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Proteinuria
DR Badi AlEnaziConsultant pediatric endocrinology and
diabetologest
Proteinuria Protein is normally found in the urine of
healthy children and adults
Since albumin has a relatively small molecular size, it tends to become the dominant constituent in proteinuria.
3 components of glomerular wallEndothelial cellBasement
membraneEpithelial cell
ABNORMAL PROTEIN EXCRETIONUrinary protein excretion in excess of 100
mg/m2 per day or 4 mg/m2 per hour
Nephrotic range proteinuria (heavy proteinuria) is defined as ≥ 1000 mg/m2 per day or 40 mg/m2 per hour.
ABNORMAL PROTEIN EXCRETIONGlomerular proteinuria
Due to increased filtration of macromolecules
May result from glomerular disease (most often minimal change disease) or from nonpathologic conditions such as fever, intensive exercise, and orthostatic (or postural) proteinuria
ABNORMAL PROTEIN EXCRETIONTubular proteinuria
Results from increased excretion of low molecular weight proteins such as beta-2-microglobulin, alpha-1-microglobulin, and retinol-binding protein
Tubulointerstitial diseases, can lead to increased excretion of these smaller proteins
ABNORMAL PROTEIN EXCRETIONOverflow Proteinuria
Results from increased excretion of low molecular weight proteins due to marked overproduction of a particular protein to a level that exceeds tubular reabsorptive capacity
ASYMPTOMATIC PROTEINURIA
Levels of protein excretion above the upper limits of normal for age
No clinical manifestations such as edema, hematuria, oliguria, and hypertension
MEASUREMENT OF URINARY PROTEINUse of a urine dipstick to detect proteinuria Dipstick proteinuria reflects primarily
albuminuria. False-positive dipstick tests are seen with
gross hematuria, concentrated urine, alkaline urine (pH >8), or contamination with chlorhexidine or certain medications (e.g., phenazopyridine therapy).
MEASUREMENT OF URINARY PROTEINUrine dipstick
Measures albumin concentration Negative Trace — between 15 and 30 mg/dL 1+ — between 30 and 100 mg/dL 2+ — between 100 and 300 mg/dL 3+ — between 300 and 1000 mg/dL 4+ — >1000 mg/dL
CAUSES OF ASYMPTOMATIC PROTEINURIA
TRANSIENT PROTEINURIAMost common causeCan occur in association with fever, seizures,
strenuous exercise, emotional stress, hypovolemia, extreme cold, epinephrine administration, abdominal surgery, or congestive heart failure
ORTHOSTATIC PROTEINURIAIncrease in protein excretion in the erect position
compared with levels measured during recumbency
Long-term studies have documented the benign nature of this condition, with recorded normal renal function up to 50 years later
PERSISTENT PROTEINURIAPresent for long periods after initial detectionAbsence of both orthostatic proteinuria and
clinical evidence of renal diseaseClinical course may be benignMay be secondary to parenchymal disease
DIFFERENTIAL DIAGNOSES OF PERSISTENT PROTEINURIA
Benign proteinuriaAcute Glomerulonephritis, mildChronic Glomerular Disease that can lead
to nephrotic syndromeChronic nonspecific glomerulonephritisChronic interstitial nephritisCongenital and acquired structural
abnormalities of urinary tract
HISTORYRecent infectionWeight changesPresence of edemaSymptoms of hypertensionGross hematuriaChanges in urine outputDysuriaSkin lesions
HISTORYSwollen jointsAbdominal painPrevious abnormal urinalysisGrowth historyMedications
Family historyRenal disease, hypertension, deafness, visual
disorders
PHYSICAL EXAMINATIONVital signsInspect for presence of edema, pallor, skin
lesions, skeletal deformitiesScreening for hearing and visual
abnormalitiesAbdominal examLung examCardiac exam
LABORATORY EVALUATIONSingle urine positive for
protein
Obtain:
1 )first morning void Pr/Cr
2 )UA in office
Pr/Cr and UA normal
Transient Proteinuria
Pr/Cr normal, UA positive
Orthostatic Proteinuria
Both specimens abnormal
Persistent Proteinuria
TRANSIENT PROTEINURIAFollow-up routinelyPatient should have a repeat urinalysis on
a first morning void in one year
ORTHOSTATIC PROTEINURIAPerform Orthostatic TestCBC BUN Creatinine Electrolytes 24-hr urine excretion
< 1.5g/day repeat UA and blood work in 1 year
> 1.5g/day refer to Pediatric Nephrologist
FURTHER EVALUATION OF PERSISTENT PROTEINURIA
Examination or urine sedimentCBCRenal function tests (blood urea nitrogen
and creatinine) Serum electrolytes CholesterolAlbumin and total protein
OTHER TESTSRenal ultrasound Serum complement levels (C3 and C4) ANA Streptozyme testing,Hepatitis B and C serologyHIV testing
PERSISTENT PROTEINURIAIf further work-up normal, urine dipstick should
be repeated on at least two additional specimens. If these subsequent tests are negative for protein, the diagnosis is transient proteinuria.
If the proteinuria persists or if any of the studies are abnormal, the patient should be referred to a pediatric nephrologist
Urinary protein excretion should be quantified by a timed collection
Nephrotic Syndrome
Nephrotic syndrome is a clinical state characterized by:Massive proteinuria (>40 mg/m2/hr)Hypoalbuminemia (albumin <2.5 g/dL)EdemaHypercholesterolemia
It is a functional state associated with many glomerular diseases.
ClassificationCongenital nephrotic syndrome (Finnish
type, diffuse mesangial sclerosis, secondary to congenital infection)
Primary or idiopathic nephrotic syndrome (minimal change disease and primary focal segmental sclerosis without any identifiable cause)
Secondary nephrotic syndrome: SLE, HSP, acute glomerulonephritis, HUS, bacterial endocarditis, bee stings, drugs, sickle cell anemias, diabetic nephropathy, chronic nephritis
Treatment (Primary or Idiopathic)
Prednisone 60 mg/m2/day in divided doses for 6 weeks, followed by 40 mg/m2/day in a single dose every other day for 6 weeks
Relapse: defined as proteinuria of >2+ for 3 consecutive daysTreat with 60 mg/m2/day in divided doses until resolved for
3 days, followed by tapering. If >4 relapses/year, consider chlorambucil or
cyclophosphamide with tapered prednisone every other day.Additional measures
Adequate protein in diet for endogenous synthesis of albumin
Restricted salt in dietFluid restriction: 600–800 mL