1. What is the prevalence of chronic kidney disease in the elderly?

Approximately 11% of patients older than age 65 years are noted to have chronic kidney disease (CKD) as estimated by using the Modification of Diet in Renal Disease (MDRD) study equation in those participating in National Health and Nutrition Examination Survey III. As the proportion of elderly increases in the population as a whole, the number of elderly patients with CKD is also expected to increase.

2. What structural changes occur in the kidney with age?

A progressive decrease in kidney weight and size occurs with increasing age as the glomeruli and the interstitium undergo fibrosis and sclerosis, tubules atrophy with drop in number and size, and vasculature scleroses and simplifies ( Fig. 49.1 ). Individual rates of kidney senescence may vary as various factors that are known to mediate fibrosis such as angiotensin II, transforming growth factor, nitric oxide, advanced glycosylated end products, oxidative stress, and factors associated with reducing sclerosis such as Klotho (antiaging transmembrane protein) and autophagy are altered as the kidney ages.

Stages of progressive vascular simplification and glomerular degeneration of cortical and juxtamedullary glomeruli and arterioles with associated microangiograms.

(From Takazakura, E., Sawabu, N., Handa, A., et al. (1972). Intravascular changes with age and disease. Kidney international, 2, 224. Reprinted by permission from Macmillan Publishers Ltd.)

3. How does age affect kidney function?

Functional changes in the kidney occur in parallel to changes in structure.

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  Decreased effective renal plasma flow (ERPF): ERPF decreases approximately 10% per decade with age in relation to progressive vascular sclerosis and loss of nephron number. Both changes in the number of functioning glomeruli and altered intrarenal signal and response to vasodilatory and vasoconstrictive mediators may affect renal plasma flow in the elderly.

  
  
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  Decrease in glomerular filtration rate (GFR): An estimated drop of 0.8 to 1.0 mL/min per 1.73 m ² /year in GFR is noted with progressive age depending on methodology used to measure clearance. Decreases in GFR with age may also be affected by race, gender, genetic variation, and underlying comorbidities including hypertension, diabetes, and cardiovascular disease.

  
  
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  Decreased ability to conserve filtered sodium: An increase in solute load per nephron in the face of decreased nephron number and increased medullary flow, and lower levels of plasma renin and aldosterone with age, likely contribute to individuals 60 years and older taking nearly twice the number of hours (31 vs. 18 hours) compared to those 30 years and younger to reach appropriate distal tubular sodium reabsorption when sodium restriction is imposed.

  
  
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  Decreased natriuretic ability: Individuals older than 40 years also handle a salt load less efficiently, as seen by taking a longer time to excrete 2 L of saline than those younger than 40 years. Although levels of the natriuretic hormone atrial natriuretic peptide appropriately increase, an incremental increase in urine sodium excretion is not evident in older compared to younger subjects, suggesting a possible decreased tubular sensitivity to natriuretic stimuli.

  
  
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  Abnormal tubular concentrating and diluting capacity: The older individual may not be able to reach maximal urinary concentration despite 12 hours of overnight water deprivation. Studies in aged animals indicate a decrease in tubular transporters, Na-K-2Cl, and ENaC beta and gamma subunits, urea transporters UT-A1, UT-B1, and intrarenal resistance to arginine vasopressin may be reasons for decreased urinary concentration. Similarly, maximally dilute urine is also not found with increasing age given that appropriate solute extraction, suppression of arginine vasopressin, and distal delivery of the filtered load is necessary.

  
  
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  Decreased net acid excretion: A diminished capacity for net acid excretion is found in older adults as both renal mass and GFR decrease are particularly noted when there is increased acid generation or acid load.

  
  
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  Changes in potassium handling: Although total body potassium is lower given a decrease in muscle mass in older individuals, lower plasma renin and aldosterone levels and decreased aldosterone response to potassium load in the elderly predispose to decreased tubular excretion of potassium. In the face of a sudden potassium load, older individuals may have a decreased ability to shift potassium into cells because Na-K-ATPase activity is decreased with increasing age.

  
  
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  Decreased kidney phosphate reabsorption: With phosphate restriction, older kidneys display evidence for decreased tubular phosphate absorption.

  
  
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  Tubular calcium excretion: Remains unchanged in the kidney with increasing age.

4. Why are the elderly subjects more susceptible to osmolar disorders such as hyponatremia and hypernatremia?

With inability to maximally dilute urine, the elderly subjects face a greater likelihood for hyponatremia when situations lead to increased arginine vasopressin (AVP) secretion or response. Medications such as morphine (high dose), nicotine, vincristine, and cyclophosphamide can enhance, whereas chlorpropamide, tolbutamide, nonsteroidal agents, and lamotrigine may promote AVP action. Age-associated decreased prostaglandin synthesis inhibits water diuresis and also predisposes the older individual to hyponatremia.

Hyponatremia with thiazide-type diuretics, commonly used to treat hypertension, is more common in the elderly. Similarly, the presence of a decreased thirst response in addition to a urinary-concentrating defect can predispose older individuals to dehydration and hypernatremia. Medications associated with decreased AVP secretion such as morphine (low dose), fluphenazine, promethazine, carbamazepine, and Haldol, or decreased AVP response including propoxyphene, demeclocycline, glyburide, and lithium, may increase likelihood of developing hypernatremia in older patients.

5. What makes older kidneys susceptible to kidney injury?

Acute kidney injury occurs with 3.5 times greater incidence in those older than 70 years. Approximately one-third of those ≥65 years of age are unable to regain kidney function defined as independence from dialysis therapy, or return of kidney function at or near baseline kidney function after an episode of acute injury. Loss of nephron number and function and decreased vascular response to vasodilation in aging contributes to decreased kidney reserve. Thus any process that further compromises kidney perfusion or loss of nephron function, including pre-renal, intrinsic, or post-renal causes, increases susceptibility to kidney injury. Volume loss, marked vasoconstriction, or decreased cardiac output are frequent pre-renal processes in the elderly with numerous comorbidities such as hypertension, diabetes, heart failure, malignancy, or atherosclerosis. Medications, including angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, and nonsteroidal agents or contrast infusion, can exacerbate the prerenal process, thereby requiring careful volume assessment before use. Intrinsic kidney processes such as toxin-associated tubular dysfunction (i.e., aminoglycosides), interstitial inflammation (i.e., antibiotic or other drug-mediated), or manipulation of the arterial tree leading to cholesterol embolization are often evident in the older individuals undergoing diagnoses and treatment for comorbid illnesses. Urinary tract obstruction can present with acute decline in kidney function in the elderly given laxity or overgrowth of pelvic structures with age and enlarged or prolapsed uterus in females and prostatic hypertrophy in male patients.

6. What are the best ways to estimate kidney clearance in the elderly?

Given loss of muscle mass with age, serum creatinine may not be the most useful marker for estimating kidney clearance. When appropriately collected, 24-hour urine creatinine clearances can be useful to measure steady-state clearances in the elderly. Formulas derived from 24-hour urine collections of populations of elderly with and without kidney disease are frequently used to estimate GFR at the bedside, minimizing frequent cumbersome 24-hour urine clearances in the elderly. Radioisotopes including iothalamate or iohexol X-ray fluorescence can be accurate; however, expense, radioactivity exposure, and availability limit these procedures for routine GFR measurements (see Chapter 3 ).

7. How does age affect blood pressure?

Data from the National Health and Nutrition Examination Survey (NHANES) report 67% of adults ≥60 years have hypertension. Changes in vascular elasticity with altered extracellular matrix cross-linking, fibrosis, and calcium deposition with age lead to stiffness and decreased capacity in the larger elastic vasculature. Older adults are thus noted to have high systolic blood pressure (SBP) and low diastolic blood pressure (DBP) with subsequent widened pulse pressure. Isolated systolic hypertension (ISH), defined as SBP >160 mm Hg and DBP <90 mm Hg, can be found in 75% of elderly patients with hypertension.

8. What is the importance of isolated systolic hypertension in the elderly?

ISH is associated with a twofold to fourfold increase in the risk of myocardial infarction, left ventricular hypertrophy, kidney dysfunction, stroke, and cardiovascular mortality. Even in patients who also have diastolic hypertension, the cardiovascular risk correlates more closely with the systolic than the diastolic BP. Among elderly patients, coronary heart disease risk varies directly with the systolic and pulse pressures and inversely with the diastolic pressure.