Top

16-05-2024 | Acute Kidney Injury | Original Article

Impacts of age, type 2 diabetes, and hypertension on circulating neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 after prolonged work in the heat in men

Authors: Ben J. Lee, Tessa R. Flood, Sophie L. Russell, James J. McCormick, Naoto Fujii, Glen P. Kenny

Published in: European Journal of Applied Physiology

Abstract

Purpose

Prolonged work in the heat increases the risk of acute kidney injury (AKI) in young men. Whether aging and age-associated chronic disease may exacerbate the risk of AKI remains unclear.

Methods

We evaluated plasma neutrophil gelatinase-associated lipocalin (NGAL) and serum kidney injury molecule-1 (KIM1) before and after 180 min of moderate-intensity work (200 W/m²) in temperate (wet-bulb globe temperature [WBGT] 16 °C) and hot (32 °C) environments in healthy young (n = 13, 22 years) and older men (n = 12, 59 years), and older men with type 2 diabetes (T2D; n = 9, 60 years) or hypertension (HTN; n = 9, 60 years).

Results

There were no changes in NGAL or KIM1 concentrations following prolonged work in temperate conditions in any group. Despite a similar work tolerance, the relative change in NGAL was greater in the older group when compared to the young group following exercise in the hot condition (mean difference + 82 ng/mL; p < 0.001). Baseline concentrations of KIM1 were ~ 22 pg/mL higher in the older relative to young group, increasing by ~ 10 pg/mL in each group after exercise in the heat (both p ≤ 0.03). Despite a reduced work tolerance in the heat in older men with T2D (120 ± 40 min) and HTN (108 ± 42 min), elevations in NGAL and KIM1 were similar to their healthy counterparts.

Conclusion

Age may be associated with greater renal stress following prolonged work in the heat. The similar biomarker responses in T2D and HTN compared to healthy older men, alongside reduced exercise tolerance in the heat, suggest these individuals may exhibit greater vulnerability to heat-induced AKI if work is prolonged.

Aengevaeren VL et al (2019) Exercise-induced cardiac troponin I increase and incident mortality and cardiovascular events. Circulation 140(10):804–814. https://doi.org/10.1161/CIRCULATIONAHA.119.041627CrossRefPubMed

Alis R, Sanchis-Gomar F, Primo-Carrau C, Lozano-Calve S, Dipalo M, Aloe, Blesa RJ, Romagnoli R, Lippi G (2014) Hemoconcentration induced by exercise: revisiting the Dill and Costill equation. Scand J Medi Sci Sports. https://doi.org/10.1111/sms.1239CrossRef

Anderson BG, Bell ML (2009) Weather-related mortality: how heat, cold, and heat waves affect mortality in the United States. Epidemiology 20(2):205–213. https://doi.org/10.1097/EDE.0B013E318190EE08CrossRefPubMedPubMedCentral

Atkins RC (2005) The epidemiology of chronic kidney disease. Kidney Int Suppl 67(94):S14–S18. https://doi.org/10.1111/J.1523-1755.2005.09403.XCrossRef

Bakris GL, Ritz E (2009) The message for World Kidney Day 2009: hypertension and kidney disease: a marriage that should be prevented. Kidney Int 75(5):449–452. https://doi.org/10.1038/KI.2008.694CrossRefPubMed

Begg DP (2017) Disturbances of thirst and fluid balance associated with aging. Physiol Behav 178:28–34. https://doi.org/10.1016/J.PHYSBEH.2017.03.003CrossRefPubMed

Carter R et al (2005) Epidemiology of hospitalizations and deaths from heat illness in soldiers. Med Sci Sports Exerc 37(8):1338–1344. https://doi.org/10.1249/01.MSS.0000174895.19639.EDCrossRefPubMed

Centre for Disease Control (2012) Older employees in the workplace. Centers for Disease Control and Prevention, Atlanta, Ga., USA. Doc 1 p6

Chapman CL et al (2019) Soft drink consumption during and following exercise in the heat elevates biomarkers of acute kidney injury. Am J Physiol Regul Integr Comp Physiol 316:R189–R198 (Preprint)CrossRefPubMed

Chapman CL et al (2020) Both hyperthermia and dehydration during physical work in the heat contribute to the risk of acute kidney injury. J Appl Physiol 128(4):715–728. https://doi.org/10.1152/japplphysiol.00787.2019CrossRefPubMedPubMedCentral

Chapman CL et al (2021) Kidney physiology and pathophysiology during heat stress and the modification by exercise, dehydration, heat acclimation and aging. Temperature 8(2):108–159. https://doi.org/10.1080/23328940.2020.1826841CrossRef

Chawla LS et al (2014) Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med 371(1):58–66. https://doi.org/10.1056/NEJMRA1214243CrossRefPubMedPubMedCentral

Denic A et al (2017) The substantial loss of nephrons in healthy human kidneys with aging. J Am Soc Nephrol JASN 28(1):313–320. https://doi.org/10.1681/ASN.2016020154CrossRefPubMed

Du Bois D, Du Bois EF (1916) Clinical calorimetry: a formula to the estimate the approximate surface area if height and weight be known. Arch Intern Med XVII(6_2):863–871. https://doi.org/10.1001/ARCHINTE.1916.00080130010002CrossRef

Ebi KL et al (2021) Hot weather and heat extremes: health risks. Lancet 398(10301):698–708. https://doi.org/10.1016/S0140-6736(21)01208-3CrossRefPubMed

Emlet DR et al (2017) 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 312(2):F284–F296. https://doi.org/10.1152/AJPRENAL.00271.2016CrossRefPubMed

Endre ZH, Pickering JW (2014) Cell cycle arrest biomarkers win race for AKI diagnosis. Nat Rev Nephrol 10(12):683–685. https://doi.org/10.1038/nrneph.2014.198CrossRefPubMed

Flouris AD et al (2018) Workers’ health and productivity under occupational heat strain: a systematic review and meta-analysis. Lancet Planet Health 2(12):e521–e531. https://doi.org/10.1016/S2542-5196(18)30237-7CrossRefPubMed

Gasparrini A, Guo Y, Hashizume M, Lavigne E, Zanobetti A, Schwartz J, Tobias A, Tong S, Rocklöv J, Forsberg B, Leone M, De Sario M, Bell ML, Leon Guo L, Wu CF, Kan H, Yi SM, De Sousa M, Paulo Nascimento H, Honda Y, Kim Ho, Armstrong B (2015) Mortality risk attributable to high and low ambient temperature: a multicountry observational study. Lancet (london, England) 386(9991):464–465. https://doi.org/10.1016/S0140-6736(14)62114-0CrossRef

Glodny B et al (2009) Normal kidney size and its influencing factors—a 64-slice MDCT study of 1.040 asymptomatic patients. BMC Urol 9(1):1–13. https://doi.org/10.1186/1471-2490-9-19/TABLES/3CrossRef

Haase M et al (2009) Accuracy of neutrophil gelatinase-associated lipocalin (NGAL) in diagnosis and prognosis in acute kidney injury: a systematic review and meta-analysis. Am J Kidney Dis 54(6):1012–1024CrossRefPubMed

Heung M, Chawla LS (2014) Acute kidney injury: gateway to chronic kidney disease. Nephron Clin Pract 127(1–4):30–34. https://doi.org/10.1159/000363675CrossRefPubMed

Ho CW et al (1997) Age, fitness, and regional blood flow during exercise in the heat. J Appl Physiol 82(4):1126–1135. https://doi.org/10.1152/JAPPL.1997.82.4.1126/ASSET/IMAGES/LARGE/JAPP0543205.JPEGCrossRefPubMed

Ho J et al (2015) Urinary, plasma, and serum biomarkers’ utility for predicting acute kidney injury associated with cardiac surgery in adults: a meta-analysis. Am J Kidney Dis 66(6):993–1005. https://doi.org/10.1053/j.ajkd.2015.06.018CrossRefPubMed

Honda T, Manjourides J, Suh H (2019) Daily ambient temperature is associated with biomarkers of kidney injury in older Americans. Environ Res. https://doi.org/10.1016/j.envres.2019.108790CrossRefPubMedPubMedCentral

Houser MC et al (2023) Inflammatory profiles, gut microbiome, and kidney function are impacted after high-fidelity firefighter training. Int J Hygiene Environ Health. https://doi.org/10.1016/J.IJHEH.2022.114107CrossRef

Ichimura T 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):4135–4142. https://doi.org/10.1074/JBC.273.7.4135CrossRefPubMed

Johnson ACM, Zager RA (2018) Mechanisms underlying increased TIMP2 and IGFBP7 urinary excretion in experimental AKI. J Am Soc Nephrol JASN 29(8):2157–2167. https://doi.org/10.1681/ASN.2018030265CrossRefPubMed

Johnson RJ, Wesseling C, Newman LS (2019) Chronic kidney disease of unknown cause in agricultural communities. N Engl J Med 380(19):1843–1852. https://doi.org/10.1056/NEJMRA1813869CrossRefPubMed

Junglee NA et al (2013) Exercising in a hot environment with muscle damage: effects on acute kidney injury biomarkers and kidney function. Am J Physiol Renal Physiol 305(6):F813–F820CrossRefPubMed

Kashani K, Cheungpasitporn W, Ronco C (2017) Biomarkers of acute kidney injury: the pathway from discovery to clinical adoption. Clin Chem Lab Med 55(8):1074–1089. https://doi.org/10.1515/cclm-2016-0973CrossRefPubMed

Kellum JA et al (2013) Diagnosis, evaluation, and management of acute kidney injury: a KDIGO summary (part 1). Crit Care (london, England). https://doi.org/10.1186/CC11454CrossRefPubMedCentral

Kenney WL, Ho CW (1995) Age alters regional distribution of blood flow during moderate-intensity exercise. J Appl Physiol 79(4):1112–1119. https://doi.org/10.1152/JAPPL.1995.79.4.1112CrossRefPubMed

Kenny GP et al (2010) Heat stress in older individuals and patients with common chronic diseases. CMAJ 182(10):1053–1060. https://doi.org/10.1503/CMAJ.081050CrossRefPubMedPubMedCentral

Kenny GP et al (2013) Older adults with type 2 diabetes store more heat during exercise. Med Sci Sports Exerc 45(10):1906–1914. https://doi.org/10.1249/MSS.0b013e3182940836CrossRefPubMed

Kenny GP, Groeller H et al (2016a) Age, human performance, and physical employment standards. Appl Physiol Nutr Metab 41(6):S92–S107. https://doi.org/10.1139/APNM-2015-0483/ASSET/IMAGES/LARGE/APNM-2015-0483F3.JPEGCrossRefPubMed

Kenny GP, Poirier MP et al (2016b) Hyperthermia and cardiovascular strain during an extreme heat exposure in young versus older adults. Temperature 4(1):79–88. https://doi.org/10.1080/23328940.2016.1230171CrossRef

Koyner JL, Parikh CR (2013) Clinical utility of biomarkers of AKI in cardiac surgery and critical illness. Clin J Am Soc Nephrol CJASN 8(6):1034–1042. https://doi.org/10.2215/CJN.05150512CrossRefPubMed

Larose J et al (2013) Whole body heat loss is reduced in older males during short bouts of intermittent exercise. Am J Physiol Regul Integr Comp Physiol 305(6):R619–R629. https://doi.org/10.1152/AJPREGU.00157.2013CrossRefPubMed

Levey AS et al (2009) A new equation to estimate glomerular filtration rate. Ann Intern Med 150(9):604–612. https://doi.org/10.7326/0003-4819-150-9-200905050-00006CrossRefPubMedPubMedCentral

Levi M, Kjellstrom T, Baldasseroni A (2018) Impact of climate change on occupational health and productivity: a systematic literature review focusing on workplace heat. Med Lav 109(3):163–179. https://doi.org/10.23749/mdl.v109i3.6851CrossRefPubMedPubMedCentral

Malhotra R, Siew ED (2017) Biomarkers for the early detection and prognosis of acute kidney injury. Clin J Am Soc Nephrol CJASN 12(1):149–173. https://doi.org/10.2215/CJN.01300216CrossRefPubMed

Mansour SG et al (2017) Kidney injury and repair biomarkers in Marathon runners. Am J Kidney Dis 70(2):252. https://doi.org/10.1053/J.AJKD.2017.01.045CrossRefPubMedPubMedCentral

McCormick JJ et al (2022) The serum irisin response to prolonged physical activity in temperate and hot environments in older men with hypertension or type 2 diabetes. J Therm Biol. https://doi.org/10.1016/j.jtherbio.2022.103344CrossRefPubMed

Meade RD et al (2016) The physical demands of electrical utilities work in North America. J Occup Environ Hyg 13(1):60–70. https://doi.org/10.1080/15459624.2015.1077966CrossRefPubMed

Meade RD et al (2017) The physiological strain incurred during electrical utilities work over consecutive work shifts in hot environments: a case report. J Occup Environ Hyg 14(12):986–994. https://doi.org/10.1080/15459624.2017.1365151CrossRefPubMed

Meade RD et al (2019) Interactive effects of age and hydration state on human thermoregulatory function during exercise in hot-dry conditions. Acta Physiol. https://doi.org/10.1111/APHA.13226CrossRef

Mehta RL et al (2007) Acute kidney injury network: report of an initiative to improve outcomes in acute kidney injury. Crit Care (london, England). https://doi.org/10.1186/CC5713CrossRef

Narang BJ et al (2020) A tool to explore discrete-time data: the time series response analyser. Int J Sport Nutr Exerc Metab 30(5):374–381. https://doi.org/10.1123/IJSNEM.2020-0150CrossRefPubMed

Nejat M et al (2012) Some biomarkers of acute kidney injury are increased in pre-renal acute injury. Kidney Int 81(12):1254. https://doi.org/10.1038/KI.2012.23CrossRefPubMedPubMedCentral

Nickolas TL et al (2008) Sensitivity and specificity of a single emergency department measurement of urinary neutrophil gelatinase-associated lipocalin for diagnosing acute kidney injury. Ann Intern Med 148(11):810–819. https://doi.org/10.7326/0003-4819-148-11-200806030-00003CrossRefPubMedPubMedCentral

Notley SR et al (2021) Heat tolerance and occupational heat exposure limits in older men with and without type 2 diabetes or hypertension. Med Sci Sports Exerc 53(10):2196–2206. https://doi.org/10.1249/MSS.0000000000002698CrossRefPubMed

Notley SR et al (2022) Heat tolerance and the validity of occupational heat exposure limits in women during moderate-intensity work. Appl Physiol Nutr Metab 47(7):711–724. https://doi.org/10.1139/APNM-2022-0003CrossRefPubMed

O’Sullivan ED, Hughes J, Ferenbach DA (2017) Renal aging: causes and consequences. J Am Soc Nephrol JASN 28(2):407. https://doi.org/10.1681/ASN.2015121308CrossRefPubMed

Romanello M et al (2021) The 2021 report of the Lancet Countdown on health and climate change: code red for a healthy future. Lancet (london, England) 398(10311):1619–1662. https://doi.org/10.1016/S0140-6736(21)01787-6CrossRefPubMed

Sabbisetti VS et al (2014) Blood kidney injury molecule-1 is a biomarker of acute and chronic kidney injury and predicts progression to ESRD in type I diabetes. J Am Soc Nephrol 25(10):2177–2186. https://doi.org/10.1681/ASN.2013070758/-/DCSUPPLEMENTALCrossRefPubMedPubMedCentral

Schlader ZJ et al (2017) Firefighter work duration influences the extent of acute kidney injury. Med Sci Sports Exerc 49(8):1745–1753CrossRefPubMed

Schlader ZJ et al (2019) The potential for renal injury elicited by physical work in the heat. Nutrients. https://doi.org/10.3390/NU11092087CrossRefPubMedPubMedCentral

Schrezenmeier EV et al (2017) Biomarkers in acute kidney injury—pathophysiological basis and clinical performance. Acta Physiol (oxford, England) 219(3):554–572. https://doi.org/10.1111/APHA.12764CrossRef

Singh A et al (2016) Heat and PAHs emissions in indoor kitchen air and its impact on kidney dysfunctions among kitchen workers in Lucknow, North India. PLoS ONE 11(2):e0148641. https://doi.org/10.1371/JOURNAL.PONE.0148641CrossRefPubMedPubMedCentral

Stapleton JM et al (2013) Do older adults experience greater thermal strain during heat waves? Appl Physiol Nutr Metab 39(3):292–298CrossRefPubMed

Statistics Canada (2011) Portrait of Canada’s labour force. Government of Canada, Ottawa

Tawatsupa B et al (2012) Association between occupational heat stress and kidney disease among 37,816 workers in the Thai Cohort Study (TCS). J Epidemiol 22(3):251–260. https://doi.org/10.2188/JEA.JE20110082CrossRefPubMedPubMedCentral

Tidbury N et al (2019) Neutrophil gelatinase-associated lipocalin as a marker of postoperative acute kidney injury following cardiac surgery in patients with preoperative kidney impairment. Cardiovasc Hematol Disord Drug Targets 19(3):239–248. https://doi.org/10.2174/1871529X19666190415115106CrossRefPubMed

Wesseling C et al (2015) Mesoamerican nephropathy: geographical distribution and time trends of chronic kidney disease mortality between 1970 and 2012 in Costa Rica. Occup Environ Med 72(10):714–721CrossRefPubMed

Witzgall R et al (1994) Localization of proliferating cell nuclear antigen, vimentin, c-Fos, and clusterin in the postischemic kidney. Evidence for a heterogenous genetic response among nephron segments, and a large pool of mitotically active and dedifferentiated cells. J Clin Investig 93(5):2175–2188. https://doi.org/10.1172/JCI117214CrossRefPubMedPubMedCentral

Yardley JE et al (2013) Do heat events pose a greater health risk for individuals with type 2 diabetes? Diabetes Technol Ther 15(6):520–529CrossRefPubMed

Yu SMW, Bonventre JV (2018) Acute kidney injury and progression of diabetic kidney disease. Adv Chronic Kidney Dis 25(2):166–180. https://doi.org/10.1053/J.ACKD.2017.12.005CrossRefPubMedPubMedCentral

Title: Impacts of age, type 2 diabetes, and hypertension on circulating neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 after prolonged work in the heat in men
Authors: Ben J. Lee
Tessa R. Flood
Sophie L. Russell
James J. McCormick
Naoto Fujii
Glen P. Kenny
Publication date: 16-05-2024
Publisher: Springer Berlin Heidelberg
Keywords: Acute Kidney Injury
Acute Kidney Injury
Type 2 Diabetes
Hypertension
Hypertension
Kidney Injury
Published in: European Journal of Applied Physiology
Print ISSN: 1439-6319
Electronic ISSN: 1439-6327
DOI: https://doi.org/10.1007/s00421-024-05505-3

EASD 2024

Springer Medicine

Impacts of age, type 2 diabetes, and hypertension on circulating neutrophil gelatinase-associated lipocalin and kidney injury molecule-1 after prolonged work in the heat in men

Abstract

Purpose

Methods

Results

Conclusion

EASD 2024

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusion

Please log in to get access to this content