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Pathophysiology of Renal Failure (2) 

Learning Outcomes

  • Causes of chronic kidney disease
  • Assessment of renal function
  • Pathophysiology and principles of management of chronic kidney disease


Chronic kidney disease

What are the causes of chronic kidney disease ?(kidney damage or decreased GFR > 3months)

  • Congenital/inherited, eg polycystic kidney disease
  • Glomerular disease
    • 1˚ glomerulonephritis
    • 2˚ eg diabetes
  • Vascular disease, eg hypertension, renovascular disease
  • Tubulointerstitial disease, eg reflux nephropathy, diabetes
  • Urinary tract obstruction


Chronic kidney disease

What are 70% of cases of chronic kidney disease due to?

  • diabetes
  • hypertension
  • atherosclerosis


Progressive impairment in chronic kidney disease

How does progressive impairment come about in CKD?

  1. What are the possible mechanisms?

glomerular scarring + proteinuria =>  deterioration

  1. Compensatory increase in glomerular pressure

    Glomerular hypertrophy

    Angiotensin II:

    - increases glomerular pressure

    - increases filtration pore size: proteinuria

    - stimulates collagen synthesis (TGFb): scarring


Chronic kidney disease

  1. What are the stages of CKD based upon?
  2. How many stages are there?
  3. List these

  1. Based on GFR (normalised to SA of a standard man: 1.73m2)

  2. 5. 

  3. Kidney Damage (normal or increased GFR), mild decrease in GFR, moderate decrease, and severe decrease, Kidney failure


Summarise the STAGES in CKD

Stage : Description : GFR (ml/min/1.73m2)

see picture


Pathophysiology of chronic kidney disease

What does the Reduced GFR cause?

  • fluid retention
    • heart failure
    • oedema
  • reduced metabolite excretion

    • uraemia

    • increased plasma creatinine
    • increased plasma urate from purine metabolism (gout)
    • increased lipids (cause unclear)
    • (increased drug levels: prolonged half life)


Pathophysiology of chronic kidney disease

What are the consequences of reduced tubular function?

  • reduced fluid reabsorption
    • polyuria/nocturia
    • loss of regulated re-absorption
    • (reduced filtration eventually dominates)
  • reduced K+ secretion
    • hyperkalaemia
  • reduced H+ secretion
    • metabolic acidosis


Pathophysiology of chronic kidney disease

Explain the anaemia present in CKD

reduced erythropoietin

  • normocytic/normochromic
  • may also be nutritional deficiency: Fe2+/B12


Pathophysiology of chronic kidney disease

Renal Bone Disease

  1. What is the main causative process?
    1. Outline the normal physiological process
  2. Give examples of the consequences of renal bone disease and how these come baout

  1. reduced vitamin D activation
    1. See picture


  • Osteomalacia = > decreased GIT Ca2+-absorption 
  • Metastatic Calcification = > Increased [PO43-] (reduced renal excretion, reduced [Ca2+])
  • 2o Hyperparathyroidism, increased AlkPhos => decreased VitD and decreased [Ca2+] leading to increased PTH
  • Bone resorption (pepperpot skull) => pTH stimulated bone resorption
  • 3o Hyperparathyroidism, increased AlkPhos => chronic stimuation due to increased Ca2+
  • Other forms bone disease


Pathophysiology of chronic kidney disease

Cardiovascular Complications

Outline these


  • Renin-angiotensin activation => increased PR => increased BP
  • Fluid retention => heart failure
  • Increased cholesterol => atherosclerosis


Pathophysiology of chronic kidney disease

Outline the following pathophysiologies associated with CKD

  1. Skin
  2. Endocrine Problems
  3. Neurological Problems

  1. Pruritis (related to retained nitrogenous waste)

  2. Various (prolactin, gonadotrophins, sex hormones, thyroid hormone)

  3. Reduced consciousness/seizures (nitrogenous waste)

    Sympathetic nervous activity

    Peripheral neuropathy



What are the signs and symptoms of chronic kidney disease?

(see picture)

  • Anaemia
  • Skin
  • CNS
  • Renal
  • Platelet Abnormality
  • GI Tract
  • Endocrine/gonads
  • Polyneuropathy
  • Renal Osteodystrophy


Generally, what does the management of chronic kidney disease involve?

  • Renoprotection: slow disease progression
  • Treat complications
  • Haemodialysis
  • Renal Transplantation


Management of CKD

Renoprotection: slow disease progression

  1. What are the targets?
  2. How can pathogenesis be reduced?

  1. normal BP, restrict proteinuria

  2. reduce AII action: ACE inhibitor, A2 receptor antagonist                                                            control BP if still elevated: + diuretic (reduce BP and K+), + Ca2+ channel blocker (reduce BP)     treat other pathogenic conditions - e.g. diabetes/smoking


Management of CKD

Treat complications

How may the following be treated?

  1. Anaemia 
  2. Hyperlipidaemia
  3. Hyperkalaemia
  4. Acidosis
  5. Hyperphosphataemia
  6. Osteomalacia and 2˚ hyperparathyroidism 


  1. EPO
  2. Statins
  3. Restrict intake
  4. Oral bicarbonate
  5. Phosphate binders
  6. activated VitD analogues


Management of CKD


Outline how this management can be beneficial

  • Deals with waste products and fluid/electrolyte overload
  • Does not counteract other features of renal failure


Management of CKD

Renal transplantation

  1. What can be a concern?
  2. How can this be avoided?

  1. graft rejection
  2. immunosuppression

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