Nephrotic & Nephritic Syndrome Flashcards by Stephanie Escobar

This patient with peripheral edema, hypoalbuminemia, and urinary protein excretion of >3.5 g/day meets all of the major criteria for ____ syndrome.

nephrotic

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Nephrotic syndrome results in
intravascular volume depletion (↑ Aldosterone, ↑ Renin) ,
and ↑ _____ pressure with ↓ ____ blood volume
resulting in total body volume overload.

↑Hydrostatic Pressure
↓ Effective Arterial Blood Volume

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Patients with nephrotic syndrome have increased risk for ____ (due to hyperlipidemia) and ____ (due to loss of antithrombin III).

atherosclerosis (MI)
thrombosis (Stroke)

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hypocomplementemic (low C3 & C4) glomerulonephritis associated with
systemic vasculitis (Purpura, Arthralgias) is usually due to ___ or ___.

MPGN: membranoproliferative glomerulonephritis (positive serum cryoglobulins)
or
lupus nephritis (positive antinuclear antibodies).

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Glomerular or nonglomerular hematuria?
RBC casts may be seen

Glomerular

(absent in non-glomerular hematuria)

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Glomerular or nonglomerular hematuria?
Proteinuria

Glomerular

(trace or negative in non-glomerular hematuria)

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Glomerular or nonglomerular hematuria?
Clots may be seen

Non-Glomerular

(No clots in glomerular hematuria)

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Glomerular or nonglomerular hematuria?
Dysmorphic RBCs may be seen

Glomerular Hematuria

(rarely seen in non-glomerular)

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Glomerular hematuria is characterized by dysmorphic red blood cells and/or ___ on urinalysis.

When these findings are absent, albuminuria and/or ___ urine suggests a glomerular source.

RBC casts

dark/tea-colored

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___ & ____ are the most common causes of nephrotic syndrome in adults in the absence of a systemic disease.

Focal segmental glomerulosclerosis (FSGS)
membranous nephropathy

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FSGS is more common in ____ patients and in those with ___, heroin use, and HIV.

African American
obesity

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______ is the most common Nephrotic Syndrome among children.

Minimal change disease

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In adults, Minimal change disease is associated with use of ___ and _____.

NSAIDs
Lymphoma (usually Hodgkin)

(work up for Lymphoma is the NBSIM if diagnosed)

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Amyloidosis Nephrotic Syndrome is usually associated with ___ or ___.

multiple myeloma (CRAB sxs)

chronic inflammatory disease (rheumatoid arthritis, bronchiectasis).

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This patient’s presentation (anasarca, pulmonary and facial edema, hypertension, and abnormal urinalysis with proteinuria and microscopic hematuria) suggests ___ with ___.

acute nephritic syndrome
with fluid overload.

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Nephritic glomerulonephritis usually presents with urinary sediment containing red blood cells, occasional white blood cells, and red cell or mixed cellular casts. Edema in these patients is due primarily to ___ and retention of sodium and water by the kidneys.

decreased GFR

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Diabetic nephropathy is characterized by glomerular hyperfiltration, _____, and ___ nodules.

Persistent proteinuria in a patient with long-standing diabetes and poorly controlled hypertension should raise suspicion for this diagnosis.

basement membrane thickening
mesangial nodules
(Kimmelstiel-Wilson lesion) Nodular Glomerular Sclerosis

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causes the formation of immune complex deposits, activation of the complement system, and subsequent damage within the glomerulus.

Presents with hematuria, hypertension, and edema in children after recent URI or Rash.
↓ C3 (CH50)
↓/– C4

Poststreptococcal glomerulonephritis

(PSGN–Nephritic)

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Young adult with recent h/o URI presents with recurrent Hematuria (micro or macro), HTN, and bilateral flank pain.

Normal C3/C4 levels

IgA Nephropathy
(Nephritic)

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MPGN is characterized by glomerular hypercellularity and capillary wall & basement membrane thickening due to deposits of:

⬩immunoglobulin complex deposits & complement factors → ____ complement cascade activation

⬩complement factors & little to no immunoglobulin complex deposits → ____ complement cascade activation

classic complement cascade (IC & Complement)

alternative complement cascade (Only Complement)

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patient with significant proteinuria and hematuria most likely has _____ (4).

Nephritic Nephrotic glomerulonephritis
- MPGN
- Diffuse Proliferative GN
- Lupus Nephritis
- IgA Nephropathy

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Heavy proteinuria (> 3.5 g/day)
Hypoalbuminemia
Generalized edema
Hyperlipidemia and fatty casts in urine → frothy urine
Hypertension
↑ Risk of thromboembolism (s/t loss of AT III)
↑ Risk of infection (via loss of IgG)

Nephrotic Syndrome

(Notice Hematuria is not part of the criteria but IgA nephropathy, MPGN, Lupus Nephritis are Nephritic Nephrotic Syndromes)

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Proteinuria (< 3.5 g/day)
Hematuria with acanthocytes (pointy RBCs)
RBC casts in urine
Mild to moderate edema
Oliguria
Azotemia (↑BUN)
Hypertension
Sterile pyuria

Nephritic Syndrome
⎯
Proteinuria (> 3.5 g/day) in Nephritic Nephrotic Syndromes (MPGN, IgA Neph, Lupus Neph)

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Complement-mediated MPGN is characterized by deposition of C3 but minimal or absent immunoglobulin deposition

______ a subtype of MPGN (causing persistent activation of the alternative complement cascade pathway resulting in kidney damage.)

Is associated with ____ and has a poor prognosis.

Dense deposit disease (DDD)

Malignancy

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**Immune complex/immunoglobulin** mediated **MPGN** is often caused by (2) Result in **both** immune complex and complement depositions leading to acute injury triggering the **classic** complement cascade.

- HCV, HBV - Autoimmune disorders

**Immune complex/immunoglobulin** mediated **MPGN** results from the renal deposition of ICs containing ______ , which are immunoglobulins generated by chronic **viral infections** or **autoimmune** diseases.

cryoglobulins

**Poststreptococcal glomerulonephritis**, a complication of group A Streptococcus infection (pharyngitis, impetigo). Management is mainly **supportive**. Complications of volume overload (hypertension, edema) require treatment with ____ & ____.

Loop Diuretics Ace-I

Kidney biopsy shows **linear Glomerular Capillary** IgG deposits. No complement deposits. Hematuria and hemoptysis is classically seen

Anti-GBM disease (Good Pasture) Nephritic Syndrome

patient's HTN, proteinuria, hematuria, significant lower extremity edema, and ↑ Cr raise strong suspicion for glomerulonephritis. The concurrent presence of: **fatigue** **arthralgia** (swollen, tender joints) **anemia** & **thrombocytopenia** suggests the underlying cause is ____.

systemic lupus erythematosus (SLE)

Lupus nephritis (seen in most patients with SLE) is s/t _____ **immune complexes deposits** above & below the glomerular basement membrane.

anti-double-stranded DNA

Because lupus nephritis often causes significant urinary protein loss, patients frequently develop **low serum albumin** with subsequent lower extremity **edema** and possibly ____.

pleural effusions

Hereditary nephritis (Alport syndrome) due to defective type ____ causes hematuria and progressive renal insufficiency.

type IV collagen

IgA nephropathy is characterized by ___ IgA deposition, usually within days after an upper respiratory infection.

mesangial

IgA nephropathy is characterized by mesangial IgA deposition, usually within days after an **upper respiratory infection**. Characteristic features include hematuria with red blood cell casts on urinalysis and ___ C3/C4 complement levels. **hypertension** and **↑ Cr** are common.

normal C3/C4 (PSGN has **low** C3/C4)

Diabetic nephropathy, a microvascular complication of diabetes mellitus, is associated with abnormal (moderately increased) albuminuria. Random urine ____ testing is the most sensitive test to detect early elevations in albumin excretion.

albumin-to-creatinine ratio (should be done **annually** in T2DM pts)

Pregnant pt (10 weeks) with h/o T1DM presents with proteinuria, ↑ Cr, and HTN. **Pregnancy** can worsen **diabetic kidney disease** (DKD), leading to hypertension, ↑ Cr, and frank proteinuria. **Preeclampsia** also causes hypertension and proteinuria but occurs **later in pregnancy**. Findings **prior** to _____ gestation are usually due to **preexisting** nephropathy.

20 weeks

**Preeclampsia** with severe features causes new-onset ___ and ___ and usually occurs **≥ 20** weeks gestation.

hypertension proteinuria

____, which can present with hematuria, flank pain, and scrotal edema (dilated and tortuous veins, in men), is an important complication of ____ syndrome.

Renal vein thrombosis nephrotic (s/t hypercoagulability)

___ is thought to be caused by direct viral infection of the renal epithelial cells and typically presents with heavy proteinuria, **rapidly progressive renal failure**, and edema. It is most common in patients of **sub-Saharan African** descent with active viral infection.

**HIV-associated** nephropathy (aka Focal Segmental Glomerulonephritis) Tx: **Antiretroviral therapy** (ART) may help kidney recovery

Kidney biopsy shows collapsing **focal segmental glomerulosclerosis**; tubuloreticular **inclusions** on electron microscopy.

**HIV-associated** nephropathy (aka Focal Segmental Glomerulonephritis)

_____ should be suspected in patients with **nephrotic syndrome** who develop **hematuria** and/or **flank pain**.

Renal vein thrombosis (RVT)

Renal vein thrombosis (RVT) can occur in ___ due to hypercoagulability caused by urinary loss of anticoagulant proteins (antithrombin III).

nephrotic syndrome

_____ results from renal deposition of heme pigments from the breakdown of hemoglobin or myoglobin after excess bloodstream release (**hemolysis, rhabdomyolysis**).

Pigment nephropathy

Patient presents with **palpable purpura**, glomerulonephritis (**hematuria, RBC casts, ↑ Cr**), **peripheral neuropathy** (hyporeflexia), **arthralgias**, and constitutional symptoms (**fever, malaise**). Such a **multisystem** involvement is suggestive of

small-vessel vasculitis (SVV)

Presents with **palpable purpura**, glomerulonephritis (Hematuria, ↑ Cr), **arthralgias**, and **gastrointestinal distress** in **children**.

IgA vasculitis (Henoch-Schönlein purpura) A small-vessel vasculitis (SVV)

_____ is a small-vessel vasculitis that commonly presents with: ⬩ palpable purpura ⬩ glomerulonephritis ⬩ peripheral neuropathy (areflexia, ↓sensation) ⬩ **arthralgias**

Mixed cryoglobulinemia syndrome (Eosinophilic GPA does **not** have arthralgia and has a history of allergies/asthma)

Chronic _____ is the most common cause of **Mixed Cryoglobulinemia syndrome**, and characteristic laboratory abnormalities include (3)

hepatitis **C** infection → **C**ryoglobulin hepatitis C antibodies rheumatoid factor hypocomplementemia

Low → total **complement** Positive → **Anti–hepatitis C virus** antibodies Positive → **Rheumatoid factor** Negative → Antineutrophil cytoplasmic antibodies Diagnosis

Mixed cryoglobulinemia syndrome

**Glomerular sources** of gross hematuria should be considered in a patient with: brown urine, red blood cell casts, proteinuria, hypertension, and/or edema. Initial evaluation includes

serum complement (C3, C4) levels

____ is diagnostic of sickle cell trait, which can cause **renal papillary necrosis** from sickling within capillaries of the renal medulla.

Hemoglobin electrophoresis

Pathophysiology of ____ includes **T-cell–mediated** injury to **podocytes** → ↑ molecular permeability to albumin

Minimal Change Disease Tx: Corticosteroids (Prednisone)

____ is the most common cause of **nephrotic syndrome in children**. Pathogenesis involves **cytokine-induced glomerular injury**, which causes **effacement of podocytes**, leading to a massive urinary loss of protein, hypoalbuminemia, and edema.

Minimal change disease

____ can cause **nephrotic** syndrome due to glomerular amyloid deposition. This condition is associated with progressive, chronic disease.

Renal amyloidosis

Onset is typically **subacute** (weeks-months), unlike other common nephrotic syndromes that present **acutely** (minimal change disease).

Membranous Nephropathy (seen in adults or children)

____ is a significant risk factor for **Membranous Nephropathy**, particularly in **children**.

chronic HBV infection Evaluating all patients with MN with HBV serologies is recommended

In pts with **Renal Amyloidosis** an **Echocardiography** is indicated due to the risk of ____.

**restrictive cardiomyopathy**

Patient presents with weeks long history of proteinuria. Renal biopsy shows diffuse, **granular** pattern of **IgG and C3** along the **capillary loops**. Electron microscopy shows **subepithelial** immune complex deposits along the glomerular basement membrane with **podocyte damage**. findings consistent with ____.

membranous nephropathy

Associated conditions in **Membranous Nephropathy** (4)

Infection (**HBV**, syphilis, HCV) Drugs (**NSAIDs**, penicillamine) **Malignancy** (usually solid tumors in adults) Autoimmune disease (**SLE**, thyroiditis)

What nephritic syndrome results in Complete recovery in a few weeks in children, but **adults** more likely to develop **CKD**?

PSGN

Minimal change disease (mcc of nephrotic syndrome in children) is a clinical diagnosis (**no biopsy needed**) and management is empiric ____.

corticosteroids (**Prednisone**)

Diffuse **thickened glomerular capillary loops** and basement membrane Granular **subepithelial** deposits of IgG and C3 (dense deposits) → spike and dome appearance

Membranous nephropathy

**Mesangial proliferation** Subendothelial ± subepithelial immune complex deposition Thickening of the capillary walls (appear as wire loops) **Congo red stain** deposition in the mesangium showing apple-green birefringence under polarized light Nodular glomerulosclerosis

Amyloid nephropathy Tx: underlying cause

**Thickening of the glomerular basement membrane** **Eosinophilic** nodular glomerulosclerosis (Kimmelstiel-Wilson nodules) Mesangial proliferation

Diabetic nephropathy

General treatment for Nephropathy (3)

Edema → **Diuretics** Proteinuria & HTN → **ACE-I** (ramipril) or **ARB** (losartan) May slow progression of any underlying renal disease (diabetic nephropathy) ± Prophylactic **anticoagulation**

Treatment of Diabetic nephropathy

**ACE-I/ ARB** Strict glycemic control

Treatment of membranous nephropathy

**ACE-I/ ARB** ⎯ If severe or refractory disease → **Prednisone & cyclophosphamide**

Most Nephritic diseases can be treated with Ace-I or ARB, but in the case of **Membranoproliferative glomerulonephritis** (type 1 and type 2 MPGN)

Ace-I or ARB & **Prednisone ± immunosuppressant**

Management of lupus nephritis includes **Induction therapy** with (2)

IV (**Prednisone**) glucocorticoids PLUS **immunosuppressant** (Cyclophosphamide)

Treatment for PSGN, if necessary (2)

1. Loop diuretic 2. ACE inhibitors or ARBs or Calcium channel blockers

Treatment of Granulomatosis with polyangiitis:

Mild disease **Glucocorticoids** + **methotrexate** Moderate - Severe disease Glucocorticoids + cyclophosphamide OR Rituximab

ENT involvement is often the **first clinical manifestation** **Chronic rhinitis/sinusitis** or **saddle nose** deformity Recurrent **lower respiratory tract** problems Glomerularnephritis on UA (Hematuria, ↑ Cr) + PR3-ANCA/c-ANCA (anti-proteinase 3) Diagnosis?

**Granulomatosis with polyangiitis** → rapidly progressive (**Necrotizing crescentic**) glomerulonephritis (RPGN) ⎯ Pauci-immune glomerulonephritis (Pauci‑immune means little evidence of immune complex/antibody deposits.)

**Hypertension** Recurrent **upper respiratory tract** problems (pulmonary vasculitis; hemoptysis) but no lower respiratory tract problems (no sinusitis or rhinitis) **palpable purpura** Glomerularnephritis on UA (Hematuria, ↑ Cr) +MPO-ANCA/p-ANCA Diagnosis?

Microscopic polyangiitis (pauci-immune glomerulonephritis) **M**icroscopic **PO**ly**A**ngiitis has **MPO** **A**ntibodies (pANCA).

Treatment of Microscopic polyangiitis & Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)?

**glucocorticoids** + cyclophosphamide

*Prodromal phase* Severe allergic **Asthma** attacks (chief concern) h/o **Allergic rhinitis/sinusitis** *Vasculitic phase* Skin nodules, **palpable purpura** *Neuro deficits* Loss of motor and sensory function with **wrist or foot drop** (Mononeuritis multiplex) Pauci-immune glomerulonephritis Glomerularnephritis on UA (Hematuria, ↑ Cr) +MPO-ANCA/p-ANCA ↑ IgE Diagnosis?

Eosinophilic granulomatosis with polyangiitis (Churg-Strauss syndrome)