ESTIMATED GLOMERULAR FILTRATION RATE Victor Trumper, The Oval, 1902 “Trumper will always remain for your true Australian the greatest batsman that ever lived… Trumper’s winged batsmanship was seen in the Golden Age of cricket, at his finest, master of some of the greatest bowlers the game has known. When he played for Australia, Clem Hill, Monty Noble, Syd Gregory and Warwick Armstrong were batsmen with him. Splendid as the cricket of these men might be, day after day, whenever Trumper got out the light seemed to go for a while from an Australian innings. The eagle is gone and now-crows and daws. We make an artist’s immortality by thinking upon and loving his work, Trumper was an artist cricketer; let him live again in the mouths of men whenever Test matches are in action. Since he accomplished some of his greatest innings in this land, English cricket owes much to his ghost…” “The Summer Game”, Sir Neville Cardus, 1929. He was Australia’s greatest batsman of the “Golden Age of Cricket” and like Sir Donald Bradman during the Great Depression years, a national hero to Australians during a time of severe economic hardship at the close of the Nineteenth century. He died tragically at the age of just 37 years in 1915, while his homeland was locked in deadly conflict at Gallipoli and the Western front. All Australia mourned. Some of his greatest accolades came from English writers. Below, a poignant entry in the death registers of New South Wales for 1915, recording the death of Victor Trumper, from “chronic parenchymatous nephritis” and “uraemic convulsions”. Nothing could have been done for Australia’s greatest hero in 1915. Remarkable advances however, have been made since Victor’s day. The medical profession that tried so desperately to keep him alive would have been astounded by the life saving technology available to sufferers of kidney disease in the 21st century. The disease that eventually killed the great cricketer may well have been taking its toll even during his greatest innings at the Oval in 1902, though no evidence of it would have been apparent at the time. Again in the 21st century advances have been remarkable in the early detection of kidney disease. By use of the eGFR test we may detect kidney disease at its earliest inception, even in those in apparently perfect health, and by so doing be able to alter the course of the disease that took one of our greatest heroes in one our history’s darkest and saddest moments. ESTIMATED GLOMERULAR FILTRATION RATE Introduction Traditionally renal function has been determined by the serum creatinine and to a lesser extent the serum urea levels, (a much less specific indicator). However there are a number of important drawbacks with using creatinine as a biomarker for renal function, including: ● The serum creatinine does not increase beyond normal limits until more than 50% of GFR has been lost. Significant renal dysfunction may therefore exist, even though the serum creatinine level is normal. ● Serum creatinine reference intervals from most laboratories quote a range of values, taken from normal distributions, which represent 95th percentile ranges for subjects of all ages and gender for the method used. However age and gender significantly affect what a normal creatinine level should be. The best measure of renal function is the glomerular filtration rate. This measurement is very difficult and not practical in most circumstances. A good estimate of the glomerular filtration rate however can be made by a formula which determines this value based on the 3 parameters of: ● Serum creatinine levels ● Age ● Gender Calculation of the eGFR: Estimated Glomerular Filtration Rate (eGFR) using the MDRD (Modification of Diet in Renal Disease) formula is the recommended method of measuring kidney function. -1.154 The revised MDRD formula (the “175” formula) eGFR = 175x (SCR x 0.0113) x (age)-0.203 x (0.742, if female) Where: ● MDRD = Modification of Diet in Renal Disease. ● eGFR = estimated glomerular filtration rate (mL/min/1.73m2). ● SCR = serum creatinine concentration (µmol/L). ● Age is expressed in years. An eGFR is now automatically provided with every laboratory request for a serum creatinine (in people aged over 18 years). If a lab has not provided the eGFR it can be estimated via the eGFR calculator available at the Kidney Health Australia Website: eGFR Calculator Utility The utility of the eGFR includes: 1. The eGFR can be used to detect renal impairment before this is apparent: ● Clinically People with chronic kidney disease (CKD) may not notice any symptoms until they reach end stage kidney disease requiring dialysis or transplant (eGFR < 15 mL/min/1.73m2). ● On routine creatinine and urea measurements. eGFR may be markedly reduced while the serum creatinine is still in the normal range Knowledge of an eGFR between 60-90mL/min/1.73m2 may be of assistance in providing an earlier warning of eGFR reduction and allowing monitoring of trends over time. 2. A guide to the need for further investigation: ● In general terms, further investigation of eGFR is only required if the eGFR is < 60mL/min/1.73m2 3. The stratification of chronic renal disease into 5 recognized clinical stages, (see appendix 1& 2 below). 4. The monitoring of the progress of chronic renal disease. 5. Guiding drug dosing where renal function is an important consideration: ● Where an eGFR (using MDRD) is on hand it is clinically appropriate to use this to assist drug dosing decision making. 6. Determining risk to renal function associated with the administration of radiological IV contrast material. Sources of Error With Creatinine Levels: Serum creatinine is an unreliable and insensitive marker for mild to moderate chronic kidney disease. Patients may lose 50% or more of their kidney function before the serum creatinine value rises above the upper limit of normal quoted values. It is affected by many factors other than kidney function including: ● Age ● Gender ● Muscle mass Serum creatinine concentration is only useful for following the trend of kidney function, in an individual over time. With eGFR levels: Clinical situations where eGFR results may be unreliable and/or misleading include: ● Acute changes in kidney function, (e.g. acute kidney failure). ● Dialysis-dependent patients. ● Exceptional dietary intake (e.g. diet, high protein diet, recent consumption of cooked meat, creatine supplements). ● Extremes of body size, high muscle mass (may overestimate). ● Diseases of skeletal muscle, paraplegia, or amputees (may underestimate). ● Children under the age of 18 years. ● Severe liver. With different racial groups: The original MDRD formula contains a factor to be applied to African-American subjects raising the possibility that other variations in the formula may be required for optimal performance in different racial groups Pending publication of validation studies it is recommended Australasian laboratories continue to automatically report eGFR in Aboriginal and Torres Strait Islander peoples and other ethnic groups. Interpretation eGFR values are automatically reported up to 90 mL/min/1.73m2. Values greater than this are reported simply as > 90 mL/min/1.73m2. eGFR Kidney disease stage Description in mls/min/1.73 M2 ≥ 90 No kidney disease OR Healthy kidneys Stage 1 Kidney damage with normal kidney function 60-89 Stage 2 Kidney damage with mild loss of function 30-59 Stage 3 Moderate loss in kidney function. 15-29 Stage 4 Severe loss in kidney function < 15 Stage 5 End-stage kidney failure. The relationship of eGFR to age: A: Median, ie 50% of subjects have an eGFR above this line. B: 80% of subjects have an eGFR above this line. C: 97.5% of subjects have an eGFR above this line. In healthy adults the eGFR falls by up to 10 mL/min/1.73m2 per decade beyond the age of 40. Reduced eGFR however is associated with increased cardiovascular risk for all ages. In people aged over 70 years of age, eGFR values between 45 and 59 mL/min/1.73m2 should be interpreted with caution. If other signs of kidney damage (e.g. proteinuria, haematuria etc) are not present, a stable eGFR in this range may be consistent with normal GFR for this age and an absence of CKD related complications. Patient Information A patient information handout sheet is available on the interpretation of the eGFR at the Kidney Health Australia Website. Kidney Health Australia Management The tables in appendix 1 and 2 below summarize the actions required according to the eGFR results. Appendix 1 eGFR Clinical Action Plan 2 Appendix 2 Management of Chronic Renal Disease, according to the level of eGFR: 2 The Batsman, “Tell you what…you be England…and I’ll be Victor Trumper!” PUNCH 25th May 1909 How PUNCH depicted the excitement of some small London boys on the arrival of Monty Nobles’ 1909 Australians, which included the great Victor Trumper. References 1. Mathew TH, et al. Chronic kidney disease and automatic reporting of estimated glomerular filtration rate: revised recommendations, Position statement, MJA vol 187 no. (8)15 October 2007, p. 459-463. 2. Chronic Kidney Disease Management (CKD) in General Practice, Kidney Health Australia, 2007 3. Kidney Health Australia: www.kidney.org.au/ Dr. J. Hayes Ms Julie Ryan, Senior Scientist, Northern Hospital Pathology Department. 2 September 2008 .