Abstract
Acute kidney injury (AKI) is a common comorbidity, affecting approximately one in five hospitalized adults. The kidney is the site for the production, metabolism or excretion of most hormones, including the production of erythropoietin (EPO), the active form of vitamin D, renin, thrombopoietin, and the excretion of insulin, catecholamines, gastrin and many other hormones. Therefore, it is reasonable to say that AKI can have a considerable impact on the endocrine system. Although the effects of AKI on various parameters, including cardiovascular parameters, serum electrolytes and acid–base disorders, neuro-humoral mechanisms and neurological outcomes have been extensively studied, the endocrinological consequences of AKI are understudied. Thyroid dysfunction, mainly euthyroid sick syndrome, hypo/hyperglycemia, bone mineral disorders, changes in EPO and atrial natriuretic peptide (ANP) levels are commonly found in AKI. EPO, thyroxine and ANP administration have been evaluated as potential tools to prevent or treat AKI with varying success, while the effects of AKI on some key hormones, including cortisol and insulin, have never been studied. Aim of this narrative review is to illustrate what is known and what is not known about the endocrinological outcomes of AKI. Few clinical trials are ongoing: however, there is a clear need for large-scale randomized controlled trials investigating the endocrinological consequences of AKI.
Graphical abstract
Similar content being viewed by others
Data availability
No data are available because this is a narrative review.
References
Susantitaphong P, Cruz DN, Cerda J, Abulfaraj M, Alqahtani F, Koulouridis I et al (2013) World incidence of AKI: a meta-analysis. Clin J Am Soc Nephrol 8(9):1482–1493
Chertow GM, Burdick E, Honour M, Bonventre JV, Bates DW (2005) Acute kidney injury, mortality, length of stay, and costs in hospitalized patients. J Am Soc Nephrol 16(11):3365–3370
Rewa O, Bagshaw SM (2014) Acute kidney injury—epidemiology, outcomes and economics. Nat Rev Nephrol 10(4):193–207
Kellum JA, Romagnani P, Ashuntantang G, Ronco C, Zarbock A, Anders HJ (2021) Acute kidney injury. Nat Rev Dis Primers 7(1):52
Singbartl K, Kellum JA (2012) AKI in the ICU: definition, epidemiology, risk stratification, and outcomes. Kidney Int 81(9):819–825
Villeneuve PM, Clark EG, Sikora L, Sood MM, Bagshaw SM (2016) Health-related quality-of-life among survivors of acute kidney injury in the intensive care unit: a systematic review. Intensive Care Med 42(2):137–146
Stengel B, Metzger M, Combe C, Jacquelinet C, Briançon S, Ayav C et al (2019) Risk profile, quality of life and care of patients with moderate and advanced CKD: the French CKD-REIN Cohort Study. Nephrol Dial Transpl 34(2):277–286
Acharya V, Olivero J (2018) The kidney as an endocrine organ. Methodist Debakey Cardiovasc J 14(4):305–307
Danzi S, Klein I (2003) Thyroid hormone and blood pressure regulation. Curr Hypertens Rep 5(6):513–520
Kotsis V, Alevizaki M, Stabouli S, Pitiriga V, Rizos Z, Sion M et al (2007) Hypertension and hypothyroidism: results from an ambulatory blood pressure monitoring study. J Hypertens 25(5):993–999
Vargas F, Moreno JM, Rodríguez-Gómez I, Wangensteen R, Osuna A, Alvarez-Guerra M et al (2006) Vascular and renal function in experimental thyroid disorders. Eur J Endocrinol 154(2):197–212
Ichihara A, Kobori H, Miyashita Y, Hayashi M, Saruta T (1998) Differential effects of thyroid hormone on renin secretion, content, and mRNA in juxtaglomerular cells. Am J Physiol Endocrinol Metab 274(2):E224–E231
van Hoek I, Daminet S (2009) Interactions between thyroid and kidney function in pathological conditions of these organ systems: a review. Gen Comp Endocrinol 160(3):205–215
Schmid C, Brändle M, Zwimpfer C, Zapf J, Wiesli P (2004) Effect of thyroxine replacement on creatinine, insulin-like growth factor 1, acid-labile subunit, and vascular endothelial growth factor. Clin Chem 50(1):228–231
Wiesli P, Schwegler B, Spinas GA, Schmid C (2003) Serum cystatin C is sensitive to small changes in thyroid function. Clin Chim Acta 338(1–2):87–90
Lo JC, Chertow GM, Go AS, Hsu C-Y (2005) Increased prevalence of subclinical and clinical hypothyroidism in persons with chronic kidney disease. Kidney Int 67(3):1047–1052
Sun MT, Hsiao FC, Su SC, Pei D, Hung YJ (2012) Thyrotropin as an independent factor of renal function and chronic kidney disease in normoglycemic euthyroid adults. Endocr Res 37(3):110–116
Zhang D, Gao L, Ye H, Chi R, Wang L, Hu L et al (2019) Impact of thyroid function on cystatin C in detecting acute kidney injury: a prospective, observational study. BMC Nephrol 20(1):41
Schmid C, Ghirlanda-Keller C, Zwimpfer C, Zoidis E (2012) Triiodothyronine stimulates cystatin C production in bone cells. Biochem Biophys Res Commun 419(2):425–430
Shin DH, Lee MJ, Kim SJ, Oh HJ, Kim HR, Han JH et al (2012) Preservation of renal function by thyroid hormone replacement therapy in chronic kidney disease patients with subclinical hypothyroidism. J Clin Endocrinol Metab 97(8):2732–2740
Iglesias P, Bajo MA, Selgas R, Díez JJ (2017) Thyroid dysfunction and kidney disease: An update. Rev Endocr Metab Disord 18(1):131–144
Weetman AP, Tomlinson K, Amos N, Lazarus JH, Hall R, McGregor AM (1985) Proteinuria in autoimmune thyroid disease. Acta Endocrinol (Copenh) 109(3):341–347
Iglesias P, Olea T, Vega-Cabrera C, Heras M, Bajo MA, del Peso G et al (2013) Thyroid function tests in acute kidney injury. J Nephrol 26(1):164–172
Kaptein EM, Levitan D, Feinstein EI, Nicoloff JT, Massry SG (1981) Alterations of thyroid hormone indices in acute renal failure and in acute critical illness with and without acute renal failure. Am J Nephrol 1(3–4):138–143
Acker CG, Singh AR, Flick RP, Bernardini J, Greenberg A, Johnson JP (2000) A trial of thyroxine in acute renal failure. Kidney Int 57(1):293–298
Acker CG, Flick R, Shapiro R, Scantlebury VP, Jordan ML, Vivas C et al (2002) Thyroid hormone in the treatment of post-transplant acute tubular necrosis (ATN). Am J Transplant 2(1):57–61
Nigwekar SU, Strippoli GF, Navaneethan SD (2013) Thyroid hormones for acute kidney injury. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD006740.pub2
Shakoor MT, Moahi K, Shemin D (2020) Hypothyroidism-induced acute kidney ınjury and hyponatremia. R I Med J 103(7):61–64
Neves PD, Bridi RA, Balbi AL, Ponce D (2013) Hypothyroidism and acute kidney injury: an unusual association. BMJ Case Rep. https://doi.org/10.1136/bcr-2013-200585
Cai Y, Tang L (2013) Rare acute kidney injury secondary to hypothyroidism-induced rhabdomyolysis. Yonsei Med J 54(1):172–176
Ghayur A, Elahi Q, Patel C, Raj R (2021) Rhabdomyolysis-induced acute kidney injury in a patient with non-compliance to levothyroxine therapy. Endocrinol Diabetes Metab Case Rep. https://doi.org/10.1530/EDM-21-0034
Bahlmann FH, Kielstein JT, Haller H, Fliser D (2007) Erythropoietin and progression of CKD. Kidney Int Suppl 107:S21–S25
Hanna RM, Streja E, Kalantar-Zadeh K (2021) Burden of anemia in chronic kidney disease: beyond erythropoietin. Adv Ther 38(1):52–75
Bernhardt WM, Eckardt KU (2008) Physiological basis for the use of erythropoietin in critically ill patients at risk for acute kidney injury. Curr Opin Crit Care 14(6):621–626
Kwak J, Kim JH, Jang HN, Jung MH, Cho HS, Chang SH et al (2020) Erythropoietin ameliorates ıschemia/reperfusion-ınduced acute kidney ınjury via ınflammasome suppression in mice. Int J Mol Sci 21(10):3453
Chou YH, Liao FL, Chen YT, Yeh PY, Liu CH, Shih HM et al (2019) Erythropoietin modulates macrophages but not post-ischemic acute kidney injury in mice. J Formos Med Assoc 118(1 Pt 3):494–503
Nakano M, Satoh K, Fukumoto Y, Ito Y, Kagaya Y, Ishii N et al (2007) Important role of erythropoietin receptor to promote VEGF expression and angiogenesis in peripheral ischemia in mice. Circ Res 100(5):662–669
Sabatino A, Ceresini G, Marina M, Fiaccadori E (2019) Endocrine system in acute kidney injury. In: Rhee CM, Kalantar-Zadeh K, Brent GA (eds) Endocrine disorders in kidney disease: diagnosis and treatment. Springer International Publishing, Cham, pp 321–331
Aoun M, Sleilaty G, Boueri C, Younes E, Gabriel K, Kahwaji RM et al (2022) Erythropoietin in Acute Kidney Injury (EAKI): a pragmatic randomized clinical trial. BMC Nephrol 23(1):100
Kim JH, Shim JK, Song JW, Song Y, Kim HB, Kwak YL (2013) Effect of erythropoietin on the incidence of acute kidney injury following complex valvular heart surgery: a double blind, randomized clinical trial of efficacy and safety. Crit Care 17(5):R254
Oh SW, Chin HJ, Chae DW, Na KY (2012) Erythropoietin improves long-term outcomes in patients with acute kidney injury after coronary artery bypass grafting. J Korean Med Sci 27(5):506–511
Song YR, Lee T, You SJ, Chin HJ, Chae DW, Lim C et al (2009) Prevention of acute kidney injury by erythropoietin in patients undergoing coronary artery bypass grafting: a pilot study. Am J Nephrol 30(3):253–260
Tasanarong A, Duangchana S, Sumransurp S, Homvises B, Satdhabudha O (2013) Prophylaxis with erythropoietin versus placebo reduces acute kidney injury and neutrophil gelatinase-associated lipocalin in patients undergoing cardiac surgery: a randomized, double-blind controlled trial. BMC Nephrol 14:136
Dardashti A, Ederoth P, Algotsson L, Brondén B, Grins E, Larsson M et al (2014) Erythropoietin and protection of renal function in cardiac surgery (the EPRICS trial). Anesthesiology 121(3):582–590
Kim JE, Song SW, Kim JY, Lee HJ, Chung KH, Shim YH (2016) Effect of a single bolus of erythropoietin on renoprotection in patients undergoing thoracic aortic surgery with moderate hypothermic circulatory arrest. Ann Thorac Surg 101(2):690–696
de Seigneux S, Ponte B, Weiss L, Pugin J, Romand JA, Martin PY et al (2012) Epoetin administrated after cardiac surgery: effects on renal function and inflammation in a randomized controlled study. BMC Nephrol 13:132
Corwin HL, Gettinger A, Pearl RG, Fink MP, Levy MM, Shapiro MJ et al (2002) Efficacy of recombinant human erythropoietin in critically ill patients: a randomized controlled trial. JAMA 288(22):2827–2835
Napolitano LM, Fabian TC, Kelly KM, Bailey JA, Block EF, Langholff W et al (2008) Improved survival of critically ill trauma patients treated with recombinant human erythropoietin. J Trauma 65(2):285–297 (discussion 97-9)
Endre ZH, Walker RJ, Pickering JW, Shaw GM, Frampton CM, Henderson SJ et al (2010) Early intervention with erythropoietin does not affect the outcome of acute kidney injury (the EARLYARF trial). Kidney Int 77(11):1020–1030
Zhao C, Lin Z, Luo Q, Xia X, Yu X, Huang F (2015) Efficacy and safety of erythropoietin to prevent acute kidney injury in patients with critical illness or perioperative care: a systematic review and meta-analysis of randomized controlled trials. J Cardiovasc Pharmacol 65(6):593–600
Erben RG (2018) Physiological actions of fibroblast growth factor-23. Front Endocrinol (Lausanne) 9:267
Leaf DE, Wolf M, Stern L (2010) Elevated FGF-23 in a patient with rhabdomyolysis-induced acute kidney injury. Nephrol Dial Transpl 25(4):1335–1337
Zhang M, Hsu R, Hsu CY, Kordesch K, Nicasio E, Cortez A et al (2011) FGF-23 and PTH levels in patients with acute kidney injury: a cross-sectional case series study. Ann Intensive Care 1(1):21
Leaf DE, Wolf M, Waikar SS, Chase H, Christov M, Cremers S et al (2012) FGF-23 levels in patients with AKI and risk of adverse outcomes. Clin J Am Soc Nephrol 7(8):1217–1223
Leaf DE, Christov M, Jüppner H, Siew E, Ikizler TA, Bian A et al (2016) Fibroblast growth factor 23 levels are elevated and associated with severe acute kidney injury and death following cardiac surgery. Kidney Int 89(4):939–948
Chang YH, Wu CH, Chou NK, Tseng LJ, Huang IP, Wang CH et al (2020) High plasma C-terminal FGF-23 levels predict poor outcomes in patients with chronic kidney disease superimposed with acute kidney injury. Ther Adv Chronic Dis 11:2040622320964161
Shaker AM, El Mohamed E, Samir HH, Elnokeety MM, Sayed HA, Ramzy TA (2018) Fibroblast growth factor-23 as a predictor biomarker of acute kidney injury after cardiac surgery. Saudi J Kidney Dis Transpl 29(3):531–539
Gupta KL, Mohanty T, Sood V, Ramachandran R (2020) Study of FGF 23 levels in patients with acute kidney injury and its outcome. Indian J Nephrol 30(4):293–294
Christov M, Waikar SS, Pereira RC, Havasi A, Leaf DE, Goltzman D et al (2013) Plasma FGF23 levels increase rapidly after acute kidney injury. Kidney Int 84(4):776–785
de Oliveira Neves FM, Araújo CB, de Freitas DF, Arruda BFT, de Macêdo Filho LJM, Salles VB et al (2019) Fibroblast growth factor 23, endothelium biomarkers and acute kidney injury in critically-ill patients. J Transl Med 17(1):121
Braun AB, Christopher KB (2013) Vitamin D in acute kidney injury. Inflamm Allergy Drug Targets 12(4):262–272
Levin A, Bakris G, Molitch M, Smulders M, Tian J, Williams L et al (2007) Prevalence of abnormal serum vitamin D, PTH, calcium, and phosphorus in patients with chronic kidney disease: results of the study to evaluate early kidney disease. Kidney Int 71(1):31–38
Vijayan A, Li T, Dusso A, Jain S, Coyne DW (2015) Relationship of 1,25 dihydroxy vitamin D levels to clinical outcomes in critically ıll patients with acute kidney ınjury. J Nephrol Ther 5(1):90
Park JW, Cho JW, Joo SY, Kim CS, Choi JS, Bae EH et al (2012) Paricalcitol prevents cisplatin-induced renal injury by suppressing apoptosis and proliferation. Eur J Pharmacol 683(1–3):301–309
Hu Z, Zhang H, Yi B, Yang S, Liu J, Hu J et al (2020) VDR activation attenuate cisplatin induced AKI by inhibiting ferroptosis. Cell Death Dis 11(1):73
Fayed A, Abdulazim DO, Amin M, Elhadidy S, Samir HH, Salem MM et al (2021) Serum sclerostin in acute kidney injury patients. Nefrologia (Engl Ed). https://doi.org/10.1016/j.nefro.2021.01.010
Seibert E, Radler D, Ulrich C, Hanika S, Fiedler R, Girndt M (2017) Serum klotho levels in acute kidney injury. Clin Nephrol 87(4):173–179
Neyra JA, Li X, Mescia F, Ortiz-Soriano V, Adams-Huet B, Pastor J et al (2019) Urine klotho ıs lower in critically ıll patients with versus without acute kidney ınjury and associates with major adverse kidney events. Crit Care Explor 1(6):e0016
Conger JD, Falk SA, Hammond WS (1991) Atrial natriuretic peptide and dopamine in established acute renal failure in the rat. Kidney Int 40(1):21–28
Roy DR (1986) Effect of synthetic ANP on renal and loop of Henle functions in the young rat. Am J Physiol 251(2 Pt 2):F220–F225
Mitaka C, Ohnuma T, Murayama T, Kunimoto F, Nagashima M, Takei T et al (2017) Effects of low-dose atrial natriuretic peptide infusion on cardiac surgery-associated acute kidney injury: a multicenter randomized controlled trial. J Crit Care 38:253–258
Swärd K, Valsson F, Odencrants P, Samuelsson O, Ricksten SE (2004) Recombinant human atrial natriuretic peptide in ischemic acute renal failure: a randomized placebo-controlled trial. Crit Care Med 32(6):1310–1315
Moriyama T, Hagihara S, Shiramomo T, Nagaoka M, Iwakawa S, Kanmura Y (2017) The protective effect of human atrial natriuretic peptide on renal damage during cardiac surgery. J Anesth 31(2):163–169
Kurnik BR, Allgren RL, Genter FC, Solomon RJ, Bates ER, Weisberg LS (1998) Prospective study of atrial natriuretic peptide for the prevention of radiocontrast-induced nephropathy. Am J Kidney Dis 31(4):674–680
Yamada H, Doi K, Tsukamoto T, Kiyomoto H, Yamashita K, Yanagita M et al (2019) Low-dose atrial natriuretic peptide for prevention or treatment of acute kidney injury: a systematic review and meta-analysis. Crit Care 23(1):41
Salzberg SP, Filsoufi F, Anyanwu A, von Harbou K, Gass A, Pinney SP et al (2005) High-risk mitral valve surgery: perioperative hemodynamic optimization with nesiritide (BNP). Ann Thorac Surg 80(2):502–506
Beaver TM, Winterstein AG, Shuster JJ, Gerhard T, Martin T, Alexander JA et al (2006) Effectiveness of nesiritide on dialysis or all-cause mortality in patients undergoing cardiothoracic surgery. Clin Cardiol 29(1):18–24
Fiaccadori E, Sabatino A, Morabito S, Bozzoli L, Donadio C, Maggiore U et al (2016) Hyper/hypoglycemia and acute kidney injury in critically ill patients. Clin Nutr 35(2):317–321
Stamou SC, Nussbaum M, Carew JD, Dunn K, Skipper E, Robicsek F et al (2011) Hypoglycemia with intensive insulin therapy after cardiac surgery: predisposing factors and association with mortality. J Thorac Cardiovasc Surg 142(1):166–173
Guimarães SM, Lima EQ, Cipullo JP, Lobo SM, Burdmann EA (2008) Low insulin-like growth factor-1 and hypocholesterolemia as mortality predictors in acute kidney injury in the intensive care unit. Crit Care Med 36(12):3165–3170
Liu P, Feng Y, Dong D, Liu X, Chen Y, Wang Y et al (2016) Enhanced renoprotective effect of IGF-1 modified human umbilical cord-derived mesenchymal stem cells on gentamicin-induced acute kidney injury. Sci Rep 6:20287
Friedlaender M, Popovtzer MM, Weiss O, Nefesh I, Kopolovic J, Raz I (1995) Insulin-like growth factor-1 (IGF-1) enhances recovery from HgCl2-induced acute renal failure: the effects on renal IGF-1, IGF-1 receptor, and IGF-binding protein-1 mRNA. J Am Soc Nephrol 5(10):1782–1791
Goes N, Urmson J, Vincent D, Ramassar V, Halloran PF (1996) Effect of recombinant human insulin-like growth factor-1 on the inflammatory response to acute renal injury. J Am Soc Nephrol 7(5):710–720
Imberti B, Morigi M, Tomasoni S, Rota C, Corna D, Longaretti L et al (2007) Insulin-like growth factor-1 sustains stem cell mediated renal repair. J Am Soc Nephrol 18(11):2921–2928
Wu Z, Yu Y, Niu L, Fei A, Pan S (2016) IGF-1 protects tubular epithelial cells during injury via activation of ERK/MAPK signaling pathway. Sci Rep 6:28066
Ficek R, Kokot F, Chudek J, Adamczak M, Ficek J, Wiecek A (2004) Plasma leptin concentration in patients with acute renal failure. Clin Nephrol 62(2):84–91
Li S, Zhuang K, He Y, Deng Y, Xi J, Chen J (2022) Leptin relieves ischemia/reperfusion induced acute kidney injury through inhibiting apoptosis and autophagy. Zhong Nan Da Xue Xue Bao Yi Xue Ban 47(1):8–17
Jin X, Chen J, Hu Z, Chan L, Wang Y (2013) Genetic deficiency of adiponectin protects against acute kidney injury. Kidney Int 83(4):604–614
Cheng CF, Lian WS, Chen SH, Lai PF, Li HF, Lan YF et al (2012) Protective effects of adiponectin against renal ischemia-reperfusion injury via prostacyclin-PPARα-heme oxygenase-1 signaling pathway. J Cell Physiol 227(1):239–249
Ahn SW, Kim TY, Lee S, Jeong JY, Shim H, Han YM et al (2016) Adrenal insufficiency presenting as hypercalcemia and acute kidney injury. Int Med Case Rep J 9:223–226
Si J, Ge Y, Zhuang S, Wang LJ, Chen S, Gong R (2013) Adrenocorticotropic hormone ameliorates acute kidney injury by steroidogenic-dependent and -independent mechanisms. Kidney Int 83(4):635–646
Funding
No funding agency granted the present study.
Author information
Authors and Affiliations
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical statement
This article does not contain any studies with human participants performed by any of the authors.
Research involving human participants and/or animals.
(1) Statement of human rights. (2) Statement on the welfare of animals. This article does not contain any studies with human participants or animals performed by any of the authors.
Informed consent
No verbal and written informed consent was necessary for this study.
Additional information
Publisher's Note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Copur, S., Demiray, A., Basile, C. et al. Endocrinological disorders in acute kidney injury: an often overlooked field of clinical research. J Nephrol 36, 885–893 (2023). https://doi.org/10.1007/s40620-022-01554-z
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s40620-022-01554-z