Approach to a child with     Hematuria :             Sunil Agrawal             1st year             MD Pediatrics, IOM
Contents:•   Introduction•   Pathophysiology•   Causes•   History•   Examination•   Investigations•   Management
IntroductionHematuria means blood in urine.It may be Gross or macroscopic and microscopic   hematuriaGross hematuria is se...
• Pathophysiology:   Structural disruption in the integrity of    glomerular basement membrane caused by    inflammatory ...
Causes of Hematuria:A) Glomerular hematuria   Isolated renal disease                 Multisystem disease-Postinfectious GN...
B) Extraglomerular hematuriaUpper Urinary tractTubulointerstitial   Pyelonephritis   Interstitial nephritis   ATN   Papill...
Vascular:•     Arterial/venous thrombosis•     Malformation (aneurysms, hemangioma)•     Nutcracker syndrome•     Hemoglob...
Lower urinary tract  Inflammation- infectious and  non infectious       Cystitis       Urethritis  Urolithiasis  Trauma  C...
Common causes of gross hematuria:•   Urinary tract infection•   Meatal stenosis•   Perineal irritation•   Trauma•   Urolit...
Glomerular cause of gross hematuria  IgA nephropathy  Alport syndrome  Thin glomerular basement membrane disease  Post inf...
Causes of Hematuria in the Newborn:• Renal vein thrombosis (Asphyxia, dehydration,  shock)• Renal artery thrombosis• Autos...
History:• Age:    2-5yrs: Wilms tumor          5-12yrs: PSGN• Sex: F>>M in >1-2yrs: UTI         F>>M: SLE nephritis       ...
Colour of urine:Colour        CausesDark yellow   Normal concentrated urineDark brown or Bile pigmentsblack         Homoge...
Characteristics of urine:• Amount of urine: Reduced in AGN, ARF• Clots in urine: Extraglomerular•  Frequency, Dysuria, re...
Associated Symptoms:• Fever: Infections, SLE, AGN• Facial puffiness, Oedema of legs, weight gain,  Shortness of breath: Ac...
• H/o exercise, menstruation, recent bladder  catheterization or passage of a calculus• Recent upper respiratory (1-2wks b...
• H/o Vision or hearing defects: Alport  syndrome• Family h/o: Hereditary glomerular diseases  (Alport syndrome, Thin glom...
Examination:• Vitals:   – BP:  in AGN, PKD   – Temperature• Oedema: in AGN• Pallor: Bleeding disorders, HUS, SLE, CRF• JV...
• Skin lesions     Purpura(HSP)     Butterfly rash (SLE)     Bruises (Trauma, Child abuse)• Abnormal external genitalia e....
General Approach toInvestigate the child with       Hematuria
Investigations:• Urine dipstick test: Based on the  peroxidase-like activity of  hemoglobin       • It can detect trace am...
Investigations:Urine microscopy: Presence of RBCs and casts (> 5RBCs per HPF) in centrifuged urineGlomerular              ...
Study on Evaluation of hematuria using the urinary albumin-to-total-protein ratio to differentiate glomerular andnonglomer...
• With respect to the albumin-to-total-protein ratio,  the mean value in the glomerular disease group was  0.72 •} 0.10, w...
Distribution of urinary albumin-to-total-protein ratio in glomerular andnonglomerular hematuria. The mean albumin-to-total...
Urine albumin-to-total-protein ratio sensitivities and specifi itiesin differentiating glomerular and nonglomerular hematu...
Cola/ brown urine?                        Proteinuria(>30mg/dl)?                               RBC cast?                  ...
Investigations:• Urine C/S• RFT: Blood urea nitrogen/serum creatinine, Na/K (↓Na in  AGN, ↑K in ARF)• Complete blood count...
Investigations:• Imaging Studies   – Renal and bladder sonography: Urinary tract anomalies,     such as hydronephrosis, hy...
Investigations:• Renal biopsy:    Relative indications -    • Significant proteinuria (3+ or more) or nephrotic      syndr...
Dx        Histology                           Clinical         LabIgA       IgA deposition in the               Gross,    ...
Dx              Histology                     Clinical               LabAlport          Some thinning of basement     Sens...
Investigations:• Cystourethroscopy: Terminal hematuria,  disturbances of micturition, suprapubic pain  (Only if strong sus...
Summary
For Asymptomatic, isolated      microscopic hematuria:Isolated microscopichematuriaRepeat urinalysis weekly x 2    Negativ...
Management:• According to cause:  – Reassurance and F/U  – Treat cystitis, pyelonephritis, AGN: Antibiotics  – Supportive ...
Management:– Idiopathic Hypercalciuria: Hydrochlorothiazide, Potassium  citrate, Sodium restriction– Calculi: Plenty of wa...
References:• Nelson Textbook of Pediatrics, 19th Ed• Nelson Essentials of Pediatrics, 6th Ed• O.P. Ghai Essential pediatri...
Approach to a child with hematuria
Approach to a child with hematuria
Approach to a child with hematuria
Approach to a child with hematuria
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Approach to a child with hematuria

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Approach to a child with hematuria

  1. 1. Approach to a child with Hematuria : Sunil Agrawal 1st year MD Pediatrics, IOM
  2. 2. Contents:• Introduction• Pathophysiology• Causes• History• Examination• Investigations• Management
  3. 3. IntroductionHematuria means blood in urine.It may be Gross or macroscopic and microscopic hematuriaGross hematuria is seen by naked eyes while microscopic hematuria needs microscope. Hematuria is defined as the presence of at least 5 red blood cells per HPF of centrifuged urine and/or 5 RBC per microliter in uncentrifuged specimen
  4. 4. • Pathophysiology:  Structural disruption in the integrity of glomerular basement membrane caused by inflammatory or immunologic processes  Toxic disruptions of the renal tubules  Mechanical erosion of mucosal surfaces in the genitourinary tract
  5. 5. Causes of Hematuria:A) Glomerular hematuria Isolated renal disease Multisystem disease-Postinfectious GN (Post streptococcal) -HSP nephritis- IgA nephropathy( Berger ds) -SLE nephritis- Alport syndrome( hereditary ) -HUS- Thin Glomerular Basement membrane -Wegener granulomatosis disease -Polyarteritis nodosa- Membranoproliferative GN -Goodpasture syndrome- Membranous nephropathy -HIV nephropathy - Focal segmental glomerulosclerosis - Antiglomerular basement membrane -Sickle cell glomerulopathy ds
  6. 6. B) Extraglomerular hematuriaUpper Urinary tractTubulointerstitial Pyelonephritis Interstitial nephritis ATN Papillary necrosis NephrocalcinosisAnatomic Hydronephrosis Polycystic kidney disease Tumor (Wilms, Rhabdomyosarcoma, Angiomyolipoma) Trauma
  7. 7. Vascular:• Arterial/venous thrombosis• Malformation (aneurysms, hemangioma)• Nutcracker syndrome• Hemoglobinopathy (Sickle cell trait/disease)Crystalluria: Calcium, Oxalate, Uric acidMedications: NSAIDs, anticoagulants
  8. 8. Lower urinary tract Inflammation- infectious and non infectious Cystitis Urethritis Urolithiasis Trauma Coagulopathy Heavy exercise Bladder tumor Factitious syndrome / by proxy
  9. 9. Common causes of gross hematuria:• Urinary tract infection• Meatal stenosis• Perineal irritation• Trauma• Urolithiasis/hypercalciuria• Coagulopathy• Tumor
  10. 10. Glomerular cause of gross hematuria IgA nephropathy Alport syndrome Thin glomerular basement membrane disease Post infectious glomerulonephritis HSP nephritis SLE nephritis
  11. 11. Causes of Hematuria in the Newborn:• Renal vein thrombosis (Asphyxia, dehydration, shock)• Renal artery thrombosis• Autosomal recessive polycystic kidney disease• Obstructive uropathy• Urinary tract infection• Bleeding and clotting disorders• Trauma, bladder catheterization• Cortical necrosis (Hypoxic/ischemic perinatal insult)• Nephrocalcinosis (Frusemide in premature)
  12. 12. History:• Age: 2-5yrs: Wilms tumor 5-12yrs: PSGN• Sex: F>>M in >1-2yrs: UTI F>>M: SLE nephritis M>F : X-linked form of Alport syndrome• Race: whites: Idiopathic hypercalciuria blacks: Sickle cell disease
  13. 13. Colour of urine:Colour CausesDark yellow Normal concentrated urineDark brown or Bile pigmentsblack Homogentisic acid, melanin, tyrosinosis, methemoglobinuriaCola coloured Glomerular hematuriaRed or pink Extraglomerular hematuria,urine Hemoglobin, Myoglobin, Porphyrins, Chloroquine, Deferoxamine, Beets, blackberries, Rifampin, Red dyes in food, Urates
  14. 14. Characteristics of urine:• Amount of urine: Reduced in AGN, ARF• Clots in urine: Extraglomerular•  Frequency, Dysuria, recent enuresis : UTI• Frothy urine: Suggests Proteinuria seen in Glomerular diseases• Timing: Initial stream – from urethra (Urethrorrhagia – spotting in underwear); Terminal (with suprapubic pain, disturbance of micturition) – from bladder
  15. 15. Associated Symptoms:• Fever: Infections, SLE, AGN• Facial puffiness, Oedema of legs, weight gain, Shortness of breath: Acute Glomerulonephritis• Hypertension (Headache, visual changes, epistaxis, seizures): AGN, ARF• Abdominal pain: Urolithiasis (Loin to groin), UTI, clots, Nutcracker syndrome• Painless: Glomerular• Abdominal mass: Hydronephrosis, PKD, Wilm’s tumour• Joint pain (HSP, SLE)• Rashes (HSP, SLE, PAN)• Neurologic – SLE, HUS (seizures, irritability)• Jaundice: Hemolysis, Obstructive jaundice
  16. 16. • H/o exercise, menstruation, recent bladder catheterization or passage of a calculus• Recent upper respiratory (1-2wks back), skin infection (3-6 wks): PSGN• GI infection: HUS, HSP nephritis• Gross hematuria precipitated by URI: Alport syndrome, IgA Nephropathy• H/o bleeding from other sites: Bleeding disorders, Hemoptysis in Good Pasture syndrome• H/o Trauma, abdominal surgery, Child abuse (Social factors - Munchausen), crush injury• H/o ingestion of drugs (ATT – Rifampicin, Ibuprofen, Chloroquine, Metronidazole, Iron), i.v. contrast agents (Toxic nephropathy, RVT)
  17. 17. • H/o Vision or hearing defects: Alport syndrome• Family h/o: Hereditary glomerular diseases (Alport syndrome, Thin glomerular Basement Membrane Disease, IgA Nephropathy), Urolithiasis, Hypercalciuria, Sickle cell disease/trait• H/o consanguinity or affected siblings in ARPKD, Metabolic disorders
  18. 18. Examination:• Vitals: – BP:  in AGN, PKD – Temperature• Oedema: in AGN• Pallor: Bleeding disorders, HUS, SLE, CRF• JVP: Raised in CHF• Per abdomen: Mass – Kidney: Hydronephrosis (Urinary tract obstruction), Wilms tumour; B/L in ARPKD, hydronephrosis – Bladder palpable: Distal obstruction – Tenderness: HSP
  19. 19. • Skin lesions Purpura(HSP) Butterfly rash (SLE) Bruises (Trauma, Child abuse)• Abnormal external genitalia e.g. ambiguous genitalia in WAGR syndrome (Wilms, aniridia, genital anomalies, mental retardation), Wilms tumour – hypospadias, cryptorchidism, Genital trauma• Signs of Congestive cardiac failure, HTNsive encephalopathy: AGN• Joint swelling, tenderness: HSP, SLE• Ophthalmologic: Alport syndrome (Anterior lenticonus, macular flecks, recurrent corneal erosions), Aniridia (Wilms)• Hearing assessment: Alport (B/L SNHL)
  20. 20. General Approach toInvestigate the child with Hematuria
  21. 21. Investigations:• Urine dipstick test: Based on the peroxidase-like activity of hemoglobin • It can detect trace amounts of hemoglobin and myoglobin. • Can detect 5-10 intact RBC per mm3 of unspun urine • False +ve: Urine pH >9, H2O2 • False –ve: High ascorbic acid, formalin• Also for urine albumin
  22. 22. Investigations:Urine microscopy: Presence of RBCs and casts (> 5RBCs per HPF) in centrifuged urineGlomerular Non - glomerular1. Brown, cola coloured or smoky 1. Bright red, pink2. RBC casts 2.Terminal hematuria/ Passage of clots3. Proteinuria 2+ or more 3. Proteinuria of < 2+4. Deformed urinary RBCs 4. Normal morphology of RBCs
  23. 23. Study on Evaluation of hematuria using the urinary albumin-to-total-protein ratio to differentiate glomerular andnonglomerular bleeding•N. Ohisa · R. Matsuki · H. Suzuki · H. Miura · Y. Ohisa · K. YoshidaDepartment of Clinical Laboratory, Tohoku University Hospital,Sendai, Japan•microscopy-based differentiation is not only tedious but the sensitivity andspecificity may vary from one examiner to another. Furthermore, oncethe specimen has been frozen, differentiation becomes difficult.•A total of 143 random urine specimens from patients seen at the Division ofNephrology, Endocrinology and Vascular Disease and the Urology Departmentat Tohoku University Hospital were included in the study. The inclusion criterionfor the study was a diagnosis of glomerular disease based on clinical featuresor histopathology with hematuria (5 or more RBCs per high-power fi eld). Of the104 patients diagnosed with glomerular disease and 39 specimens frompatients with nonglomerular disease, used as controls in the study.
  24. 24. • With respect to the albumin-to-total-protein ratio, the mean value in the glomerular disease group was 0.72 •} 0.10, whereas the mean in the nonglomerular disease group was 0.35 •} 0.17 (P < 0.001). The distribution of the albumin-to-total- protein ratio in the glomerular and nonglomerular disease groups was clearly differentiated. Sensitivity and specificity as a function of the albumin-to-total- protein ratio. At a ratio cutoff of 0.59, sensitivity and specificity was maximized at 96.2% and 100%, respectively.
  25. 25. Distribution of urinary albumin-to-total-protein ratio in glomerular andnonglomerular hematuria. The mean albumin-to-totalprotein ratio in theglomerular disease group was signifi cantly higher than that in the nonglomerulardisease group. A cutoff of 0.59 excluded all nonglomerular disease cases, whiledetecting all but three glomerular disease cases. Gl, glomerular disease; non-Gl,nonglomerular disease; vertical axis, albumin-to-total-protein ratio; horizontal axis,glomerular disease, nonglomerular disease
  26. 26. Urine albumin-to-total-protein ratio sensitivities and specifi itiesin differentiating glomerular and nonglomerular hematuria. At aratio of 0.59, sensitivity and specificity were 96.2% and 100%,respectively.
  27. 27. Cola/ brown urine? Proteinuria(>30mg/dl)? RBC cast? Acute nephritic syndrome? Yes NOGlomerular hematuria Extraglomerular hematuria• CBC Step 1• Electrolytes,Ca • Urine culture• BUN/Cr Step 2• Serum protein/albumin • Urine Ca/Cr• Cholesterol • Renal/ bladder USG• C3/C4 Step 3• ASO/Anti-DNase B • Urinalysis: siblings, parents• ANA • Serum electrolytes, Cr, Ca• Antineutrophil antibody • If crystalluria, urolitiasis or nephrocalcinosis:• Throat/ skin culture 24-hr urine for Ca, Cr, Uric acid, oxalate• 24-hour urine total protein creatinine clearance • If hydronephrosis/pyelocaliectasis: cystogram, renal scan
  28. 28. Investigations:• Urine C/S• RFT: Blood urea nitrogen/serum creatinine, Na/K (↓Na in AGN, ↑K in ARF)• Complete blood counts (CBC): Hb - ↓ in bleeding, HUS, SLE, CRF; Abnormal TC, DC in infections, HUS, ↓ in SLE;• Platelet counts and Coagulation studies: (history suggestive of bleeding disorder, HUS), Sickle cell (Hemoglobin electrophoresis)• PBS: Microangiopathic hemolytic anemia• ESR, CRP - Infections• 24 hr urinary protein, Spot urinary protein: Creatinine ratio, Serum albumin and cholesterol if associated proteinuria (Nephrotic syndrome)• Urine calcium: Hypercalciuria is a relatively common finding in children. – 24-hour urinary calcium (>4 mg/kg/d), or – Spot urine calcium-creatinine ratio >0.21
  29. 29. Investigations:• Imaging Studies – Renal and bladder sonography: Urinary tract anomalies, such as hydronephrosis, hydroureter, nephrocalcinosis, tumor, and urolithiasis, Renal parenchymal disease – X-Ray KUB: calculi – Doppler study of renal vessels and IVC: Renal vein thrombosis – Intravenous urography – Spiral CT scan - Urolithiasis, Wilms tumor and polycystic kidney disease, Renal trauma – Micturating cystourethrograms - Urethral and bladder abnormalities (eg, cystitis), in recurrent UTI to r/o VUR, anomalies – Radionuclide studies – Renal function and perfusion – Angiogram – Chest X-Ray (Pulmonary oedema, CHF)
  30. 30. Investigations:• Renal biopsy: Relative indications - • Significant proteinuria (3+ or more) or nephrotic syndrome + • Recurrent persistent hematuria (Microscopic >2yrs) • Abnormal renal function, Persistent HTN • Hematuria, Proteinuria, diminished renal function, low C3 level persist beyond 2 mo of onset of AGN • Absence of evidence of streptococcal infection • Serologic abnormalities (abnormal ANA or dsDNA levels) • A family history of end stage renal disease or evidence of Chronic renal disease in patient
  31. 31. Dx Histology Clinical LabIgA IgA deposition in the Gross, No specificNephro- mesangium, glomerular intermittent, changes,pathy sclerosis, proliferative changes, painless although crescents in severe cases hematuria increased serum IgA levels observed in some patientsHSP Same as IgA nephropathy Purpura, joint No specific pains, laboratory data abdominal pain, hematuria, etcSLE Mild glomerulitis, proliferative Hematuria, Abnormal C3, C4, changes, immune complex proteinuria, ANA, dsDNA, deposition, crescents, hypertension, anemia, immunoglobulin deposition joint pains, thrombocytopeni rashes, etc a, etc
  32. 32. Dx Histology Clinical LabAlport Some thinning of basement Sensorineural NoSyndrome membranes, "basket weave" hearing loss, corneal specific changes in the glomerular abnormalities, changes basement hematuria, renal membrane on electron failure microscopyThin Average glomerular basement Persistent NoBasement membranes thin (reported to microscopic or gross specificMembrane be 100-200 nm) hematuria, changesdisease significant family historyMesangio- Glomerular lobulations, Hematuria, C3 levelsproliferative thickening of the mesangial proteinuria, may beGN matrix and glomerular hypertension low basement membranes, crescents, etc
  33. 33. Investigations:• Cystourethroscopy: Terminal hematuria, disturbances of micturition, suprapubic pain (Only if strong suspicion of bladder ulceration, tumours)• Screening of first degree relatives in persistent hematuria
  34. 34. Summary
  35. 35. For Asymptomatic, isolated microscopic hematuria:Isolated microscopichematuriaRepeat urinalysis weekly x 2 Negative F/U Urine R/M with(No exercise x 48hrs) examination Persistent hematuriaTest parents for Positive Benign Familialhematuria Hematuria No Yes Family h/o calculi Urine Ca/Cr ratio No Normal +Hearing test, +USG, Yearly Urine R/M, +X-Ray KUB examination, BP
  36. 36. Management:• According to cause: – Reassurance and F/U – Treat cystitis, pyelonephritis, AGN: Antibiotics – Supportive treatment: Diuretics, Fluid and salt restriction, Antihypertensives – Monitoring – BP, I/O, weight, Urine R/M – Treat Hyperkalemia, ARF, CHF, acidosis, fluid overload, HTN and its complications – ACE inhibitors useful in proteinuria – Immunosuppressive therapy: Depending on cause (Steroids, cyclophosphamide)
  37. 37. Management:– Idiopathic Hypercalciuria: Hydrochlorothiazide, Potassium citrate, Sodium restriction– Calculi: Plenty of water– ESRD: Dialysis, Renal transplantation– Correct thrombocytopenia, anemia, coagulation factor deficiency– Renal vein thrombosis: Anticoagulant therapy or thrombectomy may be needed– Surgical correction: Calculi, PUJ obstruction, Posterior urethral valves, Wilms tumour
  38. 38. References:• Nelson Textbook of Pediatrics, 19th Ed• Nelson Essentials of Pediatrics, 6th Ed• O.P. Ghai Essential pediatrics, 7th Ed• Pediatric Nephrology, Shrivastava, Bagga, 4th Ed• Japanese Society of Nephrology 2007• Indian J Pediatrics 1999; 66 : 207-214• Various Websites

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