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The Aging Kidney: Physiological Changes

  • Jessica R. Weinstein
    Affiliations
    Division of Nephrology and Hypertension, Oregon Health and Science University, Portland, OR; and Medical Service, Portland VA Medical Center, Portland, OR
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  • Sharon Anderson
    Correspondence
    Address correspondence to Sharon Anderson, MD, Division of Nephrology and Hypertension, Oregon Health and Science University, OHSU Nephrology PP 262, 3314 SW US Veterans Hospital Rd., Portland, OR 97239.
    Affiliations
    Division of Nephrology and Hypertension, Oregon Health and Science University, Portland, OR; and Medical Service, Portland VA Medical Center, Portland, OR
    Search for articles by this author
      Age-associated loss of kidney function has been recognized for decades. With aging, many subjects exhibit progressive decreases in glomerular filtration rate and renal blood flow, with wide variability among individuals. The fall in glomerular filtration rate is because of reductions in the glomerular capillary plasma flow rate and the glomerular capillary ultrafiltration coefficient. In addition, a primary reduction in afferent arteriolar resistance is associated with an increase in glomerular capillary hydraulic pressure. These hemodynamic changes occur in concert with structural changes, including loss of renal mass; hyalinization of afferent arterioles and in some cases, development of aglomerular arterioles; an increase in the percentage of sclerotic glomeruli; and tubulointerstitial fibrosis. Aging is associated with altered activity and responsiveness to vasoactive stimuli, such that responses to vasoconstrictor stimuli are enhanced, whereas vasodilatory responses are impaired. Changes in the activity of the renin–angiotensin and nitric oxide systems appear to be particularly important, as is the modulating effect of gender. These changes may predispose the older kidney to acute kidney injury, including normotensive ischemic nephropathy, as well as progressive chronic kidney disease.

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      References

        • Rodrígues-Puyol D.
        The aging kidney.
        Kidney Int. 1998; 54: 2247-2265
        • Choudhury D.
        • Levi M.
        Aging and kidney disease.
        in: Brenner B.M. Brenner & Rector's the Kidney (8th ed). Saunders, Philadelphia, PA2008: 681-701
        • Zhou X.J.
        • Rakheja D.
        • Yu X.
        • et al.
        The aging kidney.
        Kidney Int. 2008; 74: 710-720
        • Davies D.F.
        • Shock N.W.
        Age changes in glomerular filtration rate, effective renal plasma flow, and tubular excretory capacity in adult males.
        J Clin Invest. 1950; 29: 496-507
        • Rowe J.W.
        • Andres R.
        • Tobin J.D.
        • et al.
        The effect of age on creatinine clearance in men: A cross-sectional and longitudinal study.
        J Gerontol. 1976; 31: 155-163
        • Coresh J.
        • Selvin E.
        • Stevens L.A.
        • et al.
        Prevalence of chronic kidney disease in the United States.
        JAMA. 2007; 298: 2038-2047
        • Lindeman R.D.
        • Tobin J.D.
        • Shock N.W.
        Association between blood pressure and the rate of decline in renal function with age.
        Kidney Int. 1984; 27: 553-557
        • Fox C.S.
        • Larson M.G.
        • Leip E.P.
        • et al.
        Predictors of new-onset kidney disease in a community-based population.
        JAMA. 2004; 291: 844-850
        • Kim R.
        • Rotnitsky A.
        • Sparrow D.
        • et al.
        A longitudinal study of low-level lead exposure and impairment of renal function. The Normative Aging Study.
        JAMA. 1996; 275: 1177-1181
        • Bleyer A.J.
        • Shemanski L.R.
        • Burke G.L.
        • et al.
        Tobacco, hypertension, and vascular disease: Risk factors for renal functional decline in an older population.
        Kidney Int. 2000; 57: 2072-2079
        • Fried L.
        • Solomon C.
        • Shlipak M.
        • et al.
        Inflammatory and prothrombotic markers and the progression of renal disease in elderly individuals.
        J Am Soc Nephrol. 2004; 15: 3184-3191
        • Vlassara H.
        • Torreggiani M.
        • Post J.B.
        • et al.
        Role of oxidants/inflammation in declining renal function in chronic kidney disease and normal aging.
        Kidney Int. 2009; 76: S3-S11
        • Foster M.C.
        • Hwang S.-J.
        • Larson M.G.
        • et al.
        Overweight, obesity, and the development of stage 3 CKD: The Framingham Heart Study.
        Am J Kidney Dis. 2008; 52: 39-48
        • de Boer I.H.
        • Katz R.
        • Fried L.F.
        • et al.
        Obesity and change in estimated GFR among older adults.
        Am J Kidney Dis. 2009; 54: 1043-1051
        • Baylis C.
        Sexual dimorphism in the aging kidney: Differences in the nitric oxide system.
        Nat Rev Nephrol. 2009; 5: 384-396
        • Ishani A.
        • Xue J.L.
        • Himmelfarb J.
        • et al.
        Acute kidney injury increases risk of ESRD among elderly.
        J Am Soc Nephrol. 2009; 20: 223-228
        • Wesson L.G.
        Renal hemodynamics in physiological states.
        in: Wesson L.G. Physiology of the Human Kidney. Grune & Stratton, New York, NY1969: 96-108
        • Hollenberg N.K.
        • Adams D.F.
        • Solomon H.S.
        • et al.
        Senescence and the renal vasculature in normal man.
        Circ Res. 1974; 34: 309-316
        • Anderson S.
        • Rennke H.G.
        • Zatz R.
        Glomerular adaptations with normal aging and with longterm converting enzyme inhibition in the rat.
        Am J Physiol. 1994; 267: F35-F43
        • Tolbert E.M.
        • Weisstuch J.
        • Feiner H.D.
        • et al.
        Onset of glomerular hypertension with aging precedes injury in the spontaneously hypertensive rat.
        Am J Physiol Renal Physiol. 2000; 278: F839-F846
        • Hoang K.
        • Tan J.C.
        • Derby G.
        • et al.
        Determinants of glomerular hypofiltration in aging humans.
        Kidney Int. 2003; 64: 1417-1424
        • Bolton W.K.
        • Benton F.R.
        • Maclay J.G.
        • et al.
        Spontaneous glomerular sclerosis in aging Sprague-Dawley rats.
        Am J Pathol. 1976; 85: 227-302
        • Wiggins J.E.
        • Goyal M.
        • Sander S.K.
        • et al.
        Podocyte hypertrophy, “adaptation”, and “decompensation” associated with glomerular enlargement and glomerulosclerosis in the aging rat: Prevention by calorie restriction.
        J Am Soc Nephrol. 2005; 16: 2953-2966
        • Cohen M.P.
        • Ku L.
        Age-related changes in sulfation of basement membrane glycosaminoglycans.
        Exp Gerontol. 1976; 18: 447-450
        • Jones C.A.
        • Francis M.E.
        • Eberhardt M.S.
        • et al.
        Microalbuminuria in the US population: Third National Health and Nutrition Examination Survey.
        Am J Kidney Dis. 2002; 39: 445-459
        • Kasiske B.L.
        • Umen A.J.
        The influence of age, sex, race, and body habitus on kidney weight in humans.
        Arch Pathol Lab Med. 1986; 110: 55-60
        • Nyengaard J.R.
        • Bendtsen T.F.
        Glomerular number and size in relation to age, kidney and body surface in normal man.
        Anat Rec. 1992; 232: 194-201
        • Emamian S.A.
        • Nielsen M.B.
        • Pedersen J.F.
        • et al.
        Kidney dimensions at sonography: Correlation with age, sex, and habitus in 665 adult volunteers.
        AJR Am J Roentgenol. 1993; 160: 83-86
        • Tauchi H.
        • Tsuboi K.
        • Okutomi J.
        Age changes in the human kidney of the different races.
        Gerontologia. 1971; 17: 87-97
        • McLachlan M.S.F.
        The ageing kidney.
        Lancet. 1978; ii: 143-146
        • Goyal V.K.
        Changes with age in the human kidney.
        Exp Gerontol. 1982; 17: 321-331
        • Ljungqvist A.
        • Lagergren C.
        Normal intrarenal arterial pattern in adult and ageing human kidney. A micro-angiographical and histological study.
        J Anat. 1962; 96: 285-300
        • Takazakura E.
        • Sawabu N.
        • Handa A.
        • et al.
        Intrarenal vascular changes with age and disease.
        Kidney Int. 1972; 2: 224-230
        • Hill G.S.
        • Heudes D.
        • Bariéty J.
        Morphometric study of arterioles and glomeruli in the aging kidney suggests focal loss of autoregulation.
        Kidney Int. 2003; 63: 1027-1036
        • Kaplan C.
        • Pasternack B.
        • Shah H.
        • et al.
        Age-related incidence of sclerotic glomeruli in human kidneys.
        Am J Pathol. 1974; 80: 227-234
        • Kappel B.
        • Olsen S.
        Cortical interstitial tissue and sclerosed glomeruli in the normal human kidney, related to age and sex. A quantitative study.
        Virchows Arch A Pathol Anat Histol. 1980; 387: 271-277
        • Neugarten J.
        • Gallo G.
        • Silbiger S.
        • et al.
        Glomerulosclerosis in aging humans is not influenced by gender.
        Am J Kidney Dis. 1999; 34: 884-888
        • Wei J.Y.
        Age and the cardiovascular system.
        N Engl J Med. 1992; 327: 1735-1739
        • Thomas S.E.
        • Anderson S.
        • Gordon K.L.
        • et al.
        Tubulointerstitial disease in aging: Evidence for underlying peritubular capillary damage, a potential role for renal ischemia.
        J Am Soc Nephrol. 1998; 9: 231-242
        • Kang D.-H.
        • Anderson S.
        • Kim Y.-G.
        • et al.
        Impaired angiogenesis in the aging kidney: Vascular endothelial growth factor and thrombospondin-1 in renal disease.
        Am J Kidney Dis. 2001; 37: 601-611
        • Barton M.
        Ageing as a determinant of renal and vascular disease: Role of endothelial factors.
        Nephrol Dial Transplant. 2005; 20: 485-490
        • Tank J.E.
        • Vora J.P.
        • Houghton D.C.
        • et al.
        Altered renal vascular responses in the aging rat kidney.
        Am J Physiol. 1994; 266: F942-F948
        • Castellani S.
        • Ungar A.
        • Cantini C.
        • et al.
        Excessive vasoconstriction after stress by the aging kidney: Inadequate prostaglandin modulation of increased endothelin activity.
        J Lab Clin Med. 1998; 132: 186-194
        • Fuaino G.
        • Sund S.
        • Mazza G.
        • et al.
        Renal hemodynamic response to maximal vasodilating stimulus in healthy older subjects.
        Kidney Int. 2001; 59: 1052-1058
        • Anderson S.
        Ageing and the renin-angiotensin system.
        Nephrol Dial Transplant. 1997; 12 ([editorial comment]): 1093-1094
        • Gilliam-Davis S.
        • Payne V.S.
        • Kasper S.O.
        • et al.
        Long-term AT1 receptor blockade improves metabolic function and provides renoprotection in Fischer-344 rats.
        Am J Physiol Heart Circ Physiol. 2007; 293: H1327-H1333
        • Ferder L.F.
        • Inserra F.
        • Basso N.
        Effects of renin-angiotension system blockade in the aging kidney.
        Exp Gerontol. 2003; 38: 237-244
        • Jung F.F.
        • Kennefick T.M.
        • Ingelfinger J.R.
        • et al.
        Downregulation of the intrarenal renin-angiotensin system in the aging rat.
        J Am Soc Nephrol. 1995; 5: 1573-1580
        • Llorens S.
        • Fernandez A.P.
        • Nava E.
        Cardiovascular and renal alterations on the nitric oxide pathway in spontaneous hypertension and ageing.
        Clin Hemorheol Microcirc. 2007; 37: 149-156
        • Delp M.D.
        • Behnke B.J.
        • Spier S.A.
        • et al.
        Ageing diminishes endothelium-dependent vasodilatation and tetrahydrobiopterin content in rat skeletal muscle arterioles.
        J Physiol. 2008; 586: 1161-1168
        • Xiong Y.
        • Yuan L.W.
        • Deng H.W.
        • et al.
        Elevated serum endogenous inhibitor of nitric oxide synthase and endothelial dysfunction in aged rats.
        Clin Exp Pharmacol Physiol. 2001; 28: 842-847
        • Abuelo J.G.
        Normotensive ischemic acute renal failure.
        N Engl J Med. 2007; 357: 797-805
        • Iseki K.
        • Iseki C.
        • Ikemiya Y.
        • et al.
        Risk of developing end-stage renal disease in a cohort of mass screening.
        Kidney Int. 1996; 49: 800-805
        • Rogers J.L.
        • Mitchell A.R.
        • Maric C.
        • et al.
        Effect of sex hormones on renal estrogen and angiotensin type 2 receptors in female and male rats.
        Am J Physiol Regul Integr Com Physiol. 2007; 292: R794-R799
        • Fortepiani L.A.
        • Yanes L.
        • Zhang H.
        • et al.
        Role of androgens in mediating renal injury in aging SHR.
        Hypertension. 2003; 42: 952-955
        • Maric C.
        • Sandberg K.
        • Hinojosa-Laborde C.
        Glomerulosclerosis and tubulointerstitial fibrosis are attenuated with 17β-estradiol in the aging Dahl salt sensitive rat.
        J Am Soc Nephrol. 2004; 15: 1546-1556
        • Baylis C.
        Age-dependent glomerular damage in the rat: Dissociation between glomerular injury and both glomerular hypertension and hypertrophy. Male gender as a primary risk factor.
        J Clin Invest. 1994; 94: 1823-1829
        • Moens A.L.
        • Kass D.A.
        Tetrahydrobiopterin and cardiovascular disease.
        Arterioscler Thromb Vasc Biol. 2006; 26: 2439-2444
        • Schulze F.
        • Maas R.
        • Freese R.
        • et al.
        Determination of a reference value for N(G), N(G)-dimethyl-L-arginine in 500 subjects.
        Eur J Clin Invest. 2005; 35: 622-626
        • Ahmed S.B.
        • Fisher N.D.
        • Hollenberg N.K.
        Gender and the renal nitric oxide synthase system in healthy humans.
        Clin J Am Soc Nephrol. 2007; 2: 926-931
        • Reckelhoff J.F.
        • Baylis C.
        Glomerular metalloprotease activity in the aging rat kidney: Inverse correlation with injury.
        J Am Soc Nephrol. 1993; 3: 1835-1838