Normal renal function supports all organs in maintaining homeostasis. The kidneys are responsible for many critical processes in the body.
Filtration: the kidneys remove waste products like urea and creatinine which accumulate as a byproduct of normal metabolic processes.
Fluid Balance: The kidneys regulate how much water is eliminated and reabsorbed. Which in turn contributes the maintenance of blood pressure.
Electrolyte Balance: The kidneys maintain the balance of electrolytes in plasma. Which in in turn maintains normal cellular function, plasma pH, osmolarity and bone strength.
Red Blood Cells: The kidneys produce erythropoietin, a hormone that stimulates the production of red blood cells.
Normal renal function varies with age, gender and body size and naturally declines as we age.
Renal Structure
Renal Artery
Plasma enters the kidneys via the renal arteries. This plasma contains the waste products of metabolic processes as well as the good stuff in blood: blood cells, clotting factors, nutrients, hormones, salts to name a few.
Glomerulus
As plasma moves through the blood vessels into the kidneys it will encounter the glomerulus.
The glomerulus is a network of tiny vessels arranged in a cluster inside the kidneys. This is where filtration occurs.
What is filtered by the glomerulus is determined by the size and charge of the molecules. Water moves freely through the glomerulus.
Filtered molecules collect into the Bowman’s capsule before entering the renal tubules.
Renal Tubules
The renal tubules are the vessels that collect water and molecules that have been filtered by the glomerulus. This is the initial formation of urine. There are distinct sections of the renal tubules that have differing functions.
- Proximal Tubule
- Descending Loop of Henle
- Loop of Henle
- Ascending Loop of Henle
- Distal Tubule
- Collecting Ducts
As urine moves through the tubules there is reabsorption of some components back into plasma as well as active secretion from plasma into the tubules.
The final urine product exists the kidneys via the collecting ducts and empties into the bladder.
Together the glomerulus and the renal tubules make up the nephron. The nephron is the basic unit of the kidneys. There are approximately 1 million nephrons in each kidney.
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Measuring Renal Function
1. Creatinine
Creatinine is a waste product of creatine degradation. Our bodies derive creatine from protein metabolism and uses it to store energy in muscle as creatine-phosphate. Once creatinine-P has donated it phosphate stores to make energy in the muscle, it once again becomes creatine. Creatine will naturally degrade overtime to become creatinine which is then cleared from the body by the kidneys.
Creatinine levels can be affected by factors such a muscle size, age and diet.
We use the waste product creatinine as a marker of renal function. Normal plasma creatinine levels range from 0.6-1.2 mg/dL. If creatinine levels exceed this the kidneys are not filtering blood as they should.
2. Blood Urea Nitrogen
Ammonia is a toxic byproduct of protein metabolism. It is converted to urea by the liver. Urea is then cleared by the kidneys.
The accumulation of urea is another marker that suggests the kidneys are not clearing as they should. It is measured as the BUN. Normal values range from 6-24 mg/dL.
3. Cystatin C
Cystatin C is protein that is produced by all the cells in the body. It is produced at a constant rate independent of age, gender and muscle mass. Once it is released into blood it is cleared by the kidneys. Its clearance is considered to be a more reliable marker for estimation of renal function rather than Scr.
Calculation of Creatinine Clearance
1. Cockcroft-Gault Equation
The Cockcroft-Gault equation uses serum creatinine in the calculation of creatinine clearance (CrCl) as a measure of renal function. The equation considers the rate of clearance of creatinine relative to a person’s age, weight and gender compared to standard benchmarks.
SCr = standardized serum creatinine in mg/dL
age = years
weight = kilograms
Because Scr is used in the denominator low Scr will result in a higher calculated CrCl. In patients who are underweight, vegetarian or elderly SCr tends to be lower. Their CrCl can be overestimated when calculated by the Cockcroft-Gault equation even in the presence of renal impairment.
This equation was previously the standard for estimation of renal function in clinical trials for many of the drugs that are currently on the market. Renal dosing recommendations from these studies are based on CrCl.
The normal range for CrCl is > 97 mL/min in men and > 88 mL/min in women.
As the superiority of Cystatin C becomes more established estimation of renal function by the glomerular filtration rate (GFR) has become the standard.
2. Glomerular Filtration Rate
The glomerular filtration rate (GFR) estimates how much blood is filtered at the glomerulus each minute. Though it can be measured directly, it is a complicated test. Instead a calculation of estimated GFR is used.
SCr = standardized serum creatinine in mg/dL
Scys = standardized serum cystatin C in mg/L
κ = 0.7 (females) or 0.9 (males)
α = -0.219 (females) or -0.144 (males)
min = indicates the minimum of SCr/κ or 1
max = indicates the maximum of SCr/κ or 1
age = years
The equation is a bit complicated. In practice it will be calculated and reported as part of the patients labs. It uses a combination of SCr and serum cystatin (Scys) to estimate renal function. Because cystatin C production is not affected by muscle mass, gender and a diet it is a better estimate of renal function.
There are 2 other version of this equation that uses Scr only and Cystatin only. The option of using Scr remains simply because SCr test are more widely available and more cost effective.
3. BUN/Scr Ratio
BUN and creatinine used for this calculation are both measured in plasma. Both are cleared by the kidneys at the glomerulus. A normal value for this ratio is 10-15:1. Anything above or below this value indicates that there is some renal dysfunction. In addition to indicating the presence of renal injury, the BUN/Scr ratio is one of five markers that we can use to identify the origin of renal injury based on location.
Interpretation of Results
How we interpret these three calculated values depends on whether renal injury is acute or chronic. Each of these categories are deserving if their own unit but briefly:
Acute Kidney Injury
Acute Kidney Injury (AKI) is a decrease in kidney function or GFR over hours, days, or even weeks. The Kidney Disease: Improving Global Outcomes (KDIGO) guidelines define AKI as:
- An increase in SCr of 0.3 mg/dL or more within 48 hours; or
- An increase in SCr > 1.5 times baseline within last 7 days
- Urinary volume less than 0.5 mL/kg/hour for at least 6 hours
Chronic Kidney Disease
The Kidney Disease Outcomes Quality Initiative (KDOQI), defines chronic kidney disease (CKD) as:
abnormalities of kidney structure or function, present for >3 months and requires one of two criteria for >3 months: either GFR <60 ml/min/1.73 m2 or markers of kidney damage, including albuminuria.
KDOQI
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