CKD Pathophysiology of Progression of Kidney Disease

Question 1

1. Describe the stages of chronic kidney disease.

Answer 1

I: Kidney damage with normal or increased GFR >90
II: Kidney damage with mildly decreased GFR 60-89
III: Moderately decreased GFR 30-59
IV: Severely decreased GFR 15-29
V Kidney failure (requiring dialysis) GFR <15

Question 2

2. Explain the use and limitations of the methods that calculate the GFR.

Answer 2

discussed earlier in block

Question 3

3. Identify the factors that contribute to the progression of CKD- HTN.

Answer 3

there is a greater decline in GFR for each increase in MAP

lower BP leads to less diminishment of GFR and longer time away from dialysis

(independently effects renal outcomes)

Question 4

3. Identify the factors that contribute to the progression of CKD- protein delivery to the glomerulus.

Answer 4

hormonal effects: release of glucagon, IGF-1, kinins all cause renal vasodilation (afferent)

intrarenal effects- increased filtered load of amino acids activates tubuloglomerular feedback and increases RBF

Question 5

3. Identify the factors that contribute to the progression of CKD- glomerular HTN

Answer 5

this occurs with systemic HTN or increased efferent artery vasoconstriction (angiotensin II) or increased afferent artery dilation (protein, CCB)

increased Pgc is not good in a kidney that is already damaged

Question 6

3. Identify the factors that contribute to the progression of CKD-hyperglycemia.

Answer 6

glucose control partially reverses glomerular hypertrophy and hyperfiltration and strict glucose control delays the onset of microalbunminuria and overt proteinuria

Question 7

4. Explain the relative importance and mechanism of blood pressure control in slowing the progression of CKD.

Answer 7

there is a more risk of progression with HTN if >1 g proteinuria (clinical goal); reduction of proteinuria is more with both ACEI and ARB or spironolactone (still debated)

Question 8

4. Explain the relative importance and mechanism of angiotensin II block in slowing the progression of CKD.

Answer 8

Angiotensin II dilates AA and constricts EC causing and increase in GFR (leading to glomerular cell injury, detachment of podocytes, and proteinuria) as well as mesangial cell stretching causing release of cytokines likeTGF B, leading to scarring and fibrosis

ACEI/ ARB leads to decreased angiotensin II, BP and proteinuria/renal disease (decreases sclerosis and also decreasing glomerular pressure)

ACEI decrease risk of ESRD by 31% independent of BP lowering effects; ARBs also reduced progression (amlodipine also reduced progression)

Question 9

4. Explain the relative importance and mechanism of protein restriction in slowing the progression of CKD.

Answer 9

in animal studies protein restriction shows slowing of renal disease

in humans the reduction of protein intake showed minimal change in declining GFR for non- diabetics; in diabetics there is a change but is is relatively “trivial”

Question 10

4. Explain the relative importance and mechanism of glycemic control in slowing the progression of CKD.

Answer 10

current evidence doesn’t show that once proteinuria has occurred, that strict control of blood sugar slow the progression of kidney disease (although it makes sense that it should)

Question 11

Name the top 3 clinical factors associated with progression of CKD.

Answer 11

hypertension
heavy proteinuria
interstitial fibrosis on biopsy

Question 12

What three factors is SNGFR directly proportional to?

Answer 12

Pgc- pressure in the glomerulus and Q- flow to the glomerulus based on the dilation/constriction of afferent and efferent arterioles

and the permeability of the glomerular filter Kf

Question 13

What is the role of aldosterone in the progression of CKD?

Answer 13

in animals and humans, blockade of aldosterone receptor reduces proteinuria more than with ACEI alone