Complications 

1. Fluid, Electrolyte & Acid–Base Complications

Complication

Mechanism (Why it occurs)

Volume overload(Edema, pulmonary edema → common ICU admission cause)

↓ GFR → Na⁺ and water retention + RAAS activation

Hyperkalemia

↓ renal K⁺ excretion + acidosis (K⁺ shifts out of cells)

Metabolic acidosis(Bone buffering → osteodystrophy + muscle wasting)

↓ H⁺ excretion + ↓ ammonia generation

Hyponatremia (dilutional)

Water retention > sodium retention


2. Cardiovascular Complications (MOST COMMON CAUSE OF DEATH)

Complication

Mechanism

Hypertension

Volume expansion + Renin-Angiotensin-Aldosterone Systemactivation

LVH

Pressure overload + anemia + volume overload

Heart failure

Diastolic dysfunction + volume overload

Accelerated atherosclerosis

Chronic inflammation + dyslipidemia + uremia

Uremic pericarditis

Uremic toxin accumulation → inflammation

Arrhythmias

Hyperkalemia + structural heart disease


3. Hematological Complications

Complication

Mechanism

Anemia (normocytic)

↓ Erythropoietin + iron deficiency + inflammation

Platelet dysfunction

Uremic toxins impair platelet aggregation


4. CKD–Mineral Bone Disorder (CKD-MBD)

Complication

Mechanism 

Hyperphosphatemia

↓ renal phosphate excretion,↑ serum phosphate → ↑ FGF-23 Leads to:

  • ↓ calcitriol
  • Secondary hyperparathyroidism
  • Vascular calcification

Hypocalcemia

↓ Vitamin D activation + phosphate retention

Secondary hyperparathyroidism

Chronic hypocalcemia → ↑ PTH

Renal osteodystrophy

Bone turnover abnormalities

Vascular calcification

Ca–phosphate deposition in vessels

Pathophysiology

1. Early CKD (Stage 2–3)

  • ↓ Nephron mass → ↓ phosphate excretion
  • Mild ↑ phosphate → triggers:

 ↑ FGF-23 (Fibroblast Growth Factor-23)

  • Secreted by osteocytes
  • Actions:
    • ↓ renal phosphate reabsorption
    • ↓ 1α-hydroxylase → ↓ calcitriol

2. Vitamin D Deficiency

  • ↓ Calcitriol
  • ↓ intestinal Ca absorption
  • Leads to:Mild hypocalcemia

3. Secondary Hyperparathyroidism

  • ↓ Ca + ↓ Vitamin D + ↑ phosphate → ↑ PTH
  • Persistent → parathyroid hyperplasia

 Effects:

  • Bone resorption ↑
  • Ca mobilization
  • Phosphate ↑ further (vicious cycle)


4. Advanced CKD (Stage 4–5)

  • Hyperphosphatemia overt
  • Severe ↓ calcitriol
  • Markedly ↑ PTH

5. Vascular Calcification

 

Bone Disease Spectrum (Renal Osteodystrophy)

1. High Turnover Bone Disease

 Osteitis Fibrosa Cystica

  • Due to ↑ PTH
  • Features:
    • Bone resorption
    • Subperiosteal erosions
    • Brown tumors

2. Low Turnover Bone Disease

 Adynamic Bone Disease

  • ↓ PTH (over-suppression)
  • Causes:
    • Excess calcium binders
    • Excess vitamin D

 Risk:

  • Fractures
  • Vascular calcification ↑


 Osteomalacia

  • Defective mineralization
  • Causes:
    • Aluminum toxicity (dialysis era classic)
    • Severe vitamin D deficiency


3. Mixed Uremic Osteodystrophy

  • Features of both high and low turnover


 Biochemical Pattern 

Parameter

Early CKD

Late CKD

Phosphate

Normal / ↑

↑↑

Calcium

Normal

↓ / Normal

PTH

↑

↑↑↑

Calcitriol

↓

↓↓↓

FGF-23

↑ (early marker)

↑↑

 Clinical Features

Bone-related

  • Bone pain
  • Proximal myopathy
  • Fractures

Extra-skeletal

  • Pruritus
  • Vascular calcification
  • Calciphylaxis (life-threatening)


 Calciphylaxis 

 Definition

  • Calcific uremic arteriolopathy

Features:

  • Painful skin necrosis
  • Black eschar
  • High mortality

Risk factors:

  • ESRD
  • High Ca × PO₄
  • Warfarin use


 Investigations 

Parameter

Stage 3

Stage 4

Stage 5

Ca, PO₄

6–12 mo

3–6 mo

1–3 mo

PTH

12 mo

3–6 mo

3 mo

ALP

As needed

↑ frequency

↑ frequency


5. Endocrine & Metabolic Complications

Complication

Mechanism

Insulin resistance

Uremia + inflammation

Hypoglycemia (late CKD)

↓ insulin degradation

Dyslipidemia

↑ triglycerides, ↓ HDL

Sexual dysfunction

Hormonal imbalance (↓ testosterone, ↑ prolactin)

Growth retardation (children)

GH resistance + malnutrition


6. Neurological Complications

Complication

Mechanism

Uremic encephalopathy

Neurotoxins (guanidino compounds)

Peripheral neuropathy

Axonal degeneration (“dying-back”)

Restless leg syndrome

Dopamine dysfunction + iron deficiency


7. Immune System Complications

Complication

Mechanism

Immunosuppression

Uremia impairs leukocyte function

Poor vaccine response

Immune dysfunction


8. Indications for Dialysis (VERY IMPORTANT)

AEIOU

  • Acidosis (refractory)
  • Electrolytes (K+ refractory)
  • Intoxication
  • Overload (fluid)
  • Uremia:
    • Pericarditis
    • Encephalopathy

9. When to Refer to Nephrology 

18.30 Criteria for referral of chronic kidney disease patients to

a nephrologist

  • eGFR <30 mL/min/1.73 m2
  • Rapid deterioration in renal function (>25% from previous or >15 mL/min/1.73 m2/year)
  • Significant proteinuria (PCR >100 mg/mmol or ACR >70 mg/mmol), unless known to be due to diabetes and patient is already on appropriate medications
  • ACR >30 mg/mmol* with non-visible haematuria
  • Hypertension that remains poorly controlled despite at least four

antihypertensive medications

  • Suspicion of renal involvement in multisystem disease

10. Progression Risk Factors

  • Proteinuria (MOST IMPORTANT)
  • Poor BP control
  • Diabetes
  • Smoking
  • Obesity
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