Declines with age and is associated with a 25-30% decrease in renal mass and a 1% per year decline in renal bloodflow.
Kidney function-declines with age of approximately 0.75 mL/min in creatinine clearance per year after the age of 40 years
The average rate of GFR decline is approximately one mL/min/1.73 m² for year in the general population, and a lifetime risk of developing a GFR of less than 60 mL/min/1.73 m² is more than 50%.
The blood of an average adult is filtered through the approximately 2 million glomeruli contained within the kidneys every five minutes.
Every 24 hours an adult human produces the equivalent of 18 ten gallon fish tanks of filtrate.
Most of this filtrate is reabsorbed downstream in the kidney tubules, resulting in the net production of a liter or two of urine, which is nearly free of protein and large molecules, but contains small waste substances.
9 risk factors associated with impaired renal function and they include: smoking, obesity, elevated cholesterol levels, hypertension, diabetes, anemia, elevated C-reactive protein, elevated homocysteine levels, and albuminuria.
In the elderly a lower GFR, as estimated by serum cystatin C levels, is linearly related to the risk of cardiovascular events, premature death, and a decline in functional status.
The majority of people with kidney disease have dysfunctional gloeruli characterized by reduced filtration of waste products from the blood stream and increase loss of proteins that would otherwise maintain oncotic pressure within the circulation.
Within each gomerulus, blood is filtered and moves under pressure through specialized capillaries which have 3 layers: fenestrated endothelial layer that retains red cells and molecules larger than approximately 6 to 8 nm, a basement membrane and a layer of podocytes.
Each podocyte has tentacle like foot processes tightly sealed to the basement membrane, tethered to it by adhesion molecules called integrins.
The proper functioning of this seal and that of the slit diaphragm, specialized junction between neighboring podocyte foot processes there is made up of structural proteins, such as nephrin, which extends from the surface of the podocyte into the slit diaphragm is critical to blood filtration process.
Pathogenic variants, in more than 60 genes encoding podocyte proteins, can cause kidney disease.
The filtering apparatus of the kidney is sensitive to circulating, inflammatory proteins, toxins, and antibodies.
Inflammatory insults caused by viral infection in integrin molecules of the foot process may become activated by the innate immune system, the soluble urokinase plasminogen activator receptor leading to changes in the nephron expression and the shortening of the slit diaphragm and eventually proteinuria.
Slit diaphragm changes induced by anti-nephrin auto antibodies can compromise glomerular filtration.
Anti-nephrin autoantibodies, wax and wain with disease activity, particularly in minimal change disease.
Age related decline in kidney function is highly variable.
Assessment of kidney function
Assessment of kidney function: symptoms and signs, as well as measurements using urine tests, blood tests, and medical imaging.
Functions of a healthy kidney include: maintaining fluid balance, maintaining an acid-base balance; regulating electrolytes including sodium, potassium, and other electrolytes; clearing toxins; regulating blood pressure; and regulating hormones, such as erythropoietin; and activation of vitamin D, absorption of glucose, amino acids, and other small molecules;
Much of renal physiology occurs the level of the nephron, the smallest functional unit of the kidney.
Each nephron begins with a filtration component that filters the blood entering the kidney.
Glomerular filtrate flows along the length of the nephron, which is a tubular structure lined by a single layer of specialized cells and surrounded by capillaries.
The lining cells function by the reabsorption of water and small molecules from the filtrate into the blood, and the secretion of wastes from the blood into the urine.
Kidney function requires that it receive and adequately filters blood at the microscopic level by many hundreds of thousands of filtration units called renal corpuscles.
The renal corpuscle is composed of a ((glomerulus)) and a Bowman’s capsule.
A global assessment of renal function is often ascertained by estimating the rate of filtration, called the ((glomerular filtration rate (GFR))).
Assessment of kidney function includes the measurement of urine and its contents.
Abnormal kidney function may cause variation in the amount of urine produced, and the ability of the kidneys to filter protein, as measured by urine albumin or urine protein levels.
Blood tests are used to assess kidney function: glomerular filtration rate (GFR), assessment of electrolyte levels such as potassium and phosphate, assessment of acid-base status by the measurement of bicarbonate levels and assessment of the blood count for anemia.
The GFR) refers tom the volume of fluid filtered from the kidney glomerular capillaries into the Bowman’s capsule per unit time.
Creatinine clearance is the volume of blood plasma that is cleared of creatinine per unit time and is a useful measure for approximating the GFR.
Creatinine clearance exceeds GFR due to creatinine secretion.
Both GFR and CCr may be accurately calculated by comparative measurements of substances in the blood and urine, or estimated by formulas using just a blood test result (eGFR and eCCr)
The GFR and CCr are used to assess the excretory function of the kidneys.
Staging of chronic kidney disease is based on categories of GFR as well as albuminuria.
The kidney filtration rate is dependent on the difference between the higher blood pressure created by vasoconstriction of the input or afferent arteriole versus the lower blood pressure created by lesser vasoconstriction of the output or efferent arteriole.
GFR is equal to the renal clearance ratio when any solute is freely filtered and is neither reabsorbed nor secreted by the kidneys.
The GFR measured is the quantity of the substance in the urine that originated from a calculable volume of blood.
The GFR is typically recorded in units of volume per time: milliliters per minute (mL/min).
The normal range of GFR, adjusted for body surface area, is 100–130, average 125 (mL/min)/(1.73 m2) in men and 90–120 (mL/min)/(1.73 m2) in women younger than the age of 40.
In children, GFR measured is 110 (mL/min)/(1.73 m2) until 2 years of age in both sexes, and then it progressively decreases.
After age 40, GFR decreases progressively with age, by 0.4–1.2 mL/min per year.
Estimated GFR (eGFR) is now recommended by clinical practice guidelines.
Measured GFR (mGFR) is recommended as a confirmatory test when more accurate assessment is required.
The kidney function can also be assessed with medical imaging.
Imaging, such as kidney ultrasound or CT scans, assess kidney function by indicating chronic disease by showing a small or shrivelled kidney.
Nuclear medicine tests, directly assess the function of the kidney by measuring the perfusion and excretion of radioactive substances through the kidneys.
When evaluating renal function it is recommended to perform a history and physical examination, a renal ultrasound and a urinalysis.
Pertinent history includes:
medications, presence of edema, nocturia, gross hematuria, family history of kidney disease, diabetes and polyuria.
Physical examination findings include: signs of vasculitis, lupus erythematosus, diabetes, endocarditis and hypertension.
A urinalysis is helpful: with no pathology suggests an extrarenal etiology.
Proteinuria and/or urinary sediment usually indicates the presence of glomerular disease.
Hematuria may be caused by glomerular disease or by a disease along the urinary tract.
Renal ultrasound helps to,determine renal sizes, echogenicity and any signs of hydronephrosis.
Renal enlargement usually indicates diabetic nephropathy, focal segmental glomerular sclerosis or myeloma.
Renal atrophy suggests longstanding chronic renal disease.
Risk factors for kidney disease include diabetes, high blood pressure, family history, older age, ethnic group and smoking.
CKD stage GFR level ((mL/min)/(1.73 m2))
Stage 1 ≥ 90
Stage 2 60–89
Stage 3 30–59
Stage 4 15–29
Stage 5 < 15
The severity of chronic kidney disease (CKD) is described by six stages.