Hematuria And Nephritis

Front 1

Hematuria

Back 1

Microscopic >2-3 RBC/Hpf
Macroscopic or gross (5 ml makes PP Red !)
Origin:
Glomerular: dysmorphic cells and RBC cast
Extra-glomerular : Ureters/prostate/bladder intact rbcs no cast fromation
Transient vs. persistent
UTI, Trauma, Fever
Older Age makes for less benign DX

Front 2

Hematuria- clues from Hx and PE

Back 2

Dysuria with Pyuria  UTI
Family history of CKD  Alport's
Recent infection suggest PIGN

Front 3

Persistent Isolated Hematuria

Back 3

Ig A nephropathy
Hereditary Nephritis-Alports
Thin basement membrane nephropathy

Front 4

Nephritis Syndrome

Back 4

Active urinary sediment
Inflammatory process
RBC casts, Dysmorphic RBC
Proteinuria 1-3 grams
HTN
Edema (Increased Na avidity of tubules)
ARF

Front 5

Nephritic Syndrome Etiologies

Back 5

PIGN (post infectious GN)

Ig A nephropathy*
-Most common GN worldwide

Hereditary Nephritis- Alport's

MPGN

Front 6

PSGN

Back 6

Post strep GN classical example of PIGN
-Can occur with other infections
(viral, Mycoplasma, S. Aureus, Strep Pneumo.)

children 2-14 yrs old.

2:1 Male/female.

Pharyngeal infection (“strep throat”) Up to 10 %
Latent period 2 weeks (1-3 weeks)

Skin infection
Up to 25 %
Latent period 4 weeks (3-6 weeks)

Infection often resolved on nephritic presentation

Front 7

PSGN Clinical Findings

Back 7

SX:
Hematuria (tea colored)
Oliguria
Edema, HTN

U/A:
RBC and RBC casts
Variable proteinuria

Labs:
**Low Complement (C3) in > 90%
Positive Streptozyme panel in > 80 %
Acute Renal failure (elevated serum Bun, Cr)

Front 8

PSGN Pathology

Back 8

Due to Immune response to infection with nephritogenic group A beta-hemolytic strep
Ab may be directed at the bacterial Ag or intrinsic glomerular epitope
Local activation of the complement cascade

Front 9

Dx of PSGN

Back 9

Bx is definitive: diffuse prolif in mesangium, enlarged tuft, and PMN (exudative GN)

IF:
C3, Ig M deposits most prevalent
Mesangial pattern
Starry-sky pattern
Deposits in mesangium and capillary loops
Garland pattern
Deposits in capillary loops

Subepithelial hump shaped deposits on EM

Front 10

Tx PSGN

Back 10

diuretics, supporive care, dialysis if needed

Front 11

Ig A Nephropathy(Berger’s disease)

Back 11

IgA nephropathy was first described by Berger and HInglais in 1968

Mesangial deposits of underglycosylated IgA1- not approp modified and becomes trapped and deposited

*Most common GN worldwide

Front 12

Ig A nephropathyClinical findings

Back 12

Male:Female 3:1
Uncommon in African Americans
Peaks in 2nd-3rd decade of life
Majority idiopathic
Secondary causes:
RA
-Inflammatory Bowel DZ
Ankylosing spond. -Cirrhosis
Psoriasis -Dermatitis herpitiformis

Front 13

Signs and Sx of IgA nephropathy

Back 13

Persistant hematuria
Synpharyngitic** hematuria
(1-3 day after viral illness)
Usually < 1 gram proteinuria
HTN/renal failure not present at time of DX
Normal Serum Complement level

Front 14

Ig A nephropathypathology

Back 14

Elevated Ig A level
Abnormal production by mucosa
(Skin, GI tract)
Defective handling by Kupfer cell in liver
LM:
Diffuse mesangioproliferative changes
Mesangial hypercellularity
Incresaed Matrix**
EM: mesangial deposits.

Front 15

IgA Nephropathy Prognosis

Back 15

20% reach ESRD in 20 years.
Gross hematuria carries a favorable prognosis
HTN, older age , heavy proteinuria, and renal failure carry higher risk of progression
Gender, Serum Ig A levels, intensity of deposits have NO impact on prognosis

Front 16

Tx for IgA Nephropathy

Back 16

ACEI/ARB for proteinuric patients
Fish oil
Decrease production of cytokines
2 year study showed favorable effects
Minimal side effect
Immunosuppression aggressive/progressive disease
Tonsillectomy
Lessens episodes of gross hematuria

Front 17

Henoch-shonlein purpura(HSP)

Back 17

Pathogenesis similar to Ig A disease
Systemic vasculitis with Ig A deposits
GI tract
Renal Tissue
Skin
Common in children with more skin manifestations
Adults tend to have more renal involvement
More common in winter
Overall good prognosis with majority recovering normal renal function

Front 18

Hereditary Nephritis(Alport’s Syd)

Back 18

Inherited progressive glomerular disease
Often associated with
Hearing loss
Ocular abnormalities
Mode of inheritance:
X-linked 80%
AR 15%
AD 5%

Front 19

Hereditary Nephritis Pathology

Back 19

Absence or abnormal distribution of Alpha-3,4,5 chains of type IV collagen
Normally present in BM of variety of tissues
Eye
Kidney
Cochlea
Mutations in COL4A5 gene on X chromosome accounts for 80% of affected patients.
AR arises from mutation in COL4A3, COL4A4

Front 20

Hereditary Nephritis Clinical Findings

Back 20

Young male (< 10 years)
Persistant microscopic hematuria & deafness
May have episodic gross hematuria
85% of cases will have hearing loss
30 % have ocular abnormalities
HTN/Proteinuria develops later in the course
> 90 % reach ESRD by Age 35
Carrier state:
female with much less aggressive disease, variable presentation, 12% ESRD by Age 40

Front 21

Hereditary Nephritis Dx

Back 21

Triad of RF/Deafness/Family HX

Renal BX, confirmatory:
Laminated Basement Membrane on EM
Immunostainig of Type IV collagen

Skin BX
Commercial assay of Ab to alpha-5 chain of type IV collagen
Absence of staining is diagnostic

Genetic testing available for prenatal DX or absolute exclusion of carrier state

Front 22

Hereditary Nephritis Prognosis and Dx

Back 22

Conservative measures
ACEI/ARB
BP control

Cyclosporine
No convincing data
Risk out weights the benefit

Renal transplant:
3-5% of patient develop de novo Anti-GBM dz
Males with X-linked type
Ab to A-5 chain
NOT a contraindication to transplant

Front 23

Thin Basement Membrane nephropathy

Back 23

Benign Familial hematuria
Microscopic hematuria
minimal proteinuria, No HTN
Affects at least 1% of the population
2/3 will have FH of hematuria
A lifelong nonprogressive disorder associated with family history
uniform thinning of the GBM

Front 24

Membranoproliferative GN MPGN

Back 24

Mostly children , equal M:F distribution
Has 3 types based on pathology findings
Clinical Findings:
Nephritic syndrome in 30 % of patients
LOW Complement ( low C3 in 90%)
DDX for nephritic syd with low complement : PIGN, MPGN, SLE,

Front 25

Primary Idiopathic MPGN

Back 25

Younger patients
Type I (30% progressive disease )
Type II : C3 nephritic factor (worse prognosis)
Type III ( course similar to type I)

Front 26

Secindary MPGN

Back 26

Hepatitis C infection
Chronic infections, Endocarditis
Visceral abscess
Malignancy
Cryoglobulinemia

Front 27

Tx MPGN

Back 27

Treat secondary causes if possible (HCV)
Steroids for Idiopathic type I
useful in kids
Not as effective for adults
Type II MPGN
Many drugs studied (Dipyridamole, steroids)
No definitive therapy

Front 28

Hematuria and Nephritis Summary

Back 28

Common causes:
PSGN:
LOW C3
Recent phrayngitis (2 weeks)
HTN, proteinuria
RBC casts

Ig A nephropathy:
Synpharyngitic hematuria episodes (1-3 day)
Persistent microscopic hematuria
No significant proteinuria

Alport’s syd
Family HX
Deafness
Younger age

MPGN

Other causes such as SLE/Vasculitis/RPGN