Structural and Functional Renal Changes Secondary to Aging

  • Nada DimkovicEmail author


Kidney aging is under the influence of different factors including genetic factors, gender, ethnicity, and comorbidities, and normal aging process has an important role in daily clinical practice. In short, the physiological process of kidney aging includes reduced weight and preserved kidney volume, increased number of sclerotic glomeruli, increased size of remaining glomeruli, loss of afferent and peripheral arterioles and redistribution of blood into the medulla, decreased glomerular filtration, increased permeability of the glomerular basal membrane, tubular atrophy and interstitial fibrosis, reduced concentration and dilution ability of the kidney, and increased kidney sensitivity to toxic ischemic damage. The above-noted changes in the kidneys need to be known for establishing diagnosis of potential kidney disease/failure by adequate measurements of glomerular filtration, in order to adapt the therapy and to prevent numerous metabolic disturbances for which the kidney is responsible. Although age-related alterations are different to those induced by diseases, sometimes the two processes cannot be easily distinguished.


Kidney aging Sclerotic glomeruli GFR decline eGFR measurement Tubular atrophy Interstitial fibrosis Concentration ability Dilution ability 


  1. 1.
    Al-Said J, Brumback MA, Moghazi S, Baugarten DA, O’Neill WC. Reduced renal function in patients with simple renal cysts. Kidney Int. 2004;65(6):2303–8.CrossRefGoogle Scholar
  2. 2.
    Rule AD, Sasiwimonphan K, Lieske JC, Keddis MT, Torres VE, Vrtiska TJ. Characteristics of renal cystic and solid lesions based on contrast-enhanced computed tomography of potential kidney donors. Am J Kidney Dis. 2012;59(6):611–8.CrossRefGoogle Scholar
  3. 3.
    Lorenz EC, Vrtiska TJ, Lieske JC, et al. Prevalence of renal artery and kidney abnormalities by computed tomography among healthy adults. Clin J Am Soc Nephrol. 2010;5(3):431–8.CrossRefGoogle Scholar
  4. 4.
    Duan X, Rule AD, Elsherbiny H, et al. Automated assessment of renal cortical surface roughness from computerized tomography images and its association with age. Acad Radiol. 2014;21(11):1441–5.CrossRefGoogle Scholar
  5. 5.
    Wang X, Vrtiska TJ, Avula RT, et al. Age, kidney function, and risk factor associate differently with cortical and medullary volumes of the kidney. Kidney Int. 2014;85(3):677–85.CrossRefGoogle Scholar
  6. 6.
    Kubo M, Kiyohara Y, Kato I, et al. Risk factors for renal glomerular and vascular changes in an autopsy –based population survey: the Hisayama study. Kidney Int. 2003;63(4):1508–15.CrossRefGoogle Scholar
  7. 7.
    Baert L, Steg A. Is the diverticulum of the distal and collecting tubules a preliminary stage of the simple cist in the adult? J Urol. 1977;118(5):707–10.CrossRefGoogle Scholar
  8. 8.
    Elsherbiny HE, Alexander MP, Kremers WK, et al. Nephron hypertrophy and glomerulosclerosis and their association with kidney function and risk factors among living kidney donors. Clin J Am Soc Nephrol. 2014;9(11):1892–902.CrossRefGoogle Scholar
  9. 9.
    Harman D. Aging: a theory based on free radical and radiation chemistry. J Gerontol. 1956;11(3):298–300.CrossRefGoogle Scholar
  10. 10.
    Dai DF, Chiao YA, Marcinek DJ, Szeto HH, Rabinovitch PS. Mitochondrial oxidative stress in aging and health span. Longev Healthspan. 2014;3:6.CrossRefGoogle Scholar
  11. 11.
    Perico N, Remuzzi G, Benigni A. Aging and the kidney. Curr Opin Nephrol Hypertens. 2011;20:312–27.CrossRefGoogle Scholar
  12. 12.
    Yang H, Fogo A. Cell senescence in the aging kidney. J Am Soc Nephrol. 2010;21:1436–9.CrossRefGoogle Scholar
  13. 13.
    Zhou X, Saxena R, Liu Z, et al. Renal senescence in 2008: progress and challenges. Int Urol Nephrol. 2008;40:823–39.CrossRefGoogle Scholar
  14. 14.
    Darmady EM, Offer J, Woodhouse MA. The parameters of the ageing kidney. J Pathol. 1973;109(3):195–207.CrossRefGoogle Scholar
  15. 15.
    Martin JE, Sheaff MT. Renal ageing. J Pathol. 2007;211(2):198–205.CrossRefGoogle Scholar
  16. 16.
    Hoy WE, Douglas-Denton RN, Highson MD, Cass A, Johnson K, Bertram JF. A stereological study of glomerular number and volume: preliminary findings in a multiracial study of kidneys at autopsy. Kidney Int Suppl. 2003;63(83):S31–7.CrossRefGoogle Scholar
  17. 17.
    Rule AD, Amer H, Cornell LD, et al. The association between age and nephrosclerosis on renal biopsy among healthy adults. Ann Intern Med. 2010;152(9):561–7.CrossRefGoogle Scholar
  18. 18.
    Huber TB, Edelstein CL, Hartleben B, et al. Emerging role of autophagy in kidney function, diseases and aging. Autophagy. 2012;8(7):1009–31.CrossRefGoogle Scholar
  19. 19.
    Wiggins JE. Aging in the glomerulus. J Gerontol A Biol Sci Med Sci. 2012;67(12):1358–64.CrossRefGoogle Scholar
  20. 20.
    Gagliano N, Arioso B, Santanbrogio B, et al. Age-dependent expression of fibrosis-related genes and collagen deposition in rat kidney cortex. J Gerontol A Biol Sci Med Sci. 2000;55(8):365–72.CrossRefGoogle Scholar
  21. 21.
    Lauks SP Jr, McClachlan MS. Aging and simple cysts of the kidney. Br J Radiol. 1981;54(637):12–4.CrossRefGoogle Scholar
  22. 22.
    Lindeman RD, Goldman R. Anatomic and physiologic age changes in the kidney. Exp Gerontol. 1986;21(4–5):379–406.CrossRefGoogle Scholar
  23. 23.
    Musso CG. Geriatric nephrology and the “nephrogeriatric giants”. Int Urol Nephrol. 2002;34:255–6.CrossRefGoogle Scholar
  24. 24.
    Takazakura E, Sawabu N, Handa A, et al. Intrarenal vascular changes with age and disease. Kidney Int. 1972;2:224–30.CrossRefGoogle Scholar
  25. 25.
    Silva FG. The ageing kidney: a review – part I. Int Urol Nephrol. 2005;37:185–205.CrossRefGoogle Scholar
  26. 26.
    Silva FG. The ageing kidney: a review – part II. Int Urol Nephrol. 2005;37:419–32.CrossRefGoogle Scholar
  27. 27.
    Hollenberg NK, Adams DF, Solomon HS, et al. Senescence and the renal vasculature in normal man. Circ Res. 1974;34:309–16.CrossRefGoogle Scholar
  28. 28.
    Emamiam SA, Nielsen MB, Pedersen JF, Ytte L. Kidney dimensions at sonography: correlation with age, sex, and habitus in 665 adult volunteers. AJR Am J Roenthenol. 1993;160(1):83–6.CrossRefGoogle Scholar
  29. 29.
    Gourtsoyiannis N, Prassopoulos P, Cavouras D, Pantelidis N. The thickness of the renal parenchyma decreases with age: a CT study of 360 patients. AJR Am J Roentgenol. 1990;155(3):541–4.CrossRefGoogle Scholar
  30. 30.
    Glodny B, Unterholzner V, Taferner B, et al. Normal kidney size and its influencing factors – a 64-slice MDCT study of 1040 asymptomatic patients. BMC Urol. 2009;9:19.CrossRefGoogle Scholar
  31. 31.
    McLachlan M, Wasserman P. Changes in sizes and distensibility of the aging kidney. Br J Radiol. 1981;54(642):488–91.CrossRefGoogle Scholar
  32. 32.
    Schwarz A, Lenz T, Klaen R, Offermann G, Fiedler U, Nussberger J. Hygroma renale: pararenal lymphatic cysts associated with renin-dependent hypertension (page kidney). Case report on bilateral cysts and successful therapy by marsupialization. J Urol. 1993;150(3):953–7.CrossRefGoogle Scholar
  33. 33.
    Smith HW. The kidney: the structure and function in health and disease. New York: Oxford University Press; 1951.Google Scholar
  34. 34.
    Davies DF, Shock NW. Age changes in glomerular filtration rate, effective renal plasma flow, and tubular excretory capacity in adult males. J Clin Invest. 1950;29(5):496–507.CrossRefGoogle Scholar
  35. 35.
    Musso CG. Renal reserve test: its methodology and significance. Saudi J Kidney Dis Transpl. 2011;22(5):990–3.PubMedGoogle Scholar
  36. 36.
    Musso CG, Reynaldi J, Martinez B, Pierángelo A, Vilas M, Algranati L. Renal reserve in the oldest old. Int Urol Nephrol. 2011;43(1):253–6.CrossRefGoogle Scholar
  37. 37.
    Alvarez Gregori J, Musso C, Macias Núñez JF. Renal ageing. In: Sastre J, Pamolona R, Ramón J, editors. Medical biogerontology. Madrid: Ergon; 2009. p. 111–23.Google Scholar
  38. 38.
    Keller F. Kidney function and age. Nephrol Dial Transplant. 1987;2(5):382.PubMedGoogle Scholar
  39. 39.
    Swedish Council on Health Technology Assessment. Methods to estimate and measure renal function (glomerular filtration rate): a systematic review, SBU Yellow Report No. 214. Stockholm: Swedish Council on Health Technology Assessment (SBU); 2011.Google Scholar
  40. 40.
    Musso CG, Álvarez-Gregori J, Jauregui J, MacíasNúñez JF. Glomerular filtration rate equations: a comprehensive review. Int Urol Nephrol. 2016;48(7):1105–10.CrossRefGoogle Scholar
  41. 41.
    Rule AD, Cornell LD, Poggio ED. Senile nephrosclerosis-does it explain the decline in glomerular filtration rate with aging? Nephron Physiol. 2011;119(Suppl):6–11.CrossRefGoogle Scholar
  42. 42.
    Eriksen BO, Lochen ML, Arntzen KA, et al. Subclinical cardiovascular disease is associated with high glomerular filtration rate in the nondiabetic general population. Kidney Int. 2014;86(1):146–53.CrossRefGoogle Scholar
  43. 43.
    Musso CG, Macías-Núñez JF. Dysfunction of the thick loop of Henle and senescence: from molecular biology to clinical geriatrics. Int Urol Nephrol. 2011;43(1):249–52.CrossRefGoogle Scholar
  44. 44.
    Lye M. Distribution of body potassium in healthy elderly subjects. Gerontologie. 1981;27:286–92.CrossRefGoogle Scholar
  45. 45.
    Phelps KR, Lieberman RL, Oh MS, et al. Pathophysiology of the syndrome of hyporeninemic hypoaldosteronism. Metabolism. 1980;29:186–99.CrossRefGoogle Scholar
  46. 46.
    Musso CG, Miguel RD, Algranati L, Farias Edos R. Renal potassium excretion: comparison between chronic renal disease patients and old people. Int Urol Nephrol. 2005;37(1):167–70.CrossRefGoogle Scholar
  47. 47.
    Musso CG, Juarez R, Vilas M, Navarro M, Rivera H, Jauregui R. Renal calcium, phosphorus, magnesium and uric acid handling: comparison between stage III chronic kidney disease patients and healthy oldest old. Int Urol Nephrol. 2012;44(5):1559–62.CrossRefGoogle Scholar
  48. 48.
    Musso CG, Alvarez Gregori J, Jauregui JR, Macías Núñez JF. Creatinine, urea, uric acid, water and electrolytes renal handling in the healthy oldest old. World J Nephrol. 2012;1(5):123–6.CrossRefGoogle Scholar
  49. 49.
    Musso CG, Michelángelo H, Vilas M, Reynaldi J, Martinez B, Algranati L, Macías Núñez JF. Creatinine reabsorption by the aged kidney. Int Urol Nephrol. 2009;41(3):727–31.CrossRefGoogle Scholar
  50. 50.
    Wagner EA, Falciglia GA, Amlal H, et al. Short-term exposure to high-protein diet differentially affect glomerular filtration rate but not acid-base balance in older compared to younger adults. J Am Diet Assoc. 2007;107:1404–8.CrossRefGoogle Scholar
  51. 51.
    Preisser L, Teillet L, Aliotti S, et al. Downregulation of aquaporin-2 and -3 in aging kidney is independent of V(2) vasopressin receptor. Am J Phyiol Renal Physiol. 2000;279:F144–52.CrossRefGoogle Scholar
  52. 52.
    Musso CG, Macías Núñez JF. Renal handling of water and electrolytes in the old and old-old healthy aged. In: Núñez M, Cameron S, Oreopoulos D, editors. Renal ageing: health and disease. New York: Springer; 2008. p. 141–54.Google Scholar
  53. 53.
    Musso CG, Liakopoulos V, Ioannidis I, Eleftheriadis T, Stefanidis I. Acute renal failure in the elderly: particular characteristics. Int Urol Nephrol. 2006;38(3–4):787–93.PubMedGoogle Scholar
  54. 54.
    Stevens PE, Levin A. Evaluation and management of chronic kidney disease: synopsis of the kidney disease improving global outcomes 2012 clinical practise guideline. Ann Intern Med. 2013;158(11):825–30.CrossRefGoogle Scholar
  55. 55.
    Murata K, Bauman NA, Saenger AK, Larson TS, Rule AD, Lieske JC. Relative performance of the MDRD and CKD-EPI equations for estimating glomerular filtration rate among patients with varied clinical presentations. Clin J Am Soc Nephrol. 2011;6(8):1863–972.CrossRefGoogle Scholar
  56. 56.
    Rule AD, Glassock RJ. GFR estimating equations: getting closer to the truth? Clin J Am Soc Nephrol. 2013;8(8):1414–20.CrossRefGoogle Scholar
  57. 57.
    Stengel B, Metzger M, Froissart M, et al. Epidemiology and prognostic significance of chronic kidney disease in the elderly –the Three-City prospective cohort study. Nephrol Dial Transplant. 2011;26(10):3286–95.CrossRefGoogle Scholar
  58. 58.
    Hallan SI, Matsushita K, Sang Y, et al. Age and association of kidney measures with mortality and end-stage renal disease. JAMA. 2012;308(22):2349–60.CrossRefGoogle Scholar
  59. 59.
    Robles NR, Felix FJ, Lozano L, Miranda I, Fernandez-Berges D, Macías JF. The H.U.G.E. formula (Hematocrit, Urea, Sex) for screening chronic kidney disease (CKD) in an age-stratified general population. J Nutr Health Aging. 2015;19(6):688–92.CrossRefGoogle Scholar
  60. 60.
    Musso CG, Maytin S, Conti P, Terrasa S, Primerano A, Reynaga A, Vilas M, Jauregui J. HUGE equation accuracy for screening chronic kidney disease: a prospective study. J Aging Res Clin Pract. 2017;6:158–62.Google Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Clinical Department for Renal DiseasesZvezdara University Medical CenterBelgradeSerbia

Personalised recommendations