CKD Flashcards
Stages of CKD:
Stage 1:
GFR>90
+ other evidence of kidney damage (eg. proteinuria, PCKD)
Stage2:
GFR 60-90
+ other evidence of kidney damage
Stage 3:
GFR 30-60
+/- other evidence of kidney damage
[Stage 3a = 45-60
Stage 3b = 30-45]
Stage 4:
GFR 15-30
+/- other evidence of kidney damage
Stage 5:
GFR <15
Established renal failure
Reflux-associated nephropathy. Aetiology of CKD in this setting?
Not due to reflux.
Congenital abnormalities underlie both the reflux and the kidney damage independently.
CKD results from renal maldevelopment (hypoplasia and dysplasia) associated with VUR.
It is now thought that VUR does not play a role in renal scar formation and potential chronic kidney disease (CKD) but is a marker for abnormal renal development, which results in decreased formation of renal parenchyma referred to as primary renal scarring.
Associations with PCKD?
Locations of cysts?
Cysts: kidney, liver, gut, pancreas.
Aortic and intracranial aneurysms.
Heart valve defects.
Recurrent UTIs and renal stones.
Best test to rule out PCKD?
Renal USS (for cysts).
Genetic mutation analysis would be better, but would need to know exact mutation of proband (usually don’t).
Mechanism of ACEi in Tx of proteinuria?
Decreased glomerular filtration pressure due to affect on angiotensin (ie. decreased single nephron GFR).
Also change in podocyte behaviour contributes.
Cause of renal anaemia?
EPO deficiency due to decreased production:
But usually not apparent until GFR t require EPO as still produce.]
Beware low Hb in patient with mild to mod CKD:
- GI bleeding common
(possible clue: urea rise out of proportion to rise in Cr)
- Other causes for bleeding possible: eg. BM abnormality, fibrosis assoc. with hyperPTH in advanced CKD.
- Look for iron deficiency: should NOT find in stages 1-3a CKD. Ability to absorb iron from gut decreases with progressive CKD, but usually still enough until EPO replacement begins (unless bleeding).
Once on EPO - require iron supplementation (aim ferritin ~200).
Target Hb in CKD and ESRD patients?
Dialysis patients: Hb 110-120 approx.
Possibly lower in CKD patients (roughly 100-110)
Note: aiming for higher levels seems to increase morbidity and mortality (strokes, VTE, cardiac events), even if don’t reach target levels.
Erythropoeitin replacement products:
Weekly dosing:
- Epprex (Erythropoeitin alpha)
- Neorecormon (Erythropoeitin beta)
Fortnightly dosing:
- Aranesp (Darbopoeitin)
Monthly dosing (after fortnightly loading period): Mircera (EPO RECEPTOR ACIVATOR - not EPO replacement).
Understanding CKD-MBD (Chronic Kidney Disease - Mineral Bone Disease).
What drives the PTH up?
High phosphate and low calcium (initially), until tertiary hyper PTH develops.
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Hyperphosphataemia due to inadequate excretion (may still have normal serum levels initially; see in stages 1-3a).
Hypocalcaemia due to
- reduce gut absorption
- inadequate active vit D (1,25-OH2 vitD) - may also have low 25-OH vitD.
Vitamin D deficiency (reduced production).
Both hyperphosphataemia and hypocalcaemia cause hyperparathyroidism:
HyperPTH may normalise calcium to some extent = SECONDARY hyperparathyroidism (phosphate will still be elevated).
Eventually PTH glands become autonomous due to hyperplasia = TERTIARY hyperparathyroidism –> hypercalcaemia develops (at expense of the bones).
High calcium + high phosphate –> high calcium/phosphate product –> deposited in vessel walls, etc.
Treatment of hyperphosphataemia in CKD?
What is the target?
- Low-phosphate diet
(note: high in coke and sodium phosphate in fast food!) - Phosphate binders
- RRT
Target:
- normal range in early CKD
- as CKD advances aim <1.8 (preferably ~1.6)
Treatment of hypocalcaemia in CKD?
What is the target?
Calcitriol: increases absorption of calcium from gut and resorption from bone.
Target: normocalcaemia (ionised calcium)
Note: if on caltrate it is as a phosphate binder, NOT for hypocalcaemia! -hypocalcaemia is due to malabsorption, due to vitD deficiency.
Treatment for vitamin D deficiency in CKD:
- Calcitriol (1,25-dihdroxycholecalciferol): provide active form of vitamin D
- Ostelin (25-hydroxycholecalciferol): treat vitamin D deficiency due to inadequate intake or inadequate sun exposure. Ie. provide substrate for remaining endogenous enzymatic conversion.
Vitamin D metabolism:
Vitamin D2 = ergocholecalciferol (plant sources)
Vitamin D3 = cholecalciferol (animal sources; 90% produced in skin exposed to UV light)
(inactive, unhydroxylated form of vitamin D).
Calcidiol = hydroxylated form of D3 (25-hydroxycholecalciferol), produced by liver.
Calcitriol (1,25-dihydroxyvitamin D3) = active form of D3. Produced in kidneys by further hydroxylation of calcidiol.
Biosynthesis:
Cholecalciferol
- -> hydroxylated in the liver by enzyme vitamin D 25-hydroxylase, produced by hepatocytes
- -> 25-hydroxycholecalciferol (calcidiol or 25(OH)D)
- -> released into the plasma, bound to vitamin D-binding protein
- -> proximal tubules of the kidneys
- -> hydroxylated by the enzyme 25-hydroxyvitamin D3 1-alpha-hydroxylase
- -> calcitriol (1,25-dihydroxycholecalciferol and abbreviated to 1,25(OH)2D).
Levels of 1-alpha hydroxylase are increased by parathyroid hormone (and additionally by low calcium or phosphate).
Treatment of hypercalcaemia in tertiary hyperparathyroidism:
- Calcitriol (suppressive) - but need to cease if increasing hypercalaemia
- Parathyroidectomy (best - if possible)
- Cinacalcet: calcimimetic (increases calcium sensing in parathyroid gland)
(Need to cease caltrate, as absorb some).
Treatment of secondary hyperthyroidism (hyperphosphataemia, hypocalcaemia)?
Target?
- Calcitriol (suppressive)
- Ostelin
Target:
- Early CKD: aim PTH in normal range (maintaining normocalcaemia should do it)
- Advanced CKD: allow to increase to 2-3xULN
