72 ‫محاضرة‬

‫ تسبيح مسارة‬، ‫ حنني توبه‬: ‫الجزء األول‬

Glomerular Diseases
Just to put things together: last lecture we start talking about nephrotic syndrome. Remember that

 The most frequent systemic causes of nephrotic syndrome are diabetes, SLE, amyloidosis.
 The most of primary glomerular lesions that lead to nephrotic syndrome are:
- Focal segmental glomerulosclerosis.- last lecture
- minimal change disease,- last lecture
- membranous nephropathy and –last lecture
- Membrano Proliferative Glomerulonephritis (MPGN) –in this lecture

So in this lecture we will continue with MPGN and then with nephritic syndrome

Remember: Lesions that can be associated with abnormality of the glomeruli. In primary glomerular disease the patient
will present to you with either one of these syndromes:

 Acute Nephrotic Syndrome

 Acute Nephritic Syndrome
 Asymptomatic urinary abnormalities( Hematuria, proteinuria )
 Rapidly Progressive Glomerulonephritis

All of these will indicate glomerular abnormality!

 If the patient comes with a nephrotic syndrome this means that we have mostly leakage of the protein, while in
nephritic syndrome we have injury and damage, and all of these changes can be brought about either by
obliteration of foot processes of the podocytes or by some abnormality (thickening) of the basement membrane.
 The mechanism of glomerular capillary injury is the deposition of immune complexes in the subendothelium, the
basement membrane itself or in the subepithelium or mesangium. They can be specifically deposited or
nonspecifically trapped, and depending on the type of these immune complexes we get to see different light
microscopic as well as immunofluorescence and electron microscopic differences according to what they have done.
 These complexes might do nothing (I mean in terms of inflammation), but having immune complexes will alter the
structure and the characteristics of the basement membrane. So in a patient with nephrotic syndrome, for example,
those complexes will cause Thickening Membranous Nephropathy; the basement membrane will be thickened and
abnormally permeable and this will cause more leakage and proteinuria with no at least significant damage by the
light microscope. With the EM we will see the thickening of the basement membrane and the loss of foot processes!
The podocytes are going to react to this minimal damage by losing their foot processes without inflammation or
necrosis. So you are going to diagnose membranous nephropathy by LM, EM and immunofluorescence where you get
to see deposits that are located subepithelially.

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 Slide 39 MembranoProliferative Glomerulonephritis (MPGN)

Now we are going to talk about another type of immune complexes where they will be associated with some sort of
inflammatory reaction and complement activation, and this will be associated with necro-inflammatory damage of the
capillaries and escape or leakage of the RBCs with proteinuria! And this proteinuria depends on the damage that it
might be so severe so as these patients are going to have nephrotic-nephritic disease at the same time OR it can be just
proteinuria with nephrotic syndrome.

One of the things that will cause the in-between condition is the MembranoProliferative Glomerulonephritis (MPGN);
where we have thickening of the basement membrane and on top of that we have proliferation,

 Hematuria always indicates damage! And whenever we have damage we will have proliferation and
neutrophilic exudate!
 If it is only proteinuria then mostly we are dealing with some membrane or foot processes abnormality.
Slide 41
MPGN morphology

 MPGN has two types: type I and type II with the basement membrane reduplicated or having tram track like
appearance.
 These two types will be classified according to the EM and immunofluorescence appearance, while with the LM
we will see proliferation and thickening of the basement membrane.
 So based on the immunofluorescence and on the character of changes in the EM the MPGN is divided into two
types.

In MPGN The immune complexes are going to either over activate the complement or the complement might be
persistently activated either because of the presence of C3 nephritic factor that is C3 convertase stabilizer (that will
stabilize C3) and C3 will cleave and persistently activate the complement! Or a deficiency in factor H which inhibits the
complement, both of these conditions can be associated with increased complement activation and
hypocomplementemia. , Those patients might have nephritic-nephrotic, not pure nephritic or pure nephrotic but a mix
of them

 Type I, If you go for immunofluorescence you are going to see immune complex deposits within the capillaries as
well as within the mesangium. Wherever these deposits sit, they can cause problems! So if they are mostly
subendothelially containing much IgG, this is type I MPGN
 While in type II you are going to see C3 only and you don’t get to see IgG. The most important thing about type II
that you are going to see dense deposits occupying the entire basement membrane, while in type I we will have
subendothelial deposits. So if they are dense deposits within the basement membrane and only with c3 without
IgG, this is usually type II.
 We like to classify type II because it is different in terms of EM, immunofluorescence and also the prognosis is
much worse! Many of these patients, more than half of them, from type II alone will get end stage kidney
disease within 20 years! And most of these diseases affect the young adults (in their 20s or 30s), and sometimes

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 teenagers! (A person in his 40s or 50s having end stage kidney disease is a really bad thing that nobody wish to
have)

Slide 51 MPGN pathogenesis

Again the old causes of immune complexes! In any patient with hematuria or proteinuria go for hepatitis C, hepatitis B, SLE
(ANA) then go for the complement to assess the complement activation, so these are going to be the screening tests that you
are going to order to any patient who has a glomerular disease.(the most common cause is lupus which can actually do
anything to the kidney because it can be associated with a variety of antibodies with different immune complexes that can be
associated with almost all of the possible manifestations of glomerular injuries).

It also sometimes can be due to a malignancy where we have circulating Ag-Ab complexes leading to that condition.

Remember MPGN may present as both nephrotic and nephritic syndromes.

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 So the patient comes with Nephrotic Syndrome:

 Edema
 Proteinuria
 Hypoproteinemia(hypoalbuminemia)
 hyperLipidemia
 Hyperlipiduria
 We look for the possible diagnoses according to age:
 Minimal change (young children)
 Membranous GN (most common in nondiabetic adults)
 Diabetes
 Amyloidosis
 Focal segmental glomerulosclerosis
 MembranoProliferative GN (can cause both nephrotic and nephritic)

Slide 52 Those are the most common causes but we still have (5%-10%) other less common causes which include:

 Diffuse mesangial hypercellularity, which is thought as a continuum with minimal change(minimal change can
cause mesangial cellularity then focal segmental)
 C1q nephropathy; abnormal activation of the complement that does not include too much of proliferation
 Fibrillary glomerulonephritis

In an infant in his first year of age we have to think about congenital causes such as the *Finnish type and diffuse
mesangial sclerosis (note: Finnish from Finland where it was discovered first, and the cause is not immune
complexes as we mentioned in other causes.
 Again according to age we can know the cause:
 4-12 year old children: minimal change
 Adults: diabetes or membranous
 Adolescence and young adults: focal segmental

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 All of this will appear in the biopsy so it is essential and mandatory to go for a biopsy in all cases of nephrotic syndrome except
in the young; because they mostly have minimal change! And we give them steroids, but if they didn't recover we go for
biopsy where It might be focal segmental or something else.

Slide 57 Nephritic Syndrome

 The patient might also come with Nephritic Syndrome, which is mainly in young children and young adults.
 Patients usually come with dark urine (red to brown in color –coca cola like) and that urine tends to be in small
quantity (oliguria 700-800 ml)
 Hypertension
 Proteinuria below the nephrotic range (if the proteinuria is high we call it nephrotic-nephritic), proteinuria results
from leakage of some protein from the blood.

 The Acute Nephritic is usually a continuum with the rapidly progressive GN, and that’s going to reflect the extent of
glomerular damage (hematuria is due to damage of the glomeruli 10%, 20%, 30 %,…)

 The damaged glomeruli are not just going to leak RBCs, but also they are not going to have normal circulation, so the
circulation and the GFR are going to drop in these patients. If that drop is so significant the patient is going to have Rapidly
Progressive Glomerulonephritis.

Note: a patient with renal failure, severe hypertension and oliguria developing persistently, then the patient is in the spectrum
of RPGN, but if it is stable and started to recover then the patient has Acute Nephritic Syndrome that is usually characterized
by the presence of RBC cast.

 In Nephritic Syndrome, you imagine that these glomeruli are going to have injury associated with glomerular cell
proliferation (endothelial cells, epithelial cells and mesangial cells).

 If the injury is significant and it's going on for a longer period of time you get to see more of these epithelial cells
proliferation. The presence of these cells denotes the severity of the injury and they will be associated microscopically
with a crescent like structure, so the more of these you see in the glomeruli the more the injury they have, and if that
exceeds 50% of the glomeruli this is what we refer to as Crescentic Glomerulonephritis that is usually associated clinically
with Rapidly Progressive Glomerulonephritis.

 The acute nephritic actually is the …spectrum of the rapidly progressive, but it is the same process that will go on. So, for
example, if we find about 10% crescent, we won't call it rapidly progressive but acute nephritic! So they are a continuum
of the same disease.

Slide 59 Nephritic syndrome histology

 We will have glomerular cell proliferation
 and definitely as long as we have damage we will have complement activation
 neutrophils are going to wait in that area, so the glomeruli are going to be filled with inflammatory cells or inflammatory
exudate
 ↓GFR and fluid retention
 ↑ azote
 The pressure will start to increase!
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Slide
 CAUSES:-

Again immune complexes! But those immune complexes are going to be different, the same immune complexes that might
cause nephrotic in a patient, can cause nephritic in another patient; they both can have hepatitis B or C but one of them might
come with nephritic while the other with nephrotic, this actually depends on the subtypes of those complexes and how the
patient's antigens are going to react with them (immune complexes are not necessarily the same in two patients with
hepatitis B). So the antigens are going to be different depending on the extent and the activity of the immune system in
forming which type and how much antibodies! And this will determine not only the antigenic but also the other biological
characteristics of the immune complexes.

Biologically the immune complexes doesn’t really have to do the same thing in all or different patients! But mostly you are
going to see immune complexes due to the post streptococcal infection, when we have antigenemia due to streptococcal
infection and antibodies will form complexes with these antigens which are going to get trapped within the capillaries of the
glomeruli leading to complement activation and neutrophilic exudation. The complement activation is going to be so
prominent that these patients are going to have hypocomplementemia!

So when the complement is low (hypocomplementemia), it means that we are consuming our complement and we have
significant ongoing formation of these immune complexes, in cases of MPGN, Acute Post Streptococcal or SLE.

→ hypocomplementemia could be seen only in certain strains of streptococcal infection in certain people, so not anyone with
streptococcal skin infection, for example, is going to have Post Streptococcal Glomerulonephritis!
Slide
61-76 Hallmark disease of nephritic syndrome is Post Streptococcal

 Nephritic syndrome is going to be a disease of older children (10,11and 12 years old children), where we get to see Post
Streptococcal Glomerulonephritis mostly in these ages. But we still get to see the disease in young adults
 If an adult is going to have the disease he will have it as soon as he gets the streptococcal infection which is going to be
mostly in his childhood. It is very rare to see an adult with Post Streptococcal Glomerulonephritis.

________________

We can actually predict what is going in these patients' kidneys, we will have damage and proliferation without much
membrane thickening and that’s why we are going to call it Diffuse Proliferative Glomerulonephritis or angiocapillary,
endocapillary or mesangiocapillary GN denoting that we have proliferation of the endothelial as well as in the mesangial cells,
and most of the cases are going to be post streptococcal infection.

 Immunofluorescence: we will see granular immune complexes which like to reside under the podocytes.
 Immune complexes aggregate under the podocytes in both membranous and Post Streptococcal Glomerulonephritis.
 What we’re going to see under EM?
Granular capillary immune complex deposits -not linear- , mostly of IgG but in early stages we can see IgM which will
be replaced later on by IgG. The deposition will be just under the podocyte (sub epithelial)
 Slide 64

A glomerulus with proliferative changes (full of cells due to proliferation), membranes are not very thick compared to
normal thickness in next slide. Neutrophils and other inflammatory cell infiltrate

 Slide 69-74

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 ‫الدكتور حكا ازا جبلنا فً االمتحان رسمة رح تكون واضحة الى حد ما‬:p ‫وحكا ممكن ٌعطٌنا‬clue ‫وازا ما اعطانا ندور ع الند مارك مثال نشوف اشً مدور‬
‫معناها هاد‬capillary ‫ممكن ٌكون فً داخلو‬RBC or WDC ‫وال‬immune deposits ‫رح ٌكون من جهة ال‬BM ‫من برا ٌعنً تحت ال‬podocyte ‫و‬
‫زي ما حكٌنا من قبل فً أي مرض بأثر ع‬capillary ‫رح ٌكون عنا‬loss of podocyte foot processes

 slide 69 the arrow indicates the large immune complexes and the most obvious like mass is a RBC
 Slides 73 and 74 are more obvious ^_^

The slides are not stained because it’s an EM slide

E.g. A 12 years child presented with HTN, red brown urine(Coca-Cola colored), creatinine level is not severely elevated
→ mostly post streptococcal GN
Most cases of acute nephritic syndrome in children are going to be post streptococcal and they will recover
spontaneously so we don’t need to go for biopsy. We might give them antibiotics and steroids then they will recover
completely without any consequences and permanent damage to glomeruli

While in an adult with acute nephritic syndrome we should take biopsy because they have more tendency to progress
to rapidly progressive GN.
Slides75+76

 These patients come with oliguria, HTN and azotemia

 Severity of oliguria will determine if and when the patient went in RPGN
 When the urine output is less than 400ml/ →definitely this is RPGN. So, in these cases we have to hospitalize these
patients in order to manage them significantly
 15-50% especially elderly people will have recurrent episodes of post streptococcal GN

: ‫ٌعنً هاد الحكً بصٌر مع المرٌض بعدها بطٌب وبعدها بفترة برجع بصٌر معو نفس االعراض والسبب‬

Some of the glomeruli that have more damage and proliferation might get fibrotic (irreversible damage)

more of them will get fibrotic ‫والموجة التانٌة‬

→Chronic glomerulo nephritis

Chronic: this process keep happens over years sometimes with minimal activity and unfortunately it might end in
chronic renal failure

_____________________

Slide 77 Rapidly Progressive Glomerulonephritis

OR the patient might come with the most severe form of acute nephritic
The patient will have sever HTN, persistent and significant oliguria and rapidly elevated creatinine level

If that elevation is constant for few days and weeks →RPGN→ hospitalized and biopsied in order not only to confirms
the diagnosis but also to know the cause and the stage

 The causes are the same of acute nephritic but here they are more prominent.
 So, again we go for biopsy and make 3 specimens :

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 -One for LM but the light microscopic changes are not enough because it doesn’t tell us what is the type of
deposits!
- another one for IF : is going to tell us what type of Ab or immune complex is there, where it’s
located(capillary or mesangial) and the pattern (linear or granular ) which is essential for diagnosis of
different types of GN
- and the last for EM
 More than 50% of glomeruli are going to have injury, necro-inflammatory process and proliferation not only of
glomerular cells but also of epithelial cells leading to crescent. And the rest glomeruli which do not have crescent are
going to have the same pathology (immune complex or Ab deposits associated with inflammatory process) but they
did not yet progress into RPGN.

‫ بالنهاٌة رح ٌصٌر فٌهم زي اللً قبلهم ف ٌا بنلحق المرٌض ومنحافظ ع جزء من وظٌفة الكلى او رح ٌصٌر عندو فشل وٌصٌر بدو نقل‬،‫ٌعنً ع الطرٌق‬
‫كلى وهاد الحكً رح ٌصٌر عندو خالل اٌام او اسابٌع قلٌلة ازا ما اعطٌناه االهتمام الكافً من البداٌة‬

 RPGN is divided into 3 types depending on the pattern and the location of immune complex deposition;
1. Type 1 RPGN (Anti glomerular BM antibody deposition): 10-15%
- Linear deposition of IgG mostly, along the capillaries ( on biopsy)
- A patient may have goodpasture’s syndrome then he could have either RPGN or acute nephritic.

- ‫فً هٌك حالة ال انتٌجٌن من الكلٌة نفسها و رح ٌٌجً ال انتً بودي ٌمسك فٌه عشان هٌك صعب نشوفهم فً الماٌكروسكوب بس منشوفهم فً امٌون‬
‫فلورٌسنس اما لما ٌكون عنا امٌون كوملٌكس جاهز جاي من الدم اسهل نشوفو ع الماٌكروسكوب النو اشً من برا الكلٌة ودخل وترسب فٌها‬

-In case of post streptococcal we have two mechanisms of injury; one is by circulating immune complexes
(predominant cause of injury) and the other by mimicry b/w our own Ag and bacterial Ag

- diagnosis:

We know the underlying cause →goodpasture’s syndrome

So, the pathogenesis implies that we have anti BM anti bodies in serum, we can detect them using ELISA. We take
biopsy also to know the extent of glomerular damage

- treatment :

Steroids and cytotoxic drugs will prevent further anti body production.

But what about the existing Abs in serum?!

→Plasma phoresis ‫غسٌل البالزما‬

Otherwise →renal failure

These patients may also come with pulmonary

hemorrhage due to the same mechanism affecting the
alveoli.

Slide 92

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 This glomerulus is stained by PAS

*PAS stain : it stains only glycogen and BM. So the epithelial cells are not stained

glomerular capsule BM ‫السهم االصفر بأشر على‬

capillaries ‫النجمة باللون االخضر هدول ال‬

‫عاملٌن زي شكل هالل‬proliferating epithelial cells ‫النجمة باللون البرتقالً هدول عبارة عن‬

Formation of crescents is initiated by increased permeability of glomerular basement membrane which leads to influx
of monocytes and exudation of plasma proteins and deposition of fibrin into the Bowman space. Fibrin stimulates the
proliferation of endothelial cells of Bowman capsule (parietal layer of Bowman’s capsule). Rapid growing and fibrosis of
crescents compresses the capillary loops and decreases the Bowman space, which leads to kidney failure within weeks
or months

Slide 87 2. RPGN II ( immune complex type)

-The same underlying causes of acute nephritic may lead to RPGN2 (hepatitis B, C, SLE, post streptococcal,
membrano-prolefrative glomerulo nephritis, Focal segmental, IgA nephropathy)

- Granular IgG complexes → not goodpasture’s syndrome → different treatment and prognosis
- Treatment of the underlying cause + Steroids and chemotherapy
- the location of the these immune complexes gives a clue of the underlying cause;
Sub epithelial: mostly post streptococcal
Sub endothelial: membrano-prolifrative
Mesangial: IgA nephropathy

Slide 19 3. RPGN III (Pauci-immune Type)

- The mechanism is not well understood

- No Abs nor complexes (negative IF), crescent is seen by LM
- By EM we get to see some electron dense deposits
- Most of these patients are going to have ANCA ( some sort of vasculitis)
- ANCA c : Wegener’s granulomatosis
- ANCA p : polyarteritis nodosa
- The vasculitis is not in the capillary tuft itself ; may be in afferent arteriol → sever hypoxia and injury in the
glomeruli

*Screening for RPGN; hepatitis, ANA for SLE, complement, ANCA c and p
In order to know the cause

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 ‫ مجيل اشتيت‬: ‫الجزء الثاني‬

Slide 14 Isolated proteinuria and hematuria:

In addition to the nephritic and nephrotic syndromes, a patient can have isolated proteinuria and hematuria and this
means that he has:

Proteinuria not associated with nephrotic syndrome and hematuria not associated with nephritic syndrome or RPGN.

1- Proteinuria :
Patients may have 3gm/day proteinuria without reaching the nephrotic syndrome, but if we have a patient with
persistent proteinuria of 1 gm/day that’s really significant, and that means the patient has an abnormal GBM
that leaks proteins due to pathologic cause.

For example the patient may have some sort of focal segmental glomerulosclerosis or membranous
nephropathy or mostly diabetes that didn’t reach the nephrotic range yet.
So these patients have to be followed to avoid reaching the nephrotic syndrome or even renal failure!

2- Hematuria :
Firstly, when we suspect hematuria in a patient we have to look for the RBCs casts.
If the patient doesn’t has a cast and he has fresh RBCs only, we can suspect stones or even tumor! Then we
have to send him to the urologist.

If we have RBCs casts we have to suspect nephritic syndrome, but if didn’t reach the nephritic range we can
suspect that he has mostly IgA nephropathy (Berger’s disease).
Slide IgA nephropathy (Berger’s disease( :
95-97
In this disease patients will overproduce IgA after upper respiratory tract infection mostly.

50% of these patients may have elevated IgA in the blood and this will get trapped in the kidney and especially in the
mesangium > the mesangial cells try to phagocyte this IgA but of its concentration is too high this will lead to its
precipitation and that will be associated with activation of the alternative pathway of the complement system >
accumulation of C3 in addition to IgA in the mesangium .

Activation of the complement pathway will be associated with many diseases in the glomeruli :

1-Increase in in mesangial cellularity 2- Focal segmental glomerulosclerosis 3- RPGN

The common symptoms of all these patients (mostly are early teens) is hematuria and if we go for a biopsy we are going
to see IgA deposits in the mesangium and this is the hallmark of this disease.

Diagnosis by immunofluorescence microscopy could be enough without using EM.

If we didn’t find IgA deposits, we can say that is not IgA nephropathy.

Slide Henoch-Schönlein purpura (HSP):

98-106
IgA against endothelial cells that cause vasculitis in small capillaries.

This is more systemic than Berger’s disease as it causes:

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 Skin rash (especially at the buttocks), arthralgia, and arthritis, hematuria and bleeding per rectum.

These patients are mostly newborns, whereas Berger’s patients are mostly teenagers.

We have to go biopsy in this case to see what exactly we have in the kidney:

Under light microscopy we have to see mesangial cellularity not neutrophils, sometimes we can see crescent (in case of
RPGN), but sometimes we can see nothing!!

 If the patient reachs the end stage kidney disease, we have to go for renal transplantation, but it unfortunately
doesn’t prevent the reoccurrence of the disease because its origin is not from the kidney itself.

 The use of immunosuppression for the treatment is very costly as it increases the risk of infections, so we have
to weigh the stage of the disease and risk of this treatment to decide to use immunosuppression or not.

 We can give some vasodilators or beta blockers in order to decrease pressure on the kidney and delay the
damage.

Slide Alport syndrome (hereditary) :

107+108
Very young children (5-20 years) with hematuria and proteinuria that don’t fit with nephritic or nephrotic
syndromes.

These young children have abnormal GBM due to abnormal collagen synthesis:

-Some cases are X-linked with mutation of the gene coding for alpha-5 chain of collagen type IV.

– Autosomal recessive cases – defect in alpha 3 and alpha 4 chains of type IV collagen.

Associated symptoms:
 Nerve deafness
 Eye abnormalities: Lens dislocation, Cataract and Corneal dystrophy.

– EM: thin and attenuated basement membrane with irregularly thickened areas and splitting of lamina
densa _ basket-weave appearance.

The disease will start with glomerular sclerosis and as it continues, it can affect the tubules leading to its
atrophy as well as interstitial fibrosis leading to chronic renal failure at the end stages.

Treatment with renal transplantation is much recommended because this won’t be associated with
reoccurrence of the disease because it is renal in origin > remember ( hereditary disease).

Slide End stage kidney disease:

109

Patients with end stage kidney disease will come with:

 Hypertension
 Anemia
 Uremia
 Discoloration of skin with dirty odor (urea odor)
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  Headache
 Symmetric contraction of both kidneys under US.

The worldwide most common cause of end stage kidney disease is Diabetes, other causes include: RPGN,
FSG, MPGN and IgA nephropathy.
The three main morphological features of end stage kidney diseases are:

 Glomerulosclerosis
 Tubular atrophy
 interstitial fibrosis
END of RENAL 3 slides

 Renal 4 slides
Glomerular Diseases II
Outline :
Diabetes
Amyloidosis
Systemic lupus erythromatosus (SLE)
Renal transplant pathology

Slide 2
Diabetes
Diabetes can affect any component of the kidney, but we usually use the term (diabetic nephropathy) to indicate the
effects of diabetes on the glomerulus that mainly includes:
 Glomerulosclerosis – Diabetic nephropathy
 Renal artery arteriosclerosis and atherosclrosis
 Papillary tip necrosis
 Acute and chronic pyelonephritis

Slide Diabetic nephropathy:

3-16

 THE FIRST CAUSE FO DEATH DUE TO DIABETES IS MI THEN RENAL FALIURE.

 THE MOST COMMON CAUSE OF RENAL FALIURE due to NEPHROTIC SYNDEOM IS DIABETES.
Nephropathy in diabetic patients will start with glycosylation and thickening of the GBM that will make the GBM leakier
for proteins leading to gradual proteinuria (protein insudation) till reaching the nephrotic syndrome.

Protein leakage is associated accumulation of the hyaline material between the mesangium (hyaline caps) and in the
Bowman’s capsule (capsular drops) and after several months that accumulated hyaline will form globules called
(Kimmelsteil-Wilson) Lesions that will end in glomerulosclerosis.

Patients with diabetes have to have regular urine analysis as well as fundal examination for suspected nephropathy or
retinopathy because these diabetic effects come simultaneously:

 Diabetic Retinopathy is associated with Diabetic Nephropathy 85-90% of the time.

 However, Diabetic Nephropathy is associated with Diabetic Retinopathy only 50-60% of the time.

Diabetic nephropathy differs from the focal segmental glomerulosclerosis in that the cause of nephropathy is diabetes.
So we can’t see the features of Diabetic nephropathy in a patient with normal glucose level!
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The increase viscosity of GBM due to glycosylation in diabetic patients will be associated with accumulation of non-
specific IgG antibodies not IgM that is associated with focal segmental glomerulosclerosis.

Slide 17 Arteriopathies:
 Arteriolosclerosis of the afferent, efferent and interstitial arterioles.
 Atherosclerosis: accelerated athermanous plaque formation in the renal artery leading to renal ischemia.
Slide 18 Pyelonephritis:
In general pyelonephritis means inflammation of the entire renal parenchyma not only the pelvis.

This inflammation starts from the interstitium (interstitial fibrosis) then it affects the tubules (tubular atrophy) and the
glomerulus (glomerulosclerosis) leading to renal failure!

Slide 19 Papillary tip necrosis (necrotizing papillitis):

Ischemic neurosis of the papillary tips of the medullary pyramids due to continuous inflammation or temporary blockage
of the supply and that will be associated with:

 Destruction and detachment of these papillae that could be seen in the urine.
 Hematuria.
 Deterioration of the renal function.

Amyloidosis
Kidney is one of the organs that is mostly affected by amyloidosis, which is one of the most common causes of
nephrotic syndrome.

In order to diagnose a patient with amyloidosis we have to have a simultaneous secondary inflammatory
process like rheumatoid arthritis , tuberculosis or bronchiectasis (secondary amyloidosis).
Patients with primary amyloidosis mostly have multiple myeloma with its manifestations.

So the deposition of IG light chains in the kidney will lead to vascular, glomerular, and tubular lesions (myeloma
kidney) leading to renal failure!

These deposits differ from that of diabetes in being more homogenous and they will be positive for the Congo
red stain and apple green birefringence under polarizing light.

Under EM we can see fibril proteins in the GMB and mesangium and that’s very characteristic for amyloidosis.

We can use immunohistochemistry against the IG light chains (kappa or lambda).

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