Diabetic Nephropathy

Question 1

Structural changes associated

Answer 1

GBM thickening
Mesangial expansion
Glomerular sclerosis

Question 2

Stage 1

Answer 2

Pre-nephropathy

• Inc GFR due to hyperfiltration
• Increased kidney size
• Glomerular and tubular epithelial cell hypertrophy, thick GBM and TBM

Question 3

Stage 2

Answer 3

Incipient nephropathy

• defined by onset of microalbuminuria (30-300mg/d)
• persistence of microalb predicts onset of clinically significant nephropathy
• GBM and TBM thickening continues and mesangial matrix exp occurs

Question 4

Path hallmark of diabetic nephropathy

Answer 4

Mesangial matrix expansion

Question 5

Stage 3

Answer 5

Overt diabetic nephropathy

• Macroalbuminuria/fixed proteinuria (Alb>300mg/d, Protein >500mg/d)
• Microscopic hematuria
• Decline in GFR
• Increase in serum Cr
• Hypertension
• Kidney shrinks due to scarring/fibrosis
• More severe mesangial matrix expansion (usually diffuse but can rarely be nodular)
• Predicts ESRD

Question 6

What do we cause nodular mesangial matrix expansion?

Answer 6

Kimmelstiel Wilson lesion (nodular glomerularsclerosis)

-If PAS positive=diabetic nephroapthy, advanced

Question 7

Path specific to diabetic nephroapthy

Answer 7

• Mesangial matrix expansion
• Afferent AND Efferent hyalinosis
• nodular sclerosis (K-W lesion)

Question 8

Stage 4

Answer 8

Advanced nephropathy

• Albuminuria and proteinuria worsens
• Hypertension worsens
• Fibrosis increases and kidney shrinks
• Dec in GFR
• Can develop nephrotic syndrome

Question 9

Treatment of diabetic nephropathy

Answer 9

• Intensive glucose control to HA1C of <7%
• Decrease in hyperfiltration with an ARB or ACEI to dilate efferent arteriole
• Treating hyperT alone improves slope of GFR decline and proteinuria/album
• Experimental TGFbeta block

Question 10

Diagnosis

Answer 10

• Persistent proteinuria
• Other microvasc diseases like retinopathy
• Absence of other diseases

Question 11

Risk factors

Answer 11

• Genetics, ethnicity, environment

- Modifiable RFs: hyperglycemia, hyperT, hyperfiltration, obesity, smoking, soluble mediators

Question 12

BP goal

Answer 12

<130/80

Question 13

HA1C goal

Answer 13

<7%

Question 14

What measures guides treatments of these pts?

Answer 14

• Proteinuria
• HA1C
• BP