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Nephrotic syndrome

BASICS

DESCRIPTION:

A syndrome comprising glomerular proteinuria (3.5 g per 1.73m2 body-surface area/day), hypoalbuminemia,

lipiduria, hypercholesterolemia and edema as a result of a primary renal disease or secondary to another disease

process.

System(s) affected: Renal/Urologic, Endocrine/Metabolic

Genetics: N/AIncidence/Prevalence in USA:

Children - 2:100,000 new cases/year

Adults - 3:100,000 new cases/year

Predominant age:Children - 1.5-6 years (MCD)Adults - all ages (FGS, MGN more common USA; IgG-IgA worldwide)

Predominant sex: Male = Female

SIGNS AND SYMPTOMS:

Fluid retention: abdominal distention, ascites, edema, puffy eyelids, scrotal swelling, weight gain, shortness of

breathAnorexia

HypertensionOliguria

Orthostatic hypotension

Retinal sheen

Skin striae

CAUSES:

Primary renal disease

Fibrillary glomerulopathy (primary)

Focal glomerulonephritisFocal glomerulosclerosis (FGS)

IgA nephropathy

Membranoproliferative glomerulonephritis (MPGN)

Membranous glomerulonephritis (MGN)

Mesangial proliferative glomerulonephritis

Minimal change disease (MCD)

Rapidly progressive glomerulonephritis (RPGN)

Congenital nephrotic syndrome

Secondary renal disease. Associated primary renal disease shown in brackets:

Allergens (snake venoms, antitoxins, poison ivy, insect stings)

Carcinoma (bronchogenic, breast, colon, stomach, kidney) [MGN, etc] Diabetes mellitus (most common)

Erythema multiformeFibrillary glomerulopathy (secondary: amyloid, cryoglobulins, multiple myeloma, chronic lymphocytic

leukemia [CLL]


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Henoch-Schnlein purpura

Heredofamilial (Alport's syndrome, Fabry's disease)

HIV infection

Hodgkin's lymphoma [MCD]

Infections: ventriculoatrial shunt infection, bacterial endocarditis [MPGN], viral (hepatitis B [MPGN,

mesangial, MGN]) other viral (hepatitis C), protozoal and helminthic

LeukemiasLymphomas [MGN]

Non-Hodgkin's lymphomaFocal glomerulosclerosis (reflux nephropathy, heroin abuse, nephron ablation, extensive glomerular

scarring in acute glomerulonephritis, chronic renal allograft rejection, end stage kidney, morbid obesity, a

thromboembolism)

Malignant hypertension

Melanoma

Nephrotoxins and drugs (gold penicillamine, mercury [MGN])Nonsteroidal anti-inflammatory drug induced nephrotic syndrome [MCD] and interstitial nephritis.

Polyarteritis nodosa

Post streptococcal glomerulonephritis [PSGN] - 20% are nephrotic

Sarcoid

Serum sicknessSjgren's syndromeSystemic lupus erythematosus (SLE) [MGN, FGS, focal, mesangial, diffuse, proliferative]

Toxemia ofpregnancy

RISK FACTORS:

Drug addiction (e.g. heroin [FGS])

Hepatitis B and C, HIV, other infections

Immunosuppression

Nephrotoxic drugs

Vesicoureteral reflux (FGS)Cancer (usually MGN, may be nil disease (MCD)

Chronic analgesic abuse

DIAGNOSIS

DIFFERENTIAL DIAGNOSIS:

See Causes.

Is the disease predominantly nephrotic (protein without hematuria) such as MCD or MGN; or predominantly

nephritic (protein plus blood) such as MPGN or FGS?

LABORATORY:Hypoalbuminemia

Hyperlipidemia

Lipiduria

Low complement in some diseases

Azotemia

HypercholesterolemiaIncreased serum beta-globulin

Increased serum IgG

Urine

Proteinuria (> 3 gm/24 hr)

Glycosuria

Hematuria

AminoaciduriaRBC casts


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Granular casts

Proteinuria

Hyaline casts

Fatty casts

Foamy appearance

Drugs that may alter lab results: See descriptionDisorders that may alter lab results: Many

PATHOLOGICAL FINDINGS:

Light microscopy

May see nothing (e.g., MCD)Disease specific: sclerosis (e.g., FGS in diabetes)

Immunofluorescence: Mesangial IgA (Schnlein-Henoch, IgG-IgA nephropathy). Other specific for disease.

Electron microscopy (specific for disease as in sub-epithelial deposits of IgG in MGN)

SPECIAL TESTS:

Complement levels

Antinuclear antibody

Serum protein electrophoresis/quantitative immunoglobulins

Urine immune electrophoresis

Blood cultures

Renal venogram for thrombosis

IMAGING:

X-ray

Ultrasound

CT

MRI or venography for renal vein thrombosis

DIAGNOSTIC PROCEDURES:

History, physical, basic laboratory including electrolytes, renal biopsy with light, immunofluorescence, electron

microscopy for definitive diagnosis

TREATMENT

APPROPRIATE HEALTH CARE:

Outpatient

GENERAL MEASURES:

Treat infections vigorously (especially bacteriuria, endocarditis, peritonitis)

Anticoagulant (heparin and warfarin) if thromboses occur

Vaccines: Pneumococcal, influenza and H. influenzae

Avoid excess sunlight

Avoid nephrotoxic drugs

Judicious use of diuretics

Severe anemia may be treated with erythropoietin

Pneumococcal vaccine

SURGICAL MEASURES:


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N/A

ACTIVITY:

Bedrest as tolerated

DIET:

Normal protein (1 g/kg/day)

Low fat (cholesterol)

Reduced sodium

Liberal potassium (unless hyperkalemic)Supplemental multivitamins and minerals, especially D and iron

Fluid restriction if hyponatremic

Caloric restriction if obese or diabetic

Hypercholesterolemia - low fat soy-protein diet, 7 g protein/kg/day

PATIENT EDUCATION:Printed material for patients: National Kidney Foundation, 30 E. 33rd Street, Suite 1100, NY, NY 10016,

(800)622-9010

"Childhood Nephrotic Syndrome" (Order #02-23NN)

"Diabetes and Kidney Disease" (Order #02-09CP) and "Focal Glomerulosclerosis" (Order #02-28NN)

MEDICATIONS

DRUG(S) OF CHOICE:

Treat underlying disorder (use decision analysis)

For steroid-responsive disease: MCD and FGS

Adults-MCD: prednisone 1.0-1.5 mg/kg/day for 4-6 weeks. After response, continue steroid for 2 additionalweeks, then shift to maintenance dose of 2-3 mg/kg q od for 4 weeks. Taper to zero during the next 4-6 months,

or 120 mg po qod same duration, same period of taper. FGS all adults should receive 3-4 months of

glucocorticoids and a cumulative dose of 6 gm of prednisolone.

Children: prednisone 60 mg/m2 or 2 mg/kg/day orally for 4 weeks. After response, continue steroid for 2

additional weeks, then shift to maintenance dose of 2-3 mg/kg q od for 4 weeks. Taper to zero during the next

four months.

MGN patients with a poor prognosis: persistent, heavy proteinuria > 8 gm/day for > 6 months; elevated serum

creatinine; hypertension; male sex; over age 50 or have a biopsy with sclerosis. Probably benefit from cytotoxic

therapy (chlorambucil or cyclophosphamide [Cytoxan]). For hepatitis B virus glomerular disease - interferon.

There are initial data for the use of cyclosporine.

For edema

Most importantly salt restriction; then judicious thiazide, loop diuretics

If resistant, a combination of loop and distal diluting segment diuretics, e.g., metolazone (Zaroxolyn) aresynergistic

It is possible that furosemide (Lasix) and albumin mixed and given IV may potentiate diuresis (eg, 150 mg

furosemide plus 25 gm human serum albumin). Be wary of possible thromboses (especially renal vein

thrombosis).

Other nephrotic renal diseases: frequently relapsing MCD, RPGN, ?MGN, SLE

Bolus steroids and/or immune suppression (cyclophosphamide, chlorambucil, cyclosporine)

Consultation often required

Hypercholesterolemia

Diet and cholesterol lowering drugs (cholestyramine and/or HMG-CoA reductase inhibitors)

Anticoagulants (heparin, followed by warfarin) for thrombotic events. There is data to suggest prophylactic

oral anticoagulation in all cases of membranous GN (Kid Int. 1994;45:578-585).

Hypocalcemia from vitamin D loss should be treated with oral vitamin D (dihydrotachysterol) 0.2 mg q day

ACE inhibitors to reduce proteinuria even in normotensive patients and to control hypertension if alsopresent. If the patient is intolerant of ACE I, angiotensin II receptor blockers should be utilized.


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Contraindications: See manufacturer's literature

Precautions: See manufacturer's literature

Significant possible interactions: See manufacturer's literature

ALTERNATIVE DRUGS:N/A

FOLLOW UP

PATIENT MONITORING:

Frequent monitoring for azotemia, hypertension, edema, nephrotoxicity, serum cholesterol, weight

PREVENTION/AVOIDANCE:

Avoid causative factors whenever possibleDetect and treat infections vigorously. Infections may involve the common (Pneumococcus) to the unusual

(Strongyloides), especially with immunosuppression.

POSSIBLE COMPLICATIONS:

Low levels of: 25-hydroxycholecalciferol, serum calcium, adrenocortical hormones, thyroid hormones

Hypercoagulability, thrombosisPulmonary emboli

Hyperlipidemia/accelerated cardiovascular disease

Acute renal failure

Progressive renal failure

Renal vein thrombosis

Protein malnutritionInfection

Pleural effusion

Ascites

Iron deficiency (uncommon)

EXPECTED COURSE AND PROGNOSIS:

Varies with specific causes. Complete remission expected if basic disease is treatable (infection, malignancy,

drug-induced). Otherwise may progress to dialysis dependence (e.g., diabetic glomerulosclerosis).

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