# Chapter 18: Nephritic & Nephrotic Syndromes

[← Table of Contents](https://urinenephrology.org/nephrology-textbook/index.html) [← Previous: Chapter 17](https://urinenephrology.org/nephrology-textbook/chapters/chapter-14-glomerular.html) [Next: Chapter 19 →](https://urinenephrology.org/nephrology-textbook/chapters/chapter-16-tubulointerstitial.html)

### 📖 Ready for a Deeper Dive?

Explore these related Lecture Series modules and Clinical Mastery reviews:

[Glomerulonephritis Module](https://urinenephrology.org/2025_UDPA_Lectures_Live/glomerulonephritis/index.html) [🏆 Mastery: Glomerular Disease](https://urinenephrology.org/mastery/glomerular/index.html) [🏆 Mastery: Nephrotic as Heart Failure](https://urinenephrology.org/mastery/cardiorenal/nephrotic-as-heart-failure.html)

## Definitions and Urine Microscopy

**Nephrotic Syndrome:** Proteinuria \>3.5 g/day, hypoalbuminemia \<3.0 g/dL, edema, hyperlipidemia. Urine microscopy shows oval fat bodies and fatty casts.

**Nephritic Syndrome:** Hematuria with RBC casts, proteinuria \<3.5 g/day, hypertension, reduced GFR. Urine microscopy is notable for dysmorphic RBCs and RBC casts.

## Serological Evaluation of Nephritic Syndrome

### Complement Evaluation

Measuring C3 and C4 helps identify the complement pathway activation and narrow the differential diagnosis.

| Complement Pattern | Renal-Limited Diseases | Systemic Diseases |
|----|----|----|
| **Low C3 & C4** (Classical Pathway) | Idiopathic MPGN Type I | SLE nephritis, Cryoglobulinemia, Endocarditis |
| **Low C3, Normal C4** (Alternative Pathway) | Post-infectious GN, C3 glomerulopathy | Atypical HUS |
| **Normal C3 & C4** | IgA nephropathy, Renal-limited vasculitis, Anti-GBM nephritis | ANCA Vasculitis (GPA, MPA), Goodpasture's, HSP, Alport syndrome |

## Immunosuppression in Nephrotic Syndrome

### Minimal Change Disease (MCD)

First-line therapy is high-dose oral corticosteroids. For frequently relapsing or steroid-dependent disease, options include cyclophosphamide, calcineurin inhibitors (cyclosporine), mycophenolate mofetil (MMF), or rituximab.

### Focal Segmental Glomerulosclerosis (FSGS)

Initial treatment is also high-dose corticosteroids. For steroid-resistant cases, calcineurin inhibitors (cyclosporine, tacrolimus) are first-line. MMF can be an alternative. Blacks and patients with the collapsing variant are often unresponsive.

### Membranous Nephropathy (MN)

Diagnosis can often be made non-invasively with a positive anti-PLA2R antibody test. Treatment is risk-stratified. Low-risk patients receive supportive care. Moderate to high-risk patients are treated with immunosuppression, with rituximab now considered a first-line option alongside cyclophosphamide-based regimens.

## Rapidly Progressive Glomerulonephritis (RPGN)

#### RPGN: A Medical Emergency

RPGN is a clinical syndrome of rapidly worsening kidney function with suspected glomerular inflammation, often with crescents on biopsy. Urgent evaluation must not wait for a 50% GFR decline or a fixed crescent percentage. It is classified by immunofluorescence pattern:

- **Type I (Linear):** Anti-GBM disease. Treat with plasmapheresis, steroids, and cyclophosphamide.
- **Type II (Granular):** Immune complex disease (e.g., Lupus, IgA). Treat the underlying cause.
- **Type III (Pauci-immune):** ANCA-associated vasculitis. Treat with high-dose steroids and either cyclophosphamide or rituximab. Plasmapheresis is indicated for severe renal failure or pulmonary hemorrhage.

## New and Emerging Treatments

#### Novel Therapies for Glomerular Disease

- **Tarpeyo (Budesonide):** A gut-targeted steroid, now fully FDA-approved for IgA nephropathy.
- **Endothelin Receptor Antagonists:** Sparsentan (dual ERA/ARB) and Atrasentan show promise in reducing proteinuria in IgAN and FSGS.
- **Biologics:** Rituximab is established; Daratumumab (anti-CD38) is being studied.
- **Other FDA-Approved Options:** FABHALTA® (alternative complement pathway inhibitor) and FILSPARI® (sparsentan) are available for IgA Nephropathy.

[← Table of Contents](https://urinenephrology.org/nephrology-textbook/index.html) [← Previous: Chapter 17](https://urinenephrology.org/nephrology-textbook/chapters/chapter-14-glomerular.html) [Next: Chapter 19 →](https://urinenephrology.org/nephrology-textbook/chapters/chapter-16-tubulointerstitial.html) [↑](https://urinenephrology.org/nephrology-textbook/chapters/chapter-15-nephritic-nephrotic-review.html#top)

### Also on this topic

The same subject at other levels of depth.

- **Student handout:** [Nephritic vs. Nephrotic Syndromes: A Comprehensive Student Guide](https://urinenephrology.org/student-resources/glomerular/nephritic-nephrotic-student-handout.html)


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