# Glomerular Filtration Rate

The glomerular filtration rate ( GFR for short ) in living beings is the amount of liquid blood components that is filtered per time in the kidney corpuscles of all kidneys present . The GFR thus represents the rate at which the primary urine is formed. In a healthy adult, the GFR is around 120 milliliters per minute or around 170 liters per day. GFR increases in infants and children with increasing size and then decreases in adult physiologically with age ( parallel to the decrease in cardiac output and therefore the decline in renal blood flow ) or pathological in kidney diseases of various kinds again.

The GFR is the most important parameter for assessing kidney function. In everyday clinical practice, it is calculated from the plasma creatinine concentration using an approximate formula.

## Physiological relationships

### Fractional elimination

Most of the substances that appear in the urine are partially reabsorbed in the tubular system or secreted into the tubular lumen . As a result, the amount of substance (amount of substance per time) excreted in the urine differs from the flow of substance via the glomerular filter . The proportion of the excreted in the filtered amount of substance for a given substance is called fractional excretion : ${\ displaystyle {\ dot {n}} _ {\ text {H}}}$${\ displaystyle {\ dot {n}} _ {\ text {g}}}$

${\ displaystyle f = {\ frac {{\ dot {n}} _ {\ text {H}}} {{\ dot {n}} _ {\ text {g}}}}}$

The fractional excretion can be a minimum of 0 (complete reabsorption, example glucose ) and a maximum of about 5 (pronounced secretion so that all of the plasma flowing through the kidney is cleared, example PAH ).

### Glomerular Filtration Rate

The mass flow of substances in the excretion can be determined by multiplying the volume flow (urine volume per time) by the concentration of the substance in question in the urine:

${\ displaystyle {\ dot {n}} _ {\ text {H}} = c _ {\ text {H}} \ cdot {\ dot {V}} _ {\ text {H}}}$

The mass flow of substances through the glomerular filter can thus be expressed as:

${\ displaystyle {\ dot {n}} _ {\ text {g}} = {\ frac {c _ {\ text {H}}} {f}} \ cdot {\ dot {V}} _ {\ text { H}}}$

The mass flow of substances through the glomerular filter can also be expressed as the product of concentration and volume flow, in this case the primary urine. If the substance under consideration is freely filtered, the concentration in primary urine is equal to the concentration in plasma:

${\ displaystyle {\ dot {n}} _ {\ text {g}} = c _ {\ text {P}} \ cdot {\ dot {V}} _ {\ text {g}}}$

The volume flow through the glomerular filter is nothing other than the glomerular filtration rate. This gives the formula:

${\ displaystyle {\ dot {V}} _ {\ text {g}} = {\ frac {c _ {\ text {H}}} {f \ cdot c _ {\ text {P}}}} \ cdot {\ dot {V}} _ {\ text {H}}}$

### Clearance

Clearance describes the fictitious plasma volume that is cleared of a certain substance per unit of time. Möller, McIntosh and van Slyke created the term in 1928 for the excretion of urea. The equation of clearance is

${\ displaystyle C = {\ frac {c _ {\ text {H}}} {c _ {\ text {P}}}} \ cdot {\ dot {V}} _ {\ text {H}}}$,

analogous to the above derivation, it results from the conversion of the mass flow of the excretion into a plasma volume flow. There is a relationship between clearance and glomerular filtration rate

${\ displaystyle C = f \ cdot {\ dot {V}} _ {\ text {g}}}$.

The determination of the clearance of a substance is possible without any problems because, unlike the determination of the GFR, it does not require knowledge of the fractional excretion. However, there are substances that are freely filtered and neither absorbed nor secreted, so that the fractional excretion is 1 and the clearance can be equated with the GFR.

### Free water clearance

Since the water concentration in the urine is practically the same as the water concentration in the plasma, the water clearance is equal to the urine flow:

${\ displaystyle C _ {\ text {W}} = {\ dot {V}} _ {\ text {H}}}$

The clearance of all osmotically active particles is called osmotic clearance and can be calculated from the urinary flow and the osmotic concentrations of urine and plasma using the usual formula :

${\ displaystyle C _ {\ text {osm}} = {\ frac {c _ {\ text {osm H}}} {c _ {\ text {osm P}}}} \ cdot {\ dot {V}} _ {\ text {H}}}$

Water that can be thought away from the urine so that it takes on the osmotic concentration of the plasma is called free water ; Water that has to be considered is considered negative free water. The clearance of the free water is obtained by subtracting the osmotic clearance from the water clearance:

${\ displaystyle C _ {\ text {fW}} = C _ {\ text {W}} - C _ {\ text {osm}} = {\ dot {V}} _ {\ text {H}} - {\ frac { c _ {\ text {osm H}}} {c _ {\ text {osm P}}}} \ cdot {\ dot {V}} _ {\ text {H}} = \ left (1 - {\ frac {c_ {\ text {osm H}}} {c _ {\ text {osm P}}}} \ right) \ cdot {\ dot {V}} _ {\ text {H}}}$

The clearance of the free water is a clinically important variable when assessing whether a patient is able to independently compensate for osmotic disturbances through the body's own regulatory mechanisms. The physiological response to hypoosmolarity is positive clearance of free water. In the case of hyperosmolarity, on the other hand, water should be retained by the action of the antidiuretic hormone , so that concentrated urine is produced, which mathematically results in a negative clearance of free water.

## Exogenous and endogenous markers

The determination of a clearance according to the above formula requires free filtration. If the determined clearance is to represent the GFR, the fractional excretion of the substance under consideration must also be 1. Since no endogenous substance perfectly fulfills these conditions, exogenous marker substances must be administered by injection or infusion to determine the GFR very precisely:

Exogenous markers are usually too time-consuming for clinical and outpatient routine diagnostics. The glomerular filtration rate is therefore (rare now) in clinical practice on the basis of endogenous marker creatinine or cystatin C determined.

## Creatinine

Creatinine is produced in muscle tissue through the breakdown of creatine ; its plasma concentration is subject to slight fluctuations. Ideally, creatinine is freely filtered in the glomerulus and is neither reabsorbed nor secreted by the kidneys. Thus, the glomerular mass flow is equal to the mass flow of the excretion and the fractional excretion 1, which justifies the equation of creatinine clearance and GFR. Because creatinine is only excreted via the kidneys, the glomerular mass flow can then be equated with the rate of creatinine formation in the metabolism . Based on these assumptions, the GFR can be calculated as the quotient of the creatinine formation rate and plasma creatinine concentration: ${\ displaystyle {\ dot {n}} _ {\ text {g}}}$${\ displaystyle {\ dot {n}} _ {\ text {H}}}$${\ displaystyle {\ dot {n}} _ {\ text {m}}}$

${\ displaystyle {\ dot {V}} _ {\ text {g}} = {\ frac {{\ dot {n}} _ {\ text {m}}} {c _ {\ text {P}}}} }$

The GFR is therefore inversely proportional to the plasma creatinine concentration: With a high glomerular filtration rate, small changes in serum creatinine correspond to large changes in the glomerular filtration rate, whereas with a low glomerular filtration rate, large changes in serum creatinine correspond to only small changes in the glomerular filtration rate. In a 60-year-old woman, for example, an increase in serum creatinine from 0.8 to 0.9 mg / dl corresponds to a decrease in the glomerular filtration rate of 10 ml / min from 78 to 68 ml / min, an equal decrease in the glomerular filtration rate from 20 to 10 ml / min, on the other hand, is associated with an increase in serum creatinine from 2.6 to 4.8 mg / dl.

Just looking at the concentration allows certain statements to be made about the kidney's filtering function , since a taller person who produces more creatinine also requires a higher GFR. In the early stages of kidney disease, however, serum creatinine is an inaccurate marker of low sensitivity , especially in people with less muscle mass, such as women, the elderly or diabetics. If only serum creatinine is used as a marker of impaired kidney function, the diagnosis of renal insufficiency can be overlooked. All creatinine-based methods for determining the GFR face the problem that 10–40% of the creatinine excreted in the urine does not come from glomerular filtration, but is secreted in the tubules .

In 1933, the pathologist Hans Popper (1903–1988) developed the creatinine clearance test to assess kidney function under Hans Eppinger (1879–1946) at the Vienna General Hospital .

### Creatinine Clearance

Since the urine flow and urinary creatinine concentration (via 24-hour urine collection ) as well as the plasma creatinine concentration (via blood sample) can be determined in the clinical setting, the creatinine clearance can be calculated from the measured values ​​using the above formula:

${\ displaystyle C _ {\ text {Creatinine}} = {\ frac {[{\ text {Creatinine}}] _ {\ text {Urine}}} {[{\ text {Creatinine}}] _ {\ text {Plasma }}}} \ cdot {\ dot {V}} _ {\ text {urine}}}$

The calculated clearance usually represents the GFR well. It can be normalized to the body surface so that a comparison with normal values ​​for a body surface of 1.73 m² is possible. The normalization is based on the formula C × 1.73 m² / KOF. The method has the following restrictions:

• Errors in collecting the urine (impair the quality of the clearance determination): The determination of the creatinine clearance requires an exact collection of the urine over 24 hours. At the beginning of the collection period, the urinary bladder must be completely emptied. All urine must be collected during the collection period. At the end of the collection period after exactly 24 hours, the bladder must be completely emptied into the urine collection container. Since the correct collection of a 24-hour urine collection is time-consuming and error-prone, the creatinine clearance is rarely determined in everyday clinical practice.
• Tubular creatinine secretion (the equation with the GFR is not justified): With normal or slightly impaired kidney function, the proportion of tubular creatinine secreted compared to the glomerularly filtered amount is low and can be neglected. In the case of severe renal impairment, the tubular portion secreted can amount to more than 50% of the excreted creatinine amount, the glomerular filtration rate may be considerably overestimated as a result. If the glomerular filtration rate is below 30 ml / min, the urea clearance should therefore also be determined. In contrast to creatinine, urea is reabsorbed in a tubular manner, the urea clearance therefore underestimates the glomerular filtration rate. If the mean value between creatinine and urea clearance is calculated, the errors of both measurements cancel each other out.

If the creatinine clearance is equated with the GFR, it can also be used to calculate the fractional excretion of a substance S (clearance of S by clearance of creatinine). The urine flow is shortened so that no 24-hour urine is necessary, but a single urine sample (to measure the concentrations).

${\ displaystyle f _ {\ text {S}} = {\ frac {[{\ text {S}}] _ {\ text {Urine}} \ cdot [{\ text {Creatinine}}] _ {\ text {Plasma }}} {[{\ text {S}}] _ {\ text {plasma}} \ cdot [{\ text {creatinine}}] _ {\ text {urine}}}}}$

### eGFR

As stated above, the GFR can be approximated by the quotient of the formation rate and the plasma concentration of creatinine. Due to the different formation rates, a serum creatinine of 1.3 mg / dl in a 20-year-old man corresponds to a glomerular filtration rate of 75 ml / min, whereas in an 80-year-old woman a glomerular filtration rate of 50 ml / min. The rate of formation depends on the muscle mass; If it is possible to estimate the formation rate from the patient's physique, the laborious urine collection can be dispensed with. Approximate formulas based on these considerations take into account, in addition to the measured creatinine concentration, easily accessible values ​​such as age, gender or skin color. Such estimated filtration rates are reported as eGFR (estimated GFR) . Various online kidney function calculators are available as aids (see web links ).

#### CKD-EPI formula

This formula was published in 2009 and takes into account the influencing variables of age, skin color, gender and creatinine ranges. This formula was revised again in 2012. If the MDRD formula was previously used to calculate the GFR, new data show that the so-called CKD-EPI formula is even more reliable, especially in the border area between healthy function and incipient renal insufficiency.

CKD-EPI uses the same parameters as the MDRD formula, but estimates the GFR better in higher GFR ranges, since different creatinine ranges are taken into account and also with regard to serum creatinine for women (</> 0.7 mg / dl) and Men (</> 0.9 mg / dl) is differentiated. However, there is no significant difference in stages 3 through 5.

For all GFR information, the calculation method should generally be specified by the laboratory, as well as a reference to the standardization.

The Levey et al. developed CKD-EPI formula is:

${\ displaystyle {\ text {eGFR}} = 141 \ times \ min ({\ text {SK}} / k, 1) ^ {a} \ times \ max ({\ text {SK}} / k, 1) ^ {- 1 {,} 209} \ times 0 {,} 993 ^ {\ text {Age}} \ times [1 {,} 018 {\ text {if female}}] \ times [1 {,} 159 { \ text {if black}}]}$

or broken down by gender, skin color and creatinine calculation:

${\ displaystyle {\ text {eGFR}} = 166 \ times ({\ text {SK}} / 0 {,} 7) ^ {- 0 {,} 329} \ times 0 {,} 993 ^ {\ text { Age}} \ quad ({\ text {female, black, SK}} \ leq 0 {,} 7)}$
${\ displaystyle {\ text {eGFR}} = 166 \ times ({\ text {SK}} / 0 {,} 7) ^ {- 1 {,} 209} \ times 0 {,} 993 ^ {\ text { Age}} \ quad ({\ text {female, black, SK}}> 0 {,} 7)}$
${\ displaystyle {\ text {eGFR}} = 163 \ times ({\ text {SK}} / 0 {,} 9) ^ {- 0 {,} 411} \ times 0 {,} 993 ^ {\ text { Age}} \ quad ({\ text {male, black, SK}} \ leq 0 {,} 9)}$
${\ displaystyle {\ text {eGFR}} = 163 \ times ({\ text {SK}} / 0 {,} 9) ^ {- 1 {,} 209} \ times 0 {,} 993 ^ {\ text { Age}} \ quad ({\ text {male, black, SK}}> 0 {,} 9)}$
${\ displaystyle {\ text {eGFR}} = 144 \ times ({\ text {SK}} / 0 {,} 7) ^ {- 0 {,} 329} \ times 0 {,} 993 ^ {\ text { Age}} \ quad ({\ text {female, not black, SK}} \ leq 0 {,} 7)}$
${\ displaystyle {\ text {eGFR}} = 144 \ times ({\ text {SK}} / 0 {,} 7) ^ {- 1 {,} 209} \ times 0 {,} 993 ^ {\ text { Age}} \ quad ({\ text {female, not black, SK}}> 0 {,} 7)}$
${\ displaystyle {\ text {eGFR}} = 141 \ times ({\ text {SK}} / 0 {,} 9) ^ {- 0 {,} 411} \ times 0 {,} 993 ^ {\ text { Age}} \ quad ({\ text {male, not black, SK}} \ leq 0 {,} 9)}$
${\ displaystyle {\ text {eGFR}} = 141 \ times ({\ text {SK}} / 0 {,} 9) ^ {- 1 {,} 209} \ times 0 {,} 993 ^ {\ text { Age}} \ quad ({\ text {male, not black, SK}}> 0 {,} 9)}$

With

• eGFR: estimated glomerular filtration rate adjusted for a standard body surface area of ​​1.73 m², unit: ml / min per 1.73 m²
• SK: serum creatinine in mg / dl (IDMS calibrated)
• ${\ displaystyle k}$: 0.7 (female), 0.9 (male)
• ${\ displaystyle a}$: −0.329 (female), −0.411 (male)

#### Cockcroft-Gault formula

The Cockcroft-Gault formula (also known as the Cockroft formula for short ) was developed in 1973 by Donald William Cockcroft and Matthew Henry Gault to estimate creatinine clearance. It was based on data from 249 men with a creatinine clearance between 30 and 130 ml / min.

${\ displaystyle C _ {\ text {creatinine}} = {\ frac {140 - {\ text {age}}} {72 \ times {\ text {SK}}}} \ times {\ text {weight}} \ times (0 {,} 85 {\ text {if female}})}$
• ${\ displaystyle C _ {\ text {Creatinine}}}$: estimated creatinine clearance in ml / min
• SK: serum creatinine in mg / dl
• Age: Age in years
• Weight: body weight in kg

The result is not related to the body surface. Unlike other formulas, the Cockcroft-Gault formula does not estimate the GFR determined by laboratory methods, but rather the creatinine clearance. Since creatinine is also secreted more or less tubularly, the creatinine clearance is always higher than the GFR, so that the Cockcroft-Gault formula systematically overestimates the GFR.

#### MDRD formula (Modification of Diet in Renal Disease)

Since 1989, the effect of a low-protein diet on the course of chronic kidney disease has been investigated in a large group of patients with impaired kidney function (Modification of Diet in Renal Disease Study, MDRD study). At the beginning of the study, serum creatinine, creatinine clearance and glomerular filtration rate (using [ 125 I] iothalamate) were determined for all study participants . The MDRD formula was developed in 1999 based on data from 1628 study participants. The inclusion of skin color takes into account the increased muscle mass of African Americans. There are several variants of the MDRD formula; the four-variable MDRD formula has become the standard, which includes age, gender, skin color and serum creatinine (given in exponential and logarithmic notation):

{\ displaystyle {\ begin {aligned} {\ text {eGFR}} & = 186 \ cdot {\ text {SK}} ^ {- 1 {,} 154} \ times ({\ text {age}}) ^ { -0 {,} 203} \ times (0 {,} 742 {\ text {if female}}) \ times (1 {,} 210 {\ text {if black skin color}}) \\ & = \ exp (5 {,} 228-1 {,} 154 \ times \ ln ({\ text {SK}}) - 0 {,} 203 \ cdot \ ln ({\ text {Age}}) - (0 {,} 299 { \ text {if female}}) + (0 {,} 192 {\ text {if black skin color}})) \ end {aligned}}}
• eGFR: estimated glomerular filtration rate adjusted for a standard body surface area of ​​1.73 m², unit: ml / min per 1.73 m²
• SK: serum creatinine in mg / dl
• Age: Age in years

The MDRD formula, which has since been modified, does not require the body weight to be stated, as it indicates the glomerular filtration rate for a standardized body surface area of ​​1.73 m². It is more accurate than the Cockcroft-Gault formula and creatinine clearance in people with moderate to severe chronic renal impairment. The value of the MDRD formula in healthy kidneys has not been clarified, and use in hospitalized patients is not recommended.

#### Counahan-Barratt formula

When applied to the laboratory values ​​of children, the previously mentioned formulas only give very incorrect results. Therefore, the specially developed Counahan-Barratt formula can be used in children.

${\ displaystyle {\ text {eGFR}} = {\ frac {0 {,} 43 \ cdot {\ text {KL}}} {\ text {SK}}}}$
• eGFR: estimated glomerular filtration rate
• KL: body length in cm
• SK: serum creatinine in mg / dl

#### Limitations of the approximation formulas

The approximate formulas have been validated for outpatients with chronic kidney disease with moderate to severe renal impairment (stages 3 and 4). The formulas are not suitable for determining the glomerular filtration rate in persons with normal kidney function or mild kidney function impairment. In particular, the MDRD formula underestimates this by approx. 10 ml / min in people with a glomerular filtration rate over 60 ml / min. The approximate formulas are also unsuitable for determining the glomerular filtration rate in hospital patients with acute deterioration in kidney function, in people who are seriously overweight, with greatly reduced muscle mass ( amputation of limbs, malnutrition ) or in people with particularly high ( food supplements for bodybuilders ) or lower ( vegetarians ) Creatine intake with food. The approximate formulas are also unsuitable as a means for population- wide screening and for monitoring kidney function in the particularly important early stage of diabetic nephropathy .

#### Creatinine blind area

The graph of the relationship between serum creatinine level and kidney filter function is hyperbolic because creatinine is in the denominator in all estimation formulas for the GFR . For example, if the GFR falls from 40 ml / min to 20 ml / min, this doubles the creatinine level. If, on the other hand, the GFR falls from 100 ml / min to 80 ml / min, this theoretically only increases the creatinine level by 25%. In fact, the increase in serum creatinine is even lower because as the GFR begins to decrease, the secretion of creatinine is increased. Only when the GFR falls by at least 50% is the rise in creatinine so great that it can no longer be explained by measurement errors or disruptive factors (muscle mass, protein intake, physical work). The range between 100 ml / min and 60 ml / min is traditionally referred to as creatine-blind . In fact, there is no clearly delimited creatine-blind area, only an increasing absolute uncertainty of higher eGFR values.

## Cystatin C

Cystatin C is a small, non- glycosylated protein (13 kDa, 122 amino acids) from the family of cysteine ​​proteinase inhibitors . Cystatin C is produced at a constant rate by all nucleated cells in the body. Due to its small size and a basic isoelectric point (pI≈9.0) , cystatin C is freely filtered in the glomerulus . In the renal tubule Cystatin C is not secreted. More than 99% of it is reabsorbed by the tubular epithelial cells, but does not get back into the bloodstream because it is broken down by the tubular cells. The concentration of cystatin C in the urine is therefore very low; a calculation of the cystatin C clearance via the urine collection is not possible, but also not necessary. Since cystatin C is constantly formed and is freely filtered in the kidneys, not tubularly secreted and does not return to the blood circulation after filtration, it is a better filtration marker than creatinine or urea, especially in the case of mild kidney function impairment, increased muscle mass or acute kidney failure.

The cystatin C determination is also not free from influencing factors. Higher cystatin C levels are found in hypothyroidism (hypothyroidism) , rheumatoid arthritis and of black African origin. Lower levels, on the other hand, are found in people with an overactive thyroid (hyperthyroidism) and women. In addition, the cystatin C determination has not yet been standardized and is more expensive than the determination of creatinine.

### Cystatin C clearance

The serum concentration of cystatin C (abbreviated to Cys) is a marker for estimating the GFR with the reference range of 0.50 mg / dl to 0.96 mg / dl (other information: <1.4 mg / l) The unit mg / dl must be omitted when inserting it into the estimation formulas. The unit of the GFR is then ml / min.

#### Cystatin C clearance

The simplest of many formulas is GFR = 80 / Cys.

#### other estimation formula

There are several other cystatin C-based GFR estimation formulas. Another example from the Pschyrembel requires a division of 74.8 by the serum concentration of cystatin C raised to the power of 1.33.

#### GFR formula

A more sophisticated formula was published in The New England Journal of Medicine in 2012. The serum cystatin C level is then divided by 0.8. The quotient is then raised to the power of -0.499 or -1.328, depending on whether the serum cystatin C concentration is less or greater than 0.8 mg / dl. This potency is first multiplied by 133, then by 99.6 percent of age (in whole years) and finally by 0.932 for women. To simplify the calculation, the factors 133 and 99.6% of age can be summarized as the product of age and 132.468. For women, GFR = potency × age × 123.46.

#### Laboratory formula

The company Siemens Healthcare Diagnostics recommended the lab formula GFR = -4.32 + 80.35 / Cys for their systems.

#### Combination formulas

There are also GFR estimation formulas in the specialist literature which, in addition to cystatin C, also ask about creatinine levels in order to improve results.

## Practical applications

It should be noted here that lower GFRs are physiological in premature infants and newborns . Premature infants have a GFR = 0.2 ml / min with a body weight of 1 kg and a GFR = 0.5 ml / min with a weight of 2 kg. Healthy full-term babies have a GFR = 1.5 ml / min with a weight of 3.2 kg. For purposes of comparison, staging and ICD-10 classification , the actual GFR is to be related to the standardized body surface area of healthy adults ( USA , 1926) of 1.73 m².

The normalized GFR (1.73 m² / BSA) is around 3.5 ml / min for a premature birth weighing 1 kg with a body surface area of ​​0.1 m². In a healthy newborn with a body surface area (BSA) of 0.2 m², the standardized GFR is about 13 ml / min. Calculation: GFR (1.73 m² / KOF) = 1.5 ml / min ÷ 0.2 m² × 1.73 m² = 12.975 ml / min. A strict distinction must therefore be made between the actual GFR (here 1.5 ml / min) and the standardized GFR (here 13 ml / min).

### Classification of kidney function

According to the recommendation of the Kidney Disease Outcome Quality Initiative (KDOQI), kidney functional performance is divided into the following levels:

Degree of kidney damage (glomerular filtration rate adjusted for a standard body surface area of ​​1.73 m², unit: ml / min per 1.73 m²):

• Stage I:> 90 means normal or increased GFR, but (as in stage II) protein in the urine or pathological findings in imaging procedures
• Stage II: 60–89 means slight loss of function
• Stage III: 30–59 means moderate loss of function
• IV stage: 15–29 means severe loss of function
• V stage: <15 means kidney failure

### Kidney function depending on age

As part of a study (NHANES III), the kidney function of 10,000 people living in the USA was checked. It was found that kidney function declines with age. This is independent of skin color and gender, in each case based on a standard body surface area of ​​1.73 m². A healthy kidney loses around 0.7% to 1% of its kidney function per year. In children and adolescents , however, the GFR initially rises roughly in proportion to the body surface.

eGFR at the respective age

Age (in years) Mean eGFR
0 1.5 ml / min
1 30 ml / min
10 70 ml / min
20-29 116 ml / min
30-39 107 ml / min
40-49 99 ml / min
50-59 93 ml / min
60-69 85 ml / min
over 70 75 ml / min

### Diagnosis of chronic kidney disease

A chronic kidney disease occurs when the adjusted glomerular filtration rate below 60 ml / min per 1.73 m² is three months or is detectable over just such a period of protein in the urine. Since the approximate formulas provide sufficiently accurate values ​​when the glomerular filtration rate is reduced below 60 ml / min and the protein excretion can be quantified using the protein / creatinine ratio in spontaneous urine, it is no longer necessary to collect the urine for 24 hours in order to diagnose chronic kidney disease necessary. The study on health in Germany (DEGS) provides representative data from Germany on the frequency of a reduction in the glomerular filtration rate to values ​​<60 ml / min per 1.73 m². According to this, 2.3% of the German resident population between the ages of 18 and 79 have impaired kidney function.

### Quantification of Chronic Kidney Disease Progression

Because of the anti-proportional correlation between serum creatinine and glomerular filtration rate, the rate of renal function loss in a certain time unit can only be estimated imprecisely from the change in serum creatinine. In a 50-year-old, an increase in serum creatinine from 1.0 to 2.0 mg / dl corresponds to a decrease in the glomerular filtration rate of 46 ml / min, and a further increase in serum creatinine from 2.0 to 3.0 mg In contrast, / dl corresponds to a drop in the glomerular filtration rate of only 14 ml / min.

### Complications of chronic kidney disease

If the glomerular filtration rate falls below 60 ml / min, various complications arise, in particular high blood pressure , malnutrition , anemia and bone diseases . Since these complications must be treated early, additional diagnostic and therapeutic measures are required if the glomerular filtration rate falls below 60 ml / min. If the glomerular filtration rate drops further below 30 ml / min, a nephrologist should be consulted, as a kidney replacement procedure such as dialysis or kidney transplantation may be necessary if the glomerular filtration rate falls below 15 ml / min .

### Dosage of drugs

Many drugs (in Germany on average every 6th active ingredient) are excreted through the kidneys. In the case of impaired kidney function, the dose must therefore often be adjusted. In particular, the Cockcroft-Gault formula, which has been in use since 1973, is used extensively in the calculation of drug doses depending on kidney function (see also dose adjustment for renal insufficiency ). The website dosing.de of the Heidelberg University Hospital is recommended as a further source of information .

### Glomerular filtration rate as a risk factor

As the glomerular filtration rate decreases, so does the incidence of cardiovascular diseases such as stroke and heart attack, as well as overall mortality . A reduced glomerular filtration rate is therefore a cardiovascular risk factor . There is a particularly high correlation between cardiovascular risk and cystatin C levels.

### Evaluation before kidney transplant

Due to the general shortage of organs, the criteria according to which a potential kidney donor is accepted have been relaxed in recent years. However, it is required that the glomerular filtration rate of a kidney donor be above 80 ml / min.

### Measurement of clearance versus approximate formulas

Due to the limitations of the approximation formulas, it is necessary to determine the glomerular filtration rate using a 24-hour urine collection

• in people with a particularly low or high body weight,
• with a particularly low-meat or meat-rich diet,
• in people with limb amputation,
• with rapid changes in kidney function,
• in diabetics in the early stages of kidney involvement ,
• if a precise knowledge of the glomerular filtration rate is required with normal or mildly impaired kidney function, e.g. B. if a kidney donation or treatment with kidney-damaging drugs is planned.

The determination of the kidney function using exogenous marker substances is usually only required in the context of research projects.

## restrictions

When using the numerous estimation formulas, the respective application restrictions must be taken into account; different formulas can produce different results. In addition, it must be taken into account whether a formula already contains a normalization for the body surface or whether it only estimates the absolute GFR. All clearance calculations and all estimation formulas assume a steady state between formation and excretion of the respective substance (e.g. creatinine) and are therefore not applicable if the GFR is currently changing. Therefore, the estimated GFR is used to classify chronic kidney failure, but not acute kidney failure . At the onset of kidney failure, the GFR would be overestimated because the creatinine has not yet accumulated to its new, higher equilibrium concentration; analogously, if the kidney function begins to recover, the GFR would be underestimated because the creatinine level is still above the equilibrium concentration.

### Tubular function

In the case of an extreme (absolute or relative) lack of fluids ( desiccosis , dehydration), there is a compensatory increase in tubular reabsorption with the result of oliguria or even anuria . The GFR can no longer be determined.

### Dialysis for uremia

With the kidney dialysis the complaints are a uremia be prevented. Corresponding symptoms in uremic encephalopathy , in uremic pericarditis and the uremic pruritus provide an indication is for the start of dialysis. The relevant clinical laboratory limits for each uremic uremic toxins and the various nephrotoxins not exist. Alternatively, andialysis is started with a reduction in the glomerular filtration rate. Renal replacement treatment is indicated even in the absence of uremia symptoms if the GFR is less than 7 ml / min. It remains unclear whether the actual GFR or the standardized GFR (1.73 m² / KOF) is meant here (for adults). A distinction is made between early dialysis (GFR <15 ml / min) and late dialysis (GFR <5 ml / min).

### Filtration ratio

All the usual radiological or nuclear medicine methods for the determination of the filtrative kidney function separately from one side only provide the filtration ratio or even only the elimination ratio of both kidneys to each other with the sum 100% without specifying the GFR.

### children

In children, the GFR determination (despite several available estimation formulas) is unusual or problematic because there are no GFR normal value tables for healthy and sick children.

When using the special GFR estimation forms for children, it remains unclear whether these formulas should determine the actual GFR or the standardized GFR (1.73 m² / KOF). The younger the children, the greater the differences between GFR and GFR (1.73 m² / KOF).

### Drug dosage

When it comes to the drug dosage , the renal excretion of the active ingredient is decisive and not the glomerular filtration of creatinine or cystatin C. If only the ineffective degradation products are excreted via the kidneys, then the knowledge of the GFR is important with regard to a possible bioaccumulation ( overdose in case of renal insufficiency) or also with regard to a too low active level ( underdosing with above-average kidney function) meaningless.

### Nephrectomy

After bilateral nephrectomy or total renal agenesis ( anephria , aplasia renalis bilateralis, renal aplasia ), the calculated GFR is the result of the dialysis. For all other dialysis patients, the GFR is the sum of machine filtration and residual renal function (residual diuresis ). But here, too, the falsifications of the GFR determination due to tubular reabsorption and tubular secretion of the substrates used must be considered. Filtration, secretion and absorption are controlled by nerves and hormones and can be influenced by drugs, especially diuretics and other blood pressure drugs .

## literature

• Robert Franz Schmidt , Florian Lang, Manfred Heckmann (eds.): Physiology of humans . 31st edition. Springer Medizin Verlag, Heidelberg 2010, ISBN 978-3-642-01650-9 , Chapter 29.10 Measurements of kidney function .
• Christian Thomas, Lothar Thomas: Renal insufficiency - determination of the glomerular function . In: Deutsches Ärzteblatt International . Volume 106, No. 51-52 / 2009 , 2009, pp. 849-854 ( aerzteblatt.de ).

## Older literature

• Richard Bright : Cases and observations, illustrative of renal disease accompanied with the secretion of albuminous urine. In: Guy's Hospital Reports. 1836, pp. 338-379.
• Franz Volhard , Theodor Fahr : Bright's kidney disease. Springer-Verlag, Berlin 1914.
• Franz Volhard : The bilateral haematogenic kidney diseases (Bright's disease). In: L. Mohr, Rudolf Staehelin (Ed.): Handbook of internal medicine. 1st edition, volume 3. Springer-Verlag, Berlin / Heidelberg 1918; Reprinted there, ISBN 978-3-662-42272-4 , 576 pages.
• Franz Volhard : The bilateral haematogenic kidney diseases. In: Gustav von Bergmann , Rudolf Staehelin (Hrsg.): Handbook of internal medicine. 2nd Edition. Volume 6 in 2 parts. Published by Julius Springer, Berlin / Heidelberg 1931; Reprint of Part 2 (pp. 1025-2140) ibid, ISBN 978-3-662-42701-9 .
• Wilhelm Nonnenbruch : The bilateral kidney diseases - Brightii disease , Ferdinand Enke Verlag , Stuttgart 1949, 212 pages.
• Gustav von Bergmann , Walter Frey (Ed.): Kidneys and lower urinary tract , in: Handbook of internal medicine , 4th edition, 8th volume, Springer-Verlag, Berlin / Göttingen / Heidelberg 1951, 1167 pages.
• Joachim Frey : Diseases of the kidneys, the water and salt balance, the urinary tract and the male genital organs. In: Ludwig Heilmeyer (ed.): Textbook of internal medicine. Springer-Verlag, Berlin / Göttingen / Heidelberg 1955; 2nd edition ibid. 1961, pp. 893-996, especially pp. 905-990.
• Herbert Schwiegk (Ed.): Kidney diseases , in: Handbook of internal medicine , 5th edition, 8th volume, 3 parts, Springer-Verlag, Berlin / Heidelberg / New York 1968, LVI, 3172 pages.

Wiktionary: Kidney  - explanations of meanings, word origins, synonyms, translations
• Renal function calculator - new: kidney function calculator eGFR online calculator takes into account formulas CKD-EPI / MDRD / Cockcroft-Gault / Majo / creatinine and cystatin C as well as formulas for young people. The website also provides helpful information on healthy kidneys, kidney diseases, the stages and the markers
• www.dosing.de - List of drugs relevant to the kidneys (dosage information, Dettli formula, GFR calculation, dose adjustment in case of renal insufficiency) from Heidelberg University Hospital
• gehealthcare-buchler.de - Calculation of the GFR according to the Cockcroft-Gault formula, here calculator as a freeware program for download
• Creatinine clearance calculator - Determination of kidney function using the MDRD and the Cockcroft Gault formula including a calculator for download (industry sponsored page)

## Individual evidence

1. Peter Reuter: Springer Clinical Dictionary 2007/2008. 1st edition. Springer-Verlag, Heidelberg 2007, ISBN 978-3-540-34601-2 , p. 595.
2. Horst Kremling: On the development of kidney diagnostics. In: Würzburg medical history reports. Volume 8, 1990, pp. 27-32; here: p. 29 f.
3. K / DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. In: American Journal of Kidney Diseases . Volume 39, Number 2 Suppl 1, February 2002, pp. S1-266. PMID 11904577 .
4. a b L. A. Stevens et al .: Assessing Kidney Function - Measured and Estimated Glomerular Filtration Rate . In: The New England Journal of Medicine . No. 354 , 2006, pp. 2473-2483 ( content.nejm.org ).
5. ^ Lesley A. Stevens & Andrew S. Levey: Measured GFR as a confirmatory test for estimated GFR . In: Journal of the American Society of Nephrology . tape 20 , no. November 11 , 2009, ISSN  1533-3450 , p. 2305-2313 , doi : 10.1681 / ASN.2009020171 , PMID 19833901 .
6. ^ HE Blum, KP Maier, J. Rodés, T. Sauerbruch: Liver Diseases: Advances in Treatment and Prevention . Springer Science & Business Media, 2004, ISBN 978-0-7923-8794-7 , pp. 216 ( google.com ).
7. Karl Schärer, Otto Mehls: Pediatric Nephrology. Springer-Verlag, Berlin, Heidelberg 2002, ISBN 978-3-642-62621-0 , p. 20. Original quote: "Ccorr = C x 1.73 / KO". This means the corrected clearance. The actual clearance C must be multiplied by 1.73 and divided by the body surface area KO. The result is the standardization of the GFR according to GFR (1.73 m² / KOF). - On page 467 there is the table by Jean-Pierre Guignard and Jean-Bernard Gouyon from 1988, cited several times. Here the GFR and the standardized GFR (1.73 m² / KOF) for eight different age groups are placed side by side.
8. So in the result probably also Jörg Dötsch and Lutz T. Weber ( kidney diseases in children and adolescents , Springer-Verlag, Berlin 2017, ISBN 978-3-662-48788-4 , p. 36), if they are in the "Kidney Protocol" of an infant give the body surface area of ​​0.24 m² and the reference value 1.73 m².
9. Andrew S. Levey, LA Stevens, CH Schmid, YL Zhang, AF Castro, HI Feldman, JW Kusek, P. Eggers & F. Van Lente: A new equation to estimate glomerular filtration rate . In: Annals of Internal Medicine . tape 150 , no. 9 , May 2009, p. 604-12 , doi : 10.7326 / 0003-4819-150-9-200905050-00006 , PMID 19414839 , PMC 2763564 (free full text).
10. Saulo Klahr, Andrew S. Levey, Gerald J. Beck, Arlene W. Caggiula, Lawrence Hunsicker, John W. Kusek, Gary Striker, The Modification of Diet in Renal Disease Study Group: The Effects of Dietary Protein Restriction and Blood-Pressure Control on the Progression of Chronic Renal Disease . In: The New England Journal of Medicine . tape 330 , no. 13 , March 31, 1994, pp. 877-884 , doi : 10.1056 / NEJM199403313301301 ( nejm.org ).
11. Andrew S. Levey, T. Greene, MD Schluchter, PA Cleary, PE Teschan, RA Lorenz, ME Molitch, WE Mitch, C. Siebert, PM Hall: Glomerular filtration rate measurements in clinical trials. Modification of Diet in Renal Disease Study Group and the Diabetes Control and Complications Trial Research Group . In: J Am Soc Nephrol . tape 4 , no. 5 , November 1, 1993, pp. 1159-1171 ( asnjournals.org ).
12. Jump up ↑ Andrew S. Levey, JP Bosch, JB Lewis, T. Greene, N. Rogers, D. Roth: A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group . In: Annals of Internal Medicine . tape 130 , no. 6 , March 16, 1999, ISSN  0003-4819 , p. 461-470 , PMID 10075613 .
13. The Modification of Diet in Renal Disease Study Equation, in short: the MDRD formula. In: The perfect formula .
14. ^ GL Myers et al .: Recommendations for Improving Serum Creatinine Measurement: A Report from the Laboratory Working Group of the National Kidney Disease Education Program . In: Clin Chem . No. 52 , 2006, p. 5-18 , PMID 16332993 ( clinchem.org ).
15. TM Barratt, R. Counahan, C. Chantler, S. Ghazali, B. Kirkwood, F. Rose: Estimation of glomerular filtration rate from plasma creatinine concentration in children. In: Archives of Disease in Childhood . tape 51 , no. 11 , p. 857-858 , PMID 1008594 .
16. ^ Lesley A. Stevens et al .: Evaluation of the Modification of Diet in Renal Disease Study Equation in a Large Diverse Population . In: J Am Soc Nephrol . No. 18 , 2007, p. 2749-2757 ( asnjournals.org ).
17. Eberhard Ritz (Ed.): Estimated GFR: Are There Limits to Its Utility? In: Journal of the American Society of Nephrology . Volume 17, 2006, pp. 2077-2085, Nephrology beyond JASN.
18. Alessandra Calábria Baxmann u. A .: Influence of Muscle Mass and Physical Activity on Serum and urinary creatinine and serum cystatin C . In: Clin J Am Soc Nephrol . No. 3 , 2008, p. 348-354 ( cjasn.asnjournals.org ).
19. M. Mussap, M. Plebani: Biochemistry and clinical role of human cystatin C . In: Crit Rev Clin Lab Sci . No. 41 (5-6) , 2004, pp. 467-550 , PMID 15603510 .
20. OF Laterza et al. a .: Cystatin C: An Improved Estimator of Glomerular Filtration Rate? In: Clinical Chemistry . No. 48 , 2002, pp. 699-707 ( clinchem.org abstract ).
21. Devraj Munikrishnappa: Limitations of Various Formulas and Other Ways of Assessing GFR in the Elderly: Is There a Role for Cystatin C? In: Geriatric Nephrology Curriculum . 2009, p. 1-6 .
22. Gerd Herold : Internal Medicine 2020 . Self-published, Cologne 2019, ISBN 978-3-9814660-9-6 , p. 968.
23. ^ EP Leumann: Kidney function tests. In: Karl Schärer, Otto Mehls (Ed.): Pediatric Nephrology . Springer-Verlag, Berlin / Heidelberg 2002, ISBN 978-3-642-62621-0 , p. 22. The unit is probably wrong. The sources given there are: A. Bökenkamp, ​​M. Domanetzki, R. Zinck, G. Schumann, D. Byrd, J. Brodehl: Cystatin C - a new marker of glomerular filtration rate in children independent of age and height. In: Pediatrics . 101, pp. 875-881; and G. Filler, F. Priem, I. Vollmer, J. Gellermann, K. Jung: Diagnostic sensitivity of serum cystatin for impaired glomerular filtration rate. In: Pediatric Nephrology. Volume 13, pp. 501-505.
24. Willibald Pschyrembel: Clinical Dictionary , 267th edition. De Gruyter , Berlin / Boston 2017, ISBN 978-3-11-049497-6 , p. 343.
25. Willibald Pschyrembel: Clinical Dictionary , 267th edition. de Gruyter , Berlin, Boston 2017, ISBN 978-3-11-049497-6 , p. 343.
26. Ulrich Kuhlmann, Joachim Böhler, Friedrich C. Luft , Mark Dominik Alscher , Ulrich Kunzendorf (eds.): Nephrology. 6th edition. Georg Thieme Verlag, Stuttgart, New York 2015, ISBN 978-3-13-700206-2 , p. 38, with the source citing there: LA Inker, CH Schmid, H. Tighiouart et alii: Estimating glomerular filtration rate from serum creatinine and cystatin C. In: The New England Journal of Medicine . 2012, Volume 361, pp. 20-29.
27. ^ Frans J. van Hoek, Frits AW Kemperman, Raymond Theodorus Krediet: A comparison between cystatin C, plasma creatinine and the Cockcroft and Gault formula for the estimation of glomerular filtration rate. In: "Nephrology, Dialysis, Transplantation", Volume 18, Issue 10, October 1, 2003, pp. 2024-2031; doi: 10.1093 / ndt / gfg349 .
28. Markus Daschner: Tabellarum nephrologicum. 3. Edition. Shaker Verlag , Aachen 2009, ISBN 978-3-8322-7967-7 , p. 67.
29. Willibald Pschyrembel: Clinical Dictionary , 251st edition. de Gruyter Verlag, Berlin / New York 1972, ISBN 3-11-003657-6 , p. 208: “In order to be comparable, the value found must be related to a body surface area of ​​1.73 m², for example one has to For a nine-year-old child with the calculated body surface area of ​​0.94 m², multiply the value by 1.73 and divide by 0.94. "
30. Markus Daschner: Tabellarum nephrologicum. 3. Edition. Shaker Verlag , Aachen 2009, ISBN 978-3-8322-7967-7 , p. 67.
31. Josef Coresh, Brad C. Astor, among others: Prevalence of chronic kidney disease and Decreased kidney function in the adult US population: Third National Health and Nutrition Examination Survey. In: American Journal of Kidney Diseases. 41, 2003, p. 1, doi: 10.1053 / ajkd.2003.50007 .
32. Glomerular Filtration Rate (GFR) Calculators
33. ^ Markus Daschner: Tabellarium nephrologicum. 3. Edition. Shaker Verlag, Aachen 2009, ISBN 978-3-8322-7967-7 , p. 67.
34. Weckmann Gesine, Chenot Jean-François, Stracke Sylvia: S3 guideline for the care of patients with chronic kidney disease that does not require dialysis in the general practitioner's practice . In: DEGAM guideline no. 22, AWMF register no. 053-048 . June 30, 2019 ( awmf.org [PDF; accessed May 12, 2020]).
35. YES Vassalotti, LA Stevens, Andrew S. Levey: Testing for chronic kidney disease: a position statement from the National Kidney Foundation. In: American Journal of Kidney Diseases . Volume 50, number 2, August 2007, pp. 169-180, doi: 10.1053 / j.ajkd.2007.06.013 . PMID 17660017 (Review).
36. ^ Matthias Girndt, Pietro Trocchi, Christa Scheidt-Nave, Silke Markau, Andreas Stang: The Prevalence of Renal Failure . In: Deutsches Aerzteblatt Online . February 12, 2016, ISSN  1866-0452 , doi : 10.3238 / arztebl.2016.0085 , PMID 26931624 , PMC 4782264 (free full text) - ( aerzteblatt.de [accessed on October 2, 2019]).
37. Dosing.de
38. Kunihiro Matsushita et al .: Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis . In: The Lancet . tape 375 , no. 9731 , June 12, 2010, ISSN  1474-547X , p. 2073-2081 , doi : 10.1016 / S0140-6736 (10) 60674-5 , PMID 20483451 .
39. ^ Emilio D. Poggio et al .: Demographic and clinical characteristics associated with glomerular filtration rates in living kidney donors . In: Kidney International . tape 75 , no. May 10 , 2009, ISSN  1523-1755 , pp. 1079-1087 , doi : 10.1038 / ki.2009.11 , PMID 19212414 .
40. Gerd Herold : Internal Medicine 2020 , self-published, Cologne 2019, ISBN 978-3-9814660-9-6 , p. 646.
41. Gerd Herold : Internal Medicine 2020 , self-published, Cologne 2019, ISBN 978-3-9814660-9-6 , p. 646.
42. Richard Fotter (Ed.): Pediatric Uroradiology. 2nd Edition. Springer-Verlag, Berlin / Heidelberg 2008, ISBN 978-3-540-33004-2 , 538 pages.
43. Markus Daschner, P. Cochat: Pharmacotherapy for renal insufficiency. In: Karl Schärer, Otto Mehls (Ed.): Pediatric Nephrology . Springer-Verlag, Berlin / Heidelberg 2002, ISBN 978-3-642-62621-0 , p. 467.
44. Peter Reuter: Springer Clinical Dictionary 2007/2008. 1st edition. Springer-Verlag, Heidelberg 2007, ISBN 978-3-540-34601-2 , p. 1292.
45. ^ Heinrich Knauf, Ernst Mutschler : Diuretika , Urban & Schwarzenberg , 2nd edition, Munich, Vienna, Baltimore 1992, ISBN 3-541-11392-8 , p. 145.
46. ^ Peter Karlson : Biochemistry. 6th edition. Georg Thieme Verlag, Stuttgart 1967, p. 347.