This is a disease of unknown aetiology which affects all age groups.
Focal segmental glomerulosclerosis (FSGS) is a rare kidney disease with an annual incidence of 0.2 to 1.8 cases/100,000 individuals (1)
It is characterized by segmental glomerular hyalinisation on light microscopy. Initially focal the condition progresses to global sclerosis. Glomeruli at the corticomedullary junction are affected first. As a result renal biopsy often results in a diagnosis of minimal change disease
- initial histological lesion on kidney biopsy is seen in some but not all glomeruli (focal) and involves part of a glomerulus (segmental)
- develops first in the juxtamedullary glomeruli and progresses to involve a greater number and portion of the glomerular tufts
- because of sampling difficulties on kidney biopsies, FSGS lesions in a few glomeruli may be missed initially and the condition is mislabelled as minimal change disease (MCD)
Primary FSGS is associated clinically with nephrotic syndrome and pathologically with > =80% foot process effacement in glomeruli on electron microscopy
- genetic and secondary forms of FSGS are more likely to present with isolated proteinuria and with < 80% foot process effacement (2,3)
Electon microscopy shows fusion of epithelial foot processes, an observation common to almost all causes of proteinuria including minimal change disease.
Immunofluorescence reveals IgM and C3 in a segmental distribution.
The condition is usually steroid resistant. About 50% of patients develop renal failure within 10 years of diagnosis. Sadly the condition often recurs in transplanted kidneys.
A systematic review concluded (4):
- for steroid-resistant FSGS, treatment with cyclosporin for at least six months was more likely to achieve complete remission of proteinuria compared with other treatments
Reference:
- Chao YC, Trachtman T, Gipson GS, Spino C, Braun TM, Kidwell KM.Dynamic treatment regimens in small n, sequential, multiple assignment, randomized trials: an application in focal segmental glomerulosclerosis. Contemporary Clinical Trials 2020;92:105989
- De Vriese AN, Sethi S, Nath KA, Glassock RJ, Fervenza FC.Differentiating primary, genetic and secondary FSGS in adults: a clinicopathologic approach. Journal of the American Society of Nephrology 2018;29(3):759-74
- Shabaka A, Tato Ribera A, Fernandez-Juarez G.Focal segmental glomerulosclerosis: state-of-the-art and clinical perspective. Nephron 2020;144(9):413-27.
- Hodson EM, Sinha A, Cooper TE. Interventions for focal segmental glomerulosclerosis in adults. Cochrane Database of Systematic Reviews 2022, Issue 2. Art. No.: CD003233. DOI: 10.1002/14651858.CD003233.pub3