BY DR WAQAR MBBS, MRCP ASSISTANT PROFESSOR NEPHROTIC SYNDROME BY DR WAQAR MBBS, MRCP ASSISTANT PROFESSOR

DEFINITION Nephrotic Syndrome is characterised by : Proteinuria( > 3.5g/day).Normal is <100mg/d Hypoalbuminemia Edema Hyperlipidemia

PATHOGENESIS Proteinuria : Glomerular pathology increases its permeability protein lost in the urine Low serum albumin: Due to loss in the urine Edema : Low serum albumin decreases oncotic pressure, so fluid leaks into the interstitium edema occurs. Hyperlipidemia: Due to increased synthesis, and also loss of apoproteins in the urine( apoproteins are lipid carriers in the blood)

COMPARISON Nephrotic Nephritic Heavy proteinuria > 3.5g/d Edema Hypoalbuminemia Hyperlipidemia Usually, no hematuria, no oliguria/uremia HTN +/- Proteinuria less than 2 g/d Usually Oliguria (uremia) HTN ( w/edema) Hematuria

S/S of Nephrotic 1) Edema: * Periorbital * Ankles/ legs * Genitals * Generalised ( anasarca) 2) HTN

Peri-orbital edema in nephrotic

CAUSES OF NEPHROTIC SYNDROME We will discuss : * Glomerular lesions which cause nephrotic syndrome.

GLOMERULOPATHIES CAUSING NEPHROTIC SYNDROME 1) Minimal change disease 2) Membranous nephropathy ( MN) 3) Focal segmental glomerulosclerosis (FSGS) 4) Diabetic nephropathy 5) Deposition disorders Some glomerular lesions can present with mixed nephrotic/nephritic picture.

Minimal Change Disease (MCD) 1) It is the commonest cause of nephrotic syndrome in children ( etiology unknown) 2) In adults, MCD can occur secondary to: * Hodgkin’s disease * Solid tumors

MCD contd Pathology : Fusion of the foot processes of the podocytes ( seen on electron microscopy) Light microscopy is normal No immune deposits seen

Treat of MCD : In children : Highly responsive to steroids * Prednisone for 4-6 wks, then tapered * Can be given again for a relapse In adults: Less response to steroids *Prednisone given for 8-12 wks, then tapered * Can be repeated for a relapse If very frequent relapses, or if steroid failure, give immunosuppressive therapy ( cyclophosphamide, cyclosporin, chlorambucil) Prognosis : V.Good. No end stage renal disease

MEMBRANOUS NEPHROPATHY Commonest cause of nephrotic syndrome in adults. 1) Primary : Idiopathic (no known cause) 2) Secondary: Associated with * SLE *Hepatitis B *Drugs (penicillamine, gold) * Solid organ cancers Pathology (biopsy) * Deposits of IgG & C3( immune deposits) * Thickening of glomerular basement memb- -rane & “spike” formation.

Diagram of membranous nephropathy

M.N. ( spike pattern)

M.N. contd Treatment Good prognosis w/ high rates of recovery Some patients no Rx Rx given if high risk of progression Rx : * Prednisone * Immunosuppressives * Rituximab (new drug)

FOCAL SEGMENTAL GLOMERULOSCLEROSIS Primary Secondary : Associated with HIV, Obesity ( HIV can also cause other glomerulopathies) Pathology: Sclerosis & immune deposits in some glomeruli,not all (so focal) and “parts” of glomeruli affected not the whole(segmental)

FSGS (contd) TREATMENT Steroids: Can be tried but not very good response In case of relapse, cyclophosphamide, cyclosporin (immunosuppressives) Prognosis : Can progress to renal failure (25% pts. at 5 yrs)

WHY IT IS CALLED FOCAL SEGMENTAL WHY IT IS CALLED FOCAL SEGMENTAL? * Focal : Only some glomeruli are affected * Segmental : only parts of the glomerulus are affected, not the whole glomerulus

DIABETIC NEPHROPATHY Most common cause of ESRD Starts w/microalbuminuria (30-300mg of albumin lost in 24 hrs. urine) Progresses to macroalbuminuria finally causes nephrotic syndrome (>3.5g/d) Pathology : * Sclerosis in the glomerulus & mesangium ( Kimmelstein Wilson nodules) * No immune deposits * Thick basement memb.

DM nephropathy (contd) TREATMENT 1) Strict DM control 2) ACE inhibitors ( first choice), or ARBs 3) Annual screening for proteinuria in DM patients. (Dipstix can not detect microalbuminuria, so do microscopic urinalysis) ( ACE inhibitors can slow & even reverse proteinuria)

DIABETIC NEPHROPATHY

DEPOSITION DISEASES Amyloidosis, Light chain deposition disease, multiple myeloma Renal biopsy shows amyloid deposition in amyloidosis, Ig chain deposition in “Light chain deposition disease”. Multiple myeloma causes amyloidosis and so causes nephrotic syndrome Rx: According to the cause

GENERAL Rx OF NEPHROTIC SYNDROME For Edema : a) Salt & water restriction b) Diuretics ( first thiazides, if no response, then furosemide (Lasix) 2) Normal protein diet * Don’t take high protein diet will worsen proteinuria & renal damage * Protein <80g/d

GEN. Rx contd. 3) For proteinuria : * Use ACE inhibitors ( 1st choice) or ARBs ( name 3 common S/E of ACE) 4) For High Cholesterol : ( pts. Wth nephrotic have high cholesterol) * Diet * drugs ( statins) 5) Pneumovac ( vaccine against pneumococci) every 5 yrs,& flu vaccine every yr. HTN : If present, ACE inhibitors will take care of it.

COMPLICATIONS OF NEPHROTIC SYND. 1) Thrombosis Loss of anticoagulant proteins(antithrombin) in the urine causes hypercoagulable state Increased risk of DVT, renal vein thrombosis Treated w/ heparin and then warfarin Prophylaxis is controversial ( some people suggest it in membranous nephropathy because there is high risk of thrombosis in that condition).

Complications (contd) 2) Infections/Sepsis * Due to urinary loss of immunoglobulins * Treat infections aggressively * Common cause of death in nephrotic pts. 3) Increased lipids in the blood

SUMMARIZE Causes of nephrotic syndrome at a glance Minimal Change Disease( primary, Hodg- kin’s, NSAIDs) 2) Membranous nephropathy(primary, SLE, Hep B, malignancies, drugs like gold, penicillamine) 3) FSGS ( HIV) 4) Diabetic Nephropathy 5) Deposition Disorders( amyloidosis, Multiple myeloma)

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