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  Table of Contents    
ORIGINAL ARTICLE  
Year : 2011  |  Volume : 54  |  Issue : 1  |  Page : 42-46
Morphologic evaluation of renal function using semi-quantitative method in primary nonproliferative glomerular diseases


1 Department of Pathology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad - 500 082, India
2 Department of Nephrology, Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad - 500 082, India

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Date of Web Publication7-Mar-2011
 

   Abstract 

Context: Fibrosis is universally accepted as a poor prognostic finding in renal pathology. Semi-quantitative assessment is widely used for prognostication in pathology. Aims: We propose a semi-quantitative method to prognosticate primary nonproliferative glomerular diseases. Settings and Design: A semi-quantitative method based on Banff schema, 97 classification has been modified to suit the requirements. Glomerular, tubulointerstitial, and vascular compartments were scored independently, and the scores were totaled to obtain total scores. Materials and Methods: Seventy-six renal biopsies were assessed by semi-quantitative scores and the individual compartmental and total scores were correlated with serum creatinine levels. Follow-up was available in 24 cases. Statistical Analysis: Pearson correlation coefficient, two-tailed t test, to determine the P value. Results: P values were significant for the total scores as well as individual compartments. There is a linear correlation between the scores and serum creatinine levels. A total score of ≥5 was significant. Conclusions: The semi-quantitative scoring system based on modified Banff schema, 1997 is useful in prognosticating renal biopsies in primary nonproliferative glomerular diseases.

Keywords: Nonproliferative, primary glomerular, prognosis, renal biopsy, semi-quantitative

How to cite this article:
Prayaga AK, Anuradha S V, Manjusha Y, Uppin M, Rapur R, Dakshina Murthy K V. Morphologic evaluation of renal function using semi-quantitative method in primary nonproliferative glomerular diseases. Indian J Pathol Microbiol 2011;54:42-6

How to cite this URL:
Prayaga AK, Anuradha S V, Manjusha Y, Uppin M, Rapur R, Dakshina Murthy K V. Morphologic evaluation of renal function using semi-quantitative method in primary nonproliferative glomerular diseases. Indian J Pathol Microbiol [serial online] 2011 [cited 2019 Nov 22];54:42-6. Available from: http://www.ijpmonline.org/text.asp?2011/54/1/42/77322



   Introduction Top


Fibrosis as harbinger of poor prognosis is universally accepted in renal pathology. Renal biopsy, initially used only for diagnorsis is now accepted also as a prognostic tool. Several studies showed that the tubulointerstitial fibrosis is the most important cause of renal insufficiency. [1],[2],[3],[4] Morphometric studies have long been studied to prove it. However, morphometric evaluations are best done for research purposes as they are time consuming. Semi-quantitative methods are more useful in routine practice. Banff schema for renal transplant biopsy evaluation, activity and chronicity scoring for lupus nephritis and the new Oxford scoring system for IgA nephropathy are examples of semi-quantitative assessments used for prognosis on renal biopsies. [5],[6],[7] In this study we have attempted to use semi-quantitative analysis for assessing renal functions in primary nonproliferative glomerular diseases.


   Materials and Methods Top


Seventy-six consecutive renal biopsies with clinical and morphologic features of primary nonproliferative glomerular diseases were retrieved from the case records of the departments of pathology and nephrology. Inclusion criteria were a minimum of 10 glomeruli and histopathologic diagnosis of a nonproliferative glomerular disease, and the availability of serum creatinine. Subjects with essential hypertension, diabetes mellitus, and other known systemic diseases were not included in the study. Follow-up was available for 24 cases with a minimum of 2 months to a maximum of 3 years.

The tissues were fixed in Bouin's fixative and then subjected to routine hematoxylin and eosin (H and E) stain and special stains included periodic acid-Schiff, Jones' silver methanamine, and Masson trichrome stains. Immunofluorescence was done in all the cases.

Semi-quantitative analysis of renal biopsies was done by a modification of Banff schema, 1997 [Table 1]. [5] Sclerosis ≥ 50% of the glomerulus was considered for glomerular score. All the compartments were assessed independently. The scores of all compartments were added to obtain the total score, which varied from 0 to 15. Statistical analysis was done by Pearson correlation coefficient, two-tailed t test, to determine the P value.
Table 1: Semi-quantitative scores based on the involvement of glomerular, tubular, interstitial, and vascular compartments-a modification of Banff schema, 1997

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   Results Top


Seventy-six consecutive renal biopsies with clinical and morphologic features of nonproliferative primary glomerular diseases were chosen. There were 26 cases of minimal change disease (MCD), 25 cases of membranous nephropathy (MN), and 25 cases of focal segmental glomerulosclerosis (FSGS) [Figure 1], [Figure 2] and [Figure 3]. Age ranges from 5 to 48 years with mean age of 24 years in MCD with a male to female ratio of 3.3:1. Age ranges from 28 to 55 years with mean age of 42 years in MN with a male to female ratio of 3:1. Age ranges from 5 to 38 years with mean age of 27 years in FSGS with a male to female ratio of 4:3. The baseline serum creatinine in MCD, MN, and FSGS was 0.8 ± 0.23, 1.2 ± 0.43, 1.2 ± 0.55, respectively. Sixteen patients had hypertension at presentation, 13 had FSGS, and 3 MN.
Figure 1: Renal biopsy shows a normal looking glomerulus, tubules, and interstitium in minimal change disease. (silver methanamine-periodic acid-Schiff stain, ×200)

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Figure 2: Renal biopsy shows a glomerulus with rigid basement membrane normal looking, tubules and interstitium in membranous nephropathy. (silver methanamine-periodic acid-Schiff stain, ×200)

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Figure 3: Renal biopsy shows segmental sclerosis in a glomerulus, atrophic tubules, and interstitial fibrosis in focal segmental glomerulosclerosis. (silver methanamine-periodic acid-Schiff stain, ×200)

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Pearson coefficient for all the three groups showed a significant correlation between serum creatinine and semi-quantitative scores, with a P value of 0.0001 [Chart 1]. In addition there was significant correlation between serum creatinine and glomerular sclerotic changes, tubular atrophic changes, interstitial fibrosis, interstitial inflammation, and vascular fibrosis intimal thickening with P values < 0.0001, < 0.001, < 0.001, < 0.0004, and < 0.01, respectively [Charts 2-6].

Serum creatinine was >1.3 mg/dL in 15 patients at the time of biopsy, and in 9 (60%) of them the total scores were ≥5. Two-tailed t test was 0.001. Pearson correlation was linear (0.000) between the total scores and serum creatinine levels. In 24 cases, the total scores were ≥5 at the time of biopsy.

Follow-up was available for 24 patients; 5 of them needed renal replacement therapy, 3 before 1 year and 2 before 2 years. In all the 5 cases, the total scores were ≥5 [Table 2].
Table 2: Total semi-quantitative scores and outcome of patients on follow-up (n=24)

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   Discussion Top


Semi-quantitative methods are in use in renal pathology from the initial days. Risdon et al. assessed the glomerular and tubular changes in patients with "persistent glomerulonephritis" and concluded that the correlation was significant between the extent of tubular damage and creatinine clearance. [8] Bohle et al. objectively assessed relative area of the cortical interstitium by stereology on routine histologic sections with the levels of serum creatinine. [9],[10]

Some of the semi-quantitative methods used for prognosis in allograft and native renal biopsies include Banff schema, activity, and chronicity indices for lupus nephritis and the new Oxford scoring system for IgA nephropathy. [5],[6],[7] However, a majority of the studies on native kidney diseases were proliferative glomerular diseases. Dumoulin et al. studied the significance of secondary FSGS in MN using semi-quantitative assessment. [11] Okoń et al.[12] have used a semi-quantitative method similar to the one used in the present study to study primary glomerular diseases, both proliferative and nonproliferative.

In the present study, semi-quantitative estimation of glomerular, tubular, interstitial, and vascular changes in primary nonproliferative glomerular diseases was done. Both the total scores and scores of individual compartments were compared with serum creatinine levels. In this study, no attempt was made to differentiate between segmental and global sclerosis. Similarly, the difference between MN and MN with secondary FSGS was also not assessed. The scoring system we have adopted was similar to the one used by Okoń et al., [12] but the vascular changes were simplified in the present study for easy applicability. In our opinion it has not adversely affected our results in the final analysis because Okoń et al.[12] did not find the vascular scores to be significant in assessing the renal function. The patients with MN were older compared with the other two groups, but we have not taken it into consideration while assessing the vascular changes. Our results compare well with their results for glomerular, tubular, and interstitial compartments. The scores of individual compartments and the total scores correlated well with serum creatinine with significant P values.

Of the 24 patients who were followed-up, 5 had to receive renal replacement therapy. The initial diagnoses were FSGS for 4 and MN with secondary FSGS for 1. These patients had total scores of ≥5; with contribution from all the 4 compartments, serum creatinine was interestingly normal in 2 and marginally elevated in 3 at the time of diagnosis. It is possible that structural damage preceded functional damage and the latter was precipitated by a possible acute insult during the course. In 2 cases with score 5 and 1 case with 6 renal function remained normal on follow-up. The total scores were ≥5 in 24 of 76 patients; in all these cases, tubular atrophy, interstitial inflammation, and fibrosis were present. Glomerular sclerosis was seen in 23 (95.8%) cases. A single case of membranous nephropathy showed a score of 5 without glomerular sclerosis. Serum creatinine was normal at presentation. However, this case had no follow-up. Vascular sclerosis was seen in 10 (41.6%) of these 24 cases.

Semi-quantitative studies done for nonproliferative glomerular diseases are fewer in number compared with proliferative glomerular diseases and transplant biopsies, and they are not systematic. Most of the studies have taken only glomerular sclerosis and interstitial fibrosis for evaluation. Almost all the studies have highlighted the role of interstitial compartment. Some studies found a strong correlation between glomerular sclerosis and interstitial fibrosis. However, Dumoulin et al.[11] showed that the interstitial changes alone were significant in their study on the significance of FSGS in membranous nephropathy. They have semi-quantitatively assessed the stage of MN, vascular lesions, and the degree of interstitial fibrosis in pure MN and MN with FSGS. Okoń et al.[12] have done morphometric study in a variety of glomerular disorders and correlated with semi-quantitative studies. In their study interstitial volume correlated with sclerotic glomeruli, tubular atrophy, and interstitial fibrosis with mesangial expansion.













The authors concluded that the strongest correlate is relative interstitial volume. In the present study all the 4 compartments show significant involvement. They argued that it is possible to have normal glomeruli with raised creatinine and sclerotic glomeruli with normal creatinine, but the interstitial volume is a consistent indicator of renal function. [12]

However, Kriz and LeHir [13] hypothesized from their experience with animal experiments, that podocytes play a crucial role in renal damage, producing atubular glomeruli and aglomerular tubules. Progressive loss of podocytes results in adhesion of glomerular tuft to the parietal epithelial cells. As the glomerulus has limited capacity for repair, adhesion results in segmental sclerosis. The capillary loops now adherent to the Bowman's capsule send out protein-rich urine directly to the interstitial compartment, resulting in fibrosis. While agreeing that glomerular proteinuria results in tubulointerstitial damage, the authors pointed that there is no convincing evidence to show that interstitial fibrosis is harmful to normal glomeruli. It is understandable as all the compartments are interconnected anatomically and functionally. Renal glomerular capillaries are unique because unlike in other tissues, they travel beyond into the interstitium to form peritubular capillaries. Interstitium is considered to be extraglomerular mesangium. Bowman's space of glomerulus continues as proximal convoluted tubule.

El Nahas [14] opined that the cells in glomerulus, tubulointerstitial compartments have plasticity and show transdifferentiation. Renal injury induces embryonic mesenchymal phenotype in glomerular and tubular epithelial cells. This reversal to embryogenesis is responsible both for healing and scarring. Renal remodeling also involves migration of hematopoietic stem cells into the kidney. In a dynamic process involving the native cells, inflammatory cells, bone marrow stem cells, collagen I and III help in renal remodeling. This understanding he felt has therapeutic implications. [14] Similar observations were made by Hugo et al.[15] who demonstrated migration of extraglomerular mesangial cells into the glomerulus.

In this study, we have tried to use semi-quantitative assessment systematically for nonproliferative glomerular diseases and suggested a cutoff value for the scores thus obtained to predict the chances for deterioration of renal function. It is not possible to point out the initial insult based on the present study, but we can conclude that strict compartmentalization is not possible and changes in one compartment lead to changes in others. This study also highlights the utility of a modification of semi-quantitative score already in use to prognosticate renal biopsies in nonproliferative glomerular diseases.


   Acknowledgment Top


The authors are thankful to Dr. Sumeet Agarwal, assistant professor in Rheumatology, Nizam's Institute of Medical Sciences for statistical support and Dr. Uttara Das and Dr. Swarnalata, assistant professors, Nephrology, Nizam's Institute of Medical Sciences, for data collection.

 
   References Top

1.Schainuck LI, Striker GE, Cutler RE, Benditt EP. Structural-functional correlations in renal disease. Part II: The correlations. Hum Pathol 1970;1:631-41.   Back to cited text no. 1
    
2.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;15:1348-56.  Back to cited text no. 2
    
3.Sund S, Grimm P, Reisæter AV, Hovig T. Computerized image analysis vs semi quantitative scoring in evaluation of kidney allograft fibrosis and prognosis. Nephrol Dial Transplant 2004;19:2838-45.   Back to cited text no. 3
    
4.Khan N, Sinniah R. Morphometric study showing the importance of distal tubular damage in impaired creatinine clearance. Am J Nephol 1993;13:178-83.   Back to cited text no. 4
    
5.Racusen LC, Solez K, Colvin RB, Bonsib SM, Castro MC, Cavallo T, et al. The Banff 97 working classification of renal allograft pathology. Kidney Int 1999;55:713-23.   Back to cited text no. 5
    
6.Roberts IS, Cook HT, Troyanov S, Alpers CE, Amore A, Barratt J, et al. The Oxford classification of IgA nephropathy: Pathology definitions, correlations, and reproducibility. Kidney Int 2009;76:546-56.  Back to cited text no. 6
    
7.Austin HA 3 rd , Muenz LR, Joyce KM, Antonovych TA, Kullick ME, Kippel JH, et al. Prognostic factors in lupus nephritis. contribution of renal histologic data. Am J Med1983;75:382-91.  Back to cited text no. 7
    
8.Risdon RA, Sloper JC, De Wardener HE. Relationship between renal function and histological changes found in renal-biopsy specimens from patients with persistent glomerular nephritis. Lancet 1968;2:363-6.  Back to cited text no. 8
    
9.Glomb BA. Grund KE, Mackensen S. Correlation between relative interstitial volume of renal cortex and serum creatinine concentration in minimal change disease with nephrotic syndrome and focal segmental glomerulonephritis. Virchows Arch Path 1977;376:221-32.  Back to cited text no. 9
    
10.Bohle A, Grund KE, Mackensen S, Tolon M. Correlations between renal interstitium and level of serum creatinine. Virchows Arch A Pathol Anat Histol 1977;373:15-22.  Back to cited text no. 10
    
11.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;41:38-48.  Back to cited text no. 11
    
12.Okoñ K, Sulowicz W, Smolenski O, Sydor A, Chrusciel B, Kirker-Nowak A, et al. predicting kidney function from renal biopsy. Semiquantitative versus quantitative approach. Pol J Pathol 2007;58:65-71.  Back to cited text no. 12
    
13.Kriz W, LeHir M. Pathways of nephron loss in glomerular diseases-Insights from animal models. Kidney Int 2005;67:404-19.  Back to cited text no. 13
    
14.El Nahas M. Kidney remodeling and scarring: The plasticity of cells. Nephrol Dial Transplant 2003;18:1959-62.  Back to cited text no. 14
    
15.Hugo C, Shankland SJ, Bowen-pope DF, Couser WG, Johnson RJ. Extraglomerular origin of the mesangial cell after injury. A new role of the juxtaglomerular apparatus. J Clin Invest 1997;100:786-94.  Back to cited text no. 15
    

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Correspondence Address:
Aruna K Prayaga
Nizam's Institute of Medical Sciences, Punjagutta, Hyderabad - 500 082
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0377-4929.77322

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