Chronic Renal Insufficiency and Renal Replacement Therapy

Question 1

Definition of CKD

Answer 1

Progressive, IRREVERSIBLE renal impairment > 3 months as evidenced by:
- GFR <60 ml/min/1.73m2
OR
- albuminuria (AER >30mg/day or ACR >3mg/mmol)

==> permanent destruction of nephrons and reduction of GFR with loss of tubular and glomerular functions

Question 2

Causes of CKD

Answer 2

Diabetic nephropathy (30%)
Hypertension (25%)
Glomerulonephritis (15%)

Question 3

Pathophysiology of CKD

Answer 3

Intact Nephron Hypothesis

• reduction of number of WHOLE NEPHRONS
• the other remaining surviving nephrons are functional

Question 4

Adaptations to CKD

Answer 4

In order to continue to excrete the daily load of a given substance
- usually at CKD stage 3/4 but fails at stage 5

Adaptation of kidney
- extent of reabsorption and excretion

Adaptation of substrates

Question 5

Adaptation of Substrates: principle and effects on creatinine

Answer 5

Limitation of output = transient fall in outflow rate which raises fluid levels in body –> until a new steady state is achieved where output is restored to match input

PASSIVE maintenance of balance and homeostasis (input = output)

Creatinine: no homeostasis (plasma [Cr] stable initially then increase exponentially)

Question 6

Adaptation of Kidney: those with stable levels until very ESRD

Answer 6

Amino acids and glucose: complete reabsorption of filtered substances (plasma concentration remains unchanged)

Na: can increase FENa to >5% (reduce reabsorption; plasma concentration unchanged until very low GFR of 2-3 ml/min and >130 mmol salt intake)

• mediated by ANP
• can’t tolerate sudden change in salt intake (narrow range of Na excretion)

K: enhanced secretion gradually (not dependent on GFR in early CKD; normal plasma concentrations until ESRD e.g. GFR <10 –> decreased flow rate)
- mediated by aldosterone

Question 7

Adaptation of Kidney: H+

Answer 7

Slightly earlier derangement e.g. GFR <20

H+: decreased NH3 production due to smaller kidney mass ==> decreased total H+ excretion ==> metabolic acidosis

• increase tubular secretion (down to pH 4.5), increase regeneration of HCO3
• NAGMA at early stage, HAGMA at later stage

Effects of metabolic acidosis:

• utilise bone buffer to control acidosis –> osteodystrophy
• adaptive increase in NH3 per nephron leads to tubulointersitital damage
• skeletal muscle breakdown, decreased albumin synthesis

Question 8

Adaptation of Kidney: Ca and PO4

Answer 8

Also earlier derangement (like H+)

Decreased nephron mass = PO4 retention

PO4 response to CKD similar to Cr –> increase [PO4]p when GFR decreases
–> leads to decreases [Ca]p which stimulates PTH response
==> Ca and PO4 maintained normal/slightly elevated by increasing PTH in early CKD (secondary hyperPTH)

Late CKD:

• reabsorption of PO4 reaches the minimum of 15% (can’t excrete more)
• persistent hyperPO4 and hypoCa develops
• decreased 1 alpha-hydroxylation of vitamin D –> decreased [Ca]p and reduced suppression of PTH
  “vitamin D resistance” towards 25-OH Vit D

==> renal osteodystrophy (prevent with Vitamin D)

• osteomalacia (defective mineralisation)
• osteitis fibrosa cystica (PTH stimulated osteoclastic activity)
• osteosclerosis (metastatic calcification due to poor treatment; rare now)

(new finding that FGF23 is a key regulator of PO4 homeostasis; increase a/w mortality in CKD)

Question 9

Renal handling of water

Answer 9

Defects in concentrating ability due to:

• low medullary hypertonicity
• medullary fibrosis
• collection tubule resistance to ADH

(scarring = medulla distorted and counter-circulation loop distorted so can’t concentrate)

==> urine Osm reaches isotonic (300 mmol/L) hence minimum output becomes 4L/day

Clinical features:

• isosthenuria
• polyuria
• nocturia
• edema, volume expansion (due to solute retention in ESRD when max urine volume limited by GFR <10 and can’t achieve obligatory solute loss)

Question 10

Clinical course of CKD (4 stages)

Answer 10

75-50% function

• reduced renal reserve
• no detectable azotaemia (urea and creatinine normal)
• asymptomatic

50-25% function

• renal insufficiency
• mild azotaemia (elevated urea and creatinine)
• HT and anaemia, developing urinary concentrating defect (polyuria)

25-12% function (15-30 ml/min)

• renal failure
• hypoCa, hyperPO4, mild metabolic acidosis
• advancing anaemia (less EPO), advancing HT and isosthenuria

<12% (<15 ml/min)

• uraemia
• marked azotaemia and worsening acidosis
• electrolyte disorders become apparent
• multisystem disorders “uraemia syndrome”

Question 11

Conservative Mx

Answer 11

keep balance and slow down rate of progression to ESRD

• prevent further insult to kidney
• prevent and promptly treat acute complications
• prevent development of bone disease
• quality of life

Question 12

Dialysis definition and indications

Answer 12

Differential transfer of solutes and water, by diffusion, osmosis or ultrafiltration, through a semipermeable membrane

Indication:

• GFR <10 ml/min
• symptoms/signs of renal failure e.g. pruritus, acid-base/ electrolyte disturbance
• inability to control volume status or blood pressure
• progressive deterioration in nutritional status refractory to dietary intervention
• cognitive impairment

Question 13

Types of Renal replacement therapy

Answer 13

Haemodialysis

• diffusion through artificial membrane in dialyser
• create arteriovenous fistula with arterial blood out to filtrate and back to vein after
• 80-160 ml/min

Peritoneal dialysis (intermittent or continuous ambulatory)

• fluid into peritoneal cavity
• diffusion through peritoneal membrane to “soak up” excess waste and solutes from blood
• takes 12 hrs (rate of 15-20 ml/min)

Haemofiltration
- convection through highly permeable membrane and replaced by fluid of desired composition

Renal transplant