CKD and Lifelong Treatment

Question 1

What is the definition of chronic kidney disease (CKD)?

Answer 1

• Abnormalities of kidney function OR structure present for >3 months.
• All patient with eGFR <60 ml/min/1.73m² on at least 2 occasions 90 days apart.
• Presence of ongoing nephrological cause of haematuria.
• Electrolyte abnormalities due to tubular disorders.
• Renal histological abnormalities.
• Renal structural abnormalities.
• Kidney transplantation.

Question 2

Describe the staging of CKD based on eGFR.

Answer 2

• I
  
  • ​eGFR >90
  • G1
• II
  
  • ​eGFR 60-89
  • G2

​​

• CKD1 and CKD2 are usually reported as haematuria / proteinuria / structural.
• IIIa
  
  • ​eGFR 45-59
  • G3a
• IIIb
  
  • ​eGFR 30-44
  • G3b
• IV
  
  • ​eGFR 15-29
  • G4
• V
  
  • ​eGFR <15
  • G5

Question 3

Describe the staging of CKD based on albumin:creatinine ratio.

Answer 3

• A1 - <3 mg/mmol
• A2 - 3-30 mg/mmol
• A3 - >30 mg/mmol

Question 4

What would prompt a nephrology referral in a patient with CKD?

Answer 4

• Evidence of CKD progression
  
  • Decrease in eGFR of 25% or more and change from CKD class.
  • A sustained decrease in eGFR of 15ml/min/1.73m² per year.
• eGFR <30 (CKD4).
• UACR >70 mg/mmol (unless known treated DM).
• UACR >30 mg/mmol + haematuria.
• Uncontrolled hypertension on 4+ drugs.
• Hereditary causes of CKD.
• Suspected renal artery stenosis.
• Haematological / biochemical abnormalities.
• Diagnostic uncertainty regarding aetiology / systemic disease present.

Question 5

Describe the community management of CKD1-3.

Answer 5

• CKD is asssociated with increased risk of CV disease and death.
• CKD G3 are more likely to suffer a CV event than they are to end up on dialysis.
• Proteinuria is independently associated with increased risk of CV disease and death.
• Appropriately timed reviews.
• Lifestyle advice.
• Statins (irrespective of serum lipid levels).
  
  • Reduce the risk of primary and secondary atherosclerotic events.
  • No reduction in all cause mortality or slowing CKD.

Question 6

How do you prevent the progression of CKD?

Answer 6

• Optimise BP management
• Reduce proteinuria
• Stop smoking
• Control diabetes
• Optimise weight

Question 7

What are the BP targets for patients with CKD?

Answer 7

• <140/90mmHg in CKD without proteinuria
• <130/80mmHg in CKD with proteinuria

Question 8

What is proteinuria?

What does proteinuria cause?

Answer 8

• Reduced number of nephrons in CKD results in glomerular hyper-hyper-perfusion and hypertension.
• Increased filtration of protein:
  
  • Xs protein in Bowman’s capsule activates inflammatory and apoptic pahthways.
  • Xs protein through podocytes releases TGF-beta1 and resultant myofibroblast differentiation of mesangial cells.
  • Xs protein in PCT results in localised toxicity with resultant cytokine and vasoactive mediator release.
    
    • INTERSTITIAL FIBROSIS
  • Proteinuria results in increased decline in renal function.
    
    • REIN - ramipril in non diabetics for 5 years halved rate of GFR decline.
      
      • Possible improvement and reversal of glomerular lesions (most beneficial at higher eGFRs).
    • Dual blockade considered too risky (ACE and ARB).
    • But recently, study suggests beneficial in diabetic population.

Question 9

What factors precipitate lactic acidosis in patients with T2DM?

Answer 9

• Cardiac failure
• MI
• Hepatic failure
• Any hypoxic state
• Clinical dehydration
• Shock (especially septic shock)
• Severe sepsis and haemodynamic instability
• Major surgery

Question 10

What effect does obesity have on the kidneys?

Answer 10

• Obesity is a risk factor for:
  
  • Hypertension
  • CKD
  • ESRD
• No substantial data associated with ‘size-reduction’ except with bariatric surgery.

Question 11

Describe how anaemia is related to kidney function.

Answer 11

• Erythropoietin is 80% produced in the kidney by fibroblastoids in the peritubular interstitium.
• Erythropoiesis is increased in hypoxia:
  
  • Acidosis causes a right shift in the oxygen-Hb dissociation curve (improving hypoxia).
• CKD results in increased hepcidin levels - reduced clearance and increased production.
  
  • Hepcidin binds to ferropoietin which blocks the exit of iron from cells - functionally rendering iron deficiency - less absorption and less utilisation.
• Anaemia:
  
  • Reduced EPO
  • Increased bleeding risk
  • Reduced red cell life span (corrected by dialysis)
• CKD3 has NN anaemia.

Question 12

Describe how levels of calcium and phosphate are related to kidney function?

Answer 12

• PO₄ and Ca are absorbed in the duodenum and jejunum - absorption increased by vitamin D.
• Calcium is freely filtered and then reabsorbed across the PCT (70%) and then 20% in the thick loop. Passive absrption occurs with Na and H₂O due to increasing concentration of calcium in the lumen pulling it across.
• 5-10% absorbed across the DCT. Active mechanism. Binds to calbindin and parvalbumin which are influenced by vitamin D.
• PO₄ is 55% not protein bound freely filtered but there is Tmax absorption so excess is lost in urine.
• 80% in PCT absorbed through the NaPO₄ cotransporter. This is reduced by PTH.

Question 13

What is the effect of PTH?

Answer 13

• Increases calcium reabsorption across the DCT.
• Reduces PO₄ reabsorption across the tubule.

Question 14

What is the effect of vitamin D on the gut?

Answer 14

• Increases calcium and PO₄ reabsorption across the gut.
• Increases calcium transport across the cell and across the Aptness transporter.

Question 15

What are the bone effects of calcium and phosphate?

Answer 15

• Acidosis increases tubular loss of both calcium and PO₄ therefore losing calcium from bone.
• PTH causes net reabsorption from bone therefore increase serum Ca and PO₄.

Question 16

What happens to vitamin D in the event of acidosis?

Answer 16

• Cholecalcidferol from skin and gut converted in liver then kidney to active form.
• Increases effect of PTH on bone so increases Ca and PO₄ reabsorption from bone.
• Inhibits PTH secretion.
• Calcium inhibits PTH secretion.

Question 17

What happens to PTH, Ca and PO₄ in:

• primary hyperPTH?
• secondary hyperPTH?
• tertiary hyperPTH?

Answer 17

Question 18

What are the drug choices in hyperPTH?

Answer 18

• Vitamin D analogues: Alfacalcidol.
• Phosphate binders: calciuim acetate, secelamer, lanthanum CO₃.
• Calcimimetics: cinacalcet

Question 19

Describe the characteristics of bone in high bone turnover.

Answer 19

• High PTH
• New bone is mainly collagen
• Increased risk of fractures

Question 20

Describe adynamic bone.

Answer 20

• Low PTH
• Reduced mineralisation
• Increased risk of hypercalcaemia
• Over suppression with vitamin D
• Previous PTHectomy
• Associated with DM

Question 21

What are the effects of acidosis on the bone.

What is the clinical picture?

Answer 21

• CaCO₃ leak out from bone to act as a buffer for the H⁺ ions causing bone loss.
• Acidosis independently increases osteoclast activity and reduces osteoblast activity.
• Clinically:
  
  • ​Bone pain
  • Tendon rupture
  • Pruritus
  • Ocular calcification
  • Vascular calcification

Question 22

What are the treatment goals in patients with CKD G4 and G5?

Answer 22

• Usually seen by nephrologist
• Aim is to slow progression of CKD
• Identify and treat complications of CKS
• Reduce incidence of CV disease
• Allow timely and informed decision making for management of ESRF (end-stage renal failure)

Question 23

At what stage of renal compromise is acidosis common?

What are the complications?

Answer 23

• eGFR <25ml/min/1.73²
• Complications include:
  
  • ​Exacerbation of bone disease
  • Increased muscle degradation
  • Reduced albumin synthesis
  • Increased inflammation
• Also increases risk of therapy:
  
  • Increased ECF volume expansion
  • Hypertension
  • Decompensation of heart failure

Question 24

At what eGFR is dialysis started?

Answer 24

• In UK, average eGFR at time of starting dialysis is 7ml/min/1.73².
• This is doctor-lead if high K⁺ / acidosis / fluid overload / weight loss.
• Patient led if lethargy / loss of concentration.
• Ideal = pre-emptive transplantation.

Question 25

Describe the preparation of a patient for dialysis (any kind).

Answer 25

• When eGFR falls below 20 consistently and is on a downward trajectory.
• Education
• Options:
  
  • Peritoneal dialysis - not suitable if previous abdominal surgery.
  • Haemodialysis - need an AV fistula created.
  • Transplantation - not all patients suitable.
  • Conservative care - patient choice or too comorbid to dialyse.

Question 26

Describe the creatinine levels in a patient on haemodialysis as opposed to peritoneal dialysis.

Answer 26

• Haemodialysis - blue
• Peritoneal dialysis - green

Question 27

Describe pre-dialysis boods compared with post-dialysis bloods.

Answer 27

• Note - creatinine and urea do not matter in patients on dialysis

Question 28

What are the arguments for transplant vs. no transplant in a patient with renal failure?

Answer 28

• Factors for:
• Patient factors
  
  • ​No dialysis
  • Better QoL
  • Better survival
• Economic factors
  
  • ​Dialysis = £30,800 / year
  • Tx = £17,000 / year
• Factors against:
• ‘Optional extra’
  
  • ​Cardiac disease
  • Respiratory disease
  • Malignancy
  • Severe PVD
  • BMI >35
  • Age?