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Functional and structural changes of the kidneys associated with aging and chronic kidney disease
https://doi.org/10.30629/0023-2149-2026-104-1-17-26
Abstract
Currently, the world is seeing an increase in life expectancy. As we age, the human body undergoes various functional and structural changes, and the kidney is no exception. We also know that the prevalence of chronic kidney disease increases with age. The changes that accompany natural aging and chronic kidney disease are similar. However, it is necessary to understand which elderly person is healthy and which has a disease and requires help. Today, thanks to kidney transplantation, when a “zero” biopsy is taken, we have a large database of kidney tissue, as well as instrumental and laboratory examination data. The advantage is that donors are extremely healthy people. As a result, we have the opportunity to study the physiology of natural kidney aging. The review article includes articles published only in peer-reviewed scientific journals, posted in the bibliographic databases MEDLINE, PubMed, Google Scholar, Scopus, eLIBRARY. The search strategy was a search query for the key terms “renal aging”, “glomerular filtration rate”, “number of nephrons”, “nephrosclerosis”. As a result, the review presents data on the main functional (changes in the total glomerular filtration rate and the glomerular filtration rate of one glomerulus) and structural (changes in the volume of renal tissue, the number of nephrons) changes that accompany kidney aging. The question of diagnosing chronic kidney disease in the elderly is also considered.
About the Authors
T. S. Ryabova
Military Medical Academy named after S.M. Kirov of the Ministry of Defense of the Russia
Russian Federation
Russian Federation
Tatiana S. Ryabova — Doctor of Medical Science, Associate Professor at the department of nephrology and efferent therapy
St. Petersburg
A. N. Belskykh
Military Medical Academy named after S.M. Kirov of the Ministry of Defense of the Russia
Russian Federation
Russian Federation
Andrey N. Belskykh — Doctor of Medical Science, Professor, head of the department of nephrology and efferent therapy
St. Petersburg
References
1. GBD 2021 Demographics Collaborators. Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950-2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021. Lancet. 2024;403(10440):1989–2056. DOI: 10.1016/S0140-6736(24)00476-8
2. López-Otín C., Blasco M.A.., Partridge L, Serrano M., Kroemer G. Hallmarks of aging: An expanding universe. Cell. 2023;186(2):243– 278. DOI: 10.1016/j.cell.2022.11.001
3. Delanaye P., Cavalier E., Pottel H., Stehlé T. New and old GFR equations: a European perspective. Clinical Kidney Journal. 2023;16(9):1375–1383. DOI: https://DOI.org/10.1093/ckj/sfad039
4. Gaillard F., Courbebaisse M., Kamar N., Rostaing L., Del Bello A., Girerd S. et al. The age-calibrated measured glomerular filtration rate improves living kidney donation selection process. Kidney Int. 2018;94(3):616–624. DOI: 10.1016/j.kint.2018.05.016
5. Glassock R.J., Rule A.D. The implications of anatomical and functional changes of the aging kidney: with an emphasis on the glomeruli. Kidney Int. 2012;82:270–277. DOI: 10.1038/ki.2012.65
6. Guppy M., Thomas E.T., Glasziou P., Clark J., Jones M., O’Hara D.V., Doust J. Rate of decline in kidney function with age: a systematic review. BMJ Open. 2024;14(11):e089783. DOI: 10.1136/bmjopen-2024-089783
7. Eriksen B.O., Palsson R., Ebert N., Melsom T., van der Giet M., Gudnason V. et al. GFR in Healthy Aging: an Individual Participant Data Meta-Analysis of Iohexol Clearance in European Population-Based Cohorts. J. Am. Soc. Nephrol. 2020;31(7):1602-1615. DOI: 10.1681/ ASN.2020020151
8. Hinchliffe S.A., Sargent P.H., Howard C.V., Chan Y.F., van Velzen D. Human intrauterine renal growth expressed in absolute number of glomeruli assessed by the disector method and Cavalieri principle. Lab. Investig. 1991;64:777–784.
9. Ryan D., Sutherland M.R., Flores T.J., Kent A.L., Dahlstrom J.E., Puelles V.G. et al. Development of the Human Fetal Kidney from Mid to Late Gestation in Male and Female Infants. EBioMedicine. 2018;27:275–283. DOI: 10.1016/j.ebiom.2017.12.016
10. Schreuder M.F. Safety in glomerular numbers. Pediatr. Nephrol. 2012;27(10):1881–1887. DOI: 10.1007/s00467-012-2169-x
11. Charlton J.R., Baldelomar E.J., Hyatt D.M., Bennett K.M. Nephron number and its determinants: a 2020 update. Pediatr. Nephrol. 2021;36(4):797–807. DOI: 10.1007/s00467-020-04534-2
12. Nyengaard J.R., Bendtsen T.F. Glomerular number and size in relation to age, kidney weight, and body surface in normal man. Anat. Rec. 1992;232(2):194–201. DOI: 10.1002/ar.1092320205
13. Hoy W.E., Douglas-Denton R.N., Hughson M.D., Cass A., Johnson K., Bertram J.F. A stereological study of glomerular number and volume: preliminary findings in a multiracial study of kidneys at autopsy. Kidney Int. Suppl. 2003;(83):S31–37. DOI: 10.1046/j.1523-1755.63.s83.8.x
14. Puelles V.G., Hoy W.E., Hughson M.D., Diouf B., Douglas-Denton R.N., Bertram J.F. Glomerular number and size variability and risk for kidney disease. Curr. Opin. Nephrol. Hypertens. 2011;20(1):7– 15. DOI: 10.1097/MNH.0b013e3283410a7d
15. Tain Y.L., Hsu CN. Preterm Birth and Kidney Health: From the Womb to the Rest of Life. Children (Basel). 2024;11(10):1213. DOI: 10.3390/children11101213
16. Hughson M.D., Douglas-Denton R., Bertram J.F., Hoy W.E. Hypertension, glomerular number, and birth weight in African Americans and white subjects in the southeastern United States. Kidney Int. 2006;69(4):671–678. DOI: 10.1038/sj.ki.5000041
17. Hughson M., Farris A.B., Douglas-Denton R., Hoy W.E., Bertram J.F. Glomerular number and size in autopsy kidneys: The relationship to birth weight. Kidney Int. 2003;63:2113–2122. DOI: 10.1046/j.1523-1755.2003.00018.x
18. Piras D., Masala M., Delitala A., Urru S.A.M., Curreli N., Balaci L. et al. Kidney size in relation to ageing, gender, renal function, birthweight and chronic kidney disease risk factors in a general population. Nephrol. Dial. Transplant. 2020;35(4):640–647. DOI: 10.1093/ ndt/gfy270
19. Wang X., Vrtiska T.J., Avula R.T., Walters L.R., Chakkera H.A., Kremers W.K. et al. Age, kidney function, and risk factors associate differently with cortical and medullary volumes of the kidney. Kidney Int. 2014;85(3):677–85. DOI: 10.1038/ki.2013.359
20. Denic A., Lieske J.C., Chakkera H.A., Poggio E.D., Alexander M.P., Singh P. et al. The Substantial loss of nephrons in healthy human kidneys with aging. J. Am. Soc. Nephrol. 2017;28(1):313–320. DOI: 10.1681/ASN.2016020154
21. Okabayashi Y., Tsuboi N., Kanzaki G., Sasaki T., Haruhara K., Koike K. et al. Aging vs. hypertension: an autopsy study of sclerotic renal histopathological lesions in adults with normal renal function. Am. J. Hypertens 2019;32:676–83. DOI: 10.1093/ajh/hpz040
22. Asghar M.S., Denic A., Mullan A.F., Moustafa A., Barisoni L., Alexander M.P. et al. Age-Based versus young-adult thresholds for nephrosclerosis on kidney biopsy and prognostic implications for CKD. J. Am. Soc. Nephrol. 2023;34(8):1421–1432. DOI: 10.1681/ASN.0000000000000171
23. Rule A.D., Amer H., Cornell L.D., Taler S.J, Cosio F.G., Kremers W.K. et al. The association between age and nephrosclerosis on renal biopsy among healthy adults. Ann. Intern. Med. 2010;152(9):561– 567. DOI: 10.7326/0003-4819-152-9-201005040-00006
24. Haruhara K., Kanzaki G., Sasaki T., Hatanaka S., Okabayashi Y., Puelles V.G. et al. Associations between nephron number and podometrics in human kidneys. Kidney Int. 2022;102(5):1127–1135. DOI: 10.1016/j.kint.2022.07.028
25. Samuel T., Hoy W.E., Douglas-Denton R., Hughson M.D., Bertram J.F. Determinants of glomerular volume in different cortical zones of the human kidney. J. Am. Soc. Nephrol. 2005;16(10):3102– 3109. DOI: 10.1681/ASN.2005010123
26. Hughson M.D., Hoy W.E., Bertram J.F. Progressive Nephron Loss in Aging Kidneys: Clinical-Structural Associations Investigated by Two Anatomical Methods. Anat. Rec. (Hoboken). 2020;303(10):2526– 2536. DOI: 10.1002/ar.24249
27. Denic A., Mathew J., Nagineni V.V., Thompson R.H., Leibovich B.C., Lerman L.O. et al. Clinical and pathology findings associate consistently with larger glomerular volume. J. Am. Soc. Nephrol. 2018;29(7):1960–1969. DOI: 10.1681/ASN.2017121305
28. Steffes M.W., Barbosa J., Basgen J.M., Sutherland D.E., Najarian J.S., Mauer S.M. Quantitative glomerular morphology of the normal human kidney. Lab. Invest. 1983;49(1):82–6.
29. Kanzaki G., Tsuboi N., Utsunomiya Y., Ikegami M., Shimizu A., Hosoya T. Distribution of glomerular density in different cortical zones of the human kidney. Pathol. Int. 2013;63(3):169–75. DOI: 10.1111/pin.12044
30. Denic A., Ricaurte L., Lopez C.L., Narasimhan R., Lerman L.O., Lieske J.C.et al. Glomerular volume and glomerulosclerosis at different depths within the human kidney. J. Am. Soc. Nephrol. 2019;30(8):1471–1480. DOI: 10.1681/ASN.2019020183
31. Molema G., Aird W.C. Vascular heterogeneity in the kidney. Semin. Nephrol. 2012;32(2):145–155. DOI: 10.1016/j.semnephrol.2012.02.001
32. Miura K. Tunica intima compensation for reduced stiffness of the tunica media in aging renal arteries as measured with scanning acoustic microscopy. PLoS One. 2020;15(11):e0234759. DOI: 10.1371/journal.pone.0234759
33. Cortinovis M., Perico N., Ruggenenti P., Remuzzi A., Remuzzi G. Glomerular hyperfiltration. Nat. Rev. Nephrol. 2022;18(7):435–451. DOI: 10.1038/s41581-022-00559-y
34. Saxena A.B., Myers B.D., Derby G., Blouch K.L., Yan J., Ho B., Tan J.C. Adaptive hyperfiltration in the aging kidney after contralateral nephrectomy. Am. J. Physiol. Renal. Physiol. 2006;291(3):F62– 634. DOI: 10.1152/ajprenal.00329.2005
35. Lenihan C.R., Busque S., Derby G., Blouch K., Myers B.D., Tan J.C. Longitudinal study of living kidney donor glomerular dynamics after nephrectomy. J. Clin. Invest. 2015;125(3):1311–8. DOI: 10.1172/JCI78885
36. Kanbay M., Copur S. Bakir C.N., Covic A., Ortiz A., Tuttle K.R. Glomerular hyperfiltration as a therapeutic target for CKD. Nephrol. Dial. Transplant. 2024;39(8):1228–1238. DOI: 10.1093/ndt/gfae027
37. Denic A., Mathew J., Lerman L.O., Lieske J.C., Larson J.J., Alexander M.P. et al. Single-nephron glomerular filtration rate in healthy adults. N. Engl. J. Med. 2017;376(24):2349–2357. DOI: 10.1056/NEJMoa1614329
38. Palmer A.K., Jensen M.D. Metabolic changes in aging humans: current evidence and therapeutic strategies. J. Clin. Invest. 2022;132(16):e158451. DOI: 10.1172/JCI158451
39. Manini T.M. Energy expenditure and aging. Ageing Res. Rev. 2010;9(1):1–11. DOI: 10.1016/j.arr.2009.08.002 40. Patel H.N., Miyoshi T., Addetia K., Henry M.P., Citro R., Daimon M. et al.; WASE Investigators. Normal values of cardiac output and stroke volume according to measurement technique, age, sex, and ethnicity: results of the world alliance of societies of echocardiography study. J. Am. Soc. Echocardiogr. 2021;34(10):1077–1085.e1. DOI: 10.1016/j.echo.2021.05.012
40. Czarkowska-Paczek B., Wyczalkowska-Tomasik A., Paczek L. Laboratory blood test results beyond normal ranges could not be attributed to healthy aging. Medicine (Baltimore). 2018;97(28):e11414. DOI: 10.1097/MD.0000000000011414
41. Denic A., Lieske J.C., Chakkera H.A., Poggio E.D., Alexander M.P., Singh P. et al. The Substantial loss of nephrons in healthy human kidneys with aging. J. Am. Soc. Nephrol. 2017;28(1):313–320. DOI: 10.1681/ASN.2016020154
42. Marumoto H., Tsuboi N., D’Agati V.D., Sasaki T., Okabayashi Y., Haruhara K. et al. Total Nephron Number and Single-Nephron Parameters in Patients with IgA Nephropathy. Kidney360. 2021;2(5):828– 841. DOI: 10.34067/KID.0006972020
43. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024;105(4S):S117–S314. DOI: 10.1016/j.kint.2023.10.018
44. Noronha I.L., Santa-Catharina G.P., Andrade L., Coelho V.A., Jacob-Filho W., Elias R.M. Glomerular filtration in the aging population. Front Med (Lausanne). 2022;9:769329. DOI: 10.3389/fmed.2022.769329
45. Schaeffner E.S., Ebert N., Delanaye P., Frei U., Gaedeke J., Jakob O. et al. Two novel equations to estimate kidney function in persons aged 70 years or older. Ann. Intern. Med. 2012;157(7):471–81. DOI: 10.7326/0003-4819-157-7-201210020-00003
46. Pottel H., Hoste L., Dubourg L., Ebert N., Schaeffner E., Eriksen B.O. et al. An estimated glomerular filtration rate equation for the full age spectrum. Nephrol. Dial. Transplant. 2016;31(5):798–806. DOI: 10.1093/ndt/gfv454
47. Li D.Y., Yin W.J., Yi Y.H., Zhang B.K., Zhao J., Zhu C.N. et al. Development and validation of a more accurate estimating equation for glomerular filtration rate in a Chinese population. Kidney Int. 2019;95(3):636–646. DOI: 10.1016/j.kint.2018.10.019
48. Wei L., Shen X., Zhang J., Yong Z., Zhang Q., Zhao W. Different equations for estimating age-related changes of glomerular filtration rate in the healthy population. BMC Nephrol. 2023;24(1):342. DOI: 10.1186/s12882-023-03397-7
49. Pottel H., Björk J., Courbebaisse M., Couzi L., Ebert N., Eriksen B.O. et al. Development and validation of a modified full age spectrum creatinine-based equation to estimate glomerular filtration rate : a cross-sectional analysis of pooled data. Ann. Intern. Med. 2021;174(2):183–191. DOI: 10.7326/M20-4366
50. Shardlow A., McIntyre N.J., Fluck R.J., McIntyre C.W., Taal M.W. Chronic kidney disease in primary care: outcomes after five years in a prospective cohort study. PLoS Med. 2016;13(9):e1002128. DOI: 10.1371/journal.pmed.1002128
51. Alfano G., Perrone R., Fontana F., Ligabue G., Giovanella S. Ferrari A. et al. Rethinking chronic kidney disease in the aging population. Life (Basel). 2022;12(11):1724. DOI: 10.3390/life12111724
52. Juric I., Kes P., Katalinic L., Godan Hauptman A. Basic-Jukic N. Extremely high prevalence of decreased GFR in the oldest elderly nursing home residents. Int. Urol. Nephrol. 2023;55(5):1393–1394. DOI: 10.1007/s11255-022-03435-7
53. Delanaye P., Jager K.J., Bökenkamp A., Christensson A., Dubourg L., Eriksen B.O. et al. CKD: A Call for an age-adapted definition. J. Am. Soc. Nephrol. 2019;30(10):1785–1805. DOI: 10.1681/ASN.2019030238
54. Liu P., Quinn R.R., Lam N.N., Elliott M.J., Xu Y., James M.T. et al. Accounting for age in the definition of chronic kidney disease. JAMA Intern. Med. 2021;181(10):1359–1366. DOI: 10.1001/jamainternmed.2021.4813
55. Musso C.G., Ricardo A.C., Aroca-Martinez G. The fourth wave in chronic kidney disease (CKD) classification: taking into account the aging kidney. Int. Urol. Nephrol. 2024;56(2):805–806. DOI: 10.1007/s11255-023-03642-w
56. O’Hare A.M., Rodriguez R.A., Rule A.D. Overdiagnosis of Chronic Kidney Disease in Older Adults-An Inconvenient Truth. JAMA Intern. Med. 2021;181(10):1366–1368. DOI: 10.1001/jamainternmed.2021.4823
57. Roth A.R., Lazris A., Haskell H., James J. Overdiagnosis of CKD in Older Adults: Unnecessary Interventions, Costs, and Worry. Am. Fam. Physician. 2023;107(6):657–658. PMID: 37327176
58. Hamarat H. Glomerular filtration rate and comorbidity factors in elderly hospitalizations. World J. Nephrol. 2025;14(1):98837. DOI: 10.5527/wjn.v14.i1.98837
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Ryabova T.S., Belskykh A.N. Functional and structural changes of the kidneys associated with aging and chronic kidney disease. Clinical Medicine (Russian Journal). 2026;104(1):17-26. (In Russ.) https://doi.org/10.30629/0023-2149-2026-104-1-17-26
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