Copyright EMAP Publishing 2017 This article is not for distribution

Nursing Practice Keywords: Ageing/Respiratory system/Respiratory tract infections/ Systems of life This article has been Renal system double-blind peer reviewed In this article... ● How age affects the normal functioning of the renal system ● Age-related changes to the kidneys, bladder, urethra and prostate ● How declining renal function can affect various conditions in older age

Anatomy and physiology of ageing 4: the renal system

Key points Authors Maria Andrade and John Knight are both senior lecturer in biomedical The renal system science, College of Human Health and Science, Swansea University. 1is the most powerful regulator Abstract The functions of the renal system include removal of waste products; of the body’s regulation of blood volume, blood pressure and red blood cells; and balancing of internal environment electrolytes and blood pH. Renal function starts to gradually decline after the third With advancing decade of life but, in the absence of disease, the renal system is able to fulfil its role 2age, renal blood throughout life. In spite of this, many anatomical and physiological changes mean flow – and therefore older people are prone to issues such as polyuria, nocturia and incontinence. This glomerular filtration fourth article in our series on the anatomy and physiology of ageing explains how age rate – are reduced affects the organs of the renal system, leading to a reduction in renal function. The mass and 3weight of the Citation Andrade M, Knight J (2017) Anatomy and physiology of ageing 3: the renal kidneys decrease system. Nursing Times [online]; 113: 5, 46-49. significantly after the age of 50 years The progressive he renal system is the most pow- to lead, obesity and increased inflamma- 4degradation of erful regulator of the body’s tory mediators in the blood (Weinstein and renal function leads internal environment. Healthy Anderson, 2010). to issues typical of Tkidneys are essential to maintain old age such as homeostasis, ensuring stable conditions Anatomical changes polyuria, nocturia in which all cells can function optimally. Pre-renal changes and incontinence They perform several functions (Montague The most important pre-renal (occurring Most men et al, 2005), including: before the kidney) change affecting kidney 5experience a l Removal of waste products such as function is vascular degeneration. In benign enlargement urea, uric acid, creatinine and toxic young adults, renal blood flow is estimated of the prostate breakdown products of drugs; to be approximately 600ml/minute; in gland as they get ● Regulation of blood volume and pressure; older people this is often reduced by half older, but this ● Electrolyte (salt) balance; (Cukuranovic and Vlajkovic, 2005) pri- prostatic hyperplasia ● Acid-base balance (regulation of marily due to normal age-related changes can also be a sign of blood pH); in blood vessels (see Part 1 of this series) malignancy ● Regulation of the number of and is often exacerbated in people with erythrocytes (red blood cells); atherosclerosis of the renal artery. ● Synthesis of vitamin D. Such blood vessel changes usually lead In the absence of disease, the kidneys to ischaemia (reduced oxygenation), par- function optimally into the third decade of ticularly in the outer portion of the kidney life, after which there is a gradual decline (renal cortex). Cells gradually die and are in renal function (Figs 1 and 2). Around 15% replaced with scar tissue, giving the outer of people over the age of 70 years have var- surface of aged kidneys a granular or mot- ying degrees of renal disease and dysfunc- tled appearance. The arterioles leading to tion (Coresh et al, 2007). Factors contrib- the glomeruli (filtration membranes) show uting to the decline in renal function deposition of hyaline (clear cartilage- include hypertension, smoking, exposure like material) and collagen below the

Nursing Times [online] May 2017 / Vol 113 Issue 5 46 www.nursingtimes.net Copyright EMAP Publishing 2017 This article is not for distribution Nursing Practice Systems of life

Fig 1. Tubule abnormalities Age-related changes to the renal system Some kidney tubules gradually degenerate and are replaced by scar tissue (tubulo- Increased collagen deposition, reduced interstitial fibrosis). This seems associated renal blood flow and glomerular filtration rate, loss of nephrons and abnormal with an increasing number of cells nephron structure showing features of senescence (Sturm- lechner et al, 2017), which reduces the area available for the reabsorption of useful Increased risk of materials such as glucose, amino acids and urinary incontinence salts. The distal convoluted tubules often due to: shrink and may develop small pouches l Reduced bladder elasticity (distal diverticula), which can in turn l Loss of sphincter become fluid-filled cysts, increasing the tone risk of kidney infection and pyelonephritis l Poor bladder (Zhou et al, 2008). control Impaired renal repair Shortened urethra in some In young adult kidneys, around 1% of renal women may increase risks cells have the ability to divide and prolif- of urinary tract infection. Prostatic erate. This declines with age, reducing the hyperplasia in men may interfere kidneys’ ability to repair. The chemical sig- with urine flow nalling pathways that coordinate cell divi- sion and repair in the kidneys also become impaired with age (Bolignano et al, 2014). endothelium; this reduces the diameter of Renal changes the vessels, thereby restricting blood flow. Both kidney mass and weight decrease sig- Diet and renal ageing The smallest blood vessels in the kidney, nificantly after the age of 50 (Zhou et al, Age-related changes in renal structure and including the capillaries that form the glo- 2008). The kidneys of people in their 20s function are thought to occur as a result of meruli, also progressively degenerate and weigh 250-270g each; in 90-year-olds this has both genetic and environmental factors are replaced with fibrous scar tissue dropped to 180-200g. It has been estimated (Bolignano et al, 2014). One factor that (Musso and Oreopoulos, 2011). that, between the ages of 40 and 80, approxi- appears to play a role is exposure to oxida- Aged blood vessels experience a general mately 20% of kidney mass is lost (Choud- tive stress, which tends to lead to the reduction in the synthesis of the potent hury et al, 2016); only 3% of people in their release of pro-inflammatory mediators. vasodilator nitric oxide (see Part 1 of this 90s have histologically normal kidney tissue. While most oxidative stress is linked to series) and this contributes to reducing There is a gradual increase in collagen free radicals produced during cellular blood flow to the kidneys (Weinstein and deposition, leading to progressive kidney metabolism, some of it comes from diet. Anderson, 2010). fibrosis. In old age, whole nephrons (the Foods cooked at high temperature (par- functional units in the kidneys) are ticularly fried or roasted) are high in pro- Reduced glomerular filtration rate replaced by fatty material or scar tissue; on oxidants; it has been suggested that lim- The glomerular filtration rate (GFR) is a average, 70-year-olds have lost 30-50% of iting their intake could reduce oxidative measure of the rate of fluid filtration their nephrons. Aged nephrons often show and inflammatory stress on the kidneys through the glomerular capillaries into a variety of physical defects (Fig 2). (Vlassara et al, 2009). Bowman’s capsule. It is expressed in millili- tres per minute, and is routinely used to Glomerular abnormalities Gender differences in renal ageing measure the progression of kidney disease The number of damaged glomeruli (glo- Although this is still poorly understood, (Bit.ly/RAStagesCKD). GFR peaks in the merulosclerosis) increases, typically oestrogens such as 17 beta-estradiol appear third decade of life, where it may be as high leading to progressive capillary collapse. to protect the renal system in women as 140ml/min/1.73m2. Blood vessel changes Fewer than 5% of glomeruli show sclerosis from the effects of ageing, while andro- progressively reduce renal blood flow and in people in their 20s but, by their 80s, this gens such as testosterone increase the risk GFR: in normal ageing, it drops by around will have risen to around 30% (Weinstein of renal dysfunction in men. One hypoth- 8ml/min per decade after the age of 30. The and Anderson, 2010). esis is that androgens promote fibrosis GFR of people in their 80s may be only in the kidney; this may partially explain 60-70% of what it was when they were Filtration membrane abnormalities why chronic kidney disease progresses young adults; at 90 years of age it has typi- Some nephrons display a progressive more quickly in men (Weinstein and cally fallen to around 65ml/min/1.73m2. thickening and wrinkling of the filtration Anderson, 2010). Reduced GFR means reduced clearance membrane in the glomerulus and Bow- of waste products. However, age-related man’s capsule, decreasing the renal fil- Physiological changes decline in GFR is not observed in all people; tering surface area. The filtration mem- Older people experience a significant indeed many maintain a stable GFR brane also becomes increasingly reduction in renal function. Even in the throughout life, which suggests that vari- permeable, allowing large molecules such absence of disease, some people over the ables other than ageing contribute to the as proteins to collect in the filtrate and age of 65 only possess 60% of the renal

CATHERINE HOLLICK CATHERINE decline (Zhou et al, 2008). appear in the urine (proteinuria). function of young adults (Razzaque, 2007).

Nursing Times [online] May 2017 / Vol 113 Issue 5 47 www.nursingtimes.net Copyright EMAP Publishing 2017 This article is not for distribution Nursing Practice Systems of life

This gradual decline has major health Fig 2. Defects found in aged nephrons and their consequences implications, particularly when long-term conditions and circulatory problems are Proximal tubule present. Reduced reabsorption Long-term conditions that lead to fluid Glomerulus and Bowman’s of amino acids, glucose overload and oedema – such as heart capsule and hormones failure, liver disease and chronic kidney l Thickened diseases (for example, diabetic and hyper- filtration tensive nephropathies) – are exacerbated membrane by poorly functioning aged kidneys. l Reduced Patients with these conditions (commonly glomerular blood flow Distal tubule managed via diuretics) need their treat- l Reduced filtration l Reduced size and ment regimens monitored and adjusted to l Glomerular development of distal compensate for age-related renal decline. degeneration diverticulae may lead Numerous studies have indicated that obe- to cyst formation sity, diabetes, high blood pressure, eth- l Reduced sensitivity to nicity and genetics can all contribute to antidiuretic hormone the onset of renal disease in older people Loop of Henle l Reduced clearance of (Kazancioglu et al, 2013). Reduced control over salt drugs and toxic Common age-related physiological reabsorption potentially metabolites changes in renal function are described leading to electrolyte below. imbalance

Electrolyte imbalance Reduced renal blood flow and GFR, together with the gradual loss of nephrons, because of the gradual reduction in skel- liver, play a role in drug metabolism and reduce the kidneys’ ability to keep electro- etal muscle mass. clearance, so their ageing also increases lytes (sodium, potassium, calcium and the risk of drug toxicity. chloride) within optimal ranges. As these Polyuria and nocturia play a major role in maintaining blood The progressive loss of nephrons makes Reduced insulin clearance pressure and generating nerve impulses, the kidneys less efficient at concentrating The kidneys remove around 50% of older people may experience hyper- or urine, therefore a greater volume of water secreted insulin from the peripheral blood. hypotension and confusion. is required to excrete toxic waste products. Although reduced GFR along with degen- Older people are also less efficient at Additionally, the effect of antidiuretic hor- eration and loss of nephrons significantly clearing salt, which may be due to reduced mone on the renal tubules is blunted in diminish older people’s ability to clear it, GFR (less sodium-laden blood is filtered), older people, leading to a larger volume of response to insulin is gradually blunted tubular degeneration, and reduced sensi- diluted urine. The result is a gradual with age, which offsets the reduced clear- tivity to hormones such as aldosterone increase in urine volume leading to poly- ance (Zhou et al, 2008). (Musso and Oreopoulos, 2011). uria (frequent urination). In older patients, it is essential to mon- Changes in erythropoietin and vitamin Reduced acid-base balance itor fluid status for signs of dehydration, D biosynthesis While the lungs play a role in regulating and ensure they have free and convenient The cells that form the tubules of the blood pH, only the kidneys can excrete access to water. Fluids drunk during the nephron, along with the peritubular cells, acidic or basic molecules directly, so they evening take longer to be processed, produce erythropoietin (EPO) and play a are the ultimate regulators of acid-base potentially leading to nocturia (nocturnal role in vitamin D biosynthesis. Tubular balance. With age, they become less effi- urination), which is experienced by degeneration often leads to reductions in cient at clearing acidic/basic metabolites/ 80-90% of people aged over 80 years EPO, which can lead, in turn, to reduced ions due to tubule degeneration. This is (Kujubu, 2009). Ideally, patients should be erythrocyte production and to anaemia. problematic in older people with diabetes, reminded to pass urine before going to bed However, some studies have demonstrated as acidic molecules such as ketones may to minimise the problem. increases in EPO secretion – these may accumulate in the blood, leading to life- be driven by age-related resistance to the threatening ketoacidosis. Reduced clearance of toxic metabolites effects of this hormone (Bolignano et Special care must be taken with drugs that al, 2014). Reduced creatinine clearance are excreted/eliminated in the urine. Dos- Reduced vitamin D biosynthesis Creatinine is a molecule that is continually ages of water-soluble drugs – such as cer- impairs the absorption of calcium and generated by skeletal muscles; serum tain antibiotics, amphetamines and digi- phosphate in the gut, which can con- levels usually remain constant because the talis – may need adjustment according to tribute to osteoporosis (Zhou et al, 2008). kidneys clear it from the blood at the same renal function to avoid toxic accumula- rate as it is produced. By the age of 80, tion. Indeed, overestimation of the GFR Post-renal changes clearance is reduced by around 30% can lead to unexpected drug toxicity in With age, the bladder gradually loses its (Choudhury et al, 2016); however, serum older patients (Zhou et al, 2008). However, elasticity due to an increase in collagen

CATHERINE HOLLICK CATHERINE creatinine levels remain fairly constant other organs and tissues, particularly the fibres in its wall. Loss in elasticity and

Nursing Times [online] May 2017 / Vol 113 Issue 5 48 www.nursingtimes.net Copyright EMAP Publishing 2017 This article is not for distribution Nursing Practice For more articles on renal function or continence care, go to Systems of life nursingtimes.net/continence

fibrosis of the bladder can contribute to Fig 3. Age cycle of the prostate incomplete emptying during micturition (urination), particularly in men with pros- tate enlargement. There is conflicting evi- Age 20–25 dence as to whether bladder volume walnut changes with age: recent research suggests Adrenal gland it rarely changes (Pfisterer et al, 2006). Age 35–40 golf ball Ageing and urinary incontinence The urinary sphincter often weakens with age and this may lead to urinary inconti- Kidney Age 50–60 nence – a problem often compounded by lemon age-related changes in the nervous system. Bladder However, urinary incontinence is not a Ureter normal consequence of ageing, as many individuals never experience it, even in Age 70–80 Prostate cricket ball extreme old age. gland Research indicates that around 11.6% of people aged 65-80 years experience incon- tinence; this rises to around 35% in those over 85, and to 69% in over-85s living in this results in a gradual compression of Coresh J et al (2007) Prevalence of chronic kidney nursing homes. Women seem to be at the urethra, making micturition more dif- disease in the United States. Journal of the American Medical Association; 298: 17, 2038-2047. greater risk of incontinence than men ficult. The onset of prostate cancer is also Čukuranović RC, Vlajković S (2005) Age related (26.6-35.0% compared with 12.6-24.0% in marked by an increase in prostate size and anatomical and functional characteristics of human those aged 85 years or older); this may be causes a similar compression of the ure- kidney. Facta Universitatis Medicine and Biology; 12: 2, 61-69. due to weakened pelvic floor muscles as a thra and reduction in strength of the urine Jaipaul N (2017) Effects of Aging on the Urinary result of childbirth. stream. Tests such as prostate-specific Tract. Bit.ly/MerkAgeingKidneys Incontinence can have a major negative antigen, together with physical examina- Kazancioğlu R (2013) Risk factors for chronic kidney disease: an update. Kidney International impact on psychological wellbeing and tion of the prostate, are often necessary to Supplements; 3: 4, 368-371. quality of life (Ranson and Saffrey, 2015). differentiate between malignancy and age- Kujubu DA (2009) Nocturia in elderly persons and related prostatic hyperplasia. nocturnal polyuria. Geriatric Nephrology Ageing of the urethra and prostate Curriculum; 19. McKiernan SH et al (2007) Adult-onset calorie Reports on age-related changes to the Conclusion restriction delays the accumulation of female urethra are contradictory: some Although it appears that little can be done mitochondrial enzyme abnormalities in aging rat indicate that the urethra shrinks and its to slow age-related changes to the renal kidney tubular epithelial cells. American Journal of Physiology Renal Physiology; 292: 6, F1751-F1760. walls become thinner and atrophied (Jai- system, research indicates that a high- Montague S et al (2005) Physiology for Nursing paul, 2017), while others report no evi- protein diet can normalise GFR in some Practice. Oxford: Baillière Tindall. dence of change in its length (Pfisterer et older people (Musso and Oreopoulos, Musso CG, Oreopoulos DG (2011) Aging and physiological changes of the kidneys including al, 2006). Age-related changes in vaginal 2011), potentially improving kidney func- changes in glomerular filtration rate. Nephron pH can encourage abnormal microbial tion. Renal function must be assessed Physiology; 119 (Suppl 1): 1-5. growth, increasing the risk of urinary tract before making any dietary changes, as pre- Pfisterer MH et al (2006) The effect of age on infections. existing renal disease can preclude high lower urinary tract function: a study in women. Journal of the American Geriatrics Society; 54: 3, Most middle-aged and older men expe- protein intake. In recent years a number of 405-412. rience a benign enlargement of the pros- studies have demonstrated the anti-aging Ranson RN, Saffrey MJ (2015) Neurogenic tate gland (prostatic hyperplasia) (Fig 3); effects of calorie-restricted diets. Long- mechanisms in bladder and bowel ageing. Biogerontology; 16: 2, 265-284. term calorific restriction appears to be Razzaque MS (2007) Does renal ageing affect effective at reducing the effects of renal survival? Ageing Research Reviews; 6: 3, 211-222. Anatomy and physiology of ageing, with vascular damage, glomerulo- Sturmlechner I et al (2017) Cellular senescence in ageing – updated series renal ageing and disease. Nature Reviews sclerosis and tubular fibrosis all reduced in Nephrology; 13: 2, 77-89. animal models (McKiernan et al, 2007). Vlassara H et al (2009) Decline of renal function in Article Date Although age-related decline in renal normal aging, role of oxidants/inflammation: when Part 1: the cardiovascular system Feb function is inevitable, the kidneys have a does it begin: Is it inevitable, preventable, or treatable? Geriatric Nephrology Curriculum. 7. Part 2: the respiratory system Mar built-in redundancy – the renal reserve – Weinstein JR, Anderson S (2010) The aging Part 3: the digestive system Apr and, in the absence of disease, will func- kidney: physiological changes. Advances in Part 4: the renal system May Chronic Kidney Disease; 17: 4, 302-307. tion adequately throughout life. NT Part 5: the nervous system Jun Zhou XJ et al (2008) The aging kidney. Kidney Part 6: the eyes and ears Jul International; 74: 6, 710-720. References Part 7: the endocrine system Aug Bolignano D et al (2014) The aging kidney Part 8: the reproductive system Sep revisited: a systematic review. Ageing Research For more on this topic go online... Part 9: the immune system Oct Reviews; 14: 65-80. (2016) Effect of ageing on the l Blood tests and age-related changes Part 10: the musculoskeletal system Nov Choudhury D et al renal function and disease. In: Skorecki K et al in older people Part 11: the skin Dec (eds) Brenner and Rector’s The Kidney, Vol II. Bit.ly/NTBloodTestsOlderPeople

PETER LAMB PETER Oxford: Saunders.

Nursing Times [online] May 2017 / Vol 113 Issue 5 49 www.nursingtimes.net