Focal segmental glomerulosclerosis
| Focal segmental glomerulosclerosis | |
|---|---|
| Other names | focal glomerular sclerosis, PAS stain. |
| Specialty | Nephrology  |
Focal segmental glomerulosclerosis (FSGS) is a histopathologic finding of scarring (sclerosis) of glomeruli and damage to renal podocytes.[2][3] This process damages the filtration function of the kidney, resulting in protein presence in the urine due to protein loss.[3] FSGS is a leading cause of excess protein loss—nephrotic syndrome—in children and adults.[4] Signs and symptoms include proteinuria and edema.[2][5] Kidney failure is a common long-term complication of the disease.[5][6] FSGS can be classified as primary, secondary, or genetic, depending on whether a particular toxic or pathologic stressor or genetic predisposition can be identified as the cause.[7][8][9] Diagnosis is established by renal biopsy,[2][10] and treatment consists of glucocorticoids and other immune-modulatory drugs.[11] Response to therapy is variable, with a significant portion of patients progressing to end-stage kidney failure.[5] An American epidemiological study 20 years ago demonstrated that FSGS is estimated to occur in 7 persons per million, with males and African-Americans at higher risk .[12][13][7]
Signs and symptoms
The most common symptoms are a result of abnormal loss of protein from the glomerulus of the kidney, and include:[2][5]
- Frothy urine (due to excess protein)
- Excess water retention (pitting edema, due to loss of serum albumin)
- Susceptibility to infection (due to loss of serum antibodies)
Common signs are also due to loss of blood proteins by the glomerulus of the kidney, including:[2][5][10]
- Protein in the urine (often in the nephrotic syndrome-range of >3.5 g/day)
- Low serum albumin (<3.5 g/dl)
- Low serum antibodies
- High serum cholesterol (compensatory by the liver to compensate for low serum oncotic pressure)
- Fatty casts in the urine (secondary to hypercholesterolemia)
Pathophysiology
FSGS is primarily a disease of the renal glomerulus, the site of filtration of ions and solutes.[14][15] Podocytes are specialized cells lining the Bowman's capsule that contribute to the filtration barrier, preventing molecules larger than 5 nm from being filtered.[16] FSGS involves damage to the renal podocytes such that larger molecules, most notably proteins, are filtered and lost through the kidney.[17][18] Thus, many of the signs and symptoms of FSGS are related to protein loss.[19]
On histology, FSGS manifests as scarring (sclerosis) to segments of glomeruli; moreover, only a portion of glomeruli are affected.[7][20][21] The focal and segmental nature of disease seen on histology help to distinguish FSGS from other types of glomerular sclerosis.[21]
FSGS can be classified by the putative cause of damage to podocytes. Primary FSGS involves cases in which no cause is readily identifiable.[22] It is presumed that a set of unidentified circulating factors in the blood contribute to podocyte damage in these cases.[22][23]
Secondary FSGS is caused by an identifiable stress or toxin that injures podocytes.[22] Many causes of secondary FSGS contribute to podocyte injury through hyperfiltration, which is a scenario of excess filtration by renal glomeruli.[24] Hyperfiltration can be caused by obesity, diabetes or loss of the contralateral kidney, among other causes.[24]
Secondary FSGS can also be caused by toxins, including anabolic steroids and heroin.[25][26]
A number of genes have been implicated in FSGS. These include: NPHS1, which encodes the protein nephrin that contributes to the filtration barrier;[27] NPHS2, which encodes the protein podocin found in podocytes;[28] and INF2, which encodes the actin-binding protein formin.[29]
The pathogenesis of HIV-associated FSGS is unclear, but may be primarily due to the presence of the G1/G2 risk alleles for APOL1. There is some data to suggest that HIV can infect tubular epithelial cells and podocytes, but much remains to be known.[30]
Diagnosis
Diagnosis of FSGS is made by
Other tests helpful in the diagnosis include urine protein, urinalysis, serum albumin, and serum lipids.[2] A clinical picture of proteinuria, low blood protein levels (albumin, antibodies), and high blood cholesterol would support a diagnosis of FSGS, although these do not help to distinguish between FSGS and other causes of proteinuria.[5][10]
Classification
Five mutually exclusive variants of focal segmental glomerulosclerosis may be distinguished by the pathologic findings seen on renal biopsy:[34]
- Collapsing variant
- Glomerular tip lesion variant
- Cellular variant
- Perihilar variant
- Not otherwise specified (NOS) variant.
Recognition of these variants may have
Treatment
First-line treatment for primary FSGS consists of anti-inflammatory drugs.
The treatment of secondary FSGS involves addressing the particular toxic or stress agent.[35]
Prognosis
The majority of untreated cases of FSGS will progress to end-stage kidney disease.[37] Important prognostic factors include the degree of proteinuria and initial response to therapy.
Patients with nephrotic-range (>3.5 g/day) proteinuria have over a 50% rate of progression to end-stage kidney disease at 10 years.[6] Only 15% of patients with sub-nephrotic ranges of proteinuria progress to end-stage renal failure at 10 years.[6]
Initial response to therapy also dictates long-term outcomes. Those defined as having a "complete response" typically manifest a proteinuria of <300 mg/day; those with a "partial response" manifest a sub-nephrotic range of proteinuria, <3.5 g/day.[38] Either complete or partial response is associated with 80% kidney survival at 10 years, compared with about 50% among non-responsive patients.[38]
Epidemiology
FSGS accounts for 35% of all cases of nephrotic syndrome, making it one of the most common causes of nephrotic syndrome in the United States.[8] FSGS accounts for 2% of all cases of kidney failure.[4] African American patients have four times the likelihood of developing FSGS. Men are about two times as likely to develop FSGS compared to women.[12]
Notable cases
See also
References
- ^ a b "focal segmental glomerulosclerosis" at Dorland's Medical Dictionary.
- ^ PMID28242845.
- ^ PMID 7861720.
- ^ PMID 15492947.
- ^ PMID 7702047.
- ^ PMID 8203357.
- ^ a b c "Focal segmental glomerulosclerosis (FSGS)". www.kidneyfund.org. 2021-10-28. Retrieved 2023-11-14.
- ^ PMID 9370176.
- ^ PMID 25447132; PMCID: PMC4772430.
- ^ PMID 21896374; PMCID: PMC3709971.
- ^ PMID 29852493; PMCID: PMC6589822.
- ^ PMID 11863085.
- PMID 12704577.
- PMID 9829131.
- PMID 24875196; PMCID: PMC4123398.
- PMID 22685655; PMCID: PMC3363986.
- PMID 27165817.
- PMID 30454752.
- ^ "Focal Segmental Glomerulosclerosis (FSGS)". Cleveland Clinic. Retrieved 2022-06-30.
- PMID 8792409.
- ^ PMID 28664408.
- ^ a b c De Vriese AS, Sethi S, Nath KA, et al. Differentiating Primary, Genetic, and Secondary FSGS in Adults: A Clinicopathologic Approach. J Am Soc Nephrol 2018; 29:759.
- ^ Rennke HG, Klein PS. Pathogenesis and significance of nonprimary focal and segmental glomerulosclerosis. Am J Kidney Dis 1989; 13:443.
- ^ PMID 22349487.
- ^ Dubrow A, Mittman N, Ghali V, Flamenbaum W. The changing spectrum of heroin-associated nephropathy. Am J Kidney Dis 1985; 5:36.
- ^ Kasiske BL, Crosson JT. Renal disease in patients with massive obesity. Arch Intern Med 1986; 146:1105.
- PMID 18614772; PMCID: PMC2551572.
- PMID 10742096.
- PMID 20023659; PMCID: PMC2980844.
- ^ Chang, Anthony, Robbins & Cotran Pathologic Basis of Disease, Chapter 20, 895–952
- ^ Fuiano G, Comi N, Magri P, et al. Serial morphometric analysis of sclerotic lesions in primary "focal" segmental glomerulosclerosis. J Am Soc Nephrol 1996; 7:49.
- ^ a b Schwartz MM, Korbet SM. Primary focal segmental glomerulosclerosis: pathology, histological variants, and pathogenesis. Am J Kidney Dis 1993; 22:874.
- license
- PMID 16518352.
- ^ PMID 26156092; PMCID: PMC4496884.
- ^ PMID 32074606.
- PMID 16301760.
- ^ PMID 15716334.