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Last updated: Lesson of the Month - October 2017…
on 17 Oct 2017

CKD GP Guidelines

Penny Ackland


Summary 

  1. It is important to be able to identify those with early chronic kidney disease (CKD), first because CKD has a very strong association with the risk of death, cardiovascular disease and hospitalisation; and, second, in order to attempt to prevent/delay the progression to end-stage renal disease (ESRD)
  2. In relation to the management of CKD, important factors to consider are the rate of change of kidney function and whether there is proteinuria or haematuria. The presence of other comorbidities, current or recent drug history, family history and the age of the patient, are additional factors that need to be taken into account
  3. If the estimated glomerular filtration rate (eGFR) is <60 mL/min/1.73m2 in the first test, retest within two weeks to exclude causes of acute deterioration of glomerular filtration rate (GFR)
  4. Significant progression of CKD is defined as a decline in eGFR of >5 mL/min/1.73m2 within 1 year, or >10 mL/min/1.73m2 within five years. AKI needs urgent referral, so please ring today. Stage 5 CKD should be discussed (at least) ASAP, even if the care is going to be GP-led
  5. All CKD patients should be checked for proteinuria
  6. In patients without diabetes, proteinuria is considered clinically significant when the albumin:creatinine ratio (ACR) is >30 mg/mmol
  7. In patients with diabetes, microalbuminuria with an ACR > 2.5 mg/mmol in men and > 3.5 mg/mmol in women, is clinically significant
  8. A nephrological referral should be considered (a) if there is significant proteinuria (ACR >70, or protein:creatinine ratio (PCR) > 100), with or without haematuria; or (b) if ACR > 30 or PCR >50 with haematuria
  9. If a young adult has haematuria (cola-coloured!) and an intercurrent illness (usually an upper respiratory tract infection), they should be suspected of having acute glomerulonephritis
  10. In general, patients with CKD stages 4 and above (and some 3b), with or without diabetes, should be considered for nephrological referral. However, other factors - including proteinuria, haematuria, poorly controlled hypertension, rate of change of eGFR (ie rate of progression) - should be taken into consideration

Introduction

Until recently, the care of kidney patients has been largely under the domain of nephrologists in secondary care

However, the increasing number of people diagnosed with chronic kidney disease (CKD; previously termed chronic renal failure) along with the more active treatment of end-stage renal disease (many more people have access to dialysis now than even a decade or so ago) means that:

  (i) more of the care has been streamlined into nurse-led clinics
  (ii) the earlier stages of renal disease are now being managed in the community by GPs

This latter strategy means that an ever-wider group of healthcare professionals is obliged to have an understanding and basic knowledge of issues in relation to patients with CKD. The aim of this section is to discuss the prevalence, detection, evaluation and management of this condition

Prevalence and Staging of Chronic Kidney Disease

Several epidemiologic studies have indicated that there is a high  prevalence of CKD in the general population. The survey conducted  by the Centers for Disease Control and Prevention in the United States from 1999 to 2004 suggested that up to 16.8% of the adult population have CKD (Centers for Disease Control and Prevention, 2007).

Another US study, the National Health and Nutrition Survey (NHANES III), based on data from 15, 635 adults and including measurements of creatinine, urine albumin:creatinine ratio (ACR) and estimate glomerular filtration rate eGFR), estimated that the prevalence of CKD was 11% (equating in 2003 to 19.2 million adults in the United States) (Coresh, 2003). Data from the United Kingdom suggests a similarly high prevalence of CKD in the general adult population (Anandarajah, 2005)

Despite the high prevalence, only a minority of those with CKD will progress to end-stage renal disease (ESRD) (Hallen, 2006); and the majority of CKD patients will be identified and managed within the primary care setting. It is important to be able to identify those with early CKD; first because CKD has a very strong association with the risk of death, cardiovascular disease and hospitalisation (Go, 2005); and, second, to prevent/delay the progression to ESRD. End-stage renal disease is associated with considerable morbidity and a high mortality (UK Renal Registry 2009), as well as affecting quality of life

Furthermore, the costs of ESRD are considerable. In the United Kingdom, the absolute cost per patient is around £30,000 - £35,000 per year for haemodialysis patients, and around £20,000 - £25,000 per year for peritoneal dialysis patients

In order to help in the early identification of patients, and enable stratification of risk and management, CKD has been categorised into stages dependent on the eGFR, whether other evidence of kidney damage is present and whether or not there is proteinuria. In September 2008, the NICE guideline on CKD (NICE 2008) updated the staging of CKD. The previous stage 3 (30–59 ml/min) was subdivided into stage 3A with an eGFR of between 45 and 59 ml/min/1.73m2, and stage 3B with an eGFR of between 30 and 44 mL/min/1.73m2

In addition, it recommended that the suffix ‘p’ be placed after the stage to denote the presence of proteinuria, where proteinuria is defined as urinary ACR >30 mg/mmol or PCR >50 mg/mmol. The rationale for these changes was an increasing realisation that most of the complications associated with CKD showed a rapid increase in prevalence in patients with an eGFR of <45 ml/min, and that the prognosis for patients with proteinuria was very much worse compared to those without proteinuria 

Detection

CKD is often asymptomatic in its early stages. Kidney disease may be detected (either as part of routine blood tests, or as part of an investigative procedure) by:

 • Blood tests for creatinine/eGFR - routine or investigative
 • Urine tests for albuminuria/proteinuria/haematuria - may be routine (change of GP, insurance medical etc) but also investigative. All hypertensive patients should have urinary ACR checks and urinalysis for haematuria (NICE 2011); while all patients with diabetes should have first-pass urine tests for ACR (NICE 2009)
 • Family history - for those who have relatives with polycystic kidney disease or other rarer causes of hereditary renal disease (such as Alport Syndrome)
 • Renal imaging - in general, renal disease could be picked up by screening for other problems, eg coincidentally during ultrasonography for suspected gallstones. Ultrasound may also detect reflux nephropathy in babies in utero, or in the neonate

In view of the high prevalence of CKD, it is becoming increasingly necessary to find a means to develop a ‘renal risk score’ in order to help identify those at risk of progressive CKD, as well as those who would benefit from referral to a nephrologist. Unfortunately, although such scores have indeed been devised (Halbesma, 2011), none is robust enough to be adopted into routine clinical  management (Taal, 2011). This is partly because there are a large number of CKD risk factors/markers, which will affect the sensitivity of a simple, universally applicable scoring system

Over 75% of CKD patients will have either diabetes, hypertension or are aged over 65 years. Data from NHANES III showed about 25% of CKD cases had diabetes, 75% had hypertension, while 11% of all patients over 65 years who did not have diabetes or hypertension had CKD. It follows that an increasing prevalence of these factors parallels a proportionate rise in CKD prevalence

According to NICE clinical guideline 73 (NICE 2008), patients should be offered testing if they have any of the following risk factors

• BP
• Diabetes
• PVD, CVD, IHD, AAA, or other forms of atheroma
• FH of CKD5/ESRD, or familial renal disease
• Structural renal disease
• Multisystems disease, eg SLE
• Opportunistic detection of haematuria or proteinuria

Evaluation

For the majority of patients with CKD there is no, or very slow,  progression of renal impairment - and only a small percentage reach end-stage renal disease. In relation to the management of CKD, it is first necessary to take a good history, which will include concurrent or recent drug history as well as family history (eg for polycystic kidney disease and Alport Syndrome). Important factors to evaluate also include the rate of change of kidney function and whether there is proteinuria or haematuria. The presence of other comorbidities (such as diabetes, hypertension, SLE) and the age of the patient are additional factors that need to be considered

Even though a decline in GFR with age is normal, there is currently no consensus around which level of GFR is considered ‘normal’ at a certain age. The eGFR takes age into consideration, but does not fully correct for the natural ageing process

Creatinine/Estimated Glomerular Filtration Rate (eGFR)

• When checking eGFR, it is important to consider other factors that influence its value - including ethnicity, weight, age, muscle mass, gender, diet (protein meal) and exercise. NICE clinical guideline 73 (NICE 2008) advises the use of the simplified MDRD equation to estimate eGFR. But

Key Point: since eGFR may be less reliable in certain situations (such as AKI, pregnancy, oedematous states, muscle wasting disorders, amputees and malnutrition), the serum creatinine should still be looked at, as well as the eGFR

• With Afro-Caribbean or African ethnicity, the eGFR should be corrected by multiplying by 1.21. Validation of the eGFR has not been well established for those of Asian or Chinese ethnicity

• Caution in eGFR interpretation should be used for people with extremes of muscle mass, or if the patient performed heavy exercise before their blood test. Protein meals may also affect the eGFR, and meat should be avoided for at least 12 hours before an eGFR blood test

• If eGFR is <60 ml/min/1.73m2 in the first test, retest within two weeks to exclude causes of acute deterioration of GFR. To identify progressive CKD, obtain a minimum of three eGFR estimations over a period of not less than 90 days

Key Point: Progressive CKD is defined as a decline in eGFR of>5 ml/min/1.73m2 within one year, or >10 ml/min/1.73m2 within five years

Albuminuria/Proteinuria

Proteinuria can be glomerular or tubular. Glomerular proteinuria results from a breakdown in the integrity of the glomerular basement membrane and, more specifically, damage to podocytes in the membrane. Proteinuria is associated with an increased risk of cardiovascular disease and is an independent risk factor for progression of renal disease

All CKD patients should be checked for proteinuria. This may easily be detected by testing urine using reagent strips, but these are not usually as sensitive as sending the sample to the biochemistry lab for measurement of ACR albumin:creatinine ratio) or PCR (protein:creatinine ratio). The ACR has greater sensitivity than PCR for low levels of proteinuria and is usually the preferred test, but nephrologists still tend to use PCR more than ACR. The opposite is true among diabetologists, who more commonly use ACR so that they can detect the very earliest stages of diabetic nephropathy, which may be amenable to treatment

• If the initial ACR is >30 mg/mmol and <70 mg/mmol, a further early-morning sample for ACR should be sent for confirmation. If the initial sample is >70 mg/mmol, no repeat sample is necessary
• In patients without diabetes, proteinuria is considered clinically significant when the ACR is >30 mg/mmol
• However, in patients with diabetes, consider microalbuminuria of an ACR > 2.5 mg/mmol in men and >3.5 mg/mmol in women to be clinically significant

Key Point: Glomerular protein largely consists of albumin, and levels of proteinuria greater than 1 g/L usually indicates glomerular proteinuria. This is equivalent to a PCR of >100 mg/mmol

Key Point: Concerning PCR, an approximation to the protein excretion (in mg/L) can be obtained by multiplying the ratio (in mg/mmol) × 10

                                          Eg PCR 100 approx = 1000 mg/L = 1 g/L (upto 0.2 g/L is normal)

With a typical Western diet, humans consume 80 g of protein per day

Key Point: A nephrological referral should be considered (a) if there is significant proteinuria (ACR >70, or PCR >100) with or without haematuria, or (b) ACR >30 or PCR >50 with haematuria

Haematuria, Urinary Dipsticks and Who to Refer to Urology and Nephrology

Haematuria can either be glomerular (from the kidney) or extra-glomerular (from a urological source). Microscopic haematuria is now more aptly termed non-visible haematuria (NVH). This can be subdivided into symptomatic NVH with the presence of lower urinary tract symptoms, or asymptomatic NVH

When screening for haematuria, urinary reagent strips should be used rather than urine microscopy. This is partly because of the lack of availability of access to quality microscopic techniques with skilled operators and partly because of the need for the microscopy testing to be performed on a relatively fresh sample of urine. Dipstick urinalysis has the advantages of simplicity and accessibility

If there is a positive urinary reagent strip test of 1+ or more of blood, microscopic confirmation (ie an MSU, with M, C and S) should be made, and further evaluation will be necessary. Why is this?

 'Blood' on the dipstick represents the reaction observed when the 'peroxidase-like' activity inherent in molecules of haem (iron within a porphyrin ring) reacts with a peroxidase substrate in the pad. So the test should be called 'Haem' which is a more accurate term for what the test is detecting, rather than the term 'blood'. Haem is found within haemoglobin (free in the urine or within erythrocytes) or myoglobin. Thus, the reaction is very sensitive and will detect haematuria, haemoglobinuria and myoglobinuria. Microscopy of the urine will determien whether there are red cells there

This 2008 article by Pravin Kumar called 'How to evaluate ‘dipstick haematuria’: What to do before you refer' is a very good summary for GPs

Any episode of visible haematuria or symptomatic NVH in the absence of a urinary tract infection (UTI) or transient cause is considered significant. Persistence of asymptomatic NVH (defined as at least two out of three positive NVH dipsticks) is also considered significant. Trace haematuria should be considered negative

It is important to Investigate symptomatic and persistent asymptomatic haematuria by:
  (i) excluding UTIs or other transient causes
  (ii) checking creatinine/eGFR
  (iii) sending urine for ACR or PCR on a random sample
  (iv) measuring blood pressure (BP)
(BAUS/RA 2008)

Key Point: all patients with significant visible or symptomatic non-visible haematuria, and patients over the age of 40 years with symptomatic non-visible haematuria, should be referred to urology, to exclude carcinoma - using the 2 week cancer wait system

An exception of referring directly to a nephrologist may be a young adult who has haematuria (cola-coloured!) and an intercurrent illness (usually an upper respiratory tract infection), and who is suspected of having acute glomerulonephritis 

For those with haematuria but no proteinuria, there should be annual testing for haematuria, albuminuria/proteinuria, eGFR and BP monitoring, as long as the haematuria persists. An adult under the age of 40 years with hypertension and isolated haematuria (ie in the absence of proteinuria) should be referred to a nephrologist. The two most common causes of this scenario are hypertensive nephropathy and IgA nephropathy 

Microscopic haematuria is seen in 3-6% of the normal population. A recent 22-year retrospective study of over 1.2 million young adults found a substantially increased risk for treated ESRD attributed to primary glomerular disease in individuals with persistent asymptomatic isolated microscopic haematuria compared to those without. However, the incidence and absolute risk of ESRD remained quite low (Vivante, 2011)

Renal Imaging

Renal ultrasound should be offered to all people with CKD who have:

  (i) progressive CKD
  (ii) visible or persistent non-visible haematuria
  (iii) symptoms of urinary tract obstruction,
  (iv) a family history of polycystic kidney disease and are over 20 years old
  (v) stage 4 or 5 CKD
  (vi) require a kidney biopsy

More Specialist Renal Screening Tests (for underlying cause of CKD)

• Doppler Ultrasound of the renal arteries may be useful in patients with uncontrolled hypertension, looking for renovascular disease. This may show asymmetric kidney size. These patients often also have peripheral vascular disease, and AAA. Though this test has a significant false positive and negative rate. CT or MT angiography, and even invasive renal angiography may also be required
• Serum immunoglobulins/protein electrophoresis/serum-free light chains may be requested to screen for myeloma
• Auto-antibodies: ANA/dsDNA, ANCA and anti-GBM antibody are used to diagnose SLE, ANCA-positive vasculitus and Goodpasture Syndrome
• Complement levels (C3 and C4) are often reduced in active SLE, and low C3 levels may indicate underlying mesangiocapillary glomerulonephritis (MCGN)
• Virology. Several glomerulonephritides may be driven by viruses and other infectious agents (eg Hep B, Hep C, HIV). A positive HIV test may suggest underlying HIV-associated nephropathy (HIVAN), which may present with renal impairment and proteinuria - and almost exclusively occurs in black people
• Renal biopsy. In patients with renal impairment and/or proteinuria of more than 1 g/L (PCR > 100), a renal biopsy may be required to elucidate the cause of underlying CKD, provided this is technically feasible. Relative contraindications may be extreme obesity, small kidneys (less than 9 cm) and single kidney 
• Genetic testing. Although two gene mutations (PKD1 and PKD2) have been identified in patients with polycystic kidney disease, the test is not widely available, and its utility remains questionable. There are potentially some instances when this test may be useful (eg in a family when the mutation is already known), but widespread adoption of this test is not considered appropriate at the present time

CKD Management - General

(i) Blood pressure control.  BP control is mandatory in any patient with CKD, first to slow down the progress of renal impairment and, second, to reduce the risk of cardiovascular events. The beneficial effects that BP control has on the kidney are largely mediated via a reduction in intraglomerular capillary pressure to preserve the integrity of the glomerulus

Key Point: In patients with CKD, keep the BP below 140/90; however, in people with diabetes and CKD, or when the ACR >70 mg/mmol, the aim should be to aim for a BP below 130/80

NICE now recommend that a diagnosis of hypertension be made using 24-hour ambulatory blood pressure monitoring (ABPM), which should be offered to patients if the clinic BP is 140/90 mmHg or higher (NICE 2011)

(ii) Diabetes control. Data from the ADVANCE trial have shown fairly convincingly that good glycaemic control can slow down the progression of renal disease (ADVANCE Collaborative Group, 2008). This was also confirmed in the UKPDS study 

(iii) Angiotensin converting enzyme inhibition (ACEI)/Angiotensin receptor blockade (ARB)

ACEIs and ARBs exert a number of positive benefits in patients with CKD. Specifically, they lower BP, and reduce proteinuria - and, importantly, they preserve renal function in the longer term. Thus, part of their action is mediated via a reduction in BP and intraglomerular pressure; but it is now apparent that other mechanisms play a part in their renoprotective effects. Their selective action on the efferent arteriole may reduce intraglomerular pressure over and above the reduction in systemic arterial pressure. In addition to its vasoconstrictive action, angiotensin II may induce other pathogenetic mechanisms, such as mesangial hypertrophy

Therefore, reducing the levels, or blocking angiotensin II, may explain why ACEIs or ARBs are renoprotective. Following the introduction of  these drugs, there may be an initial small reduction in eGFR induced by their intraglomerular effects, and a small rise in serum creatinine may be evident within two weeks

Thus, inhibition or blockade of angiotensin II will then result in a disproportionate reduction in eGFR. With the risk of exacerbating renal failure with ACEI/ARB use in those patients who may have reduced renal blood flow due to renal artery stenosis, it is advised to test renal function before treating with these drugs and after 1-2 weeks of treatment after any dose increase. No dose modification is needed if the eGFR decrease is less than 25% (or creatinine increase is <30%). If the eGFR decreases by >25% (or creatinine increase >30%) after ACEI/ARB initiation or dose increase, then other causes of renal function deterioration, such as nonsteroidal anti-inflammatory drugs (NSAIDs) or volume depletion, need to be excluded; and if no other cause is found, the ACEI/ARB will need to be stopped or reduced to a previously tolerated dose (NICE 2008)

Key Point: if the creatinine rise, after starting an ACEI or ARB, is >30%, the drug should be stopped

If the increase in creatinine level exceeds 30%, the possibility of underlying renovascular disease should be entertained. This is because a kidney that is ischaemic due to a significant renal artery stenosis is heavily dependent on angiotensin II to maintain its intraglomerular hydrostatic pressure

There is strong evidence that:
◦ Proteinuria can be reduced (and even reversed), and the progression of CKD can be slowed, by the use of ACEIs or ARBs in diabetic nephropathy (Lewis, 1993); and may delay dialysis. But it is unclear whether this prevents ESRD completely, or improves mortality
◦ The risk of CKD progression can also be reduced amongst non-diabetic CKD patients with proteinuria of >1g per day (or PCR of >100 mg/mmol) by treating with ACEIs or ARBs (Ruggenenti, 1998)

However, although microalbuminuria in non-diabetics has shown to be reversed by ACEI/ARBs, there is no significant evidence that the use of these drugs shows any long-term benefits on the kidneys, and selective treatment is not currently advocated

When using ACEIs/ARBs, it is important to monitor renal function and potassium levels, and titrate the drugs to the maximum tolerated therapeutic dose before adding a second-line agent. ACEIs/ARBs should not be started if the serum potassium is significantly above the normal reference range, and other factors that promote hyperkalaemia need to be excluded and treated. More frequent monitoring of serum potassium is required if medication that promotes hyperkalaemia is being taken, and the ACEIs/ARBs should be discontinued if the serum potassium rises to >6 mmol/L

Key Point: If the patient is already on a potassium-sparing diuretic (especailly spironolactone) then great care should be taken with ACEI/ARBs as the combination of these drugs can have a profound hyperkalaemic effect. If they are used together (which may be necessary, especially in patients with CCF and mild CKD), then potassium should be monitored at leats every two months

Lowering dietary salt intake reduces BP, and lowers proteinuria, more effectively than an ACEI; and augments the action of the ACEI if its restriction is used in conjunction with it. It is more effective, in general, in the black population

(iv) Reverse dehydration

(v) Drugs. eGFR will need monitoring in patients prescribed known nephrotoxic drugs such as lithium and calcineurin inhibitors (Ciclosporin and Tacrolimus). Those receiving long-term NSAIDs should have at least annual checks on renal function. An uncommon allergic response to protein pump inhibitors and some antibiotics can lead to acute or chronic interstitial nephritis, which is usually reversible on stopping the offending drug. Since many drugs are excreted via the kidneys, renal failure may lead to increased blood concentrations of a number of medications, including opiates and digoxin, and reduced doses are often required

(vi) Manage cardiovascular health. HMG-CoA Reductase Inhibitors ('statins') should be used for the primary prevention of cardiovascular disease in the same way as in people without CKD. In the SHARP study, patients with CKD were randomised to lipid lowering therapy (simvastatin or simvastatin/ezetimibe) versus placebo. The primary outcome (major atherosclerotic events defined as a composite of coronary death, myocardial infarction, non-haemorrhagic stroke or any revascularisation) was reduced by 17% (Baigent, 2011). Both statins (irrespective of baseline lipid values); and antiplatelet drugs should also be used for the secondary prevention of cardiovascular disease. However, the prescriber should be aware that there is an increased risk of minor bleeding in people with CKD given multiple antiplatelet drugs

Patients with CKD should be advised on the need for regular exercise, maintaining a healthy weight and stopping smoking

(vii) Malnutrition. Animal studies have indicated that a low protein diet slows the progression of renal impairment. Unfortunately the protein restriction required to protect renal function in humans was found to be impractical for patients. And it has the risk of exacerbating malnutrition. Also the MDRD study, in 1994, did not show that it slow the progression of CKD in humans. Nowadays, a normal, but not excessive, protein intake of 1 g/kg/day is recommended. Dietary advice on protein, potassium and phosphate intake may be needed for some people with progressive CKD

(viii) Anaemia. See section in Subject Chapters
 
(ix) CKD-Mineral and Bone Disorder (CKD-MBD). See section in Subject Chapters

(x) Acidosis and hyperkalaemia
 
(xi) Manage fluid overload. Manage fluid overload while avoiding deterioration in renal function from diuretic use

(xii) Dialysis and transplantation. See sections in Subject Chapters
 .
(xiii) Supportive (palliative) care 

CKD-Management - Specific

(i) Nephrotic syndrome - steroids for minimal change nephropathy
(ii) Crescentic glomerulonephritis/vasculitis - and Cyclophosphamide
(iii) Lupus nephritis (depends on WHO Class) - steroids and Cyclophosphamide; Mycophenolate
(iv) HIVAN - HAART therapy has been shown to help HIVAN
(v) Myeloma - chemotherapy Dexamethasone/Thalidomide/Melphalan/Bortezomib plus trials using high flux dialysis membranes are in progress (EuLITE study)
(vi) Drugs - interstitial nephritis - stop offending medication, eg antibiotics (especially penicillins), NSAIDs, proton pump inhibitors. Give steroids if still active

Patients will need tailored education about their condition in order to help them understand and make informed choices about treatment. There will be a large group of patients, particularly in Stage 3A CKD, who will not experience significant deterioration in renal function but may suffer disproportionate anxiety about their health without adequate explanation. Although the majority of CKD patients can be managed within the community, it is important to recognise those patients who would benefit from referral to a nephrologist. In certain cases discussing the management issues of a particular individual with a specialist may avoid the need for referral

A patient’s wishes and comorbidities need to be taken into account when referral is considered. In general, patients in stages 4 and 5 CKD, with or without diabetes, should be considered for specialist assessment. However, other factors - including proteinuria, haematuria, poorly controlled hypertension, rate of change of eGFR and consideration as to whether the rate of progression of eGFR would make renal replacement therapy likely within the person’s lifetime - would all influence the need for referral

The NICE (2008) guideline on CKD suggests referral for the following groups of people with CKD:
• Stages 4 and 5 CKD
• Higher levels of proteinuria (ACR >70 mg/mmol) unless known to be due to diabetes and appropriately treated
• Proteinuria (ACR >30 mg/mmol) together with haematuria
• Rapidly declining eGFR (>5 ml/min/1.73m2 in one year, or >10 mL/min/1.73m2 within five years)
• Hypertension, if poorly controlled despite the use of at least four antihypertensive drugs at therapeutic doses
• People suspected of having rare or genetic causes of CKD
• Suspected renal artery stenosis

When under hospital care, a patient with CKD may attend either a general nephrology clinic, a low clearance clinic or undergo dialysis. Supportive (palliative) treatment is an option for some patients with end-stage kidney disease, and management of these patients is often undertaken in the community alongside collaboration with renal/palliative care specialists

References

ADVANCE Collaborative Group, Patel A, MacMahon S et al. Intensive blood glucose control and vascular outcomes in patients with type 2 diabetes. N Engl J Med; 358: 2560-2572, 2008

Anandarajah S, Tai T, de Lusignan S et al. The validity of searching routinely collected general practice computer data to identify patients with chronic kidney disease (CKD): A manual review of 500 medical records. Nephrol Dial Transplant; 20: 2089-96, 2005

Baigent C, Landray MJ, Reith C et al. SHARP Investigators: The effects of lowering LDL cholesterol with simvastatin plus ezetimibe in patients with chronic kidney disease (Study of Heart and Renal Protection): A randomised placebo-controlled trial. Lancet; 377: 2181–92, 2011

BAUS/RA Guidelines (2008) Joint Consensus Statement on the Initial Assessment of Haematuria 

Centers for Disease Control and Prevention. Prevalence of chronic kidney disease and associated risk factors: United States, 1999-2004. Morb Mortal Wkly Rep 56: 161-5, 2007

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; 41: 1-12, 2003

Go AS, Chertow GM, Fan D, McCulloch CE, Hsu CY. Chronic kidney disease and the risks of death, cardiovascular events, and hospitalization. N Engl J Med; 351: 1296-305, 2005

Halbesma N, Jansen DF, Heymans MW et al. PREVEND Study Group: Development and validation of a general population renal risk score. Clin J Am Soc Nephrol; 6: 1731-8, 2011

Hallen SI, Dahl K, Oien CM et al. Follow-up of cross sectional health survey. BMJ; 333: 1047, 2006

HOPE Study Investigators. Effects of ramipril on cardiovascular and microvascular outcomes in people with diabetes mellitus: Results of the HOPE study and MICRO-HOPE substudy. Lancet; 355: 253-9, 2000

Kumar P, Jones S. How to evaluate ‘dipstick hematuria’: What to do before you refer. Cleveland Clinic Journal of Medicine; 75(3): 227-233, 2008

Lewis EJ, Hunsicker LG, Bain RP, Rohde RD. The effect of angiotensin-converting-enzyme inhibition on diabetic nephropathy. N Engl J Med; 329: 1456-62, 1993

NICE (2006) Clinical Guideline 34: Hypertension, http://www.nice.org.uk/nicemedia/pdf/cg034quickrefguide.pdf.
 
NICE (2008) Clinical Guideline 73: Chronic kidney disease, http://www.nice.org.uk/CG73.

NICE (2009) Clinical Guideline 87: Type 2 diabetes, http://www.nice.org.uk/nicemedia/pdf/CG87NICEGuideline.pdf

NICE (2011) Clinical Guideline 127: Hypertension, http://www.nice.org.uk/nicemedia/live/13561/56008/56008.pdf

Ruggenenti P, Perna A, Gherardi G et al. Renal function and requirement for dialysis in chronic nephropathy patients on long-term ramipril: REIN follow-up trial. Gruppo Italiano di Studi Epidemiologici in Nefrologia (GISEN). Ramipril Efficacy in Nephropathy. Lancet; 352: 1252-6, 1998

Taal M. Predicting renal risk in the general population: Do we have the right formula? Clin J Am Soc Nephrol 6: 1523-5, 2011

UK Renal Registry (2009) Annual Report, http://www.renalreg.com/Reports/2009.html.

Vivante A, Afek A, Frenkel-Nir Y. Persistent asymptomatic isolated microscopic hematuria in Israeli adolescents and young adults at risk for end-stage renal disease. JAMA 2011; 306: 729-36

Summary of Recommendations for GP CKD Referral to Nephrology

We recommend that general (family) practitioners consider referral for the following conditions:

Condition Exceptions Urgency
1. CKD3b or above (or creatinine > 150 mcmol/L) If condition unlikely to cause problem in patient's lifetime (A) < 8 weeks (< 1 week if rapidly rising creatinine)
2. Proteinuria (> 1g/L, or PCR >100) A, or has diabetes > 5y and has creatinine < 150 mcmol/L < 8 weeks
3. Proteinuria + microscopic haematuria A < 8 weeks
4. Difficult to control BP (on 3 drugs or more, with or without raised creatinine) A < 12 weeks
5. Worried. Ie concerned re missing a serious renal disease A < 12 weeks

Notes:

1. AKI.  Patients with suspected AKI should not be referred to an outpatient department. Please ring your local renal unit and ask to speak to the oncall renal registrar or consultant
2. Macroscopic haematuria. These patients should be referred to a urologist first. If the patient is > 40 years, urological malignancy must be excluded urgently 

Dr H Rayner, Dr I Dasgupta and Dr R Pal have written an excellent and comprehensive review on CKD for primary care physicians, that is available free online here.