BMJ 2014;348:g264 doi: 10.1136/bmj.g264 (Published 24 January 2014)
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PRACTICE RATIONAL TESTING
Estimated glomerular filtration rate What should you do when confronted with a patient with previously unrecognised moderate chronic kidney disease? This article gives helpful advice in this not uncommon scenario 1
Philly O’Riordan general practitioner , Paul E Stevens consultant nephrologist and medical director , 3 Edmund J Lamb consultant clinical scientist City Road Medical Centre, London, UK; 2Kent Kidney Care Centre, East Kent Hospitals University NHS Foundation Trust, Canterbury, UK; 3Clinical Biochemistry, East Kent Hospitals University NHS Foundation Trust, Canterbury CT1 3NG, UK 1
This series of occasional articles provides an update on the best use of key diagnostic tests in the initial investigation of common or important clinical presentations. The series advisers are Steve Atkin, professor, head of department of academic endocrinology, diabetes, and metabolism, Hull York Medical School; and Eric Kilpatrick, honorary professor, department of clinical biochemistry, Hull Royal Infirmary, Hull York Medical School. To suggest a topic for this series, please email us at [email protected]
A 75 year old white woman presented to the emergency department after a fall with a displaced Colles’ fracture requiring surgical management. She was euvolaemic, her blood pressure was 158/89 mm Hg, and her body mass index was 19. She consumed no alcohol, smoked 20 cigarettes a day, and was not taking regular medication. Preoperative blood tests showed a serum creatinine concentration of 140 μmol/L (reference interval 49-90 μmol/L) and estimated glomerular filtration rate (eGFR) 32 mL/min/1.73 m2. Blood electrolytes, liver function tests, and glucose concentration were normal. One day postoperatively her creatinine level remained increased (125 μmol/L, eGFR 36 mL/min/1.73 m2). On discharge, the orthopaedic team asked her general practitioner to investigate her renal function further.
What are the next investigations? Estimated glomerular filtration rate
In the UK approximately 1 in 20 people are thought to have stage 3 (moderate) and later chronic kidney disease,1 2 which is generally identified by means of estimation of glomerular filtration rate3 and detection of protein in the urine (albuminuria or proteinuria). Case finding in high risk individuals is recommended (figure⇓),4 but opportunistic detection, as here, is common. Glomerular filtration rate is the best overall index of kidney function and ideally would be measured with reference procedures that follow the clearance of an infused exogenous substance (such as EDTA labelled with chromium-51).
However, these methods are cumbersome and impractical for general detection and management of kidney disease. Estimation of glomerular filtration rate by means of equations is widely used as a surrogate measure of glomerular filtration rate. Such equations use the inverse relationship between serum creatinine concentration and glomerular filtration rate, making adjustments for the non-renal influences of age, gender, and ethnicity on that relationship.
Estimates of glomerular filtration rate are normally expressed per 1.73 m2 body surface area, which is an average surface area for an adult. Hence such estimates might overestimate true glomerular filtration rate in small individuals and vice versa. Estimated glomerular filtration rate (eGFR) may be falsely low after a meal of high meat content, as blood creatinine concentration increases after meat intake, potentially misclassifying patients as having chronic kidney disease.5 Thus patients should avoid eating meat for at least 12 hours before repeat testing.5 Blood creatinine is predominantly derived from muscle. In this patient’s case the low body mass index could suggest poor nutrition: consequently her creatinine concentration may reflect reduced muscle mass and her true glomerular filtration rate may be lower. (Note that the converse can also be true: a muscular young man may have increased serum creatinine concentration and a falsely lowered eGFR). Table 1⇓ lists the situations in which serum creatinine may give rise to unreliable estimates of glomerular filtration rate.
When is a change in eGFR significant?
Serum creatinine concentration, as with all biomarkers, has a natural biological variation, to which laboratory variation should be added: a true change in glomerular filtration rate cannot be inferred with any degree of certainty unless the so called reference change value is exceeded.6 Based on the biological and analytical variation of serum creatinine, the reference change value for eGFR is about 14%: in this patient’s case the eGFR
Correspondence to: E Lamb [email protected]
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BMJ 2014;348:g264 doi: 10.1136/bmj.g264 (Published 24 January 2014)
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Learning points • Confirm a finding of low estimated glomerular filtration rate (eGFR) with a repeat sample taken after avoidance of meat for at least 12 hours. Consider spurious causes of low eGFR such as high muscle mass. Take into account normal biological and analytical variability when interpreting eGFR results (and most other laboratory tests) • A low eGFR result should prompt a check for proteinuria by measuring urinary albumin to creatinine ratio • Stage 3 (moderate) chronic kidney disease, especially in the absence of proteinuria or haematuria, is typically stable and can be safely managed in primary care • In some instances, the cause for a patient’s chronic kidney disease may be uncertain, but this does not affect the management
would need to change by approximately 5 mL/min/1.73 m2 for that change to be considered significant with 95% certainty.
Although this woman’s eGFR is low, acute kidney injury is unlikely given that the preoperative and postoperative serum creatinine results were essentially unchanged. Nevertheless, the patient’s general practitioner should request a repeat eGFR within two weeks of discharge to exclude acute kidney injury.
Urinary albumin:creatinine ratio In addition to repeating serum creatinine measurement to obtain the eGFR, the general practitioner will need to check for proteinuria. The presence of substantial proteinuria implies that the patient is at increased risk of adverse outcome, including progressive kidney failure, acute kidney injury, cardiovascular disease, and death.7 Proteinuria is most effectively checked by requesting a urinary albumin:creatinine ratio on a random or early morning urine sample. Protein reagent strips (“dipsticks”) are notoriously unreliable, and their cost effectiveness has never been established.8 9 Laboratory measurement of urine total protein lacks sensitivity and standardisation. Urinary albumin is the main urinary protein in the vast majority of nephropathies and can be measured with sensitive, specific, and quantitative assays.8 10 In the setting of non-diabetic chronic kidney disease a urinary albumin:creatinine ratio ≥30 mg/mmol denotes significant proteinuria requiring further treatment.4 However, it is increasingly clear that morbidity and mortality risk increase at much lower levels of albuminuria,11 and recent guidance has proposed a more complex staging system in which both diabetic and non-diabetic individuals will be considered proteinuric when albumin:creatinine ratio exceeds 3 mg/mmol.7
Additional tests if chronic kidney disease is confirmed Chronic kidney disease is defined as abnormalities of kidney structure or function, present for at least three months, with implications for health.7 The abnormalities most often encountered clinically that meet this definition are a sustained low glomerular filtration rate (90, 60-89, 45-59, 30-44, 15-29, 5 mL/min/1.73 m2/year. §The aim is to avoid late referral (referral to specialist services