Synopsis
Treat FSGS as a histological pattern with multiple causes, distinguish primary podocytopathy from adaptive, genetic and secondary disease, and avoid harmful immunosuppression when it cannot help.
- Focal segmental glomerulosclerosis is a biopsy lesion, not one disease: focal means only some glomeruli and segmental means only part of an affected tuft is scarred.
- Primary FSGS is a circulating-factor podocytopathy typically causing abrupt nephrotic syndrome with diffuse foot-process effacement after secondary causes are excluded.
- Secondary adaptive FSGS follows reduced nephron mass, obesity, reflux, sickle disease or longstanding hyperfiltration and often produces proteinuria without profound hypoalbuminaemia.
- Genetic FSGS is more likely with childhood or young-adult onset, family history, syndromic features, consanguinity or treatment resistance and rarely benefits from immunosuppression.
- HIV, parvovirus, interferon, pamidronate, anabolic steroids, heroin and other exposures can produce secondary patterns; testing follows individual probability.
- A biopsy can miss FSGS because lesions are focal and juxtamedullary glomeruli may be affected first; adequate tissue and electron microscopy are essential.
- Pathology variants such as collapsing, tip, cellular, perihilar and not-otherwise-specified add prognostic context but do not replace aetiological classification.
- Primary FSGS receives high-dose glucocorticoid under specialist care for up to the defined response limit if tolerated; genetic and secondary disease should not receive this reflexively.
- Steroid-resistant primary FSGS is treated with tacrolimus or ciclosporin for at least six months before response is judged, using trough and kidney-toxicity monitoring.
- Supportive care for every cause includes blood-pressure and proteinuria reduction, salt management, suitable SGLT2 inhibition, cardiovascular prevention and nephrotoxin avoidance.
- Remission of proteinuria strongly predicts kidney survival; persistent proteinuria and falling eGFR require adherence, cause and chronicity review rather than repeated empiricism.
- Primary FSGS can recur within hours or days after kidney transplantation, so native-disease classification and previous graft history guide transplant counselling and surveillance.
Key red flags
A rapid creatinine rise with heavy proteinuria and collapsing capillary tufts may be associated with viral infection, medicine exposure or high-risk genotype and needs urgent cause assessment.
Pleuritic pain, hypoxia, unilateral swelling or flank pain during severe hypoalbuminaemia requires immediate assessment for pulmonary, limb or renal-vein thrombosis.
Very early heavy proteinuria after transplantation in someone with presumed primary FSGS raises recurrence and needs immediate transplant-centre biopsy and treatment review.
Investigation priorities
Quantify total and albumin protein, identify haematuria and establish response baselines.
Management branches
Native kidney pathology identifies a focal segmental sclerotic lesion.
- Confirm full nephrotic syndrome, review electron-microscopy effacement and adequacy, and ask renal pathology to describe variant, activity and chronicity.
- Search systematically for reduced nephron mass, obesity, reflux, infection, medicine or substance exposure, family history, early onset and syndromic features.
- Classify as primary, secondary, genetic or undetermined in the specialist record and explain how that category determines benefit or harm from immunosuppression.