SM 207: Diabetic Nephropathy

Question 1

What is the leading cause of CKD and ESRD?

Answer 1

Diabetes mellitus

Question 2

What is the difference between type 1 and type 2 DM?

Answer 2

Type 1: in kids, autoimmune destruction of pancreatic islet cells - complete insulin deficiency
Type 2: acquired, from insulin resistance to eventual deficiency, obesity is biggest risk factor

Question 3

What is the epidemiology of DM? Where is the prevalence? What does it increase the risk of?

Answer 3

Prevalence is rising quickly in each state
More common in AA’s and Hispanics
2-4x increased risk of CV events (MI/Stroke)

1/3 of all DM patients will develop diabetic nephropathy

Question 4

In the natural history of diabetic nephropathy, what are the stages?

Answer 4

1. Hyperfiltration (silent phase) - increased metabolic load on each nephron
2. Microalbuminuria - 1st clinical sign of kidney problem is more albumin in urine
3. Macroalbuminuria - more albumin in blood and GFR starts to decline
4. Advanced Nephropathy and Kidney Failure (GFR tanks down)

Question 5

What are the histopathologic manifestations of hyperfiltration?

Answer 5

1. High GFR (usually missed)
2. Glom Hypertrophy
3. GBM Thickening

Question 6

What are the histopathologic manifestations of microalbuminuria?

Answer 6

1. Normal GFR, some albumin in urine
2. GBM Thickening
3. MESANGIAL MATRIX EXPANSION (expanded by EC matrix proteins, development of kimmelsteil-wilson lesions)
4. Comorbid microvasular complications of DM also develop (retinopathy, peripheral neuropathy)

Question 7

What are the histopathologic manifestations of macroalbuminuria?

Answer 7

1. High albuminuria, even nephrotic range
2. Rapidly declining GFR
3. HTN
   High risk of progression to ESRD

Question 8

What are the histopathologic manifestations of advanced nephropathy/renal failure?

Answer 8

1. GFR falls, SCr rises
2. Proteinuria may decrease due to LOW GFR
3. HTN worsens
4. Need for renal replacement therapy (transplant or dialysis)

Question 9

What is the pathophysiology of hyperfiltration? Proteinuria?

Answer 9

Hyperfiltration: Glom Hypertrophy = more capillary surface area = EA VC and high GFR due to Ang II

Proteinuria: GBM thickening is of poor quality, podocytes become damaged and detach and apoptose, intraglomerular HTN (high GFR) worsens proteinuria

Question 10

What is the pathophysiology of intraglomerular HTN? Mesangial Matrix Expansion?

Answer 10

Intraglomerular HTN: Hyperglycemia - less Na Cl conc. to macula densa - AA VD and Ang II - EA VC = raise Pgc

Mesangial Matrix Expansion: Decreases capillary surface area, due to tubulointerstitial fibrosis and glomerulosclerosis (profibrotic cytokines released)

Question 11

What are the 3 main ways of managing diabetic nephropathy?

Answer 11

1. Intensive Glycemic Control (A1c below 7%)
2. Control BP (<130/80) with ACE-i or ARB (reno-protective by blocking AngII profibrotic effects) NEVER USE BOTH ACEi/ARB (also consider adding diuretics)
3. SGLT2-i: improves glucose excretion, blocks Na-Glu Cotransporter in PT (and helps prevent hyperfiltration through more Na in macula densa = less AA VD = lower GFR)