PROTEINURIA AND HEMATURIA CARMEN PRIET0-JIMENEZ, M.D.
Proteinuria and Nephrotic Syndrome
- 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 child <100 mg/m2/day or 150mg/day
- neonates 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 excretion
- Urinary 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
- Glomerular (increase filtration)
- Tubular (increase excretion- decrease reabsorption)
- Overflow (marked overproduction of a particular protein)
- Measurement of urinary protein
- Measurement of 24-hour protein excretion or total protein/creatinine ratio
- in a spot urine in the morning
- <0.2mg protein/mg creatinine (+2 years)
- <0.5mg protein/mg creatinine (6-24-month)
- May be necessary to differentiate glomerular from tubular protein
- Approach to the child with proteinuria
- Transient or Intermittent
- Thorough history and physical
- change in urine volume or color
- family history for renal disease and hearing loss (Alport disease)
The 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.
- Nephrotic syndrome is characterized by massive proteinuria, hypoalbuminemia, edema, and hyperlipidemia; the most common presenting symptom is edema.
- 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.
- The diagnosis of NS is the presence of urinary protein, with the albumin disproportionately greater than globulin.
Clinical Diagnostic Criteria
- 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 weight
- 4-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
- 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 NS
- The second major contributor is Thromboembolism, however anticoagulant therapy is not justified during remission.
- Growth is often impaired in NS
- There may be losses of IGF-binding protein, which could account for the depressed serum concentration of IGF-I and IGF-II.
- 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 Glomerulonephitis
- Recognition, definition, differential diagnosis, and orderly evaluation of hematuria in infants and children is often an important issue in pediatric practice
- Hematuria is defined by the presence of an abnormal quantity of red blood cells in the urine
- Macroscopic: grossly visible
- Microscopic: only upon urinalysis
- >5-10 RBC’s per high power field
- A large number of benign and serious conditions can cause hematuria in children.
- Irritation of the meatus or perineum
- Sickle cell disease/trait
- Post infectious glomerulonephritis
- Children with hematuria may present in one of three way
- 1-Onset of gross hematuria
- 2-Onset of urinary or other symptoms with incidental finding
- 3-Incidental finding during a health evaluation
- Glomerulonephritis 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)
- Throughout (no localizing value)
- History of trauma, pain, micturating symptoms, systemic signs including fever and skin and nasopharyngeal infection
- Blood on diapers of underwear
- Flank pain (loin pain hematuria syndrome)
- Blood Pressure measurement
- Assessment for edema or weight gain
- Direct visualization of the genitals
- Abdominal mass or discomfort
- -Urinalysis, urine culture, and urinary excretion studies
- -Glomerular bleeding evaluation
- (24-hour urinary protein excretion/creatinine ratio, excretion of casts, protein excretion, blood clots)
- USD of the kidney and bladder.
- Is rarely indicated. May be useful to determine if the bleeding comes from bladder or one or both ureters.
- The causes of gross and microscopic hematuria are extensive.
- A natomical abnormalities
- B ladder and kidney infection
- H ypercalciuria-hyperuricosuria-urolithiasis
- Usually gross hematuria, no proteinuria, and RBC’s that are suggestive of nonglomerular origin.
- -Exposure to cyclophosphamide
- -Left renal vein entrapment
- (Also orthostatic proteinuria)
- -Loin pain hematuria syndrome
- 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 nephropathy persistent
- -Alport Syndrome hematuria
- -Thin base membrane disease
- Hemolitic-uremic syndrome
- 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.
- Its 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 disease
- Also called benign familial hematuria , transmitted in a dominant fashion but, in most cases a heterozygous form of autosomal recessive Alport syndrome.
- Salt and water restriction.
- Depends of the etiology or severity of the disorder.