Diagnostic Considerations

In patients presenting with nephrotic syndrome, distinguishing focal segmental glomerulosclerosis (FSGS) from other glomerular diseases (eg, minimal-change disease, mesangial proliferative glomerulonephritis, membranoproliferative glomerulonephritis, membranous glomerulonephritis) is clinically difficult. Age and race may help guide diagnostic considerations:

In young Black men, FSGS is the commonest cause of nephrotic syndrome.
In young women, nephrotic syndrome may rarely be the initial manifestation of systemic lupus erythematosus (SLE). ^[27]
In young patients, amyloidosis of the kidneys (except in rare familial forms) is very uncommon as a cause of nephrotic syndrome.
Although hematuria is the most common presentation in Whites with IgA nephropathy, nephrotic syndrome and renal insufficiency may also be present.

Serologic studies such as complement C3 and antinuclear antibody (ANA) are helpful to exclude SLE. In patients with FSGS, red blood cell casts are usually not present on urinalysis.

Zhang et al reported that the urinary neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule-1 (KIM-1), N-acetyl-β-d-glucosaminidase (NAG), and retinol-binding protein (RBP) may be useful biomarkers for FSGS. In their study, levels of urinary NGAL, NAG, and RBP were higher in patients with FSGS (n=32) than in patients with minimal change nephrotic syndrome with comparable proteinuria (n=22). A cutoff value of 15.87ng/mL NGAL demonstrated 87.1% sensitivity and 59.1% specificity for the diagnosis of FSGS. Response to immunosuppressive therapy was significantly different in patients with KIM-1, NAG, and RBP levels below and above the cutoff values.^[40]

Other causes of nephrotic syndrome in adults include the following:

Minimal change disease
Membranous glomerulonephritis
IgA nephropathy
Diabetes mellitus
Amyloidosis

Workup

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Author

Sreepada TK Rao, MD, FACP Professor, Department of Medicine, State University of New York Downstate Medical Center

Sreepada TK Rao, MD, FACP is a member of the following medical societies: American Society of Hypertension, International Society of Nephrology, American Society of Nephrology

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Eleanor Lederer, MD, FASN Professor of Medicine, Chief, Nephrology Division, Director, Nephrology Training Program, Director, Metabolic Stone Clinic, Kidney Disease Program, University of Louisville School of Medicine; Consulting Staff, Louisville Veterans Affairs Hospital

Eleanor Lederer, MD, FASN is a member of the following medical societies: American Association for the Advancement of Science, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, International Society of Nephrology, Kentucky Medical Association, National Kidney Foundation

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: American Society of Nephrology<br/>Received income in an amount equal to or greater than $250 from: Healthcare Quality Strategies, Inc.

Chief Editor

Vecihi Batuman, MD, FASN Professor of Medicine, Section of Nephrology-Hypertension, Deming Department of Medicine, Tulane University School of Medicine

Vecihi Batuman, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, Southern Society for Clinical Investigation

Disclosure: Nothing to disclose.

Additional Contributors

Chike Magnus Nzerue, MD, FACP Professor of Medicine, Associate Dean for Clinical Affairs, Meharry Medical College

Chike Magnus Nzerue, MD, FACP is a member of the following medical societies: American Association for the Advancement of Science, American College of Physicians, American College of Physicians-American Society of Internal Medicine, American Society of Nephrology, National Kidney Foundation

Disclosure: Nothing to disclose.

Acknowledgements

Anjana S Soman, MD Staff Physician, Department of Pathology, Quest Diagnostics

Anjana S Soman, MD is a member of the following medical societies: American Society for Clinical Pathology and College of American Pathologists

Disclosure: Nothing to disclose.