The role of hormones in renal disease and ischemia-reperfusion injury

Document Type: Review Article


1 Social Determinants of Health (SDH) Research Center, Ardabil University of Medical Sciences, Ardabil, Iran

2 Department of Physiology, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran

3 Department of Biochemistry, School of Medicine, Ardabil University of Medical Sciences, Ardabil, Iran


The patients with renal diseases, especially end-stage renal disease (ESRD), are at high risk of developing cardiovascular disturbances. Some hormones such as brain natriuretic peptide appear to be important serum biomarkers in predicting cardiac death in ESRD patients. Renal diseases cause inflammation, anemia, uremic toxins, fluid overload, and electrolyte disturbance. Kidney transplantation is considered the choice treatment for patients with ESRD. Ischemia-reperfusion (IR), which occurs during renal transplantation is one of the factors that affect the outcome of renal transplantation. Renal graft rejection is the result of IR injury and there is no effective treatment to prevent IR injury. Reperfusion after ischemia may cause injury through generation of reactive oxygen and nitrogen species, inflammatory responses by increased levels of tumor necrosis factor-α (TNF-α) and interleukins (IL), and apoptotic processes, and leads to acute kidney injury (AKI). Thus, antioxidant, anti-apoptotic and anti-inflammatory hormones, which inhibit these pathways, can protect against IR injury and improve transplanted renal function in patients with ESRD.


Main Subjects

1. Xiao X, Tang R, Zhou X, Peng L, Yu P. Aldosterone induces NRK‑52E cell apoptosis in acute kidney injury via rno‑miR‑203 hypermethylation and Kim-1 upregulation. Exp Ther Med 2016; 12:915-924.
2. Gülçin I. Antioxidant activity of food constituents: an overview. Arch Toxikol 2012; 86:345-391.
3. Bursal E, Köksal E, Gülçin İ, Bilsel G, Gören AC. Antioxidant activity and polyphenol content of cherry stem (Cerasus avium L.) determined by LC–MS/MS. Food Res Int 2013; 51:66-74.
4. Souza PC, Santos EBd, Motta GL, Bona SR, Schaefer PG, Campagnol D, et al. Combined effects of melatonin and topical hypothermia on renal ischemia-reperfusion injury in rats. Acta Cir Bras 2018; 33:197-206.
5. Banaei S. Novel role of microRNAs in renal ischemia reperfusion injury. Ren Fail 2015; 37:1073-1079.
6. Cullingford TE, Wait R, Clerk A, Sugden PH. Effects of oxidative stress on the cardiac myocyte proteome: modifications to peroxiredoxins and small heat shock proteins. J Mol Cell Cardiol 2006; 40:157-172.
7. Wang AY-M, Lam CW-K, Chan IH-S, Wang M, Lui S-F, Sanderson JE. Sudden cardiac death in end-stage renal disease patients: a 5-year prospective analysis. Hypertension 2010; 56:210-216.
8. Aygen B, Dogukan A, Dursun F, Aydin S, Kilic N, Sahpaz F, et al. Ghrelin and obestatin levels in end-stage renal disease. J Int Med Res 2009; 37:757-765.
9. Koç M, Kumral ZNÖ, Özkan N, Memi G, Kaçar Ö, Bilsel S, et al. Obestatin improves ischemia/reperfusion-induced renal injury in rats via its antioxidant and anti-apoptotic effects: Role of the nitric oxide. Peptides 2014; 60:23-31.
10. Zhang W, Shu L. Upregulation of miR-21 by Ghrelin ameliorates ischemia/reperfusion-induced acute kidney injury by inhibiting inflammation and cell apoptosis. DNA Cell Biol 2016; 35:417-425.
11. Lian M, Hewitson TD, Wigg B, Samuel CS, Chow F, Becker GJ. Long-term mineralocorticoid receptor blockade ameliorates progression of experimental diabetic renal disease. Nephrol Dial Transplant 2011; 27:906-912.
12. Volpe M. Natriuretic peptides and cardio-renal disease. Int J Cardiol 2014; 176:630-639.
13. Möllsten A, Svensson M, Waernbaum I, Berhan Y, Schön S, Nyström L, et al. Cumulative risk, age at onset and sex-specific differences for developing end-stage renal disease in young patients with type 1 diabetes. A nationwide population based cohort study. Diabetes 2010;59:1803-1808.
14. Herrera VL, Pasion KA, Moran AM, Ruiz-Opazo N. Worse renal disease in postmenopausal F2 [Dahl S x R]-intercross rats: Detection of Novel QTLs affecting hypertensive kidney disease. PloS one 2013; 8:e56096.
15. Patil CN, Wallace K, LaMarca BD, Moulana M, Lopez-Ruiz A, Soljancic A, et al. Low-dose testosterone protects against renal ischemia-reperfusion injury by increasing renal IL-10-to-TNF-α ratio and attenuating T-cell infiltration. Am J Physiol Renal Physiol 2016; 311:F395-F403.
16. Wetmore JB, Quarles LD. Calcimimetics or vitamin D analogs for suppressing parathyroid hormone in end-stage renal disease: time for a paradigm shift? Nat Clin Pract Nephrol 2009; 5:24-33.
17. Gade K, Blaschke S, Rodenbeck A, Becker A, Anderson-Schmidt H, Cohrs S. Uremic restless legs syndrome (RLS) and sleep quality in patients with end-stage renal disease on hemodialysis: potential role of homocysteine and parathyroid hormone. Kidney Blood Press Res 2013; 37:458-463.
18. Nitta K. Vascular calcification in patients with chronic kidney disease. Ther Apher Dial 2011; 15:513-521.
19. Omland T, Hagve T-A. Natriuretic peptides: physiologic and analytic considerations. Heart Fail Clin 2009; 5:471-487.
20. Spanaus K-S, Kronenberg F, Ritz E, Schlapbach R, Fliser D, Hersberger M, et al. B-type natriuretic peptide concentrations predict the progression of nondiabetic chronic kidney disease: the mild-to-moderate kidney disease study. Clin Chem 2007; 53:1264-1272.
21. Gerbes AL, Vollmar AM, Kiemer AK, Bilzer M. The guanylate cyclase–coupled natriuretic peptide receptor: a new target for prevention of cold ischemia–reperfusion damage of the rat liver. Hepatology 1998; 28:1309-1317.
22. Yasuda K, Kimura T, Sasaki K, Obi Y, Iio K, Yamato M, et al. Plasma B-type natriuretic peptide level predicts kidney prognosis in patients with predialysis chronic kidney disease. Nephrol Dial Transplant 2012; 27:3885-3891.
23. Connell JM, Whitworth JA, Davies DL, Lever AF, Richards AM, Fraser R. Effects of ACTH and cortisol administration on blood pressure, electrolyte metabolism, atrial natriuretic peptide and renal function in normal man. J Hypertens 1987; 5:425-433.
24. Raff H, Trivedi H. Circadian rhythm of salivary cortisol, plasma cortisol, and plasma ACTH in end-stage renal disease. Endocr Connect 2012;2:23-31.
25. Arregger AL, Cardoso EM, Tumilasci O, Contreras LN. Diagnostic value of salivary cortisol in end stage renal disease. Steroids 2008; 73:77-82.
26. Gulcin I, Buyukokuroglu ME, Oktay M, Kufrevioglu OI. On the in vitro antioxidative properties of melatonin. J Pineal Res 2002; 33:167-171.
27. Gulcin İ, Buyukokuroglu ME, Kufrevioglu OI. Metal chelating and hydrogen peroxide scavenging effects of melatonin. J Pineal Res 2003; 34:278-281.
28. Beydemİr Sü, Gülçİn İ. Effects of melatonin on carbonic anhydrase from human erythrocytes in vitro and from rat erythrocytes in vivo. J Enzyme Inhib Med Chem 2004; 19:193-197.
29. Ahmadiasl N, Banaei S, Alihemmati A. Combination antioxidant effect of erythropoietin and melatonin on renal ischemia-reperfusion injury in rats. Iran J Basic Med Sci 2013; 16:1209-1216.
30. Lüdemann P, Zwernemann S, Lerchl A. Clearance of melatonin and 6‐sulfatoxymelatonin by hemodialysis in patients with end‐stage renal disease. J Pineal Res 2001; 31:222-227.
31. Wong HS-C, Chang C-M, Kao C-C, Hsu Y-W, Liu X, Chang W-C, et al. VJ combinations of T-cell receptor predict responses to erythropoietin in end-stage renal disease patients. J Biomed Sci 2017; 24:43.
32. Ahmadiasl N, Banaei S, Alihemati A, Baradaran B, Azimian E. Effect of a combined treatment with erythropoietin and melatonin on renal ischemia reperfusion injury in male rats. Clin Exp Nephrol 2014; 18:855-864.
33. Georgatzakou HT, Tzounakas VL, Kriebardis AG, Velentzas AD, Papageorgiou EG, Voulgaridou AI, et al. Pathophysiological aspects of red blood cells in end‐stage renal disease patients resistant to recombinant human erythropoietin therapy. Eur J Haematol 2017; 98:590-600.
34. Steinbrook R. Lower Erythropoietin Doses and Medicare Payment Reform: Win-Wins for Patients With End-stage Renal Disease. JAMA Intern Med 2016; 176:1749-1751.
35. Tong F, Tang X, Li X, Xia W, Liu D. The effect of insulin-loaded linear poly (ethylene glycol)-brush-like poly (l-lysine) block copolymer on renal ischemia/reperfusion-induced lung injury through downregulating hypoxia-inducible factor. Int J Nanomedicine 2016; 11:1717-1730.
36. Idorn T, Knop FK, Jørgensen M, Holst JJ, Hornum M, Feldt-Rasmussen B. Postprandial responses of incretin and pancreatic hormones in non-diabetic patients with end-stage renal disease. Nephrol Dial Transplant 2013; 29:119-127.
37. Emlet DR, Pastor-Soler N, Marciszyn A, Wen X, Gomez H, Humphries IV WH, et al. Insulin-like growth factor binding protein 7 and tissue inhibitor of metalloproteinases-2: differential expression and secretion in human kidney tubule cells. Am J Physiol Renal Physiol 2016; 312:F284-F296.
38. Harada N, Zhao J, Kurihara H, Nakagata N, Okajima K. Stimulation of FcγRI on primary sensory neurons increases insulin-like growth factor-I production, thereby reducing reperfusion-induced renal injury in mice. J Immunol 2010;185:1303-1310.