Proteinuria and nephrotic syndrome can be diagnosed through urine dipstick testing, urinary protein to creatinine ratio, and 24-hour urine collection. Minimal change nephrotic syndrome is the most common cause of nephrotic syndrome in children and is characterized by heavy proteinuria, hypoalbuminemia, edema, and hyperlipidemia. It is typically treated with steroid therapy, though some children are steroid resistant or dependent. Complications of nephrotic syndrome include increased risk of infection and thromboembolic events.

1. Proteinurea
&
Nephrotic Syndrome
By
Dr. Muhammad Rafique
Assist. Prof. Paediatrics

3. Diagnosis:
1- Urine dipstick
2- Urinary pr./cr. ratio
3- 24 hours urine collection

7. Urine dipstick test
Positive:
• If proteinurea >1+ (30mg/dl) with sp.g.<1.015
• ------------------>2+ (100mg/dl) ----------->1.015
Less sensitive:
. LMWP
. Bence Jones Proteins
. Gamma globulins
(because it mainly detects albumen)

8. 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

9. Urine dipstick test
False Negative:
-Diluted urine(sp.g.<1.005)
-Diseases in which predominant
urinary protein is not albumen
False Positive:
- Concentrated urine
- Urine PH>7
- Gross hematurea
- Antiseptic contamination

10. 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

11. 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

12. Types of protein urea
• Transient protein urea
• Postural protein urea
• Persistent protein urea

13. 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

14. 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

15. 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.

16. 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

17. 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

18. Glomerular Protein urea
Suspect if :
- U pr./ Ucr. Ratio>1.0
- Associated with hypertention, azotemia,
oedema, hematurea
Causes are:
FSGS, SCA, PSGN, IgA nephropathy, HSPN,
Alport Synd; Obesity related G nephropathy
• Evaluation is necessary including renal biopsy

19. 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

20. 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.

21. 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

24. Periorbital oedema in nephrotic
Syndrome

26. 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 glomerulonephritis
3. Congenital

28. 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

29. 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

31. PROTEINUREA

32. 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

33. 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.

34. Differential Diagnosis of MCNS
D/D of generalized oedema:
• Protein losing enteropathy.
• Hepatic failure
• Protein energy malnutrion (kwashiorkor)
• Acute and chronich glomerulonephritis
• Angioedema

35. 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

36. Managemen of MCNS
• Diet:
No added salt, fluid restriction if hyponatremia
• Steroids therapy
• Scrotal support
• Other lines of treatment.
• Treatment of complications

37. 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.

38. 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

40. 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

41. Alternate Management Agents
• Indications:
-Steroid Resistant
-Steroid Dependant
-Frequent relapser.
• These are:
Pulse steroids, cyclophophosphamide,
cyclosporin A, tacrolimus, microphenolate,
ACE inhibitors, levamisole and imuron.

42. 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.

43. 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

44. Complication of NS--Cont
Thrombo 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

45. 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.

46. 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.

47. 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

48. 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

49. 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