6. Diabetic Nephropathy
Presence of
microalbuminuria or overt
nephropathy (i.e.
macroalbuminuria) in
patients with DM who lack
indicators of other renal
diseases
7. Diabetic Nephropathy
characterized by the following:
Persistent albuminuria (>300 mg/d or >200
μg/min) that is confirmed on at least 2
occasions 3-6 months apart
A relentless decline in the glomerular filtration
rate (GFR)
Elevated arterial blood pressure
8. Diabetic Nephropathy
Major histologic changes occur in the
glomeruli of persons with diabetic nephropathy
Mesangial expansion
glomerular basement membrane thickening
glomerular sclerosis
15. DMN-PATHOGENESIS
Sorbitol
glucose + aldose reductase = sorbitol
as sorbitol levels , myoinositol levels fall
as myoinositol levels fall, Na-KATPase activity
declines, shifting the redox potential of the cell
treatment with aldose reductase inhibitors has not
been shown to be beneficial.
17. Albuminuria
Microalbuminuria
urinary albumin excretion between 30 and 300
mg/day or between 30 and 300 mg/g creatinine
on a random urine sample)
First sign of nephropathy
Predictor of overt nephropathy
Macroalbuminuria
urinary albumin excretion above 300 mg/day or
above 300 mg/g creatinine on a random urine
sample)
Without treatment, is followed by progressive
decrease in GFR
18. Progressive disease with little or no
albuminuria
the degree of albuminuria is not necessarily
linked to disease progression (type 1 or type 2
DM)
Factor(s) responsible for progressive GFR decline
in nonproteinuric diabetic nephropathy are not
known
20. Diabetic Nephropathy ….
Epidemiology
type1
20-30% will develop microalbuminuria after 15
years from onset
Less than 50% of these will progress to overt
nephropathy
ESRD in 4-17% at 20 years and 16% at 30
years
Onset of overt nephropathy typically between
10-15 yrs
Overt renal disease in pts with no proteinuria at
21. Diabetic Nephropathy
Type two
At 10 yrs following Dx (UKPDS):
Microalbuminuria: 25%
Macroalbuminuria: 5%
22. MEASURES OF ALBUMINURIA
STAGE OF
NEPHROPATHY
URINE
DIPSTICK
URINE ACR*
(mg/mmol)
24 HR ALBUMIN
COLLECTION**
Normal Negative
<2.0 (men)
<2.8 (women)
<30 mg/day
Microalbuminuria Negative
2.0-20.0 (men)
2.8-28.0 (women)
30-300 mg/day
Overt nephropathy
(macroalbuminuria)
Positive
>20.0 (men)
>28.0 (women) >300 mg/day
*ACR = albumin to creatinine ratio
**Values are for urinary albumin, not total urinary protein, which will be higher than urinary albumin levels
23. Diabetic Nephropathy
Patients with nephropathy and DM type 1 have
also retinopathy and neuropathy
Retinopathy typically precedes nephropathy in
these patients and the converse is not true
The relationship in type 2 DM is not
predictable
type 2 diabetics with marked proteinuria and
retinopathy most likely have diabetic
nephropathy
24. Adapted from Breyer JA et al. Am J Kid Dis 1992; 20(6): 535.
Time (yrs) 0 5 20 30
Onset of
Diabetes
Onset of
Proteinuria
End Stage
Renal
Disease
STRUCTURAL CHANGES
(Increasing glomerular basement
membrane
thickening and mesangial expansion)
Hypertension
OVERT NEPHROPATHY
Rising Scr,
Decreasing GFR
INCIPIENT NEPHROPATHY
Hyperfiltration,
microalbuminuria,
rising blood pressure
PRECLINICAL
NEPHROPATHY
Course of Diabetic Nephropathy
25. DMN-COURSE
can be divided into 3 stages based on degree of
albuminuria
normoalbuminuria < 30mg albumin/day
microalbuminuria 30-300 mg/day
overt nephropathy > 300 mg/day
GFR normal
GFR abnormal
once final stage is entered, renal function begins to
decline
26. DMN-COURSE
Normoalbuminuria
albumin excretion <30mg/24hrs
may hyperfiltrate
lasts about 5-10yrs
Microalbuminuria
albumin excretion between 30-300mg /24hrs
increased risk of progression to overt nephropathy
increased cardiovascular mortality
lasts about 5-10yrs
27. DMN-COURSE
Overt Nephropathy
albumin excretion >300mg/24hrs
relentless decline in renal function between 2-
20ml/min/yr
systemic hypertension (70-85%) and edema
formation
virtually all type 1 have retinopathy and neuropathy
at this stage but only 50% of type 2
29. Diabetic Nephropathy
History:
Consider DN in patients who have DM and a
history of one or more of the following:
Passing of foamy urine
Otherwise unexplained proteinuria
Diabetic retinopathy
Fatigue and foot edema secondary to
hypoalbuminemia (if nephrotic syndrome is
present)
Other associated disorders (PVD,HTN, CAD)
31. Recommendations:
Nephropathy (1)
Screening
Assess urine albumin excretion annually
In type 1 diabetic patients with diabetes duration of ≥5
years
In all type 2 diabetic patients at diagnosis
ADA. VI. Prevention, Management of Complications. Diabetes Care 2014;37(suppl 1):S42
32. A 24 hour urinalysis for urea, creatinine and
protein
Perform to r/o nephritic picture ( other
glomerulopathies)
33. Other labs
Serum and Urinary Electrophoresis
Renal Ultrasonography
Renal biopsy
34. TYPE 1 DIABETES TYPE 2 DIABETES
annually > 5yrs with ACR+SCr at Dx and annually with
ACR, SCr and urinalysis
Suspicion of non-diabetic renal disease?
Workup or referral for non-
diabetic renal disease
No Yes
Check ACR results
NORMAL
<2.0 mg/mmol for men
<2.8 mg/mmol for
women
Repeat screen in 1 year
MICROALBUMINURIA
2.0-20.0 mg/mmol for men
2.8-28.0 mg/mmol for women
MACROALBUMINURIA
>20.0 mg/mmol for men
>28.0 mg/mmol for women
Diabetic nephropathy*
diagnosed
CDA 2003 CPG
36. Diabetic Nephropathy
indication of possible non-diabetic cause of
renal disease in patients with DM
Rising Cr with little/no proteinuria
lack of retinopathy or neuropathy
Persistent hematuria
Signs or symptoms of systemic disease
Inappropriate time course (rapidly rising Cr, renal
disease in a patient with short duration of DM)
Family history of non-diabetic renal disease (e.g.
PCKD)
39. DMN-TREATMENT
Overt nephropathy
same as for microalbuminurics
early referral for dialysis or transplantation
planning is critical (GFR ~ 30 ml/min, creatinine ~
250mmol/l)
STOP SMOKING
40. DMN-SUMMARY
a slowly progressive, proteinuric (nephrotic)
disease seen in 25-40% of diabetics
progresses to ESRF over 15-20 yrs
treatment aimed at:
tight glycemic control
tight BP control
RAS inhibition (ACEi or ARB)
Cardiovascular risks reduction
early referral for dialysis or transplantation
