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Focal Segmental Glomerulosclerosis Clinical Presentation

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


The natural history of focal segmental glomerulosclerosis (FSGS) varies a great deal. Spontaneous remissions are extremely rare, although the literature contains isolated case reports. A typical course runs from edema that is difficult to manage, to proteinuria that is refractory to corticosteroids[1] and other immunosuppressive agents, to worsening hypertension and a progressive loss of renal function. In nonresponders, the average time from the onset of proteinuria to end-stage renal disease (ESRD is 6-8 years, although wide variations in the time course occur.

The prognosis is much worse in black persons than in whites. In the collapsing form of FSGS, the disease is marked by severe hypertension, more massive proteinuria, a very poor response to corticosteroids, and a much faster rate of progression to ESRD.

In HIV-associated FSGS, the renal functional deterioration is rapid, leading to ESRD within a few weeks to 1 year. Since the introduction of highly active antiretroviral therapy (HAART), however, renal function is well preserved when the viral load decreases. HAART therapy has been shown to prevent the onset of proteinuria in patients with HIV and, in those with established FSGS, to reduce proteinuria, preserve renal function, and prevent the development of ESRD in select cases. With the introduction of screening of pregnant women and early HAART therapy, no cases of HIV-associated nephropathy have been reported in children for more than a decade.[31]



FSGS is considered primary or idiopathic when no etiology can be identified. Secondary FSGS is associated with illicit drug use, HIV and other viral infections,[15] and many diverse factors, such as infections, inflammations, toxins, and intrarenal hemodynamic alterations. See Pathophysiology.


Physical Examination

The most common clinical presenting feature, found in more than 70% of patients, is nephrotic syndrome, which is characterized by generalized edema, massive proteinuria, hypoalbuminemia, and hyperlipidemia. Other causes of nephrotic syndrome in adults include minimal change disease, membranous glomerulonephritis, systemic lupus erythematosus, focal sclerosis, HIV infection,[15] IgA nephropathy, diabetes mellitus, and amyloidosis. In patients with primary (essential) hypertension and analgesic abuse, nephrotic syndrome is not a common manifestation (although hypertension may be observed in patients with nephrotic syndrome from all causes).

Occasionally, routine urinalysis may reveal proteinuria, prompting referral to a nephrologist. Less than a third of patients with FSGS present with nonnephrotic proteinuria along with microscopic hematuria and hypertension. Typically, edema develops over a few weeks, but the onset may be abrupt, with weight gain of 15-20 lb or more. Frequently, the onset of edema follows a recent upper respiratory tract infection.

Pleural effusion and ascites may be present; pericardial effusions are rare. Gross edema may predispose patients to ulcerations and infections in dependent areas (eg, lower extremities). Abdominal pain, a common finding in children, may be a sign of peritonitis. Rarely, xanthomas may be evident in association with severe hyperlipidemia. In many patients, physical examination findings are normal except for generalized or dependent edema.

Severe hypertension (ie, diastolic blood pressure of 120 mm Hg or more) is not uncommon, especially in black patients with renal insufficiency.[3] Rarely, patients experience severe renal failure with signs and symptoms of advanced uremia (eg, nausea, vomiting, bleeding, seizures) or altered mental status.

Patients with FSGS secondary to diseases such as massive obesity, reflux nephropathy, and renal dysplasia/agenesis may present with non-nephritic proteinuria. These patients often experience worsening renal function over a course of months to years.

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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