Diabetic Nephropathy - Boner

Question 1

Definitions of albuminuria

Answer 1

Definitions: Normal urine albumin: <30 mg/day
Microalbuminuria 30-300mg/day
Macroalbuminuria >300mg/day=proteinuria >500mg/day

Question 2

Stages in diabetic renal disease

Answer 2

1. Hyperfiltration and nephromegaly
2. Normoalbuminuria, mild path changes GFR normal (progressing, early on hyperfiltration)
3. Microalbuminuria, Incipient DN, GFR normal in type one but decreased in type 2
4. Macroalbuminuria or overt DN decreased GFR
5. ESRD (80% of type I and 50-80% of type II because die of CV causes more often)

Albumin excretion rate increases very quickly as diabetes progresses. BP increases but at a slower rate.

Type II has more quick deterioration than type I.

Question 3

Pathology of Diabetic Nephropathy

Answer 3

Thickening of glomerular basement membrane (GBM) and tubular basement membrane – early changes
Arteriolar hyalinosis and subendothelial accumulation of hyaline in the glomerular capillaries – 3-5 years after onset of diabetes
Increase in the fractional volume of mesangial matrix and mesangium per glomerulus – 4-5 years after onset of type 1 diabetes
Tubular hypertrophy
Diffuse diabetic glomerulosclerosis, widespread mesangial expansion within and among glomeruli
Nodular glomerulosclerosis (Kimmelstiel-Wilson nodules), segmental expansion of mesangium appearing as round fibrillar nodules – usually in proteinuria with established diabetic nephropathy

Question 4

Mechanisms of effects of angiotensin II

Answer 4

Hemodynamic effects
Systemic hypertension
Systemic & renal vasoconstriction
Stimulation of other vasoconstrictors & inhibition of vasodilators
Increased glomerular capillary pressure and permeability
Mesangial cell contraction leading to reduction in filtration surface area

Nonhemodynamic effects
Induction of renal hypertrophy and cell proliferation
Stimulation of extracellular matrix (ECM) synthesis
Inhibition of ECM degradation
Stimulation of cytokine production
Stimulation of superoxide production
Activation of nuclear factor – κB
Reduction in podocyte nephrin expression

Question 5

Factors influencing development and Progression of Diabetic nephropathy

Prevention strategies

Answer 5

Glycemic control and Duration of Disease
Increased Urine Albumin excretion at presentation
Hypertension and Family history of hypertension
Genetic factors
Smoking
Dyslipidemia
Male gender
Advancing age (type 2)

Good control of hyperglycemia (target HbA1c < 7.0%)
Maintain normotension as low as tolerated with a regimen that includes an ACE-inhibitor or AT1-receptor antagonist
Salt restriction (<6 g/d) and reduced protein intake (0.8 - 1.0 g/ kg body weight/ day
Cessation of smoking
Administration of statins
Weight loss (if obese), light regular aerobic exercise
Avoid use of minor analgesics
Avoid nephrotoxic medications (contrast media, antibiotics, nonsteroidals)