Effect of ageing on function

Changes in Kidney Function

Renal System Aging results in both structural and functional changes in the kidney that affect drug metabolism and kinetics, as well as predisposing the patient to fluid and electrolyte abnormalities. Older individuals are well known to be more susceptible to acute renal failure

Functional Changes Although baseline homeostasis of fluids and electrolytes is maintained with normal aging, there is a progressive decline in renal reserve. This results in a compromise in the kidney’s ability to respond to either a salt or water load or deficit. This manifests clinically in patients being vulnerable to superimposed renal complications during acute illnesses. Chronic conditions such as hypertension accelerate this age-related loss of renal reserve and increased vulnerability in these patients should be anticipated.

1-Renal Blood Flow Above 30 years of age the renal blood flow declines progressively at a rate of 10% per decade. The majority of this reduction occurs in the cortex, with a relative increase in blood flow to the juxtamedullary region. dropping from 600 mL per minute per 1.73 m2 to 300 mL per minute per 1.73 m2 by the ninth decade. This is accompanied by increasing resistance in both afferent and efferent arterioles. These changes occur independent of cardiac output or reductions in renal mass. This decline in renal blood flow is thought to contribute to the decline in efficiency with which the aging kidney responds to fluid and electrolyte load and loss. serum creatinines at the upper limit of the “normal range” in an older individual represent significant functional decline,

2-Glomerular Filtration Rate Glomerular filtration rate (GFR) decreases by approximately 1 ml/min/year beginning by age 40. The bulk of the population loses about 10% of (GFR) and 10% of renal plasma flow per decade after the fourth decade of life. Approximately 30%of the population shows no measurable decline in renal function with normal aging. Between 5% and 10% of the population shows accelerated loss, even in the absence of identifiable comorbidities. Since there is also a steady loss of muscle bulk with age, with concomitant reduction in creatinine production, serum creatinine should remain constant. Serum creatinine is therefore a poor indicator of GFR in these patients. Rises in serum creatinine should therefore be taken seriously and not dismissed as normal aging. Dosing intervals for drugs that are excreted by the kidney need to be altered.

Results for women should be multiplied by 0.85 In frail older women with very little residual muscle mass, this equation probably overestimates GFRs. This steady decline in renal function with age manifests itself clinically as impaired ability to excrete a salt or water load. Results for women should be multiplied by 0.85

Extra care should be taken when replacing fluids in an older individual to prevent extracellular fluid overload. MDRD formula (because it was developed as part of the Modification of Diet in Renal Disease study). Many routine laboratories now automatically calculate an MDRD glomerular filtration estimate when a basic or a comprehensive metabolic panel is ordered.

3-proteinuria Despite the significant decline in GFR that occurs with aging, proteinuria is not a normal feature of the aging process. Proteinuria is always a pathological finding and requires a full workup.

Other Functional Changes Impaired concentrating ability in the older kidney. Impaired capacity to acidify urine manifested clinically as reduced excretion of an acid load. Older individuals are less likely to be able to maintain normal homeostasis when challenged. These changes contribute to the susceptibility of older individuals to acute renal failure, volume overload, and electrolyte abnormalities. Although there is an age-related decline in tubular functions such as glucose and amino acid transport, these declines closely parallel the decline in GFR and are believed to correlate with the loss of nephrons rather than aging of the tubule. Older individuals are also more sensitive to nephrotoxic injury. Careful thought should be given to the choice and dosing of antibiotics and other nephrotoxic drugs. Increased age is a risk factor for the development of radiocontrast nephropathy.

Structural Changes Kidneys grow vigorously from birth through adolescence, reaching their maximum weight and volume during the third decade of life. In humans, this weight starts to decline after the fourth decade and continues its decline throughout the remaining life span. Most of the decline in weight and volume appears to happen in the cortex, with relative sparing of the medulla. 20% of renal mass is lost between the ages of 40 and 80, mostly from the cortex . Microscopically there is a reduction in the number of functional glomeruli, but the size and capacity of the remaining nephrons increase to partially compensate for this loss.

Glomerulus The young healthy human kidney contains roughly 1 million nephrons. There is a steady decline in nephron number with age that starts around the fourth decade. This decline is believed to underlie the decline in GFR discussed above. the development of a focal sclerosing process, accompanied by thickening of the glomerular basement membrane. Age-Related Glomerulosclerosis: Sclerotic glomeruli typically first appear in the fourth decade of life.

Tubule the tubular section of the nephron usually degenerates and is replaced by connective tissue. Tubular hypertrophy then occurs in the remaining nephrons, principally in the proximal convoluted tubule. With thinning of the cortex, there is a decrease in tubule length and development of diverticuli in the distal convoluted tubule. As nephrons are lost, there is generalized tubular interstitial fibrosis. The structure of the distal tubule does not appear to change significantly with age.

Vasculature Renal arteries undergo age-related thickening, similar to that seen throughout the circulation. Smaller arteries may become tortuous and show luminal irregularities. When a glomerulus becomes sclerosed, there is frequent formation of an arteriovenous shunt as the afferent and efferent arterioles develop a direct connection, as the glomerular capillary is lost. This shunt is very important in maintaining medullary blood flow. a decline in renal blood flow and an increase in vascular resistance with age.

the kidney is also particularly susceptible to embolization. Infarcts may occur in the kidney, just as they do in other tissues of the body. the kidney is also particularly susceptible to embolization. embolic disease should certainly be kept in mind in an older individual with widespread vascular disease who demonstrates accelerated loss of renal function. Studies of renal perfusion in healthy older individuals from a pool of potential kidney donors have shown steady declines in renal perfusion with age that exceeded the reduction in renal mass, suggesting that declines in blood flow were a significant factor in the changes seen in renal function with age. These changes contribute to the susceptibility of older individuals to acute renal failure, volume overload, and electrolyte abnormalities.

Under normal circumstances, age has no effect on electrolyte concentrations or the ability of the individual to maintain normal extracellular fluid volume. However, the adaptive mechanisms responsible for regulating fluid balance are impaired in the elderly, and the aging kidney has a decreased ability to dilute and concentrate urine. This problem is compounded by the fact that older individuals have a decreased thirst perception and fail to increase water intake when dehydrated. Age also interferes with the kidney’s ability to conserve sodium. The geriatric patient excretes a sodium load more slowly and has a decreased ability to conserve sodium if dietary sodium is restricted, possibly predisposing the elderly patient to hemodynamic instability. Thus, fluid and electrolyte status should be carefully monitored in the elderly patient.

CONSEQUENCES OF IMPAIRED KIDNEY FUNCTION kidney disease and failure are predominantly diseases of the older population. All older patients should have an estimate made of their GFR. If they have a deficit in their kidney function, they should be managed aggressively to prevent progression to kidney failure. As CKD progresses, special attention should be paid to choice of drugs and their dosing and to the use of contrast dyes for imaging

↓Kidney size, weight, ↓Number of functional glomeruli ↓Number and length of functional renal tubules ↓GFR ↓RBF ↓concentrating ability of kidney Uretheral mucosal atrophy