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Saudi Journal of Kidney Diseases and Transplantation
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RENAL DATA FROM ASIA - AFRICA  
Year : 2019  |  Volume : 30  |  Issue : 2  |  Page : 462-469
Lupus nephritis: An experience of a tertiary care center in Nepal


1 Department of Internal Medicine, B. P. Koirala Institute of Health Sciences, Dharan, Nepal
2 Department of Pathology, B. P. Koirala Institute of Health Sciences, Dharan, Nepal

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Date of Submission28-Jul-2018
Date of Decision02-Sep-2018
Date of Acceptance03-Sep-2018
Date of Web Publication23-Apr-2019
 

   Abstract 


Lupus nephritis (LN) is one of the common complications of systemic lupus erythematosus (SLE). Timely treatment will decrease progression to chronic kidney disease. Treatment varies with different stages for which biopsy is needed. Controversies still exist regarding its requirement in management. This is a retrospective study from September 2014 to August 2016 in B. P. Koirala Institute of Health Sciences, Dharan, Nepal among all patients with SLE and undergone renal biopsy. Of 92 patients, most were female 85 (92.4%) with a median age of 32 years. In this study, 80.4% had some clinical symptomatology. Of the clinical manifestations, 41.3% had polyarthritis, edema (20.7%), and malar rash (17.4%). Anti-nuclear antibody was positive in 80.4% and ds DNA in 70.7%. Renal biopsy showed more number of patients 27 (35%) had Stage IV LN, followed by Stage I, 19 (24%), and Stage II, 16 (20%) LN. Median urinary protein in Class I was 1.05 g, Class II (0.63 g), Class III (1.5 g), Class IV (2.44 g), Class V (3.99 g), and Class VI (4.7 g). Only Stage IV had Kappa of 0.269 {P = 0.003) showing agreement between proteinuria and histological staging which was statistically significant (P <0.005). However, overall Kappa analysis showed none to fair strength of agreement for different stages of LN (–0.014–0.269) with proteinuria. Kappa (k) analysis showed none to fair strength of agreement for different stages of LN and proteinuria. Hence, only proteinuria is not sufficient to replace the need of renal biopsy in LN.

How to cite this article:
Bartaula B, Subedi M, Dhakal S, Mudbhari B, Tripathi PM, Sharma SK. Lupus nephritis: An experience of a tertiary care center in Nepal. Saudi J Kidney Dis Transpl 2019;30:462-9

How to cite this URL:
Bartaula B, Subedi M, Dhakal S, Mudbhari B, Tripathi PM, Sharma SK. Lupus nephritis: An experience of a tertiary care center in Nepal. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 Jul 21];30:462-9. Available from: http://www.sjkdt.org/text.asp?2019/30/2/462/256853



   Introduction Top


Lupus nephritis (LN) is common and devastating complication of systemic lupus erythematosus (SLE).[1] Inflammatory damage of nephrons occurs during active disease and SLE flare.[2],[3],[4] About 50%–80% of patients with SLE develop LN worldwide[5] and the incidence is higher in Asians as well 33%–55%.[6],[7]

Kidney disease: Improving Global Outcomes guidelines suggested that LN should be suspected among patients of SLE presenting with proteinuria, renal dysfunction, active sediments, or hypertension and all cases should be confirmed by renal biopsy.[8] There are varying opinions regarding the time to perform biopsy in LN. The European League Against Rheumatism and European Renal Association-European Dialysis and Transplant Association recommends biopsy in patients with proteinuria >0.5 g/day,[9] whereas the American College of Rheumatology recommends if: proteinuria >1 g over 24 h, or abnormal renal function or 24 h proteinuria >0.5 g along with either active sediments or cellular casts.[10] Despite being the gold standard diagnostic modality, still there are various conflicting views for and against performing renal biopsy. Those against biopsy explains that there is good clinicopathological correlation, one can predict the class of LN by clinical and laboratory parameter and renal biopsy is invasive procedure with significant complications.[11] Contrary to this, those who are in favor of renal biopsy argue that in addition to the class of LN, renal histology also provides information which can have a significant implication on deciding treatment and prognosis such as the extent of activity and chronicity parameters, and the presence of extraglomerular involvement like thrombotic microangiopathy and tubulointerstitial nephritis. Lupus mimickers like lupus podocytopathy[11],[12] is only differentiated by biopsy. A few have emphasized that mycophenolate mofetil with glucocorticosteroids can be the first-line therapy instead of cyclophosphamide for all the serious LN (Class III, IV, and V),[13] and can eliminate the need of biopsy to differentiate between each histological class.

Hence despite having multiple studies, controversies still persists in the Western world about the necessity of biopsy in the initial stage of the disease. Moreover, the scenario for clearing this controversy is more complicated in our part of world where there are only limited studies of LN and the burden of disease is quite high.

Similarly, patients in our part of the world are always reluctant for renal biopsy. The economic factor and invasive nature of the procedure despite being safe with real-time ultrasonography, patients most of the time try to avoid it. In our part of the world, empirical treatment also cannot be afforded in all patients based on the clinical criteria alone because of the cost factor for treatment, multiple adverse effects of immunosuppressive therapy. Some may be life-threatening and proper follow-up of patients during therapy may not be possible to be ensured because of various social and economic burdens. Thus, empirical treatment modality may do more harm by treatment-related complications then benefit to patients.

We feel that there is a necessity to identify the real scenario of LN and its clinic-pathological correlation in our population. Therefore, this study was conducted to answer various queries regarding the importance of renal biopsy.


   Materials and Methods Top


Study design

This was the hospital-based retrospective study which included 92 patients with the diagnosis of SLE and underwent renal biopsy in the Internal Medicine Department of B. P. Koirala Institute of Health Sciences from September 2014 to August 2016. Patients already started on immunosuppressive therapy before biopsy were not included in the study.

Methodology

Ethical clearance for the study was obtained from the Institutional Review Committee of B. P. Koirala Institute of Health Sciences with Institutional Review Committee.

After the approval, the study was conducted in the Department of Internal Medicine, B. P. Koirala Institute of Health Sciences. The record of all the patients with the diagnosis of SLE with clinical LN and who had undergone real-time ultrasonography-guided renal biopsy over specified duration were recorded. There were a total of 92 patients in the study with the diagnosis of LN and who had undergone renal biopsy as per the criteria of American College of Rheumatology for LN. As per the American College of Rheumatology, renal biopsy was conducted if any one of the following criteria is met: 24 h proteinuria >1 g, or abnormal renal function or 24 h proteinuria >0.5 g along with either active sediments or cellular casts.[10]

Demographic characteristics, different clinical manifestations, biochemical parameters such as complete blood count, urine microscopy, serum urea, and creatinine at the time of renal biopsy were recorded. Data of 24 h urine protein were also noted in the preformed pro forma. Histopathological data of renal biopsy were also recorded.


   Statistical Analysis Top


The collected data were entered in MS Excel and converted into Statistical Package for Social Sciences version 20.0 (IBM Corp, Armonk, NY, USA), for statistical analysis. Univariate analysis was performed by calculating the mean, median, and standard deviation. Numerical variables were expressed in mean, percentage, and standard deviation. Bivariate analysis was carried out using the Chi-square and t-test to access the relationship between independent and dependent variables at the level of statistical significance 0.05.

Cohen’s Kappa (κ) analysis was used to know the agreement between proteinuria and histologic findings on renal biopsy with value ≤0 indicating no agreement, 0.01–0.20 as none to slight, 0.21–0.40 as fair, 0.41–0.60 as moderate, 0.61-0.80 as substantial, and 0.81–1.00 as almost perfect agreement. Value of P <0.05 indicates that agreement was unlikely due chance alone.


   Results Top


There were 92 patients with SLE in the study who had undergone renal biopsy. Female were predominant with 92.4% and male 7.6% in the study [Table 1]. The median age of the study patients was 32 years. Mongol ethnic group were maximum in the study (34.8%).
Table 1: Sociodemographic profile of patients with lupus nephritis.

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Of 92 patients, 80.4% had some clinical symptomatology at the time of renal biopsy. Of the clinical manifestations, 41.3% had polyarthritis, 20.7% had edema, 17.4% had malar rash as shown in [Figure 1]. Raynaud phenomenon was present only in 1.1% patient.
Figure 1: Clinical symptoms of patients with lupus nephritis.

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[Table 2] shows the biochemical parameters of SLEs patient who had undergone renal biopsy. 68.5% had low C3 and C4 was low in 47.8% of patients. Anti-nuclear antibody was found to be positive in 80.4% of patients and dsDNA was positive in 70.7% as shown in [Table 2].
Table 2: Baseline investigations of patients with systemic lupus erythematosus.

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As shown in [Table 3], among 79 patients with available biopsy reports 19 (24%) had Class I LN, 16 (20%) had Class II, nine (11%) had Class III, 27 (35%) had Class IV, five (7%) had Class V, and three (4%) Class VI LN. The median 24 h urinary protein in Class I was 1.05 g, Class II was 0.63 g, Class 3 was 1.5 g, Class IV was 2.44 g, Class V was 3.99 g, and Class VI was 4.7 g.
Table 3: Association of proteinuria with different stages on renal biopsy.

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[Table 4] shows the kappa analysis to show the agreement between proteinuria (less than or more than 1 g) and histological staging. As shown in [Table 4], Stage 1 had kappa (k) of –0.118 (P = 0.124) showing no agreement between proteinuria and histological grading. Similarly, Stage II had kappa of –0.199 (P = 0.005). Stage III had kappa of 0.049 with (p = 0.468). Only Stage IV had kappa of 0.269 (P = 0.003) showing agreement between proteinuria and histological staging which was statistically significant (P <0.005). Stage V had kappa of –0.014 with (P = 0.727) and Stage VI had kappa of 0.038 (P = 0.216). Overall kappa analysis showed none to fair strength of agreement for different stages of LN (–0.014–0.269) with proteinuria. Although only in Stage IV, P <0.05 indicating statistically significant relation between clinical renal parameters with renal biopsy, while in rest of other stages, it showed no significant relation.
Table 4: Results comparing proteinuria with biopsy staging.

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   Discussion Top


The median age of patients with LN in our study was 32 years and 81% were of age group 15–45 years. This result was similar to a study from Rus et al with more number of patients were of age group 37–50 years probably because of the autoimmune disease is more common in younger age groups.[14]

Female were the predominant study population in this study (92.4%). Similar result with female predominance in LN was seen in a study by Lahita with a female-to-male ratio 7:1 to 15:1.[15] This female predominance is attributed to estrogen,[16],[17] gene variants located on X chromosomes (IRAK1, MECP2, TLR7),[18] and gene dose effect.[19]

The clinical symptomatology of our patients differed vastly from the previous studies. Polyarthritis was present in 41% of patients which differs from the previous study by Greco CM showing its presence in 65%–70% of patients.[20]

Similarly, the malar rash (17%), photosensitivity (9%), and alopecia (8%) was lower in prevalence compared to their prevalence being 28%, 29%, and 32%, respectively.[21] Raynaud phenomenon was present in 1.08% of patients. The result was different from the study by Cervera et al where 16% of patients had Raynaud syndrome.[22] The difference in symptomatology could be attributed due to the differences in environmental factor and this was a retrospective study in which patients who underwent renal biopsy were included rather than all the patients with SLE.

Lots of discrepancies exist regarding the time of performing renal biopsy in LN for the management of patients. A study by Grande recommended performing renal biopsy in patients with proteinuria of >500 mg protein/ 24 h[23] in the absence of renal failure, while Salach recommend biopsy only when proteinuria is >1000 mg/24 h and abnormal urine sediment.[24] The potential magnitude of the increase in risk with delayed renal biopsy was illustrated in a study of 91 patients with LN who were followed for a median of six years.

The pattern of renal involvement with renal biopsy report showed more number of patients had proliferative LN (46% of Class III and IV) and Class VI was the least common which is similar to the study done by Huong et al (49% Class III and IV ? and 1% Class VI).[25] This pattern in this study is probably because the patients with proliferative LN present with hematuria, proteinuria and renal insufficiency and are more likely to undergo renal biopsy.

The kappa analysis showed no agreement for proteinuria and histological stages in this study. This result is similar to the study done by Mahmood et al which concluded staging of LN on laboratory findings did not correlate well with the underlying histopathological staging.[26] However, this study does reinforce that proteinuria alone has a limited discriminatory capacity to differentiate between stages of LN requiring aggressive immunosuppressant from those which does not.

In a study done by Wakasugi et al in which renal biopsy was offered to all patients irrespective of clinical renal involvement 15% had either Class III or IV LN, 10% had Class V disease in patients without clinical renal disease.[27] Similarly, in this study, it was shown that out of six patients with protein excretion <0.5 g/day one (16%) had Class III and one (16%) had Class V disease. However, direct comparison with this study cannot be done because renal biopsy was performed in patients with protein excretion <0.5 g only if the renal function was impaired.


   Limitations Top


Correlation of different histological class with urine RME (red blood cell [RBC], cellular casts and dysmorphic RBC) was not done. Furthermore, this was a retrospective study and biopsy reports of 12 patients were missing.


   Conclusion Top


Thus, from this study, it may be concluded that histopathological staging of LN does not correlate well with proteinuria. Therefore, renal biopsy is an essential tool to approach LN to provide timely and appropriate treatment to patients.

Conflict of interest: None declared.



 
   References Top

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Lopez R, Davidson JE, Beeby MD, Egger PJ, Isenberg DA. Lupus disease activity and the risk of subsequent organ damage and mortality in a large lupus cohort. Rheumatology (Oxford) 2012;51:491-8.  Back to cited text no. 3
    
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Danila MI, Pons-Estel GJ, Zhang J, Vilá LM, Reveille JD, Alarcón GS. Renal damage is the most important predictor of mortality within the damage index: Data from LUMINA LXIV, a multiethnic US cohort. Rheumatology (Oxford) 2009;48:542-5.  Back to cited text no. 4
    
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Seligman VA, Lum RF, Olson JL, Li H, Criswell LA. Demographic differences in the development of lupus nephritis: A retrospective analysis. Am J Med 2002;112:726-9.  Back to cited text no. 6
    
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Bastian HM, Roseman JM, McGwin G Jr., et al. Systemic lupus erythematosus in three ethnic groups. XII. Risk factors for lupus nephritis after diagnosis. Lupus 2002;11:152-60.  Back to cited text no. 7
    
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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. 8
    
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Bertsias GK, Tektonidou M, Amoura Z, 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. 9
    
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Hahn BH, McMahon MA, Wilkinson A, 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. 10
    
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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. 11
    
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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
    
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Weening JJ, D’Agati VD, Schwartz MM, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. J Am Soc Nephrol 2004;15:241-50.  Back to cited text no. 13
    
14.
Rus V, Maury EE, Hochberg MC. The epide miology of systemic lupus erythematosus. In: Wallace DJ, Hahn BH, editors. Dubois’ Lupus Erythematosus. Philadelphia: Lippincott Williams and Wilkins; 2002.  Back to cited text no. 14
    
15.
Lahita RG. The role of sex hormones in systemic lupus erythematosus. Curr Opin Rheumatol 1999;11:352-6.  Back to cited text no. 15
    
16.
Cooper GS, Dooley MA, Treadwell EL, St Clair EW, Parks CG, Gilkeson GS. Hormonal, environmental, and infectious risk factors for developing systemic lupus erythematosus. Arthritis Rheum 1998;41:1714-24.  Back to cited text no. 16
    
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Costenbader KH, Feskanich D, Stampfer MJ, Karlson EW. Reproductive and menopausal factors and risk of systemic lupus erythematosus in women. Arthritis Rheum 2007;56: 1251-62.  Back to cited text no. 17
    
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Rullo OJ, Tsao BP. Recent insights into the genetic basis of systemic lupus erythematosus. Ann Rheum Dis 2013;72 Suppl 2:ii56-61.  Back to cited text no. 18
    
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Scofield RH, Bruner GR, Namjou B, et al. Klinefelter’s syndrome (47,XXY) in male systemic lupus erythematosus patients: Support for the notion of a gene-dose effect from the X chromosome. Arthritis Rheum 2008;58:2511-7.  Back to cited text no. 19
    
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Greco CM, Rudy TE, Manzi S. Adaptation to chronic pain in systemic lupus erythematosus: Applicability of the multidimensional pain inventory. Pain Med 2003;4:39-50.  Back to cited text no. 20
    
21.
Von Feldt JM. Systemic lupus erythematosus. Recognizing its various presentations. Postgrad Med 1995;97:79, 83, 86.  Back to cited text no. 21
    
22.
Cervera R, Khamashta MA, Font J, et al. Morbidity and mortality in systemic lupus erythematosus during a 10-year period: A comparison of early and late manifestations in a cohort of 1,000 patients. Medicine (Baltimore) 2003;82:299-308.  Back to cited text no. 22
    
23.
Grande JP, Balow JE. Renal biopsy in lupus nephritis. Lupus 1998;7:611-7.  Back to cited text no. 23
    
24.
Salach RH, Cash JM. Managing lupus nephritis: Algorithms for conservative use of renal biopsy. Cleve Clin J Med 1996;63:106-15.  Back to cited text no. 24
    
25.
Huong DL, Papo T, Beaufils H, et al. Renal involvement in systemic lupus erythematosus. A study of 180 patients from a single center. Medicine (Baltimore) 1999;78:148-66.  Back to cited text no. 25
    
26.
Mahmood SN, Mukhtar KN, Deen S, Khan FN. Renal biopsy: A much needed tool in patients with systemic lupus erythematosis (SLE). Pak J Med Sci 2016;32:70-4.  Back to cited text no. 26
    
27.
Wakasugi D, Gono T, Kawaguchi Y, et al. Frequency of class III and IV nephritis in systemic lupus erythematosus without clinical renal involvement: An analysis of predictive measures. J Rheumatol 2012;39:79-85.  Back to cited text no. 27
    

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Correspondence Address:
Bijay Bartaula
Department of Internal Medicine, B. P. Koirala Institute of Health Sciences, Dharan
Nepal
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DOI: 10.4103/1319-2442.256853

PMID: 31031382

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