Nephrotic Syndrome

Is secondary phenomena that occur when substantial amts of protein are lost in the urine

Characterised by• Proteinuria >3.5g/24hrs(urine may be

frothy)• Hypoalbuminaemia < 30g/L• Oedema & Generalised fluid retention• Hyperlipidaemia• Intravascular volume depletion with

hypotension/expansion with HTN, may occur

Pathogenesis

Excessive permeability of plasma proteins - >> heavy proteinuria

Depletion of plasma proteins , mainly albumin – hypoalbuminaemia

Liver compensates but not successful - >> reversed A:G ratio

Reduced albumin -> decreased colloid oncotic pressure of the blood -> oedema

Increased Lipoprotein synthesis and decreased catabolism by liver ->> Hyperlipidaemia (mainly VLDL and /or LDL)

HDL is also lost in urine when heavy proteinuria occurs

Loss of body proteins (immunoglobulins /complement) -> frequent infection

Loss of anticoagulants antithrombin III , antiplasmin - > thrombotic and embolic phenomenon

Causes

PRIMARY• Minimal change disease• Membranous glomerulonephritis

• Mesangial proliferative glomerulonephritis• Focal & segmental glomerulosclerosis• Mesangiocapillary glomerulonephritis

Causes

Secondary• Infection: Bacteria

endocarditis,Malaria,Syphilis,Hepatitis B,HIV

• Connective tissue diseases: SLE,Rheumatoid arthritis

• Neoplasms: Hodgkin’s lymphoma,Carcinomas,Leukaemias

• Metabolic: DM,Amyloidsis• Drugs & toxins: Captopril,gold,Mercury

The diseases the cause Nephrotic syndrome all affect the glomerulus

Mechanism:

• injury to podocytes

• Changed architecture

Scarring

Deposition of matrix or other elements

Clinical Presentationsfluid retention ->abdominal distention,ascites,edema,puffy eyelids ,scrotal swelling,weight gain,shortness of breath

Anorexia

Hypertension

Oliguria

Orthostatic hypertension

Foamy urine

Periorbital edema

Pitting edema of lower limbs

Investigations

1.Urine analysis:

Protein : creatinine ratio in a spot sample of urine (PCR>100mg/mL - substantial)

proteinuria > 3.5g/L

Estimate 24 hour albumin excretion (ACR>70 mg/ml)

RBC casts and WBC in glomerulonephritis

Urea and creatinine may be elevated <- renal failure

2.Estimate serum cholesterol concentrations

3.Total cholesterol & LDL- cholesterol elevated in most patients. HDL- cholesterol is normal or decreased.

4. Blood sugar & glycosylated hemoglobin tests for diabetes.

5. Hepatitis B and C serology, HIV serology

6. Renal biopsy if cause is not clear especially in an adult patient.

Management

• Treatment of nephrotic syndrome involves three steps:

1.Measures to reduce proteinuria

2.Measures to control complications of nephrotic syndrome

3.Treatment of underlying cause

Measures to reduce proteinuria

• If immunosuppressive drugs and other measures against the underlying cause do not benefit the patient

1.ACE inhibitors -> proteinuria, intraglomerular pressure -> slows rate of progression of renal failure. Prevents development of haemodynamically mediated FSG

2.NSAIDs -> proteinuria

Measures to control complications of nephrotic syndrome

• Oedema -> salt restriction, rest, judicious use of diuretics

• In severe cases -> I.V. salt-poor albumin• Dietary proteins 0.8-1.0g/kg• Vitamin D supplementation• Hyperlipidaemia -> dietary restrictions,

lipid-lowering drugs• Anticoagulants in patients with DVT or

arterial thrombosis

Measures to treat the underlying disease

Minimal Change Disease•Children – corticosteroids (prednisolone 60mg/m2 x 4wks, followed by alternate day prednisolone 35mg/m2 for 4 additional wks)Children responding to steroid treatment in 1st 4 wks – “steroid responsive”, those who relapse on withrawal –” steroid dependent”•Patients with frequent relapses -> cyclophosphamide 2mg/kg/day x 6 wks

Focal and segmental glomerulosclerosis

•Steroids (20-30% cases)

•Cylophosphamide, cyclosporin

Membranous glomerulonephritis

•Spontaneous remission (40%)

•30-40% cases remit and relapse repeatedly

•Rest 10-20% patients develop progressive renal failure -> cyclophosphamide, cyclosporin and chlorambucil in combination with steroids may retard progression