CKD: complications and management

Question 1

What are the most important complications of CKD?

Answer 1

anemia, CV risks, and mineral metabolism

Question 2

What should I know about CV risk?

Answer 2

CV risks are dramatically greater in patients with CKD. Dialysis pts have a much much greater risk of CV death, and death and risk of CV event are inversely correlated to GFR. In particular, there is an elevated risk of stroke-related hospitalizations, cognitive impairment (about 75% have moderate to severe impairment; only 13% show no cognitive impairment)

Question 3

Why do CKD patients have such elevated CV risk?

Answer 3

both traditional and non-traditional risk factors. Non-traditional factors include anemia, proteinuria, inflammation, Ca phosphate metab problems, malnutrition, oxidative stress, sleep issues, volume overload, homocysteine

Question 4

Why is proteinuria a CV risk factor?

Answer 4

atherogenesis and microalbuminuria probably share a common pathogenesis of impaired endothelial function- impaired NO synthesis and chronic low-grade inflammation.

Question 5

How do you manage CV risk in CKD pts?

Answer 5

1. Treat traditional risk factors.
2. Statins:
   Statins make no difference for dialysis pts.
   Statins in patients BEFORE ESRD are mixed. Potentially most useful for pts with GFR between 15 and 60.

Question 6

Why aren’t statins helpful for pts in ESRD?

Answer 6

Statins reduce atherosclerotic plaques- but dialysis patients’ biggest problem is likely not atherosclerotic plaques, but rather medial cacification. Medial calcification makes it harder to push blood through the body but isn’t responsive to statin therapy. (normal atherosclerosis invovles the intima rather than the media).

Question 7

What is the biggest mineral metab problem in pts with CKD? Why do we care?

Answer 7

secondary hyperparathyroidism related to abnomalities in the metab of calcium, phosphorus, and vitamin D. This is part of the bone disorders (renal osteodystrophy) that we discussed, and may also contribute to CV risk.

Question 8

What are the types of renal bone problems?

Answer 8

1. Osteotitis fibrosa
2. adynamic bone disease
3. osteomalacia

Question 9

osteotits fibrosa

Answer 9

high turnover bone disease with high PTH and increased ostoclast and osteoblast activity.

Question 10

adynamic bone disease

Answer 10

low turnover and PTH. seen more in peritoneal dialysis pts than in hemodialysis pts.

Question 11

osteomalacia

Answer 11

defective mineralization, usually associated with aluminum deposition

Question 12

What is renal osteocardiodystrophy?

Answer 12

a set of mineral metabolism disorders where the vascular effects are more significant than the bone disorders. Typically with secondary hyperparathyroidism, we see high PTH, High phosphorus levels with high FGF23 and low klotho, low or high calcium, and low vitamin D

Question 13

What is the pathophysiology of secondary hyperparathyroidism? (that terrible diagram)

Answer 13

The kidney is broken. This had two direct effects. One, we see increased phosphorus levels. Phosphorus binds calcium, so calcium levels drop. Secondly, we see less of the active 1,25 vitamin D, since the kidney is responsible for converting 25 D into its active form. Decreased vitamin D further decreases Ca levels in the blood by decreasing calcium absorption from the gut. Together, this drop in calcium causes secretion of PTH from the thyroid. PTH has effects on both kidney and bone. In the kidney, it stimulates an increase in 1,25 vitamin D (which increases calcium absorption from the gut and nominally increases bone resorption). PTH also directly stimulates bone resporption. Bone secretes Calcium AND phosphorus. Together, this leads to the clinical lab picture of high PTH, high phosphorus, high or low calcium, and low vitamin D.

Question 14

What is the effect of the increase in circulating Ca that can be observed in secondary parathyroidism? Who is most affected?

Answer 14

increased calcium levels lead to calcification of the artery. More calcification is seen in patients as they age (more in young adults than in kids on dialysis), in patients with a higher product of Ca and phosphate in their blood (65>56), and in patients with higher doses of daily Ca. But, BP and cholesterol are NOT risk factors. This is important, because greater arterial calcification is associated with decreased surivival.

Question 15

What should I know about higher levels of circulating phosphorus?

Answer 15

High levels of phosphorus are independently associated with higher mortality (independent of calcim levels.

Question 16

What should I know about FGF23?

Answer 16

High FGF23 is associated with increased risk of death.
Normally, FGF23 is responsible for regulating phsophorus levels and is secreted by osteocytes and osteoblasts. Its secretion is induced by high levels of circulating phosphorus and high levels of 1,25 vitamin D. FGF23 induces renal phosphorus excretion and decreases 1,25 vitamin D levels. These effects are mediated by interactions with klotho receptors. FGF23 levels rise before the increase in serum phosphorus and right before the dramatic increases in PTH. In CKD patients, high levels of FGF23 are associated with increased mortality, mineralization, vascular cacification, and LVH.

Question 17

What should I know about klotho?

Answer 17

Kotho expression is decreased in patients with progressive CKD. A drop in CKD precedes the rise in FGF23 (maybe FGF23 rises because it doesn’t work without the klotho receptor?). Normally Klotho is a receptor for FGF23 and can independently act to increase Ca reabsorption and phosphorus secretion. Klotho also normally protects against renal fibrosis and promotes kindy regeneration after ischemic injury, decreases oxidative stress via inhibition of insulin growth factor signaling pathway, among many other good effects (increased NO production, vasodilation; decreased cell senescence and apoptosis).