In this presentation I've tried to cover the maximum part related to hematuria in concise way to understand it better. It covers microscopic hematuria, macroscopic hematuria, classification of glomerular and non-glomerular hematuria, hereditary and acquired causes of hematuria with diagrammatic presentation of pathogenesis for all the spectrum.

1. Dr Tushar
IgAnephropathy &
Hereditary syndrome of
Hematuria

2. • Macroscopic (gross) Hematuria
Visible (Red Urine)
• Microscopic Hematuria (AUA)
>3RBC/HPF from two of
three urinary sediments
without a urinary tract
infection, or menstruation on
microscopic evaluation
Definition

3. Causes of hematuria
Primary glomerulopathies
• Acute proliferative glomerulonephritis
• RPGN
• Membranous nephropathy
• Minimal-change disease
• FSGN
• MPGN
• Dense deposit disease
• IgA nephropathy
• Chronic glomerulonephritis
Systemic disease with glomerular involvement
• SLE
• DM
• Amyloidosis
• Goodpasture syndrome
• Microscopic polyarteritis/polyangitis
• Wegener granulomatosis
• HSP
• Bacterial endocarditis
Hereditary Disorders
• Alport syndrome
• Thin basement membrane disease
• Fabry diases
Glomerual
Upper tract
• Urolithiasis
• Plyelonephritits
• Renal cell cancer
• Transitional cell carcinoma
• Urinary obstruction
• Benign hematuria
Lower tract
• Bacterial cystitis (UTI)
• Benign prostatic hyperplasia
• Strenuous exercise (marathon runner’s
hematuria)
• Transitional cell carcinoma
• Spurious hematuria
• Instrumentation
• Benign hematuria
Non-Glomerual

4. • any glomerular disease may present with hematuria
• approximately 50% of patients with idiopathic hematuria have a
glomerular disease
• most patients also have other signs such as proteinuria, red cell casts, or
renal insufficiency
• there are three disorders that account for most cases of persistent isolated
hematuria due to glomerular disease: IgA nephropathy, hereditary nephritis
(alport syndrome), and thin basement membrane nephropathy

5. Thin basement membrane disease or
benign familial
hematuria
• Mutations of the type IV collagen genes COL4A3 and COL4A4
• TBMN is often familial, probably with autosomal dominant inheritance
• A family history of hematuria is noted in 30 to 50% of cases
• Persistent or intermittent asymptomatic microscopic hematuria
• The long-term prognosis is excellent in most patients with true thin
basement membrane nephropathy
• We don't biopsy these patients
• Slowly progressive renal insufficiency can occur and is often manifested on
renal biopsy by focal segmental glomerulosclerosis

6. uniform thinning of lamina densa of glomerular basement membrane to 200
nm in > 50% of glomerular capillaries

7. • Inherited progressive form of glomerular disease
• Often associated with sensorineural hearing loss and ocular
abnormalities
• Primary basement membrane disorder arising from mutations in genes
encoding several members of the type IV collagen protein family
• X-linked (80%), Autosomal recessive (15%), Autosomal dominant (5%)
• Initial renal manifestation of Alport syndrome is asymptomatic persistent
microscopic hematuria, which is present in early childhood in affected
patients
• ESRD usually occurs between the ages of 16 and 35 years in patients with X-
linked or autosomal recessive disease and they end up on dialysis
Alport syndrome

8. Pathogenesis

10. 4/10 criteria must be met for the diagnosis of Alport syndrome
• Family history of nephritis of unexplained haematuria in a first degree relative of the index case or in a
male relative linked through any numbers of females.
• Persistent haematuria without evidence of another possibly inherited nephropathy such as thin GBM
disease, polycystic kidney disease or IgA nephropathy.
• Bilateral sensorineural hearing loss in the 2000 to 8000 Hz range.
• The hearing loss develops gradually, is not present in early infancy and commonly presents before the age
of 30 years.
• A mutation in COL4A.
• Immunohistochemical evidence of complete or partial lack of the Alport epitope in glomerular, or epidermal
basement membranes, or both.
• Widespread GBM ultrastructural abnormalities, in particular thickening, thinning and splitting.
• Ocular lesions including anterior lenticonus, kerataconus, posterior subcapsular cataract, posterior
polymorphous dystrophy and retinal flecks.
• Macrothrombocytopenia or granulocytic inclusions.
• Diffuse leiomyomatosis of esophagus or female genitalia, or both.

11. Light microscopy shows mesangial cell proliferation and capillary wall thickening,
progressing to glomerular sclerosis and tubulo-interstitial changes

12. This shows glomerular basement membrane changes including splitting of
lamina densa and lamellation

14. IgAnephropathy

15. • IgA nephropathy is the most common cause primary glomerulonephritis
• 2:1 male to female predominance
• Greatest frequency in Asians and Caucasians
• Relatively rare in blacks
• Negative family history
• See in someone with a recent history of cold or sore throat and then they have
hematuria
• Clinical presentation
• One or recurrent episodes of gross hematuria, usually following an upper respiratory
infection
• Microscopic hematuria and usually mild proteinuria
• Nephrotic syndrome
• Acute rapidly progressive glomerulonephritis

17. Pathogenesis

19. Tubulointerstitial changes are mild (periodic acid-Schiff [PAS]) (A) In high-power views, the glomerulus shows a
cellular crescent as well as endocapillary hypercellularity (PAS) (B), diffuse mesangial and endocapillary
hypercellularity (methenamine silver) (C), and subepithelial, 'hump'-like deposits (arrow) (Masson's trichrome) (D).

22. Prognosis
• if you see high proteinuria then it is a bad prognosis. If you see little
proteinuria then there is a good prognosis.
• Patients with IgA nephropathy and little or no proteinuria (<500 mg/day)
have a low risk of progression in the short term.
• Among patients who develop overt proteinuria and/or elevated serum
creatinine concentration, progression to ESRD is approximately 15 to 25
percent at 10 years and 20 to 30 percent at 20 years.

23. Fabry’s disease
• X-linked inherited disorder
• Lysosomal storage disease
• Deficiency of the enzyme alpha galactosidase A
• Dysfunctional metabolism of sphingolipid
• Accumulation of globotriasyceramide in the blood vessels, other tissue and organs.
• Kidney involvement
• Podocytes (abundant)
• Mesangial cells
• Parietal epithelial cells
• Endothelial cells
• Nonspecific late changes reflecting chronic injury
• GBM and TBM changes, mesangial expansion
• Segmental an global glomerular sclerosis (scarring)
• Tubular atrophy and interstitial fibrosis (scarring)

26. disease. (A) Vacuolation of podocytes. (B) Tubular and interstitial deposits. (C)
Deposits in blood vessels. (D) EM: zebra bodies in the cytoplasm of podocytes.

27. Thank you