Plasma Exchange Is Highly Effective for Anti‐Neutrophil Cytoplasmic Antibody‐Associated Vasculitis Patients With Rapidly Progressive Glomerulonephritis Who Have Advanced to Dialysis Dependence: A Single‐Center Case Series
Abstract
Plasma exchange (PEX) can be an effective treatment in anti‐neutrophil cytoplasmic antibody‐associated vasculitis with severe renal damage; however, it is still controversial. Among cases of newly diagnosed AAV with rapidly progressive glomerulonephritis at our department from 2008 onward, 11 patients who received PEX (seven cases for severe renal damage [R‐PEX] and four cases for lung hemorrhage [L‐PEX]) were retrospectively analyzed. All cases of R‐PEX were dependent on hemodialysis at the beginning of PEX and all received seven sessions of PEX (50 mL/kg or 1.3 plasma volume per exchange) within 2 weeks. All cases became dialysis‐independent within 8 weeks, with 3‐ and 12‐month cumulative renal survival rates of 100% and 80%, respectively. All cases of L‐PEX retained their renal function. In rapidly developing, newly dialysis‐dependent antibody‐associated vasculitis with rapidly progressive glomerulonephritis patients with normal renal function before disease onset, standard PEX can be expected to induce sufficient renal recovery to establish dialysis independence.
Anti‐neutrophil cytoplasmic antibody (ANCA)‐associated vasculitis (AAV) is one of the major diseases of vasculitis, and it involves multiple organs (i.e. skin, ear, upper/lower respiratory tract, lung, gastrointestinal tract, kidney, and central/peripheral nervous system). In the clinical course of AAV, involvement of either the kidney or lung becomes life‐threatening, and cases with rapidly progressive glomerulonephritis (RPGN) or lung hemorrhage often add plasmapheresis as an adjunctive treatment. A prospective randomized controlled trial (RCT) by the European Vasculitis Study Group (EUVAS) comparing plasma exchange (PEX) with intravenous methylprednisolone (MP), known as the MEPEX trial and published in 2007, showed that PEX was effective for severe renal impairment (serum‐creatinine level [SCr] > 5.8 mg/dL) in short‐term renal prognosis 1, 2. Based on the evidence of the MEPEX trial and the results of meta‐analyses 3, 4 strongly influenced by this trial, the recommendation in AAV cases with severe renal impairment is for PEX to be combined with standard immunosuppressive induction treatment (i.e. glucocorticoid plus cyclophosphamide or rituximab) 5-9. On the other hand, the effectiveness of plasmapheresis (i.e. PEX or double filtration plasmapheresis [DFPP]) has not been confirmed in a retrospective nationwide research of RPGN in Japan 10, even in severe renal damage cases with dialysis dependence; however, plasmapheresis for AAV was not approved by the health insurance system until 2018, and the regimen of plasmapheresis (i.e. modalities of apheresis, number of sessions, composition of replacement fluid [either albumin solution or fresh frozen plasma (FFP)] and its volume per session) had not been verified.
In the present study, we retrospectively analyze newly diagnosed Japanese AAV‐RPGN patients who underwent PEX as an adjunctive induction treatment. We show that PEX results in sufficient renal recovery to establish dialysis independence in newly developed cases of severe AAV‐RPGN.
PATIENTS AND METHODS
Patients
Among the cases of newly diagnosed AAV patients with RPGN (AAV‐RPGN) who had a history of hospitalization at the Department of Nephrology of University of Tsukuba Hospital from January 2008 to June 2018, a total of 11 patients who received PEX were analyzed retrospectively. Of these 11 cases, seven cases received PEX for severe renal damage (R‐PEX) and four cases for lung hemorrhage (L‐PEX). For ethical consideration, treatment was selected for all cases after conducting informed consent on the risks and benefits of PEX which had not been approved by the health insurance system at the time.
Methods
We searched all cases of newly‐diagnosed AAV‐PRGN from our medical history record and extracted all cases in whom PEX was performed during the induction treatment period. The patient’s characteristics and the basic information at disease onset including age, gender, type of AAV, presence or absence of RPGN, diffuse alveolar hemorrhage, interstitial pneumonitis, clinical severity grade 9, Birmingham vasculitis activity (BVAS) score 11, SCr (at the beginning of PEX and the maximum value during the induction treatment period), minimum urinary volume during induction treatment period (mL/day), SCr (mg/dL), and ANCA titer level (IU/mL) were examined. In each patient who underwent renal biopsy, the proportion of crescent formation, glomerulosclerosis, and areas of interstitial injury were evaluated. Regarding the contents of induction treatment, the condition of PEX including number of sessions, average of replacement fluid volume per session (i.e. L, mL per kg [mL/kg], and the ratio to patient’s plasma volume [PV]), and average percentage of FFP occupied in total replacement fluid volume were examined. Furthermore, the presence or absence of MP pulse, the dose of oral glucocorticoid (GC) (mg/kg/day), and the presence or absence of cyclophosphamide and rituximab administration was also examined. For prognosis, the renal status (dialysis‐dependent or ‐independent) and SCr at the last observation if the patient became dialysis‐independent, the life prognosis, and the cause of death were examined.
Statistical analysis
To compare the patient’s basic information between R‐PEX group and L‐PEX group, for comparison of mean value of continuous data, unpaired two‐tailed t‐test was conducted. Comparison of median values such as scored data and continuous data with uneven distribution was conducted by nonparametric analysis. For category data, Fisher’s exact test was conducted. Statistical analysis was performed using spss Statistics version 24.0 for Windows (IBM).
RESULTS
Patient characteristics and basic data at diagnosis of the 11 patients are shown in Table 1 and the contents of induction treatment including PEX and the prognosis are shown in Table 2.
| Case no. | R‐PEX group | L‐PEX group | P value | |||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Case 1 | Case 2 | Case 3 | Case 4 | Case 5 | Case 6 | Case 7 | Case 1 | Case 2 | Case 3 | Case 4 | ||
| Age (years) | 75 | 60 | 70 | 82 | 64 | 80 | 71 | 69 | 84 | 74 | 72 | 0.54 |
| Gender | M | M | M | M | M | M | F | F | F | F | F | 0.015 |
| Body weight (kg) | 50 | 67 | 67 | 45 | 67 | 70 | 64 | 60 | 47 | 38 | 44 | 0.04 |
| Type of AAV | RLV | MPA | MPA | RLV | RLV | MPA | GPA | MPA | MPA | MPA | MPA | |
| RPGN | + | + | + | + | + | + | + | + | + | + | + | |
| Dialysis | + | + | + | + | + | + | + | − | − | − | − | 0.003 |
| DAH | − | + | + | − | − | + | − | + | + | + | + | 0.11 |
| IP | − | + | − | − | − | + | − | − | + | + | + | 0.20 |
| Clinical severity grade | 2 | 4 | 4 | 2 | 2 | 4 | 3 | 2 | 2 | 2 | 3 | 0.21 |
| BVAS score | 22 | 36 | 25 | 14 | 21 | 24 | 23 | 39 | 20 | 22 | 10 | 0.51 |
| CRP (mg/dL) | 0.93 | 24.52 | 12.1 | 23.47 | 4.53 | 9.99 | 10.19 | 4.62 | 6.28 | 6.2 | 4.11 | 0.16 |
| ANCA titer (IU/mL) | 78 | 457 | 287 | 38.3 | 149.2 | 8.7 | >350 (PR3) | >300 | >300 | 6.2 | >300 | |
| SCr at PEX start (mg/dL) | 6.52 | 7.56 | 11.74 | 8.24 | 5.12 | 8.09 | 5.91 | 2.96 | 1.33 | 1.4 | 1.13 | <0.0005 |
| Maximum SCr (mg/dL) | 6.55 | 7.95 | 11.74 | 9.39 | 9.76 | 9.61 | 9.06 | 2.96 | 1.33 | 1.4 | 1.22 | <0.0005 |
| Minimum urinary volume (mL/day) | 300 | 150 | 14 | 200 | 381 | 5 | 100 | 800 | 1000 | NA | NA | 0.04 |
- AAV, anti‐neutrophil cytoplasmic antibody (ANCA)‐associated vasculitis; BVAS score, Birmingham Vasculitis Activity Score (version 3); DAH, diffuse alveolar hemorrhage; F, female; GPA, granulomatosis with polyangiitis; HD, hemodialysis; IP, interstitial pneumonitis; L‐PEX, those receiving PEX for lung hemorrhage; M, male; MPA, microscopic polyangiitis; NA, not available; R‐PEX, patients receiving plasma exchange (PEX) for severe renal damage; RLV, renal limited vasculitis; RPGN, rapidly progressive glomerulonephritis; SCr, serum creatinine.
| R‐PEX group | L‐PEX group | P value | |||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Case no. | Case 1 | Case 2 | Case 3 | Case 4 | Case 5 | Case 6 | Case 7 | Case 1 | Case 2 | Case 3 | Case 4 | ||||
| Induction therapy | PEX | Average volume of replacement fluid per session | L | 1.80 | 3.33 | 3.83 | 2.31 | 2.12 | 3.41 | 3.50 | 3.73 | 2.79 | 2.23 | 1.99 | 0.68 |
| mL/kg | 36 | 49.8 | 57.2 | 51.4 | 47.2 | 48.7 | 54.7 | 62.2 | 59.3 | 58.8 | 45.2 | 0.15 | |||
| PV | 0.9 | 1.32 | 1.47 | 1.28 | 1.18 | 1.20 | 1.36 | 1.54 | 1.55 | 1.47 | 1.13 | 0.19 | |||
| Average percentage of FFP occupied in total replacement fluid volume (%) | 100.0 | 78.2 | 68.4 | 100.0 | 80.2 | 14.3 | 35.2 | 73.0 | 28.6 | 48.5 | 24.2 | 0.22 | |||
| Dose of oral GC (mg/kg) | 0.7 | 0.62 | 0.74 | 0.7 | 0.45 | 0.45 | 0.62 | 0.67 | 0.85 | 0.79 | 1.03 | 0.02 | |||
| MP | − | + | − | − | − | − | + | + | + | + | + | 0.045 | |||
| CY | − | + | − | + | − | + | + | + | − | + | − | 0.65 | |||
| Rix | − | − | − | − | − | − | − | − | + | − | − | 0.36 | |||
| Prognosis | Period from diagnosis to PEX start (day) | 3 | 21 | 1 | 16 | 5 | 12 | 3 | 1 | 1 | 1 | 1 | 0.017 | ||
| Period to dialysis independence (week) | 2 | 6 | 2 | 2 | 4 | 8 | 4 | ||||||||
| Period to the final observation (months) | Renal | 7 | 5 | 45 | 47 | 14 | 18 | 7 | 30 | 20 | 13 | 5 | |||
| Life | 7 | 25 | 45 | 47 | 14 | 18 | 7 | 30 | 20 | 13 | 5 | ||||
| Renal prognosis final SCr (mg/dL) | 3.98 | HD | 1.85 | 3.67 | HD | HD | 1.09 | 3.03 | 0.78 | 1.89 | 1.09 | 0.24 | |||
| Life prognosis | Alive | Death | Death | Death | Alive | Alive | Alive | Alive | Alive | Death | Death | 0.65 | |||
| Cause of death | Sepsis | Lung aspergillosis | Lung cancer | Gastric cancer | Heart failure | ||||||||||
- CY, cyclophosphamide; FFP, fresh frozen plasma; GC, glucocorticoid; HD, hemodialysis; MP, intravenous methylprednisolone pulse; PEX, plasma exchange; PV, plasma volume; Rix, rituximab; SCr, serum creatinine.
Patient characteristics and basic data at diagnosis
In the R‐PEX, six out of seven were men, and all four cases in the L‐PEX were women. The average body weight of the R‐PEX group was significantly heavier than that of the L‐PEX group. Of the seven R‐PEX cases, six were MPO‐ANCA positive; four of these were microscopic polyangiitis (MPA) accompanied by lung lesions (i.e. lung hemorrhage in three cases and interstitial pneumonitis in one case), and two were renal‐limited vasculitis (RLV). PR3‐ANCA showed a strong positive only in the one remaining patient, who was diagnosed with granulomatosis with polyangiitis (GPA) from a nasal mucosal biopsy. On the other hand, all the L‐PEX cases were MPA. All 11 cases including the L‐PEX cases had RPGN. Dialysis sessions were conducted in all R‐PEX cases. Compared with that of the L‐PEX group, the SCr value of the R‐PEX group (i.e. the value at the beginning of PEX and the maximum value) was significantly higher; conversely, the minimum urine volume per day of the group was significantly lower (Table 1).
Induction therapy
All L‐PEX cases started PEX within 1 day after diagnosis of pulmonary hemorrhage; however, in the R‐PEX group, it took a longer period from the diagnosis of RPGN to the start of PEX (mean 8.7 days, median 5 days, range 1–21 days). All seven R‐PEX cases were dependent on hemodialysis at the beginning of PEX, and all became hemodialysis‐independent within the period of the induction treatment (three cases at the 2‐week follow‐up, two cases at 4‐week follow‐up, one case at 6‐week follow‐up, and one case at 8‐week follow‐up). For all cases in the R‐PEX group, PEX was performed in seven sessions within 2 weeks. In the L‐PEX group, three of four cases underwent the seven sessions of PEX within 2 weeks. Only one remaining case finished PEX in three sessions because of a better clinical course.
Regarding PEX regimen, in the comparison between the R‐PEX group and L‐PEX group in the replacement volume per session, not only the simple volume but also the mL/kg and PV which were corrected for differences in body size and circulating plasma volume did not show any difference. The mean value of average percentage of FFP occupied in total replacement fluid volume of the R‐PEX group and the L‐PEX group was 68.0% and 43.6%, respectively. There was no statistical difference between the two groups. In both the absence of steroid pulse (MP) and the dose of oral GC, the steroid treatment of the R‐PEX group was significantly more mild than that of the L‐PEX group (P = 0.045 and P = 0.02, respectively).
Prognosis
In R‐PEX group, regarding the short‐term renal prognosis after the induction treatment period, the proportion of renal survivors (i.e. the patients who were dialysis‐independent) at the 3‐ and 12‐month follow‐ups were 100% (7/7) and 80% (4/5), respectively (Tables 2 and 3 ). Nonetheless, two renal survivors at the 12‐month follow‐up began maintenance hemodialysis at 14‐ and 18‐month follow‐up without relapse of disease activity. In the renal survivors, the median SCr value at the patient’s final observation (ranging from 7 to 47 months) was 3.57 mg/dL (1.09–3.98 mg/dL). Two of the four renal survivors died after 45 and 47 months (causes of death were lung fungal infection and lung cancer, respectively) (Table 2).
| Author (trial) published year | Pusey et al.12 | Jayne et al.1 (MEPEX) | Pepper et al. 13 | Chen et al. 14 | Our single‐center cohort | ||
|---|---|---|---|---|---|---|---|
| Original research design of the extracted patients | RCT | RCT | CS | CS | CS | ||
| Number of patients who were dialysis‐dependent at presentation and received plasmapheresis | 11 | 37 | 41 | 15 | 7 | ||
| Age median (range) | 59 (23–76) | 64 (28–80) | 62 (19–98) | 58 (41–67) | 71 (60–82) | ||
| MPO/PR3/double positive/negative/unknown | 4/5/0/0/0/2 | 19/12/0/0/0 | 20/19/1/1/0 | 13/2/0/0/0 | 6/1/0/0/0 | ||
| SCr at presentation day on dialysis median (range) (mg/dL) | 15.9 (8.3–20.8) | NA | NA | 5.6 (5.2–9.0) | 7.6 (5.1–11.7) | ||
| Modality of apheresis processing volume/session, numbers of session | PEX 4 L, median9 (5–14, 16–21, 24, 26–29) | PEX 60 mL/kg, 7/2 W | PEX 60 mL/kg, 7/2 W | DFPP 2PV, 3–5 | PEX 50 mL/kg, 7/2 W | ||
| Immunosuppressive agents for induction treatment | GC 60 mg POCY2‐3 mg/kg | GC1 mg/kg POCY 2.5 mg/kg | GC1 mg/kg IVCY | MP 1.5 g/3 day GC 0.6 mg/kg IVCY or MMF 0.5–1.0 | MP (2/7) GC 0.45–0.74 mg/kg CY (4/7; IV3, PO1) | ||
| Renal outcome | Cumulative renal survival rate | 3 months | 81.8% (9/11) | 64.9% (24/37) | 63.4% (26/41) | 73.3% (11/15) | 100% (7/7) |
| 12 months | 54.5% (6/11) | 51.3% (19/37) | 58.5% (24/41) | 62.9% | 80% (4/5) | ||
| 24 months | 54.5% (6/11) | NA | 51.2% (21/41) | NA | 40% (2/5) | ||
| SCr or eGFR at the last observation in renal survivors (follow‐up period) | 2.2–9.2 mg/dL (3–8 years) | NA | Median SCr 1.8 mg/dL (eGFR 34 mL/min per 1.73 m2 (24 months) | 1.0–7.0 mg/dL (6‐24 months) | 1.9–3.9 mg/dL (7–47 months) | ||
- CS, case series; CY, cyclophosphamide; DFPP, double filtration plasmapheresis; eGFR, estimated glomerular filtration rate; GC, glucocorticoid; IVCY, intravenous cyclophosphamide; MMF, mycophenolate mofetil; MP, intravenous methylprednisolone pulse; MPO, myeloperoxidase; NA, not available; PEX, plasma exchange; POCY, oral cyclophosphamide; PR3, proteinase 3; PV, plasma volume; RCT, prospective randomized controlled trial; SCr, serum creatinine; W, week.
In L‐PEX group, lung hemorrhage improved in all patients, and no death occurred during the period of induction treatment. Two of four cases died: one of heart failure and one of gastric cancer, at 5 and 13 months post‐PEX, respectively. In all cases of L‐PEX, renal function was preserved at the last observation (Table 2).
Renal biopsy
In R‐PEX group, a renal biopsy was performed in three cases (Cases 4, 3, and 7) out of seven cases at the timing of 10 days before, 4 days after, and 35 days after starting the induction treatment, respectively. In the order of Cases 4, 3, 7, the proportion of crescent formation was 77.8%, 50.0%, and 56.7%, the proportion of glomerulosclerosis was 11.1%, 12.5%, and 9.7%, and the proportion of areas of interstitial injury was >50%, >50%, and 25–50%, respectively.
In L‐PEX group, a renal biopsy was performed in only one case (Case 1) 2 months after starting induction treatment. The proportion of glomerulosclerosis, crescent formation, and areas of interstitial injury were 16%, 80%, and >50%, respectively.
DISCUSSION
The rationale for PEX in AAV is the removal of pathogenic circulating factors, such as ANCA, inflammatory cytokines, adhesion molecules, complement components promoting neutrophil migration or adhesion to vascular endothelial cells, and neutrophil microparticles 15, 16. From the PEXIVASC survey in 2004, which was distributed among the EUVAS members and was completed by 33 centers, PEX use for SCr ≤ 5.8 mg/dL, SCr > 5.8 mg/dL, RPGN, and lung hemorrhage were 15%, 21%, 61%, and 79%, respectively, and the percentage of sessions of PEX fewer than seven, seven, and more than seven were 18%, 52% and 21%, respectively. PEX use guided by ANCA‐titer comprised only 33% 16. PEX for AAV cases with severe RPGN or dialysis dependence is still a controversial issue, although certain conclusions can be drawn based on several prospective RCTs and meta‐analyses 1-4, 16, 12, 17-21. Pusey et al. published a RCT that showed a beneficial effect of PEX in 19 of 48 dialysis‐dependent patients. In this report, 10 of 11 cases in the PEX group and three of eight cases in the non‐PEX group withdrew from dialysis at a follow‐up of 1 month, while no outcome difference was found in patients with milder renal deterioration.
This RCT was the first report to support the current guidelines 7, 8. The recommendation of guidelines is essentially that routine PEX is not necessary, but when renal function is impaired to the point of requiring dialysis, the addition of PEX increases the chance of renal recovery 12, 17. Subjects to be enrolled in the MEPEX trial 1 had severe renal failure with Cr > 5.8 mg/dL, and about 70% were cases requiring dialysis within 48 h. Although there was no difference in life prognosis, the renal survival rate was significantly better in the PEX group than in the MP group at follow‐up, both after 3 months (69% vs. 49%) and after 12 months (59% vs. 43%). In addition, among dialysis‐dependent patients, PEX reduced the risk of end‐stage renal disease by 22%. In our cohort, the cumulative renal survival rate was even better than those of previous reports demonstrating the efficacy of plasmapheresis for AAV‐PRGN patients who are dependent on dialysis (Table 3) 1, 12-14. We could not clarify the reason for the exceptionally good renal results of our single‐center cohort. Our patients included many MPO‐ANCA‐positive cases and were somewhat older, but the relation of these factors to renal prognosis is not clear. Instead, there may have been, first of all, some selection bias in cases arising from a single‐center cohort. In our cohort, there were fewer cases undergoing renal biopsy than those of the cohorts from major RCTs that required detailed registration criteria, suggesting that our cohort has more cases with reversible renal damage. Cases with reversible damage are typically those with normal renal function before disease onset and whose disease has progressed over a short period; in such patients, rapid treatment is often given priority over receiving renal biopsy.
The second explanation for the difference entails differences in the PEX plasma separation method. Some cohorts from the European trial included cases in which PEX was performed using centrifugation, rather than membrane filtration which clearly removes the IgG fraction; however, the evidence supporting this explanation is poor. For instance, Walsh et al. compared the PEX regimen, that is, plasma separation method (filter or centrifuge), number of sessions, volume of replacement per session, of each study in a meta‐analysis, but the relevance between the regimen and prognosis was not clear 4. In five out of seven cases of R‐PEX, most of the replacement solution of PEX was FFP, however, there was little clear difference the prognosis of the FFP‐dominant cases and the non‐FFP‐dominant cases (Table 2 ).
There are a few reports suggesting that DFPP or immunoadsorption with a feature of selective removal of Ig fractions containing pathogens have a clinical effect with no difference from PEX 21, 14. However, PEX with large FFP replacement can be expected to have additional immunomodulatory effects similar to high‐volume intravenous immunoglobulin administration (IVIG). In R‐PEX, the dose of GC (MP and dose of oral GC) was significantly less than that of the L‐PEX group. Reduction of immunosuppression with PEX combination was a reasonable choice in the intention to avoid treatment‐related death such as infection. In our cohort, there were no treatment‐related deaths within 12 months in stark contrast to the results of major RCTs. This seems to be one of the reasons why our cohort is better in the 12‐month follow‐up of cumulative renal survivors.
In a national retrospective research by questionnaire survey from Japan (registration of patients was from 1989 to 2000) 10, the superiority of plasmapheresis (i.e. PEX or DFPP) in renal prognosis could not be confirmed, even in dialysis‐dependent cases. There are two interpretations of this result. As one interpretation, PEX enforcement cases were more severe, and therefore affected the prognosis; as another interpretation, the intensity of the PEX regimen was insufficient because at that time plasmapheresis for AAV‐RPGN was not approved by the health insurance system and there was no established regimen. According to the studies examining the factors predicting short‐term (i.e. 6‐ or 12‐month) renal prognosis for patients with severe AAV‐RPGN including dialysis dependence at diagnosis, PEX administration (which is limited in patients with dialysis dependence) and a high percentage of normal glomeruli are predictors of good renal prognosis, while dialysis dependence at diagnosis, elderly status and a high percentage of tubular atrophy /interstitial fibrosis/fibrous crescents are predictors of poor renal prognosis 22, 23. Furthermore, using the subgroups of MEPEX cohort, van Wijngaarden et al. investigated the predictive parameters that determine the chances of dialysis independence or death after 12 months in these patients 24. The point at which the chance of therapy‐related death exceeded the chance of dialysis independence was determined using a two‐step binary logistic regression analysis. In the PEX group, the chances of treatment‐related death exceeded that of dialysis independence under the condition of normal glomeruli <2.1% and severe tubular atrophy; in the MP group, the conditions were normal glomeruli <18.1% and severe tubular atrophy. The authors concluded that PEX should be considered even with very poor histologic findings. In the present study, unfortunately, four out of seven cases of R‐PEX were not histopathologically evaluated. According to van Wijngaarden’s paper 24, in clinical practice, if there is even one normal glomerulus in several specimens from a patient, dialysis independence is a more likely outcome of PEX than death. Thus, even if renal biopsy had been performed in the remaining four cases, the same decision of PEX administration would likely have been made. Recently, a large‐scale international RCT called the PEXIVAS trial was conducted to evaluate the effect of PEX, aiming to improve renal/life prognosis and reduce the glucocorticoid dose in AAV patients with renal involvement (registration criteria; <eGFR 50 mL/min with nephritis) 25. The publication of the results is much awaited; the sub‐analysis in severe RPGN cases (SCr > 5.8 mg/dL and dialysis dependent) is considered especially noteworthy. PEX and DFPP for AAV‐RPGN patients was finally approved by the Japanese health insurance system in April 2018; two courses are now covered (one course: up to seven sessions within 2 weeks). With this development, PEX with high intensity can be performed during induction treatment periods for dialysis‐dependent AAV‐RPGN; however, there is also concern about potentially excessive or unnecessary use of this treatment.
CONCLUSIONS
In newly developed anti‐neutrophil cytoplasmic antibody‐associated vasculitis‐rapidly progressive glomerulonephritis (AAV‐RPGN) patients who need dialysis, standard plasma exchange (PEX) can be expected to induce sufficient renal recovery to establish dialysis independence. In addition, PEX has the effect of reducing immunosuppression from the introduction treatment period. Using PEX, renal recovery is more likely than treatment‐related death, even in cases with severe histological damage. However, there is little evidence for using PEX in cases with mild renal impairment, cases that are not “rapidly” progressive, or cases that have advanced to irreversible damage over a long period of time since disease onset.
Acknowledgments
This work was supported by grants from the Research Committee of Intractable Renal Disease of the Ministry of Health, Labor.
Conflict of Interest
None.
