CLIPP 31: 5yo - Hematuria, proteinuria Flashcards
10yo female presents with gross hematuria (tea-colored)
diffdx of periorbital swelling = “puffy eyes”
DDX: glomerular
==> systemic sxs, brown/black urine, RBC casts, dysmorphic RBCs
- glomerulonephritis TYPES ==> post-infectious, MPGN, SLE, IgA nephropathy, HSP, HUS, Alport’s thin BM dz
DDX: non-glomerular
==> localized sxs; pink/red urine +/- clots; eumorphic RBCs
- tumors (=Wilm’s in toddlers; RCC in adults)
- trauma (fall, voiding dysfunction b/c don’t want to pee)
- infection (+ pain, discomfort, dysuria, freq, urgency, secondary enuresis)
- inflammation
- cystic dz
- congenital anomaly (esp. after minor trauma), crystalluria (calciuruia)
- stones =pain, painless hematuria (if in kidney/tract and not obstructing) ==> 50% due to underlying urinary metabolic condition
- sickle cell
10yo female presents with gross hematuria (tea-colored)
distinguish between and initiate an evaluation for glomerular and non-glomeruar hematuria
glomerular
==> systemic sxs, brown/black urine, RBC casts, dysmorphic RBCs
non-glomerular
==> localized sxs; pink/red urine +/- clots; eumorphic RBCs
MANAGEMENT
1) confirm true hematuria = UA + blood (if -blood –> beets, meds)
2) confirm RBC in urine = microscopy + RBCs (if -RBCs –> myo/hemo-globinuria; old specific; other false +)
acute glomerulonephritis
- indications for management
- management
for microhematuria ALONE
- monitor for persistence
for persistent GROSS hematuria, microscopic hematuria:
1) HEMATURIA alone ==> outpatient eval
2) HEMATURIA + sxs and/or elevated Cr, HTN==> immediate supportive management
MANAGEMENT
1) evaluate signs of severity
- electrolytes, BUN, Cr
- quantitate proteinuria
2) evaluate for etiology (depending on hx)
- CBC, C3, C4, Strep titers, ANA, ANCA, and/or anti-GBM titers
- Renal Ultrasound –> r/o other etiologies (cysts, congenital anomalies)
acute glomerulonephritis
- indications for management
- management
for microhematuria ALONE
- monitor for persistence
for persistent GROSS hematuria, microscopic hematuria:
1) HEMATURIA alone ==> outpatient eval
2) HEMATURIA + sxs and/or elevated Cr, HTN==> immediate supportive management
MANAGEMENT
1) evaluate signs of severity
- electrolytes, BUN, Cr
- quantitate proteinuria
2) evaluate for etiology (depending on hx)
- CBC, C3, C4, Strep titers, ANA, ANCA, and/or anti-GBM titers
- Renal Ultrasound –> r/o other etiologies (cysts, congenital anomalies)
3) Indications for renal biopsy
- significant proteinuria (>1gram/24hrs; or Pr/Cr > 1.0)
- significant hypertension
- elevated creatinine
Serology interpretation
low C3
(stays los)
Serology interpretation: MPGN
Serology interpretation
low C3, then nml C3 (in 8-12w)
Serology interpretation: post-infectious glomerulonephritis (PIGN)
Serology interpretation:
nml C3, C4
+ strep titers
Serology interpretation:
- recent strep infection NOT causing the concurrent glomerulonephritis
Serology interpretation:
nml C3, C4
+ strep titers
Serology interpretation:
- recent strep infection NOT causing the concurrent glomerulonephritis
- A 6 year old girl presents with red colored urine. A urinalysis with microscopy will be important because
a. If it tests positive for blood, but microscopy does not reveal RBCs, then this indicates a non-glomerular etiology
b. It may test negative for blood, indicating that this is not hematuria, but rather an ingestion, such as beets, which is discoloring the urine
c. The presence of RBC casts would mean a kidney biopsy must be performed
d. Hemolysis could be the etiology, in which case the microscopy would be positive for RBCs, but the urine dip will test negative for blood
B
b/c even with red colored could be ingesiton
If it tests positive for blood, but microscopy does not reveal RBCs ==> hemoglobinuria or myoglobinuria
== these are still glomerular etiologies
- Glomerular etiologies of hematuria can be distinguished from non-glomerular ones in that
a. Glomerular causes will have RBC casts and dysmorphic RBCs, whereas non-glomerular causes will lack casts and usually have eumorphic RBCs
b. Non-glomerular causes usually have systemic manifestations such as hypertension or edema, or may be associated with rashes or arthritis
c. Glomerular causes will often involve pink appearance and if heavy hematuria, may include passage of blood clots
d. They are difficult to distinguish on history, exam, or urinalysis which is why blood tests and renal ultrasounds are usually needed
A
. When a patient presents with glomerulonephritis, the following are indicators of severity and a need for immediate management
a. hypertension, proteinuria, gross hematuria
b. hypertension, elevated creatinine, low C3
c. elevated creatinine, hypertension, proteinuria
d. elevated creatinine, proteinuria, low C3
e. gross hematuria, abnormal ultrasound, low C3
C == more intense injury to the basement membrane
not a problem with the podocytes directly
nephritis = basement membrane problem
nephrotic sydrome = podocyte disease
- A 12 yo boy presents with an acute glomerulonephritis. Evaluation revealed a low C3 but normal C4. 3 months later, the nephritis persists, as does the low C3. The most likely etiology is:
a. Post-infectious glomerulonephritis
b. Membranoproliferative glomerulonephritis
c. Lupus nephritis
d. IgA Nephropathy
e. Alport Syndrome
B
low 3, nml C4
would be persistently low
PIGN should normalize within 6-8w (at most by 3mo)
- Hypercalciuria is the most common cause of non-glomerular gross hematuria in children. It’s clinically relevant because:
a. Recurrent episodes of gross hematuria, no matter the etiology, is not desirable
b. It results in an increased risk for nephrolithiasis
c. On a chronic basis, it can result in tubulointerstitial damage and progressive loss of kidney function
d. All of the above
D.
- IgA Nephropathy can be mistaken for Postinfectious glomerulonephritis because
a. both can be associated with upper respiratory infections—IgA Nephropathy concurrently, though Post-infectious a few weeks afterwards
b. both can be associated with a low C3, though only transiently with post-infectious GN
c. both can be associated with a hemolytic anemia, though only transiently with post-infectious GN
d. neither are associated with clinically significant proteinuria
e. neither are associated with long-term risk for progressive renal insufficiency
A
- A child presents with peri-orbital edema. To confirm nephrotic syndrome, the provider should illustrate
a. nephrotic range proteinuria, lack of hematuria, coagulopathy
b. nephrotic range proteinuria, hypoalbuminemia, coagulopathy
c. nephrotic range proteinuria, lack of hematuria, hypercholesterolemia
d. nephrotic range proteinuria, coagulopathy, hypercholesterolemia
e. nephrotic range proteinuria, hypoalbuminemia, hypercholesterolemia
E
1) nephrotic range proteinuria = d/t leakage through BM
2) hypoalbuminemia = d/t leaking thru BM
- evidence: problems with renal tubular absorption/metabolism; decreased synthesis of protein in liver
3) hypercholesterolemia = d/t decreased albumin –> liver stimulated to make lipoproteins + albumin
= decreased lipid clearance from circulation
==> later increased risk of atherosclerosis & CAD with persistent nephrotic syndrome
coagulopathy is a part of nephrotic syndrome, but not a part of the definition
lack of hematuria only suggests SOLELY nephrotic syndrome, but could have both nephrotic and nephritic in one
Asymptomatic proteinuria is most often a benign etiology. Which of the following would be more suggestive of a concerning etiology
a. An orthostatic pattern in which the first morning urine is normal or near normal for protein
b. A history of intense exercise on the day of testing
c. A 24 hour urine protein that is only 1.5 grams/day
d. A history of a concurrent febrile illness
e. A concentrated urine (spG 1.020 or higher)
C
others = are reasurring that it would resolve
- Minimal Change Disease is the most common cause of nephrotic syndrome in children. When a child presents with nephrotic syndrome, the following would suggest further evaluation would be needed rather than treating presumptively for minimal change
a. Age between 1 and 10
b. Hypertension
c. Presence of RBC casts on urine microscopy
d. A and B
e. B and C
B, C = more concerning
minimal change usually between 1-10
- In addition to edema and complications directly attributable to fluid overload (e.g. anasarca, pleural effusions, ascites and resulting peritonitis), children with nephrotic syndrome are at greater risk for
a. Infection due to T cell dysfunction
b. Anemia due to decreased erythropoiesis
c. Fractures due to secondary hyperparathyroidism
d. Non-anion gap metabolic acidosis
e. Thrombotic risk due to loss of anti-coagulants in urine
E == definitely hypercoagulable
if treated with steroids, then would be at infection risk. but nephrotic syndrome itself would not lead to higher risk of infection
the rest are related to renal failure.
7yo boy presents with tea colored urine. cold sxs 1 mo ago, now better. has a headache
- hx of T1DM (on insulin) for 4y
- increased weight from a week ago
- next step?
- management?
1) next step: UA and microscopy (==> showing red cell casts, dysmorphic RBCs)
2)
- severity: BMP (Cr, Albumin) with protein:creatinine ratio
- etiology: complement levels; Strep titers
If pos Strep titers, nml C3, C4
- IgA nephropathy
If pos Strep titers, low C3, nml C4
- post-infectious strep nephropathy
non-glomerular causes of hematuria
TICKS
- tumors, trauma
- infection, inflammation
- cystic dz, congenitalanomaly, crystalluria (calciuruia)
- stones, sickle cell
GN associated with hemolytic anemia (Coomb’s positive)
PIGN
Indications for renal biopsy
- by epidemiology, history, acute sxs, nonresponse to treatment
EPIDEMIOLOGY
- pts <6mo ==> increased chance of congenital nephrotic syndrome
- pts 3-18mo + hematuria
- pts >10yo if NOT drug rxn, or PIGN
HISTORY
- pts <18yo + hematuria, protein + Fhx mom with hematuria (Alport syndrome)
- HSP
- SLE + proteinuria, nephrotic syndrome’
- chronic renal insufficiency + persistent elevation of serum BUN, Cr
ACUTE SXS
- significant proteinuria (>1gram/24hrs; or Pr/Cr > 1.0)
- significant hypertension
- elevated creatinine
- severe AKI
- nml C3, C4 ==> b/c need to determine etiology
- NOT PIGN + low C3 at presentation
LONG-TERM
- steroid-resistance nephrotic syndrome - lack of response to steroids after 8w
- NOT PIGN + progressive decline in renal fx and UOP
- suspected lupus, + ANA, high anti DS DNA, low C3 persisting >3mo
kiddo has iga nephropathy. also been having HA. what can you do for his HTN of 150/80. which of the following would you do
a. provide reassurance. if this is post-strep GN, it will get better on its own so it does not requirement tx
b. it is severely elevated for a 7yo so warrants treatment wiht a low sodium diet and an ACE inhibitor until the GN resolves
c. it is severely elevated for a 7yo so warrants treatments with a low sodium diet, and thiazide diuretic until the GN resolves
B
if BP+5 >99%ile ==> SEVERE HYPERTENSION
ACE-inhibitor > diuretics, CCB
==> less pressure from the medication (more protective to the kidney)
= maintains GFR better
ACE-I contraindicated if had hyperkalemia, AKI in the acute setting
if had milder HTN –> would:
1) reassure
2) low-sodium diet
kiddo has iga nephropathy. also been having HA. what can you do for his HTN of 150/80. why did he gain weight?
a. with his acute GN and HTN he was more sedentary, so this is increased body fat
b. with his acute GN, his GFR may be decreased so thsi is likely fluid weight from renal failure
c. with his acute GN, renin is stimulated and his nephrons are likely absorbing salt and water, so this is fluid weight.
d. with his acute GN and being sick, he probalby actually lost weight, so this is measurement error
C
renin is JGA ==> most likely retaining the water
HTN is in response to renin stimulation
he is not in renal failure quite yet
6yo male presents with pinkish-red colored urine
- otherwise well, no known trauma, no recent meds, in school but no obvious illness, ROS completely egative
- PMHx, soc hx, family hx all normal
- exam: normal BP and vitals, 50% height and weight (otherwise completely normal)
- UA and microscopy ==> blood, trace protein, many eumorphic RBCs
non-glomerular: TICS
- tumors, trauma
- infection, inflammation
- cystic dz, congenital anomaly, crystalluria (calciuruia)
- stones, sickle cell
most common cause of nonglomerular bloody urine
hypercalciuria
Ca/Cr > 0.2
Renal US neg or positive –> +/- stones
esp. if microscopic
ddx of non-glomerular hematuria
-management
TICS
1) Urine Ca/Cr, renal US
==> if either positive for stones –> 24h urine for stone chemistries
==> signs & sxs of infection –> CBC, CMP
2) electrolytes, BUN, Cr, CBC, Pr/Cr ratio
complications of hypercalciuria
- recurrent gross hematuria is very bad
- risk of nephrolithiasis & stones (PAINFUL)
- nephrocalcinosis == deposits of calcium within tubulointerstitial parenchyma; progressive scarring loss of function
how do you treat idiopathic calciuria
a. drink lots of fluids to make a dilute urine
b. low sodium diet
c. high citrate diet
d. thiazide diuretic
All of the above, in that order
drink plenty of fluids –> to flush through
low sodium diet –> so that don’t reabsorb as much
high citrate diet –> to help be more soluble
C/I in alkaline urine ==> will make more alkaline
thiazide diuretic
C/I if have hypercalcemia ==> will retain Ca
most common types of hypercalciuria?
1) idiopathic = multifactorial (genetics, diet)
2) tubulopathies = Dent’s dz; Bartter’s syndrome
3) medication -induced
14yo boy has maroon-colored urine. otherwise healthy, playing touch football with friends earlier. denies obvious trauma / rough tackle. ROS otherwise NEgative.
soc hx = athlete , 9th grade, doing well, no substance use, not sexually active
FamHx - mother with HTN
exam - HR 60, BP 138/84,tall and thin, athletic build, no abd masses / tenderness
- UA: 1.025, pH 6, trace protein, large blood, many dysmorphic RBCs, no casts
- diffdx
- evaluation
GLOMERULAR
- glomerulonephritis (Alport)
- HUS
NON-GLOMERULAR
- trauma
- congenital anomaly + mild trauma
management
- renal ultrasound
- CBC, BMP, complement
==> Urine Ca/Cr; BMP was normal
==> Renal US revealing b/l enlarged kidneys with multiple cysts
- ADPKD
could be a milder form of it - even if no FHx (mom, even with HTN could be normal)
do lack of RBC casts preclude glomerulonephritis
NO
presentation of ADPKD
1) gross hematuria
2) HTN
management of ADPKD
1) strict BP control == RAAS inhibition (ACE-I +/- ARB): target <120/80 ==> slower deciline of renal fx
2) control of proteinuria == RAAS inhibition (ACE-I +/- ARB): delay oprogression of CKD, prevent future ESRD
3) kidneys >15cm –> restrict from high impact sports/activitys = risk of trauma and cyst rupture == massive bleeding
4) high fluid intake == ADH assoc. with cyst growth, so suppress ADH with super optimal hydration to slow progression of ESRD
5) pt education, connection with resources
6) other symptomatic control (e.g. low sodium)
in a kid with ADPKD, do you screen for berry aneurysm
ONLY if there is a Fhx of massive brain bleed
- screen at age 30yo
16yo female with diarrhea illness x2w presents with brown-colored urine
- no recent travel / new foods, no emesis, but crampy abd pain results in decreased intake
- at first thought urine was super concentrated, but now dark brown
- took cipro after 1w of illness, tylenol and motrin prn pain
- FHx for mom with grave’s disease
- EXAM: Bp normal, vitals normal, Ht 50%, Wt 10%
- otherwise completely normmal, no edema, mild non-specific diffuse abd pain
- UA = blood, proteins, LOTS of RBC casts
diffdx?
- IgA nephropathy = acute mucosal damage
- HUS = from Shigella diarrhea –> sheared RBCs
- systemic autoimmune vasculitis (SLE, polyarthritis)
- HSP - not really diarrhea (abd pain, hematuria) +/- rash (can come on later - within a week)
- post-infectious GN
EVALUATION
- CMP, CBC nml (no HUS)
- 24h urine protein 0.9g
==> diagnosed with C. diff colitis –> treated.
- everything resolved
- C3 levels normalized in 2mo
==> DX:
- post-infectious
- IgA nephropathy (if get another infection - will get nephritis again)
treatment for IgA nephropathy
ACE-I == slow decline of renal fx
SEVERE - steroids
13yo girl with elevated BP (persistent for past 6y)=130-160/90-100. only PMH for ankle sprains and fractures
- ROS mostly negative (no fever, chills, n/v/d
- Fhx - Mother with IBS, maternal GF with adult-onset CHF, maternal GM with adult onset DM
- Meds - only taking Ca
- Vitals = weight 54%ile, height 46%ile, BMI 19.4, HR 99
R arm BP = 150/104
L arm BP = 158/100
- Exam is normal - no edema, no masses in abdomen, no CVA tenderness, warm well-perfused. No bruits. No rashes (for vasculitides)
diffdx?
most likely
- meds = stimulants, OCPs, decongestants; caffeine, steroids
- essential HTN
- obesity
- anxiety/stress
- pain
most concerning
- renovascular dz (fibromuscular dysplasia, renal artery stenosis)
- pheochromocytoma
- coarctation
- tumor secreting vasoactive substance
- adrenal gland = high aldo, high glucose
- thyroid
- illicit drugs (cocaine)
- excess ADH
- structural anomaly
- pyelonephritis
- glomerular dz / vasculitis /SLE
kid with structural anomaly presents with polyuria OR oliguria as it progresses?
polyuria
kid with glomerular dz presents with polyuria OR oliguria as it progresses?
oliguria
US of chronic renovascular dz
shrunken kidneys
US of reflux nephropathy kidney
chronic scarring, dilated renal calyces
==> makes you at risk for UTI, but doesn’t mean you have to have them.
pathophysiology of VUR leading to HTN in a 13yo girl?
- RFs
- labs
- management
1) puberty == increased muscle mass
2) reflux nephropathy kidney
3) chronic damage to kidney ==> HTN
RFS
- lots of UTIs
- lots of ear infections
LABS
BUN, Cr high
BMP normal
MANAGEMENT
1) counseling that will ultimately have ESRD
2) ACE-I = even with high Cr ==> check for hyperkalemia; halt progression of ESRD
3) low-salt diet
4) no smoking, no decongestant, no NSAIDS
for someone with renal disease, what anticipatory guidance should you warn about?
no smoking, no decongestant, no NSAIDS
post-infectious GN
- If strep
==> what other conditions
==> diagnosis
- f/up plan
ASSOCIATED CONDITIONS (post-strep GN) - Strep pharyngitis = sudden onset of fever, sore throat, HA, abd pain (WITHOUT rhinorrhea, congestion, cough) + exudative tonsillitis, palatal petechiae, strawberry tongue, tender anterior cervical LN, +/- accentuation of skin lines in flexor surfaces (Pastia's lines) +/- fine, papular sandpaper rash - Strep impetigo = honey-colored crust under nares / on inset bites or wounds
DIAGNOSIS
- elevated ASO titer (antistreptolysin)
- positive streptozyme
- elevated anti-DNAase B antibodies
- low C3
FOLLOW-UP PLAN: clinically follow for 2-3mo
- C3 nml
- resolution of hematuria, proteinuria, HTN, renal insufficiency
if BP remains high == b/c can be temporary but lead to acute complications
- supportive management
- anti-hypertensives
acute glomerulonephritis
- pathophysiology and clinical sxs
pathophysiology:
1) glomerular injury
- RBC casts
- hematuria
- proteinuria
2) inflammation of glomerular capillary bed
3) decreased glomerular capillary perfusion
4) decreased GFR + increased Na, water absorption
- azotemia
- increased urine osmolality
- decreased urine sodium
5) decreased tubular fluid, increased ECF volume
6) renal failure
- decreased urine volume - oliguria
- HTN - CHF, encephalopathy
- edema
- anemia
SLE - lupus nephritis
- labs:
- sxs:
- tx:
- labs: low C3, C4
- sxs: multiorgan system manifestations
- tx: anti-inflammatories
primary MPGN
- labs:
- sxs:
- tx:
- labs: low C3
- sxs: isolated to kidney, +/- hemolytic anemia
- tx: steroids (not as good)
IgA nephropathy
- patho:
- labs:
- sxs:
- tx:
2 most common acute GN in children
- patho: Respiratory / GI muosal lining infection / immune stimulus
- labs: low C3 during illness
- tx:
1) supportive = if BP normal, urine protein near normal
2) ACE-I
3) prednisone, immnosuppressants = if severe
most common acute GN in children
1) post-infectious GN
2) IgA nephropathy
Henoch Schonlein purpura
- labs:
- sxs:
- tx:
most common vasculitis in children
50% have renal involvement
- sxs:
1) asymptomatic hematuria
2) HTN, proteinuria, renal insufficiency / failure - tx:
1) supportive = if BP normal, urine protein near normal
2) ACE-I
3) prednisone, immnosuppressants = if severe
Hemolytic uremic syndrome
- patho:
- tx:
- patho:
1) diarrhea-associated HUS ==> d/t shiga-like toxin from E. coli - tx: dialysis support during acute period
2) non-diarrhea HUS = invasive S. pneumo –> d/t deficiency of certain alternative pathway complement factors
most common glomerular cause of renal failure in children
hemolytic uremic syndrome
Alport syndrome
- patho:
- labs:
- sxs:
- tx:
- patho: hereditary nephritis d/t mutation in collagen (for BM in multiple areas - kidney, ears, eyes)
- sxs: progressive sensorineural deafness +/- eye involvement
presentationof Wilm’s tumor
- abdominal mass
- gross hematuria
congenital kidney anomalies
- and treatment
- ureteropelvic junction obstruction ==> surgery; preserve kidney fx & prevent future trauma
- polycystic kidney disease ==> identify & monitor for HTN/proteinuria –> delay progressive decline of dysfunction
evaluation for kidney stones in kids
1) 24h urine ==> prevent recurrence
2) treatment of hypercalciuria = most common etiology for stones in kids/adults
3 yo boy presents with eye swelling and progressive anasarca
Pediatrician suspects nephrotic syndrome
How to confirm diagnosis?
1) Urinalysis = Should have nephrotic range proteinuria (3+ or 4+)
2) Nephrotic Syndrome diagnostic criteria
Edema
-Nephrotic Range Proteinuria
-Hypoalbuminemia
-Hypercholesterolemia
pathophysiology of nephrotic syndrome + clinical sxs
1) glomerular injury
2) increased permeability of glomerular BM
- heavy proteinuria (foamy urine)
- occasional hematuria
3) albuminuria
4) decreased serum albumin
- hypoproteinemia
5) decreased plasma oncotic pressure
6) decreased peripheral capillary return + increased renal Na reabsorption
- decreased urine sodium
7) increased interstitial fluid
- peripheral and peirorbital edema
pathophysiology of nephrotic syndrome + clinical sxs
1) glomerular injury
- loss of polyanion charge of normal capillary wall from proteoglycans (hep sulfate)
- larger capillary wall pore size
- change in hemodynamics of capillary flow
2) increased permeability of glomerular ==> increased filtration
- heavy proteinuria (foamy urine)
- occasional hematuria
3) albuminuria
4) decreased serum albumin
- hypoproteinemia
5) decreased plasma oncotic pressure
6) decreased peripheral capillary return + increased renal Na reabsorption
- decreased urine sodium
7) increased interstitial fluid
- peripheral and peirorbital edema
predominant cause of nephrotic syndrome in children
minimal change disease (age 1-10yo)
minimal change disease
- signs and sxs
- biopsy
- tx
- prognosis
- signs and sxs: young age, no RBC cats, nephrotic syndrome, nml Cr, nml BP
- tx:
1) 2mg/kg = 60mg Prednisode daily ===> diagnosis by trial
2) treat intercurrent infections/triggers
-prognosis: majority recur ==> steroid dependent
+/- biopsy if:
- atypical findings and/or
- failure to respond to prednisone treatment and/or
- secondary steroid resistant
==> fusion, diffuse effacement of epithelial cell foot processes
complications of nephrotic syndrome
- RFs
1) infectious concerns (spiking fevers) = spontaneous bacterial peritonitis (strep pneumo, GN), pneumonia, cellulitis, UTI
- decreased IGs
- edema fluid rich for infection
- protein deficiency
- decreased leuk bactericidal activity
- steroid immunosuppression
- decreased splenic perfusion d/t hypovolemia
- urinary loss of complement properdin factor B –> opsonizes bacteria
RFs = prolonged therapeutic use of corticosteroids
PREVENTION (when in remission) = PCV, varicella (2 doses); annual influenza
TX = early treatment with broad-spectrum IV Abx
2) hypercoagulopathy = any of large vessels ==> venous thrombosis of sagittal sinus, pulmonary, renal veins
RFs
- prolonged therapeutic use of corticosteroids = thrombogenic
- urinary loss of proteins that are antithrombotic (antithrombin III) or pro-fibrinolytic
- destabilization of plts (hyperlipidemia)
- increased fibrinogen levels
- increased blood viscosity (increased Hct) –> esp. with diuretic w/out albumin replacement
overall treatment of primary nephrotic syndrome
1) low sodium diet < 50mEq = 1500-2000mg daily
2) 25% albumin + 1-2mg/kg lasix infusion ==> for symptomatic edema -
dyspnea; scrotal
3) corticosteroids = trial for kids 1-10yo without gross hematuria, normal C3
17 year old girl presents for health maintenance. She has a history of type 1 diabetes so her PCP is monitoring urinalysis
Exam – BP is normal, otherwise normal
U/A—1.025, 2+ Protein, otherwise negative
? ddx proteinuria without nephrotic syndrome
? management
? follow-up
BENIGN ==> should clear after resolution of trigger = Pr: Cr
-False positive (concentrated specimen)
- fever
-Recent exercise, dehydration, physical stress
-Orthostatic (benign positional) proteinuria
= 1.5g/24h [morning protein NEGATIVE] ==> tall adolescent or 20-something, when standing (not sitting/lying down)
PATHOLOGIC -FSGS, Membranous Glomerulonephropathy - SLE, Infection associated MPGN, IgA (usually also with hematuria) - Hereditary (e.g. podocin)
MANAGEMENT
1) quantitate proteinuria; assess positional pattern
- Split 24 hour urine collection (upright/supine)
- Split spot collections (first AM urine v. random daytime urine)
2) possible biopsy
- >1gram/day (or Pr/Cr >1.0)
- No orthostatic variation (b/c would otherwise be benign protienuria)
- Elevated blood pressure or elevated serum creatinine
FOLLOW-UP
- reassurance that this will resolve
- monitor 1-2x/year ==> for possible early presentation of pathologic lesion
diffdx of periorbital swelling
+ timing
WITHOUT ERYTHEMA / DRAINAGE == means no conjunctivitis
- seasonal / perennial allergic conjunctivitis ==> sneezing, itchy nose, clear rhinorrhea, +/- pruritis, mucoid discharge, allergic shiners, Dennie’s lines, cobblestoning of conjunctiva
==> throughout season - URI ==> nasal congestion, cough, pharyngitis
==> acute - sinusitis (ethmoid/frontal/maxillary) [in setting of URI, allergic rhinitis] ==> swelling +/- redness d/t inflammatory edema from swollen tissue obstruction venous drainage from periorbital structures through sinuses
- acute allergic rxn ==> abrupt, + urticarial rash, + swelling of face (lips, tongue, oropharyngeal structurs)
- cellulitis (h/o bite, trauma, infection) ==> U/L, erythematous
+/- extension from another site of infectino (e.g. sinusitis)
==> strep pneumo, moraxella catarrhalis, ntH.flu - heart failure ==> + S3 gallop (LV overload)
- nephrotic syndrome ==> EDEMA (esp. periorbital when child is upright –> pitting in dependent, ascites, weight gain)
+ increasing tiredness, decreased appetite (inconsistent with weight gain) d/t interstitial fluid accumulation
==> worse at the beginning of the day, improves throughout
describe the pathophysiology of edema in nephrotic syndrome
v. glomerulonephritis
1) proteinuria
2) low serum albumin ==> decreased plasma colloid osmotic pressure
3) interstitial fluid accumulation
==> severe: hypotensive
4) intravascular hypovolemia –> activated renal volume sensors, extrarenal neurohormonal & hemodynamic mechanisms
5) renal retention of salt & water : RAAS, ADH, deperssed natriureti factor
6) EDEMA
v. intravascular fluidoverload ==> acute glomerulonephritis
==> severe: hypertensive
causes of proteinuria
==> UA findings
==> any disease causing inflammation of renal parenchyma (nephritis)
- pyelonephritis
==> WBCs, WBC casts; + leukocyte esterase test - acute glomerulonephritis = “tea colored urine”
==> RBCs, RBC casts, + heme test - interstitial nephritis = minimal proteinuria, d/t infection, NSAIDs, methicillin, penicillins, cephalosporins, rifampin, sulfonamide
==> RBCs, WBCs
classification of nephrotic syndrome
==> by response to steroids
1) steroid responsive
2) relapsing/steroid dependent ==> w/ spontaneous resolution in 20s; no long-term renal damage; and no restrictions / workup when in remission
- only need steroids with flare-ups.
3) steroid-resistant ==> persistent proteinuria after 8w of therapy ==> RENAL BIOPSY
where is it best to see generalized edema in patients?
MALE - scrotum
FEMALE - labia
how to assess for abdominal fluid wave,
1) 3rd arm firmly across vertical midline of abdomen ==> to prevent transmission of fluid wave thru adipose tissue
2) hands on either side of abdomen
3) tap one side of abdomen firmly with fingertips
diffdx for fatigue, periorbital edema, abd distension
==> first signs
1) nephrotic syndrome =d/t hypoalbuminemia
==> periorbital edema
==> abdominal distention +/- ascites ==> fatigue, poor appetite inconsistent with weight gain
2) acute glomerulonephritis =d/t hypoalbuminemia (less severe v. nephrotic)
==> abdominal distention +/- ascites ==> fatigue, poor appetite
3) CHF ==> edema ==> abd distension d/t hepatomegaly \+ tachycardia, murmur, gallop ==> SOB / fatigue
4) hepatic failure
==> fatigue
+ jaundice
NO ABDOMINAL DISTENSION
1) allergic rxn
==> periorbital edema
+ abrupt, urticarial rash
2) sinusitis = inflammatory edema
==> periorbital swelling and redness (painless)
define anascara
extreme generalized edema
- periorbital edema
- facial edema
- abdominal distension +/- ascites
- pitting edema
diffdx of ankle swelling
- arthritis of the ankles ==> localized swelling, inflammation of ankle joint (limited ROM; redness)
- systemic allergic rxn ==> urticarial rash
- serum sickness = looks like multiple mosquito bites.
- HSP = darker, flatter, looks more vascular
generalized edema
- evaluation
EVALUATION ==> loss of albumin in urine v. lack of albumin production in liver
- CBC
- BMP, BUN, Br ==> indication of renal fx
- AST, ALT, cholesterol, albumin, TGs ==> hepatic inflammation and/or impairment in hepatic synthetic fx
- C3, C4 ==> MPGN, PIGN, SLE
- Streptozyme = ASO (anti-strep antigens) ==> PIGN d/t strep
MANAGEMENT
for treatment of primary nephrotic syndrome, why do you have to use 25% albumin + 1-2mg/kg lasix infusion
LASIX alone == can lower intravascular volume to very low levels ==> SHOCK ==> risk of venous thrombosis
- the problem with nephrotic syndrome is interstitial edema == can cause severe hypotension d/t hypovolemia
ALBUMIN alone == can lead to pulmonary edema due to rapid blood volume expansion
differentiate periorbital swelling with and without erythema
WITHOUT ERYTHEMA - nephrotic etiology
WITH ERYTHEMA == conjunctivitis –> allergies, chemical irritation, infection
== conjunctiva appear red & swollen + lid edema; watery/purulent drainage
1) allergic conjunctivitis == b/l red, watery, itchiness and irritation; mucoid/ropey discharge; hx of hypersensitivity to seasonal allergens
2) infectious conjunctivitis == conjunctival redness, itching –> usually begin in one eye, and can spread to the other
- viral (adults) = + pharyngitis, pre-auricular lymphadenopathy
- bacterial (<6yo) = purulent exudate + eyelids crusted closed upon waking
you see mildly enlarged tonsils in a 5yo, without exudate. should you be concerned?
NO. as long as there is no erythema or exudate, petechiae on soft palate (indicative of pharyngitis
- peak growth of lymphoid tissue at 4-6yo
- kids at this age get frequent URIs
how to assess degree of proteinuria
NORMAL:
- 24h urine protein <4mg/m2/h
- Urine Pr:Cr ratio < 0.2-0.5
ABNORMAL:
- 24h urine protein 4-40mg/m2/h
- Urine Pr:Cr ratio >1.0
- random urine specimen > 30mg/dL (1+) if spec. grav = 1.015; > 100mg/dL (2+) if spec. grav > 1.015
NEPHROTIC SYNDROME
- 24h urine protein >40mg/m2/h
- Urine Pr:Cr ratio >2.5
will treatment of strep pharyngitis / impetigo prevent theoccurnence of post-infectious glomerulonephritis?
NO
but treatment of strep pharyngitis WILL prevent acute rheumatic fever.
determine this condition that causes anascara = increased interstitial fluid:
increase in capillary hydrostatic pressure
CHF
determine this condition that causes anascara = increased interstitial fluid:
decrease in plasma protein concentration / decreased plasma colloid osmotic pressure
nephrotic syndrome
determine this condition that causes anascara = increased interstitial fluid:
increased vascular permeability to proteins
allergic reaction / sepssis
determine this condition that causes anascara = increased interstitial fluid:
impaired lymphatic flow
lymphoma / compressive effects of tumor
nephrotic syndrome: labs
1) low Na (hyponatremia)
- d/t fluid overload –> excessive Na and H2O retention
- (pseudo) d/t elevated lipids –> if lipids are high enough to cause blood to have milky appearance
2) low serum albumin
3) hyperlipidemia, hypercholesterolemia
4) high urine protein
5) hypotension
a child who has generalized edema, can he be dehydrated?
a child could be edematous (total body fluid overloaded) and intravascularly depleted at the same time.
common causes of idiopathic nephrotic syndrome
1) minimal change disease [KIDS] (85%)
2) focal segmental GN [ADULTS] (10%)
==> mesangial proliferation; segmental scarring in 1+ lobules
- progressively involve all glomeruli –> EDRD
- 20% steroid responsive
- disease can recur even in transplanted kidney
3) membranoproliferative GN, etc. (5%)
An 8-year-old boy presents with tea-colored urine, oliguria, joint pain, hypertension, and generalized edema. One month ago, he presented with fever and sore throat, headache, abdominal pain, strawberry tongue, papular sandpaper rash. At that time, he did not have runny nose, congestion or cough. He was treated with appropriate antibiotics for his symptoms and made a full recovery. Which of the following diagnostic findings supports his new symptoms?
A ANA positive B Low anti-streptolysin O titer C Normal C3 complement D Low C3 complement E Gram negative organisms on urine culture
sandpaper rash == strep pyogenes - scarlet fever
post-infectious GN
now 1 month out == PIGN takes 3 months usually to recover complement.
C3 is decreased in PSGN. This value will return to normal six to eight weeks after presentation of PSGN symptoms. Although this patient was treated appropriately for his strep throat, treatment does not prevent PSGN. However, timely and appropriate treatment of strep throat will prevent development of rheumatic fever.
C3 plays a role in bacterial killing. A low C3 > less bacterial killing > more prone to infection. A low C3 is also associated with increased risk for autoimmune diseases.
A 6-year-old male comes to the clinic with a chief complaint of scrotal swelling, recent weight gain, and decreased appetite. Vital signs are stable and there is no evidence of cardiac disease or jaundice. Further workup reveals proteinuria, hypoalbuminemia, and hyperlipidemia, consistent with nephrotic syndrome. Which of the following histological patterns is most likely to be seen on light microscopy?
A Normal glomeruli with minimal increase in mesangial cells and matrix
B Mostly normal glomeruli and mesangial proliferation but with areas of juxtamedullar glomeruli showing segmental scarring in one or more lobules
C Tram-track appearance of the glomerular basement membrane and subendothelial immune complex deposition
D Enlarged, hypercellular glomeruli with neutrophil invasion
E Glomeruli showing diffuse capillary and glomerular basement thickening
A.
scrotal swelling = generalized swelling
6yo - most likely minimal change disease
histology seen in minimal change disease. Histologically, minimal change disease is characterized by normal glomeruli on light microscopy. Minimal change disease is the most likely diagnosis of nephrotic syndrome between the ages of 1 and 10 years old, accounting for up to 85% of cases.
Katie is a 5-year-old girl with 10-day history of swelling of her face, especially around the eyes. Her mother has also noticed that her pants have become too tight for her, and that she has gained nearly 5 pounds despite a decreased appetite. About a week prior to the start of the swelling, her mother recollects an episode of rhinorrhea, cough, and sore throat. Urinalysis shows no red blood cells or casts, but you have no other data from urinalysis due to a lab error. On exam, temperature is 98.8 F, heart rate is 95 bpm, blood pressure is 95/65 mmHg. Her face is diffusely swollen. Heart and lung exams are normal. Abdominal exam shows some abdominal fullness but no masses or organomegaly. Both feet appear slightly puffy. Which of the following is the most likely cause?
A Sinusitis B Nephritis C Nephrotic syndrome D Congestive heart failure E Allergic reaction
C
post-infectious
nephrotic == more impressive proteinuria
The constellation of history and physical exam findings, with a recent viral infection and subsequent edema, suggests nephrotic syndrome. Minimal change disease is the most common form of nephrosis in pediatrics. Changes in the podocytes of the glomerular apparatus allow significant proteinuria (> 3.5 g/day), which leads to hypoalbuminemia and eventually interstitial edema and ascites. This would explain the patient’s periorbital swelling, increasing abdominal girth (ascites), and weight gain (pure fluid overload).
Nephritis classically presents with proteinuria, hematuria, and hypertension. This patient’s blood pressure is normal. Although the urinalysis unfortunately was inconclusive on the level of proteinuria, there was no hematuria.
Brian, a 5-year-old boy with swelling around both his eyes and an abdomen that looks “bigger than normal,” is brought in by his mother to your preceptor’s office. Mom explains that she noticed the puffy eyes and bigger belly starting the week before. It seemed to appear out of nowhere, and Brian has been completely healthy except he had a cold several days before these symptoms developed. When you ask Brian if he has noticed anything else weird, he says that his “pee-pee looks like Coca-cola,” at which point his mom scowls and tells him to stop being silly. His blood pressure taken by the nurse right before entering the room is elevated. Based on the above information, which of the following does Brian likely have?
A Periorbital cellulitis B Viral upper respiratory infection C Allergic conjunctivitis D Nephrotic syndrome E Acute glomerulonephritis
E. Acute glomerulonephritis would explain all aspects of Brian’s presentation. The disease presents with gross hematuria (which most patients describe as tea-colored or cola-colored), periorbital swelling and ascites due to hypoalbuminemia, and hypertension due to intravascular fluid overload. Additionally, acute glomerulonephritis frequently follows a URI.
post-infectious, tea-colored urine.
hypertension == more likely in line with nephritis (v. nephrotic == hypotension)
While nephrotic syndrome could explain the periorbital edema and ascites, it would not explain the darkened urine. Also nephrotic syndrome is more associated with normal blood pressure and Brian’s blood pressure is elevated.
A 7-year-old girl is brought to her pediatrician because of recurrent puffy eyes. She presented one week ago because of the same problem and was diagnosed with allergies. She was started on an intranasal steroid with no relief. Her mother states she has become increasingly tired and mentions that she has recently outgrown all of her shoes. The patient has no other symptoms and is at the 50th percentile for height and weight, is afebrile, and non-toxic appearing. Her heart and lung exam are normal. She has no hepatomegaly and no evidence of rash. What is your next step in diagnosis/management?
A Echocardiogram B Urinalysis C Flonase trial for an additional week D CBC with manual differential E Liver enzymes
B
generalized edema – for which intranassal steroids would not work
systemic steroids likely would have
ecause of the high suspicion of nephrotic syndrome, a urinanalysis would be the next step in diagnosis. This patient has symptoms of periorbital edema, lethargy, and pedal edema (she quickly outgrew her shoes). This test can be done in an outpatient setting and is not invasive (you do not have to stick her with a needle!). Nephrotic syndrome is defined as proteinuria > 50mg/kg. However, this cannot be detected with a UA. A UA dipstick will show high albumin concentration (graded as 3+ or 4+), and is used as a screening tool. Additional testing will be needed to confirm the diagnosis.
how to remember the clinical sxs of SLE?
MD SOAP BRAIN
M alar rash
D iscoid rash (not common in kids)
S erositis = pleruisy, pericarditis
O oral ulcers
A rthritis
P hotosensitivity
B lood disorders R enal involvement A NA I mmunologic phenomena N eurologic d/o
