Chronic Kidney Disease (CKD)

Guidelines

NICE CKD NG203 (2021)

KDIGO CKD (2024)

Abbreviations

eGFR Estimated Glomerular Filtration Rate, expressed as ml/min/1.73 m²
UACR Urine albumin:creatinine ratio
ESKD End-stage kidney disease
ASCVD Atherosclerotic cardiovascular disease

Answer True or False

FALSE
Requires ≥3 months persistence.
TRUE
Threshold ≥5% triggers referral.
FALSE
Use only after ACEi/ARB and SGLT2i.
FALSE
Safe down to eGFR 25.
TRUE
Indications for Finerenone: Type 2 diabetes, CKD stage 3 or 4, with albuminuria.
Also, serum-potassium ≤5 mmol/L and eGFR 25 to 59 mL/min/1.73 m2
TRUE
NICE NG203 recommendation.
FALSE
Only if creatinine-based eGFR unreliable.
FALSE
Benefits reduction of adverse cardiovascular and renal outcomes.
TRUE
NICE referral criterion.
FALSE
Use selectively.
FALSE
This is A2.
A3 is ACR >30 mg/mmol.
TRUE
Different mechanisms allow combined use.

Introduction

Chronic Kidney Disease (CKD) is a major global health concern associated with increased risk of cardiovascular disease, kidney failure, and mortality.
CKD is now the 4th most common global cause of non-communicable disease death.
Early diagnosis, accurate staging, and evidence-based management are essential to reduce morbidity and mortality.

Detailed advice on the management of CKD-related anaemia and hyperphosphataemia is beyond the scope of this webpage.

Definition

CKD is defined as:

Evidence of kidney damage (e.g., albuminuria ≥3 mg/mmol, abnormal urine sediment, imaging or histology abnormalities, or kidney transplant history), OR,
A sustained decrease in eGFR <60 mL/min/1.73m², persisting for at least 3 months.

To calculate eGFR, current NICE guidance recommends use of the 'Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) (2009)' equation.

Epidemiology and Risk Factors

Prevalence: ~10–15% of adult population.
Risk factors: diabetes, hypertension, cardiovascular disease, family history of CKD, recurrent urinary tract infections, nephrotoxic medications.

Screening (eGFR + UACR) and confirmation of CKD

  
        Category
        Criteria
      
        Screening (Offer eGFR + UACR Testing)
      
        Reduced eGFR
        eGFR <60 ml/min/1.73 m² (or children without diabetes but elevated age-appropriate creatinine)
      
        Diabetes
        Type 1 or Type 2 diabetes (annual screening recommended)
      
        Hypertension
        Diagnosed hypertension, regardless of control
      
        Nephrotoxic Medications
        Patients taking ciclosporin, tacrolimus, lithium, or long-term NSAIDs
      
        History of AKI
        Monitor kidney function for at least 3 years even if eGFR normalises
      
        ASCVD
        IHD, CHF, PAD, cerebrovascular disease
      
        Multisystem Diseases
        Conditions such as systemic lupus erythematosus (SLE) with potential kidney involvement
      
        Structural Renal Disorders
        Renal tract disease, recurrent renal stones, or prostatic hypertrophy
      
        Gout
        History of gout, particularly with chronic hyperuricaemia
      
        Family History
        First-degree relatives of patients with ESKD or hereditary kidney disease
      
        Incidental Findings
        Haematuria or proteinuria detected on routine testing
      
        Confirmation of CKD
      
        Repeat Testing
        Repeat eGFR and UACR after ≥3 months to confirm chronicity
      
        Urinalysis
        Use urine dipstick and microscopy if haematuria is present
      
        Point-of-Care Testing (POCT)
        Consider POCT for creatinine and uACR if laboratory access is limited

CGA Classification of CKD

The CGA system helps stratify risk, guide management decisions, and determine prognosis (KDIGO 2024).

CKD is classified by:
Cause (C): (e.g.diabetic nephropathy, hypertensive nephropathy)
GFR category (G): based on eGFR ml/min/1.73 m²
Urine Albuminuria (A): UACR, expressed in mg/mmol

Albuminuria independently predicts CKD progression, cardiovascular events, and all-cause mortality.
A confirmed ACR ≥ 3 mg/mmol is considered clinically important proteinuria.
Kidney failure is defined as G5 (eGFR <15 mL/min/1.73m²) or treatment by dialysis therapy.

CKD: Risk of Adverse outcomes (table)

As depicted in the table below, increased UACR and decreased eGFR, in combination, multiply the risk of adverse outcomes. Individuals classified as High risk or Very high risk require more
frequent monitoring, treatment intensification, +/- nephrology referral.

  
    
        eGFR Category
        A1 (UACR <3 mg/mmol)
        A2 (UACR 3–30 mg/mmol)
        A3 (UACR >30 mg/mmol)
      

    
        G1 (≥90)
        Low risk
        Moderate risk
        High risk
      

        G2 (60–89)
        Low risk
        Moderate risk
        High risk
      

        G3a (45–59)
        Moderate risk
        High risk
        Very high risk
      

        G3b (30–44)
        High risk
        Very high risk
        Very high risk
      

        G4 (15–29)
        Very high risk
        Very high risk
        Very high risk
      

        G5 (<15)
        Very high risk
        Very high risk
        Very high risk
      

  

Investigations

Full blood count, calcium, phosphate, PTH, lipids, glucose/HbA1c
Serum creatinine → eGFR calculation (prefer CKD-EPI without race adjustment)
Urine ACR (early morning sample preferred)
Renal ultrasound if rapid decline in eGFR, haematuria, anatomical concerns, or FH of hereditary kidney disease
Consider measuring Cystatin C eGFR in people where creatinine-based eGFR may be unreliable, such as: extremes of muscle mass (sarcopenia, amputees, bodybuilders), liver cirrhosis, heart failure, or cancer (KDIGO 2024).

Symptoms and Signs of CKD

Fatigue, shortness of breath, metallic taste in mouth, itching, nausea and/or vomiting, insomnia, weight loss, and confusion

Risk Prediction Tools

Kidney Failure Risk Equation (KFRE calculator)
A four-parameter calculator that determines the patient’s risk of progression to kidney failure requiring dialysis or transplant at 2 years and 5 years.
Refer to nephrology if 5-year KFRE ≥5%.

Management

1. Establish the cause of CKD
Manage any treatable causes: diabetes, hypertension, renal tract obstruction, nephrotoxic medication
Optimise Hypertension: clinic BP target of <130/80 mmHg (NICE) (KDIGO 2024 recommends SBP<120mmHg)
Optimise Diabetes: initiate metformin, SGLT2 inhibitor, GLP-1 RA therapies as recommended (NICE NG28).

2. Classify CKD and calculate 5-year KFRE (KFRE calculator)
Give adults with CKD information about their classification of CKD and 5-year risk of needing renal replacement therapy.

3. Lifestyle Interventions
Smoking cessation, weight management, and exercise: moderate-intensity physical activity (150 minutes/week)

4. Dietary optimisation:
Encourage a plant-based diet, with reduced consumption of ultra-processed foods
Salt restriction: <2 g sodium per day (or <90 mmol of sodium per day, or <5 g of sodium chloride per day)
Daily protein intake of approximately 0.8 g/kg ideal body weight (KDIGO 2024).

5. Pharmacotherapy

  
        Clinical Scenario
        Pharmacological Intervention
      
        CKD and Type 2 diabetes (eGFR ≥25, ACR ≥3 mg/mmol)
        ACEi/ARB + SGLT2 inhibitor
      
        CKD and Type 1 diabetes (eGFR ≥25, ACR ≥3 mg/mmol)
        
          ACEi/ARB

          In selected cases, secondary care specialists may add SGLT2i only if very high albuminuria or CVD risk.
        
        Type 2 diabetes + Stage 3 or 4 CKD + ACR ≥3 mg/mmol
        ACEi/ARB + SGLT2 inhibitor + Finerenone
      
        CKD with hypertension + ACR ≥30 mg/mmol
        ACEi/ARB first-line; Aim for Clinic BP target <130/80
      
        CKD with resistant hypertension despite the use of three or more agents (e.g. ACEi/ARB, BB, TZD)
        Requires 4th antihypertensive agent: Add steroidal MRA (e.g. spironolactone) if K⁺ ≤4.5 mmol/L, or Alpha/Beta blocker if K⁺ >4.5 mmol/L
      
        Without diabetes, without hypertension, CKD + ACR≥70 mg/mmol (NICE) or ACR≥20mg/mmol (KDIGO) or heart failure (irrespective of ACR)(KDIGO)
        ACEi/ARB + SGLT2i
      
        CKD and need for cholesterol lowering
        Atorvastatin 20 mg daily
      
        CKD and aspirin for secondary prevention (existing CVD)
        Aspirin for secondary prevention if history of CVD event(s)
      
  CKD and atrial fibrillation
  Use direct-acting oral anticoagulants (e.g., edoxaban, apixaban, rivaroxaban).
Reduce dose if creatinine clearance 15–29 mL/min, and avoid if creatinine clearance <15 mL/min.

        CKD and hyperuricaemia
        Allopurinol, initial dose 100 mg daily (reduce dose below 100 mg/day or increase dose interval in severe CKD)

6. Refer to Specialist

  
        Refer to Specialist
        Criteria
      
        Refer to Nephrology
        
          5-year KFRE risk ≥5%.
ACR ≥70 mg/mmol (unless attributed to diabetes and already appropriately treated).
ACR >30 mg/mmol with haematuria.
Sustained eGFR decrease ≥25% and a change in CKD category within 12 months.
Sustained eGFR decline of ≥15 ml/min/1.73m² per year.
Resistant hypertension despite ≥4 antihypertensive agents at therapeutic doses.
Suspected rare or genetic kidney disease.
Suspected renal artery stenosis.

        Refer to Urology
        
          CKD with renal outflow obstruction (unless urgent nephrological intervention required, e.g., for hyperkalaemia, severe uraemia, acidosis, or fluid overload).

Renin–angiotensin system antagonists (ACEi/ARB): extra notes

Aim of treatment:
Achieve the optimal tolerated dose of ACEi/ARB and ensure safe titration (monitoring eGFR and serum potassium).

Initiation Safety Checks:
Measure serum potassium and eGFR before starting an ACEi/ARB.
Recheck serum potassium and eGFR 1–2 weeks after initiation and after each dose increase.

Contraindications to Initiation: Do not routinely start an ACEi/ARB if pretreatment serum potassium >5.0 mM.

Monitoring After Starting or Titrating:
If eGFR falls by <25% or serum creatinine rises by <30% from baseline:
Repeat bloods in 1–2 weeks AND Continue current ACEi/ARB dose.
If eGFR falls by ≥25% or serum creatinine rises by ≥30%:
Investigate alternative causes for deterioration in kidney function (e.g., volume depletion, NSAIDs).
If no reversible cause is found, reduce ACEi/ARB dose to previously tolerated level or discontinue if necessary.

SGLT2 inhibitors: extra notes

SGLT2 inhibitors recommended by NICE: empagliflozin (TA942, 2023) and dapagliflozin (TA775, 2022).
They should be used in the management of CKD, AFTER maximising ACEi/ ARB therapy.

  
        Outcome Improved with SGLT2 inhibitors
        Additional notes
      
        Kidney Disease Progression
        Slows decline in eGFR and delays onset of kidney failure (dialysis or transplant).
      
        Albuminuria
        Reduces urinary albumin excretion (UACR).
      
        Acute Kidney Injury (AKI)
        Decreases risk of AKI episodes.
      
        Heart Failure
        Reduces hospitalisation for heart failure.
      
        Major Cardiovascular Events
        Reduces incidence of myocardial infarction and stroke.
      
        Cardiovascular Mortality
        Lowers risk of death from cardiovascular causes.
      
        All-Cause Mortality
        Improves overall survival rates.

Finerenone: extra notes

Finerenone (NICE TA877, 2023) is recommended as an option for treating chronic kidney disease (CKD) associated with type 2 diabetes, after maximised use of an ACEi/ARB and an SGLT2 inhibitor (unless contraindicated).
Finerenone is a non-steroidal, selective mineralocorticoid receptor antagonist (nsMRA) that reduces the risk of cardiovascular events and slows CKD progression in people with type 2 diabetes and albuminuric CKD stages 3–4. It does not significantly reduce all-cause mortality. Finerenone should be considered in individuals with ALL of the following criteria:

Type 2 diabetes
CKD stage 3 and CKD Stage 4 (eGFR 25–60 ml/min/1.73m²)
Persistent albuminuria (ACR ≥3 mg/mmol).

  
        Outcome Improved with Finerenone
        Additional notes
      
        Kidney Disease Progression
        Further slows decline in eGFR and reduces progression to kidney failure.
      
        Albuminuria
        Significantly reduces urinary albumin excretion (UACR).
      
        Heart Failure
        Reduces hospitalisations for heart failure, particularly HFpEF patients.
      
        Major Cardiovascular Events
        Lowers incidence of cardiovascular death, myocardial infarction, and stroke.
      
        Cardiovascular Mortality
        Reduces death from cardiovascular causes in high-risk diabetic CKD patients.
      
        Renal Composite Outcomes
        Delays time to composite kidney outcomes (≥40% eGFR decline, kidney failure, renal death).

Bone Health and Vitamin D in CKD

Blood Monitoring:

No routine bone bloods (calcium, phosphate, PTH, vitamin D) if eGFR ≥30 (CKD G1–G3).
Measure calcium, phosphate, PTH if eGFR <30 (CKD G4–G5) — adjust frequency based on results and clinical context.

Osteoporosis Management:

Offer bisphosphonates in CKD G1–G3 if osteoporosis treatment/prevention is indicated.
Refer to renal services for bone health concerns in CKD G4–G5.

Vitamin D Management:

Treat vitamin D deficiency with colecalciferol or ergocalciferol.
Activated vitamin D (alfacalcidol or calcitriol) is only indicated if symptoms persist after correction and eGFR <30.
Monitor calcium and phosphate when using activated vitamin D.

Dr Rajesh Varma23 January 2020CKD