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Renal by Minnie > SM 207a - Diabetic Nephropathy > Flashcards

SM 207a - Diabetic Nephropathy Flashcards

1
Q

What functional changes occur when a patient is in the microalbuminuria (incipient) stage of diabetic nephropathy?

A
  • 30-300 mg albumin daily
    • >300 mg = macroalbuminuria
  • GFR remains normal
  • Other microvascular complications happen on the same timeline (ex: diabetic retinopathy)
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2
Q

What is the goal blood pressure for diabetic patients?

A
  • <140/90, but probably <130/80 is better
  • <130/80 is the target BP for everyone treated for HTN with increased CV risk (which includes all patients with diabetes)
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3
Q

What defines microalbuminuria?

A

30-300 mg of albumin daily

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4
Q

Describe the steps in the typical natural history of diabetic nephropathy

A
  1. Hyperfiltration
  2. Microalbuminuria
  3. Macroalbuminuria
  4. Advanced Nephropathy/Kidney failure
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5
Q

What lesions are present in this biopsy?

Which disease is present?

A

Kimmelstiel-Wilson nodules

Diabetic nephropathy

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6
Q

Which anti-hypertensives should be prescribed to patients with diabetic nephropathy?

A

ACE Inhibitor OR ARB

  • Renoprotective
  • Relaxes the efferent arteriole
    • Angiotensin II -> efferent arteriole constriction
  • Decrease intraglomerular pressure
  • MItigate teh passage of protein into the urine
  • Prevent pro-fibrotic effects of angiotensin II
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7
Q

What fraction of patients with diabetes will develop nephropathy?

A

1/3

Increased risk in African Americans, Native Americans, and Hispanics

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8
Q

What percentage of patients with diabetes will have hyperfiltration?

A

Probably 100%, but hard to tell because difficult to detect

Not all will progress to diabetic nephropathy - only 1/3 will progress to the microalbuminuria (incipieint) phase

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9
Q

What functional changes occur during the hyperfiltration (silent) phase of diabetic nephropathy?

A
  • Increased GFR (but this is usually not detected in labs)
  • Increased kidney size
  • Glomerular hypertrophy (without proliferation of cells)
  • Glomerular basement membrane thickening
  • Usually occurs for 5-10 years
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10
Q

Which drugs are likely to reduce glomerular hypertension specifically?

A

SGLT2 inhibitors

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11
Q

What is the leading cauuse of end-stage renal disease?

A

Diabetes

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12
Q

What functional changes are seen in macroalbuminuria (overt) nephropathy?

A
  • >300 mg albuminuria
  • May have nephrotic-range (>3g) proteinuria
  • GFR declines rapidly
  • Almost all patients are hypertensive
  • Usually occurs ~15 years after diagnosis of diabetes
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13
Q

What is the goal for glycemic control in patients with diabetic nephropathy?

A

HbA1c ~7%

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14
Q

What functional changes are present in advanced diabetic nephropathy (renal failure)?

A
  • GFR declines to <15 mL/min
  • Hypertension often worsens
  • Usually occurs 15-20 years after diagnosis of diabetes
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15
Q

Why is diabetic neprhopathy easier to study in Type 1 Diabetes than Type 2 Diabetes?

A

Type 1 diabetes is usually diagnosed within weeks or months of onset due to the dramatic physiological changes that follow destruction of the pancreatic islet cells

Type 2 dibaetes develops over years and the time between onset and diagnosis is difficult to determine

Therefore, it is easier to study diabetic nephropathy in type 1 diabetics because we know more about the timeline of development

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16
Q

Why does hypertension worsen with advanced nephropathy?

A

Sodium and fluid retention

Due to decreased GFR, poor renal function

17
Q

What are the major long-term consequences of diabetes mellitus?

A
  • Microvascular
    • Nephropathy
    • Retinopathy
    • Neuropathy
  • Macrovascular
    • Cardiovascular events (MI, Stroke)
    • Peripheral vascular disease
    • Amputations
18
Q

What is the classic or almost pathognomonic histologic finding in diabetic nephropathy?

What are 2 other histologic findings in diabetic nephropathy?

A

Classic = Kimmelstiel-Wilson Nodules

Other = Mesangial matrix expansion, GBM thickening

19
Q

How long does the hyperfiltration (silent) phase of diabetic nephropathy usually last?

A

5-10 years

20
Q

What are the 3 pathogenic factors that contribute to hyperfiltration?

A
  • Glomerular hypertrophy
    • -> Increased capillary surface area
  • Afferent arteriolar vasodilation
    • -> Increased flow into capillaries
  • Efferent arteriolar vasoconstriction
    • -> Increased pressure within the glomerulus
    • Due to the action of Angiotensin II
21
Q

What are the major strategies for treatment and progression prevention for diabetic nephropathy?

A
  • Tight glycemic control
    • Reduces microalbuminuria, but may not slow GFR decline
  • Treat hypertension
    • Perhaps the most important risk factor for the progressive decline in GFR in diabetes
    • Goal is <140/90, but <130/80 is probably better
    • Use ACEI or ARB
  • SGLT-2 inhibitors
    • Inhibt Na+ and glucose uptake in the PCT
    • -> Urinary glucose loss
    • -> Prevent activation of RAAs
22
Q

What is the main cause of decreased GFR in patients with diabetic neprophathy?

A

Mesangial matrix expansion

  • Impinges on capillary loops
  • Obliterates the surface area available for filtration
  • -> Tubulointerstitial fibrosis
    • -> Nephron loss
23
Q

What structural changes are seen when a patient has microalbuminuria (incipient) nephropathy?

A
  • Basement membrane thickening
  • Mesangial matrix expansion (pictured)
    • Leads to glomerulosclerosis in a diffuse patter
    • May be nodular
    • This eventually leads to Kimmelstiel-Wilson nodules
24
Q

What are the pathogenic factors that drive diabetic nephropathy?

A 
Altered hemodynamics
\+
Metabolic stimuli (hyperglycemia)
\+
Genetic predisposition

->

  • Hyperfiltration
  • Proteinuria development
  • Intraglomerular hypertension
  • Mesangial matrix expansion
25
Q

What percentage of patients will progress to ESRD after developing macroalbuminuria in 10 years?

15 years?

A

50% in 10 years

75% in 15 years

If a paitnet lives long enough after deveopint macroalbuminuria, they will progress to ESRD

26
Q

Which patient is most likely to have diabetic nephropathy?

  1. A 50 year-old African American man with type 2 diabetes for 15 years who is being treated with laser photocoagulation therapy for diabetic retinopathy
  2. A 50 year-old Caucasian woman who has been following closely with her primary physician and was diagnosed with diabetes 3 years ago.
  3. A 50 year-old Caucasian man with type 1 diabetes for 30 years who follows with his ophthalmologist yearly and has no evidence of diabetic retinopathy.
A

a. A 50 year-old African American man with type 2 diabetes for 15 years who is being treated with laser photocoagulation therapy for diabetic retinopathy

27
Q

Why do diabetic patients develop proteinuria?

A
  • Basement membrane abnormalities
    • Get thicker, but the integrity of the membrane is compromised
  • Podocyte abnormalities
    • Damage
    • Foot processes fuse and detach from the GBM -> Apoptosis
  • Hemodynamic effects
    • Intraglomerular hypertension -> Worse albuminuria
    • Due to efferent arteriolar vasoconstriction
      • Increased glucose in the filtrate
      • -> Afferent arteriolar vasodilation
      • -> Increased SGLT2 channels in the PCT
      • -> Increased Na+ and glucose reabsorption
      • -> Decreaed Na+ delivery to the macula densa
      • -> Renin release, increased angiotensin II
        • -> efferent arteriolar constriction
      • -> Hyperfiltration and intra-glomerular hypertension
28
Q

What is the difference between microalbuminuria and proteinuria?

A

Up to 150 mg/day of general proteinuria is not concerning

However, any albumin in the urin is abnormal

Microalbuminuria is not always detected on a urine dipstick because the amount is very small (30-300 mg/day)

=> use urinary albumin / urinary creatinine rato to determine albuminuria

29
Q

How does hyperglycemia lead to diabetic nephropathy?

A

Hyperglycemia ->

  • Activation of signaling pathways + Generation of ROS
  • -> Cytokine release
    • ​TGF-beta, VEGF, Angiotensin II
  • Cytokine release is profibrotic
    • -> ​Sclerosis
  • Cytokine release contributes to altered hemodynamics
    • -> Albuminuria
30
Q

Describe the changes in GFR and proteinuria as diabetic nephropathy progresses

A
  • Hyperfiltration: Pre diabetic nephropathy
    • Usually we don’t detect this stage
      • No albuminuria
      • Increased GFR is not typically concerning
  • Microalbuminuria: Incipient diabetic nephropathy
    • GFR normal
    • Albuminuria begins (30-300 mg/day)
  • Macroalbuminuria: Overt diabetic nephropathy
    • 15+ years after onset)
    • Decline in GFR
    • Steep rise in albuminuria
  • End stage renal disease
    • GFR < 15 mL/min

Renal by Minnie (27 decks)

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