Hematuria and Nephritic Syndrome

Clinical features of nephritic syndrome

Hematuria, hypertension, decreased GFR/azotemia, oliguria.

Why nephritic syndrome causes hematuria

Subendothelial immune complex inflammation → capillary wall damage → RBC leakage.

Why nephritic syndrome causes hypertension

Reduced GFR → sodium/water retention → RAAS activation.

How to distinguish hematuria from pigmenturia

Spin urine: red sediment = hematuria; supernatant red=pigmenturia

Dipstick heme positive but no RBCs

Myoglobinuria or hemoglobinuria (rhabdomyolysis or hemolysis).

Transient hematuria causes

Exercise, fever, sexual activity, menses contamination, infection, trauma, instrumentation.

Risk factors requiring hematuria workup

Age >50, smoking, analgesic abuse, pelvic radiation, cyclophosphamide(hemorrhagic cystitis), occupational exposures.

Glomerular hematuria clues

Dysmorphic RBCs, RBC casts, proteinuria.

Non‑glomerular hematuria clues

Normal RBC morphology, clots present, no casts.

Nephritic immune complex location

Subendothelial deposits → inflammation → nephritic syndrome.

Mesangial immune complex location of damage

Mixed hematuria + mild proteinuria

Subepithelial immune complex location

Nephrotic syndrome (not nephritic).

Post‑infectious GN hallmark (LM, IF, EM)

Hypercellularity with neutrophils, subendothelial + mesangial deposits, Immune complexes: Granular IgG + C3, Subepithelial “hump” deposits.

Post‑infectious Glomerulonephritis (Cause, Presentation, Complement patterin, Tx)

Immune complex deposition causing hypercellularity, Occurs 2–3 weeks after strep pharyngitis or cellulitis (POST INFECTIOUS),

Sx: Sudden onset edema, hematuria, HTN, azotemia after infection weeks prior, Low C3

Tx: Supportive

Membranoproliferative Glomerulonephritis (MPGN) hallmark (LM, IF, EM)

Endocapillary hypercellularity + “tram‑track” GBM splitting, Subendothelial immune complexes

Membranoproliferative Glomerulonephritis (MPGN) (Cause, Presentation, Complement, Tx)

Immune complex deposition in subendothelial and mesangial areas»inc proliferation.

2ndary Causes: Hepatitis B or C(usually with cryoglobulinemia), endocarditis, chronic abscess, Lupus, lymphoma.

Low C3 and Low C4=classic

Tx: Treat underlying condition if there is one, otherwise steroids + immunosuppression

C3 glomerulopathy definition + 2 Types

Complement dysregulation with dominant C3 staining. Glomerulonephritis with dominant C3(C3GN) and Dense Deposit Disease (DDD)

Dense Deposit Disease (Microscopy, Presentation, Complement, Tx)

Disorder of complement activation» On Microscopy: Ribbon‑like electron‑dense deposits in GBM, tram track in GBM

Sx: Presents as variabel mixed nephrotic/nephritic syndrome

Complement: Low C3 levels, normal C4

Tx: Eculizumab(inhibits C5), immunosuppression

Dense deposit disease pathogenesis + Tx

C3 nephritic factor stabilizes C3 convertase → uncontrolled complement activation due to no degradation of C3 convertase. Eculizumab inhibits C5 which gets overactivated

IgA nephropathy hallmark (LM,IF,EM)

Mesangial IgA diffusely, + C3, hypercellular

IgA nephropathy (Cause, Presentation, Tx)

Generation of abnormally underglycosylated IgA→defective and get deposited in the mesangium→causes immune complex inflammatory reaction

Sx: Hematuria during mucosal infection (“syn‑pharyngitic”)

Tx: ACE/ARBs, SGLT2i, maybe immunosuppresion

IgA nephropathy associated conditions

Henoch-Schonlein Purpura (HSP)=IgA Vasculitis systemically, IBD, celiac disease, ankylosing spondylitis.

Alport syndrome (Cause, Inheritance, Presentation, Tx)

Type IV collagen X linked(of a5) mutation (α3/α4/α5). Hematuria, hearing loss, ocular abnormalities(bc type IV collagen also present in these systems)

Tx: ACE/ARBs, supportive care

Alport syndrome hallmark (LM, IF, EM)

GBM thickening with “basket‑weave” appearance, look for alpha 5 Type IV collagen mutation

Thin basement membrane disease hallmark (LM, IF, EM)

GBM thinning <250 nm.

Thin basement membrane disease (Clinical presentation, Tx, Prognosis)

Persistent microscopic hematuria with normal renal function. Monitor. Tends to be just lifelong hematuria

Why subendothelial deposits cause nephritis

Close to circulation → intense inflammation → capillary injury.

Differential fo Nephritic Syndrome (3)

Post Infectious Glomerulonephritis, Membrano-proliferative Glomerulonephritis, IgA Nephropathy