Chronic Kidney Disease I

Question 1

Definition of chronic kidney disease

Answer 1

GFR less than 60 mL/min1.73 cm for 3 or more months, with or without kidney damage, or kidney damage for 3 or more months with or without a decrease in GFR.

Question 2

Why is chronic kidney disease such a global epidemic? Why should we care?

Answer 2

increases in obesity, type II DM, HTN, AIDS, schistosomiasis, TB. care because 45% of pts with stage IV kidney disease are dead in 5 yrs, and 10% of the US population has CKD.

Question 3

What is the final common pathway of all CKD?

Answer 3

glomerulosclerosis and interstitial fibrosis

Question 4

3 stages in the pathophysiology of CKD

Answer 4

1. Inflammation
2. Proliferation
3. Fibrosis

Question 5

Pathophysiology of CKD: inflammation

Answer 5

1. Inflammation occurs due to endothelial cell damage secondary to hemodynamic, immunologic or metabolic stresses. This leads to chemokine and cytokine release with subsequent platelte attraction and aggregation. It may also lead to cell adhesion molecule expression, which recruits monocytes; foam cells infiltrate the glomeruli.

Question 6

Pathophysiology of CKD: proliferation

Answer 6

epithelial cells gets stretched; mesangial cells proliferate and de-differentiate

Question 7

Pathophysiology of CKD: fibrosis

Answer 7

Fibroblasts and myofibroblasts appear to synthesize and deposit ECM. This leads to glomerulosclerosis.The same process occurs in the interstitium: protein and glucose in the urine are major stressors. Protein is toxic to tubules; glucose causes inflammation, cell adhesion, deposition of collagen.

Question 8

What are some risk factor changes that should be attempted in CKD?

Answer 8

decrease proteinuria, control blood glucose tightly, control HTN, stop smoking, and avoid nephrotoxic mediators like NSAIDs.

Question 9

What drugs are useful in preventing the progression of CKD?

Answer 9

ACE-Is and ARBs, and aldosterone blockers. This decreases proteinuria AND decreses the progression of CKD.

Question 10

Microalbuminuria

Answer 10

defined as 30-300 mg/day or mg/gram creatinine. albuminuria is anything above 300 mg/day or mg/g Cr.

Question 11

Describe the angiotensin process again, including which body parts are involved

Answer 11

the kidney releases renin, which acts on angiotensinogen from the liver. angiotensinogen is converted to angiotensin I, which is converted to angiotensin II by ACE in the lungs. angiotensin II causes the release of aldosterone from the adrenal glands.

Question 12

What are the effects of inhibition of the angiotensin/aldo system?

Answer 12

1. dilate the efferent arteriole and decrease renal plasma flow.
2. hemodynamically decrease glomerulosclerosis
3. decrease fibrosis cause by sclerosis
4. decrease proteinuria.

Question 13

What are the effects of aldosterone? (7)

Answer 13

1. promote K loss
2. Na retention
3. Mg loss
4. NH4 loss
5. increased inflammatory molecules (ROS, TGF-B, among others): pro-inflammatory effects on COX-2 and osteopontin
6. endothelial dysfunction
7. decreased vascular compliance

Question 14

What do we know about drugs and diabetics in terms of CKD?

Answer 14

In diabetics with established nephropathy, ACE-Is decrease proteinuria by 40-50% and preserve GFR. BP control is also important.
ARBs arlso decrese the risk of developing proteinuria and DM nephropathy.

Question 15

What is a good regimen in CKD for patients without diabetes?

Answer 15

Spironolactone (aldo inhibitor) and ramipril (ACE-I) really decrease proteinuria.

Question 16

ACE-I (examples)

Answer 16

-prils. Lisinopril (elanapril)

Question 17

ARBs

Answer 17

-sartan: losartan, irbesartan

Question 18

Aldo-inhibitors

Answer 18

spironolactone, eplerenone

Question 19

renin-inhibitors

Answer 19

aliskiren (not that useful- costs too much)

Question 20

What should I know about HTN and CKD?

Answer 20

Reducing BP to less than 140/90 can slow progression- and some recommend a goal of 130/80.

Question 21

smoking and CKD.

Answer 21

smoking increases risk of ESRD by 6 fold. that’s because smoking increases sympathoadrenal activation and circulating catecholamines. that increases beta adrenergic stimulation and renin release.

Question 22

summary of general considerations with CKD

Answer 22

reduce risks like HTN, DM, smoking, proteinuria. Consider blocking angiotensin/aldo axis.