Nephrotic & Nephritic Syndrome Flashcards
This patient with peripheral edema, hypoalbuminemia, and urinary protein excretion of >3.5 g/day meets all of the major criteria for ____ syndrome.
nephrotic
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
Patients with nephrotic syndrome have increased risk for ____ (due to hyperlipidemia) and ____ (due to loss of antithrombin III).
atherosclerosis (MI)
thrombosis (Stroke)
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).
Glomerular or nonglomerular hematuria?
RBC casts may be seen
Glomerular
(absent in non-glomerular hematuria)
Glomerular or nonglomerular hematuria?
Proteinuria
Glomerular
(trace or negative in non-glomerular hematuria)
Glomerular or nonglomerular hematuria?
Clots may be seen
Non-Glomerular
(No clots in glomerular hematuria)
Glomerular or nonglomerular hematuria?
Dysmorphic RBCs may be seen
Glomerular Hematuria
(rarely seen in non-glomerular)
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
___ & ____ are the most common causes of nephrotic syndrome in adults in the absence of a systemic disease.
Focal segmental glomerulosclerosis (FSGS)
membranous nephropathy
FSGS is more common in ____ patients and in those with ___, heroin use, and HIV.
African American
obesity
______ is the most common Nephrotic Syndrome among children.
Minimal change disease
In adults, Minimal change disease is associated with use of ___ and _____.
NSAIDs
Lymphoma (usually Hodgkin)
(work up for Lymphoma is the NBSIM if diagnosed)
Amyloidosis Nephrotic Syndrome is usually associated with ___ or ___.
multiple myeloma (CRAB sxs)
chronic inflammatory disease (rheumatoid arthritis, bronchiectasis).
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.
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
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
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)
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)
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)
patient with significant proteinuria and hematuria most likely has _____ (4).
Nephritic Nephrotic glomerulonephritis
- MPGN
- Diffuse Proliferative GN
- Lupus Nephritis
- IgA Nephropathy
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)
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)
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
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 → Cryoglobulin
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)
- Loop diuretic
- 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)
Microscopic POlyAngiitis has MPO Antibodies (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)
