Glomerular Kidney Disease Flashcards
What is considered the nephrotic range of proteinuria?
normal proteinuria <150mg/day
nephrotic range: 3.5+ g/day, can be up to 10g/day!
how can nephrotic proteinuria lead to lipiduria?
Hypoalbuminemia leads to increased hepatic lipoprotein synthesis —> hyperlipidemia
—> increase total cholesterol, LDL cholesterol and triglycerides
—> lipiduria
what does it mean when proteinuria is selective versus nonselective?
selective: albumin only
nonselective: albumin + anticoagulant proteins + immunoglobulins
recall nephrotic range is 3.5+ g/day
what is the key finding in bland, urine sediment?
main finding is protein in the urine
Few cells that may be dysmorphic, but minimal to no inflammation - no RBC/WBC casts
what is the number one cause of nephrotic syndrome in children? how can this syndrome be detected?
Minimal change disease: effacement of visceral glomerular podocytes
probably due to T cell dysfunction and circulation of permeability factor
—> selective proteinuria (albumin) —> edema and lipiduria (oval fat bodies in urine)
note GFR remains stable, normal glomerulus in light microscopy (abnormal findings seen by electron microscopy only)
in adults, minimal change disease is associated with….
lymphoma or leukemia
otherwise, minimal change disease is mostly found in children following viral infection (URI), is benign, and remits spontaneously or with steroids
[minimal change disease: nephrotic syndrome, effacement of podocytes]
This nephrotic syndrome is a histological finding with multiple causes, rather than a single disease. Imaging shows sclerotic segments with collapse of capillary loops, increase in matrix, and segmental deposition of plasma proteins along the capillary wall (hyalinosis). What is?
focal segmental glomerulosclerosis (FSGS): damage to visceral podocytes —> nephrotic syndrome + symptoms of glomerular damage (HTN, hematuria, high BUN/Cr, progression to ESRD)
non-selective protein loss (not just albumin)
what is the #1 primary glomerular disease in adults?
focal segmental glomerulosclerosis (FSGS): damage to visceral podocytes —> nephrotic syndrome,
non-selective protein loss
idiopathic (likely antibody-mediated), associated with nephrin/podocin mutations or polymorphisms in apolipoprotein L1 (APOL1G, esp. West African patients)
autoantibodies against phospholipase A2 receptor are implicated in the primary form of which glomerular disease?
membraneous nephropathy: subepithelial immune deposits, massive non-selective proteinuria (nephrotic)
—> edema, infection risk (loss of Ig), hyperlipidemia/lipiduria, thrombotic risk (loss of ATIII, Protein C)
most cases are primary, generally indolent course
in patients over 60 with membraneous nephropathy, what should you consider as a secondary cause?
membraneous nephropathy: subepithelial immune deposits, massive non-selective proteinuria (nephrotic)
most cases are primary, but 1/5 of patients 60+ will have malignancy
other secondary causes include SLE, HBV, medications
what drives the process of nephrotic syndrome as a complication of diabetes mellitus?
glomerular hyper-filtration
A 14yo M presents with hematuria, visual difficulties, and sensorineural deafness following recovery from viral URI. FHx includes “kidney problems.” Urinalysis significant for acanthocytes and RBC casts.
What is the likely diagnosis?
Alport syndrome: focal nephritic syndrome, hematuria with progression to ESRD, sensorineural deafness, eye disorders (anterior lenticonus)
XLR in most cases, males with full phenotype - mutation in Type IV collagen (alpha3/4/5 chain)
what focal nephritic disorder does this describe?
- mesangial expansion/proliferation
- immune complex deposition
- with/without crescents
- 15-35yo age group
IgA nephropathy
what is the target of autoantibodies in anti-glomerular basement membrane (GBM) antibody disease?
aka Goodpasture’s Syndrome
antibodies against alpha-3 chain of type IV collagen in GBM and/or the alveolus (renal and/or pulm disease)
rare disease, trigger unknown, >90% present with rapidly progressive glomerulonephritis (RPGN)!
immunofluorescence shows linear IgG staining
what are the 2 possible clinical presentations of anti-glomerular basement membrane (GBM) antibody disease?
aka Goodpasture’s Syndrome
antibodies against alpha-3 chain of type IV collagen in GBM and/or the alveolus (renal and/or pulm disease)
renal: acute kidney injury with nephritic sediment, low GFR
pulmonary: alveolar hemorrhage with dyspnea, cough, hemoptysis
> 90% present with rapidly progressive glomerulonephritis (RPGN)!
red/brown urine + casts + proteinuria + HTN + edema is indicative of….
acute nephritic syndrome
what are the clinical features of post-streptococcal glomerulonephritis in children?
- edema, HTN
- “cola-colored” urine (hematuria)
- elevated BUN and Cr
- dysmorphic RBC/ RBC casts in urine
- mild proteinuria
- transiently low complement (C3)
what histological changes are seen in post-streptococcus glomerulonephritis?
hypercellular glomerulus with neutrophil influx, mesangial proliferation, and endothelial proliferation
immunofluorescence for IgG, C3
subepithelial humps (immune complex deposition) on electron microscopy
what are 2 specific diagnostic tools for identifying post-streptococcal glomerulonephritis?
- positive streptozyme test (ASO+) - recall PSGN most often caused by strep. pyogenes (ASO antigens)
- decline in C3/C50 complement - overactive complement depletes serum levels
post-streptococcal glomerulonephritis and membranoproliferative glomerulonephritis are both more common in children - however, how do they differ in their respective effects on serum complement levels?
PSGN: transient decrease in complement levels
MPGN: complement levels decrease and stay low
which glomerular disorder is associated with “tram track” appearance?
membranoproliferative glomerulonephritis (Type 1) - “tram track” basement membrane seen on light microscopy (looks like double membranes)
GBM thickening due to immune complex deposition, increased cellularity from mesangial proliferation/monocyte influx
Type 1 vs Type 2 membranoproliferative glomerulonephritis
Type 1: immune complex deposition + C3, “tram tracks”, preceded by neoplasm/autoimmune/HCV
Type 2: C3 deposition only, subendothelial “ribbons” of electron dense deposits, preceded by URI (C3 nephritic factor)
which glomerular disorder is associated with systemic lupus erythematosus (SLE) and Sjogren syndrome?
Type 1 membranoproliferative glomerulonephritis - immune complex deposition + C3
(also associated with neoplasms, HCV infection)
which glomerular disorder is associated with electron dense deposits?
Type 2 membranoproliferative glomerulonephritis: C3 (complement) deposits in chunky linear foci in the basement membrane
C3 nephritic factor causes stabilization of C3 convertase (alternative pathway)
what are 3 important causes of microangiopathic hemolytic anemia? (one pertains to renal!)
hemolytic anemia + thrombocytopenia
- hemolytic uremic syndrome
- thrombotic thrombocytopenic purpura
- disseminated intravascular coagulation (DIC)
also malignant HTN, malignancy, drugs (quinine), and HELLP syndrome (Hemolysis, elevated LFTs, Low Platelets)
