Quality in Practice Committee

Chronic Kidney Disease:

diagnosis and management
in primary care
AUTHOR
Dr Liam Glynn, GP

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DISCLAIMER AND WAIVER OF LIABILITY LEVELS OF EVIDENCE
Whilst every effort has been made by the Quality in Practice Level 1: Evidence obtained from systematic review of
Committee to ensure the accuracy of the information and randomised trials
material contained in this document, errors or omissions
Level 2: Evidence obtained from at least one randomised trial
may occur in the content. This guidance represents the view
of the ICGP which was arrived at after careful consideration Level 3: Evidence obtained from at least one non-randomised
of the evidence available at time of publication. controlled cohort/follow-up study
Level 4: Evidence obtained from at least one case-series, case-
This quality of care may be dependent on the appropriate control or historically controlled study
allocation of resources to practices involved in its delivery.
Resource allocation by the state is variable depending on Level 5: Evidence obtained from mechanism-based reasoning
geographical location and individual practice circumstances.
There are constraints in following the guidelines where the NOTE REGARDING LEVELS OF EVIDENCE IN THIS PAPER:
resources are not available to action certain aspects of the
Many of the recommendations in this document relate to
guidelines. Therefore individual healthcare professionals will
aspects of the organisation, or system, of care, rather than
have to decide whether the standard is achievable within
to therapeutic decisions. There are major methodological
their resources particularly for vulnerable patient groups.
problems associated with grading levels of evidence for this
type of recommendation, and for this reason many of our
The guide does not however override the individual
recommendations are level 4. All recommendations made
responsibility of healthcare professionals to make decisions
in this document are graded as level 4 evidence unless
appropriate to the circumstances of individual patients in
otherwise stated.
consultation with the patient and/or guardian or carer.

Guidelines are not policy documents. Feedback from local GRADES OF RECOMMENDATIONS
faculty and individual members on ease of implementation A: Requires at least one randomised controlled trial as part of
of these guidelines is welcomed. a body of literature of overall good quality and consistency
addressing the specific recommendation. (Evidence levels 1, 2)

EVIDENCE-BASED MEDICINE B: Requires the availability of well-conducted clinical

Evidence-based medicine is the conscientious, explicit and studies but no randomised clinical trials on the topic of
judicious use of current best evidence in making decisions recommendation. (Evidence levels 3, 4).
about the care of individual patients. C: Requires evidence obtained from expert committee
reports or opinions and/or clinical experience of respected
In this document evidence and recommendations are graded authorities. Indicates an absence of directly applicable
according to levels of evidence (Level 1 – 5) and grades of clinical studies of good quality. (Evidence level 5).
recommendations (Grades A-C) respectively. This grading
system is an adaptation of the revised Oxford Centre 2011
Levels of Evidence. ICGP QUALITY IN PRACTICE COMMITTEE 2016
Dr Paul Armstrong, Dr Patricia Carmody, Dr Regina Codd,
Dr Harry Comber, Dr Mary Kearney, Dr Niamh Moran,
Dr Maria O’Mahony, Dr Ben Parmeter, Dr Philip Sheeran
Purcell, Dr Patrick Redmond.

ACKNOWLEDGMENTS
QIP Committee would like to thank Dr Eoin Bergin,
Consultant Nephrologist, Midlands Regional Hospital
Tullamore, who carried out an external review of this
document.

Correspondence to: QRGfeedback@icgp.ie

Original Publication: 2016

Next Review Date: 2019

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QUALITY IN PRACTICE COMMITTEE – Chronic Kidney Disease: Diagnosis and Management in Primary Care

TABLE OF CONTENTS

1.0 Introduction 1
Background 1
1.2 Aims of the document 2
1.3 Clinical presentation and complications 2

2.0 Symptoms and complications of CKD 3

2.1 Diagnosis and Classification of CKD 3
2.2 Screening 5
2.3 Management and Referral Guidelines 6
2.4 Referral Information 8

3.0 References 10

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1.0 Introduction

Background
Chronic kidney disease (CKD) is becoming an increasingly common diagnosis. In
the US alone, there are over 400,000 patients with end-stage renal disease (ESRD)
with nearly ten times this number having mild CKD defined as a glomerular
filtration rate (GFR) <60 ml/min/1.73m.1 The current number of patients with
early CKD — the pool from which future ESRD patients will emerge — exceeds
the present number with ESRD by a factor of 30 to 60.2 Risk factors for the
development of CKD include age, smoking, hypertension and diabetes. The
relationship between CKD and cardiovascular disease is a very important one.
Cardiovascular disease is frequently associated with CKD, individuals with CKD are
much more likely to die of cardiovascular disease than to develop kidney failure,
cardiovascular disease in CKD is treatable and potentially preventable, and CKD
appears to be a significant risk factor for cardiovascular disease.3

It is now recognised that even mild degrees of renal insufficiency are strongly
associated with adverse cardiovascular outcomes and that CKD goes
unrecognised in many individuals due to the asymptomatic nature of the
condition. Indeed where CKD is recognised in this population, patients are often
nihilistically treated.4, 5 Despite the recognised association between reduced
estimated GFR and poorer prognosis, risk factor management is often not
optimised for such patients in the community setting5 while screening for
CKD is frequently limited to a measurement of serum creatinine which does not
accurately reflect GFR,6, 7 the best indicator of renal function in health and
disease.8 Physicians worldwide recognise the importance of cardiovascular risk
factors and strive to identify and improve them in their patients. Despite the high
prevalence of CKD in this population,9 it remains outside the group of well-
recognised cardiovascular risk factors in many healthcare settings. This is despite
the growing body of evidence demonstrating increased cardiovascular
risk associated with CKD in the general population10 , 11 as well as in patients
post-myocardial infarction,9, 12, 1 3, 14 post cardiac intervention15 and those with
diabetes.16 However, the health systems of only a minority of countries17, 18 have
emphasised the importance of CKD screening using estimated GFR (eGFR as
defined below) within primary care.

Remarkably, with CKD representing the group at highest risk from cardiovascular
complications, even above diabetes, there has been a systematic exclusion
of patients with CKD from therapeutic trials.19 Most primary and secondary
prevention of cardiovascular disease happens in the community and therefore it
is important that primary care physicians become proactive in diagnosing and
managing CKD in its most relevant setting.

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1.2 Aims of the document

The aim of this document is to provide Irish General Practitioners with an up to
date, easy to follow, evidence-based guideline on the diagnosis, management and
referral of patients with Chronic kidney disease (CKD).

1.3 Clinical presentation and complications

CKD is common and is unrecognised in most patients due to the asymptomatic
nature of the condition. Reduced kidney function is often first picked up as an
incidental finding on routine screening bloods (raised creatinine, reduced eGFR,
anaemia) or urinalysis (proteinuria or haematuria in the absence of infection)
or as a secondary cause for newly diagnosed hypertension and should always
be considered in cases of resistant hypertension.20 Symptoms and complications
of CKD that can occur are outlined in table 1 but these are generally only seen
in advanced disease. CKD is strongly associated with adverse cardiovascular
outcomes. Reduced eGFR is a potent marker for cardiovascular morbidity and
mortality and should be regarded as a risk factor for cardiovascular disease
just like hypertension, cholesterol level, diabetic status etc. The vast majority of
patients with mild to moderate CKD will not require dialysis and can be managed
in primary care. Appropriate management of patients with CKD in primary care
has the potential to reduce overall cardiovascular risk and delay progression to
renal failure.

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2.0 Symptoms and complications of CKD

Table 1. Symptoms and complications of CKD

SYMPTOMS OF CKD COMPLICATIONS OF CKD

Anorexia, fatigue, nausea, weight loss Hypertension, ↑Cardiovascular risk

Headaches GIT Blood loss, Anaemia
Itching (Pruritus), Easy Bruising Dementia, Neuropathy
Bone pain Fluid Retention, Oedema
Numbness, Muscle twitching Electrolyte disturbance (↑K+,↑PO4+ )
Foetor, Polydipsia, Vomiting Increased risk of infections
Hyperparathyroidism and Renal
Drowsiness, Shortness of breath
Osteodystrophy

2.1 Diagnosis and Classification of CKD

The diagnosis of CKD is made on the basis of two simple measures which are
available in primary care: Urinalysis (Urine Dipstick and Protein/Albumin to
Creatinine Ratio) and calculation of the Estimated Glomerular Filtration Rate
(eGFR). There is no need to collect 24 h urine samples to measure creatinine
clearance or proteinuria in primary care.21 [Level 3 Grade C]

Urinalysis18 [Level 3 Grade C]

1. Urine dipstick is first performed and is a useful screening tool though
it only provides a semi quantitative assessment of level of proteinuria
as the reported value can vary according to the hydration status of the
patient. Haematuria by dipstick is always significant and usually does not
need verification by other tests. Proteinuria does need to be standardised
and quantified so as to further stratify patients, (i.e. nephrotic versus
subnephrotic range proteinuria) and this is done using a simple spot urine to
measure Protein/Albumin to Creatinine Ratio (PCR or ACR).
2. Spot urine sample is sent to the laboratory to measure Protein/Albumin to
Creatinine Ratio (PCR or ACR depending on local practice). This will detect
even small levels of proteinuria and thus is essential for diagnosis but is
not useful for routine follow up of patients who already have established
macroalbuminuria. Table 2 below outlines the comparisons between
the various assessments of proteinuria. At the same time, a midstream
urine specimen (MSU) should be sent for culture to exclude urinary tract
infection (UTI).

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Table 2. Comparisons between the various assessments of proteinuria

ALBUMIN/ PROTEIN/
24 HOUR URINE DIPSTICK CREATININE CREATININE
PROTEINURIA (Detects all
(Detects albumin) Ratio [ACR] Ratio [PCR]
protein)
(mg/mmol) (mg/mmol)

Micro- 2.5–30 male

30–300 mg Not detected Not applicable
albuminuria 3.5–30 female
Detects
Macro-
>300 mg >150–200 mg/L <30 <40
albuminuria
as +
<3.5g/24 hours
Sub–nephrotic + to +++ Not applicable <400
Total Protein
>3.5g/24 hours
Nephrotic Usually +++ Not applicable <400
Total Protein

Note: Microalbuminuria is increasingly now referred to as ‘moderately increased

albuminuria’.
Macroalbuminuria is now largely referred to as ‘moderately increased albuminuria’,
the level of urinary protein excretion at which the urine dipstick becomes positive.

Estimated Glomerular Filtration Rate (eGFR)

The eGFR is a useful and accurate measure of renal function and is calculated
using serum creatinine as well as the variables of age, gender and race.

The most commonly used estimation equation is the abbreviated Modified Diet
in Renal Disease (MDRD) equation,21 [Level 3 Grade C]

Estimated GFR (ml/min) = 186 x (serum creatinine level [in milligrams per
deciliter])–1.154 x (age [in years])–0.203.

For women and those of Afro-Caribbean decent (ethnicity data was collected
during follow-up), the product of this equation is multiplied by correction factors
of 0.742 and 1.21, respectively. 21 This estimation equation is available within
practice software package, is now done routinely in some hospital laboratories
across the country and is available online here.

The Cockcroft Gault Formula predated the above formula, it can also be used and
it includes measurement of body weight.

Table 3 describes the classification of CKD as outlined by the National Kidney

Foundation Kidney Disease Outcomes Quality Initiative.22 The classification of
CKD is based on the use of an “estimated Glomerular Filtration Rate” (eGFR)
which is usually represented in the units of mL/minute/1.73m2. As a result, an
increasing number of clinical biochemistry laboratories nationally are
automatically calculating eGFR as part of each urea and electrolytes (U+E) request.

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Table 3. Stages of CKD as outlined by the National Kidney Foundation Kidney

Disease Outcomes Quality Initiative18

STAGE CLINICAL FEATURES GFR (ML/MIN/1.73M2)

I *Kidney damage with normal or increased GFR ≥90

II *Kidney damage with a mild decrease in GFR 60–89
III Moderate decrease in GFR 30–59
IV Severe decrease in GFR 15–29
V Kidney failure <15 or dialysis

*Other evidence of kidney damage may include any of the following:

• Persistent microalbuminuria/proteinuria/haematuria
• Structural abnormalities of the kidneys demonstrated on ultrasound
scanning or other radiological tests e.g. polycystic kidney disease, reflux
nephropathy
• Biopsy proven chronic glomerulonephritis

In the following circumstances eGFR may not be accurate:

• Acute renal failure
• Patients less than 18 years of age
• Patients with advanced muscle wasting and amputations
• Pregnancy

2.2 Screening18
Serum creatinine concentration should be measured, allowing calculation of
eGFR, at initial assessment and then at least annually in all adult patients with
[Level 3 Grade C]:

Previously diagnosed CKD, including

• polycystic kidney disease
• reflux nephropathy
• biopsy-proven chronic glomerulonephritis
• persistent proteinuria
• urologically unexplained persistent haematuria

Conditions associated with a high risk of obstructive nephropathy, including

• known or suspected bladder outflow obstruction
• neurogenic bladder caused by spina bifida or spinal cord injury
• urinary diversion surgery
• urinary stone disease

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Conditions known to be associated with a high risk of silent development of CKD:

• hypertension
• diabetes mellitus
• heart failure
• atherosclerotic coronary, cerebral, or peripheral vascular disease

Conditions requiring long-term treatment with potentially nephrotoxic drugs

including:
• NSAIDs
• Lithium carbonate
• Mesalazine and other 5-aminosalicylic acid drugs
• Calcineurin inhibitors (Cyclosporin, Tacrolimus)

Multisystem diseases that may involve the kidney, including systemic lupus
erythematosus (SLE), vasculitis, myeloma, rheumatoid arthritis

2.3 Management and Referral Guidelines

The chief goals of management of CKD are to reduce overall cardiovascular
risk, to delay progression to renal failure and to avoid complications. Guidelines
for CKD evaluation, treatment goals and referral guidelines are summarised in
Table 4. Regular reviews are recommended and should consist of blood pressure
measurement, assessment of kidney function, review of all medications, and
immunisation with Influenza vaccine and Pneumococcal vaccine in addition
to lifestyle advice regarding smoking, salt intake and weight loss. Review all
medications when renal insufficiency is first identified and avoid potentially
nephrotoxic medications (see above). Risk factors for the development of
CKD such as hypertension and diabetes mellitus should be specifically and
meticulously targeted. Cardiovascular complications can be reduced by attention
to smoking cessation, weight loss, regular aerobic exercise, thrombotic risk
(consider aspirin) and treatment of hypercholesterolemia.

The following management principles apply (see table for evidence and grades):
• Meticulous control of hypertension and diabetes if present (see section below)
• Advice on smoking cessation.
• Advice on weight loss if obese
• Reduction of dietary sodium intake to <100 mmol/day
• Encouragement to take regular aerobic exercise.
• Advice to limit alcohol intake as per low risk weekly guidelines for adults
which are:
-- up to 11 standard drinks in a week for women, and
-- up to 17 standard drinks in a week for men.
• Consideration of aspirin treatment for all patients with an estimated 10 year risk
of cardiovascular disease of >20%, so long as blood pressure is <150/90mm Hg.

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• Anaemia is common in more advanced disease and a target of 10–11.5gm/dL

should be sought.
• Consideration of lipid-lowering drug therapy for all patients (see section below)

Management of CKD patients with diabetes mellitus and microalbuminuria or

proteinuria
• Continued efforts to achieve good glycaemic control (HbA1c 6.5–7.5%,
48–58mmols/mol).
• Prescription of an ACEI (or ARB in the presence of a firm contraindication to
ACEI), titrated to full dose, followed by addition of other antihypertensive
drugs in combination to reach the blood pressure goal of 130/80.23
• Measurement of eGFR and PCR at least once a year.
• Referral to a nephrologist if there is increasing proteinuria.
• Consideration of dietary protein restriction for patients with type 1 diabetes

Lipid-lowering drug therapy in patients with kidney disease

• Patients with established macrovascular disease should receive treatment for
hyperlipidaemia according to the current ESC Guidelines. 24
• Patients with diabetes and CKD but no established macrovascular disease
should be offered lipid-lowering drug treatment according to the current ESC
Guidelines.24
• Patients with CKD who do not have diabetes and who do not have established
macrovascular disease should be offered the option of lipid-lowering
treatment according to the current ESC Guidelines if estimated 10 year risk of
cardiovascular disease is >20%.24

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Table 4. Summary of guidelines for CKD evaluation, treatment goals and referral
guidelines

CKD Frequency of
eGFR Evaluation Treatment Referral
Stage evaluation
I >90ml/min/1.73m2 12 months Exam + BP 1. BP <140/90 for patients without Referral not
U+E proteinuria, and 130/80 for those warranted unless
(with proteinuria or
eGFR with PCR >100 mg/mmol25 other problems
haematuria)
Level 2 Grade A present
ACR/PCR
II 60–89ml/ 12 months
Urinanlysis 2. ACEi/ARB if no C.I. Level 1 Grade B
min/1.73m2
3. Statin if CVD risk >20% over 10
(with proteinuria or
years25 Level 2 Grade A
haematuria)
4. Aspirin if 10 year CVD risk
III 30–59ml/ 6–12 months As above + >20% and BP <150/90mm Hg25 Referral if:29
min/1.73m2 Level 2 Grade A Level 2 Grade C
FBC, PTH, Ca,
P, Albumin 5. Diabetes: HbA1c 6.5–7.5% ↓eGFR 15%/yr
Level 1 Grade B ↑Creat. 15%/yr
Use of ACE/ARB Level 1 Grade B BP >150/90 on 3 meds
6. Anaemia: Exclude other causes of Micro. Haematuria
anaemia
PCR≥100
7. maintain at 10–11.5gm/dl26
Level 1 Grade B Unexplained anaemia
IV 15–29ml/min/1.73m2 3–6 months As for III 8. Smoking cessation27 Discussion with or
Level 2 Grade A urgent referral to
V <15ml/min/1.73m2 1–3 months As for III
nephrologist
9. Weight Loss if obese28
Level 1 Grade B

2.4 Referral Information

The following information should be included in any referral to secondary care:
1. General medical history
2. Urinary symptoms
3. Medication history
4. Examination, e.g. blood pressure, oedema, palpable bladder or other positive
findings
5. Urinalysis for blood and protein
6. In all patients who have persistent dipstick positive proteinuria, check
spot urine protein/creatinine (PCR) ratio. In diabetic patients with negative
dipstick, check spot urine albumin/creatinine (ACR) ratio
7. Relevant blood results:
-- U+E: urea, creatinine, sodium, potassium, chloride and bicarbonate
-- eGFR
-- Liver Profile: Albumin
-- Bone profile: Calcium, Phosphate
-- Fasting Cholesterol and Glucose
-- HbA1C (in diabetes)
-- Full blood count

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8. All previous serum creatinine results with dates

9. Result of renal ultrasound scan or referral for ultrasound made
Please note: Renal Ultrasound provides information on renal size and
echogenicity and also allows detection of hydronephrosis, a feature of
obstructive nephropathy. Renal ultrasound is an integral part of the
assessment of patients with acute renal failure, and of those with progressive
CKD and those in whom kidney biopsy may be indicated. Renal ultrasound
even if normal is fundamental to the further assessment of patients with
chronic kidney disease in secondary care.

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3.0 References
1. U.S. Renal Data System. USRDS Annual Data Report. Bethesda, MD: National
Institutes of Health, National Institute of Diabetes and Digestive and Kidney
Diseases, 2003 April, 2003. Report No. [Most recent version 2015, available here]
2. Hostetter TH. Chronic Kidney Disease Predicts Cardiovascular Disease. N Engl
J Med. 2004;351(13):1344-a-6.
3. Sarnak MJ, Levey AS, Schoolwerth AC, Coresh J, Culleton B, Hamm LL, et al.
Kidney Disease as a Risk Factor for Development of Cardiovascular Disease:
A Statement From the American Heart Association Councils on Kidney in
Cardiovascular Disease, High Blood Pressure Research, Clinical Cardiology,
and Epidemiology and Prevention. Hypertension. 2003;42(5):1050–65.
4. Ezekowitz J, McAlister FA, Humphries KH, Norris CM, Tonelli M, Ghali WA, et al.
The association among renal insufficiency, pharmacotherapy, and outcomes
in 6,427 patients with heart failure and coronary artery disease. Journal of
the American College of Cardiology. 2004;44(8):1587–92.
5. McCullough PA, Sandberg KR, Borzak S, Hudson MP, Garg M, Manley HJ.
Benefits of aspirin and beta-blockade after myocardial infarction in patients
with chronic kidney disease. Am Heart J. 2002;144(2):226–32.
6. Levey AS. Measurement of renal function in chronic renal disease. Kidney Int.
1990;38(1):167–84.
7. Swedko PJ, Clark HD, Paramsothy K, Akbari A. Serum Creatinine Is an
Inadequate Screening Test for Renal Failure in Elderly Patients. Arch Intern
Med. 2003;163(3):356–60.
8. Smith H. Diseases of the kidney and urinary tract. The Kidney: Structure and
Function in health and disease. New York: Oxford University Press; 1951. p.
836–87.
9. Anavekar NS, McMurray JJV, Velazquez EJ, Solomon SD, Kober L, Rouleau J-L, et
al. Relation between Renal Dysfunction and Cardiovascular Outcomes after
Myocardial Infarction. N Engl J Med. 2004;351(13):1285–95.
10. Muntner P, He J, Hamm L, Loria C, Whelton PK. Renal Insufficiency and
Subsequent Death Resulting from Cardiovascular Disease in the United
States. J Am Soc Nephrol. 2002;13(3):745–53.
11. Go AS, Chertow GM, Fan D, McCulloch CE, Hsu C-y. Chronic Kidney Disease
and the Risks of Death, Cardiovascular Events, and Hospitalization. N Engl J
Med. 2004;351(13):1296–305.
12. Tonelli M, Jose P, Curhan G, Sacks F, Braunwald E, Pfeffer M, et al. Proteinuria,
impaired kidney function, and adverse outcomes in people with coronary
disease: analysis of a previously conducted randomised trial. BMJ.
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13. Wright RS, Reeder GS, Herzog CA, Albright RC, Williams BA, Dvorak DL,
et al. Acute Myocardial Infarction and Renal Dysfunction: A High-Risk
Combination. Ann Intern Med. 2002;137(7):563–70.

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14. Al Suwaidi J, Reddan DN, Williams K, Pieper KS, Harrington RA, Califf RM, et al.
Prognostic implications of abnormalities in renal function in patients with
acute coronary syndromes. Circulation. 2002;106(8):974–80.
15. Hemmelgarn BR, A. Southern D, Humphries KH, Culleton BF, Knudtson ML,
Ghali WA, et al. Refined characterization of the association between kidney
function and mortality in patients undergoing cardiac catheterization. Eur
Heart J. 2006:ehi846.
16. Henry RMA, Kamp O, Kostense PJ, Spijkerman AMW, Dekker JM, Nijpels G, et
al. Mild renal insufficiency is associated with increased left ventricular mass
in men, but not in women: An arterial stiffness-related phenomenon: The
Hoorn Study. Kidney Int. 2005;68(2):673–9.
17. BMA. Quality and outcomes framework guidance: Summary of Indicators –
clinical domain. London: BMA; 2006; Most recent edition (2015/16) of this is
available here.
18. Levey AS, Coresh J, Balk E, Kausz AT, Levin A, Steffes MW, et al. National Kidney
Foundation Practice Guidelines for Chronic Kidney Disease: Evaluation,
Classification, and Stratification. Ann Intern Med. 2003;139(2):137–47.
19. Reddan DN. Therapy for cardiovascular disease in patients with chronic
kidney disease: appropriate caution or the absence of data. Am Heart J.
2002;144(2):206–7.
20. de Castro MS, Fuchs FD, Costa Santos M, Maximiliano P, Gus M, Beltrami
Moreira L, et al. Pharmaceutical Care Program for Patients With Uncontrolled
Hypertension: Report of a Double-Blind Clinical Trial With Ambulatory Blood
Pressure Monitoring. American Journal of Hypertension. 2006;19(5):528–33.
21. Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate
method to estimate glomerular filtration rate from serum creatinine: a new
prediction equation. Modification of Diet in Renal Disease Study Group. Ann
Intern Med. 1999;130(6):461–70.
22. 22. National Kidney Foundation. K/DOQI clinical practice guidelines for
chronic kidney disease: evaluation, classification, and stratification. Am J
Kidney Dis. 2002;39(2 Suppl 1):S1-266.
23. 23. A practical guide to integrated Type 2 Diabetes care. Author: Harkins,
Velma Dr.;ICGP; National Clinical Programme Diabetes Working Group;
Department of Health and Children; HSE 2016. Available here.
24. Available here.
25. Williams B, Poulter N, Brown M, Davis M, McInnes G, Potter J, et al. Guidelines
for management of hypertension: report of the fourth working party of the
British Hypertension Society, 2004-BHS IV. J Hum Hypertens. 2004;18:139–85.
26. Singh A, Szczech L, Tang K, Barnhart H, Sapp S, Wolfson M, et al. Correction
of anemia with epoetin alfa in chronic kidney disease. N Engl J Med.
2006;355:2085–98.
27. Schiffl H, Lang SM, Fischer R. Stopping smoking slows accelerated progression
of renal failure in primary renal disease. J Nephrol. 2002;15:270–4.

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28. Morales E, Valero, M.A., Leon, M., Hernandez, E., Praga, M. . Beneficial effects of
weight loss in overweight patients with chronic proteinuric nephropathies.
Am J Kidney Dis 2003;41(2):319–27.
29. Ismail N, Neyra, R., Hakim, R. The medical and economical advantages of early
referral of chronic renal failure patients to renal specialists. Nephrol Dial
Transplant Immunology. 1998;13(2):246–50.

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