Diabetic Nephropathy

Question 1

Describe Type 1 vs Type 2 Diabetes Mellitus

Answer 1

Type 1: autoimmune desctruction of pancreatic beta cells = absolute insulin deficiency

Type 2: most common. hyperglycemia w/ varying degrees of insulin deficiency/resistance

Question 2

What are 3 microvascular and 3 macrovascular complications of Type 2 DM?

Answer 2

Micro: Retinopathy, Nephropathy, Neuropathy

Macro: Stroke, Heart Disease, Peripheral Vasc Disease

Question 3

What are 2 characteristics of Diabetic Nephropathy?

Answer 3

1. microalbuminuria -> macroalbuminuria
2. decline in GFR -> ESRD (DN is leading cause)
   * only 20-30 DM pts get DN

Question 4

What is the first sign of Diabetic Neuropathy?

Answer 4

Microalbuminuria

Question 5

What is Natural History progression of Nephropathy in Diabetes Type 1?

Answer 5

1. Normal
2. Elevated GFR (hyperfiltration)
3. Latency (Thickened BM, expanded mesangium)
4. Microalbuminuria
5. Macroalbuminuria
6. Azotemia (Renal failure) (Decreased GFR)
7. ESRD (GFR ~ 10)

Question 6

What are Advanced glycosylation end products (AGEs) and what is the result? (3 reasons)

Answer 6

Sugar cross-links structural proteins (collagens)
cause:
1. dysfunctional signalling (PKC, DAG)
—PKC inhibitor helps with diabetic nephropathy
2. oxidative stress
3. cytokine/growth factor release
RESULTS IN RENAL DYSFUNCTION

Question 7

What happens to the glomerulus during the Hyperfiltration stage?

Answer 7

glomerular hypertrophy (inc renal size)
Intraglomerular hypertension = inc shear stress on glomerular capillaries

Question 8

What the mechanism of glomerular hyperfiltration?

Answer 8

1. IGF-1 + ANP = dilation of afferent arteriole
2. AGE formation, Sex hormones
3. RAAS Activation (Ang II - efferent constriction)
   - –>GLOMERULAR HYPERTENSION
   - –>Fibrosis

Question 9

What is the histological appearance of a diabetic glomerular capillary?

Answer 9

1. Hyalinosis
2. Basement membrane is abnormally thick
3. Mesangial cell hypertrophy
4. Reduced Podocytes
5. KIMMELSTIEL-WILSON NODULE (mesangial Sclerosis)
6. NO IMMUNE COMPLEXES

Question 10

What are risk factors for Diabetic Nephropathy

Answer 10

1. Genetics
2. Hypertension
3. Hyperfiltration
4. Glycemic control
5. African Americans, Indians
6. Obesity
7. Smoking

Question 11

What are clinical characteristics of Diabetic Neuropathy?

Answer 11

1. Hx of DM >5 years
2. Proteinuria/albuminuria (BLAND urine sediment)
3. Poor glycemic control
4. HTN
5. Retinopathy, Neuropathy, some florid nephrotic syndrome (edema, hypoalbuminemia)
6. LOW GFR (acidemia, increased Cr, ESRD)

Question 12

What is the difference between MICRO and MACROalbuminuria

Answer 12

Micro: 30-300mg/day albumin excretion
Macro: >300mg/day albumin excretion

Question 13

What 2 things does Microalbuminemia signify?

Answer 13

1. increase cardiovascular mortality

2. first sign of nephropathy

Question 14

What are some causes of transient albuminuria

Answer 14

1. Fever
2. Exercise
3. infection
4. HTN, Hyperglycemia
5. cardiac failure

Question 15

How can you tell a renal disease is not caused by diabetes?

Answer 15

1. absence of retinopathy/neuropathy
2. short duration of DM
3. very active proteinuria + RBC casts
4. rapidly progressing

Question 16

Who should be screened for nephropathy with Diabetes?

Answer 16

Type 1: 5 years after duration of diabetes (then annually

Type 2: at time of Dx, annually

Question 17

How is microalbuminuria screened for?

Answer 17

Albumin to creatinine ratio in random spot collection

24 hours urinary albumin excretion

Question 18

How is diabetic nephropathy managed?

Answer 18

1. Glycemic control (HbA1c <7%)
2. RAAS blockers, ACE inhibs, ARB
3. dietary protein restriction
4. Manage hyper lipidemia
5. be healthy

Question 19

What are the benefits of ARBs in DN?

Answer 19

ARBs prevent long-term renal damage