Download - PROTEINURIA IN CHILDREN Barbara Botelho M.D. Children’s Hospital & Research Center Oakland
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PROTEINURIA
IN CHILDREN
Barbara Botelho M.D.
Children’s Hospital & Research Center Oakland
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A CASE
• 15 year old girl presents for a sports physical
• Found to have a U/A with:– 1015/5/no blood/no sugar/no LE/no nitrites 100 mg/dL protein
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MECHANISMS OF PROTEINURIA
• GLOMERULAR– FEVER/EXERCISE/ORTHOSTATIC– GLOMERULAR DISEASE
• TUBULAR– LMW PROTEINS– TUBULOINTERSTITIAL DISEASE– FANCONI’S SYNDROME
• OVERFLOW PROTEINURIA
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SYMPTOMATIC OR ASYMPTOMATIC PROTEINURIA?
• History:– swelling, gross hematuria– joint pains, rashes– previous UTIs
• Physical:– growth– blood pressure– edema
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Our case: entirely asymptomatic with a benign exam. She has
never had a UTI.
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HOW COMMON IS PROTEINURIA?
• 5-10% OF CHILDREN WILL HAVE
1+ OR GREATER
• 0.1% WILL HAVE PERSISTENT PROTEINURIA
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IS THE PROTEINURIA REAL?
• Remember that the urine dipsticks only measure concentration.
• Evaluate urine protein/Cr ratio on a spot urine sample (normal <0.2)
• 24 hour urine collection
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IS THE PROTEINURIA DANGEROUS?
If the proteinuria is transient or orthostatic, it is benign.
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EVALUATE FOR ORTHOSTATIC PROTEINURIA
**Give patient urine collection cup to take home.***
• Void before bed
• Upon awakening: quick sitz bath
• collect mid void sample
• refrigerate sample
• send for U/A and urine pro/cr
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INTERPRETING THE FIRST AM VOID
• If the first AM void shows normal protein excretion, no further work-up is needed.
• If the first AM void is abnormal (urine pro/cr ratio >0.2):– Repeat directions– Repeat sample
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ASYMPTOMATIC PROTEINURIA
If proteinuria is persistent and not orthostatic:
REFER TO A NEPHROLOGIST!!
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DIFFERENTIAL DIAGNOSIS OF ASYMPTOMATIC
PROTEINURIA
• Focal Segmental Glomerulosclerosis– FSGS
• Reflux Nephropathy• Glomerulonephritis• Systemic Lupus Erythematosis
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ASYMPTOMATIC PROTEINURIA: WHAT IT IS
NOT.
• It is absolutely not Minimal Change Nephrotic Syndrome
• There is no indication for a steroid trial.
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ASYMPTOMATIC PROTEINURIA:WORK-UP
• Renal function• ***Albumin***• Glomerulonephritis work-up:
– C3, C4, CH50,
– Hepatitis B
– ANA, ds DNA, ?ANCA
• Renal ultrasound• ?DMSA scan
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NONORTHOSTATIC ASYMPTOMATIC
PROTEINURIA• Important to make a definitive diagnosis
• Renal Biopsy may be indicated.
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FOCAL SEGMENTAL GLOMERULOSCLEROSIS
• Some parts of some glomeruli have scars
• Frequently presents as nephrotic syndrome
• May present as asymptomatic proteinuria
• High incidence of progression to renal failure
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FSGS
• Hyperfiltration– Reduced renal mass– Hypertension– Diabetes Mellitus– Sickle Cell Nephropathy
• Immune mediated
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FSGS: TREATMENT
• Hyperfiltration– ACE inhibitors– ARB
• Immune mediated– Solumedrol – Calcineurin inhibitors– Mycophenylate
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REFLUX NEPHROPATHY
• Renal scarring related to UTIs in association with vesicoureteral reflux.
• If bilateral, may cause renal failure
• If unilateral may cause asymptomatic proteinuria and hypertension.
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REFLUX NEPHROPATHY:DIAGNOSIS
• DMSA Scan
• Consider even if there is not a clear history of UTIs
• Unilateral scarring may result in asymmetry of renal lengths on renal ultrasound
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SCREENING U/As
• The only way to detect asymptomatic proteinuria
• Cost effectiveness?– Screen first AM void– Try to avoid unnecessary testing or referrals.
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SYMPTOMATIC PROTEINURIA
• Symptoms/signs of glomerulonephritis– gross hematuria– hypertension– renal insufficiency
• Nephrotic syndrome
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We will focus on Nephrotic Syndrome.
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A CASE
Three year old boy with swelling
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HISTORY
• Previously healthy
• URI 2-3 weeks ago
• Noted periorbital swelling one week ago– Dx: Allergies
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THE CASE CONTINUES
• Swelling worsens and now involves his entire body
• Diarrhea
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PHYSICAL EXAM
• BP= 100/50 AF
• Marked periorbital edema
• Breath sounds clear but decreased at the bases
• Ascites, but nontender abdomen
• 3+ pitting edema to thigh
• Moderate scrotal edema
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WORK-UP
Urinalysis:– Yellow Micro:– s.g.= 1030 15-20 RBC– glu=neg 0 WBC– ket=neg 3-5 Granular casts– bld=small– protein=neg– nitrites=neg
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FURTHER WORK-UP
BLOOD: BUN=30 Alb=1.5 Cr=0.5 Chol=360 Na=131 Trig=300 K=3.8 Cl=115 Bicarb=24
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MORE URINE STUDIES
• Urine pro/cr ratio=15– >10 is considered nephrotic range proteinuria
• You consider a 24 hour urine collection but decide against it.– Greater than 1000 mg/M2 is considered
nephrotic range proteinuria
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CXR
• Important to consider in child with anasarca
• Risk of pleural effusions
• Extremely unusual to see pulmonary edema with nephrotic syndrome, unless:– renal insufficiency– overly aggressive management with 25%
albumin
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NEPHROTIC SYNDROME
• Criteria for diagnosis:– Edema– Nephrotic Range Proteinuria– Hypoalbuminemia– Hyperlipidemia
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HOW YOU COULD BE FOOLED
• Hypoalbuminemia without significant proteinuria:– Protein losing enteropathy– Decreased albumin synthesis– Lymphedema
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WHAT GIVES YOU NEPHROTIC SYNDROME IN
A TODDLER?
• Minimal Change Disease
• Minimal Change Disease
• Minimal Change Disease
• Focal Segmental Glomerulosclerosis
• Membranous
• Membranoproliferative GN
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HOW TO BE EVEN MORE SURE THAT THIS IS MCNS
• Sudden presentation• Normal blood pressure• No hematuria
– Hematuria in 25% with MCNS
• Normal Creatinine• Normal Complement levels• Steroid responsiveness
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OTHER BLOOD WORK TO BE DONE AT PRESENTATION
• Complement levels
• ANA
• Check on varicella status
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IT IS NOT MINIMAL CHANGE DISEASE WHEN:
• Presentation as an infant
• Asymptomatic proteinuria
• Low complement levels
• Be suspicious in teenagers
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SO WHAT IS MCNS?
• Minimally altered glomerular structure
• Fusion of podocytes
• Profound proteinuria
• Steroid responsiveness
• Relapsing course
• Can be outgrown
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NEPHROTIC SYNDROME IN CHILDREN IS CHANGING
• Incidence of FSGS is on the rise
• Dramatic increase of around 300% since the 1960’s
• FSGS is much more prevalent in African Americans
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FOCAL SEGMENTAL GLOMERULOSCLEROSIS
• Histologic Diagnosis
• More likely to be steroid resistant
• May present as asymptomatic proteinuria
• Higher chance of progression to renal failure
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INCREASED INCIDENCE OF FSGS
??Related to the obesity epidemic??
Obesity induced FSGS
Hypertension induced FSGS
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OUR CASE
• We assume our patient has minimal change disease…– No need for a renal biopsy
• Now what do we do?
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TREATMENT OF NEPHROTIC SYNDROME
• Control the edema
• Prevent complications
• Stop the proteinuria
• Minimize medication side effects
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WHY DO YOU GET EDEMATOUS?
• Starling equilibrium
• 80% of oncotic pressure is due to albumin
• With albumin less than 2.5 mg/dL edema forms
• Albumin infusions as treatment
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GENERAL MEASURE
• Diet: Low salt
• Fluid restriction
• Diuretics?
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NUTRITIONAL ADVICE
• No added salt
• No fast food
• No food in little plastic packets
• Limit milk and cheese
• 2 gm/day
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DIURETICS
• Very tempting but potentially dangerous– Potentiates intravascular depletion– Increases risk of ATN– Increases risk of thrombosis
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COMPLICATIONS FROM EDEMA
• Spontaneous Peritonitis
• Cellulitis
• Pleural Effusions
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COMPLICATIONS FROM INTRAVASCULAR
DEPLETION
• Prerenal azotemia
• Acute tubular necrosis
• Thrombosis
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WHEN TO GIVE ALBUMIN AND LASIX
• Peritonitis
• Pleural effusions
• Severe edema with skin breakdown/cellulitis
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WHEN NOT TO GIVE ALUMIN AND LASIX
• AESTHETIC PURPOSES
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HOW TO GIVE ALBUMIN AND LASIX
• 25% Albumin 1 gm/kg over 4 hours
• Lasix at hour #2 and upon completion
• Watch for hypertension and pulmonary edema
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STOP THE PROTEINURIA
• Prednisone 2 mg/kg/day (Max 80 mg/d)
• 80% WILL RESPOND WITHIN 2 WEEKS
• Best predictor of MCNS
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GOOD NEWS AND BAD NEWS
• MCNS will likely get better with steroids
• It will come back again and again and again– Especially a risk with intercurrent illness
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STRATEGIES TO PREVENT RELAPSES
• Prolong initial Prednisone therapy of
2 mg/kg/day for 6 weeks
• Taper off Prednisone over a 6 week interval
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SOME DEFINITIONS
• Frequent relapses– 4 or more relapses within a year
• Steroid dependence– 2 relapses consecutively on steroids or shortly
after stopping
• Steroid resistance– No response to steroids after 4 weeks
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THE MORE RELAPSES THE
MORE STEROIDS
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SOMETIMES STEROIDS AREN’T SO GREAT
• Side effects of chronic steroid therapy:– Obesity– Poor growth– Osteoporosis– Cataracts– Striae– Diabetes
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WHEN GOOD STEROIDS GO BAD
• When excessive steroids are required to control nephrosis, consider a steroid sparing agent.
• Don’t need to wait for development of steroid side effects.
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STEROID SPARING AGENTS
• Cyclophosphamide
• Mycophenylate
• Calcineurin inhibitors– Cyclosporine– Tacrolimus
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CHOICE OF STEROID SPARING AGENT
Depends on specific tissue diagnosis
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INDICATIONS FOR A RENAL BIOPSY
• Steroid resistance
• Need for a steroid sparing agent
• Adolescent
• Infant
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MINIMAL CHANGE DISEASE
• Steroid sparing agent of choice:– Cyclophosphamide
• 3 mg/kg/day over 8 weeks
• Monitor carefully for side effects
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SIDE EFFECTS OF CYTOXAN
• Hemorrhagic Cystitis– Encourage good intake of fluids– Monitor urine specific gravity
• Neutropenia– Frequent blood draws to follow ANC
• Infertility• Hair loss• Infections
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ADVANTAGES OF CYTOXAN
• Can anticipate a prolonged (one year or more) medication free remission
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TAKE HOME MESSAGE
• Taking care of patients with Nephrotic Syndrome is interesting and rewarding
• It is not too late to do a nephrology fellowship