1. Clinical Approach to a Child with Hematuria Careful history, physical examination, urinary dipstick & urinalysis

2. To determine the level of hematuria – Upper vs. lower urinary tract To determine the urgency of evaluation

3. Urinary dipstick False positive – Presence of menstrual blood – Alkaline urine (pH>9) – Contamination with agents used to clean the perineum prior to collection of specimen False negative – Presence of formalin as urine preservative – High urinary concentrations of ascorbic acid

4. Upper Urinary Tract Hematuria Originate from the glomerulus, convuluted or collecting tubules and interstitium Associated with brown, cola-colored or burgundy urine, proteinuria > 100 mg/dL, RBC casts and dysmorphic RBCs (within glomerulus) Presence of leukocyte or renal tubular epithelial cell casts (within convoluted or collecting tubules)

5. Lower Urinary Tract Hematuria Originate from pelvocalyceal system, ureter, bladder and urethra Associated with gross hematuria, terminal hematuria, blood clots, normal urinary RBC morphology and minimal proteinuria (<100 mg/dL)

6. Common conditions associated with HEMATURIA in children Glomerular and extraglomerular diseases – IgA nephropathy – Urinary tract infection – Poststreptococcal glomerulonephritis Multisystemic disease – SLE nephritis – Hemolytic-uremic syndrome

7. IgA Nephropathy Most common chronic glomerular disease worldwide Predominance of IgA with mesangial deposits of the glomerulus in the absence of systemic diseases Light microscopy: focal & segmental mesangial proliferation and increased mesangial matrix Electron microscopy: electron dense mesangial deposits

8. Clinical & laboratory presentation – Associated with upper respiratory or gastrointestinal infection – Gross hematuria – Proteinuria – Mild to moderate hypertension – Normal C3 levels

9. SLE Nephritis Kidney disease is one of the most common and sometime only manifestation of SLE Fever, rash, hematologic abnormalities, arthritis & involvement of heart, CNS & kidneys Manifestations are mediated by immune complexes

10. WHO class I nephritisNo histologic abnormalities WHO class II nephritis (Mesangial lupus nephritis) II-A II-B Mesangial deposits containing immunoglobulin & complexes found in the glomeruli Mild mesangial hypercellularity Moderate hypercellularity & increased matrix WHO class III nephritis (Focal segmental lupus glomerulonephritis) Mesangial deposits in almost all glomeruli & sunendothelial deposits found between endothelial cells & GBM, with occassional capillary wall necrosis, crescent formation & sclerosis lesions WHO class IV nephritis (Diffuse proliferative lupus nephritis) Most common & most severe form; all glomeruli contain massive mesangial and subendothelial deposits of immunoglobulin & complement; “wire-loop” lesions WHO class V nephritis (Membranous lupus nephritis) Least common form; resembles idiopathic membranous glomerulopathy but with mild to moderate mesangial proliferation

11. Clinical presentation – Common in adolescent females – Class II: hematuria, normal renal function, proteinuria – Class III & IV: hematuria, proteinuria, reduced renal function, nephrotic syndrome, ARF – Class V: nephrotic syndrome

12. Detection of circulating antinuclear antibodies Demonstration of antibodies that react with native dsDNA Depressed C3 & C4 levels

13. Hemolytic-Uremic Syndrome Most common cause of acute renal failure in young children (younger than 4 years of age). Triad: microangiopathic hemolytic anemia, thrombocytopenia, uremia Etiology: Shiga-like toxin-producing E. coli (80% in developed countries)initiating endothelial cell injury Transmitted by undercooked meat or unpasteurized milk

14. Clinical Manifestations Onset usually preceded by gastroenteritis (fever, vomiting, abdominal pain and diarrhea) May present after an URTI Sudden onset of pallor, irritability, weakness, lethargy and oliguria (5-10 days after initial GI or respiratory illness) PE: dehydration, edema, petechiae, hepatospenomegaly, marked irritability

15. Laboratory Criteria Anemia (acute) - with microangiopathic changes (i.e. schistocytes, burr cells, or helmet cells) on Peripheral blood smear Renal injury (acute) - evidenced by hematuria, proteinuria or elevated creatinine level (>/=1.0 mg/dl in child younger than 13y or >/=1.5 mg/dl in 13y or older or >/=50% increase from the baseline) Platelet <150,000/mm3 w/in 7 days after onset of GI illness

16. Urinary Tract Infection Caused mainly by colonic bacteria. Females: 75-90% caused by E. coli; Males < 1y/o: Proteus Considered an important risk factor for development of renal insufficiency or ESRD in children 3 Forms: Pyelonephritis, Cystitis, Asymptomatic Bacteriuria

17. Clinical Manifestations Pyelonephritis: abdominal or flank pain, fever, malaise, nausea, vomiting, occassionally diarrhea; involvement of renal parenchyma (acute pyelonephritis) Cystitis: bladder involvment; dysuria, urgency, frequency, suprapubic pain, incontinence and malodorous urine (does not result in renal injury) Asymptomatic bacteriuria: positive urine culture w/o any signs of infection; common in girls, benign, does not cause renal injury

18. Laboratory diagnosis of UTI Proper urine sample (urinalysis) Culture showing >100,000 colonies of a single pathogen or 10,000 colonies and with symptoms