Chronic kidney disease (CKD) encompasses a wide spectrum of disorders ranging from minor urinary abnormalities to end stage kidney failure. The prevalence of CKD worldwide is thought to be increasing, largely due to the rising incidence of diabetes and the rapid aging of the population.
March 12 is World Kidney Day. The message of raising awareness is particularly pertinent for primary care physicians (PCPs), who will increasingly encounter patients with CKD in its various stages. It is important, therefore, for them to know how to diagnose and manage CKD, and when to refer patients to a nephrologist.
Diagnosis
It is crucial to diagnose CKD as early as possible since complications can ensue if a referral is delayed. Indeed, most patients with CKD will die of cardiovascular disease before developing end stage kidney failure, so management of these risks by their PCP will improve outcomes. Screening of at-risk individuals is thus critical and physicians should adopt a proactive approach, as outlined in the guidelines. Diabetes is the commonest cause of CKD but a high index of suspicion should also be retained in patients with hypertension, over-50s, smokers, the obese, and those with a family history of CKD.
The diagnosis and classification of CKD should be based on a patient’s kidney function, as estimated by glomerular filtration rate (GFR) and the presence of other evidence of chronic kidney damage. These guidelines, which have been widely adopted worldwide, recognize five stages of kidney disease (Table 1).
Contrary to popular perception, a diagnosis of CKD does not routinely require 24-hour urine measurements or expensive radionuclide studies and can usually be made using three simple tests available to every PCP: serum creatinine (SCr), urine protein measurement using an early morning specimen, and urine microscopy. GFR can then be estimated by putting the patient’s data into easy-to-use mathematical formulae, which have been derived from large population studies. The 4-variable Modification of Diet in Renal Disease (MDRD) formula has widespread applicability and is currently the most commonly used formula in routine practice worldwide. Physicians can also estimate GFR using the internet: type “MDRD GFR calculator” into the search engine and input the patient’s values to calculate the estimated GFR (eGFR).
Many laboratories worldwide are already using these formulae to report eGFR but their adoption has been slower in Asia, where some nephrologists have questioned their applicability to local patients. The MDRD formula, for example, has not been validated in an Asian population, although a modified version is currently being explored in Chinese patients. Our division at National University Hospital (NUH) is also devising a Singapore-specific formula.
We should not, however, be paralyzed into inactivity while we await these new formulae. It is time to move on from the notion that 24-hour urine testing is the cornerstone of CKD diagnosis and begin routinely reporting eGFR along with SCr. It is not only easy to calculate but also more convenient for both PCPs and patients – negating the laborious and inaccurate process of collecting and labeling samples. The existing GFR formulae have limitations but they nonetheless provide a long-term view of kidney function in an individual patient, enabling CKD progression to be tracked over time. A reduction in eGFR exceeding a certain range can provide a warning sign, prompting PCPs to make an early referral to a nephrologist.
Twenty-four hour urine collection still has a place in diagnosing CKD, but should be used to further evaluate an abnormal eGFR or proteinuria rather than as a first-line diagnostic tool. Urine examination can identify protein and red cells and casts, giving further information as to the cause of CKD. Additional radiological tests are only required for further evaluation and/or in those with clinical symptoms or signs of CKD.
In evaluating patients with newly-diagnosed stage 3 to 5 CKD, clinicians should obtain previous measurements of SCr and eGFR to assess the rate of progression to date. A blood test showing an eGFR below 60 mL/min/1.73 m2 in a patient without established CKD should prompt:
· Clinical assessment for underlying conditions such as sepsis, heart failure or hypovolemia
· Clinical examination for bladder or prostate enlargement
· A review of medications, particularly non-steroidal anti-inflammatory drugs and traditional medications
· Urinalysis: haematuria and proteinuria suggest the possibility of glomerulonephritis, which may be rapidly progressive
· Repeat SCr, eGFR and potassium measurement within a maximum of 5 days
If acute kidney failure is suspected, the patient should be referred to a nephrologist. Patients with stable CKD should be followed up according to their eGFR (Table 1).
Practice Guidelines
Guidance on the diagnosis and management of CKD is available from several international sources. The guidelines from the UK Renal Association are particularly simple to follow and contain useful treatment algorithms. Helpful guidelines are also available from the US National Kidney Foundation, the Canadian Society of Nephrology, and CARI (Caring for Australasians with Renal Impairment).
Treatment
The vast majority of CKD patients being managed by PCPs will be in stages 1 and 2, but patients with early stage 3 CKD will also represent a significant proportion. Stage 3 patients who progress or are proving difficult to manage in primary care, and stage 4 and 5 patients, should be referred to nephrologists.
All CKD patients should be advised on diet and lifestyle modification as appropriate. Lipid-lowering therapy should be considered for all patients and aspirin for those at high cardiovascular risk. Meticulous control of hypertension is extremely important in CKD and most patients will need more than two drugs to achieve optimal control. Angiotensin-converting enzyme inhibitors or angiotensin receptor blockers should be given to all patients with proteinuria, diabetic patients with microalbuminuria, and patients with heart failure but combinations of these two drugs should only be initiated under specialist supervision.
Physicians should refer to the guidelines for further advice on the thresholds for initiating and maintaining antihypertensive treatment, and for who, when and how to refer. They should also familiarize themselves with the indications for early referral to a nephrologist. The need for a prompt referral is particularly pressing in acute kidney failure, as this requires emergency treatment.
Disease management tools
Partnerships with nephrologists play a crucial role in helping PCPs to recognize the variability in CKD progression and to treat each patient individually. At NUH and National Healthcare Group in Singapore we are developing a ”Right-Siting” program for patients with early CKD so that they can be managed and tracked to optimize outcomes. The initiative is still in the planning stages but is due to launch in the coming months. We hope that this program will give PCPs greater knowledge and confidence with managing CKD, facilitate referrals, and provide patients with greater continuity of care and a more holistic approach to their management.
Conclusion
Our understanding of CKD has come a long way in recent years and it is important for physicians to familiarize themselves with the latest guidelines. The use of GFR in particular should be embraced, and patients should be classified into the 5 stages of CKD to enable appropriate referrals. Forging closer ties with nephrologists will help PCPs to tackle the ever-increasing burden of CKD and improve quality of care and outcomes for patients.
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