NEPHROTIC SYNDROME

DEFINITION

THE GLOMERULAR FILTRATION BARRIER

Fenestrated Endothelium The endothelial cells have numerous openings, 70 to 100 nm in diameter, termed "fenestrae," Glomerular endothelial cells have a glycocalyx on their surface containing negatively charged sialoproteins and proteoglycans, but there is no direct evidence that the glycocalyx has a role in filtration. Glomerular Basement Membrane The glomerular basement membrane is an acellular matrix with a thickness of 300 to 350 nm that provides structural support for the capillary wall. Its main components are type IV collagen, proteoglycans, laminin The Podocyte Slit Diaphragm The podocyte slit diaphragm has an important and direct role in glomerular filtration.

THE PODOCYTE AND SLIT DIAPHRAGM

The podocyte slit diaphragm has an important and direct role in glomerular filtration. Some of its protein components are involved in the mechanism of proteinuria. These proteins form a complex that contributes to the structure of the slit diaphragm, connects the diaphragm to the intracellular actin cytoskeleton, and participates in signaling related to turnover of the glomerular filter. Most of these proteins are essential for a functional slit diaphragm and glomerular filtration, since mutation or inactivation of the corresponding genes cause proteinuria. The main protein in slit diaphragm are nephrin, neph1 and neph2, podocin, CD2AP

Hereditary Proteinuria Syndromes

Causes of Nephrotic Proteinuria

Incidence of native kidney biopsies

Incidence of native kidney biopsies in Carol Davila Hospital

NGLM IgA 20 16 12 8 4 0 GSFS GNMP NGM GNRP

19 96 19 97 19 98 19 99 20 00 20 01 20 02 20 03 20 04 20 05

Histopathological Features of Some Primary Glomerular Diseases That Can Cause the Nephrotic Syndrome

Pathophysiology of the nephrotic syndrome -Edema

Pathophysiology of the nephrotic syndrome -Edema

Pathophysiology of the nephrotic syndrome -Edema

Pathophysiology of the nephrotic syndrome -Edema

Pathophysiology of the nephrotic syndrome -Edema

Pathophysiology of the nephrotic syndrome -Hyperlipemia

There is a variable increase in the levels of very-low-density lipoprotein (VLDL), intermediate-density lipoprotein (IDL), and low-density lipoprotein (LDL) fractions, resulting in elevated serum cholesterol alone or in simultaneous elevation of serum cholesterol and triglyceride. The high-density lipoprotein (HDL) fraction is usually normal. The lipoprotein classes IDL and LDL tend to be enriched in cholesterol ester. In addition, Lp(a) lipoprotein is increased, irrespective of the apolipoprotein A isoform class, and this increase is reversed after remission of the nephrotic syndrome or after symptomatic antiproteinuric treatment. Two mechanisms contribute to nephrotic dyslipidemia: overproduction and impaired catabolism of apolipoprotein Bcontaining lipoproteins. Decreased catabolism of chylomicrons and VLDL has been documented in the nephrotic syndrome. The fractional catabolic rate of LDL apolipoprotein B is low in patients with hypercholesterolemia alone and high in patients with combined It is probable that abnormal lipoprotein catabolism results, at least in part, from urinary loss of some substance. Increased synthesis of lipoprotein is suggested by several findings. In the liver of nephrotic rats the levels of apolipoproteins and rate-limiting enzymes of lipogenesis and their messenger RNAs were increased, but cholesterol synthesis was not increased in patients with the nephrotic syndrome. The rates of synthesis and turnover of LDL apolipoprotein B were variable, depending on the presence or absence of hypertriglyceridemia.

Pathophysiology of the nephrotic syndrome -Hyperlipemia

Pathophysiology of the nephrotic syndrome -Hyperlipemia

Pathophysiology of the nephrotic syndrome Tromboembolic

Pathophysiology of the nephrotic syndrome Tromboembolic

Pathophysiology of the nephrotic syndrome Tromboembolic

Pathophysiology of the nephrotic syndrome Tromboembolic

Pathophysiology of the nephrotic syndrome Endocrine dysfunction

Pathophysiology of the nephrotic syndrome Endocrine dysfunction

Pathophysiology of the nephrotic syndrome Other consequences

Immune dysfunction
Urinary loss of opsonozing factor Antibody titers trend lower Pneumoccocal and ( pediatric) HiB vaccine

Iron-binding proteins- anemia Loss of albumin as a carrier protein

Non specific therapy of nephrotic syndrome

Non specific therapy of nephrotic syndrome

Non specific therapy of nephrotic syndrome

NSAID ACEI Cyclosporine

Non specific therapy of nephrotic syndrome-ACEI

Therapy of nephrotic syndrom Summary