Chronic Kidney Disease

Definition/diagnostic criteria Chronic kidney disease (CKD) is a sustained and irreversible reduction in kidney function. Kidney function is usually expressed as eGFR derived from serum creatinine. Several equations are available to calculate eGFR, but none is precise.1 The CKD-EPI equation is recommended by NICE.2  The eGFR must be interpreted with caution, recognising their imprecision and that serum creatinine is also dependent on meat intake and muscle mass. Five stages of CKD are defined according to eGFR. The presence and severity of albuminuria, as determined by uACR, further subclassifies the stage of CKD.

CKD stages as defined by eGFR
Stage 1: ≥90 ml/min/1.73m2, but other evidence of CKD
Stage 2: 60 to <90 ml/min/1.73m2
Stage 3: 30 to <60 ml/min/1.73m2
Stage 4: 15 to <30 ml/min/1.73m2
Stage 5: <15 ml/min/1.73m2

Epidemiology CKD is estimated to affect more than 10% of UK adults.3 Prevalence increases with age and is higher in some ethnic groups, including those form Asian and black backgrounds. CKD should not be regarded as a single disease entity. An irreversible reduction in kidney function has an underlying cause which may be pre-renal (uncommon as a cause of CKD and usually related to major renal artery disease), renal (common and has many aetiologies such as diabetes, hypertension, primary glomerular disease, drug-induced kidney injury, inherited kidney disease and infection) and post-renal (fairly common in men and usually caused by benign prostatic hyperplasia). The likelihood of an individual having a specific cause of CKD varies by age, gender, ethnicity and pre-existing comorbidities.

Diagnosis Diagnosis is often incidental or arises from screening in high-risk populations as defined in NICE guidelines.2 The diagnosis is based on eGFR and the presence/absence of albuminuria assessed by uACR. All patients should also have a urine dipstick test to look for blood. Chronicity requires a sustained reduction in eGFR on two blood tests at least two weeks apart.2 Following a diagnosis of CKD most individuals should have a urinary tract ultrasound to define renal size and to exclude obstruction. Other investigations will depend on the clinical scenario, including reason for testing, clinical context, other comorbidities and differential diagnosis for underlying cause of CKD.

Treatment Treatment strategies can be divided into those that target the underlying cause of CKD and those that aim to delay progression of established CKD where no specific therapeutic target has been identified.

The natural history of some underlying causes may be altered by directed therapy; examples include immunosuppressive drugs in some forms of glomerular disease, tolvaptan in autosomal dominant polycystic kidney disease, antiviral medication in hepatitis/HIV-related nephropathy, drug withdrawal +/- steroids in medication-related interstitial nephritis and bladder catheterisation in bladder outflow obstruction.

Generic treatments aim to delay CKD progression regardless of underlying cause and focus on reduction of blood pressure and reduction of proteinuria when present. Target blood pressure is <140/90mmHg in all and <130/80mmHg in those with significant proteinuria.2 Medication that targets the renin-angiotensin-aldosterone system (RAASi) should be used preferentially in those with proteinuria. There is no benefit of ACE inhibitors over ARBs, but they should not be given in combination.2

An SGLT2 inhibitor (SGLT-2i) should be added in people with:

  1. CKD and symptomatic heart failure.
  2. CKD and type 2 diabetes and an eGFR of 20-45 ml/min/1.73m2 or an eGFR of >45 ml/min/1.73m2 and ACR ≥ 25 mg/mmol.
  3. CKD without type 2 diabetes and an eGFR of 20-45 ml/min/1.73m2 and a urine ACR <25 mg/mmol or an eGFR ≥20 ml/min/1.73m2 together with an ACR ≥25 mg/mmol (UKKA 2023).4

The non-steroidal mineralocorticoid receptor antagonist finerenone has been approved as an additional treatment for people with CKD and Type 2 diabetes with persistent proteinuria (ACR >30 mg/mmol) despite treatment with a RAASi and an SGLT-2i, providing eGFR is ≥25 ml/min/1.73m2 and serum potassium <5 mmol/l.5 GLP-1 analogues may also reduce the risk of adverse renal outcomes in people with Type 2 diabetes.6

Serum bicarbonate should be maintained above 20 mmol/l in those with an eGFR <30 ml/min/1.73m2.2

CKD is associated with a high risk of heart failure and CV death and additional CV risk factors should also be addressed, including consideration of statins and antiplatelet drugs.2

Serum potassium will increase as eGFR falls. Maintaining serum bicarbonate in the normal range may mitigate this increase in potassium. RAASi treatment should be continued where indicated even if this means prescribing oral potassium-binding medication.7,8

All prescribed and OTC medication should be reviewed to identify potential nephrotoxins and to adjust doses of drugs excreted by the kidneys to avoid accumulation and drug toxicity. It is important to recognise that neither RAASi nor SGLT-2i are nephrotoxic, but that they do cause a predictable physiological fall in eGFR which will be exacerbated in the setting of volume depletion. All people with CKD should be advised on the importance of ‘sick day rules’ to reduce the risk of acute on CKD.

Some patients with end-stage kidney disease (ESKD) may benefit from renal replacement therapy (RRT), either dialysis or kidney transplant. If transplant is possible this should be planned before dialysis whenever possible. Most renal centres will try and list patients for preemptive transplant when eGFR is <15ml/min/1.73m2. Dialysis may be appropriate to improve symptoms of ESKD (usually when eGFR is <10 ml/min/1.73m2) but is a demanding treatment and will not always improve quality or length of life. Some people will prefer supportive care in their home. These discussions and decisions should be made in advance whenever possible which requires timely referral if RRT is a consideration.2

Many people with CKD can be managed in primary care. NICE guidelines recommend referral for a specialist opinion in the following situations:

  • A 5-year risk of needing renal replacement therapy of greater than 5% (see Prognosis).
  • An ACR of 70 mg/mmol or more, unless known to be caused by diabetes and established on appropriate treatment.
  • An ACR of more than 30 mg/mmol PLUS haematuria.
  • A sustained decrease in eGFR of 25% or more and a change in eGFR category within 12 months.
  • A sustained decrease in eGFR of 15 ml/min/1.73m2 or more per year.
  • Hypertension that is poorly controlled (above the person’s individual target) despite the use of at least four antihypertensive medicines at therapeutic doses.
  • Known or suspected rare or genetic causes of CKD.
  • Suspected renal artery stenosis.

This list does not mandate referral and there may be other reasons to refer. Any decision to refer should be discussed with the patient and should be appropriate to the clinical context and coexistent medical history.

Prognosis People with CKD may have two main concerns about prognosis. Most focus on their risk of reaching ESKD. However, most people with CKD will not progress to ESKD. The risk of ESKD can be estimated using available prediction equations. NICE recommends a 4-variable model that takes account of age, gender, eGFR and albuminuria.2,9 These equations do not take account of cause of CKD. The risk of progression is not equal for all causes.

CKD is also associated with a significantly increased risk of death, predominantly from CVD. ESKD risk prediction equations do not take account of this competing, and often greater, risk which also depends on comorbidities and cause of CKD. A comprehensive discussion of prognosis with the person with CKD and those close to them requires an understanding of the likelihood of these potential outcomes.

Written by Dr Colin Jones, a consultant nephrologist at York Teaching Hospital NHS Foundation Trust.

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