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Early detection of CKD will reduce heart disease risk

What are the risk factors for chronic kidney disease?

How should eGFR be interpreted?

Which patients need specialist intervention?

What are the risk factors for chronic kidney disease?

How should eGFR be interpreted?

Which patients need specialist intervention?

In April 2008, the Department of Health announced a strategy to reduce the adverse effects of vascular disease by focusing on its earlier detection.1 By introducing ‘vascular checks' targeting those aged between 40 and 75 years of age, it is estimated that at least 25,000 people a year with diabetes or kidney disease will be diagnosed earlier. With increasing evidence that early treatment of kidney disease can slow, if not prevent, progression to established renal failure, early detection is of clear benefit from a purely renal perspective.

However, the evidence also shows that only a minority of patients diagnosed with chronic kidney disease (CKD) will progress to established renal failure while a substantial proportion will die of cardiovascular disease. In those whose disease does progress, the mortality and morbidity risk increases exponentially.

Additionally, the comorbidities associated with CKD (cardiovascular disease, hypertension, diabetes, anaemia, metabolic bone disease, malnutrition, neuropathy) occur with increasing frequency as renal function deteriorates. With this in mind, the early detection and treatment of CKD, alongside risk factor modification to reduce associated mortality and morbidity, is essential in tackling the growing CKD epidemic.

Definition of CKD

CKD is defined as either signs of damage (proteinuria, haematuria or anatomical abnormality) or GFR <60ml/min/1.73m2 present on at least 2 occasions for >3months. CKD is staged according to the NKF-KDOQI criteria, which are based upon glomerular filtration rate (GFR). Previously, the criteria did not take into account the prognostically and therapeutically significant presence of proteinuria. It is now recommended that the presence of significant proteinuria (albumin:creatinine ratio ACR >30, or protein:creatinine ratio PCR > 50) be recognised by adding the suffix p to the patient's CKD stage. Additionally, CKD stage 3 has recently been split into 3a (GFR 45-59) and 3b (GFR 30-44) as longitudinal population studies have shown an increased risk associated with GFR 30-44 i.e. stage 3b disease.

In the NEOERICA study, of the 2,475 patients with CKD stage 3b, 43% had CVD, 16% diabetes, 87% hypertension and 4% Hb <11g/dl, comparative figures for the 8,731 patients with CKD stage 3a were 27%, 12% , 71% and 3% respectively.2

In practice, true measurement of GFR is replaced by its estimation based largely upon the patient's creatinine. As of April 2006, the reporting of the estimated GFR (eGFR) alongside all creatinine measurements has become mandatory. The MDRD equation is used to calculate eGFR. It is normalised to 1.73m2 surface area allowing the benefit of taking an individual's weight out of the equation. As a result, eGFR tends to become less reliable at extremes of body type, for example, in body builders or those who are severely malnourished. It is important to note that eGFR is not valid for those under 18. The MDRD equation was originally validated on white and black Americans and seems to equate well to the UK's white population. Data from the USA showed that creatinine values underestimated renal function in those of African and Caribbean descent by an average of 21% and also overestimated renal function in women by 26%; hence there are corrections for these factors in the abbreviated MDRD formula.

Although eGFR remains an estimate, changes in eGFR in an individual are a reliable marker of a change of renal function.

Increasing prevalence

The prevalence of CKD stages 3-5 in the UK has been estimated at 8.5% based on a large primary care study.3 The prevalence increases dramatically with age, and is also thought to be increasing year by year. The prevalence of established renal failure can be more accurately assessed based on numbers of patients requiring renal replacement therapy (RRT).

As of December 31 2007, 45,484 patients in the UK were receiving RRT.3 This equates to a population prevalence of 746 per million and roughly represents a 5% increase from the year before. Transplantation was the most common form of RRT accounting for 46.6% followed by haemodialysis (42.1%).3 The average GFR of patients commencing RRT is 7.5 thus these figures are likely to represent an underestimation of the true population prevalence of CKD stage 5. The annual incidence of patients requiring RRT in 2007 was 109 per million population, slightly lower than the previous year.3

The GP's role

The importance of the primary care team's involvement in managing CKD is reflected by its inclusion in the QOF.The role of the GP in managing CKD starts with its early detection. Traditionally, CKD has been underdiagnosed mainly as a result of a combination of complicated diagnostic criteria coupled with the asymptomatic nature of the disease. Although the adoption of the

NKF-KDOQI classification of CKD has clarified diagnosis, the large majority of patients remain asymptomatic. The majority of vascular checks will fall into the hands of the GP and will target this population of largely asymptomatic patients. Assessment of renal function is not routine in ‘vascular checks' but is reserved for those who have identifiable risk factors for kidney disease.

Risk factors

Risk factors for kidney disease include:
• hypertension
• cardiovascular disease
• structural renal tract disease
• renal calculi
• prostatic hypertrophy
• multisystem disease with potential renal involvement
• family history of established renal failure
• opportunistic detection of haematuria or proteinuria.

Assessment

Assessment involves measuring eGFR and estimating urinary protein loss by measuring urinary PCR or ACR. Both ACR and PCR are accurate estimations of urinary protein loss, and at present, neither test is better than the other. ACR is more sensitive to lower levels of protein loss and thus useful for screening, it is more accurate, and, more expensive. NICE?has directed that it be used in preference to PCR, and certainly given the current familiarity that the primary care team has with ACR this seems pragmatic. It is important to remember that the presence of symptomatic urinary tract infections can render ACR and PCR less reliable. Once kidney disease has been established the priority is to determine whether this is an acute or chronic process and then, importantly, define the risk progression.

Progression is more difficult to define and has differing implications according to the age of the individual. In healthy individuals eGFR can decline by 0.4ml/min/1.73m2 - 0.9ml/min/1.73m2 each year. The presence of CKD alone does not necessarily correspond to an increased rate of decline.

Risk factors that are associated with an increased rate of decline include:
• cardiovascular disease
• proteinuria
• hypertension
• diabetes
• smoking
• Black or Asian ethnicity
• chronic use of NSAIDs
• urinary outflow tract obstruction.

Those risk factors that are modifiable, for example hypertension, become therapeutic targets to slow progression. Progressive renal disease requiring referral to specialist services is defined as:
• a decline in eGFR > 5 ml/min/1.73m2 within 1 year or > 10 ml/min/1.73m2 within 5 years.

Although some studies in healthy individuals have shown an increasing rate of decline with age, the important question is whether a continuous decline at the current rate will result in established renal failure within the patient's lifetime. Should the answer to this question be yes, early referral is paramount.

Late presentation

The incidence of late presentations as defined by the requirement of dialysis within 3 months of referral was 21% in 2007.3 There is significant excess morbidity and mortality associated with late-presenting patients and an increased length of stay in hospital. Additionally, ‘crash landing' on dialysis does not allow adequate preparation for the transition to RRT for either the patient or their loved ones.

Planning for RRT requires a large multidisciplinary team approach involving patient education, assessment for the most appropriate form of RRT, formation of arterial venous fistula or peritoneal catheter insertion, and importantly, support.

It is also a chance to introduce the concept of renal transplantation as a form of RRT – an important opportunity with often live donation to facilitate ‘pre-emptive' transplantation thereby sparing the patient the risk and misery associated with dialysis treatments. In 2007, 5.2% of patients accepting RRT received transplants within 90 days of requiring RRT, and 21.3% were on peritoneal dialysis within 90 days.3 This requires adequate planning which in turn requires adequate time.

The specialist's role

The role of the specialist nephrologist involves treating reversible kidney disease, managing and limiting progression of CKD and its associated risk factors, and the preparation, planning, and management of patients on RRT. The treatment of reversible disease and management of those approaching and requiring RRT is complex, and requires a specialist multidisciplinary approach.

The management of those with chronic disease, not approaching established disease, involves goal-directed therapy that can be managed in the community.

This centres around:
• treatment of hypertension
• reduction of proteinuria
• treatment of dyslipidaemia, anaemia, and acidosis
• treatment of metabolic bone disease
• quitting smoking
• dietary advice.

Patients with complex disease, or where management of complications is difficult, will also require specialist intervention. In other circumstances, advice may be sought by corresponding with a specialist without specific need for referral. In considering the above, NICE recommends those patients with CKD stage 4 or 5 are referred, as well as those with progressive disease or heavy proteinuria.3 Patients with uncontrolled hypertension warrant referral as do those with, or with suspected, rare or genetic kidney disease. Those with suspected renal artery stenosis should also be referred.

Conclusion

Renal services are facing a major increase in demand in the UK and with the rising prevalence this demand will continue to increase. Only a small minority of these patients progress to CKD stage 5, but their detection and timely referral is extremely important. Although specialist input is valuable for some patients, for the majority of patients it is neither practicable nor necessary. CKD management can thus be community-based, led by the GP, with support provided by specialist services for those who need it.

There is significant excess morbidity and mortality associated with late-presenting patients and an increased length of hospital stay

Dialysis is debilitating for any patient at any age and life expectancy is around a third to a half of that of people without kidney disease. Dialysis is also expensive. Prevention saves lives and money. Early detection of CKD will reduce heart disease risk Useful information

ABC of Kidney Disease
Goldsmith D, Jayawardene SA and Ackland P (Editors). Wiley Blackwell. Oxford 2007

Renal Association
www.renal.org

Renal Association - New eGuide to CKD
www.renal.org/ckd

NHS Evidence - Kidney Disease Collection
www.nice.org.uk/aboutnice/nhsevidence/AboutNHSEvidence.jsp

NHS National Library for Health - Kidney Disease
www.library.nhs.uk/KIDNEY

Kidney Care
www.kidneycare.nhs.uk

UK Renal Registry
www.renalreg.com

UK Renal Registry 2008 report
www.renalreg.com/reports/renal-registry-reports/2008

Kidney Research UK
www.kidneyresearchuk.org

Authors

Dr Nicholas Sangala
MB BS MRCP
Guy's and St Thomas' Hospital, London

Dr David Goldsmith
MA FRCP
consultant kidney specialist, Guy's Hospital, London

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