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Diabetic nephropathy
1. BY DR IRFAN ELAHI
CONSULTANT NEPHROLOGIST
MAYO HOSPITAL LAHORE
DIABETIC
NEPHROPATHY
2. DIFFERENT HISTOLOGICAL LESIONS AND THEIR
OCCURRENCE
Pathology of Diabetic Nephropathy in Patients
with Type 1 Diabetes and Proteinuria
3. Always Present
Glomerular basement membrane thickening.
Tubular basement membrane thickening.
Mesangial expansion with predominance of
increased mesangial matrix.
Interstitial expansion with predominance of
increased extracellular matrix material.
4. Often or Usually Present
Kimmelstiel-Wilson nodules (nodular
glomerulosclerosis).
Atubular glomeruli.
Foci of tubular atrophy.
Afferent and efferent arteriolar hyalinosis.
5. Sometimes Present
Hyaline caps or fibrin caps (Highly characteristic of
diabetic nephropathy)
Capsular drops (Highly characteristic of diabetic nephropathy)
Atherosclerosis.
Glomerular micro-aneurysms.
6. The more initial changes are glomerular
hypertrophy, mild mesangial expansion (matrix),
and thickening of the glomerular capillary walls,
these changes are more evident with electron
microscopy.
7. Thickening of the glomerular basement membrane
(GBM) is the first change that can be quantitated
Basement membrane thickening compared with normal
basement membrane.
10. A normal glomerulus (GBM) thickening and
moderate mesangial
expansion
Severe diffuse mesangial
expansion
11. Mesangial thickening
global and diffuse
thickening of the
capillary walls.
In addition there is
increase of the
thickness of the
Bowman’s capsule
basement membrane.
(Masson’s trichrome,
X400).
12. Nodular glomerulosclerosis
(Kimmelstiel-Wilson nodular lesions)
This is typically a focal and segmental change
likely resulting from glomerular capillary
wall detachment from a mesangial anchoring
point with consequent microaneurysm
formation.
Subsequent filling of the ballooned capillary
space with mesangial matrix material.
Approximately 50% of proteinuric type 1
diabetic patients have at least a few glomeruli
with nodular lesions.
13. Kimmelstiel-Wilson nodules.
Spherical, eosinophilic, with a central
acellular area, and they can be surrounded by
a ring of cells.
They stain blue or green with the trichrome
stain and they are positive with PAS and
methenamine-silver stains.
14. Nodules seen in light chain deposit
disease
More homogenous in size and distribution.
Stain more weakly.
They are negative, with silver stain.
The nodules seen in amyloidosis
Do not stain with silver and they are positive
for Congo red.
17. There is an increase in
mesangium with a
microaneurysm, arrowed.
This type of lesion heals
to form a Kimmelstiel–Wilson
nodule
18. The smallest
nodules can be
more cellular and
the greatest
nodules tend to be
acellular in the
centre and
surrounded by
more cellular
zones.
19. Nodular lesion as well as
mesangial expansion;
There is a typical
Kimmelstiel-
Wilson nodule at the top of
the glomerulus (arrow)
(periodic acid–Schiff).
20. The larger nodules
usually have a laminated
aspect (arrow)
Notice the variability in
the size of nodules in
this glomerulus,
something that usually
does not happen in
amyloidosis nor in light
chain deposits disease
(Masson’s trichrome,
X400).
21. The prominent
concentric lamination
with the silver stain
(arrow).
This finding is very
characteristic of nodular
diabetic
glomerulosclerosis.
(Methenamine-Silver,
X400)
24. Advance DNP
There is severe
ischemic shrinkage of the
tuft, but a Kimmelstiel–
Wilson nodule is still seen,
adherent to Bowman’s
capsule just at the origin of
the tubule
25. Exudative lesions of diabetic nephropathy.
1) Arteriolar hyalinosis.
2) Glomerular capillary subendothelial
hyaline (hyaline caps).
3) Capsular drops along the parietal surface
of the Bowman capsule.
26. 1) Afferent and efferent glomerular arteriolar
hyalinosis within 3 to 5 years after onset of diabetes
Afferent and Efferent arteriolar
hyalinosis. Diffuse and nodular
mesangial expansion
Glomerular arteriole showing
complete replacement of the
smooth muscle wall by hyaline
material and lumeral narrowing
(PAS stain)
27. Renal biopsy specimen from
the woman of 58 with
diabetic glomerulopathy.
Arterioles have severe
hyalinosis
28. 2) Glomerular capillary subendothelial hyaline
(hyaline caps).
Green Arrow
Glomerular
hyalinosis is
formed by plasma
components that
are accumulated
in peripheral
segments of the
tuft, also it is
called hyaline
cap or fibrin cap
(Masson’s
trichrome, X400).
29.
30. 3) Capsular drops along the parietal surface of the
Bowman capsule
Homogenous, hyaline deposit, in the
Bowman’s capsule.
Usually it is rounded or elongated and it is
highly suggestive of DN.
Although non-pathognomonic (it can be
occasionally seen in hypertension and other
idiopathic nodular glomerular lesions).
32. The arrow indicates a
beautiful capsular drop.
In this image we see the
capsular drop red, but in
other cases we can see
it with a green or blue
tone;
(Masson’s trichrome,
X400).
33.
34. Hyalinematerial is seen in
capillary
loops, including in a
globally sclerosed
glomerulus, and there is a
large capsular drop on the
inside
of Bowman’s capsule of
the surviving glomerulus
35. Tubular changes in DNP
In tubules there are Nonspecific
changes:
Reabsorption of protein droplets,
Tubular damage and atrophy.
The basement membranes of atrophic tubules are
characteristically much thickened, usually more than
in other causes of tubular atrophy; this change is
another one of the alterations that can make think us
about DN.
36. Another characteristic
lesion in DN is prominent
thickening of basement
membranes in atrophic
tubules (and in Bowman’s
capsule . When we find
this finding we must think
about the possibility of
DN, although it is not a
specific finding.
(Masson’s trichrome,
X400).
37. The Armani-Ebstein change (or Armani-Ebstein
cells)
Deposits of glycogen in the tubular epithelial cells.
It is very rare to see it at the present time; it appears
in decompensated diabetics with glycemia superior
to 500 mg/dL and severe glycosuria.
38.
39. Abnormalities of the glomerular-tubular junction
Late disease manifestations largely restricted
to patients with overt proteinuria.
Focal adhesions.
Obstruction of the proximal tubular take-off
from the glomerulus.
Detachment of the tubule from the
glomerulus (atubular glomerulus)
40. Glomerulus attached to a
short atrophic tubule
Glomerulus attached to
a long atrophic tubule
42. Post transplant res0lution of DNP
Baseline biopsy
specimen,
diffuse and
nodular
(Kimmelstiel-
Wilson) diabetic
glomerulopathy
5 years after
transplantation with
persistence of the
diffuse and nodular
lesions.
10 years after
transplantation, with
marked resolution
of diffuse and
nodular mesangial
lesions and more
open glomerular
capillary lumina
43. Immunofluorescence
Deposits of IgG that are
accompanied by albumin and adopt
a linear parietal pattern.
Immunostaining with complement
components usually is not seen.
The linear staining with albumin
helps to differentiate it from anti-
GBM disease.
Red arrows indicate capillary walls
with linear positivity;
Blue arrow indicates a diabetic
nodule.