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The definition of chronic kidney disease (CKD) is based on the presence of kidney damage (ie
albuminuria) or decreased kidney function (ie glomerular filtration rate (GFR) <60 ml/minute
per 173 m) for three months or more, irrespective of clinical diagnosis. [1]
When symptoms are severe they can be treated only by dialysis and transplantation (endstage renal disease). Kidney failure is defined as a GFR of less than 15 ml/minute per 173 m,
or the need for treatment with dialysis or transplantation. [1]
Progression of CKD is defined as a decline in estimated glomerular filtration rate (eGFR) of > 5
ml/minute/1.73 m within one year, or >10 ml/minute/1.73 m within five years. [2]
Until recently, the emphasis has been on patients needing dialysis or transplantation. It is now
realised that less severe CKD is quite common, and monitoring in primary care will enable the
minority of patients who go on to develop a more severe form to be detected at any earlier
stage.[3] This is important because the earlier the intervention, the greater the impact.
Epidemiology
A large primary care study (practice population 162,113) suggests an age standardised
prevalence of stage 3-5 chronic kidney disease (CKD) of 8.5% (10.6% in females and
5.8% in males).[4]
Etiology
In developed countries, CKD is often associated with old age, diabetes, hypertension, obesity
and cardiovascular disease (CVD).[1]
Hypertension.
Glomerulonephritis.
Diabetes.
Family history of stage 5 CKD or hereditary kidney disease - eg, polycystic kidneys.
Hypercalcaemia.
Neoplasms.
Myeloma.
Risk factors
Factors other than the underlying disease process that may cause progressive renal injury
include the following:Acute insults from nephrotoxins or decreased perfusion.
Proteinuria.
Hyperlipidaemia.
Stage 1: normal; eGFR >90 ml/minute/1.73 m2 with other evidence of chronic kidney
damage (see below).
Use the suffix (p) to denote the presence of proteinuria when staging CKD.
NB: patients with a GFR of >60 ml/minute/1.73 m 2 without evidence of chronic kidney
damage should NOT be considered to have CKD and do not necessarily need further
investigation.
The other evidence of chronic kidney damage may be one of the following:
Persistent microalbuminuria.
Persistent proteinuria.
Presentation
Symptoms
it usually presents with nonspecific symptoms caused by renal failure, complications eg, anaemia in chronic renal failure (CRF), and the underlying disease.
It may be discovered by chance following a routine blood or urine test.
Specific symptoms usually develop only in severe renal failure, and include anorexia,
nausea, vomiting, fatigue, weakness, pruritus, lethargy, peripheral oedema, dyspnoea,
insomnia, muscle cramps, pulmonary oedema, nocturia, polyuria and headache.
Hiccups, pericarditis, coma and seizures are only seen in very severe renal failure.
Signs
The physical examination is often not very helpful but may reveal findings
characteristic of the underlying cause (eg SLE, severe arteriosclerosis, hypertension) or
complications of CRF (eg, anaemia, bleeding diathesis, pericarditis).
Patients who are at increased risk of developing CKD should be offered screening tests to
detect CKD, which should include assessment of the eGFR as well asurinalysis. Offer people
testing for CKD if they have any of the following risk factors: [2]
Diabetes.
Hypertension.
Differential diagnosis
Acute kidney injury (acute renal failure):
Making the distinction between AKI and CRF can be very difficult. A history of
chronic symptoms of fatigue, weight loss, anorexia, nocturia, and pruritus all suggest
CKD.
The history and examination will provide clues, but renal ultrasound will provide
the most important information. Renal abnormalities on ultrasound, such as small
kidneys in chronic glomerulonephritis or large cystic kidneys in adult polycystic
kidney disease, will almost always be present in patients with CKD.
Acute on chronic renal failure: may have features indicating CKD but also features
suggesting a cause of an acute deterioration of renal function - eg, infection.
Investigations
Investigations are focused on assessment of renal function and therefore stage of CKD,
identification of the underlying cause and assessment of complications of CKD. [1]
Serum urea is a poor marker of renal function, because it varies significantly with
hydration and diet, is not produced constantly and is reabsorbed by the kidney.
Serum creatinine also has significant limitations. The level can remain within the
normal range despite the loss of over 50% of renal function.
For most purposes in primary care, the best assessment or screening tool is the
eGFR.[5] - see separate article Assessing Renal Function and the Estimated Glomerular
Filtration Rate Calculator. Most laboratories now provide an eGFR when requesting
serum creatinine, which should be used in preference to calculator above.
Biochemistry:
Serology:
Spot urine collection for total protein:creatinine ratio allows reliable estimation of
total 24-hour urinary protein excretion. The degree of proteinuria correlates with the
rate of progression of the underlying kidney disease and is the most reliable
prognostic factor in CKD.
24-hour urine collection for total protein and creatinine clearance. 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
ECG and echocardiography: to detect left ventricular hypertrophy and ischaemia, and
to assess cardiac function.
Imaging of the renal tract:
Intravenous (IV) pyelogram: not often used because of potential for contrast
nephropathy.
Renal ultrasound:
Kidneys are usually initially large and then become normal in size in
advanced diabetic nephropathy.
Useful to screen for renal artery stenosis when performed with captopril
administration but is unreliable for GFR of less than 30 ml/minute.
Also quantifies differential renal contribution to total GFR.
CT scan: to define renal masses and cysts, seen on ultrasound, better; this is the
most sensitive test for identifying renal stones.
MRI:
For patients who require a CT scan but who cannot receive IV contrast.
Renal biopsy.
People with CKD in the following groups should normally be referred for specialist
assessment:
Hypertension that remains poorly controlled despite the use of at least four
antihypertensive drugs at therapeutic doses.
People with CKD and renal outflow obstruction should normally be referred to urological
services, unless urgent medical intervention is required.
Consider discussing management issues with a specialist in cases where it may not be
necessary for the person with CKD to be seen by the specialist.
Once a referral has been made and a plan jointly agreed, consider routine follow-up at
the person's GP surgery rather than in a specialist clinic and specify criteria for future
referral or re-referral.
Managementon
General issues[7]
Many patients equate kidney disease with renal dialysis. It is important to explain that
CKD is a spectrum of disease. Mild CKD is common and rarely progresses to a more
severe form later.
Explain eGFR and that this will need to be monitored on a regular basis to ensure that
the condition is not deteriorating.
If relevant, discuss the link between hypertension and CKD and that maintaining tight
blood pressure control can limit the damage to the kidneys.
Discuss the link between CKD and an increased risk of developing CVD.
Patients with diabetes mellitus and CKD should achieve good glycaemic control.
Avoidance of nephrotoxins - eg, IV radiocontrast agents, non-steroidal antiinflammatory drugs (NSAIDs), aminoglycosides.
Review all previous measurements of serum creatinine to estimate GFR and assess the
rate of deterioration.
Clinical assessment: eg, look for sepsis, heart failure, hypovolaemia, palpable bladder.
Repeat serum creatinine measurement within five days to exclude rapid progression.
Check criteria for referral (above). If referral is not indicated, ensure entry into a chronic
disease management register and programme.
Monitoring[6]
The eGFR should be monitored regularly. The frequency will depend on the severity of
kidney impairment.
Patients with CKD should have the level of proteinuria assessed at least annually.
Detection of an initial abnormal eGFR result should prompt clinical assessment and a
repeat test within two weeks to assess the rate of change in GFR. If the GFR is stable, a
further test should be performed after 90 days to confirm the diagnosis of CKD.
Patients with CKD should have an annual formal assessment of their cardiovascular risk
factors including lipid profile, BMI, exercise, alcohol and smoking habits, as well as a
review of interventions to reduce cardiovascular risk.
Patients with CKD and dyslipidaemia should be treated in accordance with current
guidance for the general population. Smoking status and action taken should be
documented. Patients with CKD and a BMI of >30 kg/m 2 should receive dietary advice to
assist them in losing weight.
Statins should be considered for primary prevention in all CKD stages 1-4 and
transplant patients with a 10-year risk of cardiovascular disease calculated as >20%. A
total cholesterol of <4 mmol/L or a 25% reduction from baseline, or a fasting low-density
lipoprotein (LDL)-cholesterol of <2 mmol/L or a 30% reduction from baseline, should be
achieved, whichever is the greatest reduction in all patients.
Folic acid and B vitamin supplements should be offered to all renal patients considered
nutritionally at risk from deficiency of folic acid or B vitamin deficiency. B12 levels and,
serum and red cell folate should be above the lower limit of the reference range in all CKD
patients. Red cell folate levels should be checked if MCV remains high despite normal or
high serum folate. Serum folate levels and B12 should be checked six-monthly in CKD4/5
and three-monthly in dialysis patients, or more frequently if patients remain anaemic or
deficient.
CKD patients with established CVD should be prescribed aspirin, an ACE inhibitor, a
beta-blocker, and a statin unless contra-indicated. Aspirin is indicated for secondary
prevention but not primary prevention of vascular disease in renal failure.
Patients on lipid-lowering drug treatment should have total cholesterol reduced by 25%
or to below 4 mmol/L, or LDL-cholesterol to below 2 mmol/L, or reduced by 30%,
whichever reductions are the greatest.
In patients with CKD, systolic blood pressure should be lowered to <140 mm Hg (target
range 120-139 mmHg) and the diastolic blood pressure to <90 mm Hg for the majority.
For those with diabetes mellitus or proteinuria of 1 g/24 hours or greater, the systolic
blood pressure should be lowered to <130 mm Hg (target range 120-129 mm Hg) and the
diastolic blood pressure to <80 mm Hg unless the risks are considered to outweigh the
potential benefits.
Patients with CKD and proteinuria >0.5 g/day should have their ACE inhibitor or AIIRA
and other antihypertensive treatment escalated to achieve the lowest possible level of
proteinuria.
All patients with stage 4-5 CKD should have the following parameters measured as a
minimum in order to identify undernutrition:
Oral nutritional supplements should be used if oral intake is below the levels indicated
above and food intake cannot be improved.
Anabolic agents such as androgens, growth hormone or IGF-1 are not indicated in the
treatment of undernutrition in adults. Androgens and growth hormone have shown
improvement in serum albumin levels and lean body mass but not mortality, and they
have significant side-effects.
Minimum daily dietary protein intake: a prescribed protein intake of 0.75 g/kg IBW/day
for patients with stage 4-5 CKD not on dialysis; 1.2 g/kg IBW/day for patients treated with
dialysis.
Patients should receive dietary advice to restrict their sodium intake to <2.4 g/day (100
mmol/day or <6 g/day of salt).
Serum levels of calcium, phosphate, alkaline phosphatase, PTH and calcidiol (25(OH)D)
should be monitored in patients with CKD stage 3-5, and patients on dialysis, with a
frequency based on stage, rate of progression and whether specific therapies have been
initiated.
Serum calcium, adjusted for albumin concentration, in patients with CKD stage 3-5 not
on dialysis should be kept within the normal reference range.
Serum phosphate in patients with CKD stage 3-5 (not on dialysis): serum phosphate in
patients with CKD stage 3b-5 should be maintained between 0.9 and 1.5 mmol/L.
Serum phosphate in dialysis patients (stage 5D): serum phosphate in dialysis patients,
measured before a 'short-gap' dialysis session in haemodialysis patients, should be
maintained between 1.1 and 1.7 mmol/L.
Serum PTH in patients with CKD 3b-5 (not on dialysis): treatment should be considered
in patients with CKD stages 3b-5 not on dialysis therapy in whom serum PTH levels are
progressively increasing and remain persistently higher than the upper reference limit for
the assay, despite correction of modifiable factors.
Target range of serum PTH in patients on dialysis should be between 2 and 9 times the
upper limit of normal for the assay used. Marked changes in PTH levels in either direction
within this range should prompt an initiation or change in therapy to avoid progression to
levels outside this range.
Complications
Coagulopathy.
Management of complications
Water and electrolyte balance:
Patients with CKD pass normal volumes of urine. Precise restriction of fluid intake
is only required for patients with oliguric end-stage renal failure. The usual
recommendation is for a daily intake of daily urinary output plus 500 ml (for
insensible losses).
Patients should avoid binge drinking and be vigilant in replacing extra fluid losses
in hot weather and during episodes of diarrhoea or vomiting.
Severe acute volume overload may require high-dose loop diuretics or dialysis.
Acidosis:
Treated with sodium bicarbonate as long as the patient can tolerate the
increased sodium load, as additional sodium may cause fluid overload and worsen
hypertension.
Nerological:[1]
Retained toxins are thought to have a role in these disorders, and intensive
dialysis is sometimes associated with amelioration.
Prognosis
Early diagnosis, regular monitoring and early treatment can prevent development and slow
disease progression, reduce complications and the risk of cardiovascular disease, and improve
survival and quality of life.[1]
Much of the damage caused by CKD occurs early, when interventions may be much
more effective.
Rapidly progressive diseases can lead to kidney failure within months. However, most
diseases evolve over decades and some patients do not progress during many years of
follow-up.[1]
Patients on chronic dialysis have a high incidence of morbidity and mortality. Patients
with end-stage renal disease (ESRD) who undergo renal transplantation survive longer
than those on chronic dialysis.
CVD is the most common cause of death in patients with CKD. Cardiovascular mortality
is doubled in patients with a GFR below 70 ml/minute.
Prevention
Early diagnosis and good control of potential causes - eg, diabetes, hypertension and urinary
tract obstruction.
Anaemia Management in People with Chronic Kidney Disease, NICE Clinical Guideline
(February 2011)
1.
2.
3.
4.
Stevens PE, O'Donoghue DJ, de Lusignan S, et al; Chronic kidney disease management
in the United Kingdom: NEOERICA project Kidney Int. 2007 Jul;72(1):92-9. Epub 2007 Apr
18.
5.
6.
7.
Mitra PK, Tasker PR, Ell MS; Chronic kidney disease. BMJ. 2007 Jun 16;334(7606):1273.
8.
9.
10.
Chronic Kidney Disease - Mineral and Bone Disorders, Renal Association (2010)