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Saudi Journal of Kidney Diseases and Transplantation
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ORIGINAL ARTICLE Table of Contents   
Year : 2009  |  Volume : 20  |  Issue : 3  |  Page : 417-423
Correlation of kidney biopsy findings and clinical manifestations of primary focal and segmental glomerulosclerosis


1 Department of Pathology, University of Medical Sciences, Isfahan, Iran
2 Medical Students, School of Medicine, University of Medical Sciences, Isfahan, Iran
3 Division of Nephrology-Department of Internal Medicine, University of Medical Sciences, Isfahan, Iran

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   Abstract 

To evaluate the correlation of clinical, laboratory, and pathological features at pre­sentation of focal segmental sclerosis (FSGS), we reviewed in a cross sectional study the patholo­gical findings of kidney biopsies in 64 cases of primary FSGS, and correlated them with the clinical and laboratory data obtained at the time of the biopsies. The data included blood pressure, glome­rular filtration rate (GFR), serum albumin, and the level of proteinuria. The mean level of serum crea­tinine was significantly higher in the biopsies' findings of synechiae (adhesions) in the Bowman's capsule, interstitial fibrosis, and global scars (P< 0.05), and mean level of GFR was significantly lower with the presence of interstitial fibrosis (P< 0.05). Furthermore, there was a positive correlation between the level of serum creatinine and global sclerosis (r= 2.21, P= 0.04), and a negative correlation between the level of GFR and global sclerosis(r= 2.01, P= 0.02). All the patients with renal insufficiency had interstitial fibrosis in their biopsies in comparison of only the 24 patients (48%) of the group without renal insufficiency (P< 0.05). There was no significant difference bet­ween patients with and without hypertension and nephritic-ranged proteinuria. We conclude that we found a correlation of renal insufficiency in primary FSGS patients with interstitial fibrosis, global scars and the synechiae of Bowman's capsule in their biopsies.

Keywords: Focal and segmental glomerulosclerosis (FSGS), Creatinine, Albumin, BUN, Interstitial fibrosis, Global scar, Synechiae in Bowman′s capsule

How to cite this article:
Taheri D, Chehrei A, Samanianpour P, Hassanzadeh A, Sadrarhami S, Seyrafian S. Correlation of kidney biopsy findings and clinical manifestations of primary focal and segmental glomerulosclerosis. Saudi J Kidney Dis Transpl 2009;20:417-23

How to cite this URL:
Taheri D, Chehrei A, Samanianpour P, Hassanzadeh A, Sadrarhami S, Seyrafian S. Correlation of kidney biopsy findings and clinical manifestations of primary focal and segmental glomerulosclerosis. Saudi J Kidney Dis Transpl [serial online] 2009 [cited 2019 Sep 16];20:417-23. Available from: http://www.sjkdt.org/text.asp?2009/20/3/417/50772

   Introduction Top


Primary focal and segmental glomerulosclerosis (FSGS) is a clinicopathological entity that affects both adults and children and manifests itself clinically by persistent nephrotic syndrome, non­selective proteinuria, microscopic hematuria, hy­pertension, and variable renal insufficiency. [1] The prevalence of FSGS is estimated as 20-30% in adults and 30-35% in those with age > 60 years. [2],[3]

Diagnosis of FSGS relies solely on the patholo­gic findings that include focal sclerosis in seg­ments of less than 50% of glomeruli. When all of the secondary causes of this pattern of injury are eliminated, the remaining patients are labe­led as primary FSGS. [3],[4] The clinical course of patients with FSGS is characterized by progre­ssive deterioration of renal function that results in end-stage renal disease (ESRD) over 5-10 years, and certain clinical and pathologic fin­dings have prognostic significance. [2],[3],[4],[8],[9],[10]

The clinical presentation and morphologic fea­tures of FSGS are variable. Five pathologic va­riants of idiopathic focal segmental glomeru­losclerosis (FSGS) are recognized: collapsing (COLL), cellular (CELL), glomerular tip lesion (GTL), perihilar, and non-specified (NOS). [4],[5],[6]

Studies that have assessed the clinical relevance of the pathologic findings of primary FSGS in nephrotic patients are few and conflicting. Ac­cordingly, the correlation of the clinical and la­boratory parameters such as hypertension, he­maturia, serum creatinine level and nephrotic syndrome at the time of biopsy with the mor­phologic features of FSGS remains controver­sial. [7],[8],[9],[10] Furthermore, there are no reliable clini­cal or pathologic features of FSGS that allow prediction of response to therapy.

The aim of this study was to analyze the co­rrelation of clinical, laboratory, and pathologic features of FSGS that might help predict pro­gression of the disease.


   Patients and Methods Top


This is a cross sectional study of 64 primary FSGS patients who had their kidney biopsies processed in the department of pathology of Al­Zahra hospital, Isfahan, Iran, during 2006 to 2007. All the procedures were performed in ac­cordance with the ethical standards of "Medi­cal Students Research Committee" of "Isfahan University of Medical Sciences".

The pathologic diagnosis of FSGS was ac­cording to the following criteria: (I) sclerosis involving less than 50% of glomeruli in the bio­psy [Figure 1], (II) segmental collapse of glo­merular capillaries with obliteration of capil­lary lumina with or without adhesions [Figure 2], and (III) no clinical or pathological evidence for secondary FSGS such as reflux nephropathy, nephrectomy, a solitary kidney, human immu­nodeficiency virus, or intravenous drug abuse. [4],[5],[6],[10],[11]

All kidney biopsies were obtained using a stan­dard Trucut needle. In each case, glass slides stained with hematoxylin eosin, Masson trichro­me, periodic acid Schiff, and methenamine sil­ver and also reports of immunoflurescence microscopy for definite diagnosis were available for review. Light microscopy findings were analyzed by a renal pathologist without knowledge of pa­tient identity or outcome.

The recorded morphologic features of the kid­ney biopsies included the proportion of glome­ruli with segmental scars, global scars, and hya­linosis besides the location of each segmental scar in relation to the vascular and tubular pole of the tuft. We also recorded the presence of foam cells, mesangial sclerosis, epithelial cell proli­feration (visceral and parietal), synechiae (ad­hesions) with the Bowman's capsule, interstitial fibrosis, and tubular atrophy.

Clinical and laboratory data were obtained on each patient at the time of biopsy. The data in­clude systolic and diastolic blood pressure, se­rum creatinine, blood urea nitrogen (BUN), glo­merular filtration rate (GFR), serum albumin, and 24 hour urine collection for proteinuria. The patients with diastolic blood pressures > 90 mmHg or systolic blood pressures > 140 mmHg which were considered hypertensive. Nephrotic syndrome was defined as nephritic range pro­teinuria > 3.5 g/L, and renal insufficiency (RI) was defined as the level of the serum creatinine > 1.3 mg/dL. 8

Statistical Analysis

All data were analyzed by SPSS (SPSS Inc, Chicago IL, USA, version 11). Simple descrip­tive techniques were used to describe the varia­bles. The K-S's and Levene's tests were applied to verify normal distribution and the equality of variances. According to above tests we used student "t" or Mann Withney "U" tests for com­parison of the quantitative data in grouping va­riables. Pearson correlation coefficient was used to explore the relationship between the quan­titative data. Chi square test was used to find the relationship between qualitative data.


   Results Top


The study patients included 33 (51%) men and 31 (49%) women with a mean age of 32.76 years (range 16 to 64 years).

The mean and the 95% confidence interval (mean ± 2 SE) for the relevant clinical and laboratory investigations included systolic blood pressure were 121.19 mmHg (114.8-127.6), dia­stolic blood pressure 77.52 mmHg (81.8-73.4), the level of proteinuria 1106 (1530-2310) mg/L, plasma creatinine 1.18 (1.02-1.34) mg/dL, plasma Albumin 3.29 (2.92-3.48) g/dL, BUN 26.29 (21­32.5) mg/dL, and GFR 87.18 (76-98) mL/min.

In the pathologic examination, the overall ave­rage number of glomeruli for evaluation by light microscopy was 16 ± 8.7 (in 80% of biop­sies, there were > 10 glumeruli). The mean number of the glomeruli with segmental scar (30% vascular pole and 27% tubular pole) was 4.42, and the mean number of glomeruli with global scar and the 95% confidence interval was 2 (1.8-2.2).

The frequencies of the other pathologic fea­tures were: mesangial hyperplasia 34 (53%), me­sangial sclerosis 31 (48 %), interstitial fibrosis 50 (77%), synechiae with Bowman's capsule 24 (37%), tubular atrophy 50 (77%), and visceral epithetlial cell proliferation 4 (7%) and parietal epithetlial cell proliferation 18 (28%).

Monovariate analysis showed that the mean and the 95% confidence interval of serum crea­tinine levels in the study patients with intersti­tial fibrosis in the biopsies vs those without was 0.88 (0.66-1.08) mg/dL vs 1.28 (1.20-1.36) mg/ dL, respectively (P< 0.05); the mean level of GFR in the patients with and without interstitial fibrosis and synechiae in the Bowman's capsule was 82 (69.04-94.96) and 73 (57.8-88.2) mL/min, 102 (87.44-116.56) mL and 94 (80-108) mL, res­pectively, (P< 0.05) respectively [Table 1].

There was a positive correlation between the level of plasma creatinine and global sclerosis (r= 0.24, P= 0.04), and the level of plasma albu­min and global sclerosis (r= 0.31, P= 0.02). Also there were negative correlation between the level of GFR and global sclerosis (r=-0.30, P= 0.01).

All the patients with RI revealed interstitial fibrosis in their biopsies in comparison with only 15 (30 %) patients without renal insuffi­ciency (P< 0.05). The mean number of glomeruli with global sclerosis in the patients with and without RI was 2.1 (1.7 to 2.4) and 1.0 (0.85 to 1.15) glomeruli (P< 0.05), but there were no significant differences between both groups with respect to other morphologic findings [Table 2] and [Table 3].

We found no significant difference between the hypertensive and the non-hypertensive pa­tients with respect to morphological findings on biopsies. Furthermore, there were no significant differences or correlations between the levels of proteinuria with the pathologic features, [Figure 3].


   Discussion Top


In our study, we described the clinical and laboratory features of FSGS patients and their correlations. Numerous studies have attempted to consider clinical, laboratory or histological fea­tures of FSGS patients as prognostic criteria's, [8],[9],[10],[11],[12] but few studies evaluated the correlation bet­ween the clinical or laboratory features with the prognostic pathological features.

In our study, serum creatinine and plasma albumin levels were associated with some prog­nostic significance including interstitial fibro­sis, global scars and the presence of synechiae in the Bowman's capsule. Previous studies sug­gested elevated serum creatinine levels as a sig­nificant [12],[13],[14],[15],[16] or only risk factor [8],[9],[10] for progre­ssion of FSGS patients to ESRD. Furthermore, we found in our study that the levels serum creatinine, plasma albumin, and GFR correlated with the pathologic features of FSGS. The prog­nostic role of the pathologic features and their correlation with these laboratory findings have been proven in previous studies. [11],[13],[14],[15]

In agreement with others, we found that the degree of proteinuria was not predictive of the pathologic features. Alexopoulos et al demons­trated that the severity of proteinuria did not differ significantly between untreated patients who retained stable renal function during follow­up and those who progressed to ESRD. [12] Se­veral other authors reported no link between prognosis and degree of proteinuria. [8],[9],[11] How­ever, others have found that the nephrotic-range proteinuria was consistently associated with poor outcome in primary FSGS. [17],[18],[19] In our stu­dy, we found significant correlations between se­rum creatinine, plasma albumin, and GFR with global scars in FSGS in addition to a significant difference between the mean level of serum creatinine and GFR in the patients who mani­fested interstitial fibrosis and synechiae in the Bowman's capsule.

Rydel et al found that the degree of interstitial fibrosis significantly influenced the develop­ment of ESRD. [7] Wehrman et al found that in­terstitial fibrosis, not serum creatinine, had in­dependent predictive value for progression to ESRD. The correlation between serum crea­tinine and interstitial fibrosis was also strong in their study. [16]

Furthermore, many studies d-monstrated with multivariate analysis that the extent of the in­terstitial fibrosis was the only independent pre­dictive factor for response to treatment, [7],[10],[12],[15]

However, Rydel et al found that none of the glomerular pathologic features of FSGS correla­ted with renal function at time of biopsy or were predictive of ESRD at follow up. [7]

The prognostic role of global scars and syne­chiae in the Bowman's capsule has not been proven until now by other studies. However, these two pathological features could have prog­nostic roles in FSGS patients as found in our study. Furthermore, few studies considered im­munohistologic analysis on FSGS patient, such as the study of Peruzzi et al [22] who showed that proteinuria induces integrin expression by the tubules. Integrin critically participates in matrix assembly and affect tissue remodeling, and it causes tubular interstitial fibrosis. [23],[24] Larger studies are needed to address the role of the im­munohistochemical markers in prognosis in pri­mary FSGS, since we have not studied these markers in the current study.

In conclusion, we found in our study that in addition to the interstitial fibrosis, global scars and the synechiae in the Bowman's capsule co­rrelated with serum creatinine, plasma albumin and GFR.

 
   References Top

1.Daskalakis N, Winn MP. Focal and segmental glomerulosclerosis. Cell Mol Life Sci 2006;63 (21):2506-11.  Back to cited text no. 1    
2.Haas M, Spargo BH, Coventry S. Increasing incidence of focal segmental glomerulosclerosis among adult nephropathies: a 20 year renal biopsy study. Am J Kidney Dis 1995;26(5):740-50.  Back to cited text no. 2    
3.Korbet SM. Clinical picture and outcome of pri­mary focal segmental glomerulosclerosis. Nephrol Dial Transplant 1999;14(Suppl3):68-73.  Back to cited text no. 3    
4.Thomas DB, Franceschini N, Hogan SL, et al. Clinical and pathologic characteristics of focal segmental glomerulosclerosis pathologic variants. Kidney Int 2006;69(5):920-6.  Back to cited text no. 4    
5.Deegens JK, Steenbergen EJ, Borm GF, Wetzels JF. Pathological variants of focal segmental glomerulosclerosis in an adult Dutch population epidemiology and outcome. Nephrol Dial Transplant 2007 Aug 17; [Epub ahead of print].  Back to cited text no. 5    
6.D'Agati V. Pathologic classification of focal segmental glomerulosclerosis. Semin Nephrol 2003;23(2):117-34.  Back to cited text no. 6    
7.Rydel JJ, Korbet SM, Borok RZ, Schwartz MM. Focal segmental glomerular sclerosis in adults: presentation, course, and response to treatment. Am J Kidney Dis 1995;25(4):534-42.  Back to cited text no. 7    
8.Deegens JK, Assman KJ, Steenbergen LB. Idiopathic focal segmental glomerulosclerosis; a favorable prognosis in untreted patients? Netherland J Med 2005;63:393-8.  Back to cited text no. 8    
9.Dumoulin A, Hill GS, Montseny JJ, Meyrier A. Clinical and morphological prognostic factors in membranous nephropathy: significance of focal segmental glomerulosclerosis. Am J Kidney Dis 2003;41(1):38-48.  Back to cited text no. 9    
10.Schwartz MM, Korbet SM, Rydell J, Borok R, Genchi R. Primary focal segmental glomerular sclerosis in adults: prognostic value of histo­logic variants. Am J Kidney Dis 1995;25(6):845­52.  Back to cited text no. 10    
11.McAdams AJ, Valentini RP, Welch TR. The nonspecificity of focal segmental glomerulo­sclerosis. The defining characteristics of pri­mary focal glomerulosclerosis, mesangial pro­liferation, and minimal change. Medicine (Baltimore) 1997;76(1):42-52.  Back to cited text no. 11    
12.Alexopoulos E, Stangou M, Papagianni A, Pantzaki A, Papadimitriou M. Factors influen­cing the course and the response to treatment in primary focal segmental glomerulosclerosis. Nephrol Dial Transplant 2000;15(9):1348-56.  Back to cited text no. 12    
13.Dumoulin A, Hill GS, Montseny JJ, Meyrier A. Clinical and morphological prognostic factors in membranous nephropathy: significance of focal segmental glomerulosclerosis. Am J Kidney Dis 2003;41(1):38-48.  Back to cited text no. 13    
14.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(8):2169-77.  Back to cited text no. 14    
15.Chitalia VC, Wells JE, Robson RA, Searle M, Lynn KL. Predicting renal survival in primary fo­cal glomerulosclerosis from the time of presen­tation. Kidney Int 1999;56(6):2236-42.  Back to cited text no. 15    
16.Wehrmann M, Bohle A, Held H, et al. Long­term prognosis of focal sclerosing glomerulo­ nephritis: An analysis of 250 cases with particular regard to tubulointerstitial changes. Clin Nephrol 1990;33:115-22.  Back to cited text no. 16  [PUBMED]  
17.Korbet SM, Schwartz MM, Lewis EJ. The prognosis of focal segmental glomerular scle­rosis of adulthood. Medicine 1986;65:304-11.  Back to cited text no. 17  [PUBMED]  
18.Velosa J, Holley K, Torres V, Offord K. Signi­ficance of proteinuria on the outcome of renal function in patients with focal segmental glome­rulosclerosis. Mayo Clin Proc 1983;58:568-77.  Back to cited text no. 18    
19.Abrantes MM, Cardoso LS, Lima EM, et al. Predictive factors of chronic kidney disease in primary focal segmental glomerulosclerosis. Pediatr Nephrol 2006;21(7):1003-12.  Back to cited text no. 19    
20.Banfi G, Moriggi M, Sabadini E, et al. The impact of prolonged immunosuppression on the outcome of idiopathic focal segmental glome­rulosclerosis with nephrotic syndrome in adults: A collaborative retrospective study. Clin Nephrol 1991;36:53-9.  Back to cited text no. 20  [PUBMED]  
21.Schwartz MM, Korbet SM. Primary focal seg­mental glomerulosclerosis: Pathology, histologic variants, and pathogenesis. Am J Kidney Dis 1993;22:874-83.  Back to cited text no. 21  [PUBMED]  
22.Peruzzi L, Trussolino L, Amore A, et al. Tubulo­interstitial responses in the progression of glomerular diseases: Albuminuria modulates vf5 integrin. Kidney Int 1996;50:1310-20.  Back to cited text no. 22    
23.Border WA, Noble NA. Mechanisms of disease: Transforming growth factor fi in tissue fibrosis. N Engl J Med 1994;331:1286-92.  Back to cited text no. 23  [PUBMED]  [FULLTEXT]
24.Ruoslahti E, Noble NA, Kagami S, Border WA. Integrins. Kidney Int 1994;45[Suppl 44]:S17-22.  Back to cited text no. 24    

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Correspondence Address:
Diana Taheri
Department of Pathology, Isfahan University of Medical Sciences, Isfahan
Iran
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PMID: 19414944

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    Figures

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