Dr Jack Galliford FRCP, MBBS, BSc is a Consultant Nephrologist at Hammersmith Hospital (NHS) and Bupa Cromwell Hospital.
In the mid 1990’s, due to the enormous health and economic impact of the rise in patients on dialysis, the National Kidney Foundation (NKF) introduced new clinical guidelines to re-focus the management of renal disease towards early recognition and the prevention of progression.
To put the concerns of the NKF into perspective, there are approximately 25,000 patients in the UK currently on dialysis (with a mean age of 65), at a cost of £20,000-£25,000 per patient/year.
As a result of these guidelines the term ‘Chronic Kidney Disease’ (CKD) was coined and there are now 13 evidence based initiatives to improve kidney patient care. However CKD does not specify a diagnosis, and it can be a misleading and unfairly negative label for patients who may in fact have an excellent renal prognosis (particularly for those with CKD stage 1 and 2).
End stage renal failure (ESRF) rates in British Minority Ethnic communities are three times higher than in the Caucasian population, so the importance of ethnicity cannot be underestimated. There is currently little other than western data on this issue, but it is likely that non-Caucasian populations worldwide are at a greater risk of renal disease. This may relate not only to a genetic predisposition to diabetes, but hypertension, and also to intrinsic renal disease.
Stages of Chronic Kidney Disease - the importance of stage 3 CKD
As shown in figure 1, CKD has been stratified into stages based on renal function by a calculation linked to laboratory creatinine value. The point at which CKD becomes irreversible corresponds to a glomerular filtration rate (GFR) of less than 30mls/min - the lower limit of CKD stage 3. If a reversible injury is identified after this level of function, there is insufficient renal reserve to avoid end stage renal failure. So, whilst identifying renal disease at all stages is important (and the earlier the better), CKD stage 3 represents the last opportunity for nephrological intervention.
The Renal Association suggests that most CKD stage 3 patients can be managed in primary care with 6 to 12 monthly follow up, taking into account the risk of renal progression versus the associated cardiovascular risks of renal replacement therapy. The assumption is that at this degree of renal impairment an individual’s risk of cardiovascular events is higher than their risk of needing renal replacement therapy.
As shown in figure 2, age is the most important determinant of both GFR and patient survival. The majority of CKD 3 patients are older and often have a co-morbidity (especially of a cardiovascular nature). In such a group the management in primary care may be entirely reasonable, and patients may well not progress to ESRF.
Figure 1: *National Kidney Foundation, Kidney Disease Outcome Quality Initiative (K/DOQI). Clinical practise guidelines for bone metabolism and disease in chronic kidney disease. Am J Kid Dis.2003; 42: S1-S201
Once a patient with CKD 3 has their initial assessment and the high risk of progression has been ruled out via urinalysis to exclude microscopic renal derived haematuria, and quantification of insignificant proteinuria, 6 to 12 monthly follow up can continue. This should include stringent blood pressure monitoring, smoking cessation advice, exercise encouragement, avoidance of nephrotoxic medications, and cholesterol lowering with statins as needed.
With such broad guidelines it can be hard to recognise those patients who are particularly at risk of renal progression and need referral to a specialist. However, those with proteinuria, haematuria, young patients or those with a declining GFR (>5ml/ min over one year or by > 10mls/ min over five years) may need referral. Many practitioners suggest subdividing stage 3 into stages 3a (45-59ml/min) and 3b (30-44ml/min), with those in the latter category requiring referral to specialist care.
What does the literature say?
Very few studies have looked specifically at CKD stage 3. Most literature reflects on all stages of kidney disease and compares the outcomes, particularly with regard to cardiac events. What we as practitioners need to know is how to spot those likely to do badly and those who will remain stable. Of course, since the majority of patients with CKD do well and are not referred it can be difficult to speculate.
A recent meta-analysis of 13 studies suggested that we can be relaxed about CKD 3, since ESRF was a rare outcome (seen in 4% of patients after 10 years). However only 4 of the 13 studies included ESRF as an outcome, and within these the follow up was highly variable, from 3-10 years. Also, considering the previously mentioned importance of ethnic diversity, not only was the UK not included, but the majority of patients came from Norway.
Renal specialist literature is dominated by Scandinavian data. In one study of 65,589 adults who underwent 10.3 year follow up, the population at outset consisted of 3.3% diabetics, had an average age of 50 with an average BMI of 26 and an enrolment creatinine of 90umol/l. Unsurprisingly, only 124 progressed to ESRD. This group is not representative of our more diverse patient population in the UK.
In comparison within a South Korean population with CKD stage 3 which was followed for 10 years after being referred to a specialist centre, 19% of those with CKD stage 3a and 35% of those with CKD 3b reached ESRF. 52% of all the patients progressed to CKD stage 4 or 5. Risk factors for progression included not only lower GFR at presentation but also older age, diabetes, proteinuria and microscopic haematuria. This study represents another example of a self-selected population however; those that were studied had already been identified as at risk and they did badly.
The true extent of renal disease in the UK population is unknown, and the fact that the symptoms of kidney disease are silent only compounds this problem. With an ageing population, since GFR declines as part of the normal ageing process, CKD prevalence (particularly CKD stage 3) is bound to increase, and this may not be pathological. Identifying those at risk of progression, particularly within the diverse population we serve (in London especially), is the key.
CKD stage 3 is often found incidentally in patients with other clinical problems, for example following routine blood tests. Such patients often have the added complexity of polypharmacy, with drug interactions, altered renal handling of drugs and co-morbidities, which makes their care even more challenging.
Nephrologists commonly encounter these situations and are always keen to offer reassurance or advice rather than necessarily being bound by guidelines. Moreover, we have the ability to investigate rapidly, get a diagnosis and intervene in a timely fashion, in order to improve outcomes.
K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Kidney Disease Outcome Quality Initiative. Am J Kidney Dis 2002
The Renal Association UK Renal Registry 16th Annual Report, Dec 2013
Renal Association Clinical Practice Guidelines
Sharma et al. Does stage-3 chronic kidney disease matter. BJGP June 2010
Hallan et al. Combining GFR and Albuminuria to classify CKD Improves Prediction of ESRD. J Am Soc Nephrology 2009
Baek et al. Does stage III chronic kidney disease always progress to end-stage renal disease? A ten-year follow-upstudy. Scand Journal of Urology and Nephrology 2012