The kidney has several functions, including the excretion of water, soluble waste (eg, urea and creatinine) and foreign materials (eg, drugs). It is responsible for the composition and volume of circulating fluids with respect to water and electrolyte balance and acid-base status. It has an endocrine function playing a part in the production of vitamin D and erythropoietin and as part of the renin/angiotensin/aldosterone axis. Measurements of renal function rely on measuring, in various ways the degree to which the kidney is successful in these roles.
An assessment of renal function may be required for several reasons:
- To identify renal impairment.
- To monitor disease progress.
- To assess baseline measurements prior to starting treatment with certain drugs.
- To monitor disease progress.
- The type of measurement of kidney function performed will be determined by the reason for assessing renal activity.
See also the separate article on Urine Dipstick Analysis.
- Appearance - blood, colour, turbidity.
- Specific gravity - sticks measure ionic particles only, not glucose.
- pH - normally acidic, except after a meal.
- Glucose - the presence of glucose in urine may indicate increased blood glucose, or tubular disorder.
- Proteinuria - the presence of protein in the urine may be caused by glomerular leak, raised serum low-molecular weight proteins, Bence Jones' proteins, myoglobulin, or protein of renal origin. National Institute for Health and Care Excellence (NICE) guidance highlights the importance of proteinuria as a marker for chronic kidney disease (CKD) which may be as significant as glomerular filtration rate (GFR), particularly in terms of determining the development of cardiovascular complications.
- Microscopy - urinary tract infection will show polymorphs with no casts; acute glomerulonephritis will show cells and casts; chronic glomerulonephritis shows little sediment.
Estimated glomerular filtration rate (eGFR) is the most frequent test of renal function. GFR varies as a function of normal physiology as well as disease. Its measurement is based on determining the volume of plasma from which a substance is removed by glomerular filtration during its passage through the kidney - in other words, the 'clearance' of that substance.
Clearance = (U x V)/P
|Where U = urinary concentration of X; V = rate of urine formation (ml/min); P = plasma concentration of X|
- Creatinine clearance is often used as a rough measurement of GFR, with a timed urine collection (often 24 hours) and a blood sample taken to measure plasma creatinine during that time period. It is limited by problems of accurate urine collection and tends to overestimate the GFR. It is also time-consuming.
- Inulin GFR is the gold standard for measurement but is a complex procedure used only when a more accurate result is important.
- Isotopic GFR is also sometimes performed using radioactive isotopes.
- The plasma creatinine concentration (alone) is only a very rough guide to renal function.
- Creatinine is produced by the muscles at a relatively constant level by the body and the plasma concentration therefore depends on the rate of excretion by the kidneys.
- Levels are, however, affected by age, gender, ethnic group, muscle bulk, ingestion of cooked meat, malnutrition and after use of some drugs - eg, trimethoprim.
- In people with extremes of muscle mass (eg, bodybuilders, people who have had an amputation or people with muscle wasting disorders) the eGFR should be interpreted with caution. Reduced muscle mass will lead to overestimation and increased muscle mass to underestimation of the GFR.
- Advise people not to eat any meat in the 12 hours before having a blood test for eGFR. Avoid delaying the despatch of blood samples to ensure that they are received and processed by the laboratory within 12 hours of venepuncture.
It is better to estimate the GFR taking some of these variables. There are several equations available (use your local laboratory's calculation if available, as this is likely to be more accurate as it can take into account local variations in accuracy of creatinine assays):
- Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine equation:
- Uses serum creatinine, age, gender and race.
- 4-item Modification of Diet in Renal Disease (MDRD) equation:
- Uses serum creatinine, age, gender and race
- Tends to underestimate normal or near-normal function - slightly low values should not be over-interpreted. It is not valid in those aged under 18.
- 6-item MDRD equation:
- Uses serum creatinine and albumin, blood urea nitrogen, and also age, gender and race
- Cockroft and Gault equation:
- Uses serum creatinine, age, weight and gender
- Counahan-Barrat method: used for those under 18 years.
The eGFR can then be used to assess the severity of the CKD.
NICE recommends the CKD-EPI creatinine equation because it is more accurate than the MDRD Study equation, is less biased at a GFR of more than 60 ml/min/1.73 m2 and performs better in people aged 75 years and over.
The use of the MDRD Study equation may over-diagnose CKD. The Cockcroft-Gault formula incorporates age, sex and weight in addition to creatinine, while the 4-variable MDRD formula incorporates age, sex, and ethnicity, but not weight.
A correction factor (multiply eGFR by 1.159) should be applied to GFR values estimated using the CKD-EPI creatinine equation for people of African-Caribbean or African family origin.
Stages of Chronic Kidney Disease
Use the suffix (p) to denote the presence of proteinuria when staging chronic kidney disease (CKD).
|Stage||Glomerular Filtration Rate|
Values are normalised to an average surface area (size) of 1.73 m2
|I||90+||Normal renal function (but urinalysis, structural abnormalities or genetic factors indicate renal disease).||Observation and control of blood pressure.|
|II||60-89||Mildly reduced renal function|
(Stage 2 CKD should not be diagnosed on GFR alone - but urinalysis, structural abnormalities or genetic factors indicate renal disease.)
|Observation, control of blood pressure and cardiovascular risk factors.|
|IIIa||45-59||Moderate decrease in renal function, with or without other evidence of kidney damage.||Observation, control of blood pressure and cardiovascular risk factors.|
|IIIb||30-44||Moderate decrease in renal function, with or without other evidence of kidney damage.||Observation, control of blood pressure and cardiovascular risk factors.|
|IV||15-29||Severely reduced renal function.||Planning for end-stage kidney disease.|
|V||<15||Very severe (end-stage) kidney disease.||Transplant or dialysis.|
This is a small protein produced at a relatively constant rate which is reabsorbed in the proximal tubule. One study found that it was superior to MDRD and Cockcroft-Gault formulae in estimating the GFR rate in renal allografts.
Cystatin C-based estimate of GFR should be used for the diagnosis of CKD at initial diagnosis in people with:
- An eGFR creatinine of 45-59 ml/min/1.73 m2, sustained for at least 90 days; and
- No proteinuria (albumin:creatinine ratio (ACR) less than 3 mg/mmol) or other marker of kidney disease.
Being a single injection (plasma) clearance technique, this affords an accurate measure of GFR. Iohexol is an exogenous marker that is comparable to inulin and (51)Cr-EDTA and can be measured by high-performance liquid chromatography. Iohexol can accurately measure GFR using a four-point plasma disappearance curve (10, 30, 120 and 300 min) or, in most cases, a two-point disappearance time (120 and 300 min).
It is recognised that using eGFR levels as a proxy for renal function has its limitations.Work is ongoing to develop a new method of staging CKD centred on its progression to end-stage kidney disease.
In particular, the current methods for estimating kidney function are not easy to apply in older age groups and there is a need to develop new methods for assessing renal function for the elderly.
Further reading and references
Cheung CK, Bhandari S; Perspectives on eGFR reporting from the interface between primary and secondary Clin J Am Soc Nephrol. 2009 Feb4(2):258-60.
Chronic kidney disease: early identification and management of chronic kidney disease in adults in primary and secondary care; NICE Clinical Guidelines (July 2014)
Traynor J, Mactier R, Geddes CC, et al; How to measure renal function in clinical practice. BMJ. 2006 Oct 7333(7571):733-7.
Levey AS, Inker LA, Coresh J; GFR estimation: from physiology to public health. Am J Kidney Dis. 2014 May63(5):820-34. doi: 10.1053/j.ajkd.2013.12.006. Epub 2014 Jan 28.
Diagnosis and management of chronic kidney disease; Scottish Intercollegiate Guidelines Network - SIGN (June 2008)
Qutb A, Syed G, Tamim HM, et al; Cystatin C-based formula is superior to MDRD, Cockcroft-Gault and Nankivell Exp Clin Transplant. 2009 Dec7(4):197-202.
Soveri I, Berg UB, Bjork J, et al; Measuring GFR: a systematic review. Am J Kidney Dis. 2014 Sep64(3):411-24. doi: 10.1053/j.ajkd.2014.04.010. Epub 2014 May 17.
Schwartz GJ, Furth SL; Glomerular filtration rate measurement and estimation in chronic kidney disease. Pediatr Nephrol. 2007 Nov22(11):1839-48. Epub 2007 Jan 10.
Connolly JO, Woolfson RG; A critique of clinical guidelines for detection of individuals with chronic Nephron Clin Pract. 2009111(1):c69-73. Epub 2008 Dec 5.
Eknoyan G; Chronic kidney disease definition and classification: no need for a rush to Kidney Int. 2009 May75(10):1015-8. Epub 2009 Mar 4.
Garasto S, Fusco S, Corica F, et al; Estimating glomerular filtration rate in older people. Biomed Res Int. 20142014:916542. doi: 10.1155/2014/916542. Epub 2014 Mar 20.