Definition & Key Features

What is Chronic Kidney Disease? Chronic Kidney Disease (CKD) is defined as the presence of abnormalities of kidney function or structure for more than 3 months, with implications for health. This includes:

• Individuals with a glomerular filtration rate (GFR) of less than 60 ml/min/1.73 m² on at least two occasions separated by a minimum of 90 days.
• Individuals with markers of kidney damage, irrespective of GFR, for more than 3 months. Markers include:
  • Albuminuria (Albumin:Creatinine Ratio [ACR] > 3 mg/mmol)
  • Urine sediment abnormalities
  • Electrolyte and other abnormalities due to tubular disorders
  • Histological or structural abnormalities (detected by imaging)
  • A history of kidney transplantation

Hallmark Features & Classification CKD is classified using a combination of GFR and ACR categories to stratify the risk of adverse outcomes (e.g., CKD progression, cardiovascular events, mortality).

• GFR Categories (ml/min/1.73 m²):
  • G1: ≥90 (Normal or high)
  • G2: 60–89 (Mild reduction)
  • G3a: 45–59 (Mild to moderate reduction)
  • G3b: 30–44 (Moderate to severe reduction)
  • G4: 15–29 (Severe reduction)
  • G5: <15 (Kidney failure)
• ACR Categories (mg/mmol):
  • A1: <3 (Normal to mildly increased)
  • A2: 3–30 (Moderately increased)
  • A3: >30 (Severely increased)
    • An ACR >70 mg/mmol is also a specific threshold mentioned for certain interventions and referrals.

Core Pathophysiology & Complications Untreated or progressive CKD leads to a failure of the kidney’s homeostatic, excretory, and endocrine functions, resulting in complications such as:

• Increased risk of Acute Kidney Injury (AKI)
• Cardiovascular Disease (CVD)
• End-Stage Renal Disease (ESRD) requiring renal replacement therapy (RRT)
• Anaemia of CKD: Presents with fatigue, dyspnoea, lethargy, and palpitations.
• CKD–Mineral and Bone Disorder (CKD-MBD): Includes secondary hyperparathyroidism, vitamin D deficiency, and hyperphosphataemia.
• Metabolic Acidosis
• Hyperkalaemia

Epidemiology & Risk Factors

Who should be tested for CKD? Offer testing with eGFRcreatinine and ACR to:

• Adults with:
  • Diabetes
  • Hypertension
  • Previous episode of AKI
  • CVD (ischaemic heart disease, heart failure, peripheral or cerebral vascular disease)
  • Structural renal tract disease, recurrent renal calculi, or prostatic hypertrophy
  • Multisystem diseases with potential kidney involvement (e.g., Systemic Lupus Erythematosus)
  • Gout
  • Family history of G5 CKD or hereditary kidney disease
  • Incidental finding of haematuria or proteinuria
• Children and Young People with:
  • Previous episode of AKI
  • Solitary functioning kidney
• Consider testing in Children and Young People with:
  • Low birth weight (≤ 2,500 g)
  • Diabetes or Hypertension
  • Cardiac disease
  • Structural renal tract disease or recurrent calculi
  • Multisystem diseases (e.g., Systemic Lupus Erythematosus)
  • Family history of G5 CKD or hereditary kidney disease
  • Incidental haematuria or proteinuria

Risk Factors for CKD Progression (in adults):

• Cardiovascular disease
• Proteinuria (higher ACR category)
• Previous episode of AKI
• Hypertension
• Diabetes
• Smoking
• African, African-Caribbean, or Asian family origin
• Chronic use of Non-Steroidal Anti-Inflammatory Drugs (NSAIDs)
• Untreated urinary outflow tract obstruction

Factors NOT to be used as sole indicators for testing:

• Age, gender, or ethnicity in isolation.
• Obesity in the absence of metabolic syndrome, diabetes or hypertension.

Clinical Presentation & Diagnosis

Clinical Presentation CKD is often asymptomatic in its early stages. Symptoms of anaemia (fatigue, lethargy, dyspnoea, palpitations) may develop as GFR declines.

Red Flags & Indications for Urgent Action/Referral: These are detailed in the Further Management & Escalation section under referral criteria.

Diagnostic Investigations

• Estimating GFR:
  • Use the CKD-EPI creatinine equation for adults. Report eGFR as a whole number if ≤90 ml/min/1.73 m², or as ‘>90’ if higher.
  • Caution: eGFRcreatinine is less reliable in extremes of muscle mass, pregnancy, oedematous states, and malnutrition.
  • Patient advice: Do not eat meat for 12 hours before the blood test.
  • Confirmation: Repeat an eGFR < 60 ml/min/1.73 m² within 2 weeks to confirm the result is stable.
  • Interpretation: Allow for ±5% biological/analytical variability in eGFR. For eGFR > 90, a >20% increase in serum creatinine indicates a significant reduction in kidney function.
• Assessing Proteinuria:
  • Use urine ACR for initial detection in all adults, children and young people. It is more sensitive than Protein:Creatinine Ratio (PCR).
  • Do not use reagent strips for initial identification of proteinuria unless they can specifically measure albumin and express it as an ACR.
  • Clinically important proteinuria: A confirmed ACR of ≥ 3 mg/mmol.
  • Confirmation: If the initial ACR is between 3 and 70 mg/mmol, repeat with an early morning urine sample to confirm. A repeat is not needed if the initial ACR is ≥ 70 mg/mmol.
  • PCR can be used as an alternative to ACR if the ACR is ≥ 70 mg/mmol.
• Assessing Haematuria:
  • Use reagent strips. A result of 1+ or higher requires further evaluation.
  • Do not use urine microscopy to confirm a positive result.
  • Persistent invisible haematuria: Confirmed if 2 out of 3 reagent strip tests are positive. This should prompt investigation for urinary tract malignancy in appropriate age groups.
  • Follow-up for persistent invisible haematuria without proteinuria: Annual monitoring of haematuria, ACR, eGFR, and blood pressure.
• Renal Ultrasound:
  • Offer to adults with CKD who have:
    • Accelerated progression (see definition below)
    • Visible or persistent invisible haematuria
    • Symptoms of urinary tract obstruction
    • Family history of polycystic kidney disease (if >20 years old)
    • GFR < 30 ml/min/1.73 m² (G4 or G5)
    • Are being considered for renal biopsy by a nephrologist.

Initial Management

Non-Pharmacological Measures & Patient Education

• Lifestyle: Encourage exercise, achieving a healthy weight, and smoking cessation.
• Dietary Advice: Provide advice on potassium, phosphate, calorie, and salt intake tailored to CKD severity. This should be supervised by a professional to avoid malnutrition.
• Low-Protein Diets: Do not offer low-protein diets (<0.6–0.8 g/kg/day) to adults with CKD.
• Education: Provide information on the diagnosis, its implications, treatments, and self-management. Enable shared decision-making.
• Self-Management: Support self-management by providing access to medical data (e.g., Renal PatientView).

First-Line Pharmacological Management

• Blood Pressure Control:
  • Adults with ACR < 70 mg/mmol: Aim for clinic SBP < 140 mmHg (target range 120–139 mmHg) and DBP < 90 mmHg.
  • Adults with ACR ≥ 70 mg/mmol: Aim for clinic SBP < 130 mmHg (target range 120–129 mmHg) and DBP < 80 mmHg.
  • Children/Young people with ACR ≥ 70 mg/mmol: Aim for clinic SBP below the 50th percentile for height.
• Renin-Angiotensin-Aldosterone System (RAAS) Antagonists (ACE inhibitors or ARBs):
  • Indications:
    • Hypertension with proteinuria: Offer an ACEi or ARB to adults, children, and young people with hypertension and an ACR > 30 mg/mmol (A3).
    • Diabetic Kidney Disease: Offer an ACEi or ARB to adults and children/young people with diabetes and an ACR ≥ 3 mg/mmol.
    • Non-Diabetic Kidney Disease with High Proteinuria: Offer an ACEi or ARB to adults and children/young people without diabetes if ACR is ≥ 70 mg/mmol (refer adults to nephrology). If ACR is 30-70 mg/mmol, monitor and consider specialist discussion if progression occurs.
  • Dosage: Titrate to the highest licensed dose the person can tolerate.
  • Contraindications & Cautions:
    • DO NOT offer a combination of different RAAS antagonists (e.g., ACEi + ARB).
    • DO NOT start if pre-treatment serum potassium is > 5.0 mmol/L.
    • STOP treatment if serum potassium rises to ≥ 6.0 mmol/L and other causes have been addressed.
  • Monitoring:
    • Measure serum potassium and eGFR before starting.
    • Repeat measurements 1–2 weeks after starting and after each dose increase.
  • Interpreting eGFR changes after starting/titrating ACEi/ARB:
    • Acceptable change: A decrease in eGFR < 25% or an increase in creatinine < 30% from baseline. Do not modify the dose; repeat the test in 1–2 weeks.
    • Unacceptable change: A decrease in eGFR ≥ 25% or an increase in creatinine ≥ 30% from baseline.
      • Investigate for other causes (e.g., volume depletion, concurrent NSAIDs).
      • If no other cause is found, stop the RAAS antagonist or reduce the dose to a previously tolerated lower dose.
• SGLT2 Inhibitors:
  • For adults with CKD and Type 2 Diabetes, refer to NICE guidance on Type 2 diabetes.
  • Dapagliflozin and Empagliflozin are NICE-approved options for certain adults with CKD (with or without diabetes) as an add-on to optimised standard care (including ACEi/ARB). Refer to Technology Appraisals TA775 and TA942.
• Statins & Antiplatelets:
  • Statins: Follow NICE guideline [CG181] on cardiovascular disease risk reduction for adults with CKD.
  • Antiplatelets: Offer for secondary prevention of CVD, but be aware of the increased risk of bleeding.

Further Management & Escalation

Referral to Specialist Nephrology Services

• Refer Adults if they have any of the following:
  • A 5-year risk of needing RRT of > 5% (using the 4-variable Kidney Failure Risk Equation).
  • ACR ≥ 70 mg/mmol (unless known to be caused by diabetes and appropriately treated).
  • ACR > 30 mg/mmol (A3) with persistent invisible haematuria.
  • Accelerated progression:
    • A sustained decrease in GFR of ≥ 25% and a change in GFR category within 12 months.
    • A sustained decrease in GFR of ≥ 15 ml/min/1.73 m²/year.
  • Hypertension that remains poorly controlled (> target) despite at least 4 antihypertensive agents at therapeutic doses.
  • Known or suspected rare or genetic cause of CKD.
  • Suspected renal artery stenosis.
• Refer Children and Young People if they have any of the following:
  • ACR ≥ 3 mg/mmol (confirmed on a repeat early morning sample).
  • Haematuria.
  • Any decrease in eGFR.
  • Hypertension.
  • Known or suspected rare or genetic cause of CKD, suspected renal artery stenosis, or renal outflow obstruction.
• Refer to urology for known or suspected renal outflow obstruction.

Management of CKD Complications (Specialist-led)

• Anaemia (G3b-G5):
  • Investigate: If Hb falls to ≤ 110 g/L (or ≤ 105 g/L if <2 years) or symptoms develop.
  • Iron Status: Assess using % hypochromic red cells, reticulocyte Hb, or transferrin saturation (<20%) and ferritin (<100 µg/L).
  • Iron Therapy: Offer iron (IV or oral) to correct deficiency before considering ESAs. IV iron is preferred for haemodialysis patients.
  • Erythropoiesis-Stimulating Agents (ESAs): Offer to people likely to benefit if anaemia persists despite iron repletion.
    • Target Hb: Aim for a range of 100–120 g/L for adults and children ≥2 years (95–115 g/L for children <2 years). Do not exceed 120 g/L.
  • Roxadustat: An option for symptomatic anaemia in adults with G3-G5 CKD not on dialysis.
• Hyperphosphataemia (G4-G5):
  • First-line: Specialist dietary advice and optimisation of dialysis.
  • Phosphate Binders: If serum phosphate remains high.
    • Adults: Start with calcium acetate. If contraindicated/not tolerated, use sevelamer carbonate. Combinations can be used.
    • Children: Start with a calcium-based binder.
• CKD–Mineral and Bone Disorder (G4-G5):
  • Monitoring: Measure serum calcium, phosphate, and parathyroid hormone (PTH) in G4/G5 CKD.
  • Vitamin D: Treat deficiency with colecalciferol or ergocalciferol. If symptoms persist after correction, consider alfacalcidol or calcitriol for GFR < 30 ml/min/1.73 m².
  • Osteoporosis: Offer bisphosphonates if GFR is ≥ 30 ml/min/1.73 m².
• Metabolic Acidosis (G4-G5):
  • Consider oral sodium bicarbonate supplementation for adults with GFR < 30 ml/min/1.73 m² and a serum bicarbonate concentration < 20 mmol/L.

Follow-up & Safety Netting

Frequency of Monitoring Minimum monitoring frequency (eGFRcreatinine) should be guided by GFR and ACR categories and tailored to the individual.

• GFR G1 or G2 (eGFR ≥60):
  • ACR A1 (<3): 0-1 checks per year.
  • ACR A2 (3-30): 1 check per year.
  • ACR A3 (>30): 1 or more checks per year.
• GFR G3a (eGFR 45-59):
  • ACR A1: 1 check per year.
  • ACR A2: 1 check per year.
  • ACR A3: 2 checks per year.
• GFR G3b (eGFR 30-44):
  • ACR A1: 1-2 checks per year.
  • ACR A2: 2 checks per year.
  • ACR A3: 2 or more checks per year.
• GFR G4 (eGFR 15-29):
  • ACR A1: 2 checks per year.
  • ACR A2: 2 checks per year.
  • ACR A3: 3 checks per year.
• GFR G5 (eGFR <15):
  • ACR A1, A2, or A3: 4 or more checks per year.

Monitoring Requirements:

• At each review: eGFRcreatinine, ACR, and blood pressure.
• Specific monitoring for medications (e.g., K+ and eGFR for RAAS antagonists) and complications as outlined above.

Patient Education & Safety Netting:

• Advise patients about their diagnosis, risk of progression, and management plan.
• Provide education on self-management, including diet, lifestyle, and medications.
• Warn patients about the risk of AKI with intercurrent illness, especially if taking RAAS antagonists, diuretics, or NSAIDs (“sick day rules”).
• Explain the warning signs that should prompt urgent reassessment, including symptoms of urinary obstruction or severe illness.
• Advise adults to avoid chronic use of NSAIDs if they have CKD, especially if GFR is low or other risk factors for progression are present.
• Offer Annual Vaccinations: Influenza and Pneumococcal

Key Points to Remember

• Diagnose & Classify: CKD is GFR <60 ml/min/1.73 m² or kidney damage markers for >3 months. Use GFR and ACR categories to classify and assess risk.
• Test High-Risk Groups: Actively test for CKD in patients with diabetes, hypertension, CVD, or a history of AKI.
• Use ACEi/ARBs: These are first-line for hypertension with proteinuria (ACR >30) and for diabetic kidney disease (ACR ≥3). Titrate to the maximum tolerated dose.
• Monitor after ACEi/ARB Initiation: Check eGFR and potassium 1–2 weeks after starting or changing the dose. An eGFR drop of <25% or creatinine rise of <30% is expected and acceptable.
• Do Not Combine RAAS Antagonists: Never prescribe an ACEi in combination with an ARB.
• Know Referral Criteria: Refer for ACR ≥70, ACR >30 with haematuria, rapid eGFR decline (≥15 ml/min/year or ≥25% in 12 months), resistant hypertension, or high risk of RRT (>5% in 5 years).
• Manage Complications: Be aware of and manage complications like anaemia (iron first), hyperphosphataemia (diet then binders), and metabolic acidosis.
• Use the Risk Equation: For adults, use the 4-variable Kidney Failure Risk Equation to calculate the 5-year risk of needing dialysis or a transplant and discuss this with them.
• Avoid NSAIDs: Caution patients with CKD against the long-term use of NSAIDs.
• Individualise Monitoring: Use the GFR/ACR grid to guide the minimum frequency of monitoring, but tailor it to the individual’s rate of progression and risk factors.

This MedDigest summary is intended for educational purposes only and should not be used for clinical purposes. It is an independent resource, prepared by MedDigest, to offer an accessible overview of information drawn from the NICE guidelines. The original NICE content is © Crown copyright and is used under the Open Government Licence v3.0. While MedDigest strives for accuracy in its educational summaries, this content has not been reviewed or produced by NICE. For comprehensive and definitive recommendations, please always refer to the complete NICE guidelines.

References

NICE (24 November 2021) Chronic kidney disease: assessment and management. https://www.nice.org.uk/guidance/ng203