Nephrotic Syndrome

Findings that raise suspicion for glomerular disease in general

Hematuria (dysmorphic RBCs, RBC casts) and/or proteinuria, Dec GFR

Why dysmorphic RBCs suggest glomerular disease

RBCs squeezed through damaged filtration barrier → irregular shapes.

Why RBC casts indicate glomerular disease

Casts form only when bleeding originates in the nephron → nephritic process.

Which barrier prevents albumin filtration

Negative charge of GBM + slit diaphragm size restriction.

Nephrotic vs nephritic

Nephrotic = proteinuria, leaky

Nephritic= hematuria, inflammation

Classic nephrotic syndrome features

Proteinuria >3.5 g/day, hypoalbuminemia, edema, hyperlipidemia.

Why nephrotic syndrome causes edema

Tubular sodium retention + low oncotic pressure from hypoalbuminemia.

Why nephrotic syndrome causes hyperlipidemia

Liver increases lipoprotein synthesis in response to low oncotic pressure(due to low albumin leaked out).

Oval fat bodies significance

Lipid‑laden tubular cells seen in nephrotic syndrome.

Complication: hypercoagulability in nephrotic syndrome MOA

Loss of ATIII and fibrinolytic proteins → ↑ thrombosis risk (DVT and renal vein thrombosis)

Complication: infection risk in nephrotic syndrome

Loss of IgG and complement proteins → ↑ susceptibility.

Complication: hypovitaminosis D

PT dysfunction→Loss of vitamin D–binding protein in urine.

Normal daily protein excretion? Proteinuria definition?

<150 mg/day in adults. Proteinuria= >150mg or 3.5g/day

Nephrotic Syndrome 3 Pathology Diseases

Minimal Change Disease, Membranous Glomerulopathy, Focal and Segmental Glomerulosclerosis

Minimal Change Disease hallmark (view from: LM, IF, EM)

NO Podocyte foot process(damage to podocytes), look normal on light microscopy, Infrared Fluoroscopy is negative.

Minimal Change Disease triggers

Infection, immunization, NSAIDs, lymphoma. → they can cause immunologic dysfunction

Minimal Change Disease Clinical presentation + treatment

Most common in kids»sudden onset of massive proteinuria following infection. Tx with Corticosteroids (high response rate).

Focal & Segmental Glomerulosclerosis (FSGS) hallmark (view from: LM, IF, EM)

Focal and segmental sclerosis and hyalinosis on LM; Not an immune complex disease but slight focal IgM on IF; On electron microscope: Loss of Podocytes

Focal & Segmental Glomerulosclerosis (FSGS) genetic associations (1 in particular)

APOL1 variants. NPHS2, TRPC6, ACTN4,

Primary Focal & Segmental Glomerulosclerosis (FSGS) recurrence after transplant

Can recur within 24 hours → circulating permeability factor.

Secondary Focal & Segmental Glomerulosclerosis (FSGS) causes

HIV, sickle cell, heroin, reflux nephropathy, hyperfiltration.

Focal & Segmental Glomerulosclerosis (FSGS) treatment

ACE/ARB + immunosuppression for primary disease.

Membranous nephropathy hallmark (view from: LM, IF, EM)

LM: diffuse capillary wall + GBM thickening + “spike and dome” on silver stain

IF: Immune deposits in GBM

EM: No podocytes, subepithelial immune deposits

Membranous nephropathy primary antigen

PLA2R autoantibody (adult primary membranous).

Secondary membranous nephropathy causes

Cancer (lung/colon), hepatitis B/C, lupus, NSAIDs, syphilis.

Diabetic nephropathy hallmark lesions (view from: LM, IF, EM)

LM: GBM thickening, mesangial expansion, Kimmelstiel‑Wilson nodules, afferent+efferent arteriolar hyalinosis

EM: No podocytes, GBM thickening

Diabetic nephropathy pathogenesis

Advanced Glycosylation End-products(AGEs) → basement membrane glycation → hyalinosis → hyperfiltration injury→glomerulosclerosis

Amyloidosis renal hallmark

Congo red positivity with apple‑green birefringence and cotton candy deposition in mesangium; randomly arranged fibrils

Nephrotic syndrome: mechanism of protein leakage

Loss of podocyte slit diaphragm integrity → albumin filtration.

Subepithelial deposits clinical correlate

Nephrotic syndrome (non‑inflammatory, leaky barrier).

Subendothelial deposits clinical correlate

Nephritic syndrome (inflammatory, hematuria).

Mesangial deposits clinical correlate

Mixed nephritic/nephrotic features.

Why nephrotic urine sodium is low

Tubules retain sodium to compensate for low oncotic pressure → edema formation.

Classic Nephritic Changes

Hematuria, Azotemia(high nitrogen→inc BUN), Oliguria(little peeing), Hypertension

HIV Associated Nephropathy

Caused by direct infection of glomerular/tubular cells with HIV. Tx with Anti retroviral therapy