Objective: Diabetic nephropathy is one of the most serious complications of diabetes mellitus. It develops in approximately one-third of diabetic patients, years after the onset of metabolic abnormalities. Study Design: The biopsy specimens were evaluated with the focus on light microscopy. The aim of our study was to reveal differences in the details and the frequency of occurrence of individual histomorphological changes in diabetic nephropathy and other glomerulonephritides. Results: Diabetic nephropathy accounted for 14 out of 82 analyzed biopsies. Isolated thickening of the glomerular basement membrane was not present in any case, but along with some degree of mesangial expansion, hypercellularity or glomerulosclerosis was seen in 12 out of 14 findings of diabetic nephropathy. In other glomerular diseases, mesangial changes, but without glomerular basement membrane thickening, were the most frequent findings. In addition to glomerular lesions, some of the tubular, interstitial, and vascular changes were seen in 13 out of 14 patients with diabetic nephropathy. In other glomerulonephritides the combination of all these changes was a rare finding. Conclusion: There are cases where immunofluorescence and electron microscopy cannot be performed or their results are not helpful. In such cases we must rely on light microscopic histomorphological changes.

1. 107
0884-6812/21/4303-0107/$18.00/0 © Science Printers and Publishers, Inc.
Analytical and Quantitative Cytopathology and Histopathology®
A
RTICLES
An Official Periodical of The International Academy of Cytology and the Italian Group of Uropathology
AQCH
ANALYTICAL and
QUANTITATIVE
CYTOPATHOLOGY and
HISTOPATHOLOGY®
OBJECTIVE: Diabetic nephropathy is one of the most
serious complications of diabetes mellitus. It develops in
approximately one-third of diabetic patients, years after
the onset of metabolic abnormalities.
STUDY DESIGN: The biopsy specimens were evalu-
ated with the focus on light microscopy. The aim of
our study was to reveal differences in the details and
the frequency of occurrence of individual histomor­
phological changes in diabetic nephropathy and other
glomerulonephritides.
RESULTS: Diabetic nephropathy accounted for 14
out of 82 analyzed biopsies. Isolated thickening of the
glomerular basement membrane was not present in any
case, but along with some degree of mesangial expan-
sion, hypercellularity or glomerulosclerosis was seen in
12 out of 14 findings of diabetic nephropathy. In other
Analytical and Quantitative Cytopathology and Histopathology®
The Spectrum of Histopathological Patterns in
Diabetic Kidney Disease in East Slovakia and a
Comparison with Non-Diabetic Renal Diseases
Alžbeta Blichárová, M.D., Ph.D., Zuzana Benetinová, M.D., Ph.D.,
L
’udmila Verbóová, M.D., Ph.D., Peter Petík, M.Sc., Erika Štammová, M.D., and
Terézia Kisková, D.Sc., Ph.D.
From the Department of Pathology, Faculty of Medicine, Pavol Jozef Šafárik University and Louis Pasteur University Hospital in Košice,
Rastislavova, Košice, Slovakia; and the Institute of Biology and Ecology, Faculty of Sciences, Pavol Jozef Šafárik University in Košice,
Šrobárova, Košice, Slovakia.
Alžbeta Blichárová is Assistant Professor, Department of Pathology, Faculty of Medicine, Pavol Jozef Šafárik University and Louis
Pasteur University Hospital.
Zuzana Benetinová is Assistant Professor, Department of Pathology, Faculty of Medicine, Pavol Jozef Šafárik University and Louis
Pasteur University Hospital.
L
’udmila Verbóová is Assistant Professor, Department of Pathology, Faculty of Medicine, Pavol Jozef Šafárik University and Louis
Pasteur University Hospital.
Peter Petík is Laboratory Assistant, Department of Pathology, Faculty of Medicine, Pavol Jozef Šafárik University and Louis Pasteur
University Hospital.
Erika Štammová is Assistant, Department of Pathology, Faculty of Medicine, Pavol Jozef Šafárik University and Louis Pasteur University
Hospital.
Terézia Kisková is Independent Researcher, Institute of Biology and Ecology, Faculty of Sciences, Pavol Jozef Šafárik University.
Address correspondence to: Alžbeta Blichárová, M.D., Ph.D., Department of Pathology, Faculty of Medicine, Pavol Jozef Šafárik
University, Rastislavova 43, 040 01 Košice, Slovakia (alzbeta.blicharova@upjs.sk).
Financial Disclosure: The authors have no connection to any companies or products mentioned in this article.

2. glomerular diseases, mesangial changes, but without
glomerular basement membrane thickening, were the
most frequent findings. In addition to glomerular le-
sions, some of the tubular, interstitial, and vascular
changes were seen in 13 out of 14 patients with diabetic
nephropathy. In other glomerulonephritides the combi­
nation of all these changes was a rare finding.
CONCLUSION: There are cases where immunofluores­
cence and electron microscopy cannot be performed or
their results are not helpful. In such cases we must rely
on light microscopic histomorphological changes. (Anal
Quant Cytopathol Histpathol 2021;43:107–115)
Keywords: diabetes mellitus; diabetes mellitus,
type 2; diabetic nephropathies; extraglomerular
lesions; glomerular lesions; histopathological
changes; kidney diseases; kidney failure, chronic;
metabolic syndrome; non-diabetic renal diseases.
The incidence of diabetes mellitus (DM), especial­
ly type 2, is increasing rapidly worldwide.1 DM
prevalence in Slovakia is equal to that in the
Mediterranean countries but higher than that in
West European countries.2 The reason of west-east
gradient prevalence in Europe is not clear. DM
belongs to chronic diseases that are associated
with high morbidity, disability, and mortality. The
number of diabetics in the world is increasing,
which poses problems not only in health care but
also in economic terms. Patients with DM have
been found to be at increased risk of many serious
health problems. Serious conditions affecting the
heart and blood vessels, eyes, kidneys, nerves,
and teeth can be associated with high blood glu-
cose levels, and people with diabetes also have a
higher risk of developing infections.3
Diabetic kidney disease, or diabetic nephropa­
thy (DN), is one of the most serious complica-
tions of DM. It develops in approximately one-
third of DM patients, years after the onset of
metabolic abnormalities. It is a major cause of
end-stage renal disease, which is an indication for
dialysis and transplantation.4-6 DN is a result of
progressive renal pathological changes. It is char­
acterized as DM with albuminuria or impaired
glomerular filtration rate, or both, and is the
strongest predictive factor of mortality in patients
with DM.7-9 Progression of morphological lesions
correlates with increased albumin excretion and
reduced glomerular filtration rate. Therefore, de-
termining the accurate diagnosis and histological
class of the disease in diabetic patients plays a
crucial role in their management and prognosis.7-9
Histomorphological lesions in DN are very het­
erogeneous, including vascular, tubular, and in-
terstitial lesions, and the most characteristic—
glomerular lesions.6-9 These lesions share many
similarities with other clinical conditions, produc­
ing similar histological patterns.
Detailed and complete renal biopsy, together
with light (LM), immunofluorescence (IF), and
electron microscopic (EM) assessment, represents
a significant part of diagnostics in nephrology
as it provides the key information for a precise
diagnosis.6,10,11 LM in the diagnosis of glomeru­
lar diseases is falling into oblivion nowadays.
In addition, IF and EM have many limitations.
Thus, the aim of our study was to find out if
LM is still a key player in precise diagnosis of
glomerulonephritides (GN).
Materials and Methods
Patients and Biopsy
Ninety-two patients with diverse GN were ret­
108 Analytical and Quantitative Cytopathology and Histopathology®
Blichárová et al
Table I The Presence of Different Clinical Features in Patients with Some Glomerular Disease
Clinical feature Men Women Total
Count 48 34 82
Age, years (mean±SD) 52.48±14.38 46.24±22.11 49.89±18.13
Age, years (min-max) 13–82 5–76 5–82
Proteinuria 46 32 78
Hematuria 24 15 39
Edema 36 24 60
Decreased renal functions 19 11 30
Increased urinary parameters 16 5 21
Systemic disease 6 7 13
Autoantibodies 6 9 15
Diabetes mellitus 10 4 14
Hypertension 34 24 58

3. rospectively reviewed according to their renal
biopsy. All obtained renal biopsy specimens were
evaluated histologically at the Department of
Pathology, University of Pavol Jozef Šafárik and
University Hospital of Louis Pasteur in Košice,
Slovakia, from the 2.5-year period of January 2014
to July 2016. All biopsies were performed for
various indications. Clinical features included pro-
teinuria, hematuria, renal failure, edema, or pres-
ence of systemic disease, and laboratory investi­
gations included the presence of increased urinary
parameters, complement levels, and in some cases
autoantibodies (Tables I–III).
Light Microscopy
All renal biopsies were analyzed using LM of
2–3-μm-thick tissue sections, stained routinely with
hematoxylin-eosin, periodic acid–Schiff, periodic
acid–Schiff-diastase, Masson’s trichrome, methena­
mine silver–periodic acid, and Congo red when
amyloidosis was suspected.
Groups of Patients
All specimens were divided into 6 groups accord­
ing to LM histomorphological findings, regardless
of the final diagnosis. Criteria for the division
followed changes seen in different stages of DN
in LM: Group 1, the presence of isolated thicken-
ing of the glomerular basement membrane (GBM);
Group 2, mesangial expansion/hypercellularity;
Group 3, segmental/global glomerulosclerosis;
Group 4, isolated thickening of the GBM with
interstitial, tubular, and vascular lesions; Group 5,
mesangial expansion/hypercellularity with inter-
stitial, tubular, and vascular lesions; and Group 6,
segmental/global glomerulosclerosis with intersti-
tial, tubular, and vascular lesions (Figure 1). Spe-
cimens not consistent with these histomorpholog­
ical changes were excluded (n=10). Then, a cor­
rect diagnosis for each patient, based on complex
evaluation, using IF and EM results, was stated
(Table IV). Finally, the frequency of occurrence of
the individual LM histomorphological patterns in
Volume 43, Number 3/June 2021 109
Histopathology in Diabetic Nephropathy
Table II The Presence of Different Clinical Features in Patients with Diabetic Nephropathy
Clinical feature Men Women Total
Count 11 3 14
Age, years (mean±SD) 53.82±6.93 47.33±22.68 52.43±11.12
Age, years (min-max) 43–65 30–73 30–73
Proteinuria 11 3 14
Hematuria 5 1 6
Edema 8 2 10
Decreased renal functions 9 2 11
Increased urinary parameters 9 1 10
Systemic disease 2 2 4
Diabetes mellitus 9 3 12
Hypertension 9 3 12
Table III The Presence of Different Clinical Features in Patients with Some Non-Diabetic Renal Disease
Clinical feature Men Women Total
Count 37 31 68
Age, years (mean±SD) 52.08±16.00 46.13±21.89 49.37±19.28
Age, years (min-max) 13–82 5–76 5–82
Proteinuria 35 29 64
Hematuria 19 14 33
Edema 28 22 50
Decreased renal functions 10 9 19
Increased urinary parameters 7 4 11
Systemic disease 4 5 9
Autoantibodies 6 9 15
Hypertension 25 21 46

4. 110 Analytical and Quantitative Cytopathology and Histopathology®
Blichárová et al
Figure 1 (1a) Isolated glomerular basement membrane thickening (black arrow) in a patient with membranous nephropathy
(hematoxylin-eosin, 400×). (1b) Mesangial hypercellularity (black arrow) and glomerular basement membrane thickening in a patient with
IgA nephropathy (hematoxylin-eosin, 400×). (1c) Mesangial expansion with nodular formation (black arrow) in a patient with amyloidosis
(Congo red, 400×). (1d) Isolated glomerular basement membrane thickening, interstitial inflammation (black arrow), and fibrosis (red
arrow) in a patient with diabetic nephropathy (Masson’s trichrome, 200×). (1e) Mesangial expansion, nodular sclerosis (black arrow), and
tubular atrophy (red arrow) in a patient with diabetic nephropathy (methenamine silver–periodic acid, 200×). (1f) Global sclerosis (black
arrow), hyaline arteriolosclerosis, and arteriosclerosis (red arrow) in a patient with diabetic nephropathy (hematoxylin-eosin, 200×).

5. groups 1–6 was studied. At the same time, data
from samples with the same type of LM histomor­
phological pattern from one group, since its de-
tails may vary in different final diagnoses, were
studied and analyzed.
Results
A total of 82 renal biopsies were analyzed by LM
after the exclusion of all specimens without any
histopathological similarities with DN. Different
GN from patients (ranging in age from 5–82 years)
were selected, of which 48 (58.5%) were males and
34 (41.5%) were females.
Morphological changes analyzed represent some
of the typical histomorphological lesions described
in patients with DN depending on its degree. The
spectrum of morphological lesions in LM and the
final pathological diagnosis based on the confir­
mation with IF and EM are shown in Table IV.
DN and membranous GN were the most com­
Volume 43, Number 3/June 2021 111
Histopathology in Diabetic Nephropathy
Table IV The Spectrum of Histomorphological Lesions in Different Glomerular Diseases Seen by Light Microscope
Global/segmental
Mesangial expansion/ sclerosis, mesangial
hypercellularity expansion
Lesion Lesion Lesion Lesion
Isolated (thickening (thickening (thickening (thickening
thickening of GBM) of GBM) of GBM) of GBM) Total
Diagnosis of GBM present absent present absent (82)
Minimal change disease 0 0 6 0 1 7
Focal segmental glomerulosclerosis 0 0 1 0 0 1
Membranous glomerulonephritis 0 0
0 3
0
3
Mesangial proliferative glomerulonephritis 0 0 0 0 0 0
Post-infectious glomerulonephritis 0 0
0 0
0
0
Membranoproliferative glomerulonephritis
0 2
0 0
0
2
Crescentic glomerulonephritis 0 0
0 0
0
0
Lupus nephritis 0 0
0 1
1
2
IgA nephropathy 0 0
1 1
1
3
Diabetic nephropathy 0 0
0 0
1
1
Amyloidosis 0 0
0 0
2
2
Alport syndrome 0 0
0 0
0
0
Thin basement membrane disease 0 0 0 0 1 1
Global/segmental
Mesangial expansion/ sclerosis, mesangial
hypercellularity expansion with
Isolated
with TC/IC/VC TC/IC/VC
thickening Lesion Lesion Lesion Lesion
of GBM (thickening (thickening (thickening (thickening
with of GBM) of GBM) of GBM) of GBM) Total
Diagnosis TC/IC/VC present absent present absent (82)
Minimal change disease 0 0 0 0 0 0
Focal segmental glomerulosclerosis 0 0 0 1 7 8
Membranous glomerulonephritis 1 2
1 5
2
11
Mesangial proliferative glomerulonephritis 0 0 1 0 1 2
Post-infectious glomerulonephritis 0 0
1 0
0
1
Membranoproliferative glomerulonephritis
0 5
0 1
2
8
Crescentic glomerulonephritis 0 0
0 0
1
1
Lupus nephritis 0 1
0 2
3
6
IgA nephropathy 0 1
1 0
6
8
Diabetic nephropathy 0 5
0 7
1
13
Amyloidosis 0 0
0 1
0
1
Alport syndrome 0 0
0 0
1
1
Thin basement membrane disease 0 0 0 0 0 0
TC/IC/VC = tubular/interstitial/vascular changes, GBM = glomerular basement membrane.

6. mon pathology, each accounting for 14/82 biopsy
specimens (17.1%), followed by IgA nephropathy
in 11/82 (13.4%), membranoproliferative GN in
10/82 (12.2%), focal and segmental glomeruloscle-
rosis in 9/82 (11.0%), lupus nephritis in 8/82
(9.8%), and minimal change disease in 7/82 (8.5%).
Amyloidosis was found in 3/82 cases (3.7%) and
mesangial proliferative GN in 2/82 cases (2.4%).
The less frequent findings were post-infectious
GN, crescentic GN, Alport syndrome, and thin
basement membrane disease, each accounting for
1/82 (1.2%).
Isolated thickening of the GBM in LM, without
any other pathology, was not present in any case
of DN. Of other GN, isolated thickening of the
GBM was observed in only 1 case of membranous
nephropathy. In 5/14 cases of DN, thickening of
the GBM with some degree of mesangial expan­
sion or hypercellularity, and in 7/14 cases of DN,
thickening of the GBM with mesangial expansion
and segmental or global glomerulosclerosis, was
seen. Only in 2/14 cases of DN were there mes­
angial expansion and glomerulosclerosis, without
the recognition of GBM thickening in LM. In 1
case, typical Kimmelstiel-Wilson nodules were
identified. Except DN, mesangial expansion and
glomerulosclerosis were found in almost all cases
of other GN too, although together with GBM
thickening only in 1/3 cases of amyloidosis, 2/11
of IgA nephropathy, 4/8 of lupus nephritis, 8/10
of membranoproliferative GN, 0/2 of mesangial
proliferative GN, 0/1 of crescentic GN, 0/1 of
post-infectious GN, 10/14 of membranous GN,
and 2/9 of focal segmental glomerulosclerosis. In
such cases, more detailed examination already in
LM reveals minor variations in the appearance of
thickened basement membranes and mesangial
expansion in comparison with diabetic nephrop­
athy. In 7/7 cases of minimal change disease,
only isolated mild mesangial hypercellularity was
found.
In 1/14 cases of DN, only glomerular lesions
were present. In 13/14, some of the tubular, inter­
stitial, or vascular changes were seen: in 7/14, a
combination of some degree of tubular atrophy,
interstitial fibrosis/interstitial chronic inflamma­
tion, and hyaline arteriolosclerosis/fibrous intimal
hyperplasia; in 5/14, tubular atrophy was absent;
and in 1/14, only focal interstitial fibrosis was
present. These changes were also observed in
many cases of other GN, but the combination
of tubular atrophy together with interstitial and
vascular changes was found in only 1/9 of focal
segmental glomerulosclerosis, 3/14 of membra­
nous nephropathy, 1/10 of membranoprolifera­
tive GN, 3/8 of lupus nephritis, and 1/11 of IgA
nephropathy. In minimal change disease and thin
basement membrane disease, no tubular, intersti­
tial, or vascular lesions were seen.
In 6/14 cases of DN, capsular drops, and in 2/
112 Analytical and Quantitative Cytopathology and Histopathology®
Blichárová et al
Figure 2 (2a) Mild mesangial hypercellularity (black arrow) and glomerular basement membrane thickening (red arrow), together with
interstitial inflammation (green arrow) and tubular atrophy (blue arrow), in a patient with diabetic nephropathy (hematoxylin-eosin, 400×).
(2b) Immunofluorescent microscopy in the same patient with diabetic nephropathy (400×) without specific glomerular linear IgG labeling;
electron microscopy was not made for technical reasons.

7. 14 cases of DN, crescents in <10% of glomeruli,
were found (not included in Table IV). In 8/14
cases of DN, specific fluorescence was not pres-
ent in IF, and in 3/14 cases of DN, EM was not
performed for technical reasons. No specific fluo­
rescence was detected and concurrently EM was
not performed in 1 of these cases. In such cases,
we must rely solely on LM findings (Figure 2).
Discussion
Although IF and EM have important roles in the
assessment of GN, still the most valuable is LM. In
many cases, IF and EM can reliably exclude most
other GN. However, there are cases where IF and
EM cannot be performed or their results are not
helpful, as was also demonstrated in our study.
The main limitations of EM are its high cost and
being a time-consuming procedure. As far as IF
is concerned, it is autofluorescence phenomenon,
presence of nonspecific fluorescence, or non-
detection of specific fluorescence in the early stages
of the disease. Granted, in both techniques the
representativeness of the sample also plays a role.
In such cases, we must rely on LM.12,13
In our study a huge spectrum of histomorpho­
logical patterns in biopsy specimens of DN was
confirmed. This histological variability is asso­
ciated with the progression of DN and different
degrees of renal damage. DN is therefore mor­
phologically classified according to the report by
Tervaert et al14 that was launched by the Research
Committee of the Renal Pathology Society in 2006.
This classification shows a range of glomerular
lesions, including Class I—mild changes (isolated
GBM thickening), Class IIa—mild mesangial ex-
pansion, Class IIb—severe mesangial expansion,
Class III—nodular sclerosis (at least 1 Kimmelstiel-
Wilson nodule), Class IV—advanced diabetic
glomerulosclerosis (global sclerosis in >50% of
glomeruli), with the individual classification of
tubulointerstitial and vascular changes. These in-
clude tubular atrophy, interstitial fibrosis, inter­
stitial inflammation, arteriolar hyalinosis, and arte-
riosclerosis (intimal thickening). They are present
from the beginning of the development of glo­
merular changes and are more conspicuous with
advanced stages of glomerular lesions.7,14,15 We
also demonstrated histomorphological variability
of other GNs and showed similarities with some
degrees of DN. Because we had no biopsy as-
sessed as Class I of DN (isolated thickening of the
GBM) available, we were able to compare pat-
terns of varying GN only with patterns seen in
Classes II, III, and IV of DN.
In minimal change disease, sclerotic structures
are missing, and LM is mostly completely nega­
tive.15-17 In one case in our study there was a small
sclerotic area found in one glomerulus, most likely
based on ischemia. In all our cases, mild mesan-
gial expansion or hypercellularity was described
but without GBM thickening or any tubular, inter­
stitial, or vascular changes (seen in DN).
Focal segmental glomerulosclerosis is charac­
terized by focal and segmental sclerotic lesions and
mesangial expansion with a dominant cell pro-
liferation18 (while in DN the cellular proliferation
is not very pronounced), which were confirmed
by our observation. In addition, fibrin caps and
capsular drops may also occur in this condi­
tion; therefore, they are not specific for DN.15,17,18
However, none of such lesions, as well as GBM
thickening (typical in DN), was identified in our
patients with focal segmental glomerulosclerosis.
In a typical example, membranous nephropa­
thy is characterized by isolated thickening of the
GBM only with mild mesangial expansion.15,17 In
our study, cases with mesangial expansion and
nodular or global sclerotization, as a result of some
older ischemic changes or as a secondary form of
membranous nephropathy, were described, which
may lead to a diagnostic issue. However, thicken-
ing of the GBM in this condition produces the
so-called “spike” projections15 that were observed
in non-sclerotic areas of our biopsies, too.
Mesangial proliferative GN and post-infectious
GN were rare findings in our study, presented
by mesangial expansion and pronounced hyper­
cellularity (while in DN, the cellular proliferation
is not typical), with sclerotic areas, tubulointersti-
tial and vascular changes, but with normal thick-
ness of the GBM (not seen in DN), as described in
the literature.15,19 In post-infectious GM, fibroepi­
thelial crescents were seen in 30% of glomeruli.
Membranoproliferative GN type I (this type was
diagnosed in all our patients) shows histomor­
phological patterns most like DN—global or seg­
mental glomerulosclerosis, sometimes additional-
ly resembling Kimmelstiel-Wilson nodules, diffuse
GBM thickening, seen in most of our patients,
and some degree of tubulointerstitial and vascu­
lar changes. The only difference is represented by
the “double contouring pattern” of GBM thicken­
ing,10,20 which was described in non-sclerotic areas
of our specimens, too (and is not present in DN).
Volume 43, Number 3/June 2021 113
Histopathology in Diabetic Nephropathy

8. Crescents are present in <5% of cases of dia­
betic glomerulosclerosis. We found this crescentic
proliferation in only 2 of our biopsies, with <10%
of glomeruli affected. Most of crescentic GN have
more than 50% of glomeruli affected, the rest of
them <50% of glomeruli.15 In our biopsy only 1
crescentic GN was diagnosed, with <10% of af-
fected glomeruli but with normal GBM findings in
all glomeruli (in contrast to DN).
Patterns of lupus nephritis depend on the class
of this condition (I–VI).15,17 In our biopsies, 1 pa-
tient was diagnosed as class II, 3 patients as class
III, and 4 patients as class IV of lupus nephritis.
In all these specimens, changes such as mesangial
hypercellularity, mesangial expansion, and global/
segmental sclerotization were present. In more
than half of the biopsies tubulointerstitial and
vascular changes were described, and in less than
half of the biopsies fibroepithelial crescents were
seen in <10% of glomeruli (the same patterns
as DN). On the other hand, thickened GBM was
observed by LM in only 50% of the patients, and
in all of them with the typical “wire loop” ap-
pearance, in accordance with the literature.15
IgA nephropathy typically shows mesangial
changes such as hypercellularity and expansion,
frequently with glomerular sclerosis and crescentic
formation in <50% of glomeruli,15 as was shown
in our study. In less than half of the biopsies,
crescents in <10% of glomeruli were observed.
The issue with the differentiation between IgA
nephropathy and DN using LM arose in 2 of our
cases of IgA nephropathy, where, except for pat-
terns mentioned above, GBM thickening was ob-
served. Although not typical, in rare bioptic sam­
ples, irregular thickening and thinning of GBM
may be present in IgA nephropathy.15
For amyloidosis, a wide spectrum of changes is
characteristic, from mild mesangial expansion to
massive amyloid deposits, which may resemble
nodules in DN. These nodules are eosinophilic
and acellular, sometimes with amyloid deposition
in the GBM, arterial walls, and interstitium.10,15,20
In our study all 3 patients had mesangial expan-
sion and sclerosis of a few glomeruli, in 1 patient
the deposition of amyloid in the GBM was pres-
ent, and in another patient the deposition in ar-
terial walls and interstitium was observed. The
diagnosis was made by LM. Nodules of amyloid
are negative in PAS and silver stain and positive
in Congo red stain instead (in contrast to DN).20
Alport syndrome and thin basement membrane
disease constitute rare conditions in our biopsy,
characterized by some degree of mesangial expan­
sion or sclerotization, without GBM thickening in
LM. GBM changes in these conditions are mostly
inconspicuous in LM.15
Conclusion
Methods such as IF and EM can differentiate most
glomerulonephritides. However, there are cases
where these methods cannot be performed or their
results are not helpful. In such cases we must rely
on LM. The localization of histomorphological
lesions, their appearance, mutual combinations,
and, particularly, the frequency of occurrence vary
to a large extent between diabetic nephropathy
and other glomerular diseases. There has been a
great deal of work on the occurrence of various
glomerular diseases, but the frequency of individ­
ual histomorphological changes has, so far, been
studied scarcely. In our study, in the spectrum
of the diagnoses the greatest diagnostic issue is
represented by membranoproliferative GN, fol­
lowed by amyloidosis, and in some cases by lupus
nephritis, IgA nephropathy, and membranous
nephropathy.
LM belongs to standard diagnostic tools in
many diseases. However, there is increasing at-
tention in using EM or IF instead of LM. Although
IF and EM belong to a golden standard in renal
biopsy, LM is still the most valuable method in
diagnostics and provides the widest spectrum of
information.
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