Proteinuria DR Badi AlEnazi Consultant 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 wall Endothelial cell Basement membrane Epithelial cell

ABNORMAL PROTEIN EXCRETION Urinary 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 EXCRETION Glomerular 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 EXCRETION Tubular 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 EXCRETION Overflow 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 PROTEIN Use 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 PROTEIN Urine 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 PROTEINURIA Most common cause Can occur in association with fever, seizures, strenuous exercise, emotional stress, hypovolemia, extreme cold, epinephrine administration, abdominal surgery, or congestive heart failure

ORTHOSTATIC PROTEINURIA Increase 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 PROTEINURIA Present for long periods after initial detection Absence of both orthostatic proteinuria and clinical evidence of renal disease Clinical course may be benign May be secondary to parenchymal disease

DIFFERENTIAL DIAGNOSES OF PERSISTENT PROTEINURIA Benign proteinuria Acute Glomerulonephritis, mild Chronic Glomerular Disease that can lead to nephrotic syndrome Chronic nonspecific glomerulonephritis Chronic interstitial nephritis Congenital and acquired structural abnormalities of urinary tract

HISTORY Recent infection Weight changes Presence of edema Symptoms of hypertension Gross hematuria Changes in urine output Dysuria Skin lesions

HISTORY Swollen joints Abdominal pain Previous abnormal urinalysis Growth history Medications Family history Renal disease, hypertension, deafness, visual disorders

PHYSICAL EXAMINATION Vital signs Inspect for presence of edema, pallor, skin lesions, skeletal deformities Screening for hearing and visual abnormalities Abdominal exam Lung exam Cardiac exam

LABORATORY EVALUATION Single 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 PROTEINURIA Follow-up routinely Patient should have a repeat urinalysis on a first morning void in one year

ORTHOSTATIC PROTEINURIA Perform Orthostatic Test CBC 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 sediment CBC Renal function tests (blood urea nitrogen and creatinine) Serum electrolytes Cholesterol Albumin and total protein

OTHER TESTS Renal ultrasound Serum complement levels (C3 and C4) ANA Streptozyme testing, Hepatitis B and C serology HIV testing

PERSISTENT PROTEINURIA If 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) Edema Hypercholesterolemia It is a functional state associated with many glomerular diseases.

Classification Congenital 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 days Treat 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 diet Fluid restriction: 600–800 mL