Glomerular filtration rate (GFR)

The best measure of overall kidney function in health and disease.

The glomerular filtration rate (GFR) describes the volume of fluid filtered from the kidney glomerular capillaries into the Bowman’s capsule per unit time.

The GFR is generally estimated from serum concentrations of endogenous filtration markers such as creatinine or cystatin C.

Normal rate is 120-130 mL/min per 1.73 m2 and declines with age.

The kidney glomeruli are the site of plasma ultrafiltration and urine production.

The mean value of 120-130 mL/min/min/1.73 m2 for adults younger than 40 years declines with age but a GFR OF less than 60 is considered as moderately decreased for healthy adults of any age.

The first step in urine formation is the passive process of ultrafiltration of plasma from blood into the Bowman space as it traverses glomerular capillaries.

Creatinine clearance ( CCr) is the volume of blood plasma that is cleared of creatinine per unit time and is a useful measure for approximating the GFR. 


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) 

Estimated by calculating creatinine clearance using the Cockcroft-Gault equation which uses a patient’s age in years, body weight in kilograms, serum creatinine level in milligrams per deciliter and sex to estimate the creatinine clearance: 140-age x but dry weight/72 x swum creatinine x .85 if female.

The above equation has been validated in non-obese patients.

Varies by body size.

Varies by time of the day, protein intake, pregnancy, extracellular fluid status, blood pressure extremes, use of antihypertensive, and the presence of the severity of kidney disease.

The elderly have smaller muscle mass contributing to lower creatinine values, which in turn can lead to an overestimation of GFR when using the above equation.

Deviation from expected values for creatinine generation by muscle mass and diet are major causes of error in estimated GFR.

Decreases an estimated 1mL/min per year after the age of 40 as a result of glomerular sclerosis.

Declines 1% per year for every year of life after the third decade, so that one may outlive one’s renal function.

Level less than 60 mL/min represents loss of half or more of the adult level of normal kidney function.

Lower limits of normal are 87 mL/min per 1.73 m2 for a 20 year old person and 60 mL/min per 1.73 m2 for a 75 year old person.

Is not measured directly but it is assessed from clearance measurements or estimated from serum levels of endogenous filtration markers such as creatinine or cystatin C.

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.

Patients with GFR less than 30 mL/min per 1.73m2 have an average of 4 risk factors.

Factors that may contribute to decline in the GFR and that may be potentially reversible include: hypovolemia, hypotension, cirrhosis, nephrotic syndrome, obstructive uropathy, urinary tract infection, renovascular disease, the use of nonsteroidal anti-inflammatory drugs, severe hypokalemia or hypercalcemia.

Reduction of the glomerular pressure appears mediated by constriction of the afferent arterioles. small vessels that supply the glomerular microcirculation with blood from the circulation.
The glomeruli produce as much is 180 liters of glomerular filtrate per day in healthy adults.
Diseases that reduce the glomerular capillary surface area available for filtration or that  alter the intrinsic permeability of the capillary wall reduce the GFR.

Only a very small amount of albumin leaks into the urine, the end product, which is of much smaller volume.

The amount of plasma proteins and albumin that scape with the glomerular filtrate is tiny and depends on the selective permeability of the glomerular filtration barrier.

Measurement of creatinine to determine eGFR has limitation in risk prediction, particularly in patients with reduced muscle mass.
Even small reductions in the GFR are associated with increased cardiovascular morbidity  and mortality and reduced overall survival.

Acute kidney injury affects 10-20% of hospitalized adults, and chronic kidney disease is found in more than 10% of nonhospitalized adults.Early stage kidney disease manifests 10-1000 times more commonly than kidney failure.

GFR generally accepted as the best index of kidney function in health and disease.

Albuminuria is a marker of kidney damage.

GFR and albuminuria help define the stages of acute and chronic kidney disease.

Mean GFR is lower and albuminuria is higher in older people.

There is wide variation in levels of GFR and albuminuria in older people.

Lower GFR and higher albuminuria associated with other kidney abnormalities including decreased renal plasma flow, reduced maximal urine concentration and acidification, glomerular and arterial sclerosis, and tubular atrophy.

Levels of GFR and albuminuria related to severity of vascular disease risk factors and vascular disease.

When the accuracy of GFR is in doubt, serum Cystatin C can be used as a confirmatory test.

Measured GFR for Black Americans is, on average, 15.9% higher than that for non-Black persons with the same creatinine level, sex, and age.
Observed differences of increased GFR in blacks includes tubular secretion and creatinine generation, while differences in body size or muscle mass do not explain the
Nearly all laboratories estimate GFR by using race, but recently many have removed the race coefficient for black patients over concern about differential access to kidney transportation and specialist care.
Reasons for observed differences in serum creatinine among black study participants has never been elucidated.
The current guideline uses eGFRcr as the initial test in GFR evaluation, with an equation that includes race (Black versus non-Black), because studies indicate a higher average serum creatinine level for the same measure GFR level in black participants than  in non-black participants.
Blacks have a 3 to 4 full greater risk of kidney failure and higher mortality compared with individuals of other races and ethnicities with approximately 16% to 21% better estimated glomerular filtration rate compared with other individuals.
Using equations that incorporate creatinine and cystatin C but omit race a more accurate and led to smaller differences between black participants and non-black participants than equations without race with either creatinine or cystatin C alone.
SGLT2 inhibitors have a renoprotective effect including a reduction in pressure within the glomerular capillaries, with protection of glomerular podocytes, which are the targets of glomeruli injury in most of, if not all proteinuric kidney diseases.

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