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Saudi Journal of Kidney Diseases and Transplantation
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Table of Contents   
ORIGINAL ARTICLE  
Year : 2019  |  Volume : 30  |  Issue : 4  |  Page : 775-780
Early and late effects of therapeutic plasma exchange in patients with systemic lupus erythematosus and antineutrophil cytoplasmic antibody-associated vasculitis: A single-center experience


1 Department of Medicine, Prince Mohammed Bin Abdulaziz Hospital, Riyadh, Saudi Arabia
2 Department of Pediatric Rheumatology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
3 Adult Rheumatology, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia
4 Blood Bank and Transfusion Services; Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, Riyadh, Saudi Arabia

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Date of Submission15-May-2018
Date of Decision12-Jul-2018
Date of Acceptance14-Jul-2018
Date of Web Publication27-Aug-2019
 

   Abstract 


Therapeutic plasma exchanges (TPE) is considered as one of the treatment modalities that is used in systemic autoimmune diseases. This study aimed to describe the early and late effect of TPE in patients with systemic lupus erythematosus (SLE) and antineutrophil cytoplasmic antibody-associated vasculitis (AAV) presented with acute kidney injury (AKI). Retrospective study comprised patients with SLE and AAV with AKI seen between January 2000 and June 2014 at King Faisal Specialist Hospital and Research Center in Riyadh. All patients underwent TPE. Retrospectively, all patients were assessed for early and late renal outcome at 12- month and 24-month intervals. Renal outcome was assessed according to serum creatinine level, glomerular filtration rate, active urine sediment, and proteinuria. P <0.05 was considered significant. A total of 68 patients were included, 58 patients (51 females) had SLE and 10 patients (7 females) had AAV completed TPE. All patients had active disease and had AKI. At the first 12 months, 18 patients (17 SLE and 1 AAV) showed complete response and 14 patients had partial response while 22 patients did not show therapeutic benefit. The nonresponders (22 patients) entered the late assessment interval (24 months) without any therapeutic response. Statistically, there was no significant difference between the patient’s response to TPE at the first and second assessment intervals and the baseline serum creatinine level. TPE might be an alternative rescue treatment in lupus nephritis with AKI.

How to cite this article:
Al Hamzi HA, Al-Mayouf SM, Al Shaikh AA, Al-Sheikh HA, Alshomar AA, Al Humaidan HA, Al Dalaan AN, Al Saleh SS. Early and late effects of therapeutic plasma exchange in patients with systemic lupus erythematosus and antineutrophil cytoplasmic antibody-associated vasculitis: A single-center experience. Saudi J Kidney Dis Transpl 2019;30:775-80

How to cite this URL:
Al Hamzi HA, Al-Mayouf SM, Al Shaikh AA, Al-Sheikh HA, Alshomar AA, Al Humaidan HA, Al Dalaan AN, Al Saleh SS. Early and late effects of therapeutic plasma exchange in patients with systemic lupus erythematosus and antineutrophil cytoplasmic antibody-associated vasculitis: A single-center experience. Saudi J Kidney Dis Transpl [serial online] 2019 [cited 2019 Sep 20];30:775-80. Available from: http://www.sjkdt.org/text.asp?2019/30/4/775/265452



   Introduction Top


Therapeutic plasma exchanges (TPE) is considered as one of the treatment modalities that is used in systemic autoimmune diseases related to excessive circulating immune complex and autoantibodies-mediated diseases.[1],[2] Several studies showed a favorable therapeutic effect of TPE in patients with lupus nephritis combined with thrombotic microangiopathy and patients with severe renal vasculitis[3],[4],[5] or when conventional management failed.[6],[7],[8]

Given the paucity of published data particularly from the Middle East on TPE in systemic lupus erythematosus (SLE),[9] this retrospective study was done to describe the therapeutic effect of TPE in SLE and anti-neutrophil cytoplasmic antibody-associated vasculitis (AAV) patients presented with acute kidney injury (AKI).


   Subjects and Methods Top


Retrospective study comprised all SLE and AAV patients older than 14 years of age and met the American College of Rheumatology criteria for SLE and the Chapel Hill Consensus Conference definitions for AAV, respec- tively.[10],[11] All included patients followed regularly during the treatment period and completed TPE between January 2000 and June 2014 at King Faisal Specialist Hospital and Research Center (KFSHRC), Riyadh.

The disease duration was calculated from the onset of symptoms related to SLE or AAV, while the duration of follow-up was calculated from the first visit to KFSHRC. All patients reviewed in respect to demographic features, age of onset, disease duration, clinical and laboratory variables, treatment as well as the indications for TPE.

To evaluate the treatment outcome, we considered the assessment at the time of enrollment (start point), 12- and 24-month intervals using SLE disease activity index (SLEDAI), and Birmingham Vasculitis Activity Score (BVAS).[12],[13] Renal outcome was assessed according to serum creatinine level, glome-rular filtration rate, active urine sediment, and proteinuria/creatinine ratio.

We defined the renal response as follows: for SLE patients, complete renal remission: serum creatinine of ≤1.4 mg/dL, proteinuria of ≤0.33 g/day, and no hematuria. Partial renal remission: 50% decrease in serum creatinine and proteinuria or stabilization of serum creatinine. No response: when there is no improvement at the abovementioned parameters or progression to end-stage renal disease (ESRD). For AAV patients, complete renal remission: inactive urine sediment (i.e. <10 red blood cells per high power field) and stabilization or reduction in the serum creatinine. Partial renal remission: stabilization or reduction in the serum creatinine in the presence of dys-morphic hematuria. No response: when there is no improvement at the abovementioned parameters or progression to ESRD. The getting out of respiratory failure and venti-latory support were considered as good treatment response for pulmonary hemorrhage. AKI was defined as increase in serum crea-tinine by ≥0.3 mg/dL (≥26.5 μmol/L) within 48 h, or increase in serum creatinine to ≥1.5 times baseline, which is known or presumed to have occurred within the prior seven days, or urine volume <0.5 mL/kg/h for 6 h.[14]

Furthermore, the early and late therapeutic responses were assessed at the 12 and 24 months after TPE.

All collected data were analyzed under confidentiality practice and no personal identity needed. All clinical and laboratory assessment were a result of routine medical care; informed consent was taken at the time of TPE.


   Statistical Methods Top


The data were expressed as mean ± standard deviation for continuous variables and number and percentage for categorical variables. We used nonparametric testing to assess the association between variables either by Fisher’s exact test or Mann–Whitney test as appropriate. Logistic regression analysis was carried out to examine the impact of these variables on the proposed outcome. P <0.05 was considered as statistically significant.


   Results Top


A total of 68 patients were included; 58 patients (51 female) had SLE and 10 patients (seven female) had AAV completed TPE. Each patient underwent thrice weekly 1–1.5 total plasma volume exchanges with albumin and/or plasma as replacement fluid according to the patient’s disease, indication for therapy (in patient with pulmonary hemorrhage and thrombotic thrombocytopenic purpura, fresh-frozen plasma has been used). On average, seven sessions were done for each patient. Patients with SLE were younger at the initiation of TPE; the mean age was 25 ± 8 years and the mean age of AAV patients was 48 ± 5 years (P = 0.002). However, patients with SLE and AAV had comparable time intervals between the disease onset, enrollment, and initiation of TPE (P >0.05). [Table 1] summarizes the clinical status of the patients at the time of enrollment. All patients had active disease; the mean SLEDAI was 18 ± 5 while BVAS was 13 ± 2. All patients had AKI with significant proteinuria and hematuria. Furthermore, 48% SLE patients and 50% of AAV had pulmonary hemorrhage.
Table 1: The clinical status of the patients at the time of therapeutic plasma exchange.

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The most frequent histopathological class was proliferative glomerulonephritis (16 patients had class IV and five patients had class III) followed by mixed classes (10 patients with class V and IV and two patients with class V and III) while class V seen in three patients and other three patients showed thrombotic microangiopathy. Four patients had inadequate renal biopsy, and biopsy was not repeated due to their critical clinical situation. Fifteen patients had no renal biopsy because they were critically sick and performing renal biopsy at that time was not feasible. However, they had progressive renal impairment with active sediment and proteinuria with either pulmonary hemorrhage or cerebritis. On the other hand, nine AAV patients underwent renal biopsy; all patients had pauci-immune glomerulonephritis and five patients had cellular crescents. Induction immunosuppressive was guided by medical judgment of overall disease activity and severity. Most patients received intravenous cyclophosphamide treatment (500–1000 mg/m2) monthly for six doses as induction therapy as per National Institute of Health-NIH protocol followed by maintenance therapy either with mycophenolate mofetil or azathioprine. In addition, 74% of SLE and 80% of AAV patients required hemodialysis (HD).

All patients were treated with intravenous pulse methylprednisolone (1000 mg) daily for three days followed by daily oral dose of 1 mg/kg. Other immunosuppressive medication included intravenous immunoglobulin, 25 patients (24 SLE and one AVV); mycophenolate mofetil, 10 patients (nine SLE and one AVV); rituximab, two patients (one SLE and one AVV); and azathioprine, two patients with AVV.

[Table 2] shows the therapeutic response at assessment intervals. At the first 12 months (early response interval), 18 patients (17 SLE and one AAV) showed complete response and 14 patients had partial response while 22 patients did not show therapeutic benefit. Four patients (two SLE and two AAV) lost follow-up.
Table 2: The early and late renal response after therapeutic plasma exchange.

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One patient developed frank hematuria and one patient had Staphylococcus aureus bacteremia during TPE. Unfortunately, 10 patients (nine SLE and one AAV) passed away within three months of initiation of TPE due to sepsis mostly with fungal infection and refractory pulmonary hemorrhage and one patient died because of status epilepticus. Those patients represent the most severe symptoms, six of them had severe pulmonary hemorrhage and eight underwent HD.

The nonresponders (22 patients) entered the late assessment interval (24 months) without any therapeutic response. Furthermore, 17 patients (13 SLE and 4 AAV) developed ESRD, seven of them underwent renal transplant. On the other hand, at the late assessment interval, 14 patients (12 SLE and two AAV) showed persistent complete remission but six SLE patients (four with initial complete and two with partial response) relapsed and two patients lost follow-up. Statistically, there was no significant difference between the patient’s response to TPE at the first and second assessment intervals. Furthermore, there was no statistical significant association with the response to TPE and the baseline serum creatinine level or the type of immuno-suppressive therapy that have been given.


   Discussion Top


TPE has been used in the management of various autoimmune disorders with variable results regarding its benefit and long-term outcome. It has been found to be a useful adjunctive treatment and frequently indicated in several autoimmune renal diseases involving hemolytic uremic syndrome and Goodpasture’s syndrome.[15],[16] Furthermore, TPE is suggested in patients with rapidly progressive glomerulonephritis due to pauci-immune cre-scentic glomerulonephritis particularly in the presence of pulmonary hemorrhage.[17],[18],[19]

Typically, SLE patients with major organ involvement are treated with immunosuppressive medications. However, TPE is recommended in case of acute life-threatening conditions like SLE nephritis with thrombotic microangiopathy or catastrophic antiphospho-lipid syndrome.[16],[20]

The main justification of using TPE in SLE patients is the probable removal of the pathogenic autoantibodies and the immune complexes. This process can lessen the stormy inflammatory cascade and the subsequent sequels. In addition, TPE probably has some immunomodulatory effect.

In our study, TPE was initiated in patients who suffered severe SLE and AAV disease with high disease activity. They had serious manifestations in the form of pulmonary hemorrhage and renal impairment; most of them required HD shortly after the onset of the disease. In our cohort, treatment was individualized; it was mainly based on corticosteroid and cyclophosphamide. The available evidence, which is based mainly on retrospective studies, provide efficacious therapeutic role of TPE in patients with AAV, especially during the acute phase of illness.[21],[22] Although the evidence of TPE in SLE is not clear like AAV, usually, it is reserved for critical patients.[3],[20],[23] Although our SLE patients were treated aggressively with immunosuppressive therapy, 43 patients developed acute renal failure rapidly and required HD. Furthermore, 28 patients had pulmonary hemorrhage, 24 patients had cereb-ritis, and 10 patients had thrombotic thrombo-cytopenic purpura prior at TPE treatment. However, 70% (30 out of 43) of SLE patients and 50% (4 out 8) of AVV patients went out of HD dependency, and all patients with pulmonary hemorrhage except three patients, survived respiratory failure.

Although the nature of this study does not allow comparison between SLE and AAV patients, the response rate during the first 12 months after TPE among SLE was apparently higher than AAV patients.

Long-term therapeutic effectiveness of TPE and the relation between the early and late renal outcome till now are not clearly validated. In our study, the early response rate was comparable with the late one; there was no significant difference between those who showed complete or partial response.

Furthermore, the nonresponder in the first 12 months are more likely to continue without improvement. However, our fin-dings did not show significant correlation between the early or late responses and the clinical or the laboratory findings at the time of TPE; this may be related to the relatively small number of patients.

To the best of our knowledge, there is no available published data from the Middle East about the use of TPE in SLE and AAV patients and highlighting the early and late renal outcome. Although this is a retrospective study from single center, we believe that TPE might be an alternative rescue treatment in lupus nephritis with AKI.

Conflict of interest: None declared.



 
   References Top

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Kronbichler A, Brezina B, Quintana LF, Jayne DR. Efficacy of plasma exchange and immunoadsorption in systemic lupus erythe-matosus and antiphospholipid syndrome: A systematic review. Autoimmun Rev 2016; 15:38-49.  Back to cited text no. 3
    
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Pepper RJ, Chanouzas D, Tarzi R, et al. Intravenous cyclophosphamide and plasmapheresis in dialysis-dependent ANCA-associated vascu-litis. Clin J Am Soc Nephrol 2013;8:219-24.  Back to cited text no. 5
    
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Pons-Estel GJ, Salerni GE, Serrano RM, et al. Therapeutic plasma exchange for the management of refractory systemic autoimmune diseases: Report of 31 cases and review of the literature. Autoimmun Rev 2011;10:679-84.  Back to cited text no. 7
    
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Bombardier C, Gladman DD, Urowitz MB, Caron D, Chang CH. Derivation of the SLEDAI. A disease activity index for lupus patients. The committee on prognosis studies in SLE. Arthritis Rheum 1992;35:630-40.  Back to cited text no. 12
    
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Mukhtyar C, Lee R, Brown D, et al. Modification and validation of the Birmingham vasculitis activity score (version 3). Ann Rheum Dis 2009;68:1827-32.  Back to cited text no. 13
    
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Hildebrand AM, Huang SH, Clark WF. Plasma exchange for kidney disease: What is the best evidence? Adv Chronic Kidney Dis 2014;21: 217-27.  Back to cited text no. 15
    
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Jayne DR, Gaskin G, Rasmussen N, et al. Randomized trial of plasma exchange or high-dosage methylprednisolone as adjunctive therapy for severe renal vasculitis. J Am Soc Nephrol 2007;18:2180-8.  Back to cited text no. 18
    
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Frausová D, Hrušková Z, Lanska V, Láchmanová J, Tesar V. Long-term outcome of patients with ANCA-associated vasculitis treated with plasma exchange: A retrospective, single-centre study. Arthritis Res Ther 2016; 18:168.  Back to cited text no. 19
    
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Li QY, Yu F, Zhou FD, Zhao MH. Plasmapheresis is associated with better renal outcomes in lupus nephritis patients with thrombotic microangiopathy: A case series study. Medicine (Baltimore) 2016;95:e3595.  Back to cited text no. 20
    
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22.
Chen Y, Yang L, Li K, et al. Double filtration plasmapheresis in the treatment of anti-neutrophil cytoplasmic autoantibody associated vasculitis with severe renal failure: A preliminary study of 15 patients. Ther Apher Dial 2016;20:183-8.  Back to cited text no. 22
    
23.
Hans R, Sharma RR, Marwaha N. Dramatic response to plasma exchange in systemic lupus erythematosus with acute complications: Report of two cases. Indian J Crit Care Med 2013;17:385-7.  Back to cited text no. 23
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Correspondence Address:
Hanan A Al Hamzi
Department of Internal Medicine, Prince Mohammed Bin Abdulaziz Hospital P. O. Box 106998, Riyadh 11676
Saudi Arabia
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DOI: 10.4103/1319-2442.265452

PMID: 31464233

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