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focal segmental glomerulosclerosis (FSGS)

Classification: - perihilar variant - tip variant - cellular variant - collapsing variant (HIV1, heroin, parvovirus, pamidronate) - not otherwise specifed [3] Etiology: 1) idiopathic or primary - congenital renal dysplasia 2) secondary or adaptive due to glomerular or podocyte injury, glomerular hypertension or glomerular hypertrophy - HIV1 infection: more common among IV drug abusers than homosexuals - other infections [11] - parvovirus, cytomegalovirus, tuberculosis, leishmaniasis - autoimmune disease - systemic lupus erythematosus - mixed connective tissue disease [11] - drugs or toxin exposure - heroin abuse - pamidronate - interferon - anabolic steroids [11] - reflux nephropathy - morbid obesity - sleep apnea - solitary kidneys or small kidneys with reduced function - atheroembolic disease 3) genetic: see familial focal segmental glomerulosclerosis Epidemiology: 1) 10% of cases of adult nephrotic syndrome - 36-80% of total nephrotic syndrome [3] 2) mean age of onset is 21 years 3) can occur at any age 4) most common cause of nephrotic syndrome in black persons 5) most common primary glomerular disease that causes ESRD in the U.S. Pathology: 1) light microscopy - focal & segmental sclerosis without proliferation - foam cells are often seen - immunoflurescence shows IgM & C3 deposits within the mesangium 2) electron microscopy: - fusion of epithelial (podocyte) foot processes in glomeruli 3) podocyte injury - primary focal segmental glomerulosclerosis is due to immunologic injury to podocytes - secondary focal segmental glomerulosclerosis is due to hyperfiltration in the setting of reduced renal function leading to adaptive podocyte injury Genetics: - see familial focal segmental glomerulosclerosis Clinical manifestations: 1) idiopathic focal segmental glomerulosclerosis generally manifests as an acute condition a) hypertension b) hematuria (gross or microscopic) c) renal insufficiency d) nephrotic syndrome - edema 2) secondary focal segmental glomerulosclerosis generally manifests as asymptomatic proteinuria without edema 6) slow progression to end-stage renal failure within 5-10 years Laboratory: 1) renal function test for acute renal failure - serum creatinine, serum urea nitrogen 2) urinalysis a) gross or microscopic hematuria b) pyuria (leukocytouria) 3) 24 hour urine protein - poorly-selective proteinuria (nephrotic syndrome) 3) serum complement levels are normal 4) renal biopsy a) foot process fusion by electron microscopy b) segmental sclerosis of glomeruli Complications: - end-stage renal disease (ESRD) Management: 1) no therapy has proven beneficial - weight reduction in obese patients [3] 2) renin-angiotensin-aldosterone inhibitors for sub-nephrotic range proteinuria [3,14] & secondary focal segmental glomerulosclerosis - ACE inhibitors decrease heavy proteinuria; - ARB if ACE inhibitor not tolerated 3) immunosuppressive agents for primary focal segmental glomerulosclerosis with nephrotic range proteinuria [3] a) a trial of prednisone 60 mg qd for at least 1 month - initial 1st line treatment [3,13] - may reduce proteinuria - may slow progression to chronic renal failure b) calcineurin inhibitors - cyclosporine [3] c) mycophenolate [3] d) cyclophosphamide (Cytoxan) - 2 mg/kg/day PO for 8 weeks e) chlorambucil (Leukeran) - 0.2 mg/kg/day PO for 8-12 weeks f) rituximab [3] 4) hemodialysis for evidence of uremic encephalopathy [6] 5) disease can recur after renal transplantation 6) prognosis (idiopathic focal segmental glomerulosclerosis) a) 90% of patients achieve complete remission b) 40-45% become frequently relapsing, many requiring chronic immunosuppression c) 50-55% of patients progress to end-stage renal disease d) poor prognosis if proteinuria is > 10 g/day

Interactions

disease interactions

Related

HIV nephropathy

Specific

collapsing glomerulopathy; collapsing glomerulonephropathy familial focal segmental glomerulosclerosis

General

sclerosing glomerulonephritis

References

  1. Manual of Medical Therapeutics, 28th ed, Ewald & McKenzie (eds), Little, Brown & Co, Boston, 1995, pg 268
  2. Mayo Internal Medicine Board Review, 1998-99, Prakash UBS (ed) Lippincott-Raven, Philadelphia, 1998, pg 607-608
  3. Medical Knowledge Self Assessment Program (MKSAP) 11, 15, 16, 17, 18, 19. American College of Physicians, Philadelphia 1998, 2009, 2012, 2015, 2018, 2021. - Medical Knowledge Self Assessment Program (MKSAP) 19 Board Basics. An Enhancement to MKSAP19. American College of Physicians, Philadelphia 2022
  4. Harrison's Principles of Internal Medicine, 13th ed. Isselbacher et al (eds), McGraw-Hill Inc. NY, 1994, pg 1301
  5. Swaminathan S, Leung N, Lager DJ et al Changing incidence of glomerular disease in Olmsted County, Minnesota: a 30-year renal biopsy study. Clin J Am Soc Nephrol. 2006 May;1(3):483-7 PMID: 17699249
  6. Schaefer L, Vaidya A, Rennke HG, Paik J. Interactive medical case. Itching for a diagnosis. N Engl J Med. 2015 Feb 12;372(7):e10 PMID: 25671274
  7. D'Agati VD, Fogo AB, Bruijn JA, Jennette JC. Pathologic classification of focal segmental glomerulosclerosis: a working proposal. Am J Kidney Dis. 2004 Feb;43(2):368-82. PMID: 14750104
  8. D'Agati VD, Kaskel FJ, Falk RJ. Focal segmental glomerulosclerosis. N Engl J Med. 2011 Dec 22;365(25):2398-411. Review. PMID: 22187987
  9. Brown EJ, Pollak MR, Barua M. Genetic testing for nephrotic syndrome and FSGS in the era of next-generation sequencing. Kidney Int. 2014 May;85(5):1030-8. Review. PMID: 24599252 Free PMC Article
  10. Bose B, Cattran D; Toronto Glomerulonephritis Registry. Glomerular diseases: FSGS. Clin J Am Soc Nephrol. 2014 Mar;9(3):626-32. Review. PMID: 23990165 Free PMC Article
  11. Rothaus C A 34-Year-Old Man with Nephropathy NEJM Resident 360 https://resident360.nejm.org/content_items/2689/
  12. Choung HG et al. The spectrum of kidney biopsy findings in patients with morbid obesity. Kidney Int 2019 Mar; 95:647-654 PMID: 30712921 https://www.kidney-international.org/article/S0085-2538(18)30907-4/fulltext
  13. NEJM Knowledge+ Nephrology/Urology
  14. Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. Kidney Int. 2021;100:S1-S276. PMID: 34556256