oPatientPlus articles are written by UK doctors and are based on research evidence, UK and European Guidelines. They are designed for health professionals to use, so you may find the language more technical than the condition leaflets.
Also see Abbreviated MDRD eGFR Calculator.
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.
- 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 Clinical Excellence (NICE) guidance highlights the importance of proteinuria as a marker for renal disease 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.
This 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.
- Estimated GFR (eGFR) 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.
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):
- In the UK the preferred calculation of eGFR uses the abbreviated MDRD equation v4 (MDRD = Modification of Diet in Renal Disease Study Group):
Different Equations for Assessing Renal Function
4-item MDRD Equation (preferred)
(see abbreviated MDRD eGFR calculator)
Estimated GFR (ml/min/1.73 m2) =186.3 x (Creat/88.4)-1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if black).
NB: the MDRD equation tends to underestimate normal or near-normal function - slightly low values should not be over-interpreted.
It is not valid in patients aged <18.
Local laboratories may correct for local variation in creatinine measurement (by adjusting as follows):
Estimated GFR (ml/min/1.73 m2) = F x 175 x (Creat/88.4)-1.154 x (Age)-0.203 x (0.742 if female) x (1.210 if black).
Where F is the correction factor (derived from isotope dilution mass spectrometry).
6-item MDRD Equation
Estimated GFR (ml/min/1.73 m2) = 170 x (Creat/88.4)-0.999 x (Age)-0.176 x (SU/0.257)-0.170 x (SAlb x 10) + 0.318 x (0.762 if female) x (1.180 if black).
Where Creat = serum creatinine (μmol/l); SU = serum urea (mmol/l); SA = serum albumin (g/l); Age = age in years.
Cockroft and Gault Equation
Estimated Creatinine Clearance = (((140-age) x wt x 1.2)/Creat) x (0.85 if female).
Where Creat = serum creatinine (μmol/l); and wt = weight in kg.
Use this method in children <18.
Estimated GFR (ml/min/1.73 m2) = 0.38 x (Ht)/Creat.
Where Ht = height in cm and Creat = serum creatinine (μmol/l).
This is then used to assess the severity of the chronic renal (kidney) disease.
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 endstage renal failure.|
|V||<15||Very severe (end-stage) renal failure.||Transplant or dialysis.|
It is recognised that using eGFR levels as a proxy for renal function has its limitations and work is ongoing to develop a new method of staging CKD centred on its progression to end-stage renal disease.
Methods for measuring GFR currently being researched include:
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.
Being a single injection (plasma) clearance technique, this affords a precise 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).
Further reading & references
- Diagnosis and management of chronic kidney disease, Scottish Intercollegiate Guidelines Network - SIGN (June 2008)
- Chronic kidney disease; NICE Clinical Guideline (September 2008)
- Achieving excellence in kidney care: Delivering the National Service Framework for Renal Services, Dept of Health, December 2009
- Cheung CK, Bhandari S; Perspectives on eGFR reporting from the interface between primary and secondary Clin J Am Soc Nephrol. 2009 Feb;4(2):258-60.
- UK Guidelines for the management of Chronic Kidney Disease, The Renal Association, January 2009
- No authors listed; K/DOQI clinical practice guidelines for chronic kidney disease: evaluation, classification, and stratification. Am J Kidney Dis. 2002 Feb;39(2 Suppl 1):S1-266.
- Traynor J, Mactier R, Geddes CC, et al; How to measure renal function in clinical practice. BMJ. 2006 Oct 7;333(7571):733-7.
- Schwartz GJ, Furth SL; Glomerular filtration rate measurement and estimation in chronic kidney disease. Pediatr Nephrol. 2007 Nov;22(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. 2009;111(1):c69-73. Epub 2008 Dec 5.
- Eknoyan G; Chronic kidney disease definition and classification: no need for a rush to Kidney Int. 2009 May;75(10):1015-8. Epub 2009 Mar 4.
- Qutb A, Syed G, Tamim HM, et al; Cystatin C-based formula is superior to MDRD, Cockcroft-Gault and Nankivell Exp Clin Transplant. 2009 Dec;7(4):197-202.
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Dr Huw Thomas, Prof Cathy Jackson
Dr Laurence Knott