Gender and sex in the development and progression of renal diseases
DOI:
https://doi.org/10.33393/gcnd.2023.2627Keywords:
Gender, CKD, Renal disease progression, Estradiol, TestosteroneAbstract
Sex-based disparities in nephrology have been a historically understudied area.
In nephrology, gender differences exist with regard to the epidemiology, evolution and prognosis of chronic kidney disease (CKD). In some cases, these differences run contrary to the general population trends. We discuss such gender and sex disparities, including differing impact of traditional and novel risk factors, as well as hormonal factors, all of them potentially influencing propensity, progression and biochemical and psychological aspects of CKD. The factors involved in this gender disparity may include diet, kidney and glomerular size, differences in glomerular hemodynamics, and the direct effects of sex hormones.
The progression rate of many renal diseases is affected by sex. In polycystic kidney disease, membranous nephropathy, immunoglobulin A nephropathy, and “chronic renal disease of unknown etiology,” men progress at a faster rate to end-stage renal failure than do women. In many, but not all, animal models of renal disease, estrogens slow progression rate. Animal and experimental studies have tried to offer further mechanistic explanations for gender differences in disease progression. It has been suggested that the gender dimorphism of CKD progression may represent the effects of the interaction of circulating steroids with specific kidney receptors. Endogenous estrogens have in general been considered to have anti-fibrotic and anti-apoptotic effects on the kidney. On the other hand, the faster kidney function decline in men has been attributed to the specific pro-apoptotic and profibrotic properties of androgens.
Downloads
References
García GG, Iyengar A, Kaze F, Kierans C, Padilla-Altamira C, Luyckx VA. Sex and gender differences in chronic kidney disease and access to care around the globe. Semin Nephrol. 2022;42(2):101-113. https://doi.org/10.1016/j.semnephrol.2022.04.001 PMID:35718358 DOI: https://doi.org/10.1016/j.semnephrol.2022.04.001
Carrero JJ, Hecking M, Ulasi I, Sola L, Thomas B. Chronic Kidney Disease, Gender, and Access to Care: A Global Perspective. Semin Nephrol. 2017;37(3):296-308. https://doi.org/10.1016/j.semnephrol.2017.02.009 PMID:28532558 DOI: https://doi.org/10.1016/j.semnephrol.2017.02.009
Katz-Greenberg G, Shah S. Sex and Gender Differences in Kidney Transplantation. Semin Nephrol. 2022;42(2):219-229. https://doi.org/10.1016/j.semnephrol.2022.04.011 PMID:35718368 DOI: https://doi.org/10.1016/j.semnephrol.2022.04.011
Wolfe RA, Ashby VB, Milford EL, et al. Differences in access to cadaveric renal transplantation in the United States. Am J Kidney Dis. 2000;36(5):1025-1033. https://doi.org/10.1053/ajkd.2000.19106 PMID:11054361 DOI: https://doi.org/10.1053/ajkd.2000.19106
Rolón L, Hsu RK. Adding CKD to the Alphabet Soup: A Snapshot of Kidney Health in the LGBTQ+ Population. J Am Soc Nephrol. 2023;34(4):523-525. https://doi.org/10.1681/ASN.0000000000000103 PMID:37000952 DOI: https://doi.org/10.1681/ASN.0000000000000103
Caceres BA, Sharma Y, Doan D. Hypertension risk in sexual and gender minority individuals. Expert Rev Cardiovasc Ther. 2022;20(5):339-341. https://doi.org/10.1080/14779072.2022.2075345 DOI: https://doi.org/10.1080/14779072.2022.2075345
Beach LB, Elasy TA, Gonzales G. Prevalence of Self-Reported Diabetes by Sexual Orientation: Results from the 2014 Behavioral Risk Factor Surveillance System. LGBT Health. 2018;5(2):121-130. https://doi.org/10.1089/lgbt.2017.0091 PMID:29377760 DOI: https://doi.org/10.1089/lgbt.2017.0091
Mohottige D, Lunn MR. Ensuring Gender-Affirming Care in Nephrology: Improving Care for Transgender and Gender-Expansive Individuals. Clin J Am Soc Nephrol. 2020;15(8):1195-1197. https://doi.org/10.2215/CJN.14471119 PMID:32139362 DOI: https://doi.org/10.2215/CJN.14471119
Lane PH. Estrogen receptors in the kidney: lessons from genetically altered mice. Gend Med. 2008;5(suppl A):S11-S18. https://doi.org/10.1016/j.genm.2008.03.003 PMID:18395676 DOI: https://doi.org/10.1016/j.genm.2008.03.003
Neugarten J, Kasiske B, Silbiger SR, Nyengaard JR. Effects of sex on renal structure. Nephron J. 2002;90(2):139-144. https://doi.org/10.1159/000049033 PMID:11818696 DOI: https://doi.org/10.1159/000049033
Ciarambino T, Crispino P, Giordano M. Gender and Renal Insufficiency: Opportunities for Their Therapeutic Management? Cells. 2022;11(23):382. https://doi.org/10.3390/cells11233820 PMID:36497080 DOI: https://doi.org/10.3390/cells11233820
Conte C, Antonelli G, Melica ME, Tarocchi M, Romagnani P, Peired AJ. Role of Sex Hormones in Prevalent Kidney Diseases. Int J Mol Sci. 2023;24(9):8244. https://doi.org/10.3390/ijms24098244 PMID:37175947 DOI: https://doi.org/10.3390/ijms24098244
Valdivielso JM, Jacobs-Cachá C, Soler MJ. Sex hormones and their influence on chronic kidney disease. Curr Opin Nephrol Hypertens. 2019;28(1):1-9. https://doi.org/10.1097/MNH.0000000000000463 PMID:30320621 DOI: https://doi.org/10.1097/MNH.0000000000000463
Brar A, Markell M. Impact of gender and gender disparities in patients with kidney disease. Curr Opin Nephrol Hypertens. 2019;28(2):178-182. https://doi.org/10.1097/MNH.0000000000000482 PMID:30652978 DOI: https://doi.org/10.1097/MNH.0000000000000482
Neugarten J, Golestaneh L. Gender and the prevalence and progression of renal disease. Adv Chronic Kidney Dis. 2013;20(5):390-395. https://doi.org/10.1053/j.ackd.2013.05.004 PMID:23978543 DOI: https://doi.org/10.1053/j.ackd.2013.05.004
Zdunek M, Silbiger S, Lei J, Neugarten J. Protein kinase CK2 mediates TGF-beta1-stimulated type IV collagen gene transcription and its reversal by estradiol. Kidney Int. 2001;60(6):2097-2108. https://doi.org/10.1046/j.1523-1755.2001.00041.x PMID:11737584 DOI: https://doi.org/10.1046/j.1523-1755.2001.00041.x
Neugarten J, Golestaneh L. Influence of sex on the progression of Chronic kidney disease. Mayo Clin Proc. 2019;94(7):1339-1356. https://doi.org/10.1016/j.mayocp.2018.12.024 PMID:31272577 DOI: https://doi.org/10.1016/j.mayocp.2018.12.024
Doublier S, Lupia E, Catanuto P, et al. Testosterone and 17β-estradiol have opposite effects on podocyte apoptosis that precedes glomerulosclerosis in female estrogen receptor knockout mice. Kidney Int. 2011;79(4):404-413. https://doi.org/10.1038/ki.2010.398 PMID:20962747 DOI: https://doi.org/10.1038/ki.2010.398
Neugarten J, Silbiger SR, Golestaneh L. Gender and kidney disease. In: Brenner BM, ed. Brenner and Rector’s The Kidney. 9th ed. Elsevier; 2008:674-680.
Kang AK, Miller JA. Effects of gender on the renin-angiotensin system, blood pressure, and renal function. Curr Hypertens Rep. 2002;4(2):143-151. https://doi.org/10.1007/s11906-002-0039-9 PMID:11884270 DOI: https://doi.org/10.1007/s11906-002-0039-9
Hu J, Tan S, Zhong Y. Effects of testosterone on renal function in salt-loaded rats. Am J Med Sci. 2011;342(1):38-43. https://doi.org/10.1097/MAJ.0b013e31820f835b PMID:21537151 DOI: https://doi.org/10.1097/MAJ.0b013e31820f835b
James GD, Sealey JE, Müller F, Alderman M, Madhavan S, Laragh JH. Renin relationship to sex, race and age in a normotensive population. J Hypertens Suppl. 1986;4(5):S387-S389. PMID:3553481
Klein SL, Flanagan KL. Sex differences in immune responses. Nat Rev Immunol. 2016;16(10):626-638. https://doi.org/10.1038/nri.2016.90 PMID:27546235 DOI: https://doi.org/10.1038/nri.2016.90
Sciarra F, Campolo F, Franceschini E, Carlomagno F, Venneri MA. Gender-Specific Impact of Sex Hormones on the Immune System. Int J Mol Sci. 2023;24(7):6302. https://doi.org/10.3390/ijms24076302 PMID:37047274 DOI: https://doi.org/10.3390/ijms24076302
Moulton VR. Sex Hormones in acquired immunity and autoimmune disease. Front Immunol. 2018;9:2279. https://doi.org/10.3389/fimmu.2018.02279 PMID:30337927 DOI: https://doi.org/10.3389/fimmu.2018.02279
Mills KT, Xu Y, Zhang W, et al. A systematic analysis of worldwide population-based data on the global burden of chronic kidney disease in 2010. Kidney Int. 2015;88(5):950-957. https://doi.org/10.1038/ki.2015.230 PMID:26221752 DOI: https://doi.org/10.1038/ki.2015.230
Carrero JJ, Hecking M, Chesnaye NC, Jager KJ. Sex and gender disparities in the epidemiology and outcomes of chronic kidney disease. Nat Rev Nephrol. 2018;14(3):151-164. https://doi.org/10.1038/nrneph.2017.181 PMID:29355169 DOI: https://doi.org/10.1038/nrneph.2017.181
Kramer A, Boenink R, Stel VS, et al. The ERA-EDTA Registry Annual Report 2018: a summary. Clin Kidney J. 2020;14(1):107-123. https://doi.org/10.1093/ckj/sfaa271 PMID:33564410 DOI: https://doi.org/10.1093/ckj/sfaa271
Suzuki Y, Monteiro RC, Coppo R, Suzuki H. The Phenotypic Difference of IgA Nephropathy and its Race/Gender-dependent Molecular Mechanisms. Kidney360. 2021;2(8):1339-1348. https://doi.org/10.34067/KID.0002972021 PMID:35369654 DOI: https://doi.org/10.34067/KID.0002972021
Cattran DC, Reich HN, Beanlands HJ, Miller JA, Scholey JW, Troyanov S; Genes, Gender and Glomerulonephritis Group. The impact of sex in primary glomerulonephritis. Nephrol Dial Transplant. 2008;23(7):2247-2253. https://doi.org/10.1093/ndt/gfm919 PMID:18182409 DOI: https://doi.org/10.1093/ndt/gfm919
Kovesdy CP. Epidemiology of chronic kidney disease: an update 2022. Kidney Int Suppl (2011). 2022;12(1):7-11. https://doi.org/10.1016/j.kisu.2021.11.003 PMID:35529086 DOI: https://doi.org/10.1016/j.kisu.2021.11.003
Chesnaye NC, Dekker FW, Evans M, et al. Renal function decline in older men and women with advanced chronic kidney disease-results from the EQUAL study. Nephrol Dial Transplant. 2021;36(9):1656-1663. https://doi.org/10.1093/ndt/gfaa095 PMID:32591814 DOI: https://doi.org/10.1093/ndt/gfaa095
Santoro A, Gibertoni D, Rucci P, et al. The PIRP project (Prevenzione Insufficienza Renale Progressiva): how to integrate hospital and community maintenance treatment for chronic kidney disease. J Nephrol. 2019;32(3):417-427. https://doi.org/10.1007/s40620-018-00570-2 PMID:30659519 DOI: https://doi.org/10.1007/s40620-018-00570-2
Swartling O, Rydell H, Stendahl M, Segelmark M, Trolle Lagerros Y, Evans M. CKD Progression and Mortality Among Men and Women: A Nationwide Study in Sweden. Am J Kidney Dis. 2021;78(2):190-199.e1. https://doi.org/10.1053/j.ajkd.2020.11.026 PMID:33434591 DOI: https://doi.org/10.1053/j.ajkd.2020.11.026
Neugarten J, Acharya A, Silbiger SR. Effect of gender on the progression of nondiabetic renal disease: a meta-analysis. J Am Soc Nephrol. 2000;11(2):319-329. https://doi.org/10.1681/ASN.V112319 PMID:10665939 DOI: https://doi.org/10.1681/ASN.V112319
Ricardo AC, Yang W, Sha D, et al; CRIC Investigators. Sex-Related Disparities in CKD Progression. J Am Soc Nephrol. 2019;30(1):137-146. https://doi.org/10.1681/ASN.2018030296 PMID:30510134 DOI: https://doi.org/10.1681/ASN.2018030296
Jafar TH, Schmid CH, Stark PC, et al. The rate of progression of renal disease may not be slower in women compared with men: a patient-level meta-analysis. Nephrol Dial Transplant. 2003;18(10):2047-2053. https://doi.org/10.1093/ndt/gfg317 PMID:13679479 DOI: https://doi.org/10.1093/ndt/gfg317
Nakamura I, Iwase H, Arai K, et al. Detection of gender difference and epitope specificity of IgG antibody activity against IgA1 hinge portion in IgA nephropathy patients by using synthetic hinge peptide and glycopeptide probes. Nephrology (Carlton). 2004;9(1):26-30. https://doi.org/10.1111/j.1440-1797.2003.00225.x PMID:14996305 DOI: https://doi.org/10.1111/j.1440-1797.2003.00225.x
Deng W, Tan X, Zhou Q, et al. Gender-related differences in clinicopathological characteristics and renal outcomes of Chinese patients with IgA nephropathy. BMC Nephrol. 2018;19(1):31. https://doi.org/10.1186/s12882-018-0829-1 PMID:29415664 DOI: https://doi.org/10.1186/s12882-018-0829-1
Riispere Ž, Laurinavičius A, Kuudeberg A, et al. IgA nephropathy clinicopathologic study following the Oxford classification: progression peculiarities and gender-related differences. Medicina (Kaunas). 2016;52(6):340-348. https://doi.org/10.1016/j.medici.2016.11.003 PMID:27932191 DOI: https://doi.org/10.1016/j.medici.2016.11.003
Lee H, Yoo KD, Oh YK, et al. Predictors of Relapse in Adult-Onset Nephrotic Minimal Change Disease. Medicine (Baltimore). 2016;95(12):e3179. https://doi.org/10.1097/MD.0000000000003179 PMID:27015208 DOI: https://doi.org/10.1097/MD.0000000000003179
Moroni G, Gallelli B, Quaglini S, Banfi G, Montagnino G, Messa P. Long-term outcome of renal transplantation in adults with focal segmental glomerulosclerosis. Transpl Int. 2010;23(2):208-216. https://doi.org/10.1111/j.1432-2277.2009.00977.x PMID:19793073 DOI: https://doi.org/10.1111/j.1432-2277.2009.00977.x
Beckwith H, Lightstone L, McAdoo S. Sex and gender in Glomerular disease. Semin Nephrol. 2022;42(2):185-196. https://doi.org/10.1016/j.semnephrol.2022.04.008 PMID:35718365 DOI: https://doi.org/10.1016/j.semnephrol.2022.04.008
Downloads
Published
How to Cite
Issue
Section
Categories
License
Copyright (c) 2023 The authors
This work is licensed under a Creative Commons Attribution-NonCommercial 4.0 International License.
Authors contributing to Giornale di Clinica Nefrologica e Dialisi (GCND) agree to publish their articles under the CC-BY-NC 4.0 license, which allows third parties to re-use the work without permission as long as the work is properly referenced and the use is non-commercial.
Accepted 2023-08-22
Published 2023-09-26
