Adult-Gerontology Acute Care Practice Guidelines
Definition
A.Nephrotic syndrome (NS) is a clinical syndrome with specific features of proteinuria and hypoalbuminemia or hypoproteinemia.
B.The National Kidney Foundation defines NS as total urine protein excretion in excess of 3,500 mg/d (equivalent to a total protein-creatinine ratio of >3,000 mg/g), with a decreased serum albumin concentration and edema with or without a decrease in glomerular filtration rate (GFR).
C.The term nephritic syndrome is an outdated term characterized by hematuria with red blood cell casts, hypertension, and edema with or without decreased GFR.
Incidence
A.Annual incidence in adults is three per 100,000 individuals.
B.About 80% to 90% of the NS cases are primary (idiopathic).
1.Membranous nephropathy (MN) is the leading cause of idiopathic NS.
a.MN NS is common in white individuals and focal segmental glomerulosclerosis (FSGS) is more common in black individuals.
b.FSGS NS accounts for about 30% to 35% of NS cases.
2.Minimal change disease (MCD) and immunoglobulin A nephropathy (about 15% of cases) are less frequent.
C.About 10% of NS cases are secondary (due to underlying medical conditions).
1.Systemic lupus erythematosus (SLE).
2.Malignancy.
3.Infections (hepatitis B and C, HIV, and malaria).
4.Diabetic nephropathy.
Pathogenesis
A.Pathogenesis of NS is related to increased glomerular permeability to albumin and other plasma protein as a consequence of a damaged basement membrane.
B.MN is characterized by immune deposits that form at the base of the foot processes of the glomerular visceral epithelial cell or podocyte.
C.FSGS is multifactorial, but the injury to the foot process on the podocytes seem to be the main cause. Mechanisms include a T-cell mediated circulating permeability factor, transforming growth factor (TGF), B-cell mediated matrix synthesis, and genetic podocyte abnormalities.
Predisposing Factors
A.Amyloidosis.
B.Diabetes mellitus.
C.Cryoglobulinemia.
D.Sjögren syndrome.
E.SLE.
F.Carcinoma.
G.Leukemia, lymphoma.
H.Melanoma.
I.Multiple myeloma.
J.Infection (bacterial, protozoan, viral).
K.Allergic reaction to insect stings or bites, antitoxins, position ivy, or oak.
L.Malignant hypertension.
M.Sarcoidosis.
N.Genetic syndromes (e.g., familial FSGS, hereditary nephritis [Alport syndrome]).
Subjective Data
A.Common complaints/symptoms.
1.Progressive lower extremity edema.
2.Significant fluid weight gain.
3.Fatigue.
4.Exertional dyspnea.
B.Common/typical scenario.
1.Periorbital, genital edema.
2.Ascites.
3.Pleural or pericardial effusion.
4.Adults who present with new onset of edema or ascites and do not have the typical dyspnea seen with heart failure or present with cirrhosis.
C.Review of systems.
1.Determine onset and duration of symptoms.
2.Determine if weight change has occurred (normal weight).
a.If weight gain: How much and over what period of time?
3.Ask if any changes in urine output; foamy urine?
4.Identify medication or toxin exposure: Risk factors for HIV or hepatitis and symptoms that could be indicative of other causes for edema (e.g., heart failure).
5.Underlying health conditions such as diabetes, SLE, or other systemic disease.
6.Previous history of NS; if yes, when and, if known, what was the cause and treatment?
Physical Examination
A.Check vital signs, blood pressure, temperature, heart rate, and respirations; obtain body weight.
1.Possible hypertension.
B.Inspect periorbital area, abdomen, and lower extremities assessing for edema or ascites.
C.Auscultate heart, lungs, and abdomen.
D.Palpate abdomen assessing for ascites and lower extremities for edema.
Diagnostic Tests
A.The goal of diagnostic testing is to (a) assess for complications; (b) identify underlying disease; and (c) possibly determine the histological type of idiopathic NS.
B.Serum and urine tests.
1.Serum chemistry panel to evaluate kidney function (blood urea nitrogen [BUN], creatinine, estimated GFR), electrolytes.
2.Assess for acute kidney injury (AKI; see section “Acute Kidney Injury” for specific information).
3.Glucose for diabetes mellitus.
4.Blood count and coagulation panel (abnormal suggestive of bleeding disorder).
5.Serum albumin.
6.Lipid panel to assess for hyperlipidemia.
7.Urine dipstick to confirm proteinuria; protein-to-creatinine ratio from a random (spot) urine sample to evaluate for nephrotic-range proteinuria (24-hour urine collection is cumbersome for patients and the collection is done incorrectly).
a.Early morning specimen is best.
b.Protein-to-creatinine ratio greater than 3.0 to 3.5 mg protein/mg creatinine (300–350 mg/mmol).
c.Spot urine may be inaccurate in person who exercises heavily or someone who is gaining or losing muscle mass.
d.Hematuria or casts are suggestive of nephritis.
C.Additional tests depending on patient presentation.
1.HIV screening.
2.Liver panel; elevated transaminase may indicate viral hepatitis (if abnormal, obtain viral hepatitis panel).
3.Serum or urine protein electrophoresis (amyloidosis or multiple myeloma).
4.Rapid plasma regain to determine if syphilis present.
5.Antinuclear antibodies, anti-double-stranded DNA antibody, and complement values (C3 and C4) if suspect connective tissue disorder.
D.Imaging studies.
1.Chest x-ray: To evaluate for pleural effusion.
2.CT or MRI: Possible to evaluate for neoplastic diseases as secondary cause.
3.Ultrasound.
a.Renal: For reduced GFR.
b.Abdominal to evaluate for ascites.
c.Lower extremity Doppler ultrasound, CT, MRI, or lung ventilation/perfusion scan if suspect thrombosis or pleural effusion.
4.Echocardiography: For suspected heart failure.
E.Renal biopsy.
1.The role of renal biopsy is controversial and there is a lack of evidence-based guidelines. In those with NS from a known secondary cause who are responding to treatment, the renal biopsy will not likely add to the treatment.
2.It may prove beneficial when trying to determine best treatment and prognosis in adults with idiopathic NS of unknown histologic disease type and in those in which the provider is considering underlying SLE as the cause.
Differential Diagnosis
A.Liver disease (e.g., cirrhosis).
B.Heart failure.
C.Differential for AKI in NS.
1.Allergic interstitial nephritis.
2.AKI.
a.Acute tubular necrosis.
b.Prerenal azotemia.
3.Adverse effects from drug therapy.