Chronic kidney disease prevention and management
Author Professor Tim Usherwood
Expert reviewer Associate Professor Mark Thomas
Chronic kidney disease (CKD) is defined as either kidney damage or glomerular filtration rate (GFR) less than 60 mL/min/1.73 m2, or both, persisting for at least 3 months. Kidney damage in this definition includes pathological abnormality or a marker of damage such as abnormalities in blood tests, urine tests or imaging studies.1 CKD is classified into six stages depending on GFR as outlined in Table 13.1.1,2 Note that Stage 2 CKD requires evidence of kidney damage in addition to reduced GFR, whereas Stages 3A–5 are defined entirely on the basis of measured GFR.
Table 13.1. Stages of chronic kidney disease
|Stage||Description||GFR (mL/min/1.73 m2)|
||Kidney damage* with normal or increased GFR
||Kidney damage* with mild reduced GFR
||Moderately reduced GFR
||Moderately reduced GFR
||Severely reduced GFR
||<15 or dialysis
|* Kidney damage includes pathological abnormality or a marker of damage such as abnormalities in blood tests, urine tests or imaging studies1
Aboriginal and Torres Strait Islander people have a greatly increased prevalence of CKD,3 and are approximately 10 times more likely than non-Indigenous Australians to develop end stage kidney failure.4 However, there is great variation in prevalence between Aboriginal and Torres Strait Islander communities; rates are highest in remote areas and lowest in urban areas.5 Rates also correlate strongly with socioeconomic disadvantage.6 The reasons are multifactorial7 but important modifiable risk factors in Aboriginal and Torres Strait Islander people are thought to be the same as those in non-Indigenous people: overweight and obesity, diabetes, hypertension and smoking.3,4
Reduced GFR and raised albumin excretion are independent risk factors for mortality.8 The bulk of this mortality is due to cardiovascular disease, and people with CKD are at higher risk of dying from coronary heart disease or stroke than they are of progressing to end stage kidney disease.9,10 Even mild reduction in GFR is associated with excess cardiovascular and stroke risk,11,12 while at any given level of kidney function, microalbuminuria or macroalbuminuria is associated with increased cardiovascular and stroke morbidity and mortality.13,14
In clinical practice, GFR is often estimated [as eGFR] from serum creatinine and other parameters including gender and age using a formula such as the CKD-EPI.2 Care should be taken in accepting an eGFR value. Factors such as intercurrent illness, diet, underweight, overweight or obesity can bias the estimate. Furthermore, no formula has yet been validated for Aboriginal or Torres Strait Islander people.15
Proteinuria and albuminuria testing
Abnormal proteinuria is an important marker of kidney damage. Urinary protein usually includes albumin, and the proportion of total protein that is albumin is typically increased at higher levels of proteinuria.16 In diabetes and under most other circumstances, measurement of urinary albumin is a more sensitive test for CKD than testing for proteinuria; in the AusDiab study, only 8% of adults with proteinuria tested negative for albuminuria.16 The majority of international guidelines recommend screening for albuminuria rather than proteinuria for the detection of CKD.17 However, it is important to note that not all individuals with CKD exhibit abnormal albumin or protein excretion, and also that a small proportion of patients with abnormal proteinuria, such as those with tubulointerstitial disease or myeloma, may excrete abnormal amounts of non-albumin protein only.
Abnormal albumin excretion is classified as microalbuminuria (30–300 mg/24 hr) or macroalbuminuria (>300 mg/24 hr).17 A properly performed dipstick test, if negative, rules out macroalbuminuria but not microalbuminuria; a positive result required confirmation by laboratory methods.18 It is often convenient to measure albumin-creatinine ratio (ACR) or if indicated, protein-creatinine ratio (PCR), on a spot specimen preferably taken during first morning void. Table 13.2 provides definitions for microalbuminuria and macroalbuminuria based on ACR estimation. However, the relationship between this ratio and the albumin excretion rate is influenced by many factors so that estimation of 24 hour excretion from the ACR value is not recommended.17
Definitions of normal albumin excretion, microalbuminuria and macroalbuminuria
| ||Gender||Normal albumin excretion||Microalbuminuria||Macroalbuminuria|
|Urinary albumin excretion per 24 hours
||<30 mg/24 hr
||30–300 mg/24 hr
||> 300 mg/24 hr
Albumin excretion may be increased by urinary tract infection, acute febrile illness, high dietary protein, heart failure, recent heavy exercise or some drugs. Menstruation or vaginal discharge may also increase urinary albumin measurement. Definition of abnormal albuminuria requires at least two elevated ACR measurements in a 3 month period, therefore a single abnormal test should be repeated.17
Evidence supports the efficacy and cost effectiveness of screening for CKD risk factors, and for albuminuria and reduced GFR, in Aboriginal and Torres Strait Islander people.19,20 The optimal age to start screening is, however, less clear. In a cohort of urban and rural Aboriginal children followed up for 4 years from 10 years of age, more than 70% potential markers of CKD (haematuria, albuminuria, systolic and diastolic hypertension) found at baseline did not persist on follow up.21 On the other hand, in a study of the prevalence of proteinuria, hypertension and diabetes in Aboriginal adults above the age of 25 years living in remote communities, the probability of an individual aged 25–34 years having at least one of these abnormalities was approximately three times higher than for a participant in the national AusDiab study; this differential increased further in older age groups.22 Based on this evidence, screening for CKD risk factors from age 18 years is recommended. If any risk factors are present then CKD screening for albuminuria and reduced eGFR is recommended.
The robust epidemiological evidence and plausible biological explanations for the association of overweight and obesity, diabetes, hypertension and smoking with CKD suggest that interventions to prevent diabetes,23,24 to promote exercise, healthy diet and normal weight, to limit salt intake and to discourage smoking have the potential also to reduce the incidence of CKD.25–28 Programs that promote maternal health during pregnancy and prevent streptococcal infection in childhood may also reduce future risk of CKD.29
Active treatment of CKD, once detected, can slow progression to end stage disease, and reduce cardiovascular endpoints. Patients should be assisted to quit smoking,27 reduce excess weight30 and take regular exercise.28 Limiting dietary sodium intake to 100 mmol (6 g salt) per day may reduce both blood pressure (BP) and albumin excretion.30
An ACE inhibitor or ARB is generally the firstline treatment for lowering BP and protein excretion. These two classes of drug should not normally be prescribed together; although the combination may reduce both BP and proteinuria to a greater extent than monotherapy with either, it may worsen kidney outcomes.31
Statins reduce lipid concentrations and cardiovascular endpoints in patients with CKD, irrespective of stage, but no benefit on all cause mortality has been established.32,33 The reno-protective effects of statins are uncertain because of relatively sparse data and possible outcomes reporting bias.
Reasons for referral
The interventions tabulated in this chapter are concerned with preventing kidney disease, detecting and slowing the progression of established CKD, and reducing the associated risks of cardiovascular disease and stroke. While they are all amenable to delivery in the primary care setting, patients with more advanced disease or significant comorbidities, or at risk in other ways, are likely to benefit from referral to a secondary care nephrology service.34 The Caring for Australians with Renal Impairment guidelines35 recommend referral of patients with:
- Stage 4 or 5 CKD of any cause
- persisting albuminuria (ACR >30 mg/mmol)
- Declining eGFR >5 mL/min/1.73 m2 in 6 months (average of at least three measurements)
- CKD and elevated BP that is not at target despite at least three BP lowering medications
- unexplained anaemia (<100 g/L) with eGFR <60 mL/min/1.73 m2.
Recommendations: Chronic kidney disease detection and management
|Preventive intervention type||Who is at risk?||What should be done?||How often?||Level/strength of evidence|
||All adults aged 18–29 years without any CKD risk factors
||Screen for CKD risk factors (overweight or obesity, diabetes, elevated BP and smoking, family history of kidney disease)
||As part of an annual health assessment
|People aged 18–29 years with one of the following CKD risk factors:
- family history of CKD or premature CVD
- overweight/ obesity
- elevated BP
|Screen for CKD with eGFR and urinary albumin-creatinine ratio (ACR)
A first void specimen is preferred
If urine ACR is raised then repeat once or twice over 3 months. For further quantification consider collecting a timed specimen
|Every 2 years (or more frequently if CVD risk is elevated – see Chapter 12: Cardiovascular disease prevention)
|All people ≥30 years
||Adults with any risk factors for CKD (see above)
||Offer individualised, structured education about risk factor avoidance and management
|Offer smoking cessation support (see Chapter 1: Lifestyle, section on smoking)
Advise avoidance of exposure to environmental tobacco smoke
|Encourage regular physical exercise appropriate to their physical ability and medical history (see Chapter 1: Lifestyle, section on physical activity)
|If overweight or obese encourage weight loss
Offer group diet and exercise sessions if available, especially for patients with type 2 diabetes (see Chapter 1: Lifestyle, section on overweight/obesity)
|Advise to limit dietary sodium intake to 100 mmol/day (6 g salt per day) or less
|Adults with CKD stages 1–3 (see Table 13.1)
||Lifestyle risk factor management as above
Patients with CKD should be advised not to use salt substitutes that contain high amounts of potassium salts
||As above for each risk factor27,28,30,37–39
|Advise consuming the recommended daily intake of protein for adults (0.75 g/kg/day)
|A daily fluid intake of 2–2.5 L (including the fluid content of foods) is generally sufficient, although this might need to be varied according to individual circumstances
||All people with CKD
||Regularly review medications to identify and avoid those with potential nephrotoxicity
Advise patients taking an angiotensin converting enzyme (ACE) inhibitor or angiotensin II receptor blocker (ARB) plus diuretic to avoid non-steroidal anti-inflammatory drugs (other than low dose aspirin if indicated)
|Opportunistic at every medication change
|Adults with CKD and albuminuria (see Table 13.2)
||Commence treatment with an ACE inhibitor or ARB, regardless of BP level. The goal is >50% reduction in albumin excretion without symptomatic hypotension
Alternative agents include calcium channel blockers
|An ACE inhibitor and an ARB should not normally be prescribed together
|Adults with CKD and diabetes
||Commence treatment with an ACE inhibitor or ARB regardless of BP level
|Blood glucose control in patients with CKD and diabetes should be optimised, generally aiming for an HbA1c target of 7%
|Adults with CKD and elevated BP
||Consider use of more than one drug to achieve adequate BP control. (The number of drugs required tends to increase with declining GFR)
||Opportunistic BP check at every visit
|If prescribed a BP lowering medication aim for a target of <140/90 mmHg, or <130/80 mmHg in the presence of micro- or macro-albuminuria (with or without diabetes)
|Adults with CKD
||Statins should be prescribed according to level of overall cardiovascular risk (see Chapter 12: Cardiovascular disease prevention)
||Communities with high prevalence of scabies and pyoderma
||Support the implementation of population based strategies for reduction of scabies and pyoderma among children (see Chapter 2: Child health and Chapter 5: Rheumatic heart disease)
Chronic kidney disease management in general practice, 2nd edn (Kidney Health Australia)
Caring for Australians with Renal Impairment guidelines
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- Australian Creatinine Consensus Working Group. Chronic kidney disease and automatic reporting of estimated glomerular filtration rate: new developments and revised recommendations (draft). Australian Creatinine Consensus Working Group, 2011.
- Australian Institute Health and Welfare. Chronic kidney disease in Australia 2005. Canberra: AIHW, 2005. Cited October 2011. Available at www.aihw.gov.au/ publications/index.cfm/title/10137.
- Jose M, McDonald S, Excell L, editors. End-stage kidney disease among Indigenous peoples of Australia and New Zealand. Australia and New Zealand Dialysis and Transplant Registry. Adelaide: ANZDATA Registry, 2009.
- Preston-Thomas A, Cass A, O’Rourke P. Trends in the incidence of treated end-stage kidney disease among Indigenous Australians and access to treatment. Aust N Z J Public Health 2007;31(5):419–21.
- Cass A, Cunningham J, Snelling P, Wang Z, Hoy W. End-stage renal disease in indigenous Australians: a disease of disadvantage. Ethn Dis 2002 Summer;12(3):373–8.
- Cass A, Cunningham J, Snelling P, Wang Z, Hoy W. Exploring the pathways leading from disadvantage to end-stage renal disease for indigenous Australians. Soc Sci Med 2004 Feb;58(4):767–85.
- Matsushita K, van der Velde M, Astor BC, et al. Association of estimated glomerular filtration rate and albuminuria with all-cause and cardiovascular mortality in general population cohorts: a collaborative meta-analysis. Lancet 2010 Jun 12;375(9731):2073–81.
- Weiner DE, Tighiouart H, Amin MG, et al. Chronic kidney disease as a risk factor for cardiovascular disease and all-cause mortality: a pooled analysis of community-based studies. J Am Soc Nephrol 2004;15(5):1307–15.
- National Vascular Disease Prevention Alliance. Guidelines for the assessment of absolute cardiovascular risk. National Vascular Disease Prevention Alliance, 2009.
- Di Angelantonio E, Chowdhury R, Sarwar N, Aspelund T, Danesh J, Gudnason V. Chronic kidney disease and risk of major cardiovascular disease and non-vascular mortality: prospective population based cohort study. BMJ 2010;341:c4986.
- Lee M, Saver JL, Chang KH, Liao HW, Chang SC, Ovbiagele B. Low glomerular filtration rate and risk of stroke: meta-analysis. BMJ 2010;341:c4249.
- Schmieder RE, Schrader J, Zidek W, et al. Low-grade albuminuria and cardiovascular risk: what is the evidence? Clin Res Cardiol 2007;96(5):247–57.
- Lee M, Saver JL, Chang KH, Liao HW, Chang SC, Ovbiagele B. Impact of microalbuminuria on incident stroke: a meta-analysis. Stroke 2010 Nov;41(11):2625–31.
- Maple-Brown LJ, Lawton PD, Hughes JT, et al. Study protocol: accurate assessment of kidney function in Indigenous Australians: aims and methods of the eGFR study. BMC Public Health 2010;10:80.
- Atkins RC, Briganti EM, Zimmet PZ, Chadban SJ. Association between albuminuria and proteinuria in the general population: the AusDiab Study. Nephrol Dial Transplant 2003 Oct;18(10):2170–4.
- Australasian Proteinuria Consensus Working Group. Chronic kidney disease and measurement of albuminuria/proteinuria: a position statement (draft). Australasian Proteinuria Consensus Working Group, 2011.
- White SL, Yu R, Craig JC, Polkinghorne KR, Atkins RC, Chadban SJ. Diagnostic accuracy of urine dipsticks for detection of albuminuria in the general community. Am J Kidney Dis 2011 Mar 14.
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- Haysom L, Williams R, Hodson EM, et al. Natural history of chronic kidney disease in Australian Indigenous and non-Indigenous children: a 4-year population-based follow-up study. Med J Aust 2009;190(6):303–6.
- Hoy WE, Kondalsamy-Chennakesavan S, Wang Z, et al. Quantifying the excess risk for proteinuria, hypertension and diabetes in Australian Aborigines: comparison of profiles in three remote communities in the Northern Territory with those in the AusDiab study. Aust N Z J Public Health 2007;31(2):177–83.
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