01-31 Diabetic Nephropathy

Question 1

What is the commonest cause of ESRD?

—2nd

Answer 1

Diabetes by far! (~50%)

—HTN is #2 (~25%)

Question 2

What percent of diabetics have DM1 vs DM2?

Answer 2

85-90% DM2

—Only 10-15% DM1

Question 3

Diabetic Nephropathy develops in which percentage of patients with diabetes?

Answer 3

Only about 40%
—Not tightly correlated to glycemic control.
—Suggests that this about more than blood sugar control.

Question 4

What is meant by glucose/metabolic “memory”?
—Hypothesized etiology?
—Clinical implications?

Answer 4

This concept suggests that the body somehow “remembers” hyperglycemic state and acts as if it occurring even after tight control of glucose.
—For example, patient is diagnosed with early retinopathy gets her/his diabetes under tight control, however the diabetic retinopathy continues worsening as though the patient had poor control.
—Thought to have epigenetic mechanism

Question 5

What is the earliest sign of diabetic nephropathy?

—How is it detected?

Answer 5

Microalbuminuria is first sign.
—This is a level of albumin too small to show up on a urine dipstick, so it can go unnoticed.
—Have to do a spot urine albumin/creatinine ratio.
—Tricky though, because normal healthy people can have non-pathologic microalbuminemia now and then.
—Also could have False Negatives.
—Need to repeat to ensure.

Question 6

histological ∆s seen w/ diabetic nephropathy

Answer 6

—thickened BM
—expanded mesangium
—Kimmelstiel-Wilson nodules

Question 7

Preventative Tx for diabetic nephropathy

Answer 7

Improve glucose control
Improve blood pressure
Decrease proteinuria (w/ ACEIs/ARBs, e.g.)
Exercise
Weight loss

Question 8

Effect of exercise on blood sugar

Answer 8

Increases activity of insulin receptor and IRS proteins in muscle
—Decreases insulin resistance
—Increases glucose uptake by muscle and lowers HbA1c
—Even standing (vs. sitting) or walking to the mailbox; anything to get patient moving even just a little bit more.

Question 9

New recommended BP goal for diabetic Pts

Answer 9

140/90

Question 10

The Degree of Proteinuria Predicts Stroke and CHD Events in Type 2 Diabete. Why?

Answer 10

Because proteinuria is a sign that not only the glomeruli are damaged, but also that there is systemic endothelial damage.

Question 11

How do ACE-Is/ARBs (and DRIs - direct renin inhibitors) protect the kidney in pts w/ diabetes?

Answer 11

These drugs lower BP which is important in and of itself. However, the drugs have been shown to be WAY better at preventing kidney disease.
—Angiotensin II constricts the efferent arteriole (EA)
—By blocking A-II w/ these Rx, you dilate the EA
—This lowers the pressure inside the glomerular capillaries and protects them from HTN-ive damage.
—Have to d/c when their GFR gets too low though because need to constrict the EA at that point to increase

Question 12

Why is giving NSAIDs to a pt on ACE-inhibitor a problem?

Answer 12

NSAIDs inhibits COX-2 which makes vasodilatory prostaglandins which act on the afferent arteriole (AA).
—‪↓‬ dilatory prostaglandins → constriction of AA
—add this to dilation of EA from ACE-I
—really low pressure in the glomerulus
—precipitous drop in GFR
—Pts with ESRD already have low GFR so can easily → renal failure

Question 13

Current Screening, tx and monitoring guidelines for diabetics (2013)
—Just FYI!

Answer 13

Don’t start ACEI/ARB in pts who are normotensive, normoalbuminuric
—BP goal <140/90
—Asses microalbuminuria in type 1 DM after 5 years and all type 2 DM at dx; 2 of 3 samples
—Tx with ACEI or ARB suggested in pts with microalbuminuria and recommended in patients with albuminuria
—Monitor serum Cr and K+ before and after initiation of treatment with ACEI and ARB (too watch out for drop in GFR)