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Chronic kidney disease: preventing progression and CVD complications

In the second of two articles on CKD, renal specialists Dr Mohsen El Kossi, Dr Aminu Kasarawa Bello, Dr Rizwan Hamer and Professor A Meguid El Nahas describe how tackling risk factors is key to coping with the rising tide of CKD

In the second of two articles on CKD, renal specialists Dr Mohsen El Kossi, Dr Aminu Kasarawa Bello, Dr Rizwan Hamer and Professor A Meguid El Nahas describe how tackling risk factors is key to coping with the rising tide of CKD

41186461An increasing number of patients are being treated worldwide for CKD. Globally, it has been suggested that as many as 100 million individuals may be affected. The natural course of CKD extends from susceptibility, exposure to risk factors, developing CKD and progressing to established renal failure (ERF – also known as ‘stage 5') needing renal replacement therapy (RRT) or leading to death.

A better understanding of the epidemiology, risk factors and natural history is likely to lead to better prevention and management.

CKD epidemiology

Provision of care for patients who require dialysis or transplantation is a major and growing healthcare problem in both developed and emerging nations – in terms of cost, premature mortality and economic impact.

It is estimated that more than one-and-a-half million patients with ERF worldwide are currently on RRT, with the number due to exceed two million by 2010, at a global cost of around a trillion dollars.

Some 90% of all treated ERF patients reside in the West, as the prohibitive cost precludes RRT in most developing nations.

In the US, it is estimated that RRT will cost around $29bn by 2010.

Currently in the UK, around 100 patients per million population (pmp) per year are started on RRT. Provision of RRT may consume about 2% of the NHS cost in the next decade.

There are geographical differences in the causes and prevalence of ERF – from an incidence of 15 pmp/year in China and Russia to 989 pmp/year in the black US population.

The reasons for these observed discrepancies are multi-factorial, ranging from racial and socio-economic factors as well as health services provision.

Information from developing countries in Asia, Africa and South America is scarce because of lack of renal registries and the database, and the fact that their economies cannot sustain the growing burden of ERF.

In fact, 110 of 222 countries are unable to provide RRT, leaving more than 600 million individuals without treatment for ERF. Around one million individuals die every year from untreated renal failure.

Of major concern is the fact that the number of patients with ERF is a small proportion of the entire burden of CKD, as the number of individuals with earlier stages – 1 to 4 – is likely to be 50 times more than those reaching ERF.

In the US, the third National Health and Nutrition Examination Survey (NHANES III) has estimated that 11% (19 million) of the adult American population may have CKD. Of these, only 300,000 have reached stage 5.

The burden of CKD may also be high in countries such as the UK, the Netherlands, Australia and in some developing countries such as India and Singapore.

However, many of those with signs of CKD have underlying hypertension and/or diabetes mellitus, which is often previously unrecognised or poorly controlled.

Future burden and projection forecast

There are few estimates on the future burden of CKD. Globalisation and risk transition phenomena have evolved with a growing trend in CKD risk factors and markers such as diabetes, hypertension, obesity and smoking, and therefore possible consequent increase in CKD rates.

For example, the current global diabetes population of 154 million is expected to double in the next two decades. The prevalence of hypertension is projected to increase by 60% in the next two decades, affecting one-third of the world adult population.

One-fifth of the world population (1.6 billion) is overweight or obese and 1.3 billion smoke cigarettes. Changes in lifestyle and population demographics, such as ageing, may also impact on the increasing trend of CKD in the coming decades.

CKD risk factors

The susceptibility, initiation and progression of CKD are all associated with risk markers and factors. The former refers to observed associations while the latter refers to causal ones.

Some of the risk markers and factors are implicated in both susceptibility and progression. Many are also associated with increased CVD risk.

Susceptibility to CKD is higher among certain families and races. This highlights the possibility of genetic predisposition.

In the US, racial differences in the prevalence of CKD and ERF may reflect the high prevalence of hypertension-related and diabetes-related CKD among native and African-Americans.

In the UK, Afro-Caribbeans and Indo-Asians are at increased risk of CKD. One elegant hypothesis links low birthweight among ethnic minorities to consequent fetal renal underdevelopment and a reduced number of hypertrophied nephrons – oligomeganephronia. These birth defects may, in adult life, contribute to the pathogenesis of hypertension and CKD.

Males and older age groups are also more susceptible to developing CKD. Among the known risk factors are hypertension, diabetes, hyperlipidaemia, obesity and smoking.

In developing countries, the profile of risk factors for CKD may also reflect the impact of communicable disease such as HIV, hepatitis C, malaria and schistosomiasis as well as tuberculosis.

Natural history and progression

The rate of progression and GFR decline in CKD is very variable. In the majority of patients there is little or no progression, with the majority of CKD sufferers succumbing to cardiovascular disease.

Some types of kidney diseases, however, progress significantly. Diabetic kidney disease, glomerular diseases and polycystic kidney disease are associated with a faster GFR decline than hypertensive and tubulointerstitial kidney diseases.

Irrespective of the original kidney disease, there are other modifiable and non-modifiable risk factors that influence the rate of CKD progression. African-American race (US), diabetic Asians (UK), lower baseline level of kidney function, male gender and older age are among the non-modifiable risk factors associated with a faster GFR decline.

Hypertension is the single most important risk factor associated with accelerated decline in kidney function in CKD patients.

The control of systemic hypertension is the most effective intervention to slow the progression of CKD.

Current guidelines recommend a reduction in blood pressure to levels below 130/80mmHg in patients with CKD. Furthermore, lower blood pressure targets (below 125/75mmHg) have been advocated for patients with heavy proteinuria (more than 1g/24 hours), and those suffering from diabetic nephropathy.

Heavy proteinuria is also associated with a faster rate of decline attributed by some to a direct nephrotoxic effect of protein/ albumin on renal tubules. With that in mind, it is imperative that the control of hypertension is coupled with a reduction in proteinuria to levels less than 1g/24 hours.

ACE inhibitors and ARBs may have a therapeutic advantage as they are effective at reducing both hypertension and proteinuria.

In diabetic patients, poor glycaemic control appears to contribute to a faster rate of decline of diabetic nephropathy.

Target HbA1c levels around 7% are recommended. Dyslipidaemia and smoking are also among the modifiable risk factors associated with a progressive CKD and have to be addressed (see box below).

Many, if not all, of the risk factors and markers associated with progressive CKD have also been implicated in CVD. Furthermore, albuminuria has recently been identified as a strong marker for cardiovascular disease morbidity and mortality.

The PREVEND study showed increased cardiovascular mortality in the general population with increased urine albumin excretion rate. This has also been observed in studies of patients with coronary artery disease and hypertension, where albuminuria was noted to be a stronger predictor of cardiovascular morbidity than some of the better-known CVD markers such as hypertension or hyperlipidaemia.

Therefore population screening for albuminuria may have the advantage of early detection of those at risk of both CKD and CVD.

It is most likely that cost-effective screening programmes will focus on the at-risk population including hypertensive, diabetic and obese individuals. In addition, screening of the elderly for proteinuria is more cost-effective than those under the age of 60 in view of the higher prevalence of CKD in the elderly.

Recommendations for the screening and detection of early CKD were set out in last week's article (see Detecting and preventing the progression of CKD would have major healthcare impacts and socio-economic consequences. Such an approach is the sole option in many developing countries where CKD and its progression to ERF equates to a death sentence.

Complications of CKD

The interventions discussed in the table (below, left) are primarily intended to slow the progression of CKD. It is important to appreciate that the outcome and prognosis of patients with ERF is often determined by associated uraemic complications, including CVD and malnutrition at the initiation of RRT.

Cardiovascular complications include coronary artery disease, heart failure and left ventricular hypertrophy. If these are present at the initiation of RRT this confers a poor long-term prognosis.

In order to minimise CKD-associated CVD, anaemia, hypertension and hyperparathyroidism, including the calcium/phosphate balance, need to be corrected.

In order to minimise malnutrition, attention needs to be paid to optimising dietary protein and calorie intake. Metabolic acidosis has a significant catabolic effect and should be corrected. Other complications of CKD also need to be addressed, including the early management of renal osteodystrophy.

The control of hyperphosphataemia and the reduction of raised calcium phosphate product may also have an impact on the progression of CVD-associated morbidity and mortality.

Finally, timely referral for evaluating the best way to manage progressive renal functional decline –such as pre-emptive renal transplantation, the initiation of planned RRT or conservative therapy, is essential in patients close to or at stage 5.

Most guidelines recommend starting RRT at a GFR around 10ml/min/1.73m2.

In conclusion, CKD is a growing healthcare problem that is preventable, detectable and manageable with careful strategic planning and optimal and timely interventions.

Dr Mohsen El Kossi is specialist registrar in renal and general medicine at the Sheffield Teaching Hospitals NHS Trust.

Dr Aminu Kasarawa Bello is clinical research fellow at Sheffield Teaching Hospitals NHS Trust.

Dr Rizwan Hamer is specialist registrar at Birmingham Heartlands Hospital.

Professor A Meguid El Nahas is professor of nephrology at the University of Sheffield.

This is an extract from ABC of Kidney Disease, Blackwell Publishing ISBN 978-1-4051-3675-4

ckd2 Controlling hypertension is the most effective way of slowing renal damage

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