Chronic kidney disease: diagnosis and management

WHAT IS CHRONIC KIDNEY DISEASE AND WHY IS IT IMPORTANT?

Chronic kidney disease (CKD) is defined as a reduction in kidney function, or structural damage, (or both), which is present for more than 3 months, with associated health implications.^1,2 CKD should be diagnosed in people with markers of kidney damage such as:

• Urinary albumin:creatinine ratio (ACR) greater than 3 mg/mmol
• Urine sediment abnormalities
• Electrolyte abnormalities
• Abnormalities detected by histology
• Structural abnormalities detected by imaging
• A history of kidney transplantation.^3,4

A common diagnostic marker is a persisting serum estimated glomerular filtration rate (eGFR) of lower than 60 mL/min/1.73 m².²

Causes and risk factors

Causes of CKD include conditions such as hypertension, diabetes mellitus, systemic lupus erythematosus, or glomerular disease, such as acute glomerulonephritis, current or previous history of acute kidney injury (AKI),^2,4 and conditions associated with obstructive uropathy. It can also be caused by commonly used drugs, such as angiotensin-converting enzyme (ACE) inhibitors and nonsteroidal anti-inflammatory drugs (NSAIDs).

Risk factors for CKD include a family history of CKD stage 5, or hereditary kidney disease, gout and obesity with metabolic syndrome, (obesity alone is not a risk factor for CKD). People with an incidental finding of haematuria or proteinuria are also considered to be at risk.

Incidence and prevalence

The incidence and prevalence of CKD varies depending on the population studied, including ethnic group and socio-economic class. A UK study found the prevalence of CKD was 5.9%.^5,6

Complications

There are many complications of CKD. These include:

• Acute kidney injury
• Hypertension
• Dyslipidaemia
• Cardiovascular disease
• Renal anaemia
• Mineral and bone disorders
• Peripheral neuropathy and myopathy
• End-stage renal disease (ESRD).

All of these complications lead to an increase in all-cause mortality.⁵

Decreasing eGFR and/or increasing proteinuria are independently associated with a poorer prognosis.^1,2,4

DIAGNOSIS

Investigations to assess for CKD should be carried out in people with any of the risk factors listed above, and for those who have an incidental finding of:

• A raised serum creatinine and/or an eGFR of less than 60 mL/min/1.73m²
• Proteinuria (a urinary ACR of more than 3 mg/mmol)
• Persistent haematuria (two out of three urine dipstick tests show 1+ or more of blood), after exclusion of a urinary tract infection (UTI)
• Urine sediment abnormalities, such as red blood cells, white blood cells, or granular casts and renal tubular epithelial cells.

When should I suspect chronic kidney disease?

CKD is usually asymptomatic in the early stages.^1,2,4

A history should include non-specific symptoms such as lethargy, itch, breathlessness, cramps (often worse at night), sleep disturbance, bone pain, loss of appetite, vomiting, weight loss and taste disturbance. More specific symptoms to ask about are related to urine output; polyuria, oliguria, nocturia, or anuria.^5,6

A medication history should include asking about any potentially nephrotoxic drugs, including over-the-counter or herbal medicines.

Also enquire if there are any known risk factors for CKD or a previous history of AKI. Ask about any significant family history, such as polycystic kidney disease.

Examination

When examining a person check for the following:

• Uraemic odour (ammonia-like smell of the breath)
• Pallor(due to renal anaemia)
• Weight loss
• Cognitive impairment: language, orientation, and attention may be particularly affected and you may need to cross-reference with a relative
• Signs of dehydration
• Check the blood pressure to exclude hypertension
• Palpate for any renal masses and possible hepatomegaly
• Look for a palpable distended bladder
• Examine the sacrum and ankles for signs of peripheral oedema
• Check for any signs of peripheral neuropathy
• Examine the urine. Frothy urine may indicate proteinuria.^5,6

Initial investigations

These should include blood tests for serum creatinine and eGFR. Advise the person not to eat meat for at least 12 hours before the test,1,2 and to ensure that they are well hydrated. If the eGFR is less than 60 mL/min/1.73 m², repeat the test within two weeks (unless the eGFR is stable). If the eGFR remains less than 60 mL/min/1.73 m², repeat within 3 months.^1,2

Arrange an early morning urine sample to measure the urinary ACR. If the result is less than 3 mg/mmol (no proteinuria), no action is needed. If the result is between 3 and 70 mg/mmol, repeat the test within 3 months. If the result is 70 mg/mmol or more, a repeat test is not needed as this indicates significant proteinuria.1,2 Transient increases in urinary ACR may be seen with menstruation, urinary tract infection, and strenuous exercise.^2,5

Do not use urine dipsticks to test for proteinuria unless they can measure albumin at low levels and expresses the result as a urinary ACR. If unexplained proteinuria is an incidental finding on a reagent strip, offer testing for CKD using eGFR, creatinine and urinary ACR.^1,2,4

Use a urine dipstick test to check for haematuria.2 If there is 1+ or more of blood on dipstick, arrange a mid-stream urine sample to exclude a UTI.² If there is isolated persistent haematuria (two out of three urine dipstick tests show 1+ or more of blood after exclusion of a UTI), with no decrease in eGFR and no proteinuria, then a urinary tract carcinoma needs to be excluded.²

If the eGFR and urinary ACR tests are repeated within 3 months you can make a diagnosis of CKD if:

• There is a reduction in renal function (eGFR less than 60 mL/min/1.73 m2) and/or
• There is proteinuria (urinary ACR greater than 3 mg/mmol) that has persisted for at least three months.^5,6

A diagnosis of CKD can be excluded if the eGFR is persistently greater than 60 mL/min/1.73m², and/or urinary ACR is persistently less than 3 mg/mmol, and there are no other markers of kidney damage.

If the person has not been diagnosed with CKD but has ongoing risk factors for it, then an annual check of serum creatinine, eGFR, urinary ACR, and urine dipstick testing should be arranged. In addition, you should check the person’s nutritional status, body mass index, blood pressure, serum HbA1c and lipid profile to assess for cardiovascular risk factors.² Renal tract ultrasound should also be considered, for example, if the person has suspected urinary tract stones or obstruction, or a family history of polycystic kidney disease and is aged over 20 years.²

CLASSIFICATION OF CKD

CKD is classified using a combination of eGFR and urinary ACR. See Table 1.

MANAGEMENT

Monitoring to identify disease progression

Renal function should be monitored by checking serum creatinine and eGFR, together with urinary ACR, in order to identify 'accelerated progression' of CKD.^{1, 2} This is indicated by:

• A sustained decrease in eGFR of 25% or more from baseline, and
• A change in CKD category within 12 months, or
• A sustained decrease in eGFR of 15 mL/min/1.73 m2 within 12 months.

Be aware that small fluctuations in eGFR are common and do not necessarily indicate disease progression.

To assess the rate of progression, repeat the serum eGFR three times over at least 3 months. If disease progression is identified look for any reversible cause (such as potentially nephrotoxic drugs), arrange a renal tract ultrasound scan, and arrange referral to a nephrology specialist for further management.^1,2,7 Take into account the person's baseline eGFR and likely trajectory, to help decide on management and whether specialist referral is needed.^2,5

Arrange a full blood count to exclude renal anaemia for people with CKD category stages 3b, 4, and 5, or if a person develops symptoms suggestive of anaemia.^2,5

Arrange serum calcium, phosphate, vitamin D, and parathyroid hormone tests to exclude renal metabolic and bone disorder for people with CKD category stages 4 or 5.^2,5

REFERRAL

Referral to a nephrology specialist is indicated for people who have an eGFR of less than 30 mL/min/1.73m².^2,4 It is also indicated for those who have accelerated progression of CKD.

You should also refer patients with:

• A urinary ACR of 70 mg/mmol or more, unless proteinuria is known to be associated with diabetes mellitus and appropriate management has been put in place.
• A urinary ACR of 30 mg/mmol or more, together with persistent haematuria, after excluding a UTI.
• Suspected renal artery stenosis, indicated by a greater than 25% reduction in eGFR within 3 months of starting (or increasing the dose of) a renin-angiotensin system antagonist.
• Suspected complications of CKD e.g.
  • a decline in nutritional status or malnutrition
  • persistent hyperkalaemia
  • end-stage renal disease (ESRD) who require renal replacement therapy (haemodialysis/peritoneal dialysis or kidney transplantation).1,2,5
  • Renal anaemia
• Suspected urinary tract obstruction; e.g. the bladder is palpable, or hydronephrosis is seen on renal tract ultrasound.² The urgency of referral, in this instance, is dependent on clinical judgement. Emergency admission may be required if the person is in urinary retention.

Emergency admission is also indicated if the individual has severe hyperkalaemia (potassium greater than 6 mmol/L), severe uraemia or signs of fluid overload or dehydration.^1,2

MANAGEMENT IN PRIMARY CARE

If a person has a confirmed diagnosis of CKD, regular follow-up in primary care should be arranged. See Table 2 for intervals.

Assess and manage risk factors and co-morbidities. Any potentially nephrotoxic drugs that may cause AKI in severe intercurrent illness should be reduced or stopped, as appropriate.⁷

Hypertension

Check the blood pressure. The appropriate management of hypertension in CKD, and whether referral is indicated, depends on the individual’s urinary ACR and the presence or absence of co-morbidities. In any case, DO NOT prescribe combinations of renin-angiotensin system antagonists, e.g. lisinopril and losartan, to people with CKD.

Urinary ACR of 30mg/mmol or less

Arrange appropriate management of hypertension if the person does not have diabetes.2

Urinary ACR 30mg/mmol or more

Prescribe a low-cost renin-angiotensin system antagonist (e.g lisinopril or losartan) aimng to achieve the optimal tolerated dose, depending on contraindications, cautions, and drug interactions.2,5

Urinary ACR less than 70mg/mmol

Aim for a blood pressure target of systolic less than 140 mmHg (target range 120–139 mmHg) and diastolic less than 90 mmHg.^2,5

Urinary ACR of 70 mg/mmol or more

Aim for a blood pressure target of systolic less than 130 mmHg (target range 120–129 mmHg) and diastolic less than 80 mmHg.

Prescribe a low-cost renin-angiotensin system antagonist (for example lisinopril or losartan), as above and arrange referral to a nephrology specialist unless proteinuria is known to be associated with diabetes mellitus and is being managed appropriately.

Hypertension which remains uncontrolled, despite the use of at least four antihypertensive drugs at therapeutic doses, is an indication of the need for referral to a nephrology specialist.²

Cardiovascular disease

All people with CKD should be prescribed lipid-lowering therapy with a statin, for the primary or secondary prevention of CVD. They will also need to be prescribed an antiplatelet drug for the secondary prevention of CVD.⁸

CKD and diabetes

If a person has diabetes mellitus aim for a blood pressure target of systolic less than 130 mmHg (target range 120–129 mmHg) and diastolic less than 80 mmHg.^1,2 With a urinary ACR of 30 mg/mmol or more, prescribe a low-cost renin-angiotensin system antagonist, as described above.

Adults with type 2 diabetes and CKD who are taking an angiotensin receptor blocker (ARB) or an ACE inhibitor (titrated to the highest licensed dose that they can tolerate), should also be offered an SGLT2 inhibitor (dapagliflozin), in addition to the ARB or ACE inhibitor at highest tolerated doses.

All adult patients with CKD

As of February 2022, NICE has determined that the SGLT2 inhibitor, dapagliflozin, should be considered as a treatment option for all adults with CKD as an add-on to optimised standard care, including highest tolerated licensed dose of ACE inhibitors or ARBs, unless these are contraindicated, and have an eGFR of 25–75 15 mL/min/1.73m2 or a uACR of 26 mg/mmol or more.⁹

Immunisation

Ensure the person is offered immunisations for influenza, pneumococcal disease and COVID-19.

SELF-MANAGEMENT ADVICE

Offer self-management advice in relation to the underlying cause, disease severity, associated complications, and risk of progression of the person’s CKD.2 Provide them with sources of information, advice, and support, e.g. Kidney Care UK, www.kidneycareuk.org (telephone 01420 541424).

Advise on healthy lifestyle measures, such as stopping smoking, drinking alcohol in moderation, maintaining a healthy body weight, eating a healthy diet, and taking regular exercise.²

A low-protein diet (dietary protein intake of less than 0.6–0.8/kg/day) is not routinely recommended. However, specialist dietary advice about potassium, phosphate, calorie, and salt intake may be arranged for people with end-stage CKD, following referral.^2,3,10

Patients should be advised to avoid the use of over-the-counter NSAIDs, where possible, and to avoid herbal remedies. They should also be advised to use protein supplements with caution.^1,2

CKD AND COVID-19

People should continue taking their medicines (including ACE inhibitors, ARBs, immunosuppressants, and diuretics) as normal, unless they are advised to stop. This includes people who have symptoms of COVID 19.^8,9

People with CKD who have recovered from COVID-19 should have their renal function reassessed. The urgency of reassessment should be based on the person’s premorbid eGFR, comorbidities, and their clinical circumstances. Encourage self-monitoring and self-management, where possible.^8,9

You should continue to refer people for urgent outpatient appointments if there is a clinical need, e.g. if the person has accelerated progression of CKD. If there is uncertainty about the urgency, contact the local renal specialist team for advice.^8,9

CONCLUSION

Recognition of CKD is crucially important in primary care to improve the quality of patients’ lives, reduce complications, and avoid hospital admissions. Close monitoring and a heightened awareness of adverse trends in physiological parameters or symptoms are key. requirement when caring for people with CKD.

REFERENCES

1. Kidney Disease: Improving Global Outcomes. KDIGO 2012 clinical practice guideline for the evaluation and management of chronic kidney disease. Kidney Int Suppl 2013; 3(1): 1-150. https://kdigo.org/wp-content/uploads/2017/02/KDIGO_2012_CKD_GL.pdf

2. NICE, CKS. Chronic kidney disease management. https://cks.nice.org.uk/topics/chronic-kidney-disease/management/management-of-chronic-kidney-disease/#self-management-advice

3. Fraser SDS, Blakeman T. Chronic kidney disease: identification and management in primary care. Pragmat Obs Res 2016; 7: 21-32.

4. Gaitonde DY, Cook DL, Rivera IM, et al. Chronic kidney disease: detection and evaluation. Am Fam Physician 2017; 96(12): 776-783

5. Webster AC, Nagler EV, Morton RL et al. Chronic kidney disease. Lancet 2017; 389(10075): 1238-1252.

6. Vassalotti JA, Centor R, Turner BJ, et al. Practical approach to detection and management of chronic kidney disease for the primary care clinician. Am J Med 2016; 129(2): 153-162.

7. Chawla LS, Eggers PW, Star RA, et al. Acute kidney injury and chronic kidney disease as interconnected syndromes. N Engl J Med 2014; 371(1): 58-66.

8. NICE NG203. Chronic kidney disease: assessment and management; 2021. https://www.nice.org.uk/guidance/ng203

9. NICE. Dapagliflozin for treating chronic kidney disease: final appraisal document; February 2022. https://www.nice.org.uk/guidance/gid-ta10808/documents/final-appraisal-determination-document

10. Kidney Disease: Improving Global Outcomes. KDIGO 2017 clinical practice guideline update for the diagnosis, prevention, and treatment of chronic kidney disease-mineral and bone disorder. Kidney Int Suppl 2017; 7(1): 1-59.

11. NICE NG176. COVID-19 rapid guideline: chronic kidney disease; 2020. https://www.nice.org.uk/guidance/NG176