Diagnosis and Treatment of Lupus Nephritis: Survey Results on Four Important Issues

Young Bin Joo; Yoon-Kyoung Sung; Yong-Beom Park; Chang-Hee Suh; Seung-Cheol Shim; Young Ho Lee; Jisoo Lee; Hye-Soon Lee; Hoon-Suk Cha; Sang-Cheol Bae

doi:10.4078/jrd.2013.20.3.156

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Joo, Sung, Park, Suh, Shim, Lee, Lee, Lee, Cha, and Bae: Diagnosis and Treatment of Lupus Nephritis: Survey Results on Four Important Issues

Original Article

J Rheum Dis 2013;20(3):156-165.

Published online: 31 June 2013

DOI: https://doi.org/10.4078/jrd.2013.20.3.156

Diagnosis and Treatment of Lupus Nephritis: Survey Results on Four Important Issues

Young Bin Joo¹, Yoon-Kyoung Sung¹, Yong-Beom Park², Chang-Hee Suh³, Seung-Cheol Shim⁴, Young Ho Lee⁵, Jisoo Lee⁶, Hye-Soon Lee¹, Hoon-Suk Cha⁷, Sang-Cheol Bae¹

¹Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, Seoul, Korea

²Department of Internal Medicine, Yonsei Unversity College of Medicine, Seoul, Korea

³Department of Rheumatology, Ajou University Hospital, Suwon, Korea

⁴Division of Rheumatology, Daejeon Rheumatoid & Degenerative Arthritis Center, Chungnam National University, Daejeon, Korea

⁵Division of Rheumatology, Department of Internal Medicine, Korea University Anam Hospital, Seoul, Korea

⁶Division of Rheumatology, Department of Internal Medicine, Ewha Womans University Mokdong Hospital, Seoul, Korea

⁷Division of Rheumatology, Department of Medicine, Sungkyunkwan University, School of Medicine, Samsung Medical Center, Seoul, Korea

Corresponding to : Sang-Cheol Bae, Department of Rheumatology, Hanyang University Hospital for Rheumatic Diseases, 17, Haengdang-dong, Seongdong-gu, Seoul 133-792, Korea. E-mail : scbae@hanyang.ac.kr

Received 20 September 201219 November 2012 Accepted 14 December 2012

This is a Free Access article, which permits unrestricted non-commerical use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Objectives

To investigate the perception of and treatment pattern with regard to the four important issues in the management of lupus nephritis (LN), and to identify which parts of the LN treatment are difficult for physicians to carry out in clinical practice.

Methods

Four steps were carried out: pre-survey, LN symposium, post-survey, and meeting after the symposium. The two surveys were conducted with the same contents regarding renal biopsy, induction and maintenance treatment for class III and IV LN, and treatment for class V LN. The results of the first survey and the changes in opinion re-flected in the second survey were comparatively analyzed.

Results

In the first survey, most of the respondent physicians replied that they would immediately conduct biopsy in the case of significant proteinuria. For the induction treatment of class III and IV LN, most of the respondent physicians selected high-dose cyclophosphamide. Mycophenolate mofetil and steroid combination therapy were selected for the maintenance treatment, and tacrolimus for the treatment of class V LN. There was a controversy in the drug selection, however, especially on the maintenance treatment of class III and IV LN and on the treatment of non-responsive class V LN.

Conclusion

Some discrepancies were found in the treatment of LN in the real world. Although no recommendation was made for Korean LN patients in this study, the study results will help physicians select the most rea-sonable treatment for Korean LN patients based on ex-perts’ experiences and objective evidence.

Keywords: Lupus nephritis, Treatment, Guideline

References

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Figure 1.

The four steps carried out in the study. LN: lupus nephritis.

Figure 2.

(A) First-survey results on the diagnostic performance of renal biopsy. A: Immediate conduct of renal biopsy. B: Renal biopsy when the steroid dose is decreased to 20 mg/day or lower. C: Immunosuppressant administration, but if no response, renal biopsy. D: Biopsy omitted. E: Others. (B) First-survey results on the induction therapy on LN. A: Oral administration of mycophenolatemofetil. B: Oral administration of tacrolimus. C: Intravenous cyclophosphamide administration (NIH protocol). D: Intravenous cyclophosphamide administration (Eurolupus protocol). E: Others. (C) First-survey results on the maintenance therapy on LN. A: Azathioprine. B: Azathioprine+ glucocorticoid. C: Cyclosporine. D: Cyclosporine+ glucocorticoid. E: Cyclophosphamide. F: Cyclophosphamide+ glucocorticoid. G: Mycophenolatemofetil. H: Mycophenolatemofetil+ glucocorticoid. I: Others. (D) First-survey results on the maintenance therapy on LN. A: Maintenance and observation of the current treatment. B: Cyclophosphamide IV administration. C: Oral administration of mycophenolatemofetil. D: Oral administration of tacrolimus. E: Others.

Figure 3.

(A) Change of opinion on the diagnostic performance of renal biopsy. A: Immediate conduct of renal biopsy. B: Renal biopsy when the steroid dose is decreased to 20 mg/day or lower. C: Immunosuppressant administration, but if no response, renal biopsy. D: Biopsy omitted. E: Others. (B) Change of opinion on the induction therapy on LN. A: Oral administration of mycophenolatemofetil. B: Oral administration of tacrolimus. C: Intravenous cyclophosphamide administration (NIH protocol). D: Intravenous cyclophosphamide administration (Eurolupus protocol). E: Others. (C) Change of opinion on the maintenance therapy on LN. A: Azathioprine. B: Azathioprine+ glucocorticoid. C: Cyclosporine. D: Cyclosporine+ glucocorticoid. E: Cyclophosphamide. F: Cyclophosphamide+ glucocorticoid. G: Mycophenolatemofetil. H: Mycophenolatemofetil+ glucocorticoid. I: Others. (D) Change of opinion on the maintenance therapy on LN. A: Maintenance and observation of the current treatment. B: Cyclophosphamide IV administration. C: Oral administration of mycophenolatemofetil. D: Oral administration of tacrolimus. E: Others.

Table 1.

Baseline characteristics of the physicians who participated in the first survey

	All physicians N=48	Rheumatologists who had ≥5 years experience N=21	Rheumatologists who had <5 years experience N=27	p
Age, n (%)	39.2±7.3	45.4±5.0	34.3±5.0	<.001
Man/woman, n (%)	29 (60.0)/19 (40.0)	17 (81.0)/4 (19.0)	12 (44.4)/15 (55.6)	0.010
Hospital, n (%)
University hospital	45 (94.0)	20 (95.2)	25 (92.6)	ns
Clinic	1 (2.0)	1 (4.8)	0 (0)
Others	2 (4.0)	0 (0)	2 (7.4)
Region, n (%)
Seoul	26 (54.0)	9 (42.9)	17 (63.0)	ns
Metropolitan	12 (25.0)	6 (28.6)	6 (22.2)
Others	10 (21.0)	6 (28.6)	4 (14.8)
LN patients seen per year, n (%)
≤10	4 (8.3)	0 (0)	4 (14.8)	0.001
11∼50	22 (45.8)	5 (23.8)	17 (63.0)
≥51	22 (45.8)	16 (76.2)	6 (22.2)

LN: lupus nephritis, SLE: systemic lupus erythematosus, ns: not significant.

Table 2.

Clinical scenarios and questionnaires of the surveys conducted before and after the symposium

2-1.	When would you conduct renal biopsy to determine the treatment method for the patient?
	A 35-year-old woman patient with lupus was referred to the Emergency Department due to systemic tonic-clonic seizure. As the MRI T2 weighted image showed a contrast-increasing lesion on the white matter, the patient was diagnosed with neuropsychiatric lupus. The patient was made to take 60 mg/d prednisolone orally after steroid pulse therapy (1 g/d methylprednisolone for five days), after which the seizure improved, without recurrence. Despite the improvement shown in the neuropsychiatric lupus with the treatment, however, a spot urine protein creatinine ratio of 1.5 was still present in her urinalysis.
2-2.	Which drug would you select first when considering further treatment of this patient?
	A 25-year-old woman patient with lupus visited the hospital due to edema. Her blood chemistry showed the following results: BUN25 mg/dL, creatinine 1.0 mg/dL, C3/C4 21/7 mg/dL, and 24 h proteinuria 4.5 g. The renal biopsy showed that the patient had class IV LN.
2-3.	Which drug would you select for maintenance treatment of this patient?
	A 38-year-old woman patient who visited the hospital due to generalized edema was diagnosed with class IV LN. She hada spot urine protein creatinine ratio of 8.0 and a serum creatinine level of 1.4 mg/dl. After induction treatment using high-dose CYC according to the NIH protocol, she had a spot urine protein creatinine ratio of 0.4, a serum creatinine level of 0.9 mg/dL, and normal urinary sediments.
2-4.	Which treatment method would you select for further treatment of this patient?
	A 39-year-old woman patient visited the hospital due to generalized edema. She was diagnosed with class V LN in a biopsy. She received a high-dose steroid and cyclosporine combination therapy. The steroid dose was gradually reduced. Six months later, she had a serum creatinine level of 0.7 mg/dL, a serum albumin level of 3.0 g/dL, and a 24 h proteinuria level of 1.9 g/dL.

MRI: magnetic resonance imaging, BUN: blood urea nitrogen, C3: complement3, C4: complement4, LN: lupus nephritis, CYC: cyclophosphamide, NIH: National Institute of Health

Table 3.

Responses to the four scenarios according to the length of experience in taking care of SLE patients

	All physicians N=48	Rheumatologists with ≥5 year experience N=21	Rheumatologists with <5 year experience N=27	p
Scenarios 1
Immediate renal biopsy	26 (54.2)	5 (23.8)	21 (77.8)	<.001
Renal biopsy when the steroid dose is decreased to ≤20 mg/day	5 (10.4)	2 (9.5)	3 (11.1)	ns
Immunosuppressant administration	11 (22.9)	10 (47.6)	1 (3.7)	<.001
Biopsy omitted	2 (4.2)	1 (4.3)	1 (3.7)	ns
Others	4 (8.3)	3 (14.3)	1 (3.7)	ns
Scenarios 2
MMF	7 (14.6)	2 (9.5)	5 (18.5)	ns
Tacrolimus	0 (0)	0 (0)	0 (0)	ns
CYC (NIH)	24 (50.0)	8 (38.1)	16 (59.3)	ns
CYC (Eurolupus)	17 (35.4)	11 (52.4)	6 (22.2)	0.03
Others	0 (0)	0 (0)	0 (0)	ns
Scenarios 3
AZA	10 (20.8)	5 (23.8)	5 (18.5)	ns
AZA+ steroid	14 (29.2)	5 (23.8)	9 (33.3)	ns
Cyclosporine	0 (0)	0 (0)	0 (0)	ns
Cyclosporine+ steroid	1 (2.1)	0 (0)	1 (3.7)	ns
CYC	0 (0)	0 (0)	0 (0)	ns
CYC+ steroid	3 (6.3)	2 (9.5)	1 (3.7)	ns
MMF	5 (10.4)	3 (14.3)	2 (7.4)	ns
MMF+ steroid	15 (31.3)	6 (28.6)	9 (33.3)	ns
Others	0 (0)	0 (0)	0 (0)	ns
Scenarios 4
Observation	14 (29.2)	4 (19.0)	10 (37.0)	ns
CYC IV	8 (16.7)	1 (4.8)	7 (25.9)	ns
MMF	9 (18.8)	5 (23.8)	4 (14.8)	ns
Tacrolimus	17 (35.4)	11 (52.4)	6 (22.2)	0.03
Others	0 (0)	0 (0)	0 (0)	ns

AZA: azathioprine, CYC: cyclophosphamide, MMF: mycophenolatemofetil, NIH: National Institute of Health, ns: not significant.

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