SM 207 Diabetic Nephropathy

Question 1

What is Diabetes Mellitus?

Answer 1

Diabetes Mellitus is a disorder that results in hyperglycemia due to insulin deficiency (Type I) and/or resistance (Type II)

Question 2

What is Type I Diabetes?

Answer 2

A form of DM that presents at birth or within months of development characterized by no insulin due to destruction of pancreatic islet cells

Question 3

What is Type II Diabetes?

Answer 3

A form of DM that presents later in life due to insulin resistance and eventual deficiency

Question 4

What is the pathophysiological cause of Type I Diabetes?

Answer 4

Autoimmune destruction of pancreatic islet cells early in life

Question 5

When and how does Type I Diabetes present?

Answer 5

Type I Diabetes presents early in childhood with severe illness, due to autoimmune destruction of pancreatic islet cells

Question 6

Which occurs first in Type II Diabetes, Insulin Resistance or Insulin deficiency?

Answer 6

Insulin Resistance first manifests in Type II Diabetes, due to high secretion of Insulin desensitizing cells

Insulin deficiency occurs later

Question 7

What is the major risk factor for Type II Diabetes?

Answer 7

Obesity

Question 8

What factor about Type II Diabetes effects Diabetic Nephropathy?

Answer 8

Duration - long-standing DIIM has a greater likelihood of developing Diabetic Nephropathy

Question 9

Is Diabetes Mellitus curable?

Answer 9

Only if it’s Type I, with a pancreas transplant

Type II cannot be cured and is only managed

Question 10

What do the microvascular consequences of Diabetes Mellitus refer to?

Answer 10

Nephropathy, Retinopathy, Neuropathy

Question 11

What do the macrovascular consequences of Diabetes Mellitus refer to?

Answer 11

Cardiovascular risk (MI, Stroke)

Question 12

How does Diabetes Mellitus effect the extremities?

Answer 12

Peripheral Vascular Disease, Amputations

Question 13

Which races are more at risk for Diabetes?

Answer 13

Hispanics and African Americans

Increased DIIM risk predisposes kidney disease risk

Question 14

What is the leading cause of ESRD?

Answer 14

Diabetes

Question 15

What is the leading cause of Blindness in adults?

Answer 15

Diabetes

Question 16

Is Diabetic Nephropathy inevitable in patients with Diabetes?

Answer 16

No, about 1/3 develop Diabetic Nephropathy

Question 17

Why is the natural history of Diabetic Nephropathy more predictable in patients with Type I DM than those with Type II DM?

Answer 17

Type I DM has a clear time of onset, while Type II DM may be long-standing, and the duration of Diabetic damage sets the course of Diabetic Nephropathy

Question 18

What are the 4 stages of Diabetic Nephropathy?

Answer 18

Hyperfiltration (Silent)
Microalbuminuria (Incipient)
Macroalbuminuria (Overt)
Advanced Nephropathy

Question 19

What lab abnormalities are found in the Hyperfiltration stage of Diabetic Nephropathy?

Answer 19

None - Hyperfiltration stage is not detectable on labs

Question 20

What effect does the Hyperfiltration have on GFR during Diabetic Nephropathy?

Answer 20

During the Hyperfiltration stage, single Nephron GFR increases

Question 21

Which stage of Diabetic Nephropathy is the first that can be detected in clinic on urine?

Answer 21

Microalbuminuria (Incipient)

Question 22

Silent Diabetic Nephropathy is also known as?

Answer 22

Hyperfiltration

Question 23

Incipient Diabetic Nephropathy is also known as?

Answer 23

Microalbuminuria

Question 24

Overt Diabetic Nephropathy is also known as?

Answer 24

Macroalbuminuria

Question 25

What functional changes occur during the Silent phase of Diabetic Nephropathy?

Answer 25

Silent = Hyperfiltration stage Increase in GFR (always, not normally measured) Increase in Kidney Size (sometimes, seen on ultrasound)

Question 26

What structural changes occur during the Silent phase of Diabetic Nephropathy?

Answer 26

Silent = Hyperfiltration stage ``` Glomerular Hypertrophy (no cell proliferation) Glomerular Basement Membrane Thickening ```

Question 27

What is the first sign of Diabetic Nephropathy that can be detected, ever?

Answer 27

Glomerular basement thickening, in the Silent Stage

Question 28

What are the functional changes that accompany Incipient Diabetic Nephropathy?

Answer 28

Incipient = Microalbuminuria Microalbuminuria develops Normal GFR Microvascular complications (Eyes, Feet, Sensation)

Question 29

Is GFR normal in the Incipient stage of Diabetic Nephropathy?

Answer 29

Yes

Question 30

What is Microalbuminuria?

Answer 30

30 - 300mg of albumin in urine

Question 31

Is Albuminuria the same as Proteinuria?

Answer 31

NO; proteinuria is all protein except Albumin and can have up to 150mg of protein normally

Question 32

Is Diabetic Retinopathy a predictor of Diabetic Nephropathy?

Answer 32

Yes; patients with Diabetic Retinopathy tend to have Diabetic Nephropathy

Question 33

What structural changes accompany Incipient Nephropathy?

Answer 33

Mesangial Matrix expansion

Question 34

What is the hallmark of Diabetic Nephropathy?

Answer 34

Mesangial Matrix expansion

Question 35

What is Mesangial Matrix expansion?

Answer 35

Mesangial space expanding due to increased ECM proteins like collagen and fibronectin

Question 36

How does Mesangial Matrix expansion effect the kidney?

Answer 36

ECM expansion causes loss of filtration capacity and the glomerulus loses normal function, leading to nodules known as Kimmelsteil-Wilson lesions

Question 37

What are Kimmelsteil-Wilson lesions pathopneumonic for?

Answer 37

Pathopneumonic for Diabetic Nephropathy

Question 38

What causes Kimmelsteil-Wilson lesions?

Answer 38

Mesangial Matrix expansion in Incipient Diabetic Nephropathy

Question 39

What functional changes accompany Overt Nephropathy?

Answer 39

Overt = Macroalbuminuria Albuminuria > 300mg/day GFR declines rapidly (6-12 ml/min/year) Hypertension

Question 40

Which stage of Diabetic Nephropathy reflects the first decline in GFR?

Answer 40

Overt Nephropathy (Macroalbuminuria)

Question 41

What is nephrotic range proteinuria?

Answer 41

> 3g/day

Question 42

How rapidly does GFR decline in Incipient Nephropathy?

Answer 42

It doesn't, compensation still holds

Question 43

Why does HTN occur during Overt Diabetic Nephropathy?

Answer 43

Sodium and fluid retention

Question 44

What are the pathogenic factors that drive tissue injury in Diabetic Nephropathy?

Answer 44

Hyperfiltration Proteinuria Intraglomerular HTN Mesangial Matrix Expansion

Question 45

What 3 factors cause Hyperfiltration in Diabetic Nephropathy?

Answer 45

Glomerular Hypertrophy leading to increased capillary surface area Afferent Arteriolar Vasodilation Efferent Arteriolar Vasoconstriction

Question 46

What causes Afferent Arteriolar Vasodilation in Diabetic Nephropathy?

Answer 46

``` Less NaCl to the Macula Densa = Less ATP = Less Adenosine = Less Vasodilation of Afferent Arteriole = Vasodilation of Afferent Arteriole ```

Question 47

What causes Efferent Arteriolar Vasoconstriction in Diabetic Nephropathy?

Answer 47

Less NaCl to the Macula Densa causes Vasoconstriction due to Angiotensin II

Question 48

What causes Proteinuria in Diabetic Nephropathy?

Answer 48

GBM thickens but loses quality due to hyperglycemia Podocyte abnormalites as foot processes detach Hemodynamic effects as Intraglomerular HTN worsens

Question 49

Why does Intraglomerular HTN worsen albuminuria?

Answer 49

Intraglomerular HTN = high pressure that drives protein efflux into urine

Question 50

How does Mesangial Matrix Expansion correlate with GFR?

Answer 50

Inversely; the expanding matrix impinges capillaries and lowers surface area for filtration

Question 51

What effects do cytokines like TGF-Beta have in Diabetic Nephropathy?

Answer 51

Cytokines are Inflammatory and Pro-Fibrotic

Question 52

What pathways does hyperglycemia trigger?

Answer 52

Advance Glycation End-product formation (AGE) Signaling Pathways (MAPK, HIF) ROS release

Question 53

What do cytokines do to urine protein?

Answer 53

Cytokines alter hemodynamics and promote albuminuria

Question 54

What is the primary goal in Diabetic Nephropathy treatment?

Answer 54

Intensive glycemic control down to Hb1AC < 7%

Question 55

What is the risk with pursuing intensive glycemic control in treating Diabetic Nephropathy?

Answer 55

Intensive glycemic control risks Hypoglycemia

Question 56

Does Intensive Glycemic control improve microvascular complications in Diabetic Nephropathy?

Answer 56

Yes, but no evidence for benefit of Macrovascular complications

Question 57

Does Intensive Glycemic control improve macrovascular complications in Diabetic Nephropathy?

Answer 57

No, but it does benefit Microvascular complications

Question 58

What is the most important risk factor for progressive GFR decline in diabetes?

Answer 58

Hypertension

Question 59

What is the blood pressure target in diabetic patients?

Answer 59

Since they have a CV risk factor, aim for 130/80, which may require multiple anti-hypertensives

Question 60

Which classes of anti-hypertensive are first-line in diabetes?

Answer 60

ACE-inhibitors and ARB's, because they have renoprotective effects

Question 61

What are the renoprotective effects of ACEi/ARB's?

Answer 61

They not only control BP but also relax the efferent Arteriole to decrease intraglomerular pressure and lower protein being pushed into urine Also block profibrotic effects of Angiotensin II

Question 62

Which component of the RAAS pathway is pro-fibrotic in the glomerulus?

Answer 62

Angiotensin II ACEi and ARB can block the pro-fibrotic effects, making them first line anti-HTN drugs in diabetics

Question 63

Which is better for managing Diabetic Nephropathy, ACEi or ARB?

Answer 63

No evidence one is better than the other Risk of cough in ACEi

Question 64

Should you use both an ACEi and an ARB in managing Diabetic Nephropathy?

Answer 64

NO, risk of AKI and Hyperkalemia

Question 65

What are SGLT inhibitors?

Answer 65

Inhibitors of the Na/Glucose transporter in the PCT

Question 66

What is the suffix for SGLT inhibitors?

Answer 66

-gliflozins

Question 67

How do SGLT inhibitors treat Diabetic Nephropathy?

Answer 67

Promote urinary glucose loss and reduce both microvascular and macrovascular complications in Diabetes

Question 68

Do SGLT inhibitors prevent macrovascular or microvascular complications?

Answer 68

Both!

Question 69

How do SGLT inhibitors work?

Answer 69

They block the Na/Glucose transporter in the PCT to improve Na delivery to the Macula Densa and decrease RAAS activation, lessening Glomerular HTN and diabetes-induced hyperfiltration

Question 70

What class of drugs reduces diabetes-induced hyperfiltration?

Answer 70

SGLT inhibitors

Question 71

What clinical indicators should be tracked in diabetic nephropathy?

Answer 71

Albuminuria, Kidney Function, Blood Pressure