Diabetic Nephropathy

Part II


Franco Ferrario and Maria Pia Rastaldi

Dr Franco Ferrario
Renal Immunopathology Center
San Carlo Borromeo Hospital
Milan, Italy

As reported in the previous “Renal Pathology Learning” type 2 diabetes includes various changes, including glomerulosclerosis (class 1), non specific chronic damage mostly related to vascular changes (class 2) and glomerular diseases superimposed on (class 3a), or even unrelated to, diabetes glomerulosclerosis (class 3b).

In a recent multicenter study based on 393 biopsies of type 2 diabetes mellitus (G. Mazzucco et al, Am J Kidney Dis 2002) 68 (17%) were glomerular diseases superimposed on diabetic nephropathy (class 3a) and 109 (27%) were glomerular diseases without diabetic nephropathy (class 3b) .


Tab. 1

Frequency of Glomerular Disease Superimposed on Diabetic Nephropathy (Class 3a) and without Diabetic Nephropathy (Class 3b)

No. of Cases

Class 3a

Class 3b
Total (%)
Total (%)
Membranous GN
10 (24.3)
31 (75.6)
12 (33.3)
24 (66.6)
Postinfectious GN
26 (70.2)
11 (29.7)
0 (0.0)
22 (100)
Extracapillary GN
8 (47.0)
9 (52.9)
Cryoglobulinemic GN
11 (91.6)
1 (8.3)
Other glomerular diseases
1 (8.3)
11 (91.9)
68 (38.4)
109 (61.6)

In this “Renal Pathology Learning” we show two cases of glomerular diseases superimposed on diabetic glomerulosclerosis, which emphasise the potential usefulness of renal biopsy in selected diabetics.

A 35 year old Caucasian male with a 10 year history of insulin-dependent Diabetes mellitus was admitted to our Department for overt nephrotic syndrome (Proteinuria 7.5 gr/24h – Serum Albumin 1.8 gr/dl) and severe renal insufficiency (S. Creatinine 3.7 mg/dl).
Renal ultrasound examination: normal kidneys.
Funduscopic examination: proliferative diabetic retinopathy.
He developed an oliguric rapid progression of renal insufficiency (S. Creatinine 10.1 mg/dl) necessitating hemodialysis.
A renal biopsy was performed.
There were 27 glomeruli: all glomeruli showed severe nodular mesangial sclerosis with superimposed circumferential cellular crescents totally filling the Bowman's space.
Widespread subintimal hyaline thickening of the arterioles was detected, suggestive of diabetic nephroangiosclerosis, with diffuse arterial sclerosis.








At a higher magnification and with different stainings the nodular glomerulosclerosis and circumferential cellular crescents are evident.




Silver stain

Immunofluorescence revealed very strong linear deposits of IgG along the glomerular basement membrane.

In many glomeruli, IgG deposits clearly outlined the mesangial nodules.

The extremely rare presence of diffuse circumferential crescents in diabetic glomerulosclerosis and the strong positivity of IgG linear deposits could suggest the presence of superimposed anti-glomerular basement membrane antibody disease. In fact, circulating anti-GBM antibodies were detected (titer : 86 SLI Units; normal <10 SLI) confirming the diagnostic hypothesis of anti-GBM disease.


A 69 year old Caucasian male with a history of moderate hyperglicemia and hypertension.
He was admitted to our Nephrology Department for mild proteinuria (1.5 gr/24h) with normal renal.
Renal ultrasound examination: normal kidneys.
Funduscopic examination: no diabetic retinopathy.
A renal biopsy was.
There were 14 glomeruli: about 2/3 of glomeruli showed variable mesangial matrix enlargement with segmental mesangial cell proliferation. A diffuse and regular thickening of glomerular basement membrane was also present.







In about 1/3 of glomeruli, segmental, large, isolated nodules of glomerulosclerosis were evident.



Arteries and arterioles showed a marked sclerojalinosis of the vessel wall, suggestive of diabetic nephroangiosclerosis.

The immunofluorescence was characterized by linear deposits of IgG along the GBM, typical of diabetic nephropathy.

Moreover, immunofluorescence showed a simultaneous presence of mesangial deposits of IgA.

The final diagnosis was diabetic glomerulosclerosis with superimposed IgA nephropathy.

In a recent multicenter study of the Italian Renal Immunopathology Group, kidney survival at 84 months in 580 type 2 diabetic patients was 52% in diabetic glomerulosclerosis, 58% in chronic vascular changes, 34% in glomerular diseases superimposed on diabetic glomerulosclerosis and 67% on glomerular diseases without diabetic glomerulosclerosis.

In conclusion, Diabetic nephropathy predicts an unfavourable evolution, which is further worsened by the presence of a superimposed glomerular disease.



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