Nephrotic Syndrome

dr Putra Hendra SpPD

UNIBA
 Diseases of the kidney
Glomeruli Urinary obstruction
Glomerulonephritis
 Stones
Primary
Secondary  Hydronephrosis
Chronic
Tubulointerstitium
Acute tubular necrosis
Cystic diseases of the
Pyelonephritis kidney
Acute
chronic
Vessels Tumors
Nephrosclerosis
Benign
Malignant
Glomerular disease
 Primary
 Minimal change GN
 Membranous GN
 Focal segmental GS
 Membranoproliferative GN
 Diffuse proliferative GN
 Crescentic GN
 Seconday
 SLE, DM, Amyloidosis, Goodpasture, vasculitis
 Hereditary
 Albort syndrome
 Appoach To Proteinuria
 Pengeluaran normal protein melalui ginjal:
< 150mg / day protein
 < 30mg / day albumin
EVALUATION OF THE PATIENT
WITH PROTEINURIA
 Protein

 Adanya protein (proteinuria) I merupakan petunjuk

adanya renal disease.
 False negatives dapat terjadi pada urine alkaline atau
pengenceran urine atau primary protein bukan
albumin.
 Protein in urine
 Dalam keadaan normal
Qualitative method: negative
Quantitative method: less than 150mg of
protein in 24 hours
 Proteinuria---more than 150mg proteins in
urine in 24 hours or qualitative test is (+)
 Urine dipstick measures negatively charged
proteins only = albumin
Proteinuria quantification
heavy proteinuria----＞ 4.0g/24 hours
moderate proteinuria----1.0~4.0g/24 hours
minimal proteinuria----＜1.0g/24 hours
 Proteins in “Normal” Urine
Protein % of Total Daily Maximum

Albumin 40% 60 mg
Tamm-Horsfall 40% 60 mg
Immunoglobulins 12% 24 mg
Secretory IgA 3% 6 mg
Other: 5% 10 mg
Haptoglobin, transferrin, B2 microglobulin
TOTAL 100% 150 mg
 Proteinuria
 benign (<1g/day, age < 30, fever, cold, exercise,
CCF, seizures, postural)
 importance of abnormal proteinuria:
- marker of intrinsic renal disease
- prognostic factor for progression of renal
insufficiency
- risk factor for CV mortality
- treatment target in CKD
 microalbuminuria 30-300 mg/day
 Proteinuria 2
Pathophysiology
 glomerular (terutama albumin),
 tubular (beta2microglobulin),
 overflow (light chains in myeloma),
 secretory (tumour, inflammation)
Quantity
 Mild < 1,0 g/day
 Significant 1,0 – 3,5 g/day (probably
glomerular)
 Nephrotic range > 3,5 g/day (probably
glomerular)
 Glomerular barrier
tubule

• Normally, the larger proteins are excluded at

the glomerular barrier

• Smaller proteins can pass, but are mostly

reabsorbed
 Mechanisms of Proteinuria
 Glomerular Dysfunction
 Leakage of large proteins through glomerular
membrane and podocytes
 Transient
 Fever
 Exercise
 Congestive Heart Failure
 Persistant
 Glomerular Disease
 2. Glomerular proteinuria

 Kenaikan filtrasi macromolecules

“Kebocoran” glomerular capillary barrier
memudahkan albumin (kadang2 globulin)
melewati Bowman’s space
 Dapat diakibatkan oleh
 glomerular disease (acute glomerulonephritis)
 nonpathologic conditions : demam, intensive
exercise, and orthostatic (or postural)
proteinuria
o tubular function is normal
 Kebocoran Glomerular barrier

tubule

• proteins besar dapat melewati

glomerular barrier yang abnormal
 Mechanisms of Proteinuria
 Tubular Dysfunction
 Inability of renal tubules to reabsorb small
filtered proteins
 Specific transporter dysfunction
 Misal Fanconi’s syndrome
 Generalized tubular dysfunction
 Progressive chronic renal failure
 Interstitial Disease
 Tubular proteinuria
 Results from increased excretion of low
molecular weight proteins such as beta-2-
microglobulin, alpha-1-microglobulin, and
retinol-binding protein
 Penyakit Tubulointerstitial  excresi proteins
kecil ↑
 tubule

Malfunctioning tubules unable to reabsorb the smaller

proteins filtered at the glomerulus
 Overflow
 Increased filtered protein load
 Overwhelms ability of kidney to reabsorb
protein  terdapat pada

 GFR↑ (mild proteinuria)

 Pregnancy, fever
o filtered protein↑
 Myeloma
 Glomerular barrier

tubule

• Filtered load of proteins exceeds the tubular

reabsorption rate (similar to glucosuria in
hyperglycemia)
 proteinuria>150mg/24hr

Proteinuria analysis

glomerular tubular overflow secretory

>1.5g/24hr <1.5g/24hr immunoglobulin

Selective Non Β2-micro Bence Jones

Selective globulin protein
(albumin)
(mixture)
Infection myeloma
toxicity
 Nephrotic syndrome
= clinical complex consisting of:

 Proteinuria of >3.5g / 1.73m2 / 24 hours

 Hypoalbuminaemia
 Oedema
 Hyperlipidaemia
 Lipiduria
 Hypercoagulability
 NEPHROTIC SYNDROME:
Clinical manifestations
 Decreased oncotic pressure: loss of serum
protein:
 Intravascular volume depletion with syncope, shock
and acute renal failure
 Activation of renin-angiotensin-aldosterone system
 Activation of sympathetic nervous system
 Increased secretion of vasopressin
 Hyperlipidemia: Increases hepatic VLDL production
 Loss of other plasma proteins:
 Increased susceptibility to infection
 Hypercoagulability
 Vitamin D deficiency: loss of Vit D binding protein
 Altered thyroxine binding protein/thyroid tests
Causes of Proteinuria

Functional Renal
- Severe muscular exertion - Glomerulonephritis
- Pregnancy - Nephrotic syndrome
- Orthostatic proteinuria - Renal tumor or infection
- Febrile

Pre-Renal Post-Renal
- Fever - Cystitis
- Renal hypoxia - Urethritis or prostatitis
- Hypertension - Contamination with vaginal
secretions
Table 2 CAUSES OF THE NEPHROTIC SYNDROME
Metabolic albumin turnover in healthy
subjects vs. subjects with nephrotic
syndrome.
Diagram showing pathogenetic factors leading to hypercoagulability,
tromboembolism and renal vein thrombosis.
How many pathological types
causes nephrotic syndrome?
 Complications of
Nephrotic Syndrome

 Edema
 Hypoalbuminemia
 Hyperlipidemia (Cholesterolemia)
 Hypercoaguability – loss of AT III,
protein S,C
 IgG deficiency – decreased immunity
 Differential Diagnosis
 Transient proteinuria
 Orthostatic proteinuria
 Persistent proteinuria
 Hypertensive nephrosclerosis
 Ischemic renal disease/renal artery
stenosis
 nephritis
 Infeksi saluran kencing
 Transient Proteinuria
 Paling sering
 Proteinuria dengan penyebab non-renal :
fever, exercise berat , CHF, kejang,
kehamilan, emotional stress, hypovolemia,
extreme cold, pemberian epinephrine ,
abdominal surgery, CHF
 Normal kembali bila kondisi normal.
 Intermittent proteinuria: no clear
etiology, benign condition with excellent
prognosis.
 ORTHOSTATIC PROTEINURIA

 protein excretion ↑ pada posisi berdiri

dibanding tidur.
 Biasanya Proteinuria tidak lebih dari 1-1.5
gm/day
 Mechanism diduga permeabilitas
glomerular ↑ dan renal plasma flow ↓
 Management
Supportive Care
 Edema: Cause of significant morbidity.
Rx--diuretics, sodium restriction.
 Thromboembolism in nephrotic syndrome:
Prophylactic anticoagulation not
recommended.
 Infection: may have low Ig levels,
defective cell-mediated immunity.
Consider Pneumovax.
 Recommendations
Non-specific Treatment
 BP control: < 130/80 for nondiabetics,
< 125/75 for diabetics.
 Maximization of ACE inhibitors/AII receptor
antagonists and non-dihydropyridine
calcium-channel blockers as tolerated.
 Lipid control: TChol < 200, LDL < 100
with HMG Co-A reductase inhibitors.
 Glycemic control for diabetics: A1C < 7%.
Corticosteroid therapy
Short-course therapy:
Prednisone 2mg/(kg·day) or
60mg/m2/day (Max.60mg/day)
in 3 or 4 divided doses for 4wk
→maintenance treatment:
After maintenance treatment:
Prednisone 2mg/kg , single dose for
every-other-day×4wk, tapered
gradually (2.5~5mg/2wk) 
discontinued.
 Management
Specific Therapies
 immunosuppresive agents :
- cyclophosphamid
- chlorambucil
- cyclosporine A
MANAGEMENT OF
PROTEINURIA
 Management
Dietary Protein Restriction
 Experimental data suggests reduced
metabolic load slows progression of
disease.
 Must balance potential benefit of protein
restriction with nutritional status.
 Management
ACE Inhibitors
 Have benefit over and above blood
pressure control.
 Type I Diabetes: Captopril use associated
with slower progression, less proteinuria
without or without co-existing HTN (Lewis
et al, 1993, Viberti et al, 1994)
 Type II Diabetes: Enalapril use associated
with slower progression, less proteinuria.
(Ravid et al, 1993, 1996).
PROGNOSIS OF PERSISTENT
PROTEINURIA
 Prognosis
 Diabetic nephropathy: progression to
ESRD over 10-20 years after onset of
proteinuria.
 Isolated non-nephrotic proteinuria: 20-yr
follow-up shows incidence ~40% renal
insufficiency, ~50% HTN.
 Nephrotic syndrome: variable but poorer
overall prognosis.