Patient #1 A 7y/o boy presents to your office with his mother with a CC of abdominal pain. He is an active child who was in his USOH until this morning when he began to c/o nonspecific abdominal pain. Mom also reports that his urine was darker than usual this morning. She thought it was secondary to dehydration, but became more concerned when the abd pain began. The child is noted to be active and in no distress; mom explains that the abdominal pain has since resolved and he is now asking for food On PE, pt is afebrile. Vital signs are normal except for a BP of 127/78. No other abnormalities are found. Abdominal exam is benign w/ no tenderness Patient #2 A 7 y/o girl presents to your office for a routine check up. She appears well and mom does not report any problems You have never seen this patient in the past and decide to get a screening urinalysis b/c she has never had one sent in the past The results to her urine dipstick demonstrate 2+ blood; otherwise nl A UA w/ micro is sent during the same visit and demonstrates 15-20RBCs/hpf w/ no other abnormalities Evaluation of Hematuria Morning Report January 13th 2005 Definitions Macroscopic (gross) hematuria- visible to the naked eye Microscopic hematuria- confirmed by microscopic examination of the spun urine sediment – >5 RBCs/hpf on a spun urine – Trace blood or higher by urine dipstick Absence of RBCs in the urine with a positive dipstick suggests hemoglobinuria or myoglobinuria – Visualizing a spun urine will help distinguish b/w true hematuria and other causes of red urine Glomerular vs. Non-glomerular Glomerular Extra-Glomerular Color Red, smoky brown or “coca cola” Red or Pink Clots Absent May be present (or crystals) Proteinuria May be >500mg/day <500mg/day RBC morphology Dysmorphic Normal RBC casts May be present (highly specific) Absent History Abdominal or flank pain Dysuria, frequency, urgency Trauma Strenuous exercise Menstruation Recent URI/ sore throat Skin rashes/ skin infx Diarrhea (especially bloody) Joint pains/swellings Medications/toxins h/o sickle cell disease or trait *Family history: hematuria, hearing loss, HTN, stones, renal disease, dialysis or transplant, coagulopathy, sickle cell trait Physical Exam Blood pressure Fever Abdomen for masses, tenderness (flank, suprapubic) Rashes, evidence or trauma, bruising Edema (especially periorbital) Joint erythema, swelling, warmth Paleness, jaundice Careful inspection of external genitalia If BP is elevated, further evaluation is immediately warranted General Rules At least 2 of 3 urinalyses should show microhematuria over 2-3 weeks before further evaluation is done Initial evaluation for any type of hematuria always includes: – microscopic evaluation of a spun urine – Urine culture Indications for prompt evaluation include hematuria with: – hypertension, edema, oliguria, significant proteinuria or RBC casts Macroscopic Hematuria Requires prompt evaluation to exclude potentially lifethreatening causes! Most common cause presenting to an ER is UTI Most common glomerular causes are post-strep GN and IgA nephropathy Other causes: blunt trauma, renal calculi, hypercalciuria, sickle cell trait, local irritation or trauma to perineal area, exercise, coagulopathy, tumors Macroscopic Hematuria: Evaluation OBTAIN A THOROUGH HISTORY AND PHYSICAL! GN suspected (edema, HTN, protein, RBC casts) – BMP, CBC, C3, C4, albumin, ASO titer, anti-DNAseB, ANA History of Trauma – CT scan abdomen/pelvis UTI suspected – Urine culture, +/- renal ultrasound Stones suspected or Family h/o stones – Imaging (KUB, ultrasound, CT) Urine Ca:Cr (or 24 hr urine) No obvious cause?Æ consider renal U/S, urine culture, test parents, sibs for hematuria, Hgb electrophoresis, Urine Ca:Cr ratio Microscopic Hematuria: Common causes include urinary tract infection, benign familial hematuria (or thin basement membrane nephropathy), hypercalciuria, IgA nephrophathy, Alport’s syndrome Most children with isolated asymptomatic microscopic hematuria do not have a treatable or serious cause and do not require extensive evaluation Note that most of these conditions can also present w/ gross hematuria Asymptomatic Microscopic Hematuria: Evaluation Repeat UA weekly X 2 (w/out exercise) Persistent hematuria: If work-up is negative (and no other concerning signs/sx), follow w/ yearly UA (UA w/ micro, dipsick for protein, BP) – – – – BUN/Cr, urine cx (low yield) Test parents and sibs for hematuria Urine Ca:Cr ratio or 24hr urine for calcium excretion Consider hearing test, renal ultrasound, Hgb electrophoresis, coagulation studies (LOW YIELD) Recent studies have questioned the need for a diagnostic evaluation for asymptomatic microscopic hematuria Microscopic Hematuria w/ abnormal findings (history, physical or UA) No protein, edema or HTN: – Work-up according to associated findings h/o trauma- CT if > 50 RBCs/hpf S/Sx of UTI- urine culture S/Sx of stones- imaging studies, Urine Ca:Cr Abdominal mass- renal U/S or CT +family history- hearing test, Urine Ca:Cr, imaging – If diagnosis is still unclear- refer to nephrologist Microscopic Hematuria w/ abnormal findings (history, physical or UA) Presence of protein, HTN or edema – Hematuria + proteinuria strongly suggests GN – If patient is acutely ill BMP, CBC, C3, C4, albumin; consider ASO, DNAseB titers, ANA – If patient is not acutely ill (protein w/out HTN, edema) Recheck UA in one week – Persistent hematuria/proteinuria Send labs listed above and consider referral Glomerular Causes of Hematuria Acute Post-infectious glomerulonephritis IgA Nephropathy Henoch-Schonlein purpura System lupus erythematosus Rapidly progressive glomerulonephritis Alport hereditary nephritis Benign familial hematuria (Thin basement membrane nephropathy) Note that most glomerular causes of hematuria will also have proteinuria Acute Post-infectious Glomerulonephritis poststreptococcal glomerulonephritis Most common cause is nephritogenic strains of GrA strep (can also follow other bacterial and viral illnesses) Acute onset of tea-colored urine (or microscopic) edema, HTN, oliguria, malaise, abd pain OR asymptomatic previous illness or skin infection 1-3 weeks prior to onset UA w/ protein, RBC casts; +/- elevated BUN/Cr Elevated ASO or DNaseB titer confirms infx Most useful lab: Decreased C3 Pathophysiology of GN Process Manifestation Glomerular Inflammation ⇓ ⇓ Glomerular Blood Flow ⇓ ⇑ Na+ & H2O Retention Hematuria & Proteinuria ⇓ ⇓ GFR & Azotemia ⇓ Oliguria, Edema & Hypertension Slide courtesy of Dr. Clardy Acute Post-infectious Glomerulonephritis Supportive/Symptomatic treatment Most important considerations: Gross hematuria and other Sx resolve w/in a few weeks C3 should return to normal in 6-8 wks Prognosis is excellent – Na restriction, diuretics, ACE inhibitors – monitor BP and manage hypertension – Must distinguish PSAGN from other forms of GN – Microscopic hematuria may persist for 1-2 yrs – If C3 remains elevatedÆ further evaluation is indicated Glomerulonephritis: differential Hypocomplementemic (low C3) – Post Streptococcal GN – Membranoproliferative GN – Systemic Lupus Erythematosus Normocomplementemic (normal C3) – – – – IgA Nephropathy Henoch-Schönlein Purpura Idiopathic Vasculitis Rapidly Progressive GN Slide courtesy of Dr. Clardy Indications for Biopsy all patients unlikely to have poststreptococcal GN as determined by… Biopsy – Normal initial C3 – Failure of low C3 to normalize after 8 weeks – Positive ANA – Progressive azotemia Slide courtesy of Dr. Clardy IgA Nephropathy Most common cause of glomerulonephritis Presents w/ gross hematuria during a URI or GI illness OR asymptomatic microscopic hematuria/proteinuria Episodes of gross hematuria resolve in a few days Renal biopsy is required for diagnosis ~25% develop slowly progressive renal dysfunction No specific treatment – Mesangial IgA deposits are seen on immunoflorescence – Renal bx for definitive dx in patients w/ asymptomatic hematuria is controversial Rapidly Progressive Glomerulonephritis One of the few emergencies in pediatric nephrology Clinical presentation similar to APIGN (but nl C3) Many causes of GN can present w/ rapid progression or it can be idiopathic (juvenile acute nonproliferative glomerulonephritis) Labs w/ signs of renal insufficiency; renal bx w/ glomerular crescents Untreated RPGN can progress to ESRD in a few weeks Prompt Dx and Tx with pulse steroids may prevent progression to ESRD Benign Familial Hematuria (Thin glomerular basement membrane nephropathy) common cause of persistent glomerular bleeding in children Inheritance is autosomal dominant or recessive Family history is helpful in that there are no relatives with significant renal disease Hematuria is usually microscopic (gross hematuria may occur w/ URIs); Proteinuria is rare Diagnosis of exclusion – Send UA on family members to detect hematuria Monitor w/ yearly UA for development of proteinuria and BP measurement – Any abnormal findings would suggest a dx other than BFH Interstitial and Vascular Causes of Hematuria Infectious (pyelonephritis) Tumors (esp. Wilm’s Tumor) Nephrocalcinosis Interstitial nephritis (NSAIDs) Cystic renal disease (simple,PCKD, multicystic dysplasia) Renal transplant Sickle cell disease/trait Renal vein thrombosis Renal artery thrombosis AVM Urinary Tract causes of Hematuria Infection (UTI) (bacterial or viral-esp. adenovirus) Hypercalciuria Nephrolithiasis Anatomic abnormality (UPJ obstruction, VUR) – Common presentation of UPJ obstruction is gross hematuria after minor trauma in an adolescent Hypercalciuria (w/out stones) Increased urinary excretion of calcium despite normal serum calcium Pathogenesis of hematuria is not well understood Family history of renal stones is common Asymptomatic microscopic hematuria is most common – Gross hematuria, flank pain, dysuria can occur Hypercalciuria (w/out stones) Diagnosis: Spot Urine Ca:Cr >.2 in children >6yrs is abnormal – >.42 in 19mo-6yrs is abnormal – 24hr urine for calcium: >4mg/kg/day is abnormal Treat w/ increased fluid intake – Thiazide diuretics and Na restriction can be used if +stones or family h/o stones ~15% of patients develop stones in the next 4-6 years Approach for Referral Nephrologist: Urologist: – APSGN if patient has HTN, azotemia, or hyperkalemia – Other forms of GN (especially if proteinuria, HTN, or persistent low C3 is present) – Family h/o renal failure – Systemic disease – – – – – Abnormal GU anatomy Trauma Stones (Nephrologist for metabolic w/u) Tumor Non-glomerular gross hematuria Screening Urinalysis AAP recommends that screening urinalyses be done routinely on 2 groups: – 5-year old children – Sexually active male and female adolescents (11-20 yrs) -Committee on Practice and Ambulatory Medicine. Recommendations for Preventive Pediatric Health Care. Pediatrics 2000;105