2. Background
•1 in 10 people in the UK have chronic kidney disease (CKD)
•Treatment can prevent or delay the progression of CKD
and reduce the risk of cardiovascular disease.
•CKD is frequently unrecognised, often existing with other conditions
such as cardiovascular disease or diabetes.
•30% of patients with advanced CKD are referred late to nephrology
services from primary and secondary care.
3. Definition of CKD
Structural or functional abnormalities of
the kidneys for >3 months, as
manifested by either:
1. Kidney damage, with or without decreased
GFR, as defined by
• pathologic abnormalities
• markers of kidney damage, including
abnormalities in the composition of the blood or
urine or abnormalities in imaging tests
2. GFR <60 ml/min/1.73 m2
, with or without
kidney damage
4. Prevalence of CKD and Estimated Number of Adults
with CKD in the US (NHANES 88-94)
Stage Description
GFR
(ml/min/1.73 m2
)
Prevalence*
N
(1000s)
%
1
Kidney Damage with
Normal or ↑ GFR
≥ 90 5,900 3.3
2
Kidney Damage with
Mild ↓ GFR
60-89 5,300 3.0
3 Moderate ↓ GFR 30-59 7,600 4.3
4 Severe ↓ GFR 15-29 400 0.2
5 Kidney Failure < 15 or Dialysis 300 0.1
*Stages 1-4 from NHANES III (1988-1994). Population of 177 million with age ≥20. Stage 5 from USRDS (1998), includes
approximately 230,000 patients treated by dialysis, and assuming 70,000 additional patients not on dialysis. GFR estimated
from serum creatinine using MDRD Study equation based on age, gender, race and calibration for serum creatinine. For
Stage 1 and 2, kidney damage estimated by spot albumin-to-creatinine ratio ≥17 mg/g in men or ≥25 mg/g in women in two
measurements.
5. Classification
Stages of chronic kidney disease (updated)
1 ≥ 90 Normal or increased glomerular
filtration rate (GFR), with other
evidence of kidney damage
2 60–89 Slight decrease in GFR,
with other evidence of kidney damage
3A 45–59 Moderate decrease in GFR
with or without other evidence of
kidney damage3B 30–44
4 15–29 Severe decrease in GFR, with or
without other evidence of kidney
damage
5 < 15 Established renal failure
a
Use suffix (p) to denote presence of proteinuria when staging CKD
6. Classification of CKD by Diagnosis
• Diabetic Kidney Disease
• Glomerular diseases (autoimmune diseases,
systemic infections, drugs, neoplasia)
• Vascular diseases (renal artery disease,
hypertension, microangiopathy)
• Tubulointerstitial diseases (urinary tract infection,
stones, obstruction, drug toxicity)
• Cystic diseases (polycystic kidney disease)
• Diseases in the transplant (Allograft nephropathy,
drug toxicity, recurrent diseases, transplant
glomerulopathy)
7. Early identification
– Offer testing for CKD where the following risk factors are
present:
• hypertension
• cardiovascular disease
• diabetes
• structural renal tract disease
• renal calculi
• prostatic hypertrophy
• multisystem diseases with potential kidney involvement
• opportunistic detection of haematuria or proteinuria
• family history of stage 5 CKD or hereditary kidney disease
• Monitor GFR in people prescribed nephrotoxic drugs
8. Measurement of kidney
function
•Clinical laboratories should:
–report estimated GFR (eGFR) when serum creatinine
is measured
–correct for ethnicity
•Interpret eGFR with caution at extremes of muscle mass
•In new cases of reduced eGFR confirm by retesting within
2 weeks
•Urgent despatch and testing of blood minimises
incorrect results
9. Testing for proteinuria
– To detect and identify proteinuria, use urine
albumin:creatinine ratio (ACR) in preference,
as it has greater sensitivity than protein:creatinine
ratio (PCR) for low levels of proteinuria
– For quantification and monitoring of proteinuria,
PCR can be used as an alternative
– ACR is the recommended method for people with
diabetes
10. CKD progression
– Steps to identify progressive CKD
– obtain a minimum of three eGFR over not less
than 90 days
– in new cases of reduced eGFR, repeat within 2
weeks
to exclude acute deterioration of GFR
• CKD progression is either a decline in eGFR:
of > 5 ml/min/1.73 m2 within 1 year
or > 10 ml/min/1.73 m2 within 5 years
11. Referral criteria
– Refer the following people with CKD for discussion
or specialist assessment:
•stage 4 and 5 CKD (with or without diabetes)
•higher levels of proteinuria
•proteinuria together with haematuria
•rapidly declining eGFR
•poorly controlled hypertension
•people with rare or genetic causes of CKD
•suspected renal artery stenosis
12. Cardiovascular Mortality in the General
Population and in ESRD Treated by
Dialysis
0.01
100
10
1
0.1
Annual mortality (%)
25–34 45–54 65–74 ≥8535–44 55–64 75–84
Male
Female
Black
White
Dialysis
General population
Age (years)
13. Prevalence of Abnormalities at each level of
GFR
*>140/90 or antihypertensive medication p-trend < 0.001 for each abnormality
14. Clinical Practice Guidelines for the Detection,
Evaluation and Management of CKD
Stage Description GFR Evaluation Management
At increased
risk
Test for CKD Risk factor management
1
Kidney
damage with
normal or ↑
GFR
>90
Diagnosis
Comorbid
conditions
CVD and CVD
risk factors
Specific therapy, based on diagnosis
Management of comorbid conditions
Treatment of CVD and CVD risk factors
2
Kidney
damage with
mild ↓ GFR
60-89
Rate of
progression
Slowing rate of loss of kidney function 1
3
Moderate ↓
GFR
30-59 Complications Prevention and treatment of complications
4 Severe ↓ GFR 15-29
Preparation for kidney replacement therapy
Referral to Nephrologist
5 Kidney Failure <15 Kidney replacement therapy
1
Target blood pressure less than 130/80 mm Hg. Angiotension converting enzyme inhibitors
(ACEI) or angiotension receptor blocker (ARB) for diabetic or non-diabetic kidney disease with spot
urine total protein-to-creatinine ratio of greater than 200 mg/g.
15. Importance of Proteinuria in CKD
Interpretation Explanation
Marker of kidney
damage
Spot urine albumin-to-creatinine ratio >30 mg/g or
spot urine total protein-to-creatinine ratio >200 mg/g
for >3 months defines CKD
Clue to the type
(diagnosis) of CKD
Spot urine total protein-to-creatinine ratio >500-
1000 mg/g suggests diabetic kidney disease,
glomerular diseases, or transplant glomerulopathy.
Risk factor for adverse
outcomes
Higher proteinuria predicts faster progression of
kidney disease and increased risk of CVD.
Effect modifier for
interventions
Strict blood pressure control and ACE inhibitors are
more effective in slowing kidney disease
progression in patients with higher baseline
proteinuria.
Hypothesized
surrogate outcomes
and target for
interventions
If validated, then lowering proteinuria would be a
goal of therapy.
16. Albuminuria as a Risk Factor for CVD
in PREVEND
Hillege HL et al. Circulation 2002: 106: 1777-1782
17. Clinical Practice Guidelines for
Management of Hypertension in CKD
Type of Kidney Disease Blood Pressure
Target
(mm Hg)
Preferred Agents
for CKD, with or
without
Hypertension
Other Agents
to Reduce CVD Risk
and Reach Blood
Pressure Target
Diabetic Kidney Disease
<130/80
ACE inhibitor
or ARB
Diuretic preferred,
then BB or CCB
Nondiabetic Kidney
Disease with Urine Total
Protein-to-Creatinine
Ratio ≥200 mg/g
Nondiabetic Kidney
Disease with Spot Urine
Total Protein-to-Creatinine
ratio <200 mg/g None preferred
Diuretic preferred,
then ACE inhibitor,
ARB, BB or CCB
Kidney Disease in Kidney
Transplant Recipient
CCB, diuretic, BB,
ACE inhibitor, ARB
18. Other recommendations
– Offer a renal ultrasound to all people with CKD who:
•have progressive CKD
•have visible or persistent invisible haematuria
•have symptoms of urinary tract obstruction
•have a family history of polycystic kidney disease
and are aged over 20
•have stage 4 or 5 CKD
•are considered by a nephrologist to require a renal
biopsy
19. Other recommendations
(cont’d)
–Provide people with CKD:
•high quality education at appropriate stages of their condition
to enable informed treatment choices
•tailored information to their stage and cause of CKD
• Information and education programmes should be
provided by healthcare professionals with specialist
knowledge of CKD and the skills to facilitate learning
Editor's Notes
NOTES FOR PRESENTERS: Key points to raise: The NICE guideline covers best practice advice on identifying adults who either have or who are at risk of developing CKD, and interventions to slow or prevent the progression of the disease. CKD has an asymptomatic period, but it can still be detected during this time using a simple test. Because of a lack of specific symptoms, people with CKD are often not diagnosed, or diagnosed late when CKD is at an advanced stage. Previously up to 30 per cent of people with advanced kidney disease had been referred late to nephrology services from primary and secondary care, although data from the UK Renal Registry annual report (2007) now points to a sustained and significant reduction in late referrals to nephrology services. Additional information: People with CKD carry a higher risk of cardiovascular disease. Diabetes is a key risk factor for CKD; around 31% of people diagnosed with diabetes also have CKD. Hypertension is linked as a risk factor to CKD. Over 2% of the total NHS budget is spent on renal replacement therapy. Some conditions that coexist with CKD become more severe as kidney dysfunction advances. CKD can progress to established renal failure in a small but significant percentage of people. Advanced CKD carries a high mortality risk, and the risk of CKD developing increases with age. Late referral of those diagnosed with CKD increases risks of mortality and morbidity and precludes assessment and preparation of those for whom conservative management is more appropriate. Significant costs and poor clinical outcomes are associated with the late referral of people with end-stage renal failure who require renal replacement therapy. Identification of people at earlier stages of CKD, and appropriate management and earlier referral of those who would benefit from specialist renal services would increase both economic and clinical effectiveness.
NOTES FOR PRESENTERS: Key points to raise: The NICE guidance updates stage 3 of the classification of CKD adopted by the ‘National service framework for renal services’. This classification system originated from the American ‘National Kidney Foundation Kidney disease outcomes quality initiative’ (NKF-KDOQI). At the time of publication of the NICE guidance, the US CKD stage 3 classification standard had not been updated and was still undivided. Evidence of kidney damage can include either: the presence of persistent albuminuria, persistent proteinuria or persistent haematuria in urine; structural abnormalities of the kidneys demonstrated on ultrasound scanning or other radiological tests; or biopsy-proven chronic glomerulonephritis. Studies examined in the full guideline have underlined the importance of proteinuria/albuminuria as an independent risk factor for adverse outcomes in CKD, suggesting an adoption of a ‘p’ suffix in the different stages. At any stage of CKD, management should not be influenced solely by age. Additional information: When staging CKD define proteinuria as urinary ACR 30 mg/mmol, or PCR 50 mg/mmol. The classification of stages of CKD within the NICE guideline apply to those aged 16 years and over. More details on the division of stage 3 into 3A and 3B are on the next slide. The recommendation is provided in full on the following slide.
NOTES FOR PRESENTERS: Key points to raise: All people in the at-risk groups listed should be tested annually. The quality and outcomes framework includes a diabetes management indicator that is relevant to testing for CKD. DM 14 refers to patients with diabetes who have a recorded test of serum creatinine within the previous 15 months. Whenever a serum creatinine measurement is made, clinical laboratories should report an eGFR using a prediction equation such as the IDMS-traceable simplified MDRD equation. (IDMS = isotope dilution mass spectrometry; MDRD = modification of diet in renal disease) The following two slides provides more information on CKD testing. Monitor GFR in people prescribed drugs known to be nephrotoxic such as calcineurin inhibitors and lithium. Check GFR at least annually in people receiving long-term systemic non-steroidal anti-inflammatory drug (NSAID) treatment. Additional information: In the absence of the risk factors outlined on the slide above, do not use age, gender or ethnicity as risk markers to test people for CKD. In the absence of metabolic syndrome, diabetes or hypertension, do not use obesity alone as a risk marker to test people for CKD. People with CKD should be offered high-quality information or education programmes at appropriate stages of their condition to allow time for them to fully understand and make informed choices about their treatment. Cardiovascular disease includes ischaemic heart disease, chronic heart failure, peripheral vascular disease and cerebral vascular disease. Multisystem diseases with potential kidney involvement include, for example, systemic lupus erythematosus.
NOTES FOR PRESENTERS: Note – these are not key recommendations, but are an essential part of the care pathway Key points to raise: Use the prediction equation IDMS-traceable simplified MDRD to estimate GFR, using creatinine assays with calibration traceable to a standardised reference material. Ideally creatinine assays that are specific and zero biased compared with IDMS should be used (for example, enzymatic assays). When non-specific assays are used (for example, Jaffe assays), employ adjustment factors to minimise between-laboratory variation (for example, those provided by national external quality assessment schemes). Where indicated, apply a correction factor for ethnicity to reported GFR values. Avoid delaying the despatch of blood samples to ensure that they are received and processed by the laboratory within 12 hours of venepuncture. Advise people to avoid meat for 12 hours before a blood test for GFR estimation. Additional information: Where eGFR is simply reported as 60 ml/min/1.73 m 2 or more, use a rise of more than 20% in serum creatinine concentration to infer significant reduction in renal function. Gold standard methods of assessing GFR are unsuitable for widespread identification of CKD in the ‘at-risk’ population, but may be applied in particular situations where a highly accurate measure of GFR is required – for example, during monitoring of chemotherapy (testing would use a filtration marker that may include inulin, 51 Cr-EDTA, 125 I-iothalamate or iohexol). Interpret reported values of eGFR of 60 ml/min/1.73 m 2 or more with caution – GFR estimates become less accurate as the true GFR increases. Recommendations 1.1.1, 1.1.7 and 1.1.8 in full: Whenever a request for serum creatinine measurement is made, clinical laboratories should report an estimate of GFR (eGFR) using a prediction equation (see recommendation 1.1.2) in addition to reporting the serum creatinine result (1.1.1). In cases where there are extremes of muscle mass – for example, in bodybuilders, amputees or people with muscle wasting disorders – interpret the eGFR with caution. (Reduced muscle mass will lead to overestimation and increased muscle mass to underestimation of the GFR.) (1.1.7). Advise people not to eat any meat in the 12 hours before having a blood test for GFR estimation. Avoid delaying the despatch of blood samples to ensure that they are received and processed by the laboratory within 12 hours of venepuncture. (1.1.8).
NOTES FOR PRESENTERS: Key points to raise: There are no published comparisons between ACR and protein:creatinine ratio (PCR). Albumin is the principal component of proteinuria in glomerular disease. Do not use reagent strips to identify proteinuria unless they are capable of specifically measuring albumin at low concentrations and expressing the result as an ACR. Reagent strips in current clinical practice predominantly detect albumin, not total protein, but are not reliably quantitative. ACR has far greater sensitivity than PCR for the detection of low levels of proteinuria, enhances early identification of CKD , and importantly, cardiovascular risk in people with CKD begins to increase at low levels of albuminuria (below the sensitivity limits of PCR). T here may be clinical reasons for a specialist to subsequently use PCR to quantify and monitor significant levels of proteinuria. Additional information: If the ACR is 30 mg/mmol or more and less than 70 mg/mmol this should be confirmed by a subsequent early morning sample. If initial ACR is 70 mg/mmol or more a repeat sample need not be tested. Some nephrologists disagree about the relative merits of ACR and PCR testing.
NOTES FOR PRESENTERS: Key points to raise: Acute deterioration of GFR may include acute kidney injury or initiation of angiotensin-converting enzyme inhibitor (ACE inhibitor)/angiotensin-II receptor blocker (ARB) therapy. An eGFR result less than 60 ml/min/1.73 m 2 in a person not previously tested should be confirmed by repeating the test within 2 weeks. Focus on those where decline of GFR at observed rate would lead to renal replacement therapy within their lifetime by extrapolating the current rate of decline. Work with people who have the following risk factors for progression of CKD to optimise their health: cardiovascular disease; proteinuria; hypertension; diabetes; smoking; black or Asian ethnicity; chronic use of NSAIDS; urinary outflow tract obstruction. Additional information: People with CKD should be offered education and information tailored to the stage and cause of CKD, the associated complications and the risk of progression. The chronic use of NSAIDs may be associated with progression of CKD and acute use is associated with a reversible fall in GFR. Exercise caution when treating people with CKD with NSAIDs over prolonged periods of time. Monitor the effects on GFR, particularly in people with a low baseline GFR and/or in the presence of other risks for progression. For patients with access to the internet, the Renal Patient View system may provide a convenient means of accessing the results of their blood tests and information about their diagnosis and treatment. Recommendation 1.5.1 in full: Take the following steps to identify progressive CKD: Obtain a minimum of three GFR estimations over a period of not less than 90 days; in people with a new finding of reduced eGFR, repeat the eGFR within 2 weeks to exclude causes of acute deterioration of GFR – for example, acute kidney injury or initiation of ACE inhibitor/ARB therapy; define progression as a decline in eGFR of more than 5 ml/min/1.73 m 2 within 1 year, or more than 10 ml/min/1.73 m 2 within 5 years; focus particularly on those in whom a decline in GFR continuing at the observed rate would lead to the need for renal replacement therapy within their lifetime by extrapolating the current rate of decline.
NOTES FOR PRESENTERS: Key points to raise: Take into account the individual’s wishes and comorbidities when considering referral. Consider discussing management issues with a specialist by letter, email or telephone in cases where it may not be necessary for the person with CKD to be seen by the specialist; referral does not necessarily mean a patient attends an out-patient clinic. Once an individual’s case has been discussed or assessed with a specialist clinic and a management plan agreed, it may be possible for their care to be carried out by the referring clinician. Specialist care can be provided by geriatricians, diabetologists, cardiologists, nephrologists, specialist nurses and GPs. Additional information: Higher levels of proteinuria are defined as ACR 70 mg/mmol or more, equivalent to PCR 100 mg/mmol or more, or urinary protein excretion 1 g/24 h or more – unless level is known to be because of diabetes and already appropriately treated. Where proteinuria is present with haematuria, a referral to specialist assessment should be made where levels are at ACR 30 mg/mmol or more, approximately equivalent to PCR 50 mg/mmol or more, or urinary protein excretion 0.5 g/24 h or more. Persistent, invisible haematuria in the absence of proteinuria should be followed up annually with repeat testing for haematuria, proteinuria/albuminuria and blood pressure monitoring as long as the haematuria persists. When testing for presence of haematuria, use reagent strips rather than urine microscopy. Evaluate further if there is a result of 1+ or more. Do not use urine microscopy to confirm a positive result. People with CKD who have visible or persistent invisible haematuria should be offered a renal ultrasound. A rapidly declining estimate of GFR is more than 5 ml/min/1.73 m 2 in 1 year, or more than 10 ml/min/1.73 m 2 within 5 years. If hypertension remains poorly controlled despite using at least four antihypertensive drugs at therapeutic doses a referral for specialist assessment should take place (see ‘Hypertension: management of hypertension in adults in primary care’ [NICE clinical guideline 34]). Routine follow-up can take place at the patient’s GP surgery rather than in a specialist clinic. If this is the case, criteria for future referral or re-referral should be specified. People with CKD and renal outflow obstruction should normally be referred to urological services, unless urgent medical intervention is required – for example, for the treatment of hyperkalaemia, severe uraemia, acidosis or fluid overload.
NOTES FOR PRESENTERS: Note – these are not key recommendations, but are an essential part of the care pathway Advise people with a family history of inherited kidney disease about the implications of an abnormal result before arranging their scan. Recommendations 1.4.1 and 1.4.2 in full: Offer a renal ultrasound to all people with CKD who: have progressive CKD (eGFR decline more than 5 ml/min/1.73 m 2 within 1 year, or more than 10 ml/min/1.73 m 2 within 5 years); have visible or persistent invisible haematuria; have symptoms of urinary tract obstruction; have a family history of polycystic kidney disease and are aged over 20; have stage 4 or 5 CKD ; are considered by a nephrologist to require a renal biopsy. Advise people with a family history of inherited kidney disease about the implications of an abnormal result before a renal ultrasound scan is arranged for them.
NOTES FOR PRESENTERS: Note – these are not key recommendations, but are an essential part of the care pathway Key points to raise: When developing information or education programmes, involve people with CKD in their development from the outset. The following topics are suggested: What is CKD and how does it affect people? What questions should people ask about their kidneys when they attend clinic? What treatments are available for CKD, what are their advantages and disadvantages and what complications or side effects may occur as a result of treatment/medication? What can people do to manage and influence their own condition? In what ways could CKD and its treatment affect people’s daily life, social activities, work opportunities and financial situation, including benefits and allowances available? How can people cope with and adjust to CKD and what sources of psychological support are available? When appropriate, offer information about renal replacement therapy (such as the frequency and length of time of dialysis treatment sessions or exchanges and pre-emptive transplantation) and the preparation required (such as having a fistula or peritoneal catheter). Conservative management may be considered where appropriate. Additional information: Further patient information and resources can be found at www.nhs.uk Recommendation 1.3.4 and 1.3.5 in full: Offer people with CKD high quality information or education programmes at appropriate stages of their condition to allow time for them to fully understand and make informed choices about their treatment. Healthcare professionals providing information and education programmes should ensure they have specialist knowledge about CKD and the necessary skills to facilitate learning.
