RENAL FUNCTION TEST I

Creatinine Clearance C_Cr

The creatinine clearance is not widely done any more, due to the difficulty in assuring a complete urine collection. When doing such a determination, to assess the adequacy of a complete collection, one always calculates the amount of creatinine excreted over a 24-hour period. This amount varies with muscle mass, and is higher in young people vs. old, in blacks vs. whites, and in men vs. women. An unexpectedly low or high 24-hour creatinine excretion rate voids the test. Nevertheless, in cases where estimates of creatinine clearance from serum creatinine are unreliable, creatinine clearance remains a useful test. These cases include "estimation of GFR in individuals with variation in dietary intake (vegetarian diet, creatine supplements) or muscle mass (amputation, malnutrition, muscle wasting), since these factors are not specifically taken into account in prediction equations.

 Estimated values

This formula expects weight to be measured in kilograms and creatinine to be measured in mg/dL, as is standard in the USA. The resulting value is multiplied by a constant of 0.85 if the patient is female. This formula is useful because the calculations are simple and can often be performed without the aid of a calculator

When serum creatinine is measured in µmol/L:

Where Constant is 1.23 for men and 1.04 for women.

One interesting feature of the Cockcroft and Gault equation is that it shows how dependent the estimation of CCr is based on age. The age term is (140 - age). This means that a 20-year-old person (140-20 = 120) will have twice the creatinine clearance as an 80-year-old (140-80 = 60) for the same level of serum creatinine (120 is twice as great as 60). The C-G equation also shows that a woman will have a 15% lower creatinine clearance than a man at the same level of serum creatinine.

 Estimated GFR (eGFR) using Modification of Diet in Renal Disease (MDRD)

For creatinine in µmol/L:

Creatinine levels in µmol/L can be converted to mg/dL by dividing them by 88.4. The 32788 number above is equal to 186×88.4^1.154.

Where the creatinine and blood urea nitrogen concentrations are both in mg/dL. The albumin concentration is in g/dL.

These MDRD equations are to be used only if the laboratory has NOT calibrated its serum creatinine measurements to isotope dilution mass spectroscopy (IDMS). When IDMS-calibrated serum creatinine is used (which is about 6% lower), the above equations should be multiplied by 175/186 or by 0.94086.
Since these formulae do not adjust for body mass, they (relative to the Cockcroft-Gault formula) underestimate eGFR for heavy people and overestimate it for underweight people. (see Cockcroft-Gault formula above)
Estimated GFR (eGFR) using the CKD-EPI formula
The CKD-EPI (Chronic Kidney Disease Epidemiology Collaboration) formula was published in May 2009. It was developed in an effort to create a formula more accurate than the MDRD formula, especially when actual GFR is greater than 60 mL/min per 1.73 m2.
Researchers pooled data from multiple studies to develop and validate this new equation. They used 10 studies that included 8254 participants, randomly using 2/3 of the data sets for development and the other 1/3 for internal validation. Sixteen additional studies, which included 3896 participants, were used for external validation.
The CKD-EPI equation performed better than the MDRD (Modification of Diet in Renal Disease Study) equation, especially at higher GFR, with less bias and greater accuracy. When looking at NHANES (National Health and Nutrition Examination Survey) data, the median estimated GFR was 94.5 mL/min per 1.73 m2 vs. 85.0 mL/min per 1.73 m2, and the prevalence of chronic kidney disease was 11.5% versus 13.1%.
The CKD-EPI equation, expressed as a single equation, is:

where SCr is serum creatinine (mg/dL), k is 0.7 for females and 0.9 for males, a is -0.329 for females and -0.411 for males, min indicates the minimum of SCr/k or 1, and max indicates the maximum of SCr/k or 1.
A clearer version may be as follows: For creatinine (IDMS calibrated) in mg/dL:
African American Female
If serum creatinine (Scr) <= 0.7

If serum creatinine (Scr) > 0.7

African American Male
If serum creatinine (Scr) <= 0.9

If serum creatinine (Scr) > 0.9

White or other race Female
If serum creatinine (Scr) <= 0.7

If serum creatinine (Scr) > 0.7

White or other race Male
If serum creatinine (Scr) <= 0.9

If serum creatinine (Scr) > 0.9

If Serum Creatinine < 0.8 mg/dL, use 0.8 mg/dL for Serum Creatinine

Estimated GFR for children using Schwartz formula

In children, the Schwartz formula is used.This employs the serum (mg/dL), the child's height (cm) and a constant to estimate the glomerular filtration rate:

Where k is a constant that depends on muscle mass, which itself varies with a child's age:

In first year of life, for pre-term babies K=0.33 and for full-term infants K=0.45

For infants and children of age 1 to 12 years, K=0.55

The method of selection of the K-constant value has been questioned as being dependent upon the gold-standard of renal function used (i.e., creatinine clearance, inulin clearance, etc.) and also may be dependent upon the urinary flow rate at the time of measurement
In 2009, the formula was updated to use standardized serum creatinine (recommend k=0.413) and additional formulas that allow improved precision were derived if serum cystatin measured in addition to serum creatinine importance of calibration of the serum creatinine level and the IDMS standardization effort

One problem with any creatinine-based equation for GFR is that the methods used to assay creatinine in the blood differ widely in their susceptibility to non-specific chromogens, which cause the creatinine value to be overestimated. In particular, the MDRD equation was derived using serum creatinine measurements that had this problem. The NKDEP program in the United States has attempted to solve this problem by trying to get all laboratories to calibrate their measures of creatinine to a "gold standard", which in this case is isotope dilution mass spectroscopy (IDMS). At the present time in late 2009 not all labs in the U.S. have changed over to the new system. There are two forms of the MDRD equation that are available, depending on whether or not creatinine was measured by an IDMS-calibrated assay. The CKD-EPI equation is designed to be used with IDMS-calibrated serum creatinine values only.

Cystatin C

Problems with creatinine (varying muscle mass, recent meat ingestion, etc.) have led to evaluation of alternative agents for estimation of GFR. One of these is, a ubiquitous protein secreted by most cells in the body (it is an inhibitor of cysteine protease).
Cystatin C is freely filtered at the glomerulus. After filtration, Cystatin C is reabsorbed and catabolized by the tubular epithelial cells, with only small amounts excreted in the urine. Cystatin C levels are therefore measured not in the urine, but in the bloodstream.
Equations have been developed linking estimated GFR to serum cystatin C levels. Most recently, some proposed equations have combined creatinine and cystatine
Normal ranges
The normal range of GFR, adjusted for is similar in men and women, and is in the range of 100-130 ml/min/1.73m². In children, GFR measured by inulin clearance remains close to about 110 ml/min/1.73m² down to about 2 years of age in both sexes, and then it progressively decreases. After age 40, GFR decreases progressively with age, by about 0.4 - 1.2 mL/min per year.

Chronic kidney disease stages 

Risk factors for kidney disease include diabetes, high blood pressure, family history, older age, ethnic group and smoking. For most patients, a GFR over 60 mL/min/1.73m² is adequate. But significant decline of the GFR from a previous test result can be an early indicator of kidney disease requiring medical intervention. The sooner kidney dysfunction is diagnosed and treated the greater odds of preserving remaining nephrons, and preventing the need for dialysis.

The (CKD) is described by six stages; the most severe three are defined by the MDRD-eGFR value, and first three also depend on whether there is other evidence of kidney disease

0) Normal kidney function – GFR above 90mL/min/1.73m²

1) CKD1 – GFR above 90mL/min/1.73m² with evidence of kidney damage

2) CKD2 (Mild) – GFR of 60 to 89 mL/min/1.73m² with evidence of kidney damage

3) CKD3 (Moderate) – GFR of 30 to 59 mL/min/1.73m²

4) CKD4 (Severe) – GFR of 15 to 29 mL/min/1.73m²

5) CKD5 Kidney failure - GFR less than 15 mL/min/1.73m² Some people add CKD5D for those stage 5 patients requiring dialysis; many patients in CKD5 are not yet on dialysis.

Note: others add a "T" to patients who have had a transplant regardless of stage.
Not all clinicians agree with the above classificaiton, suggesting that it may overlabel patients with mildly reduced kidney function, especially the elderly, as having a disease. A conference was held in 2009 regarding these controversies by Kidney Disease: Improving Global Outcomes (KDIGO) on CKD: Definition, Classification and Prognosis, gathering data on CKD prognosis to refine the definition and staging of CKD.