secondary glomerular disease

1. Secondary glomerular
disorders
Presented by: Farah AL-amleh 200260
Supervised by : DR. samir Brijia

2. outlines
- Overview
- Diabetic nephropathy
- Hypertensive nephropathy
- Lupus nephropathy
- Membranoproliferative GN
- Post-streptococcal GN
- Goodpasture syndrome
- Dysproteinemias
- Sickle cell nephropathy
- HIV nephropathy
- GPA
- PAN

3. Terminology of glomerular diseases
Primary: a kidney disease specifically affecting the glomeruli (e.g., minimal change glomerulonephritis)
Secondary: a disease affecting the glomeruli in the context of a systemic disease (e.g., lupus nephritis in
SLE) or a disease affecting another organ (e.g., diabetic nephropathy)
Diffuse: > 50% of glomeruli affected (e.g., diffuse proliferative glomerulonephritis)
Focal: < 50% of glomeruli affected (e.g., focal segmental glomerulosclerosis)
Global: entire glomerulus is affected
Segmental: only part of the glomerulus is affected
Proliferative: an increased number of cells in the glomerulus
Membranous: thickening of the glomerular basement membrane (e.g., membranous nephropathy)
Sclerosing: scarring of the glomerulus
Necrotizing: cell death within the glomerulus

4. pathophysiology
The glomerular filtration barrier consists of 3 parts :
Initial segment: Fenestrated glomerular capillary endothelium prevents large
proteins from passing through.
Second segment: The glomerular basement membrane (GBM) contains a
negative charge produced by heparan sulfate.
Final segment: Visceral epithelial cells produce/maintain the GBM and
contain intercellular junctions created by podocytes that prevent further
protein loss.
Damage to the glomeruli → disruption of the glomerular filtration
barrier → can lead to nephritic or nephrotic syndrome

7. Diabetic nephropathy
Most important cause of end-stage renal disease.
Pathophysiology:
Chronic hyperglycemia → glycation (also called non-enzymatic glycosylation or
NEG) of the basement membrane (protein glycation) → increased
permeability and thickening of the basement membrane and stiffening of the
efferent arteriole → hyperfiltration (increase in GFR) → increase in
intraglomerular pressure → progressive glomerular hypertrophy, increase in
renal size, and glomerular scarring (glomerulosclerosis) → worsening of
filtration capacity

8. Diabetic nephropathy
Microalbuminuria in diabetic nephropathy (DN):
In diabetes, there is progressive loss of this negative charge due to upregulation of
heparanase expression by renal epithelial cells, which results in leakage of albumin.
In the initial stages of DN, only small amounts of albumin (<300 mg/day) are lost.
This moderately increased albuminuria is detected with the use of an albumin-specific urine
dipstick as it is not detected by regular dipstick analysis.
Early administration of ACE inhibitors in patients with diabetes and albuminuria has been
shown to reduce urinary albumin excretion and slow progression to overt diabetic
nephropathy.

9. Hypertensive nephropathy
Hypertensive nephrosclerosis: a renal vascular injury secondary to long-
standing arterial hypertension
Pathophysiology: chronic hypertension → hypertrophy of medial and intimal
layers → narrowing of afferent arterioles → ↓ glomerular blood flow →
glomerular and tubular ischemia → arteriolonephrosclerosis and fibrosis
(focal segmental glomerulosclerosis) → end-stage renal disease
Clinical findings:
Initially microalbuminuria and microhematuria
↑ BUN, Cr, and uric acid levels
Nephrosclerosis with proteinuria (usually < 1 g/day) and progressive renal
failure occur with disease progression.

10. Hypertensive nephropathy
Diagnostics: renal biopsy shows vascular, glomerular, and tubulointerstitial
changes.
Arterial and arteriolar medial hypertrophy, intimal thickening, and hyalinosis
Global glomerulosclerosis (more common) or focal segmental
glomerulosclerosis
Tubulointerstitial fibrosis
Treatment: ACE-inhibitors (first-line), ARBs

11. Lupus nephritis
Most dangerous specific manifestation of SLE because of its high morbidity
and mortality .
Can manifest as nephritic syndrome and/or nephrotic syndrome
Common: found in up to 50% of individuals with SLE at presentation
Pathophysiology :
Mesangial and/or subendothelial deposition of immune complexes (e.g., anti-
dsDNA antibodies, anti-Sm antibodies) → expansion and thickening of
mesangium, capillary walls, and/or glomerular basement membrane

12. Lupus nephritis
Clinical features:
Hypertension , Edema ,Hematuria
Diagnostics :
Laboratory studies
BMP: ↑ creatinine
Urinalysis: proteinuria, hematuria, cellular casts (RBCs, hemoglobin, granular,
tubular, or mixed)
24-hour urine collection with proteinuria ≥ 0.5 g/24 hours

13. Lupus nephritis
Kidney biopsy :
LM—―wire looping of capillaries.
EM—subendothelial and sometimes intramembranous
IgG-based ICs often with C3 deposition.
IF—granular.
A common cause of death in SLE (think ―wire lupus)
Management of lupus nephritis:
General principles :All patients should receive standard
therapy for lupus and individualized management of
CKD.

14. Membranoproliferative GN
Most commonly nephritic, but severe
forms can also be nephrotic.
Type I:
—subendothelial immune complex (IC)
deposits with granular IF; “tram-track”
appearance on PAS stain D and H&E stain E
due to GBM splitting caused by mesangial
ingrowth.
Causes: diopathic or may be 2° to hepatitis
B or C infection.

15. Membranoproliferative GN
Type II—also called dense deposit disease:
deposition within the basement membrane.
i. Type II is associated with C3 nephritic
factor (IgG antibody that stabilizes C3
convertase → persistent activation of C3
→ persistent complement activation →
↓ C3 levels).

16. Poststreptococcal GN
—most common cause of nephritic syndrome
a. Most frequently seen in children. Occurs ∼ 2–4 weeks after group A
streptococcal infection of pharynx or skin. Resolves spontaneously.
b. Type III hypersensitivity reaction.
c. Presents with peripheral and periorbital edema, cola-colored urine,
hypertension.

17. Poststreptococcal GN
d. LM—glomeruli enlarged and
hypercellular A due to a combination
of leukocyte infiltration (neutrophils
and monocytes) and mesangial and
endothelial cell proliferation.
e. IF—(starry sky) granular
appearance (lumpy-bumpy) B due to
IgG,IgM, and C3 deposition along
GBM and mesangium.
f. EM—subepithelial immune
complex (IC) humps due to
deposition of immune complexes
composed of IgG. IgM, and C3.

18. Poststreptococcal GN
g. Lab findings:
i. Elevated titers of anti-streptococcal antibodies (anti-streptolysin O,anti-
DNase B, anti-cationic proteinase).
ii. Low C3 concentration.
iii. Cryoglobulins may also be present in the serum.
Age is an important prognostic factor in poststreptococcal glomerulonephritis.
95% of affected children, but only 60% of affected adults recover completely.

19. Goodpasture syndrome

20. Goodpasture syndrome
1. Classic triad of proliferative GN (usually crescentic), pulmonary hemorrhage, and
IgG anti glomerular basement membrane antibody.
2. Clinical features: rapidly progressive renal failure, hemoptysis, cough, and
dyspnea
3. Lung disease precedes kidney disease by days to weeks.
4. Renal biopsy shows linear immunofluorescence pattern.
5. Treat with plasmapheresis to remove circulating anti-IgG antibodies.
Cyclophosphamide and steroids can decrease the formation of new
antibodies.

21. Dysproteinemias
Amyloid is an abnormal protein produced in association with:
- Myeloma.
- Chronic inflammatory diseases.
- Rheumatoid arthritis.
- Inflammatory bowel disease.
- Chronic infections.
▪ There is also a primary form of amyloidosis in which the protein is produced
for unknown reasons. The kidney is the primary target of the protein.

22. Dysproteinemias
Biopsy is the most accurate test. You will
see green birefringence with Congo red
staining.
▪ Treat amyloidosis by trying to control
the underlying disease. When this is
unsuccessful or there is no primary
disease to control, the treatment of
amyloidosis is with melphalan and
prednisone.

23. Sickle cell nephropathy
If ischemic injury to the renal tubules occurs (due to hemodynamic changes or
nephrotoxins), there is increased risk of dehydration (from impaired urine
concentration), precipitating sickling crisis.
This sickling of RBCs in the microvasculature leads to infarction. In the
kidney this occurs mostly in the renal papilla. Sequelae of recurrent
papillary infarction include papillary necrosis, ATN, and renal failure, as
well as a high frequency of UTIs.
Nephrotic syndrome can also develop (which can lead to renal failure).
It progresses to ESRD in approximately 5% of the patients.
ACE inhibitors may be helpful.

24. HIV nephropathy
1. Characteristics include proteinuria, edema, and hematuria.
2. Histopathology most often resembles a collapsing form of FSGS.
3. Treat with prednisone, ACE inhibitors, and antiretroviral therapy.

25. HIV nephropathy

26. Granulomatosis with polyangiitis
Wegener granulomatosis (WG) is characterized by systemic vasculitis that
most often involves the kidney, lung, and upper respiratory tract such as the
sinuses or middle ear. It can also involve the skin (50%), joints, eyes (50%), and
GI tract. Neuropathy may be a symptom.
▪ Prominent upper respiratory tract involvement (otitis, sinusitis).
▪ All vasculitides are associated with fever, weight loss, and malaise.
▪ The best initial test specific is the antiproteinase-3 antibody (or cytoplasmic
antineutrophil cytoplasmic antibody [C-ANCA]).
▪ The most accurate test is a biopsy of the kidney, nasal septum, or lung,
looking for granulomas.
▪ Treatment for WG is steroids and cyclophosphamide.

27. Polyarteritis nodosa
- Polyarteritis nodosa (PAN) is a systemic vasculitis of medium-sized arteries
that most commonly affects the kidney.
- Virtually every organ in the body can be affected, but it tends to spare the
lung.
- Although it is of unknown etiology, it can be associated with hepatitis B (10-
30%) and all patients with PAN should be tested.
▪ Presentation:
- Besides the presentation of glomerulonephritis, PAN presents with
nonspecific symptoms of fever, malaise, weight loss, myalgias, and arthralgia
developing over weeks to months as does almost every type of vasculitis.

28. Polyarteritis nodosa

29. Case scenario

30. References
Step up to medicine ,6th edition
Amboss
Uworld Qbanks

31. Thank you