SM_207a: Diabetic Nephropathy

Question 1

Diabetic nephropathy is a _____ consequence of diabetes

Answer 1

Diabetic nephropathy is a microvascular consequence of diabetes

Question 2

____ is the leading cause of ESRD in the U.S.

Answer 2

Diabetic nephropathy is the leading cause of ESRD in the U.S.

(slow process over time)

Question 3

Natural history of diabetic nephropathy involves the following phases: _____, _____, _____, and _____

Answer 3

Natural history of diabetic nephropathy involves the following phases:

1. Hyperfiltration (silent phase)
2. Microalbuminuria (incipient nephropathy)
3. Macroalbuminuria (overt nephropathy)
4. Advanced nephropathy/kidney failure

(structural and functional changes)

Question 4

Describe the hyperfiltration (silent) phase of diabetic nephropathy

Answer 4

Hyperfiltration phase of diabetic nephropathy

• Functional changes: increased GFR, increased kidney size
• Structural changes: glomerular hypertrophy, glomerular basement membrane thickening
• Usually occurs for 5-10 years

Question 5

In hyperfiltration (silent) phase of diabetic nephropathy, glomerular basement membrane ______

Answer 5

In hyperfiltration (silent) phase of diabetic nephropathy, glomerular basement membrane thickens

Question 6

Describe the microalbuminuria (incipient nephropathy) stage of diabetic nephropathy

Answer 6

Microalbuminuria (incipient nephropathy) stage of diabetic nephropathy

• Function changes: development of microalbuminuria (30-300 mg albumin in urine daily), GFR normal, diabetic retinopathy occurs
• Structural changes: continued GBM thickening, mesangial matrix expansion (Kimmelstein-Wilson lesions)

Question 7

In microalbuminuria (incipient nephropathy) stage of diabetic nephropathy, other microvascular complications of diabetes such as _____ may also occur

Answer 7

In microalbuminuria (incipient nephropathy) stage of diabetic nephropathy, other microvascular complications of diabetes such as diabetic retinopathy may also occur

Question 8

_____ of the microalbuminuria (incipient nephropathy) phase of diabetic nephropathy is the hallmark of diabetic nephropathy

Answer 8

Mesangial matrix expansion of the microalbuminuria (incipient nephropathy) phase of diabetic nephropathy is the hallmark of diabetic nephropathy

Question 9

In microalbuminuria (incipient nephropathy) phase of diabetic nephropathy, mesangial matrix expansion leads to nodules called ______

Answer 9

In microalbuminuria (incipient nephropathy) phase of diabetic nephropathy, mesangial matrix expansion leads to nodules called Kimmelstein-Wilson lesions

Question 10

Describe the macroalbuminuria (overt nephropathy) phase of diabetic nephropathy

Answer 10

Macroalbuminuria (overt nephropathy) phase of diabetic nephropathy

• Functional changes: albumuria increased to > 300 mg/day, GFR declines rapidly, most patients hypertensive
• About 15 years after diagnosis of diabetes
• Risk of progression to ESRD high

Question 11

In the macroalbuminuria (overt nephropathy) phase of diabetic nephropathy, GFR _____

Answer 11

In the macroalbuminuria (overt nephropathy) phase of diabetic nephropathy, GFR declines rapidly

Question 12

Describe the advanced nephropathy (renal failure) phase of diabetic nephropathy

Answer 12

Advanced nephropathy (renal failure) phase of diabetic nephropathy

• GFR falls: 15 mL/min is approaching need for renal replacement therapy
• Serum Cr rises
• Proteinuria decreases as GFR falls
• HTN worsens
• 15-20 years after diagnosis of diabetes

Question 13

Pathogenic factors involved in diabetic nephropathy are _____, _____, _____, and _____

Answer 13

Pathogenic factors involved in diabetic nephropathy are hyperinflation, proteinuria development, intraglomerular hypertension, and mesangial matrix expansion

(driven by combo of altered hemodynamics, metabolic stimuli such as hyperglycemia, and genetic predisposition)

Question 14

The factors involved in hyperinflation during diabetic nephropathy are _____, _____, and _____

Answer 14

The factors involved in hyperinflation during diabetic nephropathy are glomerular hypertrophy, afferent arteriolar vasodilation, and efferent arteriolar vasoconstriction

• Glomerular hypertrophy: increased capillary surface area
• Afferent arteriolar vasodilation: increased flow into capillaries
• Efferent arteriolar vasoconstriction: raising pressure within glomerulus due to angiotensin II

Question 15

Proteinuria occurs in diabetic nephropathy because the glomerular basement is leaky due to _____, _____, and _____

Answer 15

Proteinuria occurs in diabetic nephropathy because the glomerular basement is leaky due to GBM composition becoming poorer quality, podocyte abnormalities, and hemodynamic effects

• GBM composition: becomes thicker due to metabolic effects of hyperglycemia but of poorer quality
• Podocyte abnormalities: become damaged, foot processes fuse, detach from GBM, and undergo apoptosis -> decreased function of this layer
• Hemodynamic effects: intraglomerular HTN worsens albuminuria

Question 16

In diabetic nephropathy, intraglomerular hypertension occurs because the afferent arteriole is _____ due to _____, and the efferent arteriole is _____ due to _____

Answer 16

In diabetic nephropathy, intraglomerular hypertension occurs because the afferent arteriole is dilated due to hyperglycemia, and the efferent arteriole is constricted due to angiotensin II

Question 17

Mesangial matrix expansion correlates _____ with creatinine clearance (i.e. GFR)

Answer 17

Mesangial matrix expansion correlates inversely with creatinine clearance (i.e. GFR)

(expanding matrix impinges on capillary loops and obliterates surface area available for filtration, tubulointerstitial fibrosis also occurs and decreases GFR)

Question 18

Describe the pathways involved in diabetic nephropathy

Answer 18

Question 19

Prevention of diabetic nephropathy involves ______

Answer 19

Prevention of diabetic nephropathy involves tight glycemic control

(hyperglycemia is critical in the pathogenesis of diabetic nephropathy, glycemic control reduces amount of albumin leaked but does not affect decline in GFR)

Question 20

____ is perhaps the most important risk factor for the progressive decline in GFR in diabetes

Answer 20

Hypertension is perhaps the most important risk factor for the progressive decline in GFR in diabetes

(keep BP at < 130/80)

(diabetics often on multiple antihypertensives + diuretics)

Question 21

____ and ____ are medications that have beneficial effects for proteinuria and progression of nephropathy in diabetic nephropathy

Answer 21

ACE inhibitors and ARBs are medications that have beneficial effects for proteinuria and progression of nephropathy in diabetic nephropathy

(delay worsening of renal function, do not use both together)

Question 22

SGLT2 inhibitors inhibit the _____

Answer 22

SGLT2 inhibitors inhibit the Na⁺/glucose co-transporter 2 in PCT

(lead to urinary glucose loss)

Question 23

SGLT2 inhibitors _____ microvascular and _____ macrovascular complications independent of glucose control

Answer 23

SGLT2 inhibitors decrease microvascular and decrease macrovascular complications independent of glucose control

• Microvascular effects: decreased albuminuria, slow nephropathy
• Macrovascular effects: protective against cardiovascular disease