Diabetic Nephropathy Flashcards
2 “major clinical manifestations” of diabetic nephropathy? (i.e. broad problems you can determine from usual lab studies)
Albuminuria
Chronic kidney disease (CKD)
3 characteristic structural changes in diabetic nephropathy?
GBM thickening.
Mesangial thickening.
Glomerular sclerosis.
The 4 clinical stages of diabetic nephropathy are defined by what 2 parameters?
GFR and albuminuria/proteinuria
In stage 1 diabetic nephropathy, what are GFR and urine albumin?
GFR is actually increasing, but the urine albumin has not yet increased.
What’s the deal with the increased GFR in diabetic pre-nephropathy?
Cause, probably, by increased renal blood flow… but it’s not beneficial.
The kidneys can also enlarge at this point.
What structural change is already happening in diabetic pre-nephropathy?
Increased GBM thickness.
What are the GFR and urine albumin like stage 2 of diabetic nephropathy?
GFR is still high.
Urine albumin begins to rise - “microalbuminuria”
What levels of urine albumin are typical for stage 2 diabetic nephropathy?
30-300mg/24hrs (normal is about 15mg/24hrs)
Don’t confuse this with total urine protein, which is normally <150mg/24hrs. Lots of that is Tam-Horsfall protein.
What’s the natural history for untreated stage 2 diabetic nephropathy?
Depends on T1DM vs. T2DM:
T1DM: 80% progress to overt nephropathy.
T2DM: 25-40% progress to over nephropathy.
What do you see on light microscopy of Stage 2 diabetic nephropathy?
Continued GBM (and tubular basement membrane) thickening. Mesangial expansion (there's less Bowman's space visible in the glomeruli).
Stage 4 diabetic nephropathy.. what happens to GFR and urine albumin?
Overt nephropathy with high urine albumin and low, progressively declining GFR.
2 clinical findings (other than GFR and urine albumin) that change in stage 3 diabetic nephropathy?
How about kidney size?
Microscopic hematuria is sometimes present.
Hypertension is common.
Kidney size is reduced to normal due to fibrosis/scarring.
Histological findings in the glomeruli in stage 3 diabetic nephropathy? (there are 2 different patterns)
Usually: Diffuse mesangial sclerosis.
Less common, but pathognomonic: Nodular glomerulosclerosis (aka Kimmelstiel-Wilson lesions)
What are some extra-glomerular histologic findings in stage 3 diabetic nephropathy?
Arteriolar hyalinosis (perhaps largely responsible for the HTN)
Tubular atrophy
Interstitial fibrosis
Stage 4 diabetic nephropathy?
Is really bad. Decreasing GFR, urine albumin might reach nephrotic levels.
Nephrotic syndrome (proteinuria, edema, hypoalbuminemia, hyperlipidemia) might occur.
Well on the way to ESRD.
3 aspects of a diagnosis of diabetic glomerulopathy?
Persistent proteinuria.
Absence of other causes of renal disease.
Other evidence of microvascular disease, esp retinopathy.
When would you do a biopsy when working up a patient with suspected diabetic nephropathy?
When there are funny things in the history / lab results that aren’t consistent with diabetic nephropathy or point to other possible causes.
What are 5 modifiable risk factors for diabetic nephropathy?
Hyperglycemia Hyperfiltration HTN Soluble mediators Smoking/obesity
What are 2 proposed mechanisms by which hyperglycemia causes damage that leads to diabetic nephropathy?
Hyperglycemia -> non-enzymatic glycation -> advanced glycation end products (AGEs) -> inflammation.
High glucose gets converted to sorbitol, consuming NADPH -> NADPH depletion -> less glutathione activity to neutralize bad stuff like free radicals.
How can the hyperfiltration of early diabetic nephropathy be reduced?
With an ACE inhibitor or ARB.
A-II causes constriction of efferent arteriole -> increased filtration pressure.
ACE inhibitor -> efferent arteriole relaxation.
What’s a soluble mediator of sclerosis that you might be able to inhibit to slow progression of diabetic nephropathy?
TGF-beta
