van Timmeren MM, Bakker SJ, Vaidya VS, Bailly V, Schuurs TA, Damman J, Stegeman CA, Bonventre JV, van Goor H (2006) Tubular kidney injury molecule-1 in protein-overload nephropathy. Am J Physiol Renal Physiol 29:F456–F464CrossRef
27.
Zurück zum Zitat Kim SS, Song SH, Kim IJ, Yang JY, Lee JG, Kwak IS, Kim YK (2012) Clinical implication of urinary tubular markers in the early stage of nephropathy with type 2 diabetic patients. Diabetes Res Clin Pract 97:251–257CrossRefPubMed Kim SS, Song SH, Kim IJ, Yang JY, Lee JG, Kwak IS, Kim YK (2012) Clinical implication of urinary tubular markers in the early stage of nephropathy with type 2 diabetic patients. Diabetes Res Clin Pract 97:251–257CrossRefPubMed
28.
Zurück zum Zitat Kin Tekce B, Tekce H, Aktas G, Sit M (2014) Evaluation of the urinary kidney injury molecule-1 levels in patients with diabetic nephropathy. Clin Invest Med 37:E377–E383CrossRefPubMed Kin Tekce B, Tekce H, Aktas G, Sit M (2014) Evaluation of the urinary kidney injury molecule-1 levels in patients with diabetic nephropathy. Clin Invest Med 37:E377–E383CrossRefPubMed
29.
Zurück zum Zitat Ucakturk A, Avci B, Genc G, Ozkaya O, Aydin M (2016) Kidney injury molecule-1 and neutrophil gelatinase associated lipocalin in normoalbuminuric diabetic children. J Pediatr Endocrinol Metab 29:145–151CrossRefPubMed Ucakturk A, Avci B, Genc G, Ozkaya O, Aydin M (2016) Kidney injury molecule-1 and neutrophil gelatinase associated lipocalin in normoalbuminuric diabetic children. J Pediatr Endocrinol Metab 29:145–151CrossRefPubMed
30.
Zurück zum Zitat Tesch GH (2008) MCP-1/CCL2: a new diagnostic marker and therapeutic target for progressive renal injury in diabetic nephropathy. Am J Physiol Renal Physiol 294:F697–701CrossRefPubMed Tesch GH (2008) MCP-1/CCL2: a new diagnostic marker and therapeutic target for progressive renal injury in diabetic nephropathy. Am J Physiol Renal Physiol 294:F697–701CrossRefPubMed
31.
Zurück zum Zitat Morii T, Fujita H, Narita T, Shimotomai T, Fujishima H, Yoshioka N, Imai H, Kakei M, Ito S (2003) Association of monocyte chemoattractant protein-1 with renal tubular damage in diabetic nephropathy. J Diabetes Complicat 17:11–15CrossRef Morii T, Fujita H, Narita T, Shimotomai T, Fujishima H, Yoshioka N, Imai H, Kakei M, Ito S (2003) Association of monocyte chemoattractant protein-1 with renal tubular damage in diabetic nephropathy. J Diabetes Complicat 17:11–15CrossRef
32.
Zurück zum Zitat Gupta S, Gambhir JK, Kalra O, Gautam A, Shukla K, Mehndiratta M, Agarwal S, Shukla R (2013) Association of biomarkers of inflammation and oxidative stress with the risk of chronic kidney disease in Type 2 diabetes mellitus in North Indian population. J Diabetes Complicat 27:548–552CrossRef Gupta S, Gambhir JK, Kalra O, Gautam A, Shukla K, Mehndiratta M, Agarwal S, Shukla R (2013) Association of biomarkers of inflammation and oxidative stress with the risk of chronic kidney disease in Type 2 diabetes mellitus in North Indian population. J Diabetes Complicat 27:548–552CrossRef
33.
Zurück zum Zitat Shoukry A, Sel-A Bdeer, El-Sokkary RH (2015) Urinary monocyte chemoattractant protein-1 and vitamin D-binding protein as biomarkers for early detection of diabetic nephropathy in type 2 diabetes mellitus. Mol Cell Biochem 408:25–35CrossRefPubMed Shoukry A, Sel-A Bdeer, El-Sokkary RH (2015) Urinary monocyte chemoattractant protein-1 and vitamin D-binding protein as biomarkers for early detection of diabetic nephropathy in type 2 diabetes mellitus. Mol Cell Biochem 408:25–35CrossRefPubMed
34.
Zurück zum Zitat Zoja C, Benigni A, Remuzzi G (2004) Cellular responses to protein overload: key event in renal disease progression. Curr Opin Nephrol Hypertens 13:31–37CrossRefPubMed Zoja C, Benigni A, Remuzzi G (2004) Cellular responses to protein overload: key event in renal disease progression. Curr Opin Nephrol Hypertens 13:31–37CrossRefPubMed
35.
Zurück zum Zitat Mora C, Navarro JF (2005) The role of inflammation as a pathogenic factor in the development of renal disease in diabetes. Curr Diab Rep 5:399–401CrossRefPubMed Mora C, Navarro JF (2005) The role of inflammation as a pathogenic factor in the development of renal disease in diabetes. Curr Diab Rep 5:399–401CrossRefPubMed
36.
Zurück zum Zitat Bian ZM, Elner SG, Yoshida A, Elner VM (2004) Differential involvement of phosphoinositide 3-kinase/Akt in human RPE MCP-1 and IL-8 expression. Invest Ophthalmol Vis Sci 45:1887–1896CrossRefPubMed Bian ZM, Elner SG, Yoshida A, Elner VM (2004) Differential involvement of phosphoinositide 3-kinase/Akt in human RPE MCP-1 and IL-8 expression. Invest Ophthalmol Vis Sci 45:1887–1896CrossRefPubMed
37.
Zurück zum Zitat Yap HL, Frankel AH, Tam FWK (2017) MCP-1: a potential target for diabetic microvascular complications? Open Urol Nephrol J 5:00171 Yap HL, Frankel AH, Tam FWK (2017) MCP-1: a potential target for diabetic microvascular complications? Open Urol Nephrol J 5:00171
38.
Zurück zum Zitat Ha H, Yu MR, Choi YJ, Kitamura M, Lee HB (2002) Role of high glucose-induced nuclear factor-kappaB activation in monocyte chemoattractant protein-1 expression by mesangial cells. J Am Soc Nephrol 13:894–902PubMed Ha H, Yu MR, Choi YJ, Kitamura M, Lee HB (2002) Role of high glucose-induced nuclear factor-kappaB activation in monocyte chemoattractant protein-1 expression by mesangial cells. J Am Soc Nephrol 13:894–902PubMed
Metadaten
Titel
Association of urinary monocyte chemoattractant protein-1 (MCP-1) and kidney injury molecule-1 (KIM-1) with risk factors of diabetic kidney disease in type 2 diabetes patients
verfasst von
Khalid Siddiqui
Salini Scaria Joy
Khalid Al-Rubeaan
Publikationsdatum
19.06.2019
Verlag
Springer Netherlands
Erschienen in
International Urology and Nephrology / Ausgabe 8/2019
Print ISSN: 0301-1623
Elektronische ISSN: 1573-2584
DOI
https://doi.org/10.1007/s11255-019-02201-6

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