1. HEMATURIA IN CHILDREN Ali Derakhshan MD Shiraz University of Medical Sciences, Shiraz-Iran

2. HematuriaHematuria Transient phenomenon of little significance Transient phenomenon of little significance Sign of serious renal disease Sign of serious renal disease

3. Microscopic Hematuria Definition > 3-5 RBC/HPF μL > 5 RBC/ μL > 8000 RBC/ml Definition > 3-5 RBC/HPF μL > 5 RBC/ μL > 8000 RBC/ml

4. Hematuria >3-5 RBC/HPF in 10cc centrifuged urine >3-5 RBC/HPF in 10cc centrifuged urine >5RBC/μL uncentrifuged urine >5RBC/μL uncentrifuged urine Prevalence:0.5-2%in school age children Prevalence:0.5-2%in school age children Normal child excretes>100000RBC/12hr Normal child excretes>100000RBC/12hr Dipstick detects >3 RBC/ μL of urine Dipstick detects >3 RBC/ μL of urine False Negative (formalin,Ascorbic acid) False Negative (formalin,Ascorbic acid) False positive (urine PH>9, oxidizing detergents, hypochlorite and microbial peroxidase in UTI) False positive (urine PH>9, oxidizing detergents, hypochlorite and microbial peroxidase in UTI) Screening U/A at 5 yrs and during 2 nd decade Screening U/A at 5 yrs and during 2 nd decade

5. Causes of Hematuria Glomerular disease Lesions along the urinary tract Conditions unrelated to kidney and urinary tract

6. Hematuria not representing kidney or urinary tract disorder Following exercise Febrile disorders Gastroenteritis with dehydration Contamination from external genitalia

7. Classification of hematuria Macroscopic (gross)- symptomatic or asymptomatic Microscopic -symptomatic or asymptomatic In ≈70% of cases of gross hematuria cause is found In ≈70%of cases of microscopic hematuria either transient or cause is not found Isolated Microscopic Hematuria Non-Isolated Hematuria

8. Causes Of Discolored Urine Red or pink urine Heme (+) : RBC (hematuria), Hburia, Myoglobinuria Heme (+) : RBC (hematuria), Hburia, Myoglobinuria Heme (-) : Heme (-) : Drugs: Chloroquine, Deferoxamine, ibuprofen, metronidazole, rifampin, phenazopyridine, salicylates, iron, sulphasalazine, Phenothiazines, phenolphthalein, Metabolites: Urates, porphyrins, Drugs: Chloroquine, Deferoxamine, ibuprofen, metronidazole, rifampin, phenazopyridine, salicylates, iron, sulphasalazine, Phenothiazines, phenolphthalein, Metabolites: Urates, porphyrins, Dyes(veg./fruits) :Beets, black berries, food coloring Dyes(veg./fruits) :Beets, black berries, food coloring Dark brown or black urine Metabolites: Bile pigments, Meth.Hb, Alanine, Resorcinol,, Alkaptonuria(Homogenistic acid), Melanin, thymol, tyrosinosis Metabolites: Bile pigments, Meth.Hb, Alanine, Resorcinol,, Alkaptonuria(Homogenistic acid), Melanin, thymol, tyrosinosis

9. Origin of Hematuria Glomerular hematuria: glomeruli, tubules and interstitium Non-glomerular or urinary tract hematuria collecting syst., ureters, bladder and urethra Coca color or brown urineCoca color or brown urine Proteinuria >30mg/dl Proteinuria >30mg/dl RBC cast RBC cast >30%Dysmorphic RBC >30%Dysmorphic RBC Acute nephritic syndrome Acute nephritic syndrome Almost always associated with glomerulonephritis with glomerulonephritis or vasculitis Virtually exclude extra-renal causes of bleeding extra-renal causes of bleeding

10. Glomerular versus extraglomerular bleeding Urinary findingGlomerularExtraglomerular Red cell castsMay be presentAbsent Red cell morphology DysmorphicUniform ProteinuriaMay be presentAbsent ClotsAbsentMay be present ColorCola,Red or brownRed

11. Clinical Approach to Hematuria Not to miss serious conditions Avoid unnecessary and expensive tests Reassure the family Guidelines for further studies according to changes in the course of illness Careful history

13. History Timing of hematuria and associated symptoms Trauma, exercise, stone passage, URI, skin infection and medications Dysuria, frequency, urgency, back pain, skin rash, joint symptoms and edema Sickle cell disease or trait Family History: hematuria, stone, hypertension, renal failure, transplantation, deafness & coagulopathy Menarche

14. Physical Exam General P/E, BP, inspection of genitalia ± Hypertension and edema determines how urgent the diagnostic evaluation should be Rash and arthritis→ SLE, Henoch schonlein nephritis Fever and flank pain→ pyelonephritis Renal mass: hydronephrosis, polycystic kidney, tumor

15. Child with Lower Urinary Symptoms Hematuria with dysuria, frequency, urgency, flank or abdominal pain is suggestive for : UTI, hypercalciuria or nephrolithiasis UTI : In 1/3 of cases associated with hematuria usually microscopic Hemorrhagic cystitis by adenovirus type 11 and 21 (5days GH then 2-3days micro-hematuria) Schistosomiasis

16. Child with Clinical Features of Glomerulonephritis Acute nephritic syndrome: edema, ↑BP, oliguria, hematuria, ↓renal function Work up for different types of glomerulonephritis according to the History: ASO, C3,C4,ANA, DsDNA, ANCA, Serum IgA.

17. Asymptomatic Child : Incidental Microscopic Hematuria in U/A In routine check up or in a child with febrile illness or any other presentation Repeat U/A after resolution of current illness Repeat U/A twice within1- 2 weeks if 2of the 3→+ further evaluation UA of siblings and Parents Common causes of persistent micro-hematuria: Benign familial hematuria (TBMN), idiopathic hypercalciuria, IgA nephropathy and Alport syndrome

18. Hypercalciuria Noted in 1981. Increase urinary excretion calcium with normal serum calcium levels. Ca/Cr ratio>0.21mg/mg * or >4mg/kg/day Measurement of urinary calcium excretion has become the standard part of the evaluation of hematuria in children. Had family history of renal stones. No restrict calcium in children—osteopenia. Rx: hydrochlorothiazide * >7 years old

20. Cola or brown, RBC cast proteinuria >30mg/dl acute nephritic synd. Yes Yes Glomerular H CBC,Diff,ESR,BUN,Cr, Elect,Ca, P,Protein, Alb, lipid profile C3, C4,ASO, Anti-Dnase-B,ANA, ANCA Throat/skin culture 24h U protein, Cr Audiometry ±Kidney Biopsy Follow up No 1- U/C 2- U Ca/Cr, Uric acid/Cr ratio Sickle prep, US ± Doppler 3- UA of siblings BUN,Cr,Elect,Ca,P If Crystaluria or stone or Nephrocalcinosi: 24h urine for Ca,Cr,Uric acid,Oxalate,citrate and cystine If hydronephrosis:VCUG±scan Follow up Q 3 MO if persisted *1yr refer to Ped neph.

21. Indications of Renal Biopsy In follow up of Hematuria if any of the following: - Proteinuria -Hypertension -Renal isufficiency Persistent low C3 following PSAGN Systemic disease with proteinuria: SLE, HSP, ANCA+vasculitis Family history suggestive of Alport syndrome Recurrent gross hematuria of unknown etiology To have : light, EM, IF microscopic evaluation for biopsy specimens To have : light, EM, IF microscopic evaluation for biopsy specimens Important Consideration For Family Anxiety, Insurance.

22. Causes of Glomerular and Non- Glomerular Hematuria Upper U Tract Dis Familial benign hematuria or non-familial benign hematuria Glomerulonephritis (GN) Primary GN(Postinfectious, MPGN, MGN, RPGN, IgAN) Secondary GN SLE,HSP,PN,WG Alport syndrome TIN Vascular(HUS,, RVT, Sickle, Hemangioma, Aneurysm, Nutcracker syndrome Cystic dis Anatomic Abn. Tumor Lower U Tract Dis. Non-glomerular UTI (cystitis, urethritis) chemical cystitis (CTX) Hypercalciuria, stone, trauma, exercise coagulopathy, Bladder tumor Menarche factitious

23. Confirm hematuria Dipstick and microscopic exam Step1 Evaluate for pigment → Dipstick + No RBC Symptom and sign of acute nephritic syndrome: edema, HTN, oliguria, renal failure Significant RBC ↓ Step2 yes → Protein/Cr,BUN, Cr, Na, K,Alb.C3,C4,ASOT, ANA,Anti-dsDNA, ANCA Macroscopic hematuria: exclude exercise Isolated micro-hematuria: repeat weekly * 2 investigate if persistent Step3 ↓ NO ↓ Urine phase contrast microscopy Protein/Cr ratio NON-GLOMERULAR Isomorphic RBC, no casts, no protein Step4 Step5 GLOMERULAR dysmorphic RBC,RBC casts, proteinuria