Renal Syndromes Flashcards
When a patient presents with gross or microscopic hematuria, what else should you be checking?
serum creatinine urine protein dysmorphic RBCs urinary casts sx of systemic disease
If a patient presents with hematuria in the setting of normal renal function, no proteinuria, no urinary casts, and no
symptoms, what are the next steps?
Repeat urinalysis (UA) to see if hematuria is persistent
If a patient presents with persistent hematuria in the setting of normal renal function, no proteinuria, no urinary casts, and no
symptoms, what is the next step?
If persistent, pursue urological work-up (imaging of kidneys/ureters/bladder +/-cystoscopy to rule out
urological cause of bleeding)
If a patient presents with abnormal renal function, dysmorphic RBCs, proteinuria, casts, and/or symptoms of systemic
disease, what is the next step?
further renal work-up is indicated to look for glomerular cause of hematuria
If patient presents with significant degree of proteinuria and/or if seen alongside hematuria, urinary casts, or abnormal renal
function, what is the next step? What is one special lab result you should get in this process?
immediate renal work-up is indicated
This includes quantification of the proteinuria using a urinary albumin/creatinine ratio
What are some common causes of transient proteinuria?
exercise, fever, or infection
When a patient presents with a combination of hematuria and proteinuria, what renal syndrome should you be looking for?
glomerular disease
What helps classify a patient with nephritic v. nephrotic syndrome?
Degree of proteinuria and other lab/clinical findings help classify whether the patient has a nephritic or
nephrotic syndrome
What is an important step in diagnosis and management of a possible glomerular disease?
renal biopsy
What do RBC casts indicate?
glomerular hematuria and nephritic syndrome
what do lipid/fatty casts or oval fat bodies indicate?
nephrotic syndrome
What is the maltese cross sign when looking at urine under polarized light?
oval fat bodies which indicate nephrotic syndrome
How is renal biopsy usually done?
ultrasound guided with 2-5 cores extracted
How is tissue from a renal biopsy examined?
light microscopy
immunofluorescence
electron microscopy
What does light microscopy look for in a renal biopsY?
ook for cell proliferation, glomerular basement membrane abnormalities, and to identify worrisome lesions such as crescents or necrosis
What does immunofluorescence look for in a renal biopsy>
Ig or complement staining
What does electron microscopy look for in a renal biopsy?
immune complex deposition, mainly
Proteinuria >3 g/day o Hypoalbuminemia o Hyperlipidemia o Lipiduria o Edema
This constellation of findings indicate what syndrome?
nephrotic syndrome
What are the primary and secondary causes of nephrotic syndrome?
Primary kidney disease or systemic disease
What are examples of primary kidney disease leading to nephrotic syndrome?
Membranous nephropathy, Focal segmental glomerulosclerosis, Minimal change disease
What are secondary kidney disease that can cause nephrotic syndrome?
diabetic nephropathy or amyloidosis
What effect does nephrotic syndrome have on coagulability of blood?
Hypercoagulability due to many factors including the relative loss of more anti-coagulant than pro-
coagulant proteins in the urine
What happens to vitamin D levels in nephrotic syndrome?
Low levels due to loss of vitamin D binding protein in urine
What is the most common cause of nephrotic syndrome in Caucasian adults?
membranous nephropathy
What is the clinical presentation of membranous nephropathy?
swelling of extremities over days to weeks
What kind of nephrotic syndrome is Often associated with other systemic conditions such as solid tumor cancers, medication exposure (NSAIDs, Gold), infections (ex/ Hepatitis B or C), or autoimmune disease (ex/ SLE)
membranous nephropathy
Thick glomerular basement membranes on light microscopy
“Spikes” and “holes” can be seen on Jones (silver stain)
Granular IgG staining on immunofluorescence microscopy
Sub-epithelial immune-complex deposits on electron microscopy
Staining for phospholipase A2 receptor (PLA2R) may be positive
These kidney biopsy findings would point to what condition?
membranous nephropathy as the cause of nephrotic syndrome
What would lab values be in membranous nephropathy?
o Urine will show significant proteinuria (>3g/d but can be as much as 10-20 g/d)
o Can have hematuria but less common
o Oval fat bodies, lipid/fatty casts can be seen in urine sediment (maltese cross on polarized light) o Serum creatinine may be normal or elevated
o Dyslipidemia
What are the primary treatment methods in membranous nephropathy with low degrees of proteinuria?
o Lower degrees of proteinuria, focus is on RAAS blockade, salt restriction, and diuresis
For higher levels of proteinuria in membranous nephropathy, what are the treatments?
For higher levels of proteinuria, immunosuppressive therapy is used to modulate the immune system
Cyclophosphamide or Calcineurin inhibitors + steroids Rituximab may also be effective
What kind of nephrotic syndrome is common in AA and linked to APOL1 mutations?
Focal Segmental glomerulosclerosis (FSGS)
Is FSGS usually primary or sednoary?
usually primary
Although more uncommon, what are some causes of secondary FSGS?
Can be secondary to other conditions such infection (HIV), medication (Heroin, Interferon, Lithium, Pamidronate),
Genetic mutation, Reduced renal mass or hyperfiltration injury (genitourinary reflux, congenital malformations,
sickle cell disease, obesity)
What is the clinical presentation of FSGS?
o Edema if often present but may be absent, especially in secondary forms
o HTN is common
What are the lab findings for FSGS?
o Renal function may be abnormal (elevated creatinine in ~1/3)
o Proteinuria may be sub-nephrotic range in secondary forms
o Hematuria may be present
In a kidney biopsy, you see: - 1 or more lesions of segmental sclerosis on light microscopy
- Scant or non-specific staining of IgM, C3, or C1q seen on immunofluorescence
- Podocyte foot process effacement (focal or diffuse) on electron microscopy
What type of renal syndrome is this?
nephrotic syndrome caused by FSGS
What is the first step in treating FSGS?
treating the secondary causes (HIV, obesity)
If a patient has primary or idiopathic FSGS, what is the treatment flow?
- steroids.
2. if no response, a calcineurin inhibitor or cellcept
What kind of nephrotic syndrome is most common in children under 6 years of age?
minimal change disease
In adults, when can minimal change disease occur?
more likely to have a secondary cause such as hematologic malignancy (leukemia,
lymphoma) or medication (NSAIDs, Lithium, Penicillamine) in adults
What is the clinical presentation of minimal change disease?
Often sudden-onset, “explosive” swelling that may involve face in addition to extremities
o May be preceding infection
In evaluating a patient, the following is found:
o Significant proteinuria; hematuria in <30%
o Oval fat bodies, lipid/fatty casts can be seen in urine sediment (maltese cross on polarized light)
o Renal function often normal but 1 in 5 can have acute kidney injury
o Complications of nephrotic syndrome (profound edema, renal vein thrombosis, severe dyslipidemia).
What is the most likely diagnosis?
minimal change disease causing nephrotic syndrome
Who is always biopsied to diagnose minimal change disease?
adults - children may be empirically treated with steroids first
On biopsy:
Glomeruli appear normal on light microscopy and immunofluorescence
Diffuse podocyte foot process effacement on electron microscopy
What disease may this be?
minimal change disease
How is minimal change disease treated?
steroids. If relapsed or steroid-dependent, other “c” agents can be trialed (calcineurin inhibitors, cyclophosphamide, cellcept)
What is the most common cause of nephrotic range proteinuria?
diabetes
How is diabetic nephrotic syndrome treated?
by treating and delaying progression of the diabetes
How is nephritic syndrome defined?
as the clinical sequelae of acute glomerular inflammation
o Hematuria (gross or microscopic)
o Dysmorphic red blood cells and/or RBC casts
o Proteinuria usually <3 g/ay
o Varying degrees of renal insufficiency (w/ or w/o oliguria, azotemia), HTN, and/or edema
These findings are all consistent with what renal syndrome?
nephritic syndrome
What are the 3 major categories of nephritic syndrome?
immune complex mediated
pauci-immune
anti-GBM disease
“A pulmonary-renal syndrome caused by autoantibodies that bind to type IV collagen found in the glomerular basement membrane.” - what syndrome is this?
nephritic syndrome caused by anti-GBM disease
What is Goodpasture’s disease?
anti-GBM disease that has lung involvement (the autoantibodies find to type IV collagen in the alveolar basement membrane)
With what additional nephritic syndrome does anti-GBM nephritic syndrome classically present?
rapidly progressive glomerulonephritis
Ill-appearing patient with malaise, weight loss
o Often have hemoptysis (coughing up blood) and hypoxia
o Slightly more common in men; often with hydrocarbon exposure (ex/ gast station attendant)
This clinical presentation is consistent with what disease?
anti-GBM nephritic syndrome
o Hematuria with dysmorphic RBCs and/or RBC casts
o Proteinuria (typically <3 g/day)
o Varying degree of renal insufficiency but often presents with quickly rising serum creatinine
This lab evaluation is consistent with what disease? what else would also be found?
anti-GBM disease
Would also have + anti-GBM antibody
diffuse crescentic glomerulonephritis on light microscopy and classic “linear” IgG
staining on immunofluorescence microscopy is classic for what disease?
anti-GBM disease
What is the treatment for anti-GBM?
Steroids + Cyclophosphamide + Plasmapheresis (to remove the autoantibodies causing the disease)
What are the sub-categories of immune complex mediated glomerulonephritis? (5)
post infectious GN
lupus nephritis
IgA nephropathy
membranoproliferative glomerulonephritis
• Characterized by the onset of the nephritic syndrome approximately 10 to 14 days after an infection
• Classic scenario is child who had recent pharyngitis with group A beta-hemolytic streptococcal infection (can also
be seen in adults)
What kind of nephritic syndrome is this?
post infectious GN
o Symptom onset 10-14 days after strep infection of throat or skin o Fever, malaise
o HTN, Edema, sometimes oliguria (reduced urine output)
o Can have gross hematuria
What kind of nephritic syndrome is this?
post infectious GN
o Hematuria with dysmorphic RBCs and/or RBC casts o Proteinuria
o Elevated serum creatinine
o Low complement levels (C3 and C4)
What kind of nephritic syndrome would this indicate? What other clear giveaway can there be?
post infectious GN
+ASO titer
On kidney biopsy:
Glomerular hypercellularity or proliferation on light microscopy
“Lumpy-bumpy” or “starry sky” appearance of IgG, IgM, and C3 staining Large sub-epithelial immune complex deposits (known as “humps”)
what kind of nephritic syndrome is this?
post infectious GN
in severe cases of post infectious GN, what can be given?
steroids to reduce inflammation
In up to 1/3 of patients, what is the first sign of lupus?
lupus nephritis
Patient presents with joint and muscle pain, skin rash, oral ulcers, pleuritis (chest pain from lung inflammation), pericarditis (chest pain from cardiac inflammation) as well as edema and HTN, which indicate kidney involvement. What disease is this?
lupus nephritis
Hematuria (usually microscopic) and/or proteinuria (variable amount, can be >3g/day) o +ANA, + anti-dsDNA
5
o Low complement levels (C3 and C4)
o Anemia common
These results would suggest what nephritic syndrome?
lupus nephritis
What guides treatment of lupus nephritis?
the kidney biopsy findings
How is mild lupus nephritis treated?
If mild kidney involvement with minimal inflammation, treatment is supportive and focused on systemic SLE symptom management (ACE inhibitor, Angiotensin receptor blocker, Hydroxychloroquine, sometimes steroids or less immunosuppressive drugs)
how is more severe lupus nephritis treated?
If active inflammation/necrosis on biopsy, treat with high-dose steroid and immune-modulating drugs such as Cyclophosphamide or Cellcept (Mycophenolate Mofetil)
What is the most common glomerulonephritis worldwide?
IgA nephropathy
This nephritic syndrome can be benign in some, proceed to cKD in others, and cause severe renal failure in others.
IgA nephropathy
What kind of nephritic syndrome is associated with IBD and cirrhosis?
IgA nephropathy
What is Henoch-Scholein purpura?
Henoch-Scholein purpura (abdominal pain, rash following a URI) is felt to be a form of IgA vasculitis
o Classically presents concomitantly or 1-2 days after URI (or diarrheal illness)
o Gross or microscopic hematuria; dysmorphic RBCs and/or RBC casts
o Some have recurrent gross hematuria w/ mucosal infection; others have persistent microscopic hematuria
o Proteinuria of variable degree
this clinical presentation would be consistent with what?
IgA nephropathy ( question stem will usually be “young Asian male with sore throat and hematuria…”
o Serum creatinine can be normal or elevated o HTN may be present
o Serum complement levels are normal
These lab values would be consistent with what disease?
IgA nephropathy
Mesangial proliferation on light microscopy
IgA deposits on immunofluorescence microscopy
Mesangial/Paramesangial immune-complex deposits on electron microscopy
These findings indicate what nephritic syndrome?
IgA nephropathy
How is IgA nephropathy treated if it is mild?
ACE i or ARB +/- fish oil and low salt diet
How is IgA nephropathy severity established?
by degree of proteinuria (>1 g/d is higher risk)
Which kind of nephritic syndrome has overlapping qualities with nephrotic syndromes?
membranoproliferative glomerulonephritis
This syndrome is Often associated with underlying infection such as Hepatitis C but can also be related to genetic mutation (ex/ C3 nephritic factor) or be idiopathic
MPGN
Mesangial proliferation and “lobular” appearance of glomeruli common on light microscopy
Classic “tram track” appearance on PAS stain or Jones stain due to GBM splitting
Immunofluorescence often stains for C3 and IgG
Electron microscopy shows various types of immune-complex deposits
this would indicate what syndrome?
MPGN
What are pauci-immune glomerulonephritis?
Group of glomerular diseases that have characteristics of proliferative GN on light microscopy but no evidence of immune complex deposition on immunofluorescence and electron microscopy
What are the prototypical pauci-immune GNs?
ANCA (Anti-Neutrophil Cytoplasmic antibodies)-associated diseases
What is GPA/Wegeners granulomatosis?
a type of pauci-immune GN
Which pauci-immune GN are pulmonary renal?
granulomatosis with polyangitis and microscopic polyangitis
• Often presents as a pulmonary-renal syndrome
o Pulmonary involvement ranges from a chronic sinusitis to hemoptysis
o More upper resp. tract involvement (sinuses, noses, trachea)
• Often affects middle-age or older individuals
What disease is this?
granulomatosis with polyangitis (GPA)
o Fever, weight loss, malaise
o Nasal crusting, nosebleeds, “saddle nose deformity”
o Sinusitis, subglottic stenosis (narrowing of the windpipe)
o Dyspnea and/or hypoxia if lung involvement; hemoptysis less common but can occur
o Skin lesions (palpable purpura)
This clinical presentation suggests which disease?
GPA
o Hematuria with dysmorphic RBCs and often RBC casts
o Proteinuria of variable degree (<3g/d)
o Elevated serum creatinine (sometimes with oliguria, azotemia, renal failure) o + ANCA (usually c-ANCA, PR3 pattern***)
o Kidney biopsy shows necrotizing crescentic glomerulonephritis
This suggests which disease?
GPA
Where does microscopic polyangitis tend to show up in the lung?
lower lung with hemoptysis due to hemorrhage
o Fever, weight loss, malaise
o Skin lesions (palpable purpura)
o Peripheral nerve involvement (mononeuritis multiplex)
o Hemopytsis, dyspnea and/or hypoxia if lung involvement
This suggests what disease?
microscopic polyangitis
o Hematuria with dysmorphic RBCs and often RBC casts
o Proteinuria of variable degree (<3g/d)
o Elevated serum creatinine (sometimes with oliguria, azotemia, renal failure) o + ANCA (usually p-ANCA, MPO pattern**)
o Kidney biopsy shows necrotizing crescentic glomerulonephritis
What disease is this?
microscopic polyangitis
What is rapidly progressive glomerulonephritis?
a term referring to glomerular inflammation that causes renal failure in weeks to months
o These are often associated with crescentic glomerulonephritis such as ANCA-associated vasculitis, Anti- GBM disease, or Lupus nephritis, although any glomerulonephritis can present rapidly
A 4-year old boy wakes up one morning with difficulty opening his eyes due to puffiness and has swelling in his arms and legs. His mother takes him to the pediatrician’s office where blood and urine tests are done. Results show that his kidney function is normal but his urinalysis shows 4+ protein (and no blood). Which of the following is the most likely diagnosis?
A. IgA Nephropathy
B. Minimal Change Disease C. Membranous Nephropathy D. Amyloidosis
b - minimal change disease
A 25-year old woman presents to her internist’s office with complaints of joint swelling and a rash on her face that occurs every time she goes in the sun. She has also been feeling fatigued and states that her ankles are swelling. Initial blood tests are notable for serum creatinine of 1.2 mg/dL and hemoglobin 8.5 g/dL along with positive ANA (anti-nuclear antibody) at a titer of 1:1280. Her urine dipstick shows blood and protein. Which of the following findings would you NOT expect in this patient? A. Normal C3 and C4 levels B. Positive anti-dsDNA C. Dysmorphic RBCs on urine sediment D. Negative p-ANCA and c-ANCA
A - normal complement levels
