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Focal Segmental Glomerulosclerosis Workup

  • Author: Sreepada TK Rao, MD, FACP; Chief Editor: Vecihi Batuman, MD, FACP, FASN  more...
Updated: Jun 06, 2016

Laboratory Studies

In patients with focal segmental glomerulosclerosis (FSGS), urinalysis reveals large amounts of protein, along with hyaline and broad waxy casts, whereas red blood cell (RBC) casts are generally absent. Broad casts may be observed in persons with advanced cases. Serum creatinine (SCr) concentration or creatinine clearance (CrCl) is usually within reference ranges in early stages.

In patients with idiopathic FSGS, investigational findings for an underlying etiology are generally negative. Such conditions may include the following:

  • Systemic lupus erythematosus (serum complement C4/C3 levels, antinuclear antibody/anti-DNA titers)
  • Hepatitis B or C infection
  • Vasculitis (antineutrophil cytoplasmic antibody titers, serum protein electrophoresis)

In patients thought to have secondary FSGS, obtain HIV antibody, CD4, and viral load studies; serology for hepatitis B and C; and parvovirus testing. Diagnosis of FSGS in massively obese patients is by excluding other causes. FSGS can be considered in patients with proteinuria on the basis of nephrotic syndrome; however, in young patients with an absence of RBC casts and negative serologic study findings, definitive diagnosis rests on a kidney biopsy.



See the list below:

  • Kidney biopsy is the most definitive way to establish the diagnosis.

Histologic Findings

The characteristic lesion in FSGS is segmental solidification of the glomerular tuft, usually in the perihilar region and sometimes in the peripheral areas, including the tubular pole. In the affected glomeruli, capillaries are segmentally obliterated by accumulation of acellular matrix and hyaline deposits, along with adhesion to the Bowman capsule. Coarsely granular deposits of IgM and C3 are often found in these areas.

Diffuse foot process fusion occurs, predominantly in the sclerotic segments, although partial effacement may be observed overlying normal-appearing lobules. Many morphologic subsets, such as a cellular variant (endocapillary and extracapillary hypercellularity), a collapsing variant (FSGS with mesangial hypercellularity), and FSGS with tip lesions, have been described. Whether these diverse lesions reflect different pathogeneses or can account for the differences in the prognosis in patients with FSGS is unclear.

In HIV-associated FSGS, in addition to collapsing glomerular lesions with microcystic dilatation of renal tubules, electron microscopy of the kidney reveals tubuloreticular inclusions in endothelial and mesangial cells, an indirect marker of viral disease.[4, 5]



The presence of interstitial fibrosis on an initial kidney biopsy specimen is a uniform predictor of poor renal prognosis. The collapsing variant is generally associated with a very rapid loss of renal function.

The level of proteinuria greatly influences the outcome in FSGS. In patients with non-nephritic proteinuria, renal function remains stable and less than 15% progress to ESRD in 10 years. More than 50% of patients with persistent nephritic syndrome develop ESRD in 10 years. In those with massive proteinuria greater than 10-15 g/day, renal functional deterioration is even more rapid (2-3 years). In the early 1980s, before the introduction of antiretroviral drugs, patients with HIV-associated FSGS developed ESRD in less than a year. With the introduction of HAART, the natural history is now dramatically different, including both prevention of nephropathy and preservation of renal function, in those with established disease.



In the early stages of FSGS, ultrasound examination reveals normal or large kidneys with increased echogenicity, suggesting diffuse intrinsic medical renal disease. In patients with advanced renal failure, kidneys are small and shrunken, indicating severe glomerular scarring and interstitial fibrosis. In HIV-associated FSGS, ultrasound generally reveals large echogenic kidneys.

Contributor Information and Disclosures

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, International Society of Nephrology, American Society for Biochemistry and Molecular Biology, American Federation for Medical Research, American Society for Bone and Mineral Research, American Society of Nephrology, American Society of Transplantation, Kentucky Medical Association, National Kidney Foundation, Phi Beta Kappa

Disclosure: Received grant/research funds from Dept of Veterans Affairs for research; Received salary from American Society of Nephrology for asn council position; Received salary from University of Louisville for employment; Received salary from University of Louisville Physicians for employment; Received contract payment from American Physician Institute for Advanced Professional Studies, LLC for independent contractor; Received contract payment from Healthcare Quality Strategies, Inc for independent cont.

Chief Editor

Vecihi Batuman, MD, FACP, FASN Huberwald Professor of Medicine, Section of Nephrology-Hypertension, Tulane University School of Medicine; Chief, Renal Section, Southeast Louisiana Veterans Health Care System

Vecihi Batuman, MD, FACP, FASN is a member of the following medical societies: American College of Physicians, American Society of Hypertension, American Society of Nephrology, International Society of Nephrology

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.


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.

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