Background
Definition: Nephrotic syndrome is defined by the presence of peripheral edema, heavy proteinuria (protein excretion greater than 3.5 g/24 hours), and hypoalbuminemia (less than 3 g/dL). In other words, nephrotic syndrome is the triad of edema, proteinuria, and hypoalbuminemia. NS is usually associated with hyperlipidemia.
Proteinuria in Nephrotic syndrome is due to increased filtration of macromolecules across the glomerular capillary wall.
Diagnosis
H&P:
Risk Factors: See secondary causes of nephrotic syndrome.
Complications/manifestations of Nephrotic Syndrome.
Common presentation: The typical patient presents with peripheral edema and fatigue but shows no evidence of heart failure or liver disease on evaluation. Lower extremity edema is the most common presenting symptom of nephrotic syndrome.The edema often causes them to gain weight. Patients may have secondary causes of NS, like diabetes, but not always because most causes of NS are idiopathic.
Causes of Nephrotic Syndrome.
Ddx of peripheral edema.
Diagnostic studies
-First morning urinary protein-to-creatinine ratio from a single urine collection (usually > 3 to 3.5 mg protein/mg creatinine in NS). Approximates 24-hr urine protein without the difficulties and errors in collection. 24-hr urine collection still used for very limited cases.
–Serum albumin measurement.
-Serologic studies: Consider ANA, complement (C3/C4 and total hemolytic complement), serum free light chains, urine protein electrophoresis and immunofixation, syphilis serology (RPR), HIV, HBV and HCV serologies, and the measurement of cryoglobulins.
-Renal biopsy required to establish diagnosis if the cause of NS is unknown.
–CBC, Coagulation studies (PT / INR, PTT)
–CMP: Electrolytes, kidney function (to r/o AKI), liver enzymes (to r/o viral hepatitis), Glucose to r/o DM.
-Lipid panel.
-Consider CXR (if a pleural effusion is suspected), Echo (if HF is suspected), Abdominal U/S (if ascites/liver), Kidney U/S (if eGFR low), viral hepatitis (if liver enzymes elevated).
Treatment
-Sodium restriction (< 3g/day), fluid restriction (<1500 ml/day)
-Loop diuretics,
-ACE-I or ARB to lower the pressure inside the glomeruli,
-Statins for dyslipidemia (lipid d/o in NS resolve when NS is treated).
-Assess and treat complications. E.g. Heparin bridged to Warfarin if VTE.
-No prophylaxis for VTE or infection is recommended.
-Consult nephrology if a biopsy is needed or for assistance with care as needed.
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“The initial evaluation of this patient should include testing for hyperlipidemia. Nephrotic syndrome is associated with an increased risk of deep vein thrombosis but does not cause a coagulopathy. Diabetes mellitus can be a secondary cause of nephrotic syndrome but is not a finding in primary nephrotic syndrome. Relative hypocalcemia may be found in patients with nephrotic syndrome due to low protein, but hypercalcemia is not associated with nephrotic syndrome. Children and patients with relapses of nephrotic syndrome have an increased risk of infection.” ABFM
“This patient has type 2 diabetes mellitus and presents with new-onset edema in her lower extremities, the most common presenting symptom of nephrotic syndrome (NS). Patients with NS may also report foamy urine, exertional dyspnea or fatigue, and significant fluid-associated weight gain. A 24-hour urine collection for protein (not creatinine) can be used to diagnose proteinuria, but the collection process is cumbersome and the specimen is often collected incorrectly. The protein-to-creatinine ratio from a single urine sample is commonly used to diagnose nephrotic-range proteinuria. The role of a renal biopsy in patients with NS is controversial and there are no evidence-based guidelines regarding indications for a biopsy. Renal ultrasonography may be appropriate to assess for underlying conditions and/or disease complications if the glomerular filtration rate is reduced. There is no data to support using MRI in the diagnosis and management of nephrotic syndrome” ABFM critique 2017
References / Further Reading
Kodner C: Diagnosis and management of nephrotic syndrome in adults. Am Fam Physician 2016;93(6):479-485. http://www.aafp.org/afp/2016/0315/p479.html
http://us.bestpractice.bmj.com/best-practice/monograph/875.html Last Accessed October 28, 2017