Role of Digital Image Analyser in Evaluation of Chronicity Index for Lupus Nephritis
Authors: Hussien Nashwa Mohamed , Abd EL Salam Magda Mohamed , Salman Manal Ibrahim , Mahmoud Heba Ahmed 
Published: November 2024

Abstract

Introduction
Lupus nephritis is the most important cause of morbidity and mortality in systemic lupus erythematosus. Lupus nephritis patients with high chronicity index especially with moderate to severe tubular atrophy and interstitial fibrosis detected in renal biopsy are at much higher risk of developing end stage renal disease and death. The assessment of glomerular sclerosis and fibrous crescent percentages can be easily done without inter-observer variability, On the other hand, the assessment of the percentages of tubular atrophy and interstitial fibrosis is routinely done by visual assessment, that is subjective and might lack accuracy or interobserver agreement. The challenge is to quantify the interstitial fibrosis and tubular atrophy with accuracy and to minimize the inter-observer variability. Digital image analysis is an easily used objective tool with more accurate measurements, which can be used in conjunction with visual assessment.

Material & Methods
The study included renal biopsy stained sections of 50 cases with lupus nephritis having chronic lesions. Tubular atrophy and interstitial fibrosis (IFTA)were evaluated in Masson Trichrome and PAS stained sections. IFTA was graded on a scale from I to III through visual assessment according to the percentage of IFTA of the cortex(&lt;25%, 25-50% and &gt;50% respectively). Sequential imaging of the whole renal cores was done by microscopic camera and the IFTA score was evaluated using a software image analyser digitally as a percentage of the total cortical area. The results of the same cases obtained by the two methods were compared and statistically analyzed.

Results
The study included 15 cases ISN/RPS class III (A/C), 23 cases ISN/RPS class IV (A/C), 10 cases ISN/RPS class V (4 cases combined with class III, 2 cases combined with class IV and 4 cases were pure class V) and 2 cases ISN/RPS class VI. The NIH activity indices ranged from 2-21out of 24 and the chronicity indices ranged from 2-9 out of 12. The IFTA scores evaluated by subjective visual assessment were classified into three grades. 34 cases were grade I (68%), 14 cases were grade II (28%) and 2 cases were grade III (4%). Regarding digital image analysis results, the cortical area of studied cases ranged from 296801µm²to1809799µm² (mean=670643.92 ± SD 216343.94). The Sum of areas of IFTA in studied cases ranged from 45987µm² to 656231 µm² (mean=222409.30 ± SD 152016.67). The Percentage (Sum of areas of IFTA / Cortical area) ranged from 6.08% to 74.02% (mean=30.56 ± SD 17.13). The grades of IFTA calculated by digital image analysis were: 26 cases grade I (52%), 15 cases grade II (30%) and 9 cases grade III (15%). Comparing the visually assessed IFTA grades with the image analyzer results revealed that in grade I IFTA, 23 cases were also graded I by digital image analysis (concordant in 67.65%), while 11 cases were upgraded to grade II by digital image analysis (32.35%). In IFTA grade II, 4 cases were also graded II by digital image analysis (concordant in 28.57), while 7 cases were upgraded to grade III (50%), and 3 cases were downgraded to grade I (21.43%) by digital image analysis. All cases with IFTA grade III by visual assessment were also graded III by digital image analysis (concordant in 100%). There was a fair agreement between the two methods (weighted Kappa measure for agreement = 0.40) with an overall concordance 58%, over grading in 36% and under grading in 6%. Any change (either increase or decrease) in cortical area had no significant correlation with IFTA score (P value 0.94). As regard the validity of visual assessment of IFTA grade compared to digital image analyser in different IFTA grades, in IFTA grade I, the accuracy was 72%, the sensitivity and specificity were 67.6% and 81.3% respectively, PPV 88.5%and NPV 54.2%. IFTA grade II has shown less accuracy 58%, less sensitivity and specificity (28.6% and 69.4%) respectively, with a lower PPV 26.7% and a higher NPV 71.4%. On the other hand, IFTA grade III has shown the highest accuracy 86%, highest sensitivity and specificity 100% and 85.4% respectively. The highest NPV100% and the least PPV 22.2%. This means that the severe IFTA grade can’t be missed by visual assessment, also the very low IFTA grade can also be easily identified by the visual assessment, but between the two extremes, the precise determination of the involved area will be difficult to assess without the help of digital image analyser.

Conclusion
Digital image analysis is an easily used tool that can improve the accuracy of measurement of chronicity index in lupus nephritis which has a great impact on treatment strategies and prognosis in these patients. Preferably it is recommended to be widely used in assessment of renal biopsy in lupus nephritis as well as different renal lesions