UROLOGIC DISORDER Clinical evaluation of a child with;

HEMATURIA definition: presence of at least intact 5 RBCs/PHF in 10ml of freshly voided centrifuged urine causes: * colour change of urine varies from smoky to red, with naked eye according to RBC contents - fever & exercise RBC excretion in urine - colour of urine could be changed dt other causes other than hematuria Heme-POSITIVE urine - Without RBC - Caused by either the presence of hemoglobin (favism) or myoglobin Heme-NEGATIVE urine Red/cola-colored/burgundy urine in ingestion of various drugs, food or food dye Dark brown (or black) - by various urinary metabolites Transient proteinuria +ve dipstick for the 1st time normal values on repeated measurement causes : - temp >38.3oC - exercise - dehydration - cold exposure - HF - seizures - stress does NOT exceed 2+ with dipstick NO evaluation/ therapy needed PROTEINURIA - demonstration by urine analysis Urine boiling Dipstick test test - bed side - rough qualitative + diagnostic test semi-quatitative - rough qualitative -ve trace 1+ 2+ 3+ 4+ 10-20 mg/dl 30 mg/dl 100 mg/dl 300 mg/dl 1000-2000 mg/dl Spot urine protein/creatinine ratio (UPr/Cr) - quantitative - in persistent proteinuria
st

Timed (24hr) urine collection - upper limit of normal protein excretion in a healthy children :

- best performed in 1 morning voided urine specimen normal excretion <2y/o 2y/o <0.5 <0.2 nephrotic-range: >3

normal protein excretion abnormal nephrotic range

4 mg/m2/hr 4-40 2 mg/m /hr > 40 2 mg/m /hr

Classification according to the source of hematuria Glomerular Extra-glomerular colour Brown/cola-coloured/burgundy Gross hematuria (red), urine terminal hematuria, blood clots proteinuria >100mg/dl by dipstick <100mg/dl by dipstick microscopic - RBC cast findings - deformed urinary RBC - normal urinary RBC DDx: Glomerular Isolated Multisystem - Post infectious - SLE glomerulonephritis - HUS - IgA nephropathy - HSP - Alport syndrome - Thin glomerular BM disease Extra-glomerular URT LRT - hydronephrosis - cystitis - pyelonephritis - urethritis - PCK - urolithiasis - tumor - trauma - coagulopathy -heavy exercise

Orthostatic proteinuria Supine = normal protein excretion Upright = up to 10 folds, up to 1000mg/24hr most common cause of persistent proteinuria in school age- children & adolescent NO hematuria, HTN, hypoalbuminemia, edema, renal dysfx *If hematura + UPr/Ucr >0.2 need referral NO further evaluation, just reassurance to parents

Fixed proteinuria significant proteinuria on 1st morning sample on 3 consecutive days (> 1+ on dipstick OR UPr/UCr ratio >0.2) - indicates renal disease Glomerular Extra glomerular proteinuria proteinuria dt permeability of dt tubulointerstitial glomerular capillary compartment involvement wall glomerular low grade proteinuria proteinuria - UPr/Cr < 1.0 <1g to >30g /24hr causes: - MCGN - PSAGN - MGN/MPGN - HSP initial evaluation : - serum Cr/electrolyte st - 1 morning UPr/Cr ratio - Serum albumin - C3 level

Incidence Etiology

Post-Strep Acute Glomerulonephritis (PSAGN) - most common in children aged 5-12 yrs - uncommon before age of 3 years - follows infection of throat/skin by certain nephritogenic strains of group A Bhemolytic strep - Immune-complex mediated Typical pt develops acute nephritic syndrome; i) 1-2 wks after an antecedent strep. pharyngitis, or ii) 3-6 wks after strep. pyoderma Severity of CP depends on the extent of parenchymal renal involvement. They may be presented with: 1) Asymptomatic PSAGN - only with asymptomatic microscopic hematuria 2) Classical NEPHRITIC TRIAD : sudden onset of EDEMA Mild (eye & face puffiness) to moderate edema of extremities) - dt GFR salt & water retention GROSS Smoky/red/tea/cola colored urine HEMATURIA + oliguria HTN - dt GFR salt & water retention hypervolaemia - usually mild & asymptomatic - severe HTN headache - diastolic > 110mmHg HTN encephalopathy - may be accompanied by non-specific symptoms ; fever, malaise, lethargy and abdominal/flank pain 3) by COMPLICATION(S) Hypertensive Irritability, vomiting, blurry vision, altered sensorium, encephalopathy convulsion - 10% of cases HF & pulmonary Early: tachypnea, tachycardia, enlarged tender liver edema Late: dyspnea, orthopnea, basal crepitation, galloping heart * GFR severe salt & water retention hypervolaemia + HTN cardiac decompensation + pulmonary edema ARF Early : appear well Late : severe oliguria, vomiting, anaemia, may pass to coma, convulsion

C/P

Minimal Changes Nephrotic syndrome - Commonest type of NS - between 2-6 y/o, male:female ratio = 2:1 glomerular basement membrane permeability proteinuria hypoproteinemia plasma oncotic pressure fluid shifts from vascular to interstitial compartment effective blood volume stimulation of RAAS system (salt reabsorption) + stimulation of ADH ( water reabsorption) edema Characteristics : - TETRAD of : EDEMA + PROTEINURIA + HYPOPROTEINEMIA + HYPERCHOLESTEROLEMIA - ABSENCE of nephritic manifestation = hematuria + HTN + RF + hypocomplementemia - Good response to steroid Pathology: - glomeruli appear normal on LM - finding in IF microscopy are typically negative - EM reveals shortening of epithelial cell foot processes - initial episodes & subsequent relapse may follow minor infections - common symptoms : anorexia, irritability, abdominal pain, diarrhea - uncommon symptoms : HTN, gross hematuria EDEMA (dt hypoproteinemia) - usually present with mild edema, initially noted around the eyes and lower limb - with times, become generalized + development of ascites, pleural effusion + scrotal edema Fever + ascites suspect peritonitis ! (do ascitic culture) Complications: 1. susceptibility to infections why more susuceptible? common organism most common sites - immunity ( dt loss of Igs & - strep. Pneumonia - spontanoues bacterial T-cell dysfx) (commonest!) peritonitis (SBP) - edema fluid is a good culture - gram -ve organism - sepsis medium - pneumonia - malnutrition - cellulitis - immunosuppressive therapy - urinary TI Manifestation of infections during steroid therapy - fever + physical findings are minimal need HIGH suspicion index + PROMPT evaluation (including culture of blood & peritoneal fluid) + EARLY initiation of antibiotic therapy! 2. Thromboembolic complications, dt - prothrombotic factor - fibrinolytic factor

Most common site: renal vein

Lab findings Urinary changes

PSAGN volume: oliguria color : normal/gross hematuria mild to moderate proteinuria microscopic : PMNL + red cell cast + granular cast

MCNS volume: normal/ appearance: clear, if boiled turbidity. (dt protein coagulation) that does not disappear on acidification with acetic acid (unlike phosphate) proteinuria: - urinary protein excretion >40mg/m2/hr - PrCr Ratio in random urine sample >2.0/ 3.0 or 3+/4+ by dipstick microscopic : hyaline casts + transient microscopic hematuria normal complement C3 & C4 serum albumin <2.5g/dl serum cholesterol : , serum TG Renal Fx: - blood urea maybe slightly dt renal perfusion (hypovolaemia) - normal/ slightly 1. other causes of edema - allergic, nutritional, hepatic, cardiac causes 2. other cause of nephrotic range proteinuria 3. PSAGN, hematuria, HTN, impairment of renal fx, low C3

Serum & blood

Others

C3 (formation of immune complex) blood urea serum creatinine Evidence of GABHS infection: - ASO titer

DDx

1. other causes of hematuria - IgA nephropathy, benign familial hematuria, SLE, HUS, HSP, non-minimal change NS, trauma, stone, exercise, infection 2. other causes of edema + proteinuria - minimal changes NS 3. other typed of GN - in PASGN, +ve evidence of GABHS infection + C3 - complete recovery : 95 % of cases - avoidance of mortality in acute stages by proper management of the complications (ARF, HF, HTN) - recurrence : RARE NO specific treatment! 1. Hospitalization and monitoring BP, body weight, UOP, RFx. 2. Restriction of activity : no need except in ARF or RF 3. Diet : no restriction except in acute oliguric phase (1-2 wks), HTN, HF, RF (restrict protein, sodium, potassium and fluid) 4. Rx of strep. Infection : single dose long acting penicillin IM limit the spread of nephritogenic strain to other person Prevention: 1. Early systemic antibiotic therapy for strep.infection of throat & skin infection does NOT limit the risk of GN 2. Family member of pt w PSAGN should be cultures for GABHS and treated if culture is positive

Prognosis

prognosis of steroid-responsive MCNS: - repeated relapses which usually resolves by the end of 2nd decade - NO residual renal dysfx Principal lines of treatment: i) reduce edema ii) specific therapy with prednisone 1. Hospitalization, investigation & exclusion of contraindication of steroids - physical exam to exclude infection - tuberculin test, CXR, urine culture - monitoring body weight, BP, urine volume & proteinuria 2. Physical activity : NOT restricted, as tolerated by the child 3. Diet & fluids: Salt: DO NOT add salt to diet until edema resolves Water : moderate restriction with hypoproteinemia

Rx

Treatment: 1. Hospitalization & monitoring body weight, BP, UOP & RFx 2. Restriction of activity - NOT needed except in ARF/HF 3. Diet NO restriction except in acute oliguric phase/HTN/HF/RF (where protein + Na + K + fluids are restricted) 4. Treatment of streptococcal Infection - single IM Benzathine penicillin (ONCE) OR procaine penicillin(10days) - to limit the spread of nephritogenic strain to others, doesnt change the natural history of APSGN Treatment of complications 1. Hypertension Mild HTN diastolic BP <90 mmHg only water & salt restriction Moderate HTN diastolic BP 90-100 mmHg oral anti HTN drugs - diuretics, B-blocker, CCB, ACE inhibitor Severe HTN diastolic BP 100 mmHg + HTN encephalopathy nifedipine/methyldopa/ hydralazine *when BP falls <110 mmHg, oral antiHTN is given (like moderate HTN)

4. Diuretics: should be reversed for pt with severe symptoms (ascites, pleural effusion) and must be closely monitored - furosemide : for marked edema - swollen scrotum may be elevated with pillows to enhance fluid removal by gravity ** overused of diuretics hypovolaemia hypotension iatrogenic shock 5. Specific treatment PREDNISONE - 60mg/m2/day (2mg/kg/day) in a single day or 3 divided daily doses for at least 4-6 consecutive weeks (after 4-6 weeks initial course), PREDNISONE 40mg/m2/day every other day as single dose with breakfast [ALTERNATE DAY THERAPY] - alternate day dose is given for 4-6 weeks then slowly tapered and discontinued over the next 3 months * Relapse (3+ to 4+ dipstick & edema) - DAILY STEROID THERAPY until proteinuria is negative or only trace with dipstick for 3 consecutive days prednisone dose is then changed to ALTERNATE-DAY DOSING for one month and tapered over 1-2 months * Steroid resistant = children who continue to have proteinuria (2+ or greater) after 8 weeks of steroid therapy - diagnostic renal biopsy should be performed

2. HF & pulmonary edema - reduce water & salt intake - treat HTN - diuretics : furosemide -peritoneal dialysis (in refractory period) reduce blood volume 3. ARF