Clinicopathological study of primary focal segmental glomerulosclerosis: A new vision of all variants
Keywords:
Primary Focal Segmental Glomerulosclerosis, immunofluorescence, Nephrotic syndrome, Variant.
Abstract
Background: This study is a detailed clinical and histomorphological analysis of Primary Focal Segmental Glomerulosclerosis diagnosed by combined approach of histopathology and direct immunofluorescence. The aim was to identify the morphologic variants with histopathological prognostic features of primary focal segmental glomerulosclerosis and to establish the clinical, laboratory & pathologic findings in nephrotic syndrome & renal insufficiency associated with primary focal segmental glomerulosclerosis.Methods: It was a prospective & retrospective analysis of 41 cases of primary Focal Segmental Glomerulosclerosis. Routine & special stains were done all renal biopsies. Immunofluorescence studies were performed. Multiple comparisons among the groups were performed using ANOVA. Mean comparison of two groups was performed using independent sample t-test. A categorical variable was tested using Chi-square test and fishers exact test.Results: Out of 718, all the 41 renal biopsies of primary FSGS classified into morphologic variants. Primary Focal segmental glomerulosclerosis constituted 5.7% of total kidney biopsies. Mean age was 35.93 years having male preponderance. Proteinuria was highest in Perihilar variant while hematuria was more in the cellular variant. Nephrotic syndrome was most commonly associated with the cellular and perihilar variant. It was only histological parameter whose distribution among the different variants was statistically significant. A statistically significant correlation (p<0.05) was noted between the percentage of globally sclerosed glomeruli with hypertension & serum creatinine. A significant correlation was found between serum creatinine and mesangial hypercellularity, serum albumin, podocyte hyperplasia, arteriolar hyalinosis, intimal sclerosis and medial hypertrophy.Conclusions: This comprehensive study of primary FSGS reiterates that different histological variants of FSGS have substantial differences in clinical and histological features.References
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10. Korbet SM, Schwartz MM. The prognosis of focal segmental glomerular sclerosis of adulthood. Medicine (Baltimore). 1986; 65: 304-11.
11. Rydell JJ, Korbet SM, Borok RZ, Schwartz MM, et al. Focal segmental glomerular sclerosis in adults:Presentation, course and response to treatment. Am J Kidney Dis. 1995; 25: 534.
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24. Alexopoulous Efstathios, Stagnou Maria,Papagianni Aikaterini,Pantzaki Aphroditi Pantazaki, Papadimitriou. Factors influencing the course and the response to treatment in primary focal segmental glomerulosclerosis. Nephrol Dial Transplant. 2000;15:13348-1356.
25. Diana T, Ali C, Pargol S, Amar H, Shohreh S, Shiva S. Correlation of kidney biopsy findings and clinical manifestations of primary focal and segmental glomerulosclerosis. SJKDT. 2009; 20(3):417-42.
26. Diana T, Ali C, Pargol S, Amar H, Shohreh S, Shiva S. The predictive role of histopathological findings in renal insufficiency and complete remission in a sample of Iranian adults with primary focal segmental glomerulosclerosis. JRMS. 2010;15(1):14-19.
27. Barisoni L, Schnaper HW, Kopp JB. A Proposed Taxonomy for the Podocytopathies: A Reassessment of the Primary Nephrotic Diseases. Clinical Journal Of The American Society Of Nephrology. 2007; 2: 529-542.
28. Gubler MC, Waldherrs R, Levy M, Habib R. Idiopathic nephrotic syndrome with focal and segmental sclerosis and/or hyalinosis: clinical course, response to therapy, and long- term outcome. In: Strauss J, ed. Nephrotic syndrome: current concepts in diagnosis and management. New York: Garland, 1979: 193-212.
29. Velosa JA, Donadio JV Jr, Holley KE. Focal sclerosing glomerulonephropathy: a clinicopathologic study. Mayo Clin Proc. 1975; 50: 121-33.
30. Brown CB, Cameron JS. Focal segmental glomerulosclerosis with rapid decline in renal function (“malignant FSGS”). Clin Nephrol. 1978; 10: 51-61.
31. Lee HS, Spargo BH. Significance of renal hyaline arteriolosclerosis in focal segmental glomerulosclerosis. Nephron.1985; 41: 86-93.
32. Schoeneman MJ, Bennett B, Greifer I. The natural history of focal segmental glomerulosclerosis with and without mesangial hypercellularity in children. Clin Nephro. 1978; 9: 45-54.
33. Shi SF, Wang SX, Zhang YK, Zhao MH, Zou WZ. Clinicopathologic study of different variants of focal segmental glomerulosclerosis. Zhonghua Bing Li Xue Za Zhi. 2007;36 (1):11-4.
34. Luis F AriasI, Carlos A, JiménezII, Mariam J ArroyaveI. Histologic variants of primary focal segmental glomerulosclerosis: presentation and outcome. J Bras Nefrol. 2013;35(2):112-119.
35. Silverstein DM, Craver R. Presenting features and short-term outcome according to pathologic variant in childhood primary focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2007; 2:700–707.
2. Nadasay T, Silva FG. Adult Renal Diseases. In: Mills SE, Carter D, Reuter VE, Greenson JK, Stoler MH, Oberman HA. editors. Sternberg’s Diagnostic Surgical Pathology. 4th edition, Philadelphia: Lippincott -Williams & Wilkins; 2004. 1863-1954.
3. D’ Agati V, Fogo AB, Bruijn JA, Jennette JC. Pathologic classification of Focal segmental Glomerulosclerosis : A working Proposal. American Journal of Kidney Diseases. 2004;43: 368-82.
4. Cameron JS. The enigma of focal segmental glomerulosclerosis. Kidney Int. 1996; 57: S-119-31.
5. D’Agati V. Pathologic classification of focal segmental glomerulosclerosis. Semin Nephrol. 2003; 23:117 –134.
6. Rao TKS, Soman Anjana S. Focal segmental glomerulosclerosis. e-medicine Nephrology, http://emedicine.medscape.com/article/245915-overview.
7. Newman WJ, Tisher CC, McCoy RC, Krueger RP, Clapp JR, et al. Focal glomerular sclerosis:Contrasting clinical patterns in children and adults. Medicine. 1976;55:67.
8. Cameron JS, Turner DR, Ogg CS, Chantler C, Williams DG, et al. The long-term prognosis of patients with focal segmental glomerulosclerosis. Clin Nephrol. 1978;10:213-218.
9. Ingulli E, Tejani A. Racial differences in the incidence and renal outcome of idiopathic focal segmental glomerulosclerosis in children. Pediatr Nephrol. 1991;5:393.
10. Korbet SM, Schwartz MM. The prognosis of focal segmental glomerular sclerosis of adulthood. Medicine (Baltimore). 1986; 65: 304-11.
11. Rydell JJ, Korbet SM, Borok RZ, Schwartz MM, et al. Focal segmental glomerular sclerosis in adults:Presentation, course and response to treatment. Am J Kidney Dis. 1995; 25: 534.
12. Habib R. Focal glomerular sclerosis [Editorial]. Kid Int. 1973; 4: 355-61.
13. Kitiyakara DC, Kopp J B, Eggers DP. Trends in the epidemiology of focal segmental glomerulosclerosis. Semin Nephrol. 2003;23:172.
14. Banfi G, Moriggi M, Sabadini E, Fellin G, D'Amico G, Ponticelli C. The impact of prolonged immunosuppression on the outcome of idiopathic focal-segmental glomerulosclerosis with nephrotic syndrome in adults. Clin Nephrol. 1991;36: 53-59.
15. Shiiki H, Nishino T, Uyama H, Kimura T, Nishimoto K, Iwano M, et al. Clinical and morphological predictors of renal outcome in adult patients with focal and segmental glomerulosclerosis (FSGS). Clin Nephrol. 1996; 46: 362-368.
16. D’Agati Vivette D. Spectrum of FSGS new insight. Current Opinion in Nephrology and Hypertension. 2008;17:271-281.
17. Stokes MB, Glen SM, Julie L, Anthony MV, D'Agati V. Glomerular tip lesion: A distinct entity within the minimal change disease/focal segmental glomerulosclerosis spectrum. Kidney Int. 2004; 65: 1690-02.
18. Ritambhara N, Kaur KJ, Amulyajit B, Walker MR, Sakhuja V, Joshi K. Primary focal segmental glomerulosclerosis in adults: is the Indian cohort different? Nephrol Dial Transplant. 2009; 24 (12): 3701-3707.
19. Laurinavicius A, Rennke HG: Collapsing glomerulopathy: A new pattern of renal injury. Semin Diagn Pathol. 2002; 19: 106 –15.
20. Thomas DB, Franceschini N, Hogan SL, Holder S, Jennette CE, Falk RJ and Jennette JC. Clinical and pathologic characteristics of focal segmental glomerulosclerosis pathologic variants. Kidney In. 2006; 69: 920-2.
21. Stokes MB, Valeri AM, Markowitz GS and D'Agati VD. Cellular focal segmental glomerulosclerosis: Clinical and pathologic features. Kidney Int. 2006; 70: 1783-92.
22. Chun MJ, Korbet SM, Schwartz MM, Lewis EJ. Focal Segmental Glomerulosclerosis in Nephrotic Adults: Presentation, Prognosis, and Response to Therapy of the Histologic Variants. J Am Soc Nephrol. 2004;15: 2169-77.
23. Deegens JK, Steenbergen EJ, Borm GF, Wetzels JF. Pathologic variants of focal segmental glomerulosclerosis in an adult Dutch population – epidemiology and outcome. Nephrol Dial Transplant. 2008; 23:186–192.
24. Alexopoulous Efstathios, Stagnou Maria,Papagianni Aikaterini,Pantzaki Aphroditi Pantazaki, Papadimitriou. Factors influencing the course and the response to treatment in primary focal segmental glomerulosclerosis. Nephrol Dial Transplant. 2000;15:13348-1356.
25. Diana T, Ali C, Pargol S, Amar H, Shohreh S, Shiva S. Correlation of kidney biopsy findings and clinical manifestations of primary focal and segmental glomerulosclerosis. SJKDT. 2009; 20(3):417-42.
26. Diana T, Ali C, Pargol S, Amar H, Shohreh S, Shiva S. The predictive role of histopathological findings in renal insufficiency and complete remission in a sample of Iranian adults with primary focal segmental glomerulosclerosis. JRMS. 2010;15(1):14-19.
27. Barisoni L, Schnaper HW, Kopp JB. A Proposed Taxonomy for the Podocytopathies: A Reassessment of the Primary Nephrotic Diseases. Clinical Journal Of The American Society Of Nephrology. 2007; 2: 529-542.
28. Gubler MC, Waldherrs R, Levy M, Habib R. Idiopathic nephrotic syndrome with focal and segmental sclerosis and/or hyalinosis: clinical course, response to therapy, and long- term outcome. In: Strauss J, ed. Nephrotic syndrome: current concepts in diagnosis and management. New York: Garland, 1979: 193-212.
29. Velosa JA, Donadio JV Jr, Holley KE. Focal sclerosing glomerulonephropathy: a clinicopathologic study. Mayo Clin Proc. 1975; 50: 121-33.
30. Brown CB, Cameron JS. Focal segmental glomerulosclerosis with rapid decline in renal function (“malignant FSGS”). Clin Nephrol. 1978; 10: 51-61.
31. Lee HS, Spargo BH. Significance of renal hyaline arteriolosclerosis in focal segmental glomerulosclerosis. Nephron.1985; 41: 86-93.
32. Schoeneman MJ, Bennett B, Greifer I. The natural history of focal segmental glomerulosclerosis with and without mesangial hypercellularity in children. Clin Nephro. 1978; 9: 45-54.
33. Shi SF, Wang SX, Zhang YK, Zhao MH, Zou WZ. Clinicopathologic study of different variants of focal segmental glomerulosclerosis. Zhonghua Bing Li Xue Za Zhi. 2007;36 (1):11-4.
34. Luis F AriasI, Carlos A, JiménezII, Mariam J ArroyaveI. Histologic variants of primary focal segmental glomerulosclerosis: presentation and outcome. J Bras Nefrol. 2013;35(2):112-119.
35. Silverstein DM, Craver R. Presenting features and short-term outcome according to pathologic variant in childhood primary focal segmental glomerulosclerosis. Clin J Am Soc Nephrol. 2007; 2:700–707.
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