Nephrotic Syndrome (NS) Qiang Yao Renal Division, Renji Hospital Shanghai 2nd Medical Universigy

Nephrotic Syndrome (NS)

Qiang Yao

Renal Division, Renji Hospital

Shanghai 2nd Medical Universigy

Diagnosis:

Proteinuria: >3.5g/d Hypoalbuminemia: SAlb <30g/L Edema; Hyperlipidemia.

Pro ++++

Hypoproteinemia

Albumin Immunoglobulins Metal binding proteins Erythropoietin urinary loss Transferrin Complement deficiency Coagulation components

Hyperlipidemia

Hypercholesterolemia Hypertriglyceridemia Low-density lipoproteins (LDL) Very low- density lipoproteins (VLDL)

chemical composition of plasma lipoprotein (%)

CM VLDL LDL HDLprotein 2 10 20 45lipide 98 90 80 55 triglyceride 88 55 8 10

phospholipid 6 20 24 22

cholesterol total 4 15 48 23 free 1 5 8 6 ester 3 10 40 17

lipide/protein 40~50 9 4 1~1.5

Mechanisms of Hyperlipidemia

Increased hepatic synthesis of LDL, VLDL and lipoprotein (a) in response to hypoalbuminemia

Urinary loss of HDL

Enzymatic changes with abnormal lipid biosythesis and degradation

Edema

Lower colloid osmotic pressure?

15mmHg H2O

colloid osmotic pressure 26 mmHg

Edema

Edema

Water and sodium retention?

Does it related with renin-angiotensin-aldosterone system?

How many pathological types causes nephrotic syndrome?

Glomerular diseases that cause NS–-- Minimal Change Glomerulopathy

Epidemiology: It is most common reason of NS in children, a

ccounting for 80-90% of young patients with nephrotic syndrome , while only 20-25% in adults.

There appears to be a male preponderance, especially in children, in whom the male- to- female ratio is 2~3 :1


Pathology No glomerular lesions by lig

ht microscopy No staining with antisera sp

ecific for immunoglobulins or complement components.

Effacement of visceral epithelial cell foot processes


Clinical features: The cardinal clinical feature of minimal chang

e glomerulopathy in children is the relatively abrupt onset of proteinuria and development of the NS.

Hematuria, hypertension and impaired renal function are not common.

Glomerular diseases that cause NS–-- mesangial proliferative GN

Epidemiology: It is a common reason of NS in our country, a

ccounting for 30% of primary nephrotic syndrome, higher than those in western.

Glomerular diseases that cause NS–-- mesangial proliferative GN

Pathology Diffuse proliferation of mes

angial cells and ECM Positive staining with IgA, I

gG, IgM or C3 in mesangial area

Dense deposits in mesangial area

Glomerular diseases that cause NS–-- Mesangial Proliferative GN

Clinical features: 50% has infection before onset of renal disea

se. Non-IgAN: 50% with NS, 70% with hematuria IgAN:15% with NS, almost all with hematuria

Glomerular diseases that cause NS–-- Mesangial Capilary Glomerulonephritis

Epidemiology: It is accounting for 10% of nephrotic syndrom

e patients in our country .


Pathology Severe diffuse proliferation of

mesangial cells and ECM, demonstrating doubling and more complex replication of glomerular basement membranes

Peripheral granular to bandlike staining for C3 and IgG

Dense deposits in mesangial subendothelial area


Clinic feature: 30% has infection before onset of renal disea

se (nephritic syndrome), half of them present as a nephrotic syndrome.

Almost all of patients with hematuria Early onset of impairment of renal function, h

ypertension, anemia Progressive procedure (10 year renal survival

rate was less than 65%)

Glomerular diseases that cause NS–-- Membranous Glomerulopathy

Epidemilology Idiopathic membranous glomerulopathy is the

most common cause for nephrotic syndrome in adults

Glomerular diseases that cause NS–-- Membranous Glomerulopathy

Pathology Subepithelial immune c

omplex; projections of basement membrane; deposits surrounded by basement membrane; thickened basement membrane

IgG and C3 positive staining in capillary

Glomerular diseases that cause NS–--

Membranous Glomerulopathy

Clinic feature: 80% with NS 5-10 years later, renal function declined Renal vein thrombosis is not uncommon (4-

52%)

Glomerular diseases that cause NS–-- Focal Segmental Glomerulosclerosis

Epidemilology Over the past two decades, there has been a

n increased incidence of FSGS, accounting for 10% in our country.

Some cases developed from minimal changes GN.


Pathology It is characterized by fo

cal and segmental glomerular sclerosis

Nonsclerotic glomeruli and segments usually have no staining for immunoglobulins or complement.


Clinic feature: NS With hematuria Hypertension and renal function declining are

common

Diagnosis

Diagnosis:

NS?

Primary or secondary?

Complications?

Differential diagnosis

Primary Secondarychildren minimal change allergic purpura nephritis

Teenager mesangial proliferative FSGS

nephritis

Middle age mesengial capillary SLE LN

nephritis

old age membranous myeloma, amyloidosis

nephropathy

Complications

Infection

malnutrition

loss of immunoglobulins

corticosteroids

Thrombosis

coagulation, coricosteroids, PLT activity

Complications

Acute renal failure( ARF)

Hypoalbuminemia Hypovolemia pre-renal

azotemia

Dyslipidemia

Treatment

Support care Rest in bed; limitation of protein intake(0.8-1.

0g/kg/d); limitation of salt intake (<3g/d)

Diuretic therapy

Diminishing proteinuria: ACEI and ARB

Treatment

Inhibition of inflammation and immune response

Corticosteroid therapy (onset): for children: prednisone 60mg/m2/d for adult: prednisone 1mg/kg/d (<80mg/d) 4-6 weeks later , complete remission of proteinturia

occurs, the dosage then decreased (10% every 1-2 weeks).

Be careful for the side effects of corticosteroid therapy

Patterns of response of cordicosteroids

Prognosis:

Primary responder, no relapse (steroid sensitive)

Primary responder with only one relapse in the first 6 mo after an initial response

Initial steroid response with two or more relapses within 6 mo (frequent relapse)

Initial steroid-induced remission with relapses during tapering of corticosteroid, or within 2 wk after their withdrawal (steroid dependent)

Steroid-induced remission, but no response to a subsequent relapse

No response to treatment (steroid resistant)

Treatment

Cytotoxic drugs with corticosteroid: (for steroid dependent or steroid resistant)Cyclophosphamide (CTX): p.o. or intravenously Side effects: liver injury, inhibition of bone marrow, etc.

Cyclosporine (for those failed responsing to combination of steroid and cyto

toxic drugs)Dose: 5mg/kg/d, bid, p.o.Side effects: renal and liver toxic injury, expensive, etc.

Treatment

Mycophenolate mofetil, MMF (for steroid dependent or steroid resistant)

Dose:1.5-2g/d, bid, p.o. for 3-6 months, maintaining 0.5 year

Treatment

Minimal changes: sensitive to steroids; single drug; reuse when relapse; combined with cytotoxic drugs when resistant or dependent on steroids

Membranous GN: combine steroid with cytotoxic drugs or cyclosporin; avoid using drugs when Scr>354umol/L; for the patients with risks for progressing, otherwise, investigate 6 months (antihypertensive).

Treatment

FSGS: sensitive to steroids in 30-50% of patients; slow response to therapy; steroids therapy (onset) for 3-4 months; if not response until 6 month (resistant), then try cyclosporine.

Mesangial proliferative GN: no evidence show that adults will response to steroids; aspirin

Treatment

Treatment for complications Infection Thrombosis ARF（ HD; cordicosteroids, diuresis, SB） dyslipidemia

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Nephrotic Syndrome (NS) Qiang Yao Renal Division, Renji Hospital Shanghai 2nd Medical Universigy