Nephrology Flashcards
Causes of glomerulonephritis associated with low C3 (immune complex deposition)
- Lupus nephritis
- post-strep nephritis
- cryoglobulinemic GN
- other immune complex GN (MPGN)
Causes of glomerulonephritis associated with anti-GBM autoantibodies
goodpastures, anti-GBM nephritis
most common cause of microscopic hematuria
benign familial hematuria (autosomal dominant) 63%
Alport’s disease
usually x-linked (85%) defect in COL4A5 gene, presents with microscopic hematuria, sensorineural hearing loss, ESRD by 4th decade (males)
gross hematuria presenting 1-3 days after a URTI
IgA nephropathy
gross hematuria presenting 7-21 days after a pharyngitis
post-strep GN
methods to measure proteinuria
protein:creatinine ratio (normal < 20 mg/mmol)
OR
24 hour protein collection (normal < 4 mg/m2/hr, nephrotic > 40 mg/m2/hr)
DO NOT DO URINANALYSIS
Hematuria: 4 tests on urinanalysis that would indicate a glomerular origin
- colour = tea or cola-coloured
- dysmorphic RBCs (acanthocytes)
- RBC casts
- proteinuria
Triad seen with post-strep GN
gross hematuria
generalized edema
hypertension
Long term complications of Fanconi syndrome
FTT, growth failure, intellectual impairment, ocular abnormalities (cataracts, glaucoma), enamel defects
Medical treatment of overactive bladder
treat constipation (PEG), anticholinergic (oxybutynin) or alpha-blockers (doxazosin)
Definition of nephrotic range proteinuria
> 40 mg/m2/hr
> 50 mg/kg/day
Most common cause of nephrotic syndrome
Minimal change disease
Nephrotic syndrome, finding on biopsy of glomerulus
effacement of podocyte foot processes
What organisms are patients with nephrotic syndrome at increased risk of?
Streptococcus pneumoniae and haemophilus influenza - due to loss of complement factor C3b, opsonins and immunoglobulins
What should you do before starting a patient with nephrotic syndrome on immunosuppressant medication?
PPD, give polyvalent pneumococcal vaccine (23-serotype and 7-valent conjugate vaccines)
Treatment of nephrotic syndrome
prednisone x 4-6 weeks
Most common cause of peritonitis in nephrotic syndrome
strep pneumoniae
Secondary infectious causes of nephrotic syndrome
malaria, schistosomiasis, hep B/C, HIV
Options for surgical repair of urinary reflux - 2 methods
Deflux (injection of stuff into ureter), reimplanation of ureter
Gross hematuria, nephrotic syndrome. what to worry about?
renal vein thrombosis
Five criteria of nephritis
- hematuria (gross, red cell casts)
- hypertension
- azotemia (elevated urea, cr)
- edema (fluid overload, high JVP)
- proteinuria
Alports - extra-renal manifestations
eye - anterior lenticonus, recurrent corneal erosions, macular flecks
ear - deafness (bilateral)
BP tables depend on…
height
age
gender
What is cysteinuria?
Urinary loss of COLA amino acids (cysteine, ornithine, lyseine and arginine)
Diagnosis of cystinosis
leukocyte cysteine levels
Usual cause of renal vein thrombosis in infant
IDM
In gestation, when is formation of nephrons complete?
36-40 weeks GA
Approx how many nephrons are in the kidney?
1 million
What factors modify glomerular filtration?
- glomerular hydrostatic pressure
- glomerular oncotic pressure
- rate of flow
- permeability of glomerular capillary wall
Definition of hematuri
> = 5 RBCs/hpf
Causes of false positive for hematuria on dipstick
oxidizing agents (ie. H2O2 used to clean perineum prior to obtaining sample) betadine alkaline urine (pH >9) rhabdomyolysis
causes of false negative for hematuria on dipstick
presence of formalin in sample
high concentrations of ascorbic acid (as a result of high vit c intake)
what does a dipstick read as positive for blood?
hemoglobin
RBCs
myoglobin
What can differentiate glomerular vs non-glomerular hematuria on urinanalysis?
presence of RBC casts and dysmorphic RBCs = glomerular origin!
what condition should you think of with isolate microscopic hematuria (on repeated samples)
hypercalciuria (test by checking calcium:creatinine ratio)
most common form of primary GN
IgA nephropathy
Pathology characteristics of IgA nephropathy
mesangial proliferation, crescents/sclerosis, IgA deposition + C3
IgA nephropathy can present as….
gross hematuria
microscopic hematuria
nephritic
nephrotic
What is the C3 in IgA nephropathy?
NORMAL
What can decrease the rate of progression of IgA nephropathy in adults
fish oil (omega 3)
what proportion of IgA nephropathy patients progress to have significant renal disease?
30%
Alports - pathology
mesangial proliferation
lipid-laden cells (foam cells)
How do you work-up / diagnose alports?
Fam hx
Audiogram
Ophtho - presence of anterior lenticonus is pathognomonic!
Risk of ESRD in Alports
High! 75% of males (x-linked hemizygotes) and homozygotes (AR form) develop ESRD by age 30
Tx: control hypertension, ACEi
Recurrent episodes of hematuria with occasional gross hematuria post-URTI
Family members w/ same sxs
No hearing loss
What syndrome?
Thin basement membrane disease!
AKA benign familial hematuria
post-strep GN
clinical situations and latency period
strep pharyngitis: 5-21 days
pyoderma/impetigo: 3-6 weeks
natural hx of post-strep GN
acute phase resolves in 6-8 weeks, can have persistent microscopic hematuria x 1-2 yrs
Lab tests for post-strep GN
decreased C3
normal C4
low CH50
confirmation of strep diagnosis (positive throat cx, rising ASOT or anti-DNase B, streptozyme screen)
Types of GN with a normal C3
Alports IgA nephropathy ANCA-positive GN Goodpastures Anti-GBM
Types of GN with a LOW C3
post-strep post-infectious shunt nephritis MPGN cryoglobulinemia SLE bacterial endocarditis
Common causes of membranous nephropathy in children
SLE
Hep B
Congenital syphilis
Most common cause of membranous nephropathy world wide
malaria
What can cause membranoproliferative GN?
Think of infections!
Hep B/C, syphilis, endocarditis
If someone has a low C3 GN which doesn’t improve after 2 months, what conditions should you think of?
SLE
MPGN
cryoglobulinemia
When should you biopsy a patient with SLE and evidence of renal involvement?
always!
no correlation between SLE disease activity and severity of renal involvement. the extent of disease will be used to guide therapy
How do you treat lupus nephritis?
prednisone x 4-6 mos (or azathioprine as steroid-sparing agent)
if very severe, can tx with cyclophosphamide
which class of lupus nephritis has the highest risk of progression to ESRD?
Class IV lupus nephritis
Henoch Schonlein Purpura
Clinical features
palpable purpura
abdominal pain
arthritis
50% develop nephritis
How should you monitor for nephritis in patients with HSP?
Urinanalysis weekly during period of active disease, then monthly x 6 mos
If anything abnormal - refer to nephro!
Which types of GNs are associated with crescenteric / rapidly progressive GN?
SLE
HSP (if severe)
ANCA positive granulomatosis with polyangiitis (formerly, Wegeners)
Clinical features of Goodpasture’s disease
pulmonary hemorrhage
glomerulonephritis
(due to antibodies against GBM)
HUS - triad
“RAT”
renal failure
anemia (MAHA)
thrombocytopenia
TTP - features
"FAT RN" fever anemia (MAHA) thrombocytopenia renal failure neurologic sxs
Diagnostic criteria of HUS
An acute illness with HUS features (renal failure, MAHA, thrombocytopenia) occurring within 3 wks after an episode of acute or bloody diarrhea
Common bacterial etiologies of diarrhea in HUS
Vero-toxin producing e.coli (0157:H7)
Shiga-toxin producing Shigella
Common foods contaminated with e.coli 0157:H7
unpasteurized milk
undercooked meat (beef)
apple cider
Genetic forms of HUS are due to…
Deficiencies in
ADAMTS13
Complement factor H, I or B
Intestinal complications of HUS
severe inflammatory colitis ischemic enteritis bowel perforation intussusception pancreatitis
Should you give platelets in HUS?
NO! They are immediately consumed, may worsen clinical course
Should you give RBCs in HUS?
Maybe!
If you suspect pneumococcus-associated HUS, then you should wash the RBCs before transfusion (IgM on cell surface can worsen course)
Treatment of HUS
Supportive care (NO PLATELETS)
Plex if ADAMTS13 or factor H deficient
Eculizumab for atypical HUS
Nephrotic syndrome characteristics
Nephrotic range proteinura
Hypoalbuminemia
Edema
Hyperlipidemia
Definition of nephrotic range proteinuria
> 40 mg/m2/hr on a 24 hr collection
Genetic disorders causing nephrotic syndrome
Finnish-type congenital nephrotic syndrome
Denys-Drash
Alport syndrome
Nail-patella syndrome
Causes of idiopathic nephrotic syndrome
Minimal change disease
FSGS
Membranous nephropathy
Hallmark pathologic finding of idiopathic nephrotic syndrome
Effacement of podocyte foot processes
Why is nephrotic syndrome a hypercoagulable state?
Vascular stasis (due to 3rd spacing, low intravascular volume)
Increase in clotting factor production (due to increased hepatic protein synthesis)
Loss of anti-coagulants via kidneys
Immunofluorescence in FSGS
IgM and C3 deposits
Natural history of FSGS
does not respond well to steroids, often leads to ESRD
What should you do before starting tx for nephrotic syndrome?
PPD
Pneumococcal vaccine
Tx for nephrotic syndrome
Prednisone DAILY x 4-6 weeks
relapse rate of nephrotic syndrome (if given 4-6 weeks of initial steroids at diagnosis)
30-40%
what is steroid dependent nephrotic syndrome?
kids that relapse while steroids are being weaned (on alternate day schedule) OR within 28 days of completing steroid course
definition of frequent relapser in nephrotic syndrome?
relapse >= 4x in 12 mos
definition of steroid resistant nephrotic syndrome
fail to respond to 8 weeks of steroid tx (usually FSGS)
how can you treat steroid-dependent and frequently relapsing nephrotic syndrome?
cyclophosphamide
monitor for neutropenia
how can you treat steroid resistant nephrotic syndrome?
cyclosporine, tacrolimus
side effects of cyclosporine
nephrotoxicity
hirsutism
gingival hypertrophy
PRES
Bugs causing SBP in nephrotic syndrome
strep pneumo
e.coli
Clinical features of Denys-Drash
early-onset nephrotic syndrome
wilms tumour
ambiguous genitalia
progressive renal insufficiency
Child with suspected proteinuria - how do you test?
First void urine protein to creatinine ratio (abnormal > 20)
or 24 hr urine collection (> 40 mg/m2/hr = nephrotic)
Causes of transient proteinuria
fever dehydration exercise cold stress seizures
what is orthostatic proteinuria?
Increased urinary protein excretion when in the upright position
how do you diagnose orthostatic proteinuria?
first void spot protein:creatinine ratio x 3 demonstrating absence of proteinuria
(other evaluations showing + proteinuria)
definition of hypertension
SBP or DBP >= 95th %ile on 3 occasions
when should you start measuring BP in kids? how often?
at every visit in children > 3 yrs
should measure at EVERY visit regardless of age if prem, NICU, CHD, UTIs, kidney anomaly, malignancy, BMT, etc
