Focal Segmental Glomerulosclerosis

Original Editors - Jessie O'Donley from Bellarmine University's Pathophysiology of Complex Patient Problems project.

Lead Editors -

Definition/Description

Focal Segmental Glomerulosclerosis (FSGS) is a kidney disease that involves the formation of scar tissue in the glomeruli. “Sclerosis” meaning scarring and “glomerulo-” which are tiny filters that filter circulating blood producing urine as an end-product.[1] When these filters are damaged they become scarred and are no longer able to filter blood appropriately.[2] “Focal” meaning that only some of the filters are damaged while some are normal and “segmental” is included because often only parts of the filters are scarred.[2] <span id="fck_dom_range_temp_1301955815947_461" /><span id="fck_dom_range_temp_1301955815947_204" />

Glomerular damage produces two types of syndromes: the nephrotic syndrome and the nephritic syndrome.[1] The nephrotic syndrome is not a specific kidney disease rather it occurs as a result of any disease that causes damage to the kidney-filtering units.[1] Nephrotic syndrome is commonly associated with proteinuria, protein in the urine, which occurs in diseases such as diabetes, amyloidosis, and membranous glomerulopathy.[1] FSGS is a nephrotic syndrome due to massive amounts of protein found in the urine. The nephritic syndrome is commonly associated with hematuria, blood in the urine, which occurs in diseases such as lupus nephritis, immunoglobulin A (IgA) nephropathy, and acute diffuse proliferative glomerulonephritis.[1]

Prevalence

Typically, idiopathic FSGS is observed in people the age of 18-45 years, although no age group is free from the disease. In children, FSGS is found in 7-10% of renal biopsies.[3] In adults, the lesion is more common in men and is observed in 20-30% of patients with nephrotic syndrome.[3] FSGS is 3-7 times higher in young African American males when compared to Caucasian males.[3] The annual incidence of FSGS in patients aged 18-45 years was 20 cases per one million in African Americans.[3]

Characteristics/Clinical Presentation

It is possible for there to be no signs or symptoms when in the early stages of FSGS. Typically the first sign that a patient commonly recognizes is edema, especially in the legs, and sudden weight gain.[2]

Signs and Symptoms: [2][3][4][5]
     • Massive proteinuria and foamy urine appearance
     • Edema, swelling and associated weight gain
     • Hypertension
     • Renal dysfunction with increased creatinine levels
     • Hypoalbuminemia
     • Hyperlipidemia
     • Microscopic hematuria is occasionally present
     • Fatigue
     • Poor appetite
     • Headache
     • Itchy skin
     • Shortness of air
     • Nausea

Associated Co-morbidities

See etiology/causes for a full list of co-morbidities associated with primary and secondary FSGS.

Medications

The goals of pharmacotherapy are to preserve renal function, reduce morbidity, and to prevent complications.[3] Patients with FSGS should be treated with angiotensin inhibition, an ACE inhibitor or an angiotensin II receptor blocker in order to help decrease protein loss and blood pressure.[4] Patients with nephrotic syndrome should be treated with a statin. The primary disorder should be treated in patients with secondary FSGS. A trial of immunosuppressive therapy, corticosteroids and sometimes cytotoxic drugs, is indicated in idiopathic FSGS if proteinuria reaches the nephrotic range or if renal dysfunction is present.[4]

Diagnostic Tests/Lab Tests/Lab Values

A Urinalysis is commonly used to evaluate Blood Urea Nitrogen (BUN), serum creatinine, and 24-hour urinary protein excretion.[4] A Urinalysis usually reveals large amounts of protein, along with hyaline and broad waxy casts, whereas RBC casts are generally absent.[3] A Kidney biopsy however, is the most definitive way to establish the diagnosis of FSGS. The biopsy typically shows focal and segmental hyalinization of the glomeruli, often with immunostaining showing IgM and complement (C3) deposits in a nodular and coarse granular pattern.[4] In HIV-associated FSGS, an ultrasound generally reveals large echogenic kidneys.[3]

Etiology/Causes

FSGS can be placed into two categories: primary and secondary. Primary FSGS is idiopathic without an exact known cause. Secondary FSGS can have many different causes/associations. The scarring may be the result of an infection, or drug toxicity, or a disease that affects the entire body, such as diabetes, HIV infection, sickle cell disease or lupus disease.[6]


• Primary (idiopathic) FSGS [2][3][4][6][7]
        • FSGS with hyalinosis
        • Progression from minimal-change disease
        • Progression from immunoglobulin M (IgM) nephropathy
        • Progression from mesangial proliferative glomerulonephritis
        • Superimposed on other primary glomerulonephritis conditions 
        • Variants of primary FSGS 
               • Collapsing form
               • Cellular variant (endocapillary and extracapillary hypercellularity)
               • FSGS with mesangial hypercellularity
               • FSGS with glomerular tip lesions

• Secondary FSGS [2][3][4][6][7]
        • Drugs
               • Intravenous heroin
               • Analgesics

        • Viruses 
               • Hepatitis B
               • HIV
               • Parvovirus
        • Hemodynamic factors - With reduced renal mass 
               • Solitary kidney
               • Renal allograft
               • Renal dysplasia
               • Renal agenesis
               • Oligomeganephronia
               • Segmental hypoplasia
               • Vesicoureteric reflux
        • Hemodynamic causes - Without reduced renal mass 
               • Massive obesity
               • Sickle cell nephropathy
               • Congenital cyanotic heart disease
        • Malignancies 
               • Lymphomas
               • Other malignancies
        • Scarring - Post inflammatory in post infectious glomerulonephritis
        • Miscellaneous 
               • Hypertensive nephrosclerosis
               • Alport syndrome
               • Sarcoidosis
               • Radiation nephritis

Systemic Involvement[3]

“The natural history of FSGS varies a great deal. A typical course runs from edema that is difficult to manage to proteinuria refractory to corticosteroids and other immunosuppressive agents to worsening hypertension and progressive loss of renal function. In patients who do not respond to therapy, the average time from the onset of gross proteinuria to End Stage Renal Disease (ESRD) is 6-8 years, although wide variations in the time course occur. One of the key factors that determine renal survival is the persistence and degree of proteinuria. In patients with unresponsive massive proteinuria of greater than 10 g/d, most will develop ESRD within 5 years.” 

“Pleural effusion and ascites may be present; pericardial effusions are rare. Gross edema may predispose patients to ulcerations and infections in dependent areas, such as the lower extremity. 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 with a diastolic blood pressure of 120 mmHg or more is not uncommon, especially in African American patients with renal insufficiency. Rarely, patients experience severe renal failure with signs and symptoms of advanced uremia (nausea, vomiting, bleeding, seizures) or altered mental status.”

Medical Management (current best evidence)

Some of the medical management for FSGS can already be found in the medication section above. However, treatment for FSGS can be divided into nonspecific or specific treatment.

Nonspecific Treatment[3]
“Treatment goals include maintenance of adequate nutrition, minimization or elimination of proteinuria, and prevention of complications resulting from edema. Controlling hypertension is one of the most important aspects of overall management. Lowering lipid levels is necessary to reduce cardiovascular risk and to possibly delay the progression of renal disease. It is recommended to reduce salt intake to 2g of sodium and to also alter the use of diuretics accordingly. A high level of protein intake may further aggravate proteinuria, adversely affecting renal function. Current recommendations advise intake of 1-1.3g of high biologic protein per kilogram of body weight and a reduction of fat intake.”

Specific Treament[3]
“Idiopathic FSGS is difficult to treat because of its highly variable clinical course. The specific treatment approach is still experimental, and no consensus has evolved because of a lack of prospective controlled trials. However, current evidence is mostly derived from retrospective analyses and favors the use of prolonged corticosteroid therapy, 6 months or longer, to induce remission in patients with idiopathic FSGS.”

Physical Therapy Management (current best evidence)

Due to varying results in case studies and case reports it is however recommended to also monitor patients for bone marrow suppression, and encourage them to drink adequate fluids to prevent hemorrhagic cystitis.[3] Despite attempts, some patients continue to deteriorate and progress to ESRD.[3] As a Physical Therapist we should have the appropriate tools and resources to inform the patient and their families about treatment choices for ESRD and how to control hypertension and hyperlipidemia. Regular exercise or sports and an appropriate diet should be encouraged in order to help decrease or maintain blood pressure and cholesterol levels. Appropriately informing our patients could also help them in choosing among maintenance hemodialysis, continuous ambulatory peritoneal dialysis, or cadaver or living donor transplantation, when appropriate.[3]

Although there are no published studies on exercise or physical therapy management and its effect on FSGS, as physical therapists we must be able to screen for this disease based on patient and family history, etiology/cause, and signs and symptoms. We should ask questions regarding the possible presence of kidney pain that may produce referral patterns, any history of kidney problems, do you have a family history of kidney disease, are you urinating blood or notice any changes in urine, drug use, etc. All of these questions evolve around the characteristics of FSGS and the primary and secondary causes of FSGS. As mentioned in the systemic involvement section, on physical examination patient’s typically present normal except for edema, we should also ask follow up question regarding the edema. If suspicious of a kidney problem, or specifically FSGS, refer to a Medical Doctor for further evaluation.
[8]

Dietary Management (current best evidence)

Low sodium or sodium free diets, as well as Vitamin D supplementation are usually recommended to patients with FSGS.[5] This is important to help lower high lipid values that can place a patient at risk for cardiovascular complications and could help delay the progression toward End Stage Renal Disease. 

Differential Diagnosis

Potential differential diagnoses:[3]
     • minimal-change disease
     • mesangial proliferative glomerulonephritis
     • membranoproliferative glomerulonephritis
     • membranous glomerulonephritis

Case Reports/ Case Studies

Resources

The Nephcure Foundation: http://www.nephcure.org/
National Kidney Foundation: http://www.kidney.org/

Recent Related Research (from Pubmed)

Failed to load RSS feed from http://eutils.ncbi.nlm.nih.gov/entrez/eutils/erss.cgi?rss_guid=1HYeX0emtvY9HZ70pvPGrp: There was a problem during the HTTP request: 500 Internal Server Error

References

  1. 1.0 1.1 1.2 1.3 1.4 Goodman C, Fuller K. Pathology. Implications for the Physical Therapist. 3rd edition. St. Louis, MO: Saunders Elseveir; 2009. 949-950.
  2. 2.0 2.1 2.2 2.3 2.4 2.5 University of North Carolina Kidney Center. Focal Segmental Glomerulosclerosis (FSGS). Available at: http://www.unckidneycenter.org/kidneyhealthlibrary/fsgs.html. Accessed March 16, 2011.
  3. 3.00 3.01 3.02 3.03 3.04 3.05 3.06 3.07 3.08 3.09 3.10 3.11 3.12 3.13 3.14 3.15 3.16 Rao TS, Soman AS. eMedicine from WebMD. Focal Segmental Glomerulosclerosis. February 17, 2009. Available at: http://emedicine.medscape.com/article/245915-overview. Accessed March 16, 2011.
  4. 4.0 4.1 4.2 4.3 4.4 4.5 4.6 McMillan JI. The Merck Manuals Online Medical Library. Nephrotic Syndrome (Focal Segmental Glomerulosclerosis). January 2010. Available at: http://www.merckmanuals.com/professional/sec17/ch235/ch235c.html#sec17-ch235-ch235c-879. Accessed March 16, 2011.
  5. 5.0 5.1 Patel P. Medline Plus. Focal Segmental Glomerulosclerosis. May 20, 2009. Available at: http://www.nlm.nih.gov/medlineplus/ency/article/000478.htm. Accessed March 16, 2011.
  6. 6.0 6.1 6.2 National Kidney Foundation. Focal Segmental Glomerulosclerosis. September 2008. Available at: http://www.kidney.org/atoz/content/focal.cfm. Accessed March 17, 2011.
  7. 7.0 7.1 National Institute of Diabetes and Digestive and Kidney Diseases. Glomerular Disease Primer: Selected Glomerular Diseases (Focal Segmental Glomerulosclerosis (FSGS)). February 25, 2011. Available at: http://www2.niddk.nih.gov/NIDDKLabs/Glomerular_Disease_Primer/SelectedGlomerularDiseases.htm#d. Accessed March 16, 2011.
  8. Alonzo Mourning. Overcomes Disease and Inspires Others. Available from: http://www.youtube.com/watch?v=mvvsSDQS4G4 [Last Accessed 04/05/11]
  9. Glick A. Focal segmental glomerulosclerosis: a case study with review of pathophysiology. Nephrology Nursing Journal. 2007 March; 34(2):176-183.
  10. Lim A, Lydia A, Rim H, Dowling J, Kerr P. Focal segmental glomerulosclerosis and Guillain-Barre syndrome associated with Campylobacter enteritis. Internal Medicine Journal. 2007 October; 37(10):724-728.
  11. Lowik M, Groenen P, LP, et al. Focal segmental glomerulosclerosis in a patient homozygous for a CD2AP mutation. Kidney International. 2007 November; 72(10):1198-1203.
  12. Osunkoya A, Agte S, Laszik Z. A 67-year-old woman with chronic proteinuria. Focal segmental and global glomerulosclerosis with light microscopic and ultrastructural features consistent with Fabry disease. Archives of Pathology & Laboratory Medicine. 2006 June; 130(6):e93-e95.
  13. Hristea D, et al. Successful treatment of recurrent focal segmental glomerulosclerosis after kidney transplantation by plasmapheresis and rituximab. Transplant International. 2007 January; 20(1):102-105.