SM 204a/206a - CKD, CKD Clinical

Question 1

What is the mechanism of SGLT2 inhibitors?

Where do they act?

Which patients will benefit most from them?

Answer 1

SGLT2 inhibitors block Na+ and glucose absorption in the proximal tubule

This increases solute delivery to the macula densa

• -> Downregulation of RAAS
  
  • ​-> Less Angiotensin II
  • -> Less efferent arteriolar vasoconstriction
  • -> Prevents intra-glomerular hypertension
• -> Decreased Na+ uptake along the rest of the tubule
• -> Decreased filtration

Question 2

What are the acute (emergent) indications for starting dialysis?

Answer 2

AEIOU

• Acidosis
• Electrolytes (Hyperkalemia)
• Ingestions (Lithium, ASA)
• Overload (Volume overload)
• Uremia
• Nutrition (in pediatrics)

Usually dialysis is not started unless the patient is in distress/discomfort/generally is not doing well

Question 3

Why do we get increased filtration in early-stage diabetic renal disease?

Answer 3

Diabetes

• -> Increased glucose load
• -> More SGLT2 channels = increased Na+ and glucose absorption in the proximal tubule
• -> less Na+ delivery to macula densa
• -> less Adenosine released
• -> Afferent vasodilation
  
  • Macula densa mediates increased filtration
• -> Intraglomerular hypertension, increased filtration

SGLT2 inhibitors prevent afferent vasodilation and efferent vasoconstriction, thus reducing hyperfiltration and reducing intraglomerular hypertension

Question 4

Why are patients with CKD at increased risk of free iron deficiency?

Answer 4

CKD = buildup of hepcidin

Hepcidin inhibits ferroportin, a protein necessary for iron reabsorption and recycling

CKD -> Hepcidin -> Decreased free iron

(Ferroportin is the channel through which iron is released from enterocytes and macrophages)