Diabetic Nephropathy

Question 1

What is Diabetes mellitus?

Answer 1

refers to diseases of abnormal carbohydrate metabolism characterized by hyperglycemia.

It is associated with a relative or absolute impairment in insulin secretion and varying degrees of peripheral resistance to insulin action

Question 2

What things suggest DM?

Answer 2

symptoms of hyperglycemia (thirst, polyuria, polydipsia, weight lose, visual blurring), and has a fasting blood glucose concentration of 126 mg/dL or higher, or a random value of 200 mg/dL or higher, and confirmed on another occasion.

Question 3

T or F. Diabetes is the most common cause of ESRD

Answer 3

T. contributes to over 40% of ESRD

Question 4

What are the three categories of complications that occur in diabetes?

Answer 4

metabolic, macrovascular, and microvascular.

Question 5

What are diabetic macrovascular complications?

Answer 5

affect large blood vessels and include coronary, cardiovascular, cerebrovascular, and peripheral vascular disease (most common reason for extremity amputation).

Question 6

What are microvascular complications?

Answer 6

Diabetic microvascular complications (DMC) affect small blood vessels and include:

diabetic neuropathy,
diabetic nephropathy, and
diabetic retinopathy including diabetic macular edema.

Question 7

T or F. DMC can occur in patients with either Type 1 or Type 2 diabetes

Answer 7

T, even among those who have been able to obtain optimal management of glucose, blood pressure, and lipid levels. The clinical manifestations of DMC among patients with diabetes are similar, and it can affect nerves, kidneys, and eyes.

Question 8

How prevalent is diabetic nephropathy among diabetics?

Answer 8

Only 30 to 40% of type 1 and type 2 diabetics develop diabetic nephropathy

Question 9

Does family history play a part in risk of developing diabetic nephropathy in type I diabetes?

Answer 9

Yes, positive family history for diabetes mellitus with diabetic nephropathy in first degree relative results in risk for development of DN of 83% while a negative Hx for diabetic nephropathy results in risk of 17%

Question 10

What races have the highest risk of developing diabetic nephropathy?

Answer 10

African-Americans, Native Americans, Mexican Americans, Polynesians have a greater risk for the development of DN than Caucasians.

Question 11

What is the first sign of development of DN?

Answer 11

microalbuminuria that over time (wouldn’t be picked up by normal urinalysis), leads to overt proteinuria, reduced GFR, and then hypertension

Question 12

We can describe 5 stages or phases of diabetic nephropathy. What is Stage 1 defined as?

Answer 12

Hyperfiltration, or an increase in glomerular filtration rate (GFR) (predominantly by afferent dilation) occurs. Kidneys increase in size.

Question 13

What is Stage 2 defined as?

Answer 13

Glomeruli begin to show damage and that manifests as microalbuminuria (30 -300 mg/g creatinine- untimed sample) occurs.

Blood pressure usually begins to rise about the same time that microalbuminurea occurs.

NOTE: Individuals with type 1 and type 2 diabetes may remain at stage two for many years with good control of blood glucose and blood pressure.

Question 14

What is Stage 3 defined as?

Answer 14

loss of albumin and other proteins exceeds 300 mg/day or 200 micrograms/minute. When this occurs, the patient is diagnosed as having clinical albuminuria.

During this stage the kidneys also demonstrate an inability to adequately filter wastes from the blood, and creatinine and urea-nitrogen blood levels begin to rise.

Question 15

What is Stage 4 defined as?

Answer 15

aka “advanced clinical nephropathy”. A decrease in GFR (less than 75) signals that the patient is progressing to kidney failure.

If an increase in blood pressure was not evident in prior stages, it is usually evident at this time.

Question 16

What is Stage 5 defined as?

Answer 16

aka Kidney failure, or end stage renal disease (ESRD). GFR is less than 10 ml/min.

The glomeruli function at low levels and patients in this phase require dialysis or transplantation to survive.

Question 17

How fast is the progression of DN usually?

Answer 17

The average length of time to progress from Stage 1 to Stage 4 kidney disease is 17 years for a person with type 1 diabetes (developing over proteinemia heralds lowered GFR).

The average length of time to progress to Stage 5, kidney failure, is 23 years.

Question 18

T or F. Diabetics with Macroalbuminuria are More ikely to Die than develop ESRD

Answer 18

T.

Question 19

How is DN distinguished from other forms of chronic kidney disease?

Answer 19

The glomeruli and kidneys are typically normal or increased in size initially, whereas other forms of CKD are characterized by reduced renal size

Question 20

Why do the glomeruli (and kidneys) initially increase in size?

Answer 20

Glucose provides an osmotic diuretic effect resulting in increased renal filtration, leading to glomerular hypertrophy

Question 21

What does glomerular hypertrophy cause?

Answer 21

Glomerular pressure increases and the kidneys respond with hypertrophy of epithelium and endothelium, which decreases GFR

Question 22

What does the hypertrophy of epithelium and endothelium result in?

Answer 22

injury to the glomerular basement membrane causing it to leak plasma proteins into the urine.

Question 23

How does the kidney respond to increased proteinuria?

Answer 23

The PT attempts to reabsorb this filtered protein causing injury to the tubular cells, and activating an inflammatory response, and is associated with the development of lipid metabolic abnormalities that create further oxidative stress on the already compromised glomerulus.

Question 24

What is the eventual end result of the resultant tubular inflammatory response and renal microvascular injury?

Answer 24

This activate pathways that lead to fibrosis and scarring of both glomerular and tubular elements of the nephron.

Question 25

How does the kidney respond to decreased GFR?

Answer 25

Ang II is increased and causes AT1 receptor-mediated constriction of efferent arterioles to increase single nephron glomerular filtration rate and raises intraglomerular pressure, causing further glomerular hypertension

Question 26

What else does angio II do?

Answer 26

Angiotensin II can both stimulate the production of TGF-β by tubuloepithelial cells and fibroblasts.

Question 27

What does TGF-β do?

Answer 27

Causes further proliferation of fibroblasts and tubuloepithelial cells to increased extracellular matrix synthesis and inhibition of enyzmes that degrade matrix breakdown

Question 28

T or F. TGF-B has been involved with kidney scarring in many diseases

Answer 28

T. Including DN

Question 29

There are changes in the glomerular BM structure that occur even BEFORE microalbuminuria is seen in DN. How do we know?

Answer 29

Type IV collagen is directly stimulated by hyperglycemia and increased urinary levels indicate changes in the BM due to glycosylation of the capillary BM

Question 30

What is unique about ACEIs and ARBs?

Answer 30

while most others only reduce arterial pressure, these lower glomerular capillary pressures as well

Question 31

T or F. ACEIs and ARBs don’t drop GFR as much as you would predict

Answer 31

T. Because Kf increases even though the filtration pressure decreases. Will only see a slight rise in creatinine

Question 32

What is the goal of treatment in DN?

Answer 32

get HTN under control

Question 33

What things are at increased risk with Diabetes mellitus?

Answer 33

• pyelonephritis
• papillary necrosis
• type 4 RTA
• neurogenic bladder

Question 34

T or F. Immunoflourescence in DN is negative

Answer 34

T. Mostly diagnosed with LM because EM doesnt change much throughout stages