Keeping on top of CKD management
GPs are increasingly managing chronic kidney disease in its early stages. Dr Kathryn Griffith advises on the clinical implications
GPs are increasingly managing chronic kidney disease in its early stages. Dr Kathryn Griffith advises on the clinical implications
For many years we have had poor indicators of renal function in primary care. Renal function has to deteriorate by about 50% before creatinine levels go up. Creatinine assays were in themselves thought to be inaccurate, and there was a lot of variation between different labs depending on the method used. Even when creatinine levels rose, we were led to believe that it was part of the ageing process, and that we could expect to see deteriorating renal function with a loss of glomerular filtration of 10ml/min each decade after the age of 40.
Although there was a lack of interesting renal disease in primary care, renal physicians were busy managing patients with end stage renal disease (ESRD) and starting them on dialysis at ever increasing ages. Some patients arrived so late that they needed to start dialysis immediately (so-called crash-landers), sometimes with disastrous results. These patients have a particularly poor prognosis related to poor vascular access, infection of lines and metabolic complications. There was a clear need to identify patients at high risk of developing ESRD sooner.
But all this changed after 2003 when the US National Kidney Foundation produced practice guidelines for the evaluation and classification of CKD. They used estimated glomerular filtration rates (eGFR), derived from the MDRD equation to produce five stages of CKD. UK laboratories now report eGFR to primary care, CKD is in the quality framework, and the rest, as they say, is history.
Where does the MDRD equation come from?
The gold standard test to assess kidney function is insulin clearance. This involves radioisotopes, is time-consuming and costly and so is not suitable for widespread use. It is used in secondary care when real and not estimated glomerular filtration rate is needed – for example, in a live donor before transplantation. The Modification of Diet in Renal Disease study gave researchers the opportunity to devise a short-cut method of estimating GFR using age, sex, creatinine and ethnic group (those of African ethnic groups having larger muscle mass and thus? higher serum creatinine levels). They produced a complicated equation giving a result in ml/min1.73mm² thus correcting for standard body surface area.
This is not the same as the Cockroft-Gault equation (which does not calculate GFR but estimates creatinine clearance, corrects for weight and is still used in therapeutics to calculate drug doses). The Cockcroft-Gault equation is not interchangeable with MDRD eGFR and it cannot be used to categorise patients for the QOF.
The MDRD equation has a major benefit in that it can be easily calculated by the laboratories using the standard data on the request form and since 2005 laboratories have been recommended, by the Renal National Standard Framework part 2, to routinely calculate eGFR from U&E results. Despite this, because of problems related to the creatinine assays, some areas have only just been routinely getting the results.
If the value is not routinely available it is easy to use the calculator on the Renal Association website www.renal.org, a good source of information for both professionals and patients. The value you calculate using the online calculator will not be the same as the one provided by your laboratory. This is because your lab should also use a correction factor to allow for the type of assay they use and to standardise to national values.
The benefit of the online calculator is that it will give you a standard error. This should remind you that you are calculating an estimated value. The MDRD study involved patients with known chronic renal disease. The calculation is most accurate when renal function is worse and has most error nearer to normal values between 60 and 90, which is where we have the most problems in primary care. Laboratories are discouraged in national guidance from calculating eGFR where creatinine levels are normal as the equation is not valid at these levels. Despite this some labs currently continue to send eGFR values when creatinine levels are normal. It is recommended not to include these patients in QOF registers.
The test is not appropriate in:
• pregnant women
• where renal function is rapidly changing
• when body habitus is abnormal for example body builders or amputees.
Why is it important to identify patients with early kidney disease?
Patients with CKD are at increased risk of premature death but this is related to cardiovascular events, not renal failure. They are more likely to die of a heart attack or stroke than need dialysis.
Management is targeted at slowing the deterioration of their renal function and reducing cardiovascular risk. Renal patients have not only the traditional risk factors of age, hypertension, diabetes, and smoking but also additional ones related to calcium metabolism, anaemia, electrolyte and fluid balance, uraemia and oxidative stress.
CKD is a sign of target organ damage and management should include treatment of hyperlipidaemia, aspirin and of course blood pressure.
Patients should only be coded as having CKD if the changes are persistent (lasting at least three months). Patients over 80 can be expected to have a GFR of 60 or less because of age-related deterioration (10% per decade after 40), and although this will be ‘normal for age', it will be associated with increased risk and problems with some medications, particularly NSAIDs.
What clinical assessment should patients with early CKD have?
The majority will have CKD related to hypertension or diabetes, and obviously fasting glucose is an important investigation in those not known to have diabetes. It is also important to rule out the most important reversible cause of CKD, which is bladder outlet obstruction. All guidelines stress the importance of asking for symptoms of bladder outlet obstruction. It's likely that most men over 65 will have these symptoms and so assessment should include examination of the abdomen to assess the presence of a palpable bladder and urological referral if found.
Urine should also be stick-tested for both blood and protein. Haematuria is most commonly associated with a renal stone, urological tumour or glomerular disease and is also likely to warrant an initial urological, rather than renal, referral.
It is important to review the patients' medication and look for nephrotoxic drugs, particularly NSAIDs, which should be withdrawn if possible.
‘A' drugs for all? The importance of blood pressure control and proteinuria
The most important intervention to reduce the progression of CKD is to treat blood pressure to optimum levels and not just what the BHS guidelines refer to as the ‘minimally acceptable' level, which has been used for QOF. This means that we should treat to <130/80 not just 140/85 and even lower if proteinuria is present. There is little clinical evidence for these targets and they are likely to need multiple drug therapy, which may not be tolerated by the patient.
There is much debate about the importance of blood pressure lowering per se, or the class of the drugs used. Patients with significant CKD were excluded from traditional trials and the evidence for CKD patients is largely from trials of those with proteinuria and or diabetes, and funded by the manufacturers of the newer classes of therapy – in other words, ACE-inhibitors or ARBs. There is little evidence for the use of these drugs in elderly patients with early CKD and no proteinuria.
A recent consensus meeting at the College of Physicians of Edinburgh produced a helpful document that can guide primary care in the management of these patients, and can be easily accessed from its website www.rcpe.ac.uk.
Persistent proteinuria is the most important indicator of patients likely to have deterioration of renal function and cardiovascular complications. All patients with CKD should have stick-testing of urine to check for blood and protein and the protein-to-
creatinine ratio (PCR) measurement if stick-testing is persistently positive. Early morning urine sampling reduces the effect of orthostatic proteinuria or exercise, and thus false positive results. Patients with a PCR of >100 should be referred to a renal physician, and should receive an ACE or ARB.
It is still recommended that patients with diabetes should have a microalbumin assessment if the protein dipstick is negative. These patients are at highest risk and this method will detect the earliest signs of renal damage, and they should obviously then receive an ACE or ARB.
The consensus document recommends that in patients without diabetes or proteinuria, the management of blood pressure should follow national guidelines and may include thiazide diuretics and calcium channel blockers in the elderly. It concludes that where blood pressure is controlled there is no indication to change to an ‘A' drug, and that these patients can be exempted from this section of QOF.
A new coding for stage 3?
The prevalence of CKD 3 is about 4% of the population. Not all these patients have the same risk of progression, and the renal consensus meeting suggested we could use the level of eGFR and the presence of proteinuria to identify those at highest risk who will need more monitoring, intervention and referral. The stage was divided by level of GFR and the presence of proteinuria. GFR levels of 45-59 were 3A and 30-44 3B, presence of proteinuria was identified by the suffix p so 3Bp have the highest risk.
What about management of stage 4 patients in primary care?
Guidelines recommend that all patients with an eGFR of <30 should be referred to a renal physician. Patients with deteriorating renal function should obviously be referred; however this could include a large number of elderly patients who have had stable creatinine levels monitored by the practice cardiovascular clinics for many years. Many renal teams are offering the option of telephone or email advice to continue the management of these patients in primary care, and indeed are discharging stable patients from long-term follow-up back to primary care.
Metabolic complications are more likely to occur when eGFR falls below 30 (or 45 in patients with diabetes), and so the management of patients with CKD 4 should involve more frequent monitoring (every three to four months), including haemoglobin and calcium levels. Despite earlier advice, it is not helpful to check PTH levels if calcium levels are normal.
Management of renal anaemia is now being directed towards primary care. Initiation of erythropoesis stimulating agents (ESA) usually involves a specialist, but administration and follow-up commonly occurs ‘closer to home' in the GP surgery. I have several patients in their 90s with CKD 4 and 5 and symptoms of anaemia or heart failure having EPO, although they would not be suitable for renal replacement therapy. It is also important to ensure that these patients are iron replete, and because ferritin can be raised as an acute phase protein reaction, levels of under 100ug/l (WOT? µg/l?) are considered abnormal and transferrin saturation levels are used as a better indicator of iron stores.
All patients with CKD 3-5 should have influenza and pneumococcal vaccination. Those with deteriorating function who may require renal replacement therapy should also have hepatitis B vaccination. If the initiation of this is delayed until they have CKD 5 then the chances of them sero-converting reduce, so the sooner they get started the better. There is therefore a role for general practice initiating vaccination where renal function is deteriorating at 5ml/min/year or more.
What do you tell your patients?
The identification of a new ‘disease' from a blood test result that the patient was previously told was ‘normal' is fraught with difficulties. Even when you explain the benefits of closer monitoring and my particular interest in their problem, you are often confronted with anger or tears. Until recently there have been few helpful information leaflets that don't imply that it is likely that CKD leads to renal failure and a kidney machine. There are helpful leaflets from the Renal Association and the Edinburgh renal unit, and a new leaflet from the Royal College of General Practitioners to match the one sent to general practice last year.
The important message is to translate eGFR to percentage renal function and explain that a fit healthy person can donate a kidney to have 50% function and a normal life. It is not until function deteriorates to less than 15% that people feel unwell and to less than 10% before dialysis may be required. We do know that the majority of patients with CKD will not require renal replacement therapy and that there are treatments that we can give to slow the deterioration of the kidneys.
What can patients do to help themselves?
The most important change involves strict salt restriction and means avoidance of convenience foods and ready meals. Patients with CKD are salt sensitive and benefit from improved blood pressure control. Weight loss also has benefits for blood pressure, but also obesity may be a contraindication to renal transplant if required. Smoking cessation advice is obviously particularly important.
Dr Kathryn Griffith is a GP in York and GP lead at York and Harrogate Renal Local Implementation Group
Competing interests Dr Griffith has received payment from Takeda to lecture on CKD and an unrestricted grant from Sanofi-Aventis to set up a renal clinic within her practiceTake-home points Take-home points
• Only use the MDRD equation to estimate eGFR when the creatinine is abnormal
• GFR calculated in this way is an estimate and it may have a wide standard error when values are close to 60
• Patients with early CKD are much more likely to have a cardiovascular event than develop End Stage Renal disease
• Patients with highest risk of renal and cardiovascular complications are those with the presence of proteinuria and more rapid decline in renal function
• Treatment of blood pressure is to lower targets and audit standards in patients with CKD, QOF audit standard being 140/85 but recommended target for treatment of those with proteinuria is <130>130>
• CKD patients are likely to need more than one drug to treat blood pressure. In patients with persistent proteinuria this should include an ACE or ARB. Patients without proteinuria and good blood pressure control can be exempt from the need for an A drug in QOF.
• Metabolic complications are more common in patients with eGFR <30 or="" diabetic="" patients="" with="" egfr="">30><45. patients="" should="" be="" monitored="" with="" regular="" haemoglobin="" and="" calcium="">45.>
• The majority of these patients will have stable renal function with rate of fall of GFR < 2ml/min="" over="" six="" months="" and="" can="" be="" managed="" well="" in="" primary="">
CKD patients are more lilely to die of a heart attack than need dialysis