Nephroticsyndrome

DIAGNOSIS OF NEPHROTIC SYNDROME

Definition of the nephrotic syndrome

The NS is a clinical state characterized by Massive albuminuria and heavy hypoalbuminemia, often associated with edema, hypercholesterolemia, and generalized hyperlipidemia

Changes in Nephrotic Syndrome Glomerular membrane - Normally impermeable to large proteins - Becomes permeable to proteins, especially albumin - Albumin lost in urine (hyperalbuminuria) - Serum albumin decreased (hypoalbuminemia) - Fluid shifts from plasma to interstitial spaces -Hypovolemia -Ascites

Epidemiolog y

Clinical classification of the NS 1. Primary NS : 90% of childhood cases Minimal Change NS (MCNS)  70-80% Focal Segmental Glomerulosclerosis (FSGS) Mesangiocapillary Glomerulonephritis Membranous Nephropathy 2. Secondary NS : as a part of a systemic disease or related to a drug or other toxin

Clinical classification of the NS 1. Congenital, the Finnish type of NS Placenta enlargement Massive edema Genetic mutation on chromosome 19 2. Steroid sensitive NS Steroid responsive : largely of children with MCNS 3. Steroid resistant Steroid nonresponsive : other glomerular diseases (FSGS)

NS - ISKDC Histology Minimal change disease Focal Global GS Focal segmental GS Diffuse Mesangial Hypercellularity Proliferative and Sclerosing GN Membranoproliferative GN Membranous nephropathy Chronic GN Unclassified Total

Patients 363 8 37 9 12 29 6 3 4 471

Prevalence % 83 1.7 7.9 1.9 2.5 6.1 1.2 0.6 0.8 100

Steroid Response % 93.1 75 29.7 55.6 25 6.9 0 0 75 78.1

Diagnosis of the NS 1. Clinical diagnosis Clinical features Clinical laboratories

2. Histopathologic diagnosis Light microscopic  structural changes Immunofluorescence findings Electron-microscopic findings

Clinical diagnosis of NS A child with nephrotic syndrome has these signs: 1. high levels of protein in the urine, a condition called proteinuria 2. low levels of protein in the blood 3. swelling resulting from buildup of salt and water 4. less frequent urination 4. weight gain from excess water

Clinical diagnosis of the NS clinical features ● Edema Accumulates in gravity dependent tissues Puffiness around eyes Anasarca is frequently present ● Pathogenesis of edema 80% of oncotic pressure due to albumin Below 2 gr/dL edema accumulates Intravascular volume depletion Renin-aldosterone activation

Clinical diagnosis of NS clinical features ● Evidence against of the pathogenesis Analbuminemia Steroid induced diuresis Increased intravascular volume Low renin/aldosterone levels

Ascites

Pretibial edema

Genital edema

Clinical diagnosis of the NS Laboratory Features ● Albumin Hypoalbuminemia due to loss via the kidney Urinary excretion Proximal tubular cells catabolism ● Immunoglobulins IgG levels reduced IgM levels elevated IgM-IgG-Switching ●

Clinical diagnosis of NS Laboratory Features ● Hyperlipidemia - hypercholesterolemia ● Hypovolemia is present Not all patients are hypovolemic Hematocrite may be elevated ● Hyponatremia is common ● Plasma creatinine is generally normal

Volume distribution in nephrotic syndrome?

❚*

Hypovolemia is characteristic for the early phases of MCNS (Donckerwolcke 2001 [110 MCNCS]) (underfilled theory)

Hypervolemia is characteristic for secondary nephrotic syndromes (overfilled theory)

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Clinical diagnosis of NS Laboratory Features ● Increased synthesis of cholesterol, triglycerides and lipoproteins ● Decreased catabolism of lipoproteins Decreased activity of lipoprotein lipase Decreased LDL receptor activity Increased urinary loss of HDL Lp(a) levels are elevated

Clinical diagnosis of NS Laboratory Features Proteinuria is the primary abrormality - “Selective”- almost entirely albuminuria > 40 mg/m2/hr or > 50 mg/kg BW/24hs - Urine protein to creatinine ratio Normal : < 0.2 (< 0.15 adolescents) Mild to moderate : 0.2 to 1.0 Heavy or severe : > 1.0 (suspected NS) Unusual to see tubular>proteinuria 2,5 (established NS)

Histopathologic diagnosis of the NS Norma l

MCNS

❚Van den Berg, Weening, Clinical Science (2004) 107, 125–136

Light microscopy of the MCNS

Immunofluorescence Microscopy

Electron Microscopy

Histopathologic diagnosis of the NS

Histopathologic diagnosis of the NS

Histopathologic diagnosis of the NS

For clinical application Clinical diagnosis of the NS is generally based on 1. Edema 2. Massive proteinuria 3. Heavy hypoabuminemia 4. Hypercholesterolemia

Thank you

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