Chronic kidney disease (CKD) is endemic in the UK population with around 2.9 million people in CKD stages III to V (moderate kidney damage or greater). CKD is defined and categorised by levels of glomerular filtration rate (GFR) and its recognition has traditionally been confined to nephrology.
However, a simple calculation of estimated GFR (eGFR) according to serum creatinine has brought the diagnosis of renal disease to the fore and resulted in the inclusion of eGFR monitoring in the recent quality framework revision. It is vital, therefore, that primary care has a full understanding of the calculation and how it will affect clinical practice.
What is eGFR?
GFR is used as a measure of kidney function and can be accurately determined using isotopic measurements. A useful rule of thumb is to consider GFR as the percentage of kidney function that a patient has, since a healthy patient has a GFR above 90ml/min/1.73m2 (>90 per cent) and kidney failure occurs below a GFR of 15ml/min/1.73m2 (<15 per cent).
However, isotopic testing is not a practical way to screen large populations for the presence of kidney disease, particularly in primary care. More practical is eGFR, which is an estimate of the GFR based on the serum creatinine and other variables such as weight, age and ethnicity of a patient.
There are many formulae for estimating GFR. The two best known are Cockcroft and Gault and the formulae derived from the Modification of Diet in Renal Disease (MDRD) study. The Cockcroft and Gault estimate requires the patient’s weight — information which is not routinely available in the biochemistry laboratory. Therefore, in the UK, we have adopted the isotope dilution mass spectrometry (ID-MS) traceable version of the MDRD equation, which is based on serum creatinine, age, sex and ethnicity.
Measuring eGFR
The parameters described above are put into the MDRD equation to determine the eGFR and thus the level of CKD that a patient may have. This will be done at the laboratory and should appear on the test results as a figure in ml/min/1.73m2 or can be calculated using the eGFR calculator on the Renal Association website: www.renal.org/eGFR calc/GFR.pl.
To be diagnosed with CKD in stages I or II there must also be evidence of kidney damage to accompany the GFR estimate. This could be the presence of persistent microalbuminuria or proteinuria, haematuria, or abnormalities in imaging tests and must be present for more than three months. Therefore the urinary albumin level (or urinary albumin to creatinine ratio) and tests for the presence of blood in the urine should be performed in those patients found to have a reduced eGFR.
However, eGFR is only an estimate and there are some limitations to the calculation. But eGFR is still a significantly better determinant of CKD than of serum creatinine alone.
People with a large muscle mass may have elevated levels of serum creatinine but normal kidney function. Similarly, it has been shown that many patients with serum creatinine within the ‘normal’ range actually had moderately reduced kidney function.
Therefore eGFR is a helpful tool in practice, but where precise knowledge of GFR is important, for example dosing in cancer chemotherapy where there is a narrow therapeutic margin, formulae-based GFR estimates should be avoided.
Inter-laboratory variation in serum creatinine estimation can cause differences in estimates of GFR. To overcome this, the UK National External Quality has provided each laboratory with recommended correction factors for the MDRD equation to adjust for differences in assay technique.
Precision and accuracy of eGFR also changes at the extremes — for example accuracy decreases as GFR increases. Therefore, when eGFR exceeds 89ml/min/1.73m2 it should be reported as greater than 90 ml/min/1.73m2 rather than as an exact number.
How to manage eGFR?
The first question is how many new patients will eGFR identify and how many will already be known to us because they also have diabetes, hypertension or cardiovascular disease?
Our local findings show that 97 per cent of patients on our recently introduced CKD register are also on one of the other quality framework vascular registers.
When to refer is also an important consideration when managing CKD. All patients with stages IV and V CKD should be referred urgently, or at least discussed formally with a nephrologist, and offered the options of renal replacement therapy or conservative therapy. Immediate referral is also required for those with acute renal failure, malignant hypertension, hyperkalaemia (potassium >7mmol/l) and nephrotic syndrome.
Further information is available from the UK CKD guidelines, which can be accessed at www.renal.org/CKDguide/ckd. html. These highlight that deteriorating eGFR, raised protein creatinine ratio, anaemia, uncontrolled hypertension and the metabolic disorders of CKD are areas where a specialist renal opinion may add value to the care plan for those in the earlier stages of CKD.
Primary care
Those who have CKD stages I to III can, in the majority of cases, be managed in primary care. Many of these, as previously mentioned, will already be on treatment for diabetes, hypertension or other cardiovascular disease.
All those with CKD require cardiovascular risk reduction and regular assessment. BP should be monitored by BHS methods at least once a year and target BP should be <130/80mmHg or in the presence of proteinuria less than 120/75mmHg. Blockage of the renin-angiotensin-aldosterone system (RAAS) is recommended in those with increased levels of urinary albumin.
There are a variety of RAAS interventions which improve renal outcomes. In the HOPE study, the ACE inhibitor ramipril was shown to have a renoprotective effect in patients with diabetes independent of its ability to lower BP. In a similar study in patients with diabetes, the ARB irbesartan was shown to reduce the risk of the composite end point by 20 per cent compared to BP control without RAAS intervention.
There are often concerns about treating patients with decreased renal function with RAAS interventions. Indeed, there are rare occasions where it can cause acute kidney injury by interfering with the autoregulation of renal blood flow.
However, if properly monitored these drugs can be used in patients with reduced renal function. There is also evidence that RAAS interventions may be effective in reducing the progression of some types of CKD as well as reducing mortality and morbidity in patients with heart failure.
Serum creatinine and potassium concentrations should be checked before starting ACE inhibitors and/or ARBs within two weeks of starting or increase in dose, and where another illness can increase risk of hyperkalaemia. Thereafter, monitor at six-month intervals in stage III CKD.
A rise in serum creatinine concentration of >20 per cent, or a fall in eGFR >15 per cent should be followed by further measurements within two weeks. If there is deterioration in kidney function, seek a specialist opinion on whether the treatment should be stopped or if more tests are needed.
Hyperkalaemia (serum potassium >6mmol/L) should result in the stopping of concomitant nephrotoxic drugs and reducing potassium-retaining diuretics.
Early diagnosis
It is important to diagnose CKD early since if it is left untreated it increases cardiovascular risk and can lead to renal failure. These two diseases represent a major burden on the NHS, with renal replacement therapy costing approximately 2 per cent of the entire NHS budget.
From April 2006, many GPs have been receiving an eGFR figure alongside their patient’s serum creatinine results. This will help GPs identify high cardiovascular risk patients and will improve the management of patients with declining renal function. Furthermore, treatment of the risk factors for cardiovascular disease reduces the risk of progression of CKD.
Dr O’Donoghue is consultant renal physician and clinical director, Hope Hospital, Salford, and Dr Wilkinson is a GPSI in renal medicine in Oldham, Lancashire
| STAGES OF CKD | ||
| Stage | Description | GFR (ml/min/1.73m2) |
| 1 | Kidney damage with normal or increased GFR | ≥90 |
| 2 | Kidney damage with mildly decreased GFR | 60–89 |
| 3 | Moderately decreased GFR | 30–59 |
| 4 | Severely decreased GFR | 15–29 |
| 5 | Kidney failure | <15 or dialysis |
Calculating eGFR
eGFR = 186 x (Creat/88.4) -1.154 x age -0.203
x 0.742 (if female)
x 1.210 (if black)
Source: Modification of Diet in Renal Disease Study
References
de Lusignan S, Chan T, Stevens P et al. Identifying patients with chronic kidney disease from general practice computer records. Fam Pract 2005; 22: 234–41.
Levey A S, Bosch J P, Lewis J B et al. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of Diet in Renal Disease Study Group. Ann Int Med 1999; 130: 461–70.
K/DOQI Clinical Practice Guidelines for chronic kidney disease: Evaluation, Classification, and Stratification, 2000.
Chronic Kidney Disease in Adults. UK Guidelines for Identification, Management and Referral, Royal College of Physicians, 2006.
Mann J F E, Gerstein H C, Yi Q-L et al. Development of renal disease in people at high cardiovascular risk: results of the HOPE randomised study. J Am Soc Nephrol 2003; 14: 641–7.
Lewis E J, Hunsicker L G, Clarke W R et al. Renoprotective effect of the angiotensin-receptor antagonist irbesartan in patients with nephropathy due to type-2 diabetes. N Engl J Med 2001; 345: 851–60.
