This case discusses a 5-year-old male admitted with blood-tinged urine. He had a history of cough and fever 1 week prior. Examination found elevated blood pressure, edema, gross hematuria, and urinalysis showed red blood cells and white blood cells. The admitting diagnosis was acute post-streptococcal glomerulonephritis based on the history of a preceding infection and exam findings. Differentials considered included other causes of glomerulonephritis. Laboratory results on subsequent days showed elevated creatinine and ASO titer consistent with post-streptococcal glomerulonephritis.

1. Case presentation DOROMAL 13 August 2010

2. CASE OBJECTIVES GENERAL To present a case of acute glomerulonephritis SPECIFIC Discuss history and physical examination results Discuss salient features and differentials Discuss plan of management

3. The patient

4. General data A.N.D. 5 years old, male, born on 13 August 2005, Filipino, Roman Catholic, from Rosario, Pasig Admitted for the first time at present institution: (5 August 2010) Informant: Mother w/ 80% reliability

5. Chief Complaint “umihingdugo” (blood-tinged urine)

6. History

8. Cefalexin

10. Cefalexin continued

12. Review of systems General No fever, no weight gain/loss, weakness, fatigue Skin No rashes, no sores, no changes in hair/nails, no gout MSK No muscle/ joint pains, no joint swelling HEENT No headache, blurring of vision, tinnitus, deafness Respiratory No dyspnea, hemoptysis Cardiovascular No palpitations, chest pains Gastrointestinal No nausea, vomiting, dysphagia, heartburn, rectal bleed Genitourinary No dysuria, NO FREQUENCY, NO Endocrine No excess sweat, heat intolerance, polyuria, excessive thirst, cold intolerance

13. Past medical History Bacterial Meningitis (2005) superimposed with Nosocomial Pneumonia, RITM (1 month) Surgeries None Allergies None to food or medications

14. Past medical History Immunization (Local Health Center) BCG HepB 1-2-3 DPT 1-2-3 OPV 1-2-3 Measles

15. Maternal and Birth history Full-term via Normal Spontaneous Delivery to a 22 year old G3P3 (3003) at Home assisted by a Midwife Spontaneous cry, Good activity Birth weight and APGAR unrecalled No significant maternal illness/ comorbidities IrregPNCu

16. Feeding History Breastfed until 1 year, then weaned Formula milk (Sustagen) at 2 years old Current diet: Chicken, rice, some vegetables, pancit canton, cooked by mother

17. Developmental History Smiled at 2 months Mama, dada at 8 months Walks alone at 1 year Jumps at 2 years Stories at 3 years Writes name, alphabet, dresses w/o supervision at 4 years Draws complete person without clothing, basic math at 5 years

18. Family History Kidney failure Stroke 32 33 Asthma Diabetes 7 5 10 3

19. Personal and Social History Home Informal settlers House near the road Family shares 1 room Water source NAWASA Parents are unemployed Education Patient at local daycare Older siblings at local elementary school

20. Physical Examination

21. Physical Examination General Awake, ambulatory, anxious, not in cardiorespiratory distress Vital Signs BP 110/80 (>99th %) HR 97 RR 20 T 37.1°C Anthropometrics Height 103cm Weight 17.4kg BMI 16.4kg/m2 Height for age 25th p Height for weight 50th p Weight for age 25th p

22. Physical Examination Skin No lesions, rashes, or color changes Good skin turgor (CRT <1 second) Head and Scalp No lesions, infections, infestations Abundant, fine black hair Eyes Conjugate gaze, anicteric sclera, pink palpebral conjunctiva No edema, deformities, lesions, ptosis, erythema, or discharge Pupils 2mm BRTL, no RAPD EOMs full and equal Presence of Red Orange Reflex, Anterior Chamber deep

23. Physical Examination Ears External ears retractable, no pain, gross deformities or discharge Canals intact, abundant cerumen, foreign body noted on right canal Cone of light present, tympanic membrane intact both ears Nose Septum midline, nares patent Turbinates pink, no discharge Mouth Lips and buccal mucosa pink and moist Cavities on teeth Tongue midline Tonsillopharyngeal congestion

24. Physical Examination Neck Supple, Cervical Lymphadenopathies present No pulsations, neck engorgement, lesions or masses Lungs No lesions, rashes, or changes in color Symmetric chest expansion, equal tactile fremiti in all lung fields Bronchovesicular breath sounds, no rales/crackles, no rhonchi Chest Adynamic pericardium Apex beat at 4th ICS MCL Normal rate, regular rhythm No murmurs

25. Physical Examination Abdomen Flat, smooth, no lesions, rashes Hypoactive bowel sounds Tympanic in all quadrants No masses, tenderness, organomegaly (-) Goldflam test Genitourinary Grossly male Testes descended No phimosis Extremities No cyanosis or clubbing, no fractures or deformities Full and equal pulses, no edema

26. Physical Examination Neuroexamination General Behavior was appropriate, cooperative to examiner, euthymic, appropriate affect, normal and spontaneous speech Sensorium Awake, Oriented to person, place and time, Memory intact, Calculation intact Fund of information, Insight, Judgment and Planning appropriate for age No agnosia or apraxia GCS 15/15

27. Physical Examination Neuroexamination Cranial Nerves I – not tested II – visual acuity intact, gaze conjugate III, IV, VI – no ptosis, EOMs full and equal V – masseter and temporalis muscle bulk and strength symmetric and normal, present corneal reflex VII – facial muscles bulk and strength symmetric and normal VIII – (+) finger rub test both ears IX, X – palatal elevation and swallow are symmetric, normal XI – SCM and trapezius contour, bulk and strength normal XII – tongue is midline, no atrophy or fasciculations

28. Physical Examination Neuroexamination Motor Normal gait and rhythm No hypertrophy/atrophy, involuntary movements Muscle tone symmetric and equal Strength 5/5 in all Superficial sensory Briskly withdraws to pain DTR 3+ in all Cerebellar Intact Meningeals Neck supple, (-) Kernigs, (-) Brudzinski, (-) Ankle clonus

29. Laboratories Urinalysis (Non-institutional) Amber-colored, turbid urine WBC TNTC*/hpf RBC TNTC*/hpf Albumin ++++ many Sugar (-) Bacteria many Hyaline casts +++ many * Too numerous to count

30. Salient Features and Differentials Admitting diagnosis

31. Acute post-Streptococcal glomerulonephritis Working Impression

32. Salient Features 5 year old Male History of URTI 1 week PTA BP elevated for age Edema Gross hematuria No headache/ blurring of vision No abdominal pain No skin lesions

33. SaLIENT FEATURES

34. Differentials

35. Differentials

36. Course in the Wards

37. Day 1 Urinalysis Amber, turbid urine WBC TMTC/hpf RBC TMTC/hpf Albumin ++++ Sugar (-) Bacteria many Hyaline many

38. Day 2 CBC+PC Hgb105.0 Hct0.33 PC 387 WBC 10.6 Neu 0.52 Lym 0.43 Eos 0.05 Serum electrolytes Na+ 140 K+ 3.9 Ca2+ 2.24 Crea 41 mmol/L  ASO 1600 IU/mL

39. Day 4

40. Day 5

41. Post-streptococcal Glomerulonephritis Case Discussion

42. PSGN

43. A. DEFINITION Glomerulonephritis Glomerular injury with evidence of proliferation and inflammation of glomerulus such as leukocyte infiltration, antibody deposition, and complement activation

44. A. DEFINITION Characterized by hypertension, edema, gross hematuria, proteinuria, azotemia Incidence All age groups Greatest frequency in 4-12 years Peak 5-6 years Male:Female 2:1 Seasonal Pattern Winter-Spring: Streptococcal pharyngitis related AGN Summer-Fall: Pyoderma related post strep AGN

45. B. CLASSIFICATION Etiology Post-infectious Bacterial Streptococcus Pneumococcus Staphylococcus Gonococcus Syphilis Viral Measles, mumps, varicella, Inf mononucleosis, CMV, HepB, Coxsackie Non-infectious Clinical Manifestation Primary Renal failure Secondary Systemic diseases (SLE, HSP) Most Common Causative Agent Group A Beta hemolytic streptococcusType 12

46. C. immunopathogenesis Antigen-IgG-C3 complex Antigen-Antibody Immune Response Infiltration of Inflammatory cells Proliferation of glomerular cells Matrix expansion  Basement membrane permeability  Antibody titers Antistreptolysin O Antihyaluronidase DNAse-B Streptokinase  Glomerular filtration surface  Glomerular Filtration Rate Na+ and water retention Oliguria, Hypertension, Edema, Hematuria

47. D. Clinical course Latent Phase (~10 days) Onset of infection to development of clinical disease Strep pharyngitis Strep pyoderma

48. D. Clinical course Oliguric Phase (~7-10 days) Edema (85%) Appears abruptly, most common symptom Periorbital, later generalized Dependent on Severity of glomerular involvement Fluid intake Degree of hypoalbuminemia Resolves in 5-10 days

49. D. Clinical course Oliguric Phase (~7-10 days) Hematuria (30-50%) Dark brown, rusty, cola Disappears within 1-3 wks Microscopic: 1-2wks after initial presentation

50. D. Clinical course Oliguric Phase (~7-10 days) Hypertension (50-90%) Pathogenesis unknown  ECF volume expansion Occurs early, lasts 3-5 days Severe after a brief 2-5 days Magnitude of increase is variable Systolic 200mmHg Diastolic 120mmHg Persistent BP elevation for 1-2 wks Returns to normal within 2-3 wks, persists up to 6 wks

51. D. Clinical course Oliguric Phase (~7-10 days) Other signs and symptoms Anuria Azotemia

52. D. Clinical course Diuretic Phase (7-10 days) Spontaneous voiding Clinical improvement Convalescent Phase (7-10 days) Urinary protein excretion Microscopic hematuria

53. E. Diagnostic work-up Urinalysis High specific gravity High osmolality Low pH Proteinuria rarely exceeds +3 Disappears in first 2-3months or may decrease slowly over 6 months RBC casts  60-85% hospitalized w/ AGN Leukocyturia, hyaline, and granular casts common CBC Anemia (dilutional) may be present

54. E. Diagnostic work-up Serum Chemistries Serum function test BUN, Crea BUN elevated, disproportionate to serum creatine Serum electrolytes Hyponatremia, Hypokalemia

55. E. Diagnostic work-up Immunologic ASO titer Rises over 10-14 days to several wks in 70-80% after strep infection, peak in 3-5 months Slowly decreases in 1-6 months Poor titer following pyoderma AGN titer C3 Depressed in 90-100% patients in first 2wks of illness (Although not always low) Normal in 3-8 weeks Persistent levels suggest ongoing, chronic process

56. E. Diagnostic work-up Radiologic KUB Ultrasound Prominent pyramids Echogenic cortex No detectable architecture Chest Xray “sunburst” pattern

57. F. Confirmatory investigation Bacteriologic demonstration of group A ß hemolytic strep on throat and skin Serology High ASO titers  Bacteriologic Anti-DNAseHyaluronidase  Pyoderma Streptozyme test  100% Confirmatory of Strep Depressed C3

58. F. Confirmatory investigation Kidney Biopsy Atypical presentation Absence of infection prior to onset Absence of serologic evidence of streptococcal etiology Absence of depression of serum complement or C3 Early clinical course Anuria Presence of nephrotic syndrome Azotemia out of proportion to other clinical findings

59. F. Confirmatory investigation Kidney Biopsy Miscellaneous Age <2 yrs and >12 yrs Prior history of renal disease

60. F. Confirmatory investigation Delay in Resolution Early Oliguria + Azotemia >2 wks HPN >3 yrs Gross hematuria >3 wks C3 persistently depressed >6wks Late Proteinuria + hematuria > 6 mos. Proteinuria > 6 months Hematuria > 12 mos.

61. G. Treatment Supportive Low salt diet, Fluid restriction BSA + ½ of the UO if on Furosemide or 20-30ml/kg/BW Indications for Hospitalization Edematous Hypertension Oliguric w/ Azotemia S/Sx of Congestion

62. G. Treatment Medications Uncomplicated (80%) Diuretics Furosemide (0.5-1mkd, max 8-15mg) Antihypertensive beta-blockers Hydralazine (0.15-0.30mg/kg) Propanolol (1mkday every 6-12 hours)

63. G. Treatment Medications Complicated HPN Encephalopathy HTN severe + Nervous System dysfunction Headache, vomiting, depressed sensorium, confusion, visual disturbances, Aphasia, memory loss, coma, convulsion Anti-convulsants (Diazepam, Phenobarbital) Anti-hypertensive CHF Dyspnea, orthopnea, cough, rales often IV furosemide Careful digitalization Phlebotomy

64. G. Treatment Medications Complicated Acute Renal Failure IV Furosemide Peritoneal dialysis Other medications Pen G 100,000 ‘U’ for PSAGN 7-10 days

65. H. Indications for referral Atypical presentation – massive proteinuria Systemic signs Complications

66. I. Prognosis Prognosis for complete recovery from AGN in children is excellent (80-90%). Recovery without any measurable renal abnormality is expected Clinical recovery at 1 month Gross hematuria – 1-2 wks Microscopic hematuria – 6months to 1 year Serologic tests C3 – 8-12 wks Biopsy Histologic resolution – 1-2 years

67. I. Prevention Early treatment does not eliminate risk of GN Family members should be cultured for Grp A ß hemolytic strep and treated if culture positive

68. Case presentation DOROMAL 13 August 2010