ppt

1. Approach to a child with
protienuria
Dejene L

2. Introduction
 10% of children aged 8-15 yr test positive for
proteinuria by urinary dipstick at some time.
 The urinary dipstick test offers a qualitative
assessment of urinary protein excretion (mainly
albumin).
 The dipstick is reported as
negative, trace (10-20 mg/dL),
1+ (30 mg/dL),
2+ (100 mg/dL),
3+ (300 mg/dL), and
4+ (1000-2000 mg/dL).

3. Intr…
 A dipstick should be considered positive for protein
if:-
 it registers >trace (10-29 mg/dL) in a urine sample in
which the specific gravity is <1.010 OR
 ≥1+ to be considered clinically significant if the
specific gravity is >1.015
 Dipstick reaction offers only a qualitative
measurement of urinary protein excretion.

4. Quantitative measurement of protienuria
1.Upr:Ucr(urine protein to urine creatinine ratio)
 It is best performed on a first morning voided urine
specimen to avoid orthostatic (postural) proteinuria .
 Ratios <0.5 in children <2 yr of age and <0.2 in
children ≥2 yr of age suggest normal protein
excretion.
 A ratio >2 suggests nephrotic-range proteinuria

5. Quantitative…
2. Timed (24-hr) urine collections:-
 offer more precise information regarding UPr
excretion
 normal protein excretion in children is defined as
≤4 mg/m2/hr(<100 mg/m2 per day) or less than
150mg/day.
 abnormal is defined as 4-40 mg/m2/hr;
 nephrotic range is defined as >40 mg/m2/hr (≥1000
mg/m2 per day).

6. Normal protein excretion
 Daily normal protein excretion shouldn’t exceed
150mg/day or 4mg/m2/hr.
 Approximately 1/2 of normal protein excreted is
secreted by tubular epithelium, mostly Tamm-Horsfall
protein (uromodulin) and
 Half of excreted protein is albumin(40%) and low
molecular weight protein.
 The normally low rate of urinary protein excretion is
due to two factors:
1.Restriction of the filtration of proteins across the
glomerular capillary wall
2.Reabsorption of freely filtered LMW proteins (less
than 25,000 Daltons) by the proximal tubule

7. Normal protein excretion
 The glomerular filtration barrier:-
is both size and charge selective,
composed of 3 layers: the fenestrated
endothelium, GBM, and the podocyte foot
processes.
The foot processes are interconnected by bridging
structures, the slit diaphragms, which act as a size
selective filter and
 The GBM restricts molecules based on their ionic
charge

8. Structure of glomerulus

9. Types of protienuria
1.Transient protienuria
2.postural(orthostatic)protienuria
3.Fixed protienuria
1.Transient protienuria
major form of protienuria in children
10 % of children have positive dipstick for protien
but most do have negative result on repeat
dipstickTransient protienuria

10. Transient pro…
 The proteinuria usually does not exceed 1-2+ on the
dipstick.
 No evaluation or therapy is needed for children with
this benign condition.
 The cause is not known.
 Contributing factors:-temperature >38.3 , exercise,
dehydration, cold exposure, heart failure, seizures,
or stress.

11. 2.postural(orthostatic)protienuria
 It is the most common cause of persistent proteinuria
in school-aged children and adolescents(60% of
persistent proteinuria).
 Children are usually asymptomatic, and the condition
is discovered on routine U/A.
 Patients excrete normal or minimally increased
amounts of protein in the flat position and excretion
increases as high as 10 fold (up to 1gm/day) in
supine position.
 The cause of this condition is not known.

12. Postural…
 In children with persistent proteinuria, postural
proteinuria should be ruled out.
let the child completely void before sleep and
collect first void morning urine The absence of
proteinuria (dipstick negative or trace and Upr:Ucr
<0.2) for 3 consecutive days confirms the dx of
orthostatic proteinuria.
 Hematuria, hypertension, hypoalbuminemia, edema,
and renal dysfunction are absent.
 No need for further evaluation as it is a benign
process

13. Fixed proteinuria
 children found to have significant proteinuria on a
first morning urine sample on 3 consecutive days
(>1+ on dipstick or Upr: Ucr>0.2) have fixed
proteinuria.
 Fixed proteinuria indicates renal disease
 Caused by either glomerular or tubular
disorders.
 Glomerular proteinuria results from alterations in the
permeability of any of the 3 layers of the glomerular
capillary wall.

14. Glomerular proteinuria
 Suspect in any patient with a first morning Upr:Ucr
>1.0, or proteinuria of any degree, accompanied by
hypertension, hematuria, edema, or renal
dysfunction.
 Diseases with glomerular proteinuria:-
MCNS, FSGS, mesangial proliferative GN,
membranous nephropathy, membranoproliferative
GN, amyloidosis, diabetic nephropathy, etc

15. Tubular Proteinuria
 Tubular disorder can cause low-grade fixed
proteinuria (Upr:Ucr <1.0).
 Tubular disorder associated with proteinuria:-
Fanconi syndrome, Dent disease,
tubulointerstitial nephritis, Heavy metal
poisoning, etc
 Asymptomatic pts having persistent proteinuria
generally have glomerular rather than tubular
proteinuria.
 Glomerular proteinuria can be differentiated from
tubular by electophoresis showing albumin as major
protein in glomerular disease(not in tubular
proteinuria)

16. Nephrotic syndrome/NS
 Glomerular disease characterized by:-
1) Nephrotic range proteinuria protein excretion
of > 40 mg/m2/hr or a first morning UPr:UCr of >2
2) Hypoalbuminemia (<2.5 g/dL)
3) Hyperlipidemia and
4) Edema

17. Pathophysiology of NS
 Protienuria is mainly due to an increased
permeability of the glomerular capillary wall.
 significant protienuria leads to hypoprotienemia
(mainly Hypoalbuminemia).
 Edema in NS:-
 Mechanism is not completely understood.
1. Massive proteinuria hypoalbuminemia
↓plasma oncotic pressurefluid from
intravascular compartment to the interstitial
space.
2.Reduction in intravascular volume leads to:-

18. Pathophysiology of NS…
a. decreases renal perfusion pressure activating the
RAAS stimulates tubular reabsorption of sodium.
b. release of ADH enhances the reabsorption of
water in the collecting duct.
 serum lipid levels (cholesterol, triglycerides) are
elevated due to:-
a. hypoprotienemiaof generalized hepatic protein
lipstimulates synthesis, including synthesis
oproteins.
b. lipid catabolism is diminished as a result of reduced
plasma levels of lipoprotein lipase

19. Etiology of NS
 IDIOPATHIC NS(90%):-
 Minimal change disease
 Focal segmental glomerulosclerosis
 Membranous nephropathy
 SECONDARY NS(10%):-
 Systemic diseases (SLE, HSP,APSGN, MN
 Malignancy (lymphoma and leukemia)
 Infections (hepatitis, HIV, malaria, Syphilis, toxoplasmosis)
 Drugs (Penicillamine, NSAIDS, heroin , gold etc)
 Immunologic or Allergic Disorders ( Bee sting)
 CONGENITAL NS:-
 primary or secondary

20. Idiopathic NS
 Comprises more than 90% of children with NS
 is associated with primary glomerular disease
without evidence of a specific systemic cause.
 3 histologic subtypes:-
1. Minimal change NS(MCNS) in 85% of cases
2. Mesangial proliferation in 5% of cases.
3. focal segmental glomerulosclerosis (FSGS) in
10% of cases.

21. Clinical manifestation of idiopathic NS
 It is more common in boys than in girls (2 : 1).
 most commonly appears b/n the ages of 2 and 6 yrs(
6 mo through adulthood)
 MCNS is present in 85-90% of patients <6 yr of age
but in only 20-30% of adolescents .
 FSGS is more common in older age groups.
 Most initial and recurrence episodes of idiopathic NS
is preceded by minor infections.

22. Clinical…
 Children usually present with mild edema, initially
noted around the eyes and in the lower
extremities.
 With time, the edema becomes generalized (ascites,
pleural effusions, and genital edema)
 Absence of hypertension and hematuria (important
feature of idiopathic NS)
 MCNS shouldn’t be considered in children <1 yr of
age, a positive family history of NS, presence of
extrarenal findings (e.g., arthritis, rash, anemia),
HTN, acute or chronic renal insufficiency, gross
hematuria

23. Diagnosis
 Urine dipstick shows 3+ or 4+ proteinuria
 A spot Upr:Ucr > 2.0, and urinary protein excretion
exceeds 40 mg/m2/hr.
 Microscopic hematuria in 20% of cases.
 The serum albumin level is <2.5 g/dL.
 serum cholesterol and triglyceride levels are
elevated.
 Serum creatinine and complement levels are
normal.
 renal biopsy is not routinely performed if the patient
fits the standard clinical picture of MCNS.

24. Management of idiopathic NS
 prednisone at a dose of 60 mg/m2/day (maximum
daily dose, 80 mg) in a single daily dose for 4-6
consecutive wk.
 Increased dose of steroids and a prolonged duration
of therapy reduce the risk of relapse.
 After remission, prednisone 40 mg/m2/day given
every other day as a single daily dose for at least
4 wk. Then tapper slowly and stop over 1-2 month.

25. Management…
 Children with first episode of NS and mild to
moderate edema may be managed as outpatients.
 Children with severe symptomatic edema ( large
pleural effusions, ascites, or severe genital
edema) should be hospitalized
salt restriction in addition to predinsolone
elevation of scrotal swelling.
diuretics (furosemide) IV/PO should be used with
caution.
 Slow IV infusion of 25% of albumin in patients with
generalized edema.

26. Important Terms related to NS
 Remission: Urinary protein excretion <4 mg/m²/h; nil
or trace by dipstick on spot sample for 3
consecutive days
 Relapse: Urinary protein excretion >40 mg/m²/h;
> 3+ by dipstick for 3 consecutive days after
remission
 Infrequent relapses: less than 4 relapses in 12
month period.
 Frequent relapses: Two or more relapses in 6
months of initial response; 4 or more relapses in any
12 month period.

27. Important…
 Steroid dependence: relapse while on alternate-
day steroid therapy or within 28 days of completing a
successful course of prednisone therapy(patients
respond while on steroid).
 Steroid resistance: failure to respond to prednisone
therapy within 8 wk of therapy (proteinuria 2+ or
greater).
 Steroid-dependent patients, frequent relapsers, and
steroid-resistant patients are candidates for
alternative therapies( Cyclophosphamide,
Cyclosporine, Levamisole)

28. Complications
1.infection:-due to
-urinary losses of immunoglobulins,
-defective cell-mediated immunity,
- immunosuppressive therapy,
- malnutrition,
- edema or ascites w/h serves as culture
media for bacterial growth.
 Spontaneous bacterial peritonitis(SBP) is the
commonest infection
 Other infection include sepsis, pneumonia, cellulitis,
and UTI

29. Complication…
 S.pneumoniae is the most common organism
causing SBP.
 Also, gram negatives like E.coli are attributed.
 high index of suspicion for bacterial peritonitis and
early initiation of antibiotic therapy is critical.
 Vaccination with pneumococcal vaccine is important
inaddition to routine vaccine.
 Avoid vaccination with live attenuated vaccine

30. Complication…
2. Thromboembolic events(2-5%):-due to
a. Increased prothrombotic factors:- fibrinogen,
thrombocytosis, hemoconcentration, relative
immobilization.
b. Decreased fibrinolytic factors:-urinary losses of
antithrombin III, proteins C and S.
c. Aggressive use of diuretics and indwelling
catheters will exacerbate the condition
 Both arterial and venous thromboses(renal vein
thrombosis, pulmonary embolus, sagittal sinus
thrombosis)
 Prophylactic anticoagulation is not recommended
unless a previous thromboembolic event

31. Complication…
3. Cardiovascular complication:-
 Rare complication in children
 Hyperlipidemia is the major risk for the development
of CV complication
 Patients with persistent NS should be treated with
lipid reducing agents.
4. Progressive renal insufficiency and growth
impairment.

32. Prognosis
 > 95% of children with MCNS respond to
corticosteroid therapy.
 50% of patients with mesangial proliferation and only
20% with FSGS respond to cortico steroid therapy.
 Recurrence after prolonged use of steroid is 30-40%
 Most children with steroid-responsive NS have
repeated relapses but relapse decreases as the child
grows.
 Children with steroid-resistant NS,(mainly FSGS)
generally have a much poorer prognosis.

33. Secondary NS
 NS can occur as a secondary feature of many forms
of glomerular disease.
 Secondary NS should be suspected in patients
>8 yr and those with HTN, hematuria, renal
dysfunction, extrarenal symptoms (rash,
arthralgias, fever) or depressed serum
complement levels.
 The main part of management of secondary NS is
treatment of underlying causes.

34. Causes of secondary NS
a) Glomerular and systemic disease:-
Membranous nephropathy, membranoproliferative
glomerulonephritis, postinfectious
glomerulonephritis,
lupus nephritis
Henoch-Schonlein purpura nephritis
b) Infectious agents:-
malaria, schistosomiasis, hepatitis B and C,
Syphilis, Toxoplasmosis, HIV, leprosy

35. Causes…
c) Drugs:-
Penicillamine, Gold, NSAIDs, Interferon, Mercury,
Heroin, Lithium
d) Malignancies:-
Lymphoma, Leukemia

36. Congenital and infantile NS
 Congenital NS:- is NS that manifests at birth or
during the first 3 months of life
 Infantile NS:- is NS occurring during infany period
after 3 months of life.
 The causes can be primary or secondary.
 Primary congenital NS is due to a variety of
syndromes inherited as autosomal recessive
disorders.
Finnish-type congenital NS
Focal segmental glomerulosclerosis
Diffuse mesangial sclerosis
Denys-Drash syndrome

37. Finnish-type congenital NS
 caused by mutations in the NPHS1 or NPHS2
genes, which encode nephrin and podocin, critical
components of the slit diaphragm.
 Affected infants most commonly present at birth
with edema due to massive proteinuria.
 Severe hypoalbuminemia, hyperlipidemia, and
hypogammaglobulinemia result from loss of filtering
selectivity at the glomerular filtration barrier.
 Patients carry poor prognosis

38. Secondary congenital NS
 Occurs due to many etiologies
in utero infection with CMV, toxo, syphilis, hepatitis
B and C, HIV, malaria
 infantile systemic lupus erythematosus
drug exposure(toxins, mercury)
hemolytic uremic syndrome
 can resolve with treatment of the underlying cause.