Objectives: High recurrence and inferior graft survival rates have been reported for kidney transplant recipients with primary focal segmental glomeru-losclerosis. Plasmapheresis is widely used to treat posttransplant relapsing focal segmental glomer-ulosclerosis, but the effectiveness of prophylactic plasmapheresis remains controversial.

Materials and Methods: In this single-center retro-spective study, 21 adult deceased-donor kidney transplant recipients who received prophylactic plasmapheresis were analyzed. Of these, 10 received posttransplant prophylactic plasmapheresis only (less-intensive regimen) and 11 received pre- and posttransplant prophylactic plasmapheresis (more-intensive regimen). Patients with recurrence were treated with steroids and plasmapheresis. Median follow-up was 45 months (interquartile range, 30-107 mo).

Results: At last visit, 20/21 patients (95%) were alive and 17/21 (81%) had functioning grafts. Cumulative focal segmental glomerulosclerosis recurrence rate was 38% (8/21): 30% (3/10) in the less-intensive and 45% (5/11) in the more-intensive group (P = .6594). Four of 8 patients (50%) with relapse eventually had graft loss due to recurrence: 100% (3/3) in the less-intensive and 20% (1/5) in the more-intensive group (P = .1429). Complete remission was observed in 25% (2/8) of recipients with recurrence: 0% (0/3) in the less-intensive and 40% (2/5) in the more-intensive group (P = .4643). Two of 8 patients (25%) remained plas-mapheresis dependant: 0% (0/3) in the less-intensive and 40% (2/5) in the more-intensive group (P = .4643). Response rate (complete/partial) was higher in the more-intensive group (80% [4/5] vs 0% [0/3]; P = .1429); however, overall, the 2 regimens did not show signi-ficantly different outcomes. Comparison between this series and a historical control group of 52 patients with primary focal segmental glomerulos-clerosis trans-planted at our center and not receiving plasmapheresis prophylaxis did not demonstrate any advantages.

Conclusions: No benefits from prophylactic plasma-pheresis in deceased-donor kidney transplant recipients with primary focal segmental glomerulo-sclerosis were shown. Prospective randomized studies comparing alternative preemptive strategies are warranted.

Key words : End-stage renal disease, Prophylaxis, Recurrence, Renal transplant

Introduction

Focal segmental glomerulosclerosis (FSGS) is the most common cause of nephrotic syndrome in Western countries.¹ Rather than a disease, it is more properly defined as a pattern of histologic injury involving podocytes and determining complex damage to glomerular capillaries.^2,3 Two main forms have been identified: primary (idiopathic) and secon-dary (adaptive). Compared with secondary variants, idiopathic FSGS is rare (global incidence of 0.2-1.8/100 000 population per year), more aggressive, and has a higher risk of recurrence after kidney transplant.4 Nephrotic-range proteinuria is frequently associated with hypertension, and its cause is unclear. A not yet identified circulating factor may cause podocyte injury and progression to glomeru-losclerosis.⁵ Proposed candidates are tumor necrosis factor alpha,6 cardiotrophin-like cytokine factor 1,7 apoA1b,⁸ anti-CD40 antibody,⁹ and serum urine-type plasminogen activator receptor.¹⁰

For patients who develop end-stage renal disease (ESRD), kidney transplant represents the best thera-peutic option. However, due to the high recurrence rates (40% for first transplants and up to 100% for retransplants),^5,11-14 inferior outcomes have been reported for recipients with primary FSGS.^13,15-17 Recognized risk factors for recurrence include white ethnicity, young age at diagnosis, mesangial proli-feration at biopsy, rapid progression (< 3 y) to ESRD in the native kidneys, a previous transplant lost due to recurrence, and early-onset proteinuria posttransplant.^18,19 A living donor seems to offer the best graft survival, but careful selection of the candidate is mandatory.^15,17

Unfortunately, up to 50% of the recipients with relapsing FSGS eventually lose their transplant due to relapse.^13,20,21 Recurrence is probably due to the same circulating factor deemed to be responsible for the primary disease.^3,6-10,22 Management of post-transplant FSGS is still controversial and mostly based on empirical strategies not supported by randomized clinical trials.^23,24 Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are commonly administered to reduce proteinuria and control hypertension. Cyclosporine, tacrolimus, cyclophosphamide, and steroids have been used in various combinations and dosages with mixed results.²⁵ To date, plasmapheresis represents the most widely used treatment. It has been demonstrated to reduce proteinuria and induce remission in more than 50% of recipients with recurrence.^21,26-28 More recently, improved outcomes have been achieved with rituximab.^29,30 The drug may lower the production of the circulating factor directly acting on B cells or indirectly affecting the interaction between T and B lymphocytes. Furthermore, it seems to stop podocyte dysfunction and apoptosis by modulating sphingomyelinase activity.³¹ Costimulation blockers abatacept and belatacept have also been used.³²

B7-1 blockade may prevent podocyte injury and proteinuria through inhibition of B7-1-mediated β1-integrin inactivation, but effectiveness has not been confirmed.³²

With consideration of the positive results obtained with therapeutic plasmapheresis, some authors have advocated the use of prophylactic plasmapheresis.^33,34 The rationale behind this approach is to prevent FSGS relapse by removing the circulating factor before it interacts with the allograft and triggers podocyte injury. Despite interesting reports suggesting reduced recurrence rates and better graft survival, solid data supporting this hypothesis are lacking.

We report our experience with prophylactic and therapeutic plasmapheresis in a cohort of deceased-donor kidney transplant recipients with primary FSGS.

Materials and Methods

In this single-center retrospective study, we analyzed data from 21 consecutive adult patients with biopsy-proven primary FSGS who had undergone deceased-donor kidney transplant and prophylactic plasmapheresis at our institution. Patients trans-planted between August 2003 and August 2008 received posttransplant prophylactic plasmapheresis only; this less-intensive regimen included 3 sessions per week for 3 consecutive weeks from post-transplant day 1. Patients transplanted from September 2008 to August 2014 received pre- and posttransplant prophylactic plasmapheresis; this more-intensive regimen included 1 session immediately before surgery and 3 sessions per week for 3 consecutive weeks from posttransplant day 1. For patients with recurrence (see below), plasmapheresis was not stopped until 24-hour proteinuria was < 0.5 g.

As induction treatment, patients received intra-venous basiliximab (Simulect, Novartis Pharma, Basel, Switzerland) 20 mg on day 0 and day 4 and intravenous methylprednisolone 250 mg on day 0, 125 mg on day 2, and 125 mg on day 3. As maintenance immunosuppression, recipients were given oral tacrolimus (Prograf, Astellas Pharma, Tokyo, Japan) 0.1 mg/kg/day (daily dose was adjusted according to target trough levels: 8-12 ng/mL in the first 6 posttransplant months and 5-8 ng/mL thereafter), mycophenolate mofetil (Cell Cept, Hoffmann-LaRoche, Nutley, NJ, USA) 2 g/day tapered after 6 months to 1.5 g/day or less according to patient’s tolerance, and prednisone 20 mg/day (progressively tapered to 5 mg/day by day 45).

All patients received prophylaxis for Pneumocystis jiroveci infection with oral trimethoprim/-sulfamethoxazole (80/400 mg/day 3 times/wk) for 6 months. Recipients at high risk of cytomegalovirus (CMV) disease (ie, donor positive/recipient negative CMV immunization) were also administered prophylaxis with oral valganciclovir (Valcyte, Hoffmann-LaRoche) titrated according to renal function for 6 months.

The following outcomes were evaluated: patient survival, graft survival, FSGS recurrence, response to treatment, serum creatinine concentration, 24-hour proteinuria, hypertension, perioperative (within 30 days) surgical complications (ie, intraoperative bleeding > 500 mL, postoperative bleeding requiring transfusion or reexploration, graft thrombosis, urinary leakage, and surgical site infection), throm-bocytopenia, delayed graft function, biopsy-proven rejection, CMV disease, polyomavirus-associated nephropathy (PVAN), and new-onset diabetes after transplant.

Recurrence of FSGS was clinically suspected when posttransplant proteinuria was ≥ 1 g/24 hours. Whenever feasible, a biopsy was performed to confirm the diagnosis. Specimens were evaluated under light microscopy and immunostaining by our expert pathologists. Relapse of FSGS was always treated with intravenous methylprednisolone (1 g for 3 consecutive days) and therapeutic plasmapheresis (3 sessions/wk for at least 3 wk or until proteinuria was < 0.5 g/24 h). Prophylactic and therapeutic plasmapheresis were performed using a MultiFiltrate system (Fresenius Medical Care, Bad Hamburg, Germany) with 1 plasma volume exchange per session and 5% albumin replacement. No plasma and no immunoglobulin were given during volume replacement. Response to treatment was defined as (1) complete (proteinuria < 0.5 g/24 h for at least 4 consecutive weeks); (2) partial (decrease in proteinuria ≥ 50% of the posttransplant peak); or (3) absent (lack of reduction in protein excretion or decrease in proteinuria < 50% of the posttransplant peak). Patients who could not stop therapeutic plasmapheresis due to rapid increase in proteinuria after plasmapheresis withdrawal were considered plasmapheresis dependent.

At baseline, patients were thoroughly evaluated by clinical examination and laboratory tests. Serum creatinine and 24-hour proteinuria were assessed daily for the first 2 posttransplant weeks. After hospital discharge, patients were followed at in-creasing intervals from 3 times per week to quarterly. A graft biopsy was performed for creatinine increase ≥ 20% from baseline and/or proteinuria ≥ 1 g/24 hours in 2 consecutive measurements within the same week in the absence of any other potential causes (ie, vascular complications, urologic com-plications, hemodynamic changes, infections, or tacrolimus-related toxicity). Histologic lesions were scored according to the revised Banff 2005 classification.³⁵ Delayed graft function was defined as the need for dialysis in the first posttransplant week. Patients requiring medications to control their systemic blood pressure were diagnosed with hypertension. New-onset diabetes after transplant was defined according to the American Diabetes Association guidelines (fasting plasma glucose ≥ 126 mg/dL). Cytomegalovirus disease and PVAN were diagnosed by quantitative polymerase chain reaction analysis on whole blood samples and histology.

As a complementary analysis, outcomes of patients treated with prophylactic plasmapheresis were compared with outcomes of a historical control group of recipients with primary FSGS transplanted at our institution who were not receiving plasma-pheresis prophylaxis.³⁶

Written informed consent was obtained from all patients. Immunosuppression and plasmapheresis regimens were approved by our Ethical Committee. The study was conducted according to the Helsinki Declaration and applicable regulatory requirements.

Categorical and numerical variables were des-cribed using proportions, percentages or medians (with 1st to 3rd interquartile range [IQR]) and were compared using Fisher exact test, chi-square test, or Mann-Whitney U test as appropriate. Outcomes of the entire cohort of patients receiving prophylaxis were collectively described as actuarial incidences and median values at last visit. Given the fact that recipients in the less-intensive and more-intensive regimens had different lengths of follow-up, outcomes of the 2 groups were compared considering the first 3 years only. P < .05 was considered statistically significant. Analyses were run using SPSS (version 23.0; IBM Corp., Armonk, NY, USA).

Results

From August 2003 to August 2014, 21 white adult patients with biopsy-proven primary FSGS were transplanted at our institution and received prophylactic plasmapheresis. Of these, 10 recipients (from August 2003 to August 2008) received the less-intensive regimen, and 11 recipients (from September 2008 to August 2014) received the more-intensive regimen. All transplants were from brain-dead (heart-beating) donors, and all recipients were treated with basiliximab, tacrolimus, mycophenolate mofetil, and steroids. Median recipient age was 41 years (IQR, 38-52 y). Median time from diagnosis of FSGS to dialysis was 5 years (IQR, 1-10 y). Fifty-two percent (11/21) of the recipients were at high risk for recurrence because of rapid progression (< 3 y) to ESRD or a previous transplant failed due to relapsing FSGS. No patients were lost to follow-up. Baseline characteristics of the cohort are shown in Table 1.

Median follow-up was 45 months (IQR, 30-107 mo). At the end of the study, 95% (20/21) of the patients were still alive. One recipient died from acute liver failure 31 months after transplant. He did not experience FSGS recurrence and maintained good graft function (serum creatinine of 1.5 mg/dL) with normal proteinuria (0.2 g/24 h) throughout the study. Actuarial incidence of death-censored graft loss at last visit was 19% (4/21). All losses were due to FSGS recurrence.

During follow-up, 48% (10/21) of the patients developed proteinuria ≥ 1 g/24 hours. Median time between transplant and onset of proteinuria was 40 days (IQR, 16.25-68.75 d). Seventy percent (7/10) of the recipients with proteinuria were biopsied, with histology confirming FSGS recurrence in 5 patients. The other 2 biopsied patients showed acute calcineurin inhibitor toxicity and chronic vascular damage mainly related to the donor. In 2 more cases, it was considered unnecessary to perform a biopsy because both of these patients developed massive proteinuria (> 3 g/24 h) within a few hours after surgery (clinical diagnosis of recurrence). Another patient refused the procedure. Because FSGS was the most likely diagnosis, these 3 patients were treated with therapeutic plasmapheresis and steroids. Overall, 38% (8/21) of the recipients experienced FSGS relapse (5 biopsy-proven and 3 clinical). Median time between transplant and diagnosis of recurrence was 40 days (IQR, 15-58.25 d). All episodes of recurrence were recorded during the first year of follow-up. Fifty percent of the relapses (4/8) were detected within posttransplant day 15 while patients were still receiving prophylactic plas-mapheresis. Characteristics of patients with and without FSGS recurrence are shown in Table 2.

Treatment was always initiated within 2 weeks after diagnosis of recurrence. Fifty percent (4/8) of the patients with relapsing FSGS failed to respond to treatment and eventually lost their graft due to recurrence. Among these recipients, 75% (3/4) relapsed while still on prophylactic plasmapheresis. Median time from recurrence to graft failure was 3.9 months (IQR, 3.3-13.8 mo). Twenty-five percent (2/8) of the patients with recurrence showed complete response to treatment. At last follow-up, graft function and proteinuria were both normal in these 2 patients (serum creatinine 1.1 and 1 mg/dL; 24-hour proteinuria 0.2 and 0.15 g, respectively). Twenty-five percent (2/8) of the relapsing patients showed partial response to treatment and became plasmapheresis dependent. At last visit, these 2 patients showed satisfactory graft function and proteinuria (serum creatinine 1.6 and 1.5 mg/dL; 24-hour proteinuria 1.5 and 0.6 g, respectively). Overall (complete and partial) response to treatment was 50% (4/8). Characteristics of responders and those who did not respond are shown in Table 3.

Delayed graft function was observed in 9.5% (2/21) of the patients, whereas the cumulative incidence of acute rejection was 14% (3/21). At last follow-up visit, median serum creatinine and median proteinuria were 1.3 mg/dL (IQR, 1-1.6 mg/dL) and 0.2 g/24 hours (IQR, 0.15-0.4 g/24 h), respectively. During the study period, 52% (11/21) of the patients were given antihypertensive medications. Among them, 43% (9/21) received angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, or both. Fourteen percent (3/21) of the recipients developed new-onset diabetes after transplant.

There were no episodes of CMV disease or PVAN. Peri-operative surgical complications were recorded for 9.5% (2/21) of the patients. These included 1 episode of urinary leakage and 1 episode of posttransplant anemia requiring blood transfusion. No plasmapheresis-related adverse effects were recorded.

As shown in Table 4, baseline characteristics of the recipients in both treatment groups were similar. Three-year patient survival and death-censored graft survival rates in less-intensive versus more-intensive groups were 90% (9/10) versus 100% (11/11) and 70% (7/10) versus 91% (10/11), respectively (P = .4762 and P = .3108). Graft losses were due to death with functioning graft (n = 1) and relapsing FSGS (n = 4). Within 3 years of follow-up, proteinuria ≥ 1 g/24 hours was detected in 40% (4/10) of the recipients in the less-intensive group versus 54.5% (6/11) in the more-intensive group (P = .6699). Focal segmental glomerulosclerosis recurrence rate was 30% (3/10; 2 biopsy-proven and 1 clinical) in the less-intensive and 45% (5/11; 3 biopsy-proven and 2 clinical) in more-intensive group (P = .6594). All recurrences were recorded during the first posttransplant year (accordingly, incidences were not adjusted for length of follow-up). Three patients in the less-intensive (3/3, 100%) and 1 patient in the more-intensive group (1/5, 20%) relapsed while still on prophylaxis (P = .1429). Complete response to treatment was 40% (2/5) in the more-intensive and 0% (0/3) in the less-intensive group (P = .4643), whereas partial response was observed in 40% (2/5) of the recipients in the more-intensive and 0% (0/3) in the less-intensive group (P = .4643). One patient (1/5, 20%) in the more-intensive and 3 recipients (3/3, 100%) in the less-intensive group failed to respond and developed graft failure (P = .1429). Rate of delayed graft function was 10% (1/10) in the less-intensive and 9% (1/11) in the more-intensive group (P = 1.000). Three-year cumulative rejection rate was 20% (2/10) in the less-intensive and 9% (1/11) in the more-intensive group (P = .5865). Three-year median serum creatinine and 24-hour proteinuria in the less-intensive and more-intensive groups were 1.5 mg/dL (IQR, 0.9-1.8 mg/dL) versus 1.25 mg/dL (IQR, 1.1-1.6 mg/dL) and 0.2 g/24 hours (IQR, 0.12-0.28 g/24 h) versus 0.19 g/24 hours (IQR, 0.16-0.4 g/24 h), respectively (P = .5028 and P = .9840). After 3 years of follow-up, the proportion of patients on antihypertensive medications was 70% (7/10) in the less-intensive and 36% (4/11) in the more-intensive group (P = .1984). Perioperative surgical complication rates were 10% (1/10) in the less-intensive and 9% (1/11) in more-intensive group (P = 1.000).

As a control group, we chose a cohort of 52 adult kidney transplant patients with FSGS not receiving prophylactic plasmapheresis who were seen at our center between 1988 and 2008. Detailed characteristics, treatment protocols, and long-term outcomes of this historical series have been previously described.36 Actuarial 3-year patient and death-censored graft survival rates for patients not receiving or receiving prophylaxis were similar: 100% (52/52) versus 95% (20/21) and 84% (44/52) versus 81% (17/21), respectively (P = .2877 and P = .7022). The proportion of patients who had biopsy-proven recurrence was 24% (5/21) in the prophylaxis group versus 23% (12/52) in the no-prophylaxis group (P = .9465). All episodes of recurrence were recorded during the first posttransplant year. Recurrence (biopsy-proven and clinical) was associated with graft loss in 50% (4/8) of the recipients who received prophylaxis versus 58% (7/12) of the recipients without prophylaxis (P = 1.000). Overall (partial and complete) response to treatment was 80% in both groups (P = 1.000).

Discussion

Plasmapheresis for posttransplant FSGS recurrence was first described by Zimmerman in 1985.³⁷ Since then, several studies supporting aphaeretic techniques for relapsing FSGS have been published.^5,21,27,38 Experience with therapeutic plasmapheresis showed that the sooner it is administered after recurrence, the better is the response to treatment. Following this principle, prophylactic plasmapheresis protocols were proposed by Iguchi and colleagues,³³ Ohta and colleagues,³⁹ and Gohh and associates.³⁴ Although these were limited because of small populations, lack of randomization, inclusion of both deceased-donor and living-donor transplant recipients, and admin-istration of no standardized immunosup-pressive or plasmapheresis protocols, these studies showed reduced recurrence rates and better graft survival compared with historical controls.

In the present paper, we describe our experience with prophylactic and therapeutic plasmapheresis in adult deceased-donor kidney transplant recipients with biopsy-proven primary FSGS. We observed excellent patient and death-censored graft survival. Recurrence rate of FSGS was not different from that reported by our center in 2010 in patients not receiving prophylaxis³⁶ and was overall similar to that described by Alasfar and colleagues in a more recent trial evaluating plasmapheresis and rituximab.³⁰ Furthermore, no clear benefit of extra preoperative plasmapheresis could be demonstrated.

Patient survival in this series was 95%, with no significant differences shown between the 2 plasmapheresis regimens (100% vs 90%). Only 1 patient died during follow-up, with cause of death not related to FSGS, plasmapheresis, or transplant. These data further support kidney transplant in primary FSGS, as expected lifespan for patients on dialysis remains significantly worse.⁴⁰ Our experience also confirms that perioperative plas-mapheresis is overall safe and does not significantly increase the risk of surgical, hematologic, or infectious complications.

The rate of death-censored graft survival was also extremely good (81%). Recent data from the Australian and New Zealand Dialysis and Transplant Registry, which were not sorted by primary or secondary forms of FSGS and did not discriminate between first transplants or retransplants, have shown 5-year graft survival rates of 52% and 83% for patients with and without FSGS recurrence.¹⁵ We observed that graft loss was numerically lower in patients receiving pretransplant plasmapheresis (30% vs 9%); however, given the small sample size, no survival benefit from the more intensive protocol could be demonstrated. As expected, recurrence was the leading cause of transplant failure. Overall FSGS recurrence rate in this study was 38%, with no significant differences between the 2 plasmapheresis regimens. The reported incidence of FSGS recurrence after transplant is about 30% in low-risk patients but as high as 100% for high-risk patients.^5,11-14 Consi-dering that one-third of our patients had lost a previous graft due to recurrence and given the fact that more than one-half of the study population was affected by an aggressive variant of the disease, our results are encouraging. Nevertheless, as already suggested by Gonzalez and colleagues⁴¹ and Alasfar and colleagues,³⁰ our experience shows that prophylactic plasmapheresis does not prevent FSGS recurrence. Subanalysis also failed to demonstrate any benefit arising from extra preoperative plas-mapheresis. Risk factors for recurrence have been extensively investigated,¹⁴ but individual charac-teristics suggesting which patient might benefit from prophylactic plasmapheresis or which subgroup will respond to plasmapheresis treatment have not been identified.²⁷ The possible role of genetic mutations of the slit diaphragm components in predicting the risk of recurrence after transplant is currently under investigation.⁴²

Some authors have suggested that transplant patients with FSGS have higher rejection rates than those without FSGS.¹⁹ Because most studies refer to patients treated with cyclosporine, our use of tacrolimus instead of cyclosporine may explain the lower incidence of rejection. Despite the small number, we could not find any relationship between rejection and recurrence or between rejection and response to treatment.

We observed that one-half of the recipients with recurrence did not respond to plasmapheresis and developed graft failure. Twenty-five percent showed complete response, whereas another 25% became plasmapheresis dependent but maintained good renal function and acceptable proteinuria for many years. These outcomes are in line with a recent comprehensive review and meta-analysis²⁷ and support plasmapheresis as first-line treatment for relapsing FSGS. Our experience also supports prolonged plasmapheresis for patients with partial remission.^27,36 Nevertheless, alternative or at least complementary options such as rituximab³⁰ or abatacept³² should be offered to patients who fail to respond to plasmapheresis or become plasma-pheresis dependant.

As discussed here, preoperative plasmapheresis does not seem to reduce the risk of recurrence. However, response to treatment was only observed in patients who received a more intensive prophylactic plasmapheresis regimen (80% vs 0%). A possible explanation is that pretransplant plasmapheresis, removing or at least reducing the concentration of the circulating factor before allograft implant, might limit podocyte damage and slow the progression of recurrence. Direct anti-T-cell and indirect anti-B-cell effects of basiliximab and tacrolimus may also play a role.

Our study has several limitations, including its retrospective nature, the relatively small population, and the lack of statistical power to address subtle differences between the 2 plasmapheresis regimens. However, we present a homogeneous cohort of patients (52% at high risk of recurrence) with standardized immunosuppression and plasma-pheresis protocols. Another limitation is that we could not use electron microscopy and genetic testing during pretransplant workup to confirm histology findings. Nevertheless, considering how our under-standing of FSGS has evolved over the past decade, it is likely that many patients previously diagnosed with the idiopathic variant will be in the future reassigned to alternative forms of the disease.³ We also recognize that differences in follow-up between the 2 treatment groups can account for the chance of new recurrences to appear and more grafts to fail. However, all relapses observed in the present study were recorded within the first year post-transplant, and late relapses, albeit described, are less common.

Overall, our experience represents additional evidence of the inadequacy of current anti-B-cell-targeted therapies and antibody-removal strategies for the prevention and treatment of FSGS recurrence after kidney transplant. The fact that recurrence rate was not affected by prophylactic plasmapheresis and a significant proportion of relapses was not responsive to therapeutic plasmapheresis suggest a possible involvement of antibody-producing B cells or plasma cells that are somehow resistant to plasmapheresis and rituximab. Such a subgroup of immune cells may require a more specific and aggressive approach with a proteasome inhibitor and/or an anti-CD38 monoclonal antibody.

Conclusions

Prophylactic plasmapheresis does not reduce the risk of FSGS recurrence after deceased-donor kidney transplant. Whether preoperative prophylactic plasmapheresis may improve response to treatment or reduce the aggressiveness of the relapse remains unclear, and more powerful studies are needed to confirm this preliminary finding. Therapeutic plasmapheresis is still a valid option for first-line treatment of relapsing FSGS. Patients with partial remission should be offered prolonged treatment, as sustained graft function can be achieved in plasmapheresis-dependent recipients. For patients who do not respond to plasmapheresis or become plasmapheresis dependent, a trial with rituximab should be also considered. Properly designed clinical trials evaluating alternative prophylactic and thera-peutic strategies against plasma cells are warranted.

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