PROTEINURIA AND PROTEINURIA AND HEMATURIAHEMATURIA

CARMEN PRIET0-JIMENEZ, M.D.

Proteinuria and Nephrotic Proteinuria and Nephrotic SyndromeSyndrome

Occurrence of proteinuria in a single urine is relatively common.Will present in 5% to 15% of normal children in a random urine specimen.

-Proteinuria is a marker of renal disease.

-The dilemma for the PCP is to differentiate the child with transient or any other benign forms of proteinuria from children with renal disease.

PATOPHYSIOLOGY AND CLASSIFICATION

Normal protein excretionnormal child <100 mg/m2/day or

150mg/dayneonates is higher up to 300 mg/m2 (reduced reabsorption of filtered protein)

The normally low rate of urinary protein excretion is:

-Restriction of the filtration-Reabsorption of freely filtered low

molecular weight protein

Abnormal protein excretionUrinary protein excretion in excess of

100 mg/m2/day or 4mg/m2/hr Nephrotic range proteinuria is defined as

>1000 mg/m2/day or 40mg/m2/hr

Three main mechanism:Glomerular (increase filtration)

Tubular (increase excretion- decrease

reabsorption)Overflow (marked overproduction

of a particular protein)

Measurement of urinary protein

Urine dipsticknegativetrace between 15-30mg/dl1+ 30-100 mg/dl2+ 100-300mg/dl3+ 300-1000mg/dl4+ >1000mg/dl

Quantitative assessmentMeasurement of 24-hour protein

excretion or total protein/creatinine ratio

in a spot urine in the morning normal in children: <0.2mg protein/mg creatinine (+2

years) <0.5mg protein/mg creatinine (6-24-

month)

Qualitative assessment

May be necessary to differentiate glomerular from tubular protein

Approach to the child with proteinuriaTransient or IntermittentOrthostaticPersistent

History and physicalThorough history and physical

change in urine volume or coloredemaincrease BPrecent strep infectionfamily history for renal disease and

hearing loss (Alport disease)

The Need for Renal BiopsyThe Need for Renal Biopsy

The key indication for biopsy in any renal disorder are the need to make specific diagnosis for therapeutic reasons or to provide a prognosis.

Neprotic SyndromeNeprotic Syndrome

Nephrotic syndrome is characterized by massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia; the most common presenting symptom is edema.

IntroductionIntroduction

The annual incidence of Nephrotic syndrome in healthy children is 2 to 7 new case per 100,000 children younger than 18 years of age.The peak age lf onset is at 2 to 3 years.

DefinitionDefinition

The diagnosis of NS is the presence of urinary protein, with the albumin disproportionately greater than globulin.

Clinical Diagnostic CriteriaClinical Diagnostic Criteria

1- Generalized edema 2- Hypoproteinemia <2 g/dL (disproportionately low albumin in relation to globulin)

3-Urine protein to urine creatinine ratio in excess of 2 (first A.M. void) or a 24- hour urine that exceeds 50mg/Kg body weight4-Hypercholesterolemia (>200 mg/dL)

The mechanisms for edema include:

-Transudation of fluid from the intravascular space into the intestitium secondary to decreased albumin and

- Increased renal tubular reabsorption of sodium and water

The hyperlipidemia is secondary to:

-Increase in lipoprotein synthesis by the liver and

-Decrease in lipid catabolism resulting from reduced activity of the enzyme lipoprotein lipase and lecithin cholesterol acetyltransferase.

INCIDENCE FOR UNDERLYING PATHOLOGY

TREATMENT

ComplicationsComplications

One true complication of NS is the tendency to developed infections.

IgG antibody is lost in the urine, and complement activation is impaired by concomitant loss of factor B.

Marked intravascular depletion causes diminished splachnic blood flow and hypoxia, and a marked tendency to thrombosis cause microinfarction, lowering resistance of the bowel wall to bacteria passage.

Peritonitis is a major contributor to the 1% to 2% mortality in NSThe second major contributor is Thromboembolism, however anticoagulant therapy is not justified during remission.

Growth is often impaired in NSThere may be losses of IGF-binding protein, which could account for the depressed serum concentration of IGF-I and IGF-II.

PrognosisPrognosis

Mortality in minimal-change NS is approximately 2%Of the remaining 98%, most are steroid-responsive

about 2/3 experience 1/3 possible

single relapse developing protracted series of

relapses

Hematuria and Hematuria and GlomerulonephitisGlomerulonephitis

IntroductionIntroduction

Recognition, definition, differential diagnosis, and orderly evaluation of hematuria in infants and children is often an important issue in pediatric practice

DefinitionDefinition

Hematuria is defined by the presence of an abnormal quantity of red blood cells in the urine Macroscopic: grossly visibleMicroscopic: only upon urinalysis

>5-10 RBC’s per high power field

A large number of benign and serious conditions can cause hematuria in children.

Gross hematuriaUTIIrritation of the meatus or perineumTraumaNephrolithiasisSickle cell disease/traitPost infectious glomerulonephritisIgA nephropathy

Microscopic hematuriaGlomerulopathiesHypercalciuriaMicrolithiasisUTI

Children with hematuria may present in one of three way

1-Onset of gross hematuria2-Onset of urinary or other

symptoms with incidental finding3-Incidental finding during a

health evaluation

Historical cluesThe color of the urineGlomerulonephritis may be brown and/or frothy urine,while bleeding is suggested by the presence of blood clots, or pink or clearly red urine

The timing of the hematuria Initial (urethral bleeding)Terminal (bladder)Throughout (no localizing

value)

Circumstances associated History of trauma, pain,

micturating symptoms, systemic signs including fever and skin and nasopharyngeal infection

Age of onsetPeriodicityBlood on diapers of underwearExposure to medicationsRelation with exerciseFlank pain (loin pain hematuria syndrome)

Physical examinationPhysical examination

Should Include Blood Pressure measurementAssessment for edema or weight gainClose skin examinationDirect visualization of the

genitalsAbdominal mass or discomfort

Laboratory evaluationLaboratory evaluation

-Urinalysis, urine culture, and urinary excretion studies-Glomerular bleeding evaluation

(24-hour urinary protein excretion/creatinine ratio, excretion of casts, protein excretion, blood clots)

Imaging studiesUSD of the kidney and bladder.

Cytoscopy Is rarely indicated. May be

useful to determine if the bleeding comes from bladder or one or both ureters.

EtiologyEtiology

The causes of gross and microscopic hematuria are extensive.

Anatomical abnormalitiesBladder and kidney infectionCoagulation/hematologyDrugsExerciseFamilial hematuriaGlomerulonephritisHypercalciuria-hyperuricosuria-urolithiasisInterstitial nephritisTrauma and tumors

Extrarrenal causesUsually gross hematuria, no

proteinuria, and RBC’s that are suggestive of nonglomerular origin.

-Neprholithiasis-UTI -Adenovirus-Kidney tumor-Polycystic kidney-Urethral irritation

-Obstructive uropathy-Post-traumatic kidney-Onset of menarche-Exposure to cyclophosphamide-Thrombogenic condition-Sickle cell trait

-Vascular bleeding-”Nutcracker syndrome”-Left renal vein entrapment

(Also orthostatic proteinuria)-Loin pain hematuria syndrome-Urethrovesical bleeding

Renal Causes (Glomerular causes)

Most patients also have proteinuria, red cell casts, and/or renal insufficiency. The clinical context is also suggestive.

-Postinfectious glomerulonephritis-Henoch-Schonlein purpura

(tetrad: rash, arthralgias, abdominal pain and renal disease)-IgA nephropathypersistent

-Alport Syndromehematuria

-Thin base membrane disease(heterozygote carrier)

-Systemic diseasesLupusShunt nephritisHemolitic-uremic syndrome

Unexplained hematuria-Factitious hematuria

Poststreptococcal glomerulonephritis

The most common type in children results through immunologic process, from A Beta-hemolytic streptococcus.

Immunoglobulin A nephropathy

The most common variety of primary glomerulonephritis. Usually negative family history.

Mesangial IgA deposition is the most prominent finding on renal biopsy.

Alport SyndromeIts classically X-linked form,

suggested by hematuria in a male.Positive family history of

hematuria, deafness, and renal failure.

Abnormal collagen IV composition.

Thin base membrane diseaseAlso called benign familial

hematuria, transmitted in a dominant fashion but, in most cases a heterozygous form of autosomal recessive Alport syndrome.

TreatmentTreatment

General managementSalt and water restriction.

Specific treatment Depends of the etiology or severity

of the disorder.