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ChroniC renal failure

Epidemiology and causes of chronic renal failure

Terry feest

Abstract

recent studies have shown that the prevalence of chronic renal failure (Crf) is higher than was widely believed. The prevalence of renal replacement therapy (rrT) is rising progressively, although the rising incidence has stabilized in some developed countries. needs may differ widely between countries depending on ethnic mix, social deprivation, prevalence of diabetes, and quality of healthcare. Diabetic nephropathy is the single most common cause of Crf, leading to over 40% of rrT in some countries, and will increase significantly in the next decade. Making a precise renal diagnosis identifies reversible causes, predicts prognosis, predicts recurrence after transplantation and aids counselling in familial conditions. renal failure is less common in children than in adults, with a different spectrum of causes. renal failure is common in developing countries, particularly in tropical areas and in young indi- viduals: secondary glomerular diseases related to infection are common. rrT is an expensive but effective therapy, which will inevitably consume increasing resources in the next decade as numbers grow and the growing proportion of elderly patients and others with co-morbid conditions and social problems will place greater demands on healthcare resources.

Keywords chronic kidney disease; chronic renal failure; diabetic nephropathy; eGfr; renal replacement therapy

Renal replacement therapy (RRT) is an expensive but effective treatment for chronic renal failure (CRF). In the UK, it consumes over 2% of the NHS budget: this is predicted shortly to reach 3%. Worldwide, the number of patients receiving RRT is increasing progressively. The prognosis of patients starting RRT is improv- ing annually, and as fewer die each year than start therapy, the prevalence will continue to rise even if acceptance rates for ther- apy stabilize. In the UK, more than 640 patients/million popula- tion are currently receiving therapy: in the USA, this figure is 1500/million population, and in Japan 1800 patients/million. As the prevalence of patients on RRT increases, expenditure will increase. This will be accentuated by the growing proportion of elderly patients and others with comorbid conditions and social problems who place greater demands on healthcare resources. 13 It is important to understand the incidence and causes of such a major drain on healthcare resources, both for prevention of renal failure and for planning future services for RRT.

Terry Feest FRCP is Consultant Nephrologist at the Richard Bright Renal Unit, Bristol, UK. His research interests include epidemiology, treatment and audit of care of renal failure. Competing interests:

none declared.

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Definitions

Progressive renal failure should be monitored by changes in serum creatinine, from which an estimate of renal function related to age, gender, ethnicity and possibly body weight can be calculated. The most widely used estimate is the estimated

glomerular filtration rate (eGFR), calculated by the Modification

of Diet In Renal Disease (MDRD) equation, on which the widely

used Kidney Disease Outcomes Quality Initiative (K/DOQI) classification of chronic kidney disease (CKD) is based. 4 The term ‘CRF’ is difficult to define. Some symptoms may develop with only modest renal impairment, but ‘failure’ is prob- ably best defined as occurring when there are severe symptoms related to uraemia which can be relieved only by RRT. This is usually when eGFR falls to 15 ml/minute (CKD stage 5). Estab- lished renal failure (ERF), also called end-stage renal failure (ESRF), is the irreversible deterioration of renal function to a degree that is incompatible with life without RRT, either by dia- lysis or transplantation. Even this is variable: most nephrologists now tend to dialyse patients at an earlier stage, when eGFR has fallen to about 8–15 ml/minute, rather than wait for it to fall to 5–6 ml/minute as in the past.

Incidence and epidemiology

There are two main sources of data on the incidence and causes

of CRF. Community-based studies give information on the preva-

lence and incidence of CRF, while renal registries report on the use of RRT.

Community-based studies Several recent studies suggest the prevalence of renal impair- ment is greater than was widely appreciated, especially in the

elderly (Table 1). 46 The majority of these patients do not start RRT, sometimes because their renal disease does not progress, and other times because they die of other conditions first, mostly cardiovascular disease for which CKD is a potent marker. 7 There are fewer community-based studies of the incidence of CRF. Three such studies from the UK show a similar pattern of

a progressive increase in incidence with age, from 58/million

population/year in 20–49-year-olds to 588/million population/ year in people over 80 years old.

Renal registries International and national registries provide the largest volume of data on RRT. There are many registry-based reports contain- ing data on large numbers of patients, which are fairly precise in terms of diagnosis and incidence. These are not studies of the incidence of CRF, but of the incidence of treatment of CRF, and thus, in addition to varying population needs, also reflect the attitudes of nephrologists and more importantly of primary care doctors and other physicians towards referral for nephro- logical opinion and treatment. Clinical thresholds for treatment are changing: studies of physicians and nephrologists in the last decades show a liberalization of attitudes. 8

Gender: among those with CRF, men outnumber women by at least 1.5:1. This ratio is higher over the age of 70 years, despite the greater longevity of women.

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ChroniC renal failure

Prevalence of chronic renal failure

Study

Year

Country

Age

Definition

% prevalence

nhaneS iii

1988–1994

uSa

>20

eGfr

 

CKD stage 3

4.3%

CKD stages 4 & 5

0.4%

ausdiab

2002

australia

>24

C&G eCCr

 

CKD stage 3

10.9%

CKD stages 4 & 5

0.3%

De lusignan, et al

2004

uK

all

eGfr

 

CKD stage 3

4.6%

CKD stages 4 & 5

0.2%

eGfr, glomerular filtration rate; CKD, chronic kidney disease; C&G eCCr, estimated creatinine clearance by Cockcroft and Gault method.

Table 1

Racial differences: in the UK and USA, the incidence of initia- tion of RRT in African-Caribbean and South Asian populations

in any age group is at least 3–5-times greater than that in a com- parable Caucasian population. As these relatively young ethnic minority populations mature over the next two decades there will be a significant increase in demand for RRT. 9 In some popu- lations, particularly many indigenous American and Australasian groups, the incidence of ERF is very much higher, largely due to

a combination of the effects of a massive prevalence of diabe-

tes and hypertension. 3,10 However, data from London and else- where indicate that other renal diseases are also more common in the African-Caribbean and South Asian populations. Whilst CRF is more common in areas of social deprivation, this does not explain the high incidence of CRF in ethnic minorities. 11

Changing patterns: whilst the worldwide total acceptance rate per million population for RRT is rising, in some developed countries it has been stable in the last three years (including USA [total 341: whites 259, blacks 996], New Zealand [110], the Netherlands [100], Australia [95], the Scandinavian countries) whereas in others it is still rising (Germany [194], Austria [154], UK [105]). The pattern does not seem to be related to the accep- tance rates of individual countries. In the UK, there has been

a more than fourfold increase since 1980, to an annual accep-

tance rate of over 105/million population/year (Figure 1) with many more elderly and diabetic patients receiving treatment.

Patients are increasingly older. In 1982, in the UK, only 11% of new patients were over 65 years old compared with 50% now (Figure 2). 2 The total acceptance rate needed to meet the demand for RRT

is unknown, may be rising, and will vary with the age, racial,

and social make-up of the population. Population projections suggest an increase in over-65-year-olds during the next two

decades, which will lead to a significant increase in demand.

A study comparing the UK and Germany, where the acceptance

rates are very different, suggests that a large part of the difference is due to differing needs related to the prevalence of diabetes and hypertension, effectiveness of therapy for hypertension, and perhaps differing attitudes to offering supportive care rather than dialysis. 12

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Causes of CRF

Precise diagnosis of the cause of renal failure is mainly of impor- tance in identifying and treating reversible causes. It also helps in assessing prognosis and planning for RRT, in assessing the likelihood of recurrence of primary renal disease after renal trans- plantation, and in counselling families in which familial conditions, such as polycystic kidney disease, vesico-ureteric reflux, or Alport’s syndrome, occur. The causes of ESRF in patients starting dialysis in the UK, Germany, Australasia and three major racial groups in the USA are listed in Table 2. In a significant percentage of patients the

Age and diagnosis-specific acceptance rates of patients starting renal replacement therapy in the UK, 1980–2001
Age and diagnosis-specific acceptance rates of
patients starting renal replacement therapy in the
UK, 1980–2001
350
<44 years of age
45–64 years of age
300
>65 years of age
Diabetics
250
Total
200
150
100
50
0
Rate per million population
1980 1981 1982 1983 1984 1985 1986 1987 1988 1990 1991 1992 1993 1994 1995
1980
1981
1982
1983
1984
1985
1986
1987
1988
1990
1991
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004

Year

The annual rates are per million alive in the population in the specified age range.

Figure 1

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ChroniC renal failure

Age and gender distribution of patients starting renal replacement therapy in the UK, 2004 700
Age and gender distribution of patients starting
renal replacement therapy in the UK, 2004
700
Males
Females
600
All UK
500
400
300
200
100
0
Rate per million population
20–24 25–29 30–34 35–39 40–44 45–49 50–54 55–59 60–64 65–74 75–79 80–84 85–88 90+
20–24
25–29
30–34
35–39
40–44
45–49
50–54
55–59
60–64
65–74
75–79
80–84
85–88
90+

Age group

Figure 2

diagnosis is uncertain; many of these patients present with renal failure with two small kidneys and no further clues to the aetiology. Renal biopsy can be dangerous and unhelpful in these circumstances. In the UK, uncertain diagnosis is more common in those aged over 65 years (28%) than in younger patients (16%). 2,3,13

Hypertensive renal disease The most striking difference between the UK and the USA is the apparent incidence of hypertensive renal disease, which appears markedly more common in the USA. This also illustrates the imprecision of diagnosis. The diagnosis of hypertensive renal disease is usually made on clinical grounds and not following biopsy, but several European biopsy studies have shown that many such patients have underlying glomerulonephritis or other renal disease.

Diabetic nephropathy Diabetic nephropathy is the most common cause of ESRF in developed countries, constituting 46% in the USA, 41% Japan, 40% New Zealand, 34% Germany, 30% Australia, 18% in the UK and 15% in Norway. This variation probably reflects both

a variation in the incidence of diabetes and a variation of the

willingness of physicians to offer dialysis to patients with many diabetic complications. The diabetic ESRF population is increas- ingly elderly, with type II diabetics outnumbering type I by over 10:1 in some countries. 14,15

Glomerulonephritis Many forms of glomerulonephritis progress to CRF. Despite the many recent advances in understanding the underlying mecha- nisms of disease, relatively few forms of glomerulonephritis have been shown in controlled trials to respond to currently available therapies.

Other important causes of CRF

It is important to exclude less common but potentially revers-

ible causes of CRF. The majority are not associated with heavy proteinuria. These include renovascular disease (which may be

Causes of established renal failure in patients starting renal replacement therapy

Country/Year

UK 2004

Germany

Australia

New Zealand

 

USA 2000–2004

 
 

2004

2004

2004

 

White

Black

Native American

 

%

pmp

%

pmp

%

pmp

%

pmp

%

pmp

%

pmp

%

pmp

Diabetes

18.0

18.9

34.0

66.0

30.0

28.5

40.0

44.0

44.6

115.5

43.6

434.3

73.1

271.2

Glomerulonephritis

10.4

10.9

12.0

23.3

25.0

23.8

24.0

26.4

8.4

21.8

7.1

70.7

7.5

27.8

Pyelonephritis/

7.0

7.4

8.0

15.5

3.0

2.9

3.0

3.3

0.6

1.6

0.1

1.0

0.4

1.5

reflux

Polycystic kidney

5.4

5.7

5.0

9.7

7.0

6.7

5.0

5.5

2.8

7.3

1.0

10.0

0.7

2.6

disease (PKD)

hypertension

5.5

5.8

< 4

13.0

12.4

16.0

17.6

21.1

54.6

33.8

336.6

8.0

29.7

renovascular

7.5

7.9

22.0

42.7

n.a.

n.a.

2.6

6.7

0.4

4.0

0.4

1.5

disease

uncertain

23.0

24.2

9.0

17.5

7.0

6.7

5.0

5.5

4.5

11.7

3.1

30.9

2.5

9.3

Missing data

9.2

9.7

n.a.

-!

n.a.

-!

n.a.

-!

1.0

2.6

1.0

10.0

0.2

0.7

Pmp, annual incidence per million population.

note how percentages of the total may be misleading with regard to the annual incidence per million population (e.g. as the annual incidence of rrT in Black americans is nearly ten times that in the uK, the low percentage of PKD in them actually represents a higher annual incidence pmp than in the uK).

Table 2

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ChroniC renal failure

unmasked by the use of ACE inhibitor drugs), acute interstitial nephritis and other drug reactions, use of non-steroidal anti- inflammatory drugs (NSAIDs), and renal vasculitis in which rapid diagnosis enables effective therapy. Obstructive uropathy must always be considered; prostatic disease is the most common cause of renal impairment in elderly men.

Renal failure in children

Renal failure is much less common in children than in adults; the annual incidence is about 6/million population. The causes dif- fer markedly from adult practice. Dysplastic kidneys and reflux nephropathy are relatively common and there are many more hereditary diseases, of which cystinosis is one of the most impor- tant. Haemolytic uraemic syndrome is relatively common in chil- dren, although the majority recover renal function. Other forms of glomerulonephritis are less common than in adults and often do not lead to renal failure until adult life.

Renal failure in developing countries

Renal failure is common in developing countries, particularly in tropical areas and in young individuals. Secondary glomerular diseases related to infection are common. Socioeconomic and local environmental factors determine the pattern of disease. HIV nephropathy is a growing problem. In many countries, post-streptococcal glomerulonephritis remains a common problem. In endemic areas, Schistosoma haematobium may cause obstructive uropathy, and S. mansoni causes several types of glomerulopathy, including mesangiocapillary glomeru- lonephritis that often progresses to CRF. Plasmodium malariae and hepatitis B cause membranous and membranoproliferative glomerulonephritides, which may progress to CRF. Amyloidosis

secondary to various chronic infections is another common cause of nephrotic syndrome and renal failure; it is usually secondary to tuberculosis in India, and to leprosy in Papua New Guinea. The incidence of HIV nephropathy is increasing. The incidence of CRF in developing countries could be reduced by improved economic conditions and eradication of endemic infections. In these areas, dialysis is unaffordable for all but the very wealthy; survival depends on early transplantation. There is commonly a lack of cadaver donors leading to pressure on relatives and friends to become living donors, and a trade in paid

organ donation.

REFERENCES

1 feest TG, rajamahesh J, Byrne C, et al. Trends in adult renal replacement therapy in the uK: 1982–2002. QJM 2005; 98: 21–28.

2 ansell D, feest T, rao r, Williams a, Winearls C. uK renal registry 8th annual report. 2005. (available at: www.renalreg.com)

3 uS renal Data System. uSrDS 2006 annual Data report: atlas of end-stage renal disease in the united States. uSrDS, 2006. (available at: www.usrds.org)

4 Coresh J, astor BC, Greene T, eknoyan G, levey aS. Prevalence of chronic kidney disease and decreased kidney function in the adult uS population: Third national health and nutrition examination Survey. Am J Kidney Dis 2003; 41: 1–12.

5 Chadban SJ, Briganti eM, Kerr PG, et al. Prevalence of kidney damage in australian adults: The ausDiab kidney study. J Am Soc Nephrol 2003; 14(suppl 2): S131–38.

6 de lusignan S, Chan T, Stevens P, et al. identifying patients with chronic kidney disease from general practice computer records. Fam Pract 2005; 22: 234–41.

7 Keith DS, nichols Ga, Gullion CM, Brown JB, Smith Dh. longitudinal follow-up and outcomes among a population with chronic kidney disease in a large managed care organization. Arch Intern Med 2004; 164: 659–63.

8 McKenzie JK, Moss ah, feest TG, Stocking CB, Siegler M. Dialysis decision making in Canada, the united Kingdom, and the united States. Am J Kidney Dis 1998; 31: 12–18.

9 roderick PJ, raleigh VS, hallam l, Mallick nP. The need and demand for renal replacement therapy in ethnic minorities in england. J Epidemiol Community Health 1996; 50: 334–39.

10 hoy W. renal disease in australian aborigines. Nephrol Dial Transplant 2000; 15: 1293–97.

11 Caskey fJ, roderick P, Steenkamp r, et al. Social deprivation and survival on renal replacement therapy in england and Wales. Kidney Int 2006; 70: 2134–40.

12 Caskey fJ, Schober-halstenberg hJ, roderick PJ, et al. exploring the differences in epidemiology of treated eSrD between Germany and england and Wales. Am J Kidney Dis 2006; 47: 445–54.

13 McDonald S, excell l. australia and new Zealand Dialysis and Transplant registry 28th annual report. 2005. (available at:

14 Muntner P, Coresh J, Powe nr, Klag MJ. The contribution of increased diabetes prevalence and improved myocardial infarction and stroke survival to the increase in treated end-stage renal disease. J Am Soc Nephrol 2003; 14: 1568–77.

15 lippert J, ritz e, Schwarzbeck a, Schneider P. The rising tide of eSrf from diabetic nephropathy type ii – and epidemiological analysis. Nephrol Dial Transplant 1995; 10: 462–67.

Practice points

numbers of patients on renal replacement therapy are rising, with an increasing proportion elderly: this has major implications for resources

The incidence of Crf increases with age and is at least three- to five-fold higher in many ethnic minority populations

Making a precise renal diagnosis identifies reversible causes, predicts prognosis, predicts recurrence after transplantation and aids counselling in familial conditions

renal failure is less common in children than in adults and the spectrum of causes differs

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