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 Table of Contents  
EDITORIAL
Year : 2017  |  Volume : 12  |  Issue : 1  |  Page : 2-3

Renal biopsy in lupus nephritis: To do or not to do?


1 Department of Nephrology, Post Graduate Institute of Medical Education and Research, Chandigarh, India
2 Department of Internal Medicine, Post Graduate Institute of Medical Education and Research, Chandigarh, India
3 Department of Histopathology, Post Graduate Institute of Medical Education and Research, Chandigarh, India

Date of Web Publication23-Feb-2017

Correspondence Address:
Manish Rathi
Department of Nephrology, Post Graduate Institute of Medical Education and Research, Sector-12, Chandigarh - 160 012
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0973-3698.199132

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How to cite this article:
Rathi M, Sharma A, Nada R. Renal biopsy in lupus nephritis: To do or not to do?. Indian J Rheumatol 2017;12:2-3

How to cite this URL:
Rathi M, Sharma A, Nada R. Renal biopsy in lupus nephritis: To do or not to do?. Indian J Rheumatol [serial online] 2017 [cited 2017 Mar 28];12:2-3. Available from: http://www.indianjrheumatol.com/text.asp?2017/12/1/2/199132

Kidneys are one of the most common major organs to be involved in systemic lupus erythematosus (SLE). Although lupus nephritis (LN) is the most common renal involvement in SLE, and is reported to occur in 50%–80% of cases,[1] kidneys can also be involved due to other lesions.[2] Till date, renal biopsy is the gold standard for diagnosis LN and all major guidelines recommend performing renal biopsy in suspected cases of LN. Kidney Disease: Improving Global Outcomes recommends that LN should be suspected in SLE patients with proteinuria, renal dysfunction, active sediments, or hypertension and further all LN cases should be confirmed by renal biopsy.[3] The European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association recommends to do renal biopsy if there is reproducible proteinuria of >0.5 g/day,[4] whereas the American College of Rheumatology recommends to do renal biopsy in SLE cases if they have one of the following: 24 h proteinuria >1 g, or abnormal renal function or 24 h proteinuria >0.5 g along with either active sediments or cellular casts.[5] The importance of renal biopsy is further stressed by the Systemic Lupus International Collaborative Clinics criteria, according to which renal biopsy finding characteristic of LN in the presence of either positive antinuclear antibody or anti-double stranded (anti-dsDNA) antibody is sufficient to classify the patient as SLE.[6] However, despite all these recommendations and guidelines, there is always a debate and doubt about the necessity of doing renal biopsy in the cases of LN. The arguments put forward against the need of doing renal biopsy are that usually there is good clinicopathological correlation; one can predict class of LN by clinical and laboratory parameters; all forms of LN can be well treated by immunosuppressive drugs; and the renal biopsy is an invasive and painful procedure with significant complications.[7] The last argument at least is well settled beyond doubt and with latest advancements in technique of renal biopsy, it is now a simple day-care procedure without any major complications.[8]

Considering the wide spectrum of LN, attempts have been made to classify it. In 2003, the International Society of Nephrology and Renal Pathology Society came out with the present classification.[9] The main purpose of this classification was to standardize the diagnostic definitions, and to improve inter-observer reproducibility and clinicopathological correlations. However, this classification has several limitations:First, it is solely based on glomerular lesions and does not take the tubulo-interstitial and vascular compartments into consideration; second, sclerotic lesions are considered the part of disease and sometimes it is difficult to differentiate sclerosed glomeruli due to the disease process from those which are age-related or ischemic; and finally, it takes into account the light and immunofluorescence microscopy findings but not the electron microscopic examination and immune deposits may be more widespread in location on the ultra-structural examination.[10] However, despite these limitations, this classification is now well accepted as the standard of care and helps in deciding the most appropriate immunosuppressive therapy.[11]

The proponents of renal biopsy argue that in addition to the class of LN, renal histology provides other important information also, all of which can have significant implication on deciding treatment and prognosis. Some of these are extent of activity and chronicity parameters, presence and extent of crescents, and the presence of extra-glomerular involvement such as thrombotic microangiopathy (TMA) and tubulo-interstitial nephritis. Occasionally, one can also encounter glomerular lesions other than LN like lupus podocytopathy.[2],[12]

In the current issue of Indian Journal of Rheumatology, Chelliah et al. have published an article “Is renal biopsy always necessary to start immunosuppressive therapy in lupus nephritis?”[13] The basic question in this paper is whether a renal biopsy is required before starting immunosuppressive therapy in LN and whether one can predict proliferative LN with serological markers. In this study, authors have studied fifty female patients between the age group of 15 and 45 years with biopsy proven LN and correlated them with the positivity of anti-dsDNA antibodies and low complements levels. Of fifty patients, 35 patients (70%) had Class IV LN, 7 (14%) Class II, 4 (8%) Class V, and four patients (8%) had Class IV + V LN. Thus, a total of 39 patients (78%) had proliferative LN (Class IV/IV + V).

A total of 41 (82%) patients had anti-dsDNA positivity, 34 (68%) had low C3 levels, and 37 (74%) had low C4 levels. The rates of anti-dsDNA positivity and low C3 and C4 were higher in patients with proliferative LN as compared with nonproliferative classes. A logistic regression analysis was performed to analyze the correlation between these three serological variables and proliferative LN. The authors noted that all these three variables independently predicted proliferative LN. Of the 39 patients with proliferative LN, 28 (72%) had the combination of positive anti-dsDNA, low C3, and low C4 levels, whereas, none of the patients with nonproliferative LN had similar combination. They noted that the positive predictive value of combination of these three serological markers was 100% for proliferative LN, that is, whoever had the combination of anti-dsDNA positivity, low C3 and low C4 showed only proliferative LN on renal biopsy and thus, the authors concluded that biopsy may not be required in such patients and treatment can be started directly.

However, still 28% of proliferative LN patients did not have this combination of serological markers and could have been picked up only on biopsy. An important limitation of this study is that there were no Class III/III + V patients in the study. As these classes also come under proliferative LN, we are not sure if these results apply to these classes also and whether these serological markers can differentiate between Class III and Class IV LN. This is important as the treatment may be different for the two classes. Similarly, the authors have not studied whether this combination can differentiate between Class IV and IV + V. As per the emerging evidence, the treatment options may be different for these two classes, where multi-targeted therapy is more effective for Class IV + V.[14] Although the authors state that the serological markers can predict class IV LN, this class is quiet heterogeneous. There is Class IVS and IVG and also there is IV A versus IV C. In addition, there is crescentic Class IV LN. This heterogeneity is important to know and differentiate as it can have both therapeutic and prognostic implications. Similarly, the authors have not discussed about other additional information that can be received on histology and can have therapeutic implications. This includes activity and chronicity indices, vascular lesions, TMA, presence, type, and extent of crescents, etc., The authors concluded that serological profile of SLE had significant correlation with histopathology of LN, which is probably wrong. These serological markers just correlated with the proliferative LN and not with entire histopathology. The authors have also excluded patients with serum creatinine of more than 1.8 mg/dl, childhood LN and the male patients from the study and thus, these results may not be applicable to these patient groups.

Although it is true as claimed by authors that there can be a case for starting immunosuppressive therapy without renal biopsy, which immunosuppressive treatment to give and what will be the expected prognosis can be decided better with renal biopsy. The issue of whether one should start immunosuppressive drugs first and do renal biopsy subsequently if the patient does not improve remains a point of contention and researchers believe that it might be late by that time and we would have lost a window of opportunity by that time.[7]

 
  References Top

1.
Mittal T, Rathi M. Rheumatological diseases and kidneys: A nephrologist's perspective. Int J Rheum Dis 2014;17:834-44.  Back to cited text no. 1
    
2.
Baranowska-Daca E, Choi YJ, Barrios R, Nassar G, Suki WN, Truong LD. Nonlupus nephritides in patients with systemic lupus erythematosus: A comprehensive clinicopathologic study and review of the literature. Hum Pathol 2001;32:1125-35.  Back to cited text no. 2
    
3.
Kidney Disease: Improving Global Outcomes (KDIGO) Glomerulonephritis Work Group. KDIGO clinical practice guideline for glomerulonephritis. Kidney Int Suppl 2012;2:139-274.  Back to cited text no. 3
    
4.
Bertsias GK, Tektonidou M, Amoura Z, Aringer M, Bajema I, Berden JH, et al. Joint European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association (EULAR/ERA-EDTA) recommendations for the management of adult and paediatric lupus nephritis. Ann Rheum Dis 2012;71:1771-82.  Back to cited text no. 4
    
5.
Hahn BH, McMahon MA, Wilkinson A, Wallace WD, Daikh DI, Fitzgerald JD, et al. American College of Rheumatology guidelines for screening, treatment, and management of lupus nephritis. Arthritis Care Res (Hoboken) 2012;64:797-808.  Back to cited text no. 5
    
6.
Petri M, Orbai AM, Alarcón GS, Gordon C, Merrill JT, Fortin PR, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum 2012;64:2677-86.  Back to cited text no. 6
    
7.
Haladyj E, Cervera R. Do we still need renal biopsy in lupus nephritis? Reumatologia 2016;54:61-6.  Back to cited text no. 7
    
8.
Golay V, Sarkar D, Thomas P, Trivedi M, Singh A, Roychowdhary A, et al. Safety and feasibility of outpatient percutaneous native kidney biopsy in the developing world: Experience in a large tertiary care centre in Eastern India. Nephrology (Carlton) 2013;18:36-40.  Back to cited text no. 8
    
9.
Weening JJ, D'Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 2004;15:241-50.  Back to cited text no. 9
    
10.
Rathi M, Gupta KL, Joshi K, Gupta PK, Sharma A, Kohli HS, et al. Histopathological indicators of disease outcome in class IV lupus nephritis: A revisit of various indices. Rheumatol Int 2015;35:1511-7.  Back to cited text no. 10
    
11.
Rathi M, Goyal A, Jaryal A, Sharma A, Gupta PK, Ramachandran R, et al. Comparison of low-dose intravenous cyclophosphamide with oral mycophenolate mofetil in the treatment of lupus nephritis. Kidney Int 2016;89:235-42.  Back to cited text no. 11
    
12.
Parikh SV, Alvarado A, Malvar A, Rovin BH. The kidney biopsy in lupus nephritis: Past, present, and future. Semin Nephrol 2015;35:465-77.  Back to cited text no. 12
    
13.
Chelliah V, Balaraman V, Ilango S, Ramesh S, Bhaba VK, Shivakumar D. Is renal biopsy always necessary to start immunosuppressive therapy in lupus nephritis? Indian J Rheumatol 2017;12:12-6.  Back to cited text no. 13
  Medknow Journal  
14.
Yap DY, Chan TM. Lupus nephritis in Asia: Clinical features and management. Kidney Dis 2015;1:100-9.  Back to cited text no. 14
    




 

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