Association Between Aging and Decreased Glomerular Filtration Rate

Introduction

The glomerular filtration rate is the rate at which the kidneys filter blood. According to studies from the 1950s, there was a gradual decline in the glomerular filtration rate (GFR) due to normal aging. The decline in GFR started at 30 to 40 years of age, and the rate of decline accelerated after 50 to 60 years. This article provides relevant information on GFR decline with age.

When Was the Estimation of the Glomerular Filtration Rate Developed?

The process of glomerular filtration was first recognized by Ludwig in 1844. But, it took several years to develop a mechanism to estimate glomerular filtration. Between 1934 and 1935, Inulin was used to measure glomerular filtration rate. Constant insulin infusion and timely urine collection were the gold standard for glomerular filtration rate estimation. Following this, several techniques were devised for assessing GFR by approximating Inulin clearance. One of the techniques developed was measuring the clearance of endogenous creatinine (non-enzymatic dehydration of creatine). However, the measurement of endogenous creatinine overestimates inulin clearance by 22 percent, as renal tubules normally secrete creatinine.

What Are the Functions of the Kidney?

The kidney receives 20 to 25 percent of the cardiac output. Glomerular filtration by kidneys helps excrete metabolic waste products and helps maintain the internal homeostasis of water and electrolytes. The primary role of renal hemodynamics is to keep blood flow and pressure within the glomerular capillary at levels that facilitate an adequate filtration rate and help maintain tubular reabsorption and secretion function. The filtration rate depends on the optimal structure of the filtration apparatus. GFR is the best measurement tool to determine kidney function. In normal individuals, adequate GFR is 100 to 125 mL/min (milliliter per minute).

As an individual age, all organs, including kidneys, suffer from a progressive decline in biological function and structural changes regardless of the presence or absence of the disease. There is a decline in the GFR value of kidneys as individuals age. But, the magnitude of the decline in renal function with age has not been estimated. Few longitudinal studies point to a median loss of approximately 1 mL/min per year in healthy individuals.

What Is the Renal Manifestation of Normal Aging?

Some of the renal findings of the normal aging process are:

• Progressive loss of nephron mass.

• Global glomerulosclerosis (end-state for glomeruli).

• Arterio-nephrosclerosis (renal scarring caused by prolonged hypertension).

• Increase in interstitial volume.

• A decline in GFR.

Renal manifestation of aging associated with co-morbid conditions:

• The decline in glomerular filtration rate.

• Proteinuria (protein in urine).

Old age is a risk factor for chronic kidney disease (CKD). When aging is associated with co-morbid conditions like diabetes, the GFR decline accelerates.

How Does Aging Affect the Glomerular Filtration Rate?

With the measurement of endogenous creatinine, a gradual decline in GFR was recorded with age. Half of the adults above 70 years have a GFR estimated below 60 mL/min. The reduction in endogenous creatinine was independent of blood pressure and other co-morbid conditions in old age. Most of the experimental evidence suggests that a decrease in GFR is part of a normal biological process like senescence and is a phenomenon that tends to occur in individuals over 30 years of age. Changes in renal structure and function accompany the decline of GFR with aging:

Structural Changes:

Structural changes to the kidney are associated with the senescence kidney process. Along with the decline in GFR with aging, there are changes to renal plasma flow, glomerular capillary plasma flow rate, and the glomerular capillary ultrafiltration coefficient. The number of nephrons (basic unit of the kidney) tends to decline in healthy individuals with aging. Loss of nephrons is suggestive of a progressive degree of glomerulosclerosis.

Due to glomerulosclerosis, the remaining nephrons undergo compensatory hypertrophy responses. The hypertrophy changes exert increased tension in glomerular capillary walls, resulting in hypertension, hyperfiltration (excess urine filtrate produced), and damage to remaining nephrons. Compensatory hypertrophy can also cause podocyte (cells that filter urine and retain urine) injury and loss.

Renal mass reduction is caused by telomere shortening, DNA (deoxyribonucleic acid) instability, increased oxygen radicals, reduced Klotho expression, and overexpression of proteins that occur in the aging kidney. Klotho is expressed in distal convoluted tubules of the kidney and is a pivotal modulator of aging. Deficiency of Klotho expression due to aging can accelerate aging-related diseases.

Other age-related structural changes in kidneys are tubular atrophy, interstitial fibrosis, arteriolar hyalinosis, and atherosclerosis (build-up of fats in artery walls). If the individual has comorbidities, abnormal urinary albumin excretion, and elevated blood pressure, there can be more disease-related pathological changes to the kidney. The number of renal cysts tends to increase with aging.

Functional Changes

1. Impairment in Vasodilation Response in Renal Hemodynamics

   1. Kidneys develop greater sensitivity to stimuli from vasoconstrictors like angiotensin, norepinephrine, and endothelin.

   2. There is a decline in vasodilatory response with a decrease in response to triggers from acetylcholine, dopamine, and nitric oxide.

2. Decreased Capacity to Concentrate and Dilute Urine

   1. Urine Concentration: Kidneys develop 50 percent less capacity to conserve water and solutes under water deprivation.

   2. Urine Dilution: The kidneys develop a reduced diluting capacity after fluid overload, as there is a defect in generating free water.

3. Impaired Renal Regulation of Sodium or Potassium Balance

   1. With aging kidneys, there is a reduced capacity for sodium excretion. Therefore resulting in a sodium overload and causing fluid volume expansion.

   2. Aging kidneys have a lowered capacity to excrete potassium when consuming a high-potassium diet.

4. Acid-Base Dysregulation

   1. Kidneys have a reduced capacity to buffer metabolic changes.

   2. Kidneys have a reduced capacity to excrete excess hydrogen ions load and ammonium.

5. Calcium Homeostasis

   1. There is an impairment of vitamin D production in the skin.

   2. Increased secretion of parathyroid hormone.

Women tend to show a decline in GFR with aging. Since the GFR in women is less than that of men, the final GFR value at advanced age in women will be lower than in men.

How Is GFR in the Elderly Measured?

Conventional techniques of GFR measurements use the renal clearance of various endogenous and exogenous substances. Exogenous markers are creatinine and cystatin C, whereas the exogenous markers are Inulin or radiolabeled compounds. For accurate estimation, these substances must be exclusively excreted by glomerular filtration with minimal or no secretion from tubules. Measuring GFR in older people is difficult because of inaccuracy and bias. Efforts are ongoing for improved methods of GFR estimation, such as using serum cystatin C levels.

How Are Age Related Renal Changes Managed?

GFR in old age must be measured with sensitivity for accurately analyzing age-related kidney dysfunction.

In the elderly, adequate doses of medicine must be prescribed based on kidney function to avoid overdosing. Since older people may have several medications that require renal excretion, the dose must be modified based on compensated GFR level.

Since most elderly have joint pain or neuralgia (nerve pain), non-steroidal anti-inflammatory drugs (NSAID) are prescribed for pain relief. The NSAIDs are nephrotoxic with a high risk of GFR decline and must be carefully used.

Using iodinated contrast media for the aged can cause kidney injury, resulting in adverse outcomes such as renal dysfunction and abrupt GFR decline, eventually requiring dialysis. Therefore, the decision on contrast media use for the senior population must be based on risk and benefit analysis.

Conclusion

Aging slows down the biological process of the body. The effects can be noted in all organs, including the kidney. In kidneys, the aging process is quantified by reduced glomerular filtration rate, nephron loss, and other structural and functional changes. Age-related changes cannot be prevented, but individuals can continue leading good quality of life with few modifications to lifestyle.