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