Download - Diabetic nephropathy
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BY DR IRFAN ELAHICONSULTANT NEPHROLOGIST
MAYO HOSPITAL LAHORE
DIABETIC NEPHROPATHY
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DIFFERENT HISTOLOGICAL LESIONS AND THEIR OCCURRENCE
Pathology of Diabetic Nephropathy in Patients with Type 1 Diabetes and
Proteinuria
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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.
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Often or Usually Present
Kimmelstiel-Wilson nodules (nodular glomerulosclerosis).
Atubular glomeruli.
Foci of tubular atrophy.
Afferent and efferent arteriolar hyalinosis.
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Sometimes Present
Hyaline caps or fibrin caps (Highly characteristic of diabetic nephropathy)
Capsular drops (Highly characteristic of diabetic nephropathy)
Atherosclerosis.
Glomerular micro-aneurysms.
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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.
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Thickening of the glomerular basement membrane (GBM) is the first change that can be
quantitated
Basement membrane thickening compared with normal basement membrane.
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Normalglomerulus (periodic acid–Schiff).
Diffuse glomerularlesion: widespread mesangial expansion (periodic acid–Schiff).
Acellular mesangial proliferation
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Acellular mesangial proliferation
Normal mesangium compared with mesangial expansion
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A normal glomerulus (GBM) thickening and moderate mesangial expansion
Severe diffuse mesangial expansion
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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).
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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.
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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.
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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.
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A capillary microaneurism (mesangiolysis) at 11 o'clock
Nodule formation within a capillary microaneurism
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Nodular glomerulosclerosis (Kimmelstiel-Wilson nodules),
End-stage diabetic glomerular changes with nearly complete capillary closure.
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There is an increase in mesangium with a microaneurysm, arrowed.
This type of lesion healsto form a Kimmelstiel–Wilson nodule
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The smallest nodules can be more cellular and the greatest nodules tend to be acellular in the centre and surrounded by more cellular zones.
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Nodular lesion as well asmesangial expansion;
There is a typical Kimmelstiel-Wilson nodule at the top of the glomerulus (arrow)
(periodic acid–Schiff).
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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).
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The prominent concentric lamination with the silver stain (arrow). This finding is very characteristic of nodular diabetic glomerulosclerosis.
(Methenamine-Silver, X400)
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Nodular lesion: methenaminesilver staining showing the marked nodularexpansion of mesangial matrix.
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Advance DNP
There is severeischemic shrinkage of the tuft, but a Kimmelstiel–Wilson nodule is still seen, adherent to Bowman’scapsule just at the origin of the tubule
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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.
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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)
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Renal biopsy specimen from the woman of 58 with diabetic glomerulopathy.
Arterioles have severe hyalinosis
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2) Glomerular capillary subendothelial hyaline (hyaline caps).
Green ArrowGlomerular 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).
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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).
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Glomerulus with minimal mesangial expansion and a capsular drop at 3 o'clock (PAS stain).
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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).
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Hyalinematerial is seen in capillaryloops, including in a globally sclerosed glomerulus, and there is a large capsular drop on the insideof Bowman’s capsule of the surviving glomerulus
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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.
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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).
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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.
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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)
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Glomerulus attached to a short atrophic tubule
Glomerulus attached to a long atrophic tubule
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Glomerulus attached to an atrophic tubule with no observable opening
Atubular glomerulus
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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
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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.
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THE END
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