CKD

Question 1

What are the three mechanistic stages of CKD?

Answer 1

Injury, structural damage/scarring, progression

Question 2

What is maladaption in CKD?

Answer 2

Cycles of damage and attempted repair that lead to scarring and impaired physiology

Question 3

What are the relative levels of phosphate, calcium, PTH, and FGF23 associated with end stage CKD?

Answer 3

High phosphate, low calcium, high PTH, high FGF23

Bricker hypothesis - renal clearance of phosphate is diminished –> increases FGF23 (which works to decrease vitamin D activation) –> decreases calcium levels –> increases PTH

Question 4

What are the effects of excess PTH/FGF23 on remaining nephrons in CKD?

Answer 4

Hyperfiltration, hypertrophy, intraglomerular hypertension

Question 5

What is the major mediator of nephron hypertrophy in CKD?

Answer 5

RAAS system - tubular response to maintain glomerulotubular balance
If Na intake exceeds output, ECF volume expands, which ultimately leads to arteriolar vasodilation and increased GFR in remaining nephrons

Question 6

What is the maladaptive response to metabolic acidosis in CKD?

Answer 6

Increased ammoniagenesis to increase acid excretion –> leads to a proinflammatory state that contributes to tubular injury, fibrosis, and loss of nephron function

Question 7

How do ROS cause disease in CKD?

Answer 7

They can alter thiol bonds, alter receptors, alter protein structures, and react with lipids to propagate more free radicals

Question 8

What is hypoxia-inducible factor?

Answer 8

A factor present in fibrotic kidneys that contributes to CKD pathogenesis

Question 9

What are five renal cellular stress responses in CKD?

Answer 9

Inflammation, innate immunity, abnormal protein folding, autophagy, apoptosis

Question 10

What are 6 predisposing factors that affect per-nephron load?

Answer 10

• low birth weight (low nephron number)
• prematurity (low nephron number)
• obesity (increased metabolism and filtration)
• hypertension (hyperfiltration, RAAS activation)
• history of AKI
• anemia (worsens oxygen delivery)

Question 11

What is the clinical definition of CKD?

Answer 11

Abnormal kidney function persisting for more than 3 months with health implications

Question 12

What are the three classification criteria for CKD?

Answer 12

cause, GFR category, and albuminuria

Question 13

What are the clinical definitions of CKD progression?

Answer 13

Decline in GFR category or a 25% or greater drop in eGFR from baseline

Question 14

What is the clinical definition of rapid progression of CKD?

Answer 14

Sustained decline in eGFR of more than 5/ml/min/1.73 m2/yr

Question 15

How often should GFR and albuminuria be assessed in people with CKD?

Answer 15

At least annually, more often for people at higher risk of progression

Question 16

What category of GFR/albuminuria is associated with the worst outcomes in CKD?

Answer 16

People with low GFR and high albuminuria have the worst prognosis

Question 17

What percent of CKD racial disparities are explained by lack of health insurance/routine healthcare?

Answer 17

10% (according studies with the veterans affairs health system)

Question 18

Why does access to prenatal care create disparities in CKD?

Answer 18

African Americans generally have less access to prenatal care, which can lead to preterm complications and lower birth weight, which leads to fewer functional nephrons

Question 19

Explain disparities in access to kidney transplant?

Answer 19

African American patients are less likely to be identified as transplant candidates, receive evaluation referrals, and be be placed on a wait list

Question 20

What is the effect of environment/geography on racial disparities in CKD?

Answer 20

Racial segregation often leaves Black people in areas with poor air quality, fewer walkable areas for exercise, more food deserts, and fewer dialysis facilities (that are often worse performing)

Question 21

What is APOL1?

Answer 21

A gene that has been linked to increased risk of non-diabetic CKD and ESKD among African Americans (only if they have two mutated allele copies)

Question 22

What is the heterozygous advantage of APOL1?

Answer 22

It has a survival advantage against African trypanosomiasis

Question 23

How do APOL1 mutations factor into CKD?

Answer 23

Increased CKD risk associated with homozygotes (G1/G1, G2/G2) or compound heterozygotes (G1/G2), but not for heterozygotes with wild type alleles (G1/G0, G2/G0). Even with the risk alleles, there is incomplete penetrance