Kidney Dysfunction & Kidney in Aging

• The kidney's primary role is to maintain body fluid homeostasis, which means keeping the amount of water and salts in the body balanced so that our bodies function correctly. This is essential for maintaining blood pressure and preventing dehydration or fluid overload.

• Mechanisms of sodium balance are impaired with normal kidney aging.
    - In simpler terms, as we age, our kidneys don’t handle sodium as well anymore. Sodium is a key element that helps to regulate blood pressure and fluid balanc in the body.
    - Aging kidneys show a defective natriuretic response to excess sodium, meaning they are less capable of getting rid of excess sodium when we consume a lot of salt. Conversely, they have an impaired anti-natriuretic response when sodium is depleted, which affects how well our bodies retain sodium when we need it.
    - These changes can have significant effects on volume (how much fluid is in the body) and blood pressure control. For example, this can lead to issues like high blood pressure or swelling if too much sodium is retained.

• Delay in responses to changes in potassium and acid-base balance.
    - This means that the kidneys take longer to react when the levels of potassium (a crucial electrolyte for cell function) or the acidity/alkalinity of the blood change, which can be critical for overall health.

• Urinary concentrating ability is impaired due to various mechanisms.
    - Essentially, as we age, our kidneys become less efficient at concentrating urine, which can lead to increased fluid loss.

• Glomerular filtration rate (GFR) declines with age; interpretation of plasma creatinine levels requires caution due to loss of lean muscle mass affecting creatinine production.
    - GFR is a measure of how well the kidneys are filtering blood. With age, this filtering rate naturally decreases, meaning the kidneys are less effective.
    - Creatinine is a waste product from muscle metabolism, and as we age and lose muscle mass, it becomes trickier to use creatinine levels alone to assess kidney function because lower levels of creatinine might misleadingly suggest better kidney function when the decline is actually due to muscle loss, not improved kidney function.

• Structural damage in the kidney and renal vasoconstriction contribute to reduced filtration rates.
    - Over time, the kidneys can suffer from physical damage that affects how well they can filter blood. Renal vasoconstriction refers to the narrowing of the blood vessels within the kidneys, which can also decrease blood flow and filtering capacity.

Impact of Age on Kidney Function

• Loss of kidney function with age greatly influences drug dosing and susceptibility to superimposed injuries.
    - This means that as kidney function declines with age, doctors need to adjust how much medication they prescribe because the kidneys are less effective at filtering out drugs, increasing the chance of side effects.

• Difficulties in differentiating normal aging from superimposed diseases.
    - It can be challenging to determine whether kidney issues in older adults are due to normal aging or other underlying health problems.

• Physiological functions decline with time, illustrated by a decrease in renal reserve capacity.
    - Renal reserve capacity is the extra filtering capacity that healthy kidneys have. When this reserve decreases, it signifies a decline in the kidneys' ability to handle extra stress or illness.

• In young individuals, there is high filtration rate and ample spare kidney function, allowing resilience against injury.
    - Young kidneys are robust and can handle temporary stresses or damage well due to their high filtration capabilities.

• Aging kidneys lose spare capacity, heightening vulnerability to diseases.
    - As we age, kidneys become less capable of coping with stressors, making older individuals more susceptible to complications from illnesses or injuries.

Changes in Renal Excretory Function with Age

• Excretory functions decrease, leading to reduced abilities to maintain sodium, potassium, and acid-base homeostasis.
    - This change means that older kidneys are not as effective at regulating important electrolytes and maintaining the right acid-base balance, which is crucial for organ function.

• Reduction in urinary concentrating and diluting capabilities.
    - Older kidneys have more trouble balancing urine concentration, which means they might not retain water effectively when needed or might not excrete enough water during hydration.

• Aging leads to decreased renin production and impaired formation of 125-dihydroxyvitamin D.
    - Renin is a hormone that helps regulate blood pressure and fluid balance, and a decrease in its production can further complicate these functions. The decrease in vitamin D production is concerning as vitamin D is essential for bone health and calcium balance.

Sodium Balance Alterations

• Sodium conservation in states of restriction and natriuretic responses in overload states become impaired.
    - This means that in situations where sodium intake is low, the kidneys struggle to retain sodium effectively, and when sodium is in excess, they don’t respond as well to eliminate it.

Volume Contraction Due to Sodium Depletion

• Normal physiological responses to volume contraction include sympathetic nervous system activation and the renin-angiotensin-aldosterone system (RAAS).
    - When sodium levels drop, the body usually activates these systems to help restore balance and increase blood volume.
    - Aging leads to a loss of beta-adrenergic nerve activity affecting renin release. The activation of this system can become inefficient in older adults.
    - Loss of functional juxtaglomerular apparatus due to decreased glomeruli results in fewer renin secretion sites. The juxtaglomerular apparatus is crucial for sensing blood volume changes and releasing renin, so its degradation impacts blood pressure regulation.
    - Circulating renin, angiotensin, and aldosterone levels fall, contributing to sodium depletion.

Volume Expansion Responses

• In a healthy young kidney, volume expansion inhibits sodium retention by deactivating the vasoconstrictor systems (e.g., renal nerves, angiotensin II) and activating natriuretic factors (e.g., nitric oxide, cAMP, prostaglandins).
    - When we drink enough fluids, young kidneys effectively signal the body to get rid of excess sodium. This is not as effective in healthy older kidneys due to age-related changes.

• Aging kidneys exhibit increased sympathetic alpha-adrenergic activity and activation of the intrarenal angiotensin system.
    - This means that when older kidneys encounter volume changes, they may actually respond by trying to retain more sodium rather than excreting it, which can lead to high blood pressure.
    - Circulating renin-angiotensin-aldosterone levels decrease with aging but intrarenal renin activity may increase.
    - Diminished nitric oxide and prostaglandin production leads to elevated sodium retention influences.
    - Blunted natriuretic response to acute sodium loading can cause dangerous volume overload in elderly patients receiving saline IV treatments. This could lead to heart problems due to the additional fluid overload.

Salt-Sensitive Hypertension in the Elderly

• Aging kidneys are prone to salt-sensitive hypertension, more common with advancing age.
    - This means that as people age, their blood pressure is more likely to increase when they consume high sodium diets, leading to health risks.

• Acute pressure natriuresis response is blunted in the aged kidney.
    - The body's ability to excrete excess sodium in response to increasing blood pressure becomes less effective.
    - Increased alpha-adrenergic activity and decreased nitric oxide production contribute to this blunting, which further raises blood pressure levels.

• Aging kidneys demonstrate a rightward shift in renal function curve leading to increased blood pressure with sodium intake, even at normal levels.
    - This means the kidneys are less efficient in regulating sodium and fluid balance, leading to increased blood pressure, and most people often consume sodium far in excess of what is healthy.

• Normal sodium intake is often excessive in the US and Western countries (15 times the needed balance).
    - Many people consume much more sodium than their bodies need, worsening hypertension and related health problems.

• Increased total peripheral resistance due to vasoconstriction worsens hypertension in the elderly.
    - This refers to the narrowing of blood vessels that raises blood pressure, compounding the effects of sodium overload.

Effects of Diuretics in the Elderly

• Diuretics are the first-line treatment for hypertension but need careful administration due to age-related kidney changes.
    - Diuretics are medications that help the body remove excess water and salt through urine. However, older adults may face risks when using them because of their declining kidney functions.

• Common diuretics include:
    - Lasix (Furosemide): Acts on the thick ascending limb of the loop of Henle, inhibiting the sodium-potassium-chloride transporter; important for ~25% sodium reabsorption.
      - This medication is powerful; however, it can lead to significant fluid loss if not monitored carefully.
    - Thiazide diuretics: Act on the distal tubule, targeting the sodium-chloride co-transporter; responsible for ~5-7% sodium reabsorption.
      - These are milder diuretics but can still lead to loss of important electrolytes.
    - Amiloride: A potassium-sparing diuretic, blocking epithelial sodium channels (ENaC); responsible for ~1-3% sodium reabsorption.
      - This medication helps retain potassium while getting rid of sodium, which is important as older adults are at risk for low potassium levels when on diuretics.

• Age-related impairment in sodium handling can result in significant volume depletion when using diuretics, particularly Lasix which causes substantial diuresis.
    - Using powerful diuretics in older adults can lead to dehydration and low blood pressure, making monitoring vital.

• Thiazides also carry risks of volume depletion and hypokalemia.
    - Hypokalemia is a condition characterized by low potassium levels, which is dangerous and can lead to heart issues if not managed.

• Mechanism of potassium excretion under diuretic use discussed.
    - It’s crucial to have strategies in place to monitor potassium levels when using diuretics to prevent potential complications.

Changes to Potassium and Acid-Base Balance

• Changes to potassium balance lead to slower renal responses to body potassium and acid content alterations.
    - Abnormal potassium levels can affect heart function and overall health, making timely responses critical, but slower kidney reaction times pose a risk.

• Diminished thirst mechanism leads to decreased fluid intake in the elderly.
    - Many older adults may not drink as much water as they should because their body doesn’t signal thirst effectively, which can lead to dehydration affecting kidney function.

• Impaired kidney concentrating ability due to reduced medullary interstitial osmotic gradient, affecting urine concentration.
    - This means that older kidneys do not create a strong enough gradient to concentrate urine effectively, leading to excess fluid loss.

• Reductions in sodium reabsorption in the thick ascending limb diminish sodium chloride accumulation in the medullary interstitium.
    - This further complicates fluid balance and can lead to wide ranging health issues.

• Slow responses to antidiuretic hormone (ADH) from reduced adenyl cyclase responsiveness impair water balance restoration.
    - ADH helps the kidney retain water, and when the response is slow, it can lead to dehydration and electrolyte imbalances.

Mineral Metabolism Changes with Aging

• Reduced tubular phosphate reabsorption in aging kidneys can lead to phosphate wasting.
    - Phosphate is critical for bone health and energy production, and losing it can contribute to conditions like osteoporosis.

• Age-related decline in 125 dihydroxyvitamin D production contributes to increased osteoporosis risk.
    - Vitamin D helps the body absorb calcium and maintain strong bones, meaning its decline adds to the risk of fractures and bone disorders.

Hemodynamic Changes in Aging Kidneys

• Declines in renal plasma flow result in decreased GFR.
    - This decrease can lead to insufficient filtering of waste from the blood, posing health risks.

  - Changes due to renal vasoconstriction and structural alterations in kidney blood vessels and glomeruli:
  - Thickening of the basement membrane and expansion of mesangial cells lead to fibrosis (glomerulosclerosis).
    - This means that the kidney structures become scarred and less effective at filtering blood.
  - Ischemia of glomeruli may occur due to significant blood vessel constriction.
    - If blood flow to the glomeruli (the filtering units of the kidney) is limited, it can lead to further kidney damage and dysfunction.
  - Tubulointerstitial damage observed is a hallmark of the aging kidney.
  - This refers to damage outside the glomeruli that also affects kidney function.

Age-Related Decline in GFR

• GFR falls approximately 1% annually after age 50 (10% decline per decade).
    - This steady decline means older adults may experience increasing difficulty maintaining fluid and electrolyte balance.

• Findings consistent across populations and studies.
    - Research has shown that this decline is a common trend irrespective of varying health conditions.

• Females experience a delayed onset of GFR decline by about 10-15 years, potentially due to ovarian hormone protection.
    - Hormonal differences may contribute to a lesser decline at earlier ages among women compared to men.

Interpretation of Plasma Creatinine

• Plasma creatinine levels must be contextualized concerning age and sex; GFR estimation using serum creatinine can be misleading due to associated lean mass loss.
    - This means that when interpreting creatinine levels, we must consider the individual’s age and muscle mass to get an accurate reading of kidney function.

  - Parallel decline in creatinine production affects interpretation leading to potentially normal serum creatinine despite reduced GFR.
  - In older adults, reduced muscle mass can produce lower creatinine levels, masking the fact that their kidney function is worsening.

Mechanisms of GFR Decline

• GFR decrease is driven by increased renal vasoconstriction and loss of glomerular function.
    - This decrease can lead to a buildup of harmful substances in the blood over time as filtering becomes less efficient.

• Time-dependent increase in glomerular damage correlates with age.
    - The older we get, the more damage accumulates in the kidneys, reducing their function and health.

• Variability in glomerular injury across ages is noted in studies showcasing sclerosed glomeruli.
    - Not all individuals age the same way; some may have more severe kidney damage than others, depending on a variety of factors like health history and genetics.