CKD Flashcards
What are the three mechanistic stages of CKD?
Injury, structural damage/scarring, progression
What is maladaption in CKD?
Cycles of damage and attempted repair that lead to scarring and impaired physiology
What are the relative levels of phosphate, calcium, PTH, and FGF23 associated with end stage CKD?
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
What are the effects of excess PTH/FGF23 on remaining nephrons in CKD?
Hyperfiltration, hypertrophy, intraglomerular hypertension
What is the major mediator of nephron hypertrophy in CKD?
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
What is the maladaptive response to metabolic acidosis in CKD?
Increased ammoniagenesis to increase acid excretion –> leads to a proinflammatory state that contributes to tubular injury, fibrosis, and loss of nephron function
How do ROS cause disease in CKD?
They can alter thiol bonds, alter receptors, alter protein structures, and react with lipids to propagate more free radicals
What is hypoxia-inducible factor?
A factor present in fibrotic kidneys that contributes to CKD pathogenesis
What are five renal cellular stress responses in CKD?
Inflammation, innate immunity, abnormal protein folding, autophagy, apoptosis
What are 6 predisposing factors that affect per-nephron load?
- 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)
What is the clinical definition of CKD?
Abnormal kidney function persisting for more than 3 months with health implications
What are the three classification criteria for CKD?
cause, GFR category, and albuminuria
What are the clinical definitions of CKD progression?
Decline in GFR category or a 25% or greater drop in eGFR from baseline
What is the clinical definition of rapid progression of CKD?
Sustained decline in eGFR of more than 5/ml/min/1.73 m2/yr
How often should GFR and albuminuria be assessed in people with CKD?
At least annually, more often for people at higher risk of progression
What category of GFR/albuminuria is associated with the worst outcomes in CKD?
People with low GFR and high albuminuria have the worst prognosis
What percent of CKD racial disparities are explained by lack of health insurance/routine healthcare?
10% (according studies with the veterans affairs health system)
Why does access to prenatal care create disparities in CKD?
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
Explain disparities in access to kidney transplant?
African American patients are less likely to be identified as transplant candidates, receive evaluation referrals, and be be placed on a wait list
What is the effect of environment/geography on racial disparities in CKD?
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)
What is APOL1?
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)
What is the heterozygous advantage of APOL1?
It has a survival advantage against African trypanosomiasis
How do APOL1 mutations factor into CKD?
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
