Prophylactic Therapy for a Second Graft After FSGS Recurrence
A first graft lost within months to recurrent disease makes a near-certain case for prophylactic treatment on paper — but the evidence for actually doing anything about it before the disease reappears is thinner than the risk itself feels like it should demand.
Marisol T. is twenty-six, and has spent most of her adult life measuring plans against how her kidneys were doing rather than the other way around — a habit that started with her first transplant, six years ago from her father, which failed faster than anyone had prepared her for. Her native disease was steroid-resistant FSGS, diagnosed in childhood and grinding toward end-stage renal disease by her mid-teens — the kind of history that made her transplant team cautious even the first time. That caution turned out to be warranted: massive proteinuria appeared within eight months of that transplant, and a biopsy confirmed recurrent FSGS in the graft itself, not rejection, not anything else. Eight months is the part her team keeps circling: recurrence inside the first post-transplant year is the aggressive form rather than the indolent late one, and hers bore that out — the kidney was gone sixteen months after the recurrence was caught, two years, near enough, from the day it was implanted.
She is now facing a second living-donor transplant, this time from a distant cousin, and the history that shaped her first graft's course is the single most concrete piece of information the team has about what to expect from her second. Recurrence in a first graft is one of the most consistently documented predictors of recurrence in a second — not a mild elevation in risk, but a pattern strong enough that Gohh's prospective study of preemptive plasmapheresis used prior-graft recurrence as its definition of high risk in the first place, rather than as one factor among several. Marisol does not merely resemble that cohort; her history is its entry criterion. What the team disagrees about isn't whether she's at real risk; it's whether that risk, known in advance rather than discovered after the fact this time, justifies treating before any sign of disease, or whether the honest evidence for doing so is thinner than her history alone makes it feel.
She remembers the first recurrence in specific, physical terms rather than as a lab value — the swelling in her ankles that she noticed before anyone drew blood, the dosage change that came too late to matter. That memory is part of why she has asked, more than once in the pre-transplant workup visits, whether there is anything that can be done "before it happens this time" rather than after, a question her team has tried to answer honestly rather than simply reassure her about, since the honest answer is that the evidence for acting before it happens is exactly what the team is still working through.
Pre-transplant planning, second graft
Her history places her in the highest recurrence-risk category there is — a first graft already lost to this exact process. Gohh's prospective series of preemptive plasmapheresis enrolled exactly that population — high-risk recipients defined by a prior graft lost to recurrence — and while it was small and uncontrolled, it is the study that speaks to her situation directly, and starting around the time of transplant gives the best real chance of blunting what otherwise looks like a near-certain repeat of what happened before.
I'd want to be honest that the prophylactic-PLEX evidence is genuinely weak — small, mostly retrospective, and the kind of literature where publication bias plausibly favors reporting apparent successes more than failures. Plasmapheresis carries real access-line and procedural risk, and there's no proof it changes an outcome that may occur, or not occur, regardless of whether she was pre-treated. I'd rather transplant, watch her proteinuria closely from day one, and treat immediately and aggressively — rescue PLEX plus rituximab — the moment recurrence actually shows up, rather than treat empirically before there's any evidence of disease activity to respond to.
I'm not disputing her risk is real — her history is about as strong a predictor as this field has. I'm disputing that "very high risk" automatically means "treat before evidence of disease," when the specific intervention being proposed hasn't been shown to change what happens next.
There's a third option between prophylactic PLEX and pure watch-and-rescue. Pre-transplant rituximab targets the same underlying process — a circulating permeability factor thought to drive recurrence — through a genuinely different mechanism than PLEX's antibody removal. Fornoni's work is what makes that more than hand-waving: rituximab was shown to bind SMPDL-3b on the podocyte itself and stabilize it, an effect on the target cell that doesn't depend on B-cell depletion at all, which is why it could plausibly outlast a course of antibody removal. It's also logistically simpler: it doesn't need to be timed tightly around the operating room the way a PLEX course does.
I don't think this settles the argument either way — the evidence for rituximab prophylaxis in this exact scenario is also not randomized. But it captures some of the physician's rationale for acting on her known risk in advance, without asking the nephrologist to accept a procedure whose evidence base is the specific thing being questioned.
Agreed: a single dose of rituximab two weeks before transplant, with weekly proteinuria monitoring beginning immediately post-transplant and a pre-committed rescue plan of PLEX plus repeat rituximab at the first sign of recurrence. The pharmacist's middle-path proposal was accepted by both other voices as addressing each side's core concern without fully resolving the underlying evidence disagreement.
Not agreed: whether rituximab prophylaxis should become the standing recommendation for every future prior-graft-recurrence FSGS patient at this program, or whether her case should be treated as one data point pending more evidence. The physician wants it adopted as a default going forward given her risk category; the nephrologist wants each future case reassessed individually, arguing one patient's outcome, whatever it turns out to be, shouldn't settle a question the literature itself hasn't settled.