Year : 2001 | Volume
: 12 | Issue : 4 | Page : 525--529
Sustained Remission in a Case of Lupus Nephritis with Cyclosporin Therapy
Malik Anas Rabbani, Syed Mansoor Ahmad Shah, Aasim Ahmad
Department of Medicine, Aga Khan University Hospital, Stadium Road, Karachi, Pakistan
Malik Anas Rabbani
Department of Medicine, Aga Khan University Hospital, Stadium Road, P.O. Box 3500, Karachi-74800
Systemic lupus erythematosus (SLE) in severe form still presents a major therapeutic challenge. Aggressive treatment of severe renal lesions has improved the prognosis of renal disease over the last decade. However, this benefit is quite frequently offset by the side effects and toxicity of the treatment. Moreover, the disease may appear to be poorly responsive to treatment with steroids and cytotoxic drugs. We report a case of lupus nephritis that relapsed despite having adequate steroid and cytotoxic therapy, but later was successfully treated with cyclosporin. Fifteen months after discontinuing the treatment with cyclosporin, the patient continued to remain in remission.
|How to cite this article:|
Rabbani MA, Shah SM, Ahmad A. Sustained Remission in a Case of Lupus Nephritis with Cyclosporin Therapy.Saudi J Kidney Dis Transpl 2001;12:525-529
|How to cite this URL:|
Rabbani MA, Shah SM, Ahmad A. Sustained Remission in a Case of Lupus Nephritis with Cyclosporin Therapy. Saudi J Kidney Dis Transpl [serial online] 2001 [cited 2020 Jun 5 ];12:525-529
Available from: http://www.sjkdt.org/text.asp?2001/12/4/525/33549
Systemic lupus erythematosus (SLE) in severe form still presents a major therapeutic challenge. Renal involvement in SLE is variable; some patients have minimal clinical and histological involvement, while others have fulminant renal failure and severe proliferative renal lesions on biopsy. 
The World Health Organization (WHO) classification,  which defines six major patterns of renal involvement, has greatly helped to study lupus nephritis. Transformation from one pattern of lupus nephritis to another may occur.  The optimal treatment of lupus nephritis varies with the type of disease. Aggressive immunosuppression is required for the more severe renal lesions such as diffuse or more severe focal proliferative glomerulonephritis (GN) and severe and progressive membranous GN (WHO Classes III, IV and V) as these lesions are at high risk for progressing to renal failure.  Aggressive treatment of the severe renal lesions has improved the prognosis of renal disease over the last decade. However, this benefit is quite frequently offset by the side effects and toxicity related to drugs.  Moreover, disease may itself be poorly responsive to treatment with steroids and cytotoxic drugs.
Cyclosporin A (CSA) is used as a corner stone in the prevention of graft rejection inpatients who receive organ transplants. It has also been used in various autoimmune disorders including systemic lupus erythematosus (SLE) because of its selective immunosuppressive effect.
We report here a case of lupus nephritis, which had frequently relapsed despite high dose steroids and cyclophosphamide and later was successfully managed with CSA based therapy.
A sixteen year old boy was admitted at the Aga Khan University Hospital with a one week history of high grade fever associated with chills and rigors, arthralgias involving hands, feet, knee and ankle joints and generalized purpuric rash. On examination, the pulse was 110/min, blood pressure 140/90 mm Hg, respiratory rate 27/min and temperature 39°C. Chest examination revealed bilateral pleural effusions. Abdominal examination revealed hepatosplenomegaly without ascites. Mild pedal edema was noted.
Laboratory investigations revealed hemoglobin of 102 gm/L, WBC 1.6 × 10 9 /L, platelets 2.8 × 10 9 /L, ESR 61 mm/hour.
Serum creatinine and electrolytes were within normal range. Serum C3 was 0.123u (N-0.5-0.9), serum C4  Several inflammatory and cell growth modifying processes also contribute to tissue destruction.
Lupus nephritis may run an extremely variable course and though specific therapy is not required in mild cases, a careful surveillance is required to detect possible transformation to a more severe disease state and flare ups.  Vigorous treatment should be started early in patients with more severe forms of lupus nephritis that show active lesion in the renal biopsy such as glomerular cell proliferation, necrosis, crescent formation, significant subendothelial immune complex deposition and inflammation.  Therapeutic modalities currently employed in lupus nephritis include oral corticosteroids, high dose pulse steroid therapy, cytotoxic drugs like cyclophosphamide and azathioprine, used either singly or in combination with steroids. Other therapeutic approaches such as mycophenolate mofetil and Tacrolimus have been used in the treatment of severe and difficult cases of SLE and have been shown to prolong life span, reduce proteinuria and prevent progression to nephropathy. , Intravenous immunoglobulins and monoclonal antibodies have also been used in experiments, but their efficacy was modest. , Plasma exchange therapy has been used for bulk depletion of immunoreactants. However, multicentre studies have confirmed no additional role of plasma exchange therapy in combination with cytotoxics when compared with sole shortterm use of cytotoxics in terms of patient survival, frequency of renal failure and other complications.  Total lymphoid radiation has been claimed to be effective in some cases of refractory lupus nephritis, a practical perspective on this form of immunosuppressive therapy has yet to be developed. 
Cyclosporin A (CSA) is a highly lipophilic cyclic peptide with 11 amino-acids. It blocks IL-2 synthesis by preventing transcription of IL-2 gene. Key steps are binding of CSA to a specific immunophillin, blocking calcineurin and preventing the transcription of the gene of IL-2.  Studies have shown that CSA is effective in reducing the activity of SLE and in controlling changes in clinical and laboratory parameters associated with disease especially in patients with poor response to conventional regimens.  The overall clinical benefit is usually observed within 2-4 months of CSA therapy. Therefore, prolonged treatment should be aimed at consolidating rather than achieving further improvement.  A large single center, prospective randomized study published from Italy evaluated disease activity according to systemic lupus activity measure (SLAM Score) in 27 patients who completed at least 24 months of treatment with CSA. It confirmed that the mean disease activity score could significantly be reduced in terms of stabilizing renal function, reducing proteinuria, and normalizing leukopenia and thrombocytopenia after six months of CSA therapy. This result was maintained through out the study. 
However, the use of CSA is limited mainly by its tendency to induce hypertension and nephrotoxicity as well as the tendency to relapse after discontinuing the treatment.  Despite this, we believe that the use of CSA still needs to be further evaluated as an alternative to cyclophosphamide in the management of lupus in young patients, especially in pregnant females in view of its established safety concerning teratogenicity,  or as a second line agent for patient whose condition is poorly responsive or less tolerant to more conventional therapy. Prognosis and overall success certainly varies widely among geographically and racially diverse populations. 
We reported a case of lupus nephritis that relapsed despite having adequate steroid and cytotoxic therapy, but later was successfully treated with cyclosporin. Fifteen months after discontinuing the treatment with cyclosporin, the patient continued to remain in remission.
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