Chronic Kidney Disease (CKD)

1. Clinical Overview

Summary

Chronic Kidney Disease (CKD) is defined as a reduction in kidney function (eGFR less than 60 ml/min/1.73m2) OR markers of kidney damage (Albuminuria, Haematuria, Structural abnormalities) present for > 3 months.

It is a silent killer. Most patients are asymptomatic until advanced stages (eGFR less than 15). However, even mild CKD is a potent risk factor for Cardiovascular Disease (Section 9). Patients are far more likely to die of a heart attack than to reach dialysis.

The modern classification (KDIGO) uses a "Heat Map" combining eGFR (G-Stage) and Albuminuria (A-Stage) to predict prognosis. Albuminuria is toxic to the tubule and drives progression.

Management pivots on:

1. Slowing Progression: Strict BP control (RAS inhibition) and SGLT2 inhibitors.
2. Managing Complications: Anaemia, Bone Disease (CKD-MBD), Acidosis.
3. Preparation for RRT: Early education about Dialysis/Transplant when eGFR less than 20.

Key Facts

• Prevalence: 10% of the globalpopulation.
• Causes: Diabetes (40%) and Hypertension (30%) account for the vast majority.
• SGLT2 Inhibitors: The biggest breakthrough in 20 years. Dapagliflozin slows progression by ~30% even in non-diabetics.
• eGFR vs Creatinine: eGFR is inaccurate at extremes of muscle mass. Creatinine 120 in a bodybuilder is normal; in a frail granny it is Stage 4 CKD.
• "Acute on Chronic": Always exclude reversible causes (Dehydration, NSAIDs, Obstruction) when eGFR drops.

Clinical Pearls

The "ACEi Dip" Pearl: When starting Ramipril/SGLT2i, eGFR will drop (up to 20-30%) due to efferent arteriolar vasodilation. This helps reduce glomerular pressure. DO NOT STOP the drug unless the drop is > 30% or Potassium is uncontrollable.

The "No Symptoms" Pearl: Uraemic symptoms (nausea, itch, fatigue) generally do not appear until eGFR less than 10-15. If a patient with eGFR 40 complains of fatigue, look for another cause (Anaemia/Depression).

The "Fistula" Pearl: "Save the Vein". In any patient with eGFR less than 30, preserve the non-dominant arm veins for future fistula creation. No venepuncture or cannulation in that arm.

The "Bone" Pearl: Low Calcium + High Phosphate = Renal Bone Disease. The earliest sign is a rise in PTH (Secondary Hyperparathyroidism).

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2. Epidemiology

Burden of Disease

• 1 in 10 adults have some form of kidney damage.
• Risk increases with age (> 50% of over 75s have CKD Stage 3).
• Cost: Treating End Stage Kidney Disease (Dialysis) consumes 2% of total NHS budget for less than 0.1% of the population.

Aetiology (Causes)

1. Diabetic Kidney Disease (Diabetic Nephropathy)

• Most common cause.
• Driven by Hyperfiltration and accumulation of AGEs (Advanced Glycation End-products).

2. Hypertensive Nephrosclerosis

• Ischaemic scarring of glomeruli due to stiff afferent arterioles.
• Common in Afro-Caribbean ethnicity.

3. Glomerulonephritis (GN)

• IgA Nephropathy (commonest primary GN).
• Membranous Nephropathy.
• Lupus Nephritis (SLE).

4. Tubulointerstitial Disease

• Reflux Nephropathy (scars from childhood UTI).
• Drugs (NSAIDs, Lithium).
• Polycystic Kidney Disease (ADPKD) - Genetic.

5. Obstructive Uropathy

• Prostate (BPH).
• Stones.

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3. Pathophysiology

The "Final Common Pathway"

Regardless of the cause (Diabetes, HTN, GN), the progression mechanism is similar:

1. Nephron Loss: Initial insult kills nephrons.
2. Hyperfiltration: Surviving nephrons hypertrophy and increase their filtration rate (SNGFR) to compensate.
3. Glomerular Hypertension: High pressure damages the delicate podocytes.
4. Proteinuria: Damaged barrier leaks Albumin.
5. Inflammation: Albumin is toxic to the proximal tubule cells, triggering inflammation and fibrosis.
6. Glomerulosclerosis: Specific scarring of the filtering unit.

Uraemia (The Toxin Load)

When GFR falls less than 15, toxins accumulate:

• Urea: Nausea, Anorexia.
• Middle Molecules (Beta-2 Microglobulin): Amyloid.
• Potassium: Arrhythmia.
• Acid: Metabolic Acidosis (Bone buffering).
• Phosphate: Calcification.

The Cardiorenal Link

CKD causes stiffening of large arteries (Arteriosclerosis) and Calcification.

• FGF-23: A hormone released by bone to excrete phosphate. High FGF-23 causes Left Ventricular Hypertrophy (LVH).
• Outcome: Most CKD patients die of Heart Failure or Sudden Death before needing dialysis.

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4. Classification (KDIGO 2012)

(CRITICAL REFERENCE SECTION) Staging combines G (GFR) and A (Albuminuria).

G-Stage (Glomerular Filtration Rate)

A-Stage (Albuminuria - ACR)

Urine Albumin:Creatinine Ratio (ACR).

Note: A patient with G3a and A3 has worse prognosis than G3b and A1.

Causes of "Acute on Chronic" Kidney Injury

When stable eGFR suddenly drops (e.g. 35 -> 20).

• Pre-Renal (Hypoperfusion):
  • Dehydration (Gastroenteritis).
  • Hypotension (Sepsis, CCF).
  • Renal Artery Stenosis (with ACE inhibitor).
• Renal (Intrinsic):
  • Drugs (NSAIDs, Gentamicin).
  • New GN flare (Vasculitis).
• Post-Renal (Obstruction):
  • Prostate (Urinary Retention).
  • Stones (Unlikely to cause failure unless solitary kidney).

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5. Clinical Presentation

Symptoms (Uraemic Syndrome)

Not usually present until Stage G4/G5.

• General: Fatigue, Cold intolerance.
• Skin: Pruritus (Itch - Phosphate/Uraemia), Sallow pigmentation ("Lemon tinge").
• GI: Anorexia (especially for meat), Nausea (morning), Hiccups.
• Neuro: Restless legs, Peripheral neuropathy, Confusion (late).
• Fluid: Ankle swelling, Breathlessness (Pulmonary oedema).

Examination Signs

• Hands: Arteriovenous Fistula (AVF)? Leukonychia (Low albumin). Lindsay's Nails (Half and Half - distal brown, proximal white).
• Arms: Excoriations (Scratch marks).
• Face: Pallor (Anaemia). Periorbital oedema (Nephrotic).
• Chest: Fluid overload (Crackles). Pericardial Rub (Uraemic Pericarditis - Check BUN!).
• Abdomen: Palpable Kidneys (Polycystic?). Transplant scar (RLQ/LLQ).

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6. Investigations

Bloods

• U&Es: Creatinine (Trend is key), Urea, Potassium, eGFR.
• Bone Profile: Calcium (Low?), Phosphate (High?), ALP (High? - Bone turnover).
• PTH: Secondary Hyperparathyroidism.
• FBC: Normocytic Normochromic Anaemia.
• Bicarbonate: Metabolic Acidosis (less than 22).

Urine

• Urinalysis (Dipstick): Blood? Protein?
• uACR: Quantify proteinuria (Prognostic).
• PCR (Protein:Creatinine): Accurate for massive proteinuria.

Imaging

• Renal Ultrasound:
  • Small/Echogenic: Chronic scarring (Irreversible).
  • Large: Diabetes, Polycystic, Amyloid, HIV.
  • Asymmetry: Renovascular disease (stenosis).
  • Hydronephrosis: Obstruction.

Biopsy

• Indicated if diagnosis unclear AND result would change management (e.g., suspecting Vasculitis or Lupus). not done if small fibrotic kidneys (risk > benefit).

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7. Management: Slowing Progression

1. Blood Pressure Control

The single most important intervention.

• Target: less than 140/90 mmHg. Include ACR target less than 130/80 if proteinuria (A3).
• Drug of Choice: ACE Inhibitor (Ramipril) or ARB (Losartan).
  • Mechanism: Reduce intraglomerular pressure.
  • Caution: Stop if K+ > 6.0 or Creatinine rises > 30%.

2. SGLT2 Inhibitors

Standard of care for CKD (Diabetic AND Non-Diabetic).

• Drug: Dapagliflozin 10mg / Empagliflozin 10mg.
• Evidence: DAPA-CKD, EMPA-KIDNEY trials.
• Limit: Can initiate down to eGFR 20. Continue until Dialysis.

3. Cardiovascular Risk Management

• Lipids: Atorvastatin 20mg (Primary Prevention).
• Smoking: Cessation mandatory.
• Aspirin: Only if established CVD (Secondary prevention). Primary prevention not recommended (Bleeding risk high in uraemia).

4. Diet and Fluds

• Salt: less than 6g/day.
• Fluid: Drink to thirst. Avoid dehydration.
• Protein: Avoid high protein loading (increases hyperfiltration), but avoid malnutrition.

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8. Management: Complications

(Expanded Section)

1. Renal Anaemia

Mechanism: Reduced EPO production + Functional Iron Deficiency.

• Target: Hb 100 - 120 g/L.
• Treatment:
  1. Iron: IV Iron (e.g. Ferric Derisomaltose/Monofer) is often required as oral absorption is poor (Hepcidin block). Aim Ferritin > 100, TSAT > 20%.
  2. ESA (Erythropoiesis Stimulating Agent): Epoetin / Darbepoetin injections. Risk: Hypertension, Thrombosis.

2. CKD-MBD (Mineral Bone Disorder)

Mechanism: Low Vit D activation -> Low Ca -> High PTH. Also High Phosphate.

• Hyperphosphataemia:
  • Dietary restriction (Cola, Dairy, Processed foods).
  • Phosphate Binders: Take with meals. (Calcium Acetate, Sevelamer, Lanthanum).
• Hyperparathyroidism (SHPT):
  • Active Vit D: Alfacalcidol / Calcitriol. (Suppresses PTH).
  • Calcimimetics: Cinacalcet (Sensitises parathyroid to calcium).

3. Metabolic Acidosis

Kidney fails to excrete H+ and regenerate Bicarbonate.

• Consequence: Muscle wasting (catabolism is triggered by acid) and Bone demineralisation (bone buffers acid).
• Treatment: Oral Sodium Bicarbonate capsules. Target Bicarb > 22.

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9. Renal Replacement Therapy (RRT)

(For Stage G5 - "The Options")

1. Kidney Transplant

Gold Standard.

• Living Donor (LDKT): Best outcomes. Can be pre-emptive (before dialysis).
• Deceased Donor (DDKT): Waiting list (Average 3 years).
• Immunosuppression: Tacrolimus + Mycophenolate + Prednisolone.

2. Haemodialysis (HD)

• Blood cleaned via extracorporeal circuit.
• Access: AV Fistula (Gold standard) or Tunnelled Line.
• Schedule: 4 hours, 3 times a week (In-centre or Home).
• Pros: Staff do the work.
• Cons: Hospital visits. "Washout" fatigue post-dialysis.

3. Peritoneal Dialysis (PD)

• Fluid (Glucose) instilled into peritoneum via catheter. Peritoneum acts as semi-permeable membrane.
• CAPD: Manual exchanges 4x day.
• APD: Machine cycles while sleeping.
• Pros: Independence. Gentler on heart.
• Cons: Infection (Peritonitis). Body image.

4. Conservative Care

• Decision NOT to dialyse.
• Focus on symptom control (Palliative).
• Appropriate for frail, elderly with multiple comorbidities where dialysis would not improve Quality of Life.

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10. Drug Prescribing in CKD

(Safety Critical)

"The Sick Day Rules"

Stop these drugs during acute illness (Dehydration/Sepsis) to prevent AKI.

• Diuretics.
• ACE Inhibitors / ARBs.
• Metformin.
• NSAIDs.
• SGLT2 Inhibitors.

Dose Adjustments

• Metformin: Reduce if eGFR less than 45. Stop if less than 30 (Lactic Acidosis risk).
• NOACs: Apixaban/Rivaroxaban need dose reduction. Avoid in eGFR less than 15 (Use Warfarin).
• Opiates: Morphine accumulates (Toxic metabolites). Use Fentanyl/Oxycodone with caution.
• Antibiotics: Clarithromycin/Cipro/Trimethoprim may need reduction.

The "Renal Diet" (Deep Dive)

Managing Electrolytes through Diet.

1. Potassium Restriction (for K+ > 5.5):
   • Avoid: Bananas, Tomatoes, Avocados, Chocolate, Coffee, Crisps (Chips), Dried Fruit.
   • Safe: Apples, Pears, Rice, Pasta, Bread.
   • Cooking: Boiling vegetables and throwing away the water ("Potassium leaching") reduces K+ load.
2. Phosphate Restriction (for High Phosphate):
   • Avoid: Cola drinks, Processed Cheese, Nutella, Liver, Shellfish.
   • Note: Phosphate binders must be taken WITH food to work.
3. Salt Restriction:
   • Standard (less than 6g/day) for BP control. Avoid "Lo-Salt" substitutes (they are Potassium Chloride!).

Antibiotic Dosing in CKD (GFR less than 30) Table

Always check the BNF / Local Policy.

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11. Evidence & Guidelines

Guidelines

1. KDIGO 2012 / 2024 Update: Global standard.
2. NICE NG203 (2021): Chronic kidney disease: assessment and management.
   • Recommended SGLT2i for routine use.
   • Updated eGFR reporting (Race-free).

Key Trials

• DAPA-CKD (2020): Dapagliflozin reduced risk of renal progression/death by 39% in CKD patients (with OR without diabetes). NNT = 19.
• EMPA-KIDNEY (2022): Confirmed benefit of Empagliflozin in broader range of patients (down to GFR 20).
• MDRD Study: Provided the original modification of diet data (low protein doesn't help much) and the equation for eGFR.

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12. Patient Explanation

What is CKD?

Your kidneys are filters. CKD means the filters are scarred and working less efficiently. We measure this with a percentage called eGFR.

• Stage 1-2: Mild damage (90-60%).
• Stage 3: Moderate (30-60%).
• Stage 4: Severe (15-30%).
• Stage 5: Kidney Failure (less than 15%).

Will I end up on dialysis?

Most people (90%+) with CKD never need dialysis. The condition usually progresses very slowly or stays stable. We are more worried about your Heart than your kidneys. The main goal is protecting your heart.

What can I do?

1. Blood Pressure: Take your tablets. This is the Pressure forcing damage into the filter.
2. Salt: Eat less salt. Salt raises BP and fights against your tablets.
3. Smoking: Stop. Smoking hardens the arteries feeding the kidney.
4. Sick Days: If you have D&V, stop your "Water tablets" and "Blood pressure tablets" for a few days to protect the kidneys.

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13. References

1. Kidney Disease: Improving Global Outcomes (KDIGO) CKD Work Group. KDIGO 2024 Clinical Practice Guideline for the Evaluation and Management of Chronic Kidney Disease. Kidney Int. 2024 (In Press).

2. Heerspink HJL et al (DAPA-CKD). Dapagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2020 Oct 8;383(15):1436-1446. PMID: 32970933

3. Herrington WG et al (EMPA-KIDNEY). Empagliflozin in Patients with Chronic Kidney Disease. N Engl J Med. 2023 Jan 12;388(2):117-127. PMID: 36331946

4. National Institute for Health and Care Excellence (NICE). Chronic kidney disease: assessment and management. NICE Guideline [NG203]. Published: 25 August 2021.

5. Webster AC et al. Chronic kidney disease. Lancet. 2017 Mar 25;389(10075):1238-1252. PMID: 27887750

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14. Examination Focus

Common Exam Questions

1. "Patient with CKD and hyperkalaemia (6.2). Management?"
   • Answer: ECG (check for tall tented T waves). Calcium Gluconate (Stabilize membrane). Insulin/Dextrose (Shift K+). Stop ACEi/Spironolactone.
2. "Anaemia in CKD vs Iron Deficiency?"
   • Answer: Check Ferritin. In CKD it is often functional iron deficiency (High Ferritin, low Saturation).
3. "Target BP in CKD with Proteinuria?"
   • Answer: Stricter. less than 130/80 mmHg.
4. "Contraindications to Peritoneal Dialysis?"
   • Answer: Extensive abdominal surgery (adhesions), Severe Hernias, Inability to perform technique (dementia/poor dexterity).

Viva Points

• FGF-23: Know it as the hormone that rises early to excrete phosphate and causes LVH.
• Calcipylaxis: A rare condition of systemic calcification causing painful skin necrosis. High mortality.
• SGLT2i Mechanism: Not just glucosuria. Tubulo-glomerular feedback reset (Adenosine acting on macula densa).

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Last Reviewed: 2026-01-04 | MedVellum Editorial Team