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Saudi Journal of Kidney Diseases and Transplantation
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CASE REPORT Table of Contents   
Year : 1995  |  Volume : 6  |  Issue : 4  |  Page : 412-416
The Role of Plasmapheresis in the Treatment of Severe Lupus Nephritis: A Case Report

Department of Nephrology and Dialysis, Al Hada Armed Forces Hospital, Taif, Saudi Arabia

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There is still controversy about the efficacy of plasma exchange in the treatment of severe lupus nephritis. Some studies have reported no beneficial effect with plasma exchange, while others claim its usefulness when used in combination ("synchronization") with immunosuppressive drugs, particularly intravenous (i.v.) pulse doses of cyclophosphamide. We report here a 13 year old girl who presented twice with severe exacerbation of lupus nephritis (WHO class IV) leading to acute renal failure (ARF) necessitating dialysis, and who on both occasions responded well to i.v. pulse doses of cyclophosphamide and methylprednisolone plus plasma exchange. The second episode of ARF had occurred in spite of the patient being on maintenance therapy with prednisolone and i.v. cyclophosphamide. The course in this patient supports the view that the addition of plasma exchange to i.v. pulse cyclophosphamide might be effective in patients with severe lupus nephritis unresponsive to immunosuppressive drugs alone.

Keywords: Lupus nephritis, Acute renal failure, Plasma exchange, Cyclophosphamide.

How to cite this article:
Hussein M, Mooij J, Roujouleh H, El Sayed H. The Role of Plasmapheresis in the Treatment of Severe Lupus Nephritis: A Case Report. Saudi J Kidney Dis Transpl 1995;6:412-6

How to cite this URL:
Hussein M, Mooij J, Roujouleh H, El Sayed H. The Role of Plasmapheresis in the Treatment of Severe Lupus Nephritis: A Case Report. Saudi J Kidney Dis Transpl [serial online] 1995 [cited 2022 Aug 15];6:412-6. Available from: https://www.sjkdt.org/text.asp?1995/6/4/412/40560

   Introduction Top

There is still some controversy concerning use of plasmapheresis in the treatment of lupus nephritis. Lewis, et al in a control prospective study involving 86 patients with severe lupus nephritis, reported that plasmapheresis plus a standard regimen of prednisone and oral cyclophosphamide did not improve the clinical outcome of these the patients as compared with the standard regimen alone [1] . Additionally, the outcome in the patients who had plasmapheresis was consistently worse than in the other patients. However, the report was criticized by some other groups, arguing that plasma計heresis was not performed in conjunction with intravenous (i.v.) pulse doses of cyclophosphamide ("synchronization") [2],[3],[4] in their study. According to Schroeder, et al the pulse dose of cyclophosphamide should be given shortly after the plasma exchange, thereby "utilizing" the increased proliferation of B-cells occurring after plasmapheresis [5] , although in some other reports cyclophosphamide was given before plasma exchange [6] .

An extensive literature review about the role of plasmapheresis in severe lupus nephritis had been published in this Journal by Boobes et al in 1992 [7] .

We report here on the outcome in a 13 year old female, in whom the clinical course seems to underline the role of plasmapheresis in the treatment of lupus nephritis.

   Case Report Top

This female patient, born in 1981, presented to another hospital in November 1993 with intermittent fever, joint pain, butterfly rash on the face and palmar erythema. Investigations showed microscopic hematuria and cylindruria with an anti要uclear antibodies (ANA) titer of 1/1280 and an anti-double stranded (ds)-DNA titer more than 50 IU/L. A diagnosis of systemic lupus erythematosus (SLE) was made and she was given oral prednisone in a dose of 15 mg per day. One month later, in December 1993, she developed acute renal failure combined with vasculitic lesions on the lips, and was transferred to our hospital.

At admission to our hospital, she was anuric with a serum creatinine level of 691 痠ol/Land a blood urea nitrogen level of 32.4 mmol/L. The hemoglobin level was 9.8 g/dl, hematocrit (Hct) 29%, the total white blood cell (WBC) count was 5.7 x 10 9 /L and the platelet count was 180 x 10 9 /L. Urinalysis showed mild proteinuria and microscopy revealed 8-15 red blood cells (RBC), 40-50 WBC per high power field (hpf), and granular casts. The ANA-titer was 1/10200, anti-ds DNA > 50 IU/L and the serum C3 level was 0.29 mg/L (normal 0.55-1.2 mg/L). Circulating immune complexes were present. Ultrasound showed slightly swollen kidneys with decreased echogenicity.

A kidney biopsy showed diffuse membranoproliferative glomerulonephritis with granular deposits of IgG, IgA and C3. Crescents were not seen and there were no interstitial infiltrates. The diagnosis of acute renal failure due to lupus nephritis was made. She was given three i.v. pulse doses of 1 gm methylprednisolone followed by one i.v. pulse dose of 0.5 gm/square meter body surface area (BSA) of cyclophosphamide. Since no improvement was seen upto four days after the cyclophosphamide was administered, she was subjected to five sessions of plasmapheresis with two liters exchange during each session [Figure - 1]. She was also treated with regular hemo苓ialysis during this period. The renal function started to improve after the fourth plasma exchange and two weeks later it was almost normal.

The patient was discharged in February 1994, with a serum creatinine of 68 痠ol/L, WBC count of 7.0 x 10 9 /L, platelets 310 x 10 9 /L and a proteinuria of 100 mg per 24 hours with an unremarkable urine sediment. Her maintenance immunosuppression consisted of low-dose prednisone 0.25 mg/kg (15 mg per day), cyclosporine 3 mg/kg and i.v. pulses of cyclophosphamide (0.5 gm/sqm BSA), which she received in March and May 1994.

In March 1994, leucocyturia and micro貞copic hematuria reappeared while urinecultures were negative. In April 1994, proteinuria increased to 2.6 gm per 24 hrs and there was a steady rise in the ANA titer (May 1994, 1:320; June 1994, 1:1280; July 1994, 1:2560), with an anti-dsDNA titer of more than 50 IU/L.

On 19 July 1994, she was again hospi負alized with fever, oliguria and renewed signs of vasculitis in the mouth and palms. Laboratory investigations showed a markedly deteriorated renal function (creatinine, 571 痠ol/ L; urea nitrogen, 44.5 mmol/L) with a hemoglobin of 11.5 g/dl, WBC count of 4.6 x 10 9 /L and platelet count of 94 x 10 9 /L. The serum cyclosporine level was 202 ng/ml.

Urinalysis showed proteinuria with 12-14 WBC and 7-8 RBC/hpf with normal sized kidneys on ultrasound. She was given one pulse dose of 750 mg cyclophosphamide i.v. followed by three i.v. pulse doses of 1 gm methylprednisolone and five sessions of plasmapheresis. The patient had again to be treated with hemodialysis. After the ninth day, there was a gradual improvement in the renal function which became normal after about three weeks [Figure - 2].

   Discussion Top

This patient was admitted in January 1994 with acute renal failure due to severe lupus nephritis (biopsy: WHO class IV). She responded well to a combination of three pulse doses of methylyprednisolone and one pulse dose of cyclophosphamide followed by five sessions of plasmapheresis.

In an attempt to reduce the dosage of i.v. cyclosphosphamide (by diminishing the frequency from monthly to every 2 months), she was given oral cyclosporine in a dosage of 3 mg/kg BW, as some studies have reported beneficial effects of cyclosporine in the treatment of severe lupus nephritis [8],[9],[10] . She was discharged home one month after admission with normal renal function. Prednisone was continued in a dosage of 0.25 mg/kg BW and she also received i.v. cyclophosphamide every other month.

However, six months after the first admi貞sion she developed recurrence of acute renal failure. This occurred despite the fact that she was on maintenance immunosup計ression with prednisolone, cyclosporine and pulse cyclophosphamide. Although a kidney biopsy was not repeated at this stage, we assumed that the renal insufficiency was due to a relapse of lupus nephritis, as the patient also had recurrence of vasculitic lesions (mouth, handpalms), active urinary sediment, and increase of ANA and anti苓sDNA titers. As the cyclosporine level at admission was at the higher side of the desired range, there was no indication that the patient was not compliant with the medication.

In the maintenance treatment of this patient cyclophosphamide was given every two months, while in the studies initiated by the National Institute of Health (Bethesda, USA) a monthly dose schedule for at least six months has been recommended [11] . However, there is still no general consensus about the optimal treatment of severe lupus nephritis [12],[13] , as cyclophosphamide is associated with severe side-effects such as teratogenicity and oncogenicity [14],[15],[16] and any attempt to reduce the total dose to as low a level as possible should therefore be considered.

The exacerbations of lupus nephritis res計onded on both occasions (January and July 1994) to treatment, which included besides i.v. pulse cyclophosphamide, three pulse doses of methylprednisolone and plasma計heresis.

The effectiveness of a short course of i.v. pulse methylprednisolone in severe lupus nephritis is not yet clarified, with one report showing a high rate of exacerbation and/or persistent disease activity [17] . Also, pulse methylprednisolone therapy has been shown to be less effective than pulse cyclophosphamide therapy [18] . The course in our patient during both admissions showed that there was a delay of at least 5-7 days after the last dose of methylprednisolone before there was any improvement in the renal function. This observation makes it unlikely that methylprednisolone was responsible for the remission noted.

Plasmapheresis was added to the treatment of this patient in the acute stage of lupus nephritis, when treatment with pulse methylprednisolone and cyclophosphamide had already begun and no response was observed. The association of plasmapheresis with the impressive response that could be achieved in our patient cannot be ignored. Thus, we would like to conclude that plasmapheresis might still have a role to play in the management of patients with severe lupus nephritis who do not respond to immunosuppressive drugs alone. Such patients should be given the benefit of doubt and treated with plasmapheresis in conjunction with immunosuppressive drugs before labelling them as treatment failures.

   References Top

1.Lewis EJ, Hunsicker LG, Lan SP, Rohde RD, Lachin JM. A controlled trial of plasma計heresis therapy in severe lupus nephritis. The lupus nephritis collaborative study group. N Engl J Med 1992;326(21):1373-9.   Back to cited text no. 1    
2.Euler HH, Schroeder JO. Plasmapheresis for lupus nephritis. Lupus Nephritis Study Group. (Letter) N Engl J Med 1992;327(14):1028.  Back to cited text no. 2    
3.Robinson JA. Plasmapheresis for lupus nephritis (Letter). N Engl J Med 1992;327(14): 1028-9.14  Back to cited text no. 3    
4.Wallace DJ. Plasmapheresis for lupu . nephritis (Letter).N Engl JMed1992;327(14):1029.   Back to cited text no. 4    
5.Schroeder JO, Euler HH, Loffler H. Synchronization of plasmapheresis and pulse cyclophosphamide in severe systemic lupus erythematosus. Ann Intern Med 1987;107:344-6.  Back to cited text no. 5    
6.Sieberth HG. Pathophysiology in therapeutic plasma exchange. In: Bambauer R, Malchesky PS, Falkenhagen D (eds). Therapeutic plasma exchange and selective plasma separation. Stuttgart Schattauer 1987;177-83.  Back to cited text no. 6    
7.Boobes Y, Miah MN, Baz M. Plasma exchange in severe lupus nephritis. A case report and review of the literature. Saudi Kidney Dis Transplant Bull 1992;3(2):105-11.  Back to cited text no. 7    
8.Feutren G, Querin S, Tron F, et al. The effects of cyclosporine in patients with systemic lupus. Transplant Proc 1986;18:643-44.  Back to cited text no. 8    
9.Favre H, Miescher PA, Huang YP, Chatelanat F, Mihatsch MJ. Cyclosporine in the treatment of lupus nephritis. Am J Nephrol 1989;9(Suppl 1):57-60.  Back to cited text no. 9  [PUBMED]  
10.Hussein MM, Mooij JM, Roujouleh H. Cyclosporine in the treatment of lupus nephritis including two patients treated during pregnancy. Clin Nephrol 1993;40:160-3.  Back to cited text no. 10  [PUBMED]  
11.Austin HA 3d, Klippel JH, Balow JE, et al. Therapy of lupus nephritis. Controlled trial of prednisone and cytotoxic drugs. N Engl J Med 1986;314:614-9.  Back to cited text no. 11    
12.Balow JE. Treatment and monitoring of patients with lupus nephritis. Nephrol Dial Transplant 990;5(Suppl l):58-9.  Back to cited text no. 12    
13.Valeri A, Radhakrishnan J, Estes D, t al. Intravenous pulse cyclophosphamide treatment of severe lupus nephritis: a prospective five軌ear study. Clin Nephrol 1994;42(2):71-8.  Back to cited text no. 13    
14.Greenberg LH, Tanaka KR. Congenital anomalies probably induced by cyclophosphamide.JAMA 1964;188:423-6.   Back to cited text no. 14  [PUBMED]  
15.Kirshon B, Wasserstrum N, Willis R, Herman GE, McCabe ER. Teratogenic effects of first-trimester cyclophosphamide therapy. Obstet Gynecol 1988;72:462-4.   Back to cited text no. 15  [PUBMED]  
16.Gilchrist DM, Friedman JM. Teratogenesis and iv cyclophosphamide. J Rheumatol 1989;16:1008-9.  Back to cited text no. 16  [PUBMED]  
17.Ballou SP, Khan MA, Kushner I. Intravenous pulse methylprednisolone followed by alternateday corticosteroid therapy in lupus erythematosus: a prospective evaluation. J Rheumatol 1985;12:944-8.  Back to cited text no. 17  [PUBMED]  
18.Boumpas DT, Austin HA 3d, Vaughn EM, et al. Controlled trial of pulse methylprednisolone versus two regimens of pulse cyclophosphamide in severe lupus nephritis. Lancet 1992;340:741-5.  Back to cited text no. 18    

Correspondence Address:
Magdi Hussein
Department of Nephrology and Dialysis, Al Hada Armed Forces Hospital, P.O. Box 1347, Taif
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

PMID: 18583750

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