Serum Relaxin and Renal Vascular Resistance in Diabetic and Non-Diabetic Patients with Different Grades of Chronic Kidney Disease

Ehab Abdelatti¹, Tarek E. Korah¹, Alaa Dawood^1, , Ahmed Ragheb¹, Waleed M. Fathy², Waleed Mousa³ and Ashraf Anas Zytoon³

¹Internal Medicine Department, Faculty of Medicine, Menoufiya University, Egypt

²Clinical Pathology Department, Faculty of Medicine, Menoufiya University, Egypt

³Radiology Department, Faculty of Medicine, Menoufiya University, Egypt

Cite this paper:
Ehab Abdelatti, Tarek E. Korah, Alaa Dawood, Ahmed Ragheb, Waleed M. Fathy, Waleed Mousa and Ashraf Anas Zytoon. Serum Relaxin and Renal Vascular Resistance in Diabetic and Non-Diabetic Patients with Different Grades of Chronic Kidney Disease. American Journal of Medical Sciences and Medicine. 2013; 1(6):114-119. doi: 10.12691/ajmsm-1-6-4

Abstract

Objectives: To evaluate serum relaxin and renal vascular resistance in diabetic and non-diabetic patients with different grades of chronic kidney disease and to correlate serum relaxin to various clinical and Doppler renal hemodynamic parameters. Materials and methods: Sixty patients with chronic kidney disease were divided into two groups: group 1 (30 patients with creatinine clearance of less than 30 ml/minute), and group 2 (30 patients with creatinine clearance of more than 30 ml/minute). Twelve patients (40%) had diabetes mellitus type 2 in group 1 and 18 (60%) in group 2. In addition, group 3 (20 healthy controls), compatible for age and gender, was included. Resistive index and pulsatility index were measured by Doppler ultrasonography of renal arteries. Serum relaxin was measured with ELISA method, and correlated with clinical and Doppler parameters. Results: Serum relaxin levels of groups 1 and 2 were significantly lower than group 3 and that of group 1 were significantly lower than group 2. Resistive index and pulsatility index of groups 1 and 2 were significantly higher than group 3, but there was no significant difference between group 1 and 2. There was an inverse correlation between serum relaxin levels, and serum creatinine in groups 1 and 2. In contrast, there was a positive correlation between serum relaxin and creatinine clearance in groups 1 and 2. There was an inverse correlation between serum relaxin levels, and both resistive index and pulsatility index, in group 2 but not in group 1. Finally, serum relaxin was significantly lower in diabetic compared to non-diabetic patients. Conclusions: We found that serum relaxin levels are significantly lower in patients with advanced stages of chronic kidney disease, as well as, in diabetic compared to non-diabetic patients. Also, serum relaxin is negatively correlated with patients’ age, resistive index and pulsatility index in patients with chronic kidney disease.

Keywords:
relaxin diabetes mellitus renal vascular resistance diabetic nephropathy

This work is licensed under a Creative Commons Attribution 4.0 International License. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/

Figures

References:

[1]	Sherwood OD. Relaxin’s physiological roles and other diverse actions. Endocr Rev 2004; 25: 205-234.
[2]	Bathgate RAD, Hsueh AJ, Sherwood OD. Physiology and molecular biology of the relaxin peptide family. In: Knobil E, Neill JD, eds. Physiology of reproduction, 3rd ed. San Diego: Elsevier 2006; 679-770.
[3]	Samuel CS, Hewitson TD. Relaxin in cardiovascular and renal disease. Kidney Int 2006; 69: 1498-1502.
[4]	Nistri S, Bigazzi M, Bani D. Relaxin as a cardiovascular hormone: physiology, pathophysiology and therapeutic promises. Cardiovasc Hematol Agents Med Chem 2007; 5: 101-108.
[5]	Garber SL, Mirochnik Y, Brecklin CS, et al. Relaxin decreases renal interstitial fibrosis and slows progression of renal disease. Kidney Int. 2001; 59: 876-882.
[6]	Robert G. Bennett. Relaxin and its role in the development and treatment of fibrosis. Transl Res. 2009; 154 (1): 1-6.
[7]	Samuel CS, Hewitson TD. Relaxin and the progression of kidney disease. Curr Opin Nephrol Hypertens. 2009 Jan; 18 (1): 9-14.
[8]	Conrad KP. Mechanisms of renal vasodilation and hyperfiltration during pregnancy. J Soc Gynecol Invest 2004; 11: 438-448.
[9]	Platt JF, Ellis JH, Rubin JM, et al. Intrarenal arterial Doppler sonography in the detection of renal vein thrombosis of the native kidney. Am J Roengenol 1994; 162: 1367-1370.
[10]	Petersen LJ, Petersen JR, Ladefoged SD, et al. The pulsatility index and the resistive index in renal arteries in patients with hypertension and chronic kidney disease. Nephrol Dial Transplant 1995; 10: 2060-2064.
[11]	Asbun J, Villarreal FJ. The pathogenesis of myocardial fibrosis in the setting of diabetic cardiomyopathy. J Am Coll Cardiol 2006; 47: 693-700.
[12]	Svensson M, Sundkvist G, Arnqvist HJ, Björk E, Blohmé G, Bolinder J, Henricsson M, Nyström L, Torffvit O, Waernbaum I, Ostman J, Eriksson JW. Signs of nephropathy may occur early in young adults with diabetes despite modern diabetes management: results from the nationwide population-based Diabetes Incidence Study in Sweden (DISS). Diabetes Care 2003; 26: 2903-2909.
[13]	Uhlig K, Macleod A, Craig J, et al. Grading evidence and recommendations for clinical practice guidelines in nephrology. A position statement from Kidney Disease: Improving Global Outcomes (KDIGO). Kidney Int 2006; 70: 2058-2065.
[14]	Hall ML. Serum Relaxin Concentrations in Systemic Sclerosis. Br. J. Pharmacol, 2007; 150: 677.
[15]	Ikee R, Kobayashi S, Hemmi N, et al. Correlation between the resistive index by Doppler ultrasound and kidney function and histology. Am J Kidney Dis 2005; 46: 603-609.
[16]	Wynn TA. Common and unique mechanisms regulate fibrosis in various fibroproliferative diseases. J Clin Invest 2007; 117: 524-529.
[17]	Bell DS. Treatment of heart failure in patients with diabetes: clinical update. Ethn Dis 2002; 12 (suppl 1): S12-S18.
[18]	Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. The Collaborative Study Group. N Engl J Med 1993; 329: 1456-1462.
[19]	Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat M-L, Gabbiani G. The Myofibroblast: One Function, Multiple Origins. Am J Pathol. 2007; 170: 1807-16.
[20]	McDonald GA, Sarkar P, Rennke H, Unemori E, Kalluri R, Sukhatme VP. Relaxin increases ubiquitin-dependent degradation of fibronectin in vitro and ameliorates renal fibrosis in vivo. Am J Physiol Renal Physiol. 2003; 285: F 59-67.
[21]	Heeg MH, Koziolek MJ, Vasko R, Schaefer L, Sharma K, Muller GA, et al. The antifibrotic effects of relaxin in human renal fibroblasts are mediated in part by inhibition of the S mad 2 pathway. Kidney Int. 2005; 68: 96-109.
[22]	Masterson R, Hewitson TD, Kelynack K, Martic M, Parry L, Bathgate R, et al. Relaxin down-regulates renal fibroblast function and promotes matrix remodelling in vitro. Nephrol Dial Transplant. 2004; 19: 544-52.
[23]	Mookerjee I, Hewitson TD, Halls ML, Summers RJ, Mathai ML, Bathgate RAD, et al. Relaxin inhibits renal myofibroblast differentiation via RXFP1, the nitric oxide pathway, and S mad 2. FASEB J. 2008: 120857.
[24]	Szepietowska B, Gorska M, Szelachowska M. Plasma relaxin concentration is related to beta-cell function and insulin sensitivity in women with type 2 diabetes mellitus. Diabetes research and clinical practice 2008: 79: e1-e3.
[25]	Samuel CS, Unemori EN, Mookerjee I, Bathgate RA, Layfield SL, Mak J, Tregear GW, Du XJ. Relaxin modulates cardiac fibroblast proliferation, differentiation and collagen production and reverses cardiac fibrosis in vivo. Endocrinology 2004; 145: 4125-4133.
[26]	Chen S, Jim B, Ziyadeh FNDiabetic nephropathy and transforming growth factor-beta: transforming our view of glomerulosclerosis and fibrosis build-up. Semin Nephrol. 2003 Nov; 23 (6): 532-43.
[27]	Erikson MS, Unemori EN 2001 Relaxin clinical trials in systemic sclerosis. In: Tregear GW, Ivell R, Bathgate RA, Wade JD, eds. Relaxin 2000: Proceedings of the Third International Conference on Relaxin and Related Peptides. Amsterdam: Kluwer; 373-381.
[28]	Van Drongelen J, Ploemen IH, Pertijs J, et al. Aging attenuates the vasodilator response to relaxin. Am J Physiol Heart Circ Physiol. 2011; 300 (5): H1609-H1615.
[29]	Petersen LJ, Petersen JR, Talleruphuus U, et al. The pulsatility index and the resistive index in renal arteries. Associations with long-term progression in chronic kidney disease. Nephrol Dial Transplant 1997; 12: 1376-1380.
[30]	Debrah DO, Conrad KP, Jeyabalan A, et al. Relaxin increases cardiac output and reduces systemic arterial load in hypertensive rats. Hypertension 2005; 46: 745-750.
[31]	Jeyabalan A, Novak J, Danielson L, et al. Essential role for vascular gelatinase in relaxin-induced renal vasodilation, hyperfiltration and reduced myogenic reactivity of small arteries. Circ Res 2003; 93: 1249-1257.
[32]	Conrad KP, Novak J. Emerging role of relaxin in renal and cardiovascular function. Am J Physiol Regul Integr Comp Physiol 2004; 287: 250-261.