proteinurea & nephrotic syndrome
DESCRIPTION
Lecture - Proteinurea and Nephrotic SyndromeTRANSCRIPT
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Proteinurea &
Nephrotic SyndromeBy
Dr. Muhammad RafiqueAssist. Prof. Paediatrics
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Diagnosis:
1- Urine dipstick
2- Urinary pr./cr. ratio
3- 24 hours urine collection
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Urine dipstick testPositive:• If proteinurea >1+ (30mg/dl) with sp.g.<1.015• ------------------>2+ (100mg/dl) ----------->1.015Less sensitive: . LMWP . Bence Jones Proteins . Gamma globulins (because it mainly detects albumen)
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Urine dipstick test
Classification of Proteinurea:• Negative—No proteins• Traces------10-20 mg/dl• 1+-----------30 mg/dl• 2+-----------100 mg/dl• 3+-----------300 mg/dl• 4+-----------1000-2000 mg/dl
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Urine dipstick test
False Negative: -Diluted urine(sp.g.<1.005) -Diseases in which predominant urinary protein is not albumenFalse Positive: - Concentrated urine - Urine PH>7 - Gross hematurea - Antiseptic contamination
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Urinary protein/creatinine ratio
• First morning voided urine should be tested.• This ratio is age dependent:
< 2years <0.5
>2years <0.2• Nephrotic range ------------ >3
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24 Hour Urine Collection
• Start and stop after voiding.• Normal proteinurea:
<4mg/m2/h or <150mg/d• Abnormal proteinurea:
>4mg/m2/hour• Nephrotic range proteinurea:
>40mg/m2/hour
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Types of protein urea
• Transient protein urea• Postural protein urea• Persistent protein urea
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Transient protein urea
Causes:
High fever, exercise, dehydration, exposure to cold, stress, seizures, heart failure
Note: • Usually does not exceed 2+• It is benign • No need of any evaluation
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Postural Protein urea
• Morning voided urine- absent/traces of protein • Urine pr./cr. <0.2 for 3 consecutive days.• Most common cause :
In(60%) of school age and adolescent children.• In standing position may increase up to 10-folds• Usually asymptomatic• In supine position no or mild only • Usually not exceed 1 g/m2/day • No BP increase,azotemia,odema,hypoalbumenemia
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Persistent protein urea
• In it necessary to R/O postural protein urea• Exact cause unknown.• Possible causes: -altered renal hemodynamic -partial renal vein obstruction.• If persists: -long term follow-up for renal disease detection.
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Fixed Protein urea
• Significant protein urea in first morning voided urine for 3 consecutive days
• >1+ on dipstick • >0.2 Upr./U cr.• It usually indicates renal disease• Classified on the basis of site of origin: - Glomerulous - Tubular
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Glomerular Protein urea
• Due to increase glomerular capillary permeability
• Range is <1g - >30 g/day• It is always selective• Selective protein urea:
-Excretory protein molecular wt.<albumen.• Non selective pritein urea:
-Excretary protein, molecular wt.>albumen
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Glomerular Protein urea
Suspect if : - U pr./ Ucr. Ratio>1.0 - Associated with hypertention, azotemia, oedema, hematureaCauses are: FSGS, SCA, PSGN, IgA nephropathy, HSPN, Alport Synd; Obesity related G nephropathy• Evaluation is necessary including renal biopsy
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Tubular protein urea
• MW <albumen, proteins filter- reabsorb• Reabsorption reduce in proximal tubular
injury diseases.• Low MW proteins• <1g/d• Urinary pr./cr. <1.0• Oedema absent• Asymptomatic before detection
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Tubular proteinurea
Causes:
Cystinosis, willson’s disease, Lowe syndrome,
ATN, polycystic K D, reflux nephropathy, • May be associated with:
glucosurea, phosphateurea, NaHCo3
wasting, amino acid urea• D/D between glomerular and tubular cause by
urine electrophoresis is possible.
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Nephrotic Syndrome
• Incidence : 2-3/100,000 children /year• 15 times more common in children.• Characterized by:
-Heavy protein urea >40mg/m2/hour
-Hypoalbumenemia <2.5 g/dl
-Oedema
-Hypercholesterolemia/hyperlipidemia>200mg/dl
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Periorbital oedema in nephrotic Syndrome
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Classification of Nephrotic Syndrome
1. Idiopathic: (90%) -Minimal change 85% (95 % respond to steroids) -Mesengial proliferative 5%(50% respond to steroids) -FSGS10% (20% respond to steroids)2. Secondary: (10%) -Membranous nephropathy -Membranoproliferative glomerulonephritis3. Congenital
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Pathophysiology of MCNS
• Increase G. capillary permeability due to:
- loss of – ve charge glycoproteins.• Odema :
- low oncotic pressure ,high aldosterone and ADH• Hyperlipidemia due to:
- more lipoproteins production
- urinary loss of lipase• Hypoproteinemia due to loss of urinary albumen
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Signs/ Symptoms of Idiopathic N S
• Periorbital oedema - marked in the morning.• Pedal (lower limbs) oedema• Ascites and pleural effusion• Genetal (labial/scrotal) oedema• Generalised body swelling (anasarca) • Increased BP in few cases(10-20%) • Hematurea in 10% cases
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PROTEINUREA
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MCNS(Lipoid Nephrosis)
• Commonest cause of nephrotic syndrome(70%) • Common in Males M:F 2:1 • Common age 2-7 years• 15 times more common in children• Oedema, annorexia, irritability, abdominal pain,
diarrhoea• Blood pressure is normal• Hypertention and gross hematuea is uncommon
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Diagnosis of MCNS • Urine analysis: Protein urea 3-4+ (selective)• Microscopic hematurea 10-20% • Spot urine, Urinary pr./ cr. >2• 24 h urine collection: >40mg/m2/h protein urea• S. albumen <2.5g/dl• High s. cholesterole & triglyceride >200mg/dl• S. urea, creatinine, C3, C4 levels normal• Renal biopsy E/M fusion of epith.cells foot process• -ve immunoflourescence on microscopy.
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Differential Diagnosis of MCNS
D/D of generalized oedema:• Protein losing enteropathy.• Hepatic failure• Protein energy malnutrion (kwashiorkor)• Acute and chronich glomerulonephritis• Angioedema
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Managemen of MCNS
• Hospitalization for 1st time for Dx./serious cases.• Fluid chart (intake/ output)• I.V. 5% albumen if necessary, 0.5g/kg/dose Q 12h• Diuretics in severe symptoms.
-Chlorthiazoids 10mg/kg/dose Q 12h/ or
- metrolozone 0.1mg/kg/ dose Q 12 h followed by
- furosemide 30 min. later, 1-2mg/kg/dose Q 12h
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Managemen of MCNS
• Diet:
No added salt, fluid restriction if hyponatremia• Steroids therapy• Scrotal support• Other lines of treatment.• Treatment of complications
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Steroids Therapy• 1-8 years pts. Start without renal biopsy• Prednisone 60mg/m2 or 2mg/kg/day in 2-3 DD
with antacids, for at least 6 weeks. • After absence of protein urea/1+ taper to
40mg/m2 on AD single morning dose.• Slowly taper and discontinue in 2-3 months.• If age<1 or >8ys, hypertension, hematurea,
azotemia, hypocomplementemia hypoalbumenemia , do renal biopsy before starting steroids.
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Treatment of Relapse
• Relapse rate mentioned is 60-80%. • It is 30-40% if first episode is treated prolong.• Many children have at least one relapse(3-4+
protein urea with oedema)• Give daily DD steroids until remission(urine
protein traces/- ve for 3 consecutive days) then change to AD dose and taper in 1-2 mo
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NS Definations
Steroid Dependant: Relapse while on AD therapy /within 28 days after stopping steroids.
Frequent Relapser: Respond well to steroids but relapse >4 times in one year.
Steroid Resistant: Persistent protein urea >2+ continues after 8 weeks DD steroid therapy.
-Diagnostic renal biopsy is must. -Mostly FSGS(80%), MCNS(20%), and rarely MP
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Alternate Management Agents
• Indications:
-Steroid Resistant
-Steroid Dependant
-Frequent relapser.• These are:
Pulse steroids, cyclophophosphamide, cyclosporin A, tacrolimus, microphenolate, ACE inhibitors, levamisole and imuron.
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Complication of N S Infection: Increase susceptibility due to -Urinary loss of Ig. and properdon factor B -Defective cell mediated immunity -Immunosuppressive therapy (steroids etc.) -Odematous fluid is a good culture media -Malnutrition• Spontaneous bacterial peritonitis• Strept. Pneumoniae and E-coli are more common• High index of suspicion, early evaluation and Mx.
Including antibiotics is essential.
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Complication of NS---Con.
• During steroid treatment fever and other physiological findings are minimal.
• Vaccines: -Polyvalent pneumococcal: When pts. are in remission and off daily DD steroid therapy. -Varicella: If varicella titer is -ve
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Complication of NS--ContThrombo embolic events:• Risk 2-5% (much less than adults)• Arterial & venous thrombosis, RVT, pulm.
embolism, saggital sinus and A & V catheters thrombosis.
• Risk increased due to :• High level of thrombotic factors (fibrinogen,
thrombocytosis, hemoconcentration)• Low fibrinolytic factos (Urinary loss of antithrombin
III , protein C& S)• Note: Avoid overaggressive diuretics and
indwelling catheters
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Compaclications of NS—Cont.
C V Diseases:• Hyperlipidemia may be a risk factor.• Use of 3-hydroxy 3-methylglutaryl Co-enzyme
A (HMG-CoA) reductase inhibiting drugs to reduce it.
• In MCNS no need because spontaneously reduces
• Needed in familial verities like FSGS etc.
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Prognosis of MCNS
• Steroid responders--Relapses decrease with age – spontaneous cure in 2nd decade of life.
• Rapid response to steroids, if no relapse in 1st 6 months after Dx.- infrequent relapser course
• Counsel parents:• Non heriditary disease, non ch. Renal disease,
no infertility.• In remission consider normal. no restriction of
diet and activity, no test for proteinurea etc.
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Prognosis of N S
• Steroid Resistant like FSGS:• Poor prognosis• Use of cyclophosphamide leads to infertility• Proggressive renal disease- ESRD • Require dialysis/ renal transplant• 30-50 % renal transplant develop recurrence
of NS
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Secondary N S
• Suspect when age <1 & >8 ys, hypertention, hematurea, azotemia, hypocomplementemia &
extra renal S/S like (fever, rash, arthralgia etc.)Causes:• Infections: HBV, HCV, Malaria• Drugs: pencillamine, NSAID, captopril• Systemic diseases: SLE, HSP
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Congenital N S
• Develope with in 3 months of life.• FINNISH type:
Causes:
Congenital infections like HIV, HBV, TORCHS
Treatment: • ACE inhibitors, indomethacin and Unilatemal
nephrectomy etc.• Poor prognosis