PRESENTED BY
INGEBORG M. BAJEMA

Presentation Summary

Written by Jasna Trbojevic-Stankovic
Reviewed by Ingeborg M. Bajema

Systemic lupus erythematosus is an autoimmune disease affecting numerous organs and systems. Approximately 60% of patients with systemic lupus tend to develop renal manifestations known as lupus nephritis (LN). The histopathological findings in LN show considerable individual and time-related variations and represent an important tool for treatment decisions.

The Lupus Nephritis Classification System
The Lupus nephritis classification is was the first histopathological classication system for renal disease. A range of publications in the 1950’s and 1960’s identified three main patterns in lupus nephritis: the mesangial pattern, the so-called ‘proliferative’pattern to which we refer to today as a pattern with endocapillary hypercellularity and the membranous pattern. These three patterns are still the pillar of the contemporary classification and are contained in classes II to V. Classes I and VI have either minimal histologic changes (class I) or are severely affected by glomerular sclerosis (Class VI) (Figure 1).

Figure 1. ISN/RPS (2003) classification of LN [1]

 

 

Further analysis with immunofluorescence and electron microscopy may reveal the presence of deposits whose specific site may impact further development of histological lesions. Endothelial deposits are characteristic for classes III and IV, the subepithelial ones produce the membranous pattern of the LN class V, while those located in the mesangial area are characteristic for class II. A combination of all these locations is usually found. The condition of lesions can further be graded as acute or chronic, which is especially important to emphasize in classes III and IV.

In spite of all efforts to somehow categorize histological patterns of LN, the numerous combinations and variations of the mentioned alterations that are often found in clinical practice, can make it difficult to determine the dominant pattern and fit the finding into one of the predetermined classes. Thus a rather refined classification system has been suggested in 2003, which again recognizes 6 main classes but with more subclasses [2]. Such a sophisticated system may, however, lead to interobserver discrepancy and disagreements as any particular item – the type of lesions, predominance, acuteness or chronicity, may be a subject of dispute.

As an example, the following histological sample is discussed, presenting a case of a glomerulus with mostly mesangial lesion (Figure 2, green arrow), but uncertain endocapillary hypercellularity indicated by small black arrows.

Figure 2. An example of mostly mesangial LN [3]

 

 

Several options may be considered in the pathology evaluation of such histological sample: purely mesangial hyperplasia, typical for Class II LN, or concomitant inflammatory lesions, which would allocate this case to Class III or even class IV LN, depending on the findings in the other glomeruli of the biopsy Importantly, such a finding in just one glomerulus might significantly change the pathohistological classification and further treatment decisions. Not only inflammatory cells in the capillary lumen but also those in the mesangial areas are considered indicate of class III/IV lesions, which may be present in Figure 2, as indicated by the blue arrow. A perspective of what may be hiding behind mesangial proliferative lesions is presented in Figure 3, presenting a nice example of a cause of possible interobserver disagreement should not all elements of endocapillary and mesangial hypercellularity be strictly and meticulously described.

Figure 3. Ultrastructural features of a glomerulus affected by LN [4]

 

 

 

The presented cases put before us a new challenge to decide how all of these considerations help in the clinical setting and whether we should start anew and find out the clinical importance of LN histological lesions, putting aside the classification. Whether a new classification could be the key or relying on the existing one but separating glomerular, interstitial and vascular lesions – some of which are not even incorporated in the current classification scheme – is a discussion currently held by scientists and clinicians involvedin the clinical management of LN. A recent study by Rijnink et al. in which the LN classification was set aside and multiple, individual histopathological lesions were scored and related to outcome, suggested that at least fibrinoid necrosis, fibrous crescents, and interstitial fibrosis/tubular atrophy warrant explicit independent scoring to assess the risk of progressive renal dysfunction. The study suggest that the LN classification should include an index of evidence-based prognosticators, also in conjunction with clinical findings. [5].

In the spirit of change, apart from looking at the various patterns, another important point when reporting histopathological findings is assessing and stating the activity and chronicity indices, especially when multiple biopsies are available from the same patient. This recommendation, together with new definitions for glomerular lesions and other recommendations can be found in a recent consensus report on the LN classification (4).

Conclusion
The histopathological classification for LN is an important determinator for the therapy of LN. The latest edition of the classification is hampered by interobserver disagreement amongst pathologists and the creation of multiple subclasses of which the clinical utility is uncertain. Recommendations to adjust the classification scheme were recently made, and there is a continuous effort to make the definitions more clear, point all variants of histological classes and ultimately to improve the pathohistological classification of LN in hope that it will contribute to better clinical management of the patients.

 

References

1. Markowitz GS, D’Agati VD. The ISN/RPS 2003 classification of lupus nephritis: An assessment at 3 years. Kidney Int 2007;71:491-495. DOI: 10.1038/sj.ki.5002118

2. Weening JJ, D’Agati VD, Schwartz MM, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 2004;15:241-250. DOI:10.1097/01.asn.0000108969.21691.5d

3. Bajema I. M. Histological classification of lupus nephritis – time for a change. Presented at 56th ERA-EDTA Congress, Budapest, Hungary, June 15, 2019. Available on ERA-EDTA Virtual Meeting

4. Bajema IM, Wilhelmus S, Alpers CE, et al. Revision of the International Society of Nephrology/Renal Pathology Society classification for lupus nephritis: clarification of definitions, and modified National Institutes of Health activity and chronicity indices. Kidney Int. 2018;93(4):789-796. DOI: 10.1016/j.kint.2017.11.023.

5. Rijnink EC, Teng YKO, Wilhelmus S, et al. Clinical and Histopathologic Characteristics Associated with Renal Outcomes in Lupus Nephritis. Clin J Am Soc Nephrol. 2017;12(5):734-743. DOI: 10.2215/CJN.10601016.

NDT-E Summary Articles