De novo collapsing glomerulonephritis after kidney transplantation

Someone asked: how do you manage de novo collapsing glomerulonephritis in a kidney transplant recipient?

Short answer: we don’t know!

It is safe to say we are in an evidence free zone here. This condition is certainly rare – limited to case reports or small case series. The first thing to say is that collapsing GN is a pattern of injury that can be seen in background of many glomerular disease, and results from more than one pathogenetic mechanism. It, however, confers a uniformly poor prognosis to all of them.

Once recurrence of glonerular disease has been ruled out, we should consider what could be the possible cause because that will have a bearing on management. Postulated mechanisms include Parvovirus B19 infection (treatment: reduction of immunosuppression and IVIG), microvascular injury secondary to sirolimus, or drug induced TMA (take off the offending drug, ?try plasmapheresis), or a situation where the allograft comes from a donor harboring mutations in the APOL1 gene, which predisposes to collapsing GN in the face of a second hit (such as infection – CMV, bacterial, etc). Not much you can do in the last case.

Given that microvascular injury can cause collapse, one can wonder whether antibody-mediated endothelial injury can also lead to this presentation. Indeed some of the initial descriptions were described in association with “chronic rejection”.

Clearly, an entity looking for someone to latch on to in terms of developing a research career…

4 thoughts on “De novo collapsing glomerulonephritis after kidney transplantation

  1. N Gopalakrishnan

    I have come across ‘collapsing glomerulopathy’ in the allograft — donated by the mother to son. A feature of worry and excitement was that the patient not just had collapsing glomerulopathy (tuft collapse + podocyte proliferation), but also,had marked cystic tubular dilatation — a classical description of HIVAN. We kept repeating HIV serology , which turned out to be negative. His immunosuppression didn’t include sirolimus nor his biopsy showed any evidence for AMR. He had not been on any drugs known to be associated with collapsing GN (bisphosphonates,anabolic steroids,etc.,) Parvovirus was negative.
    The only positive report was CMV! Literature mentions CMV as a possible cause for collapsing GN. But, CMV treatment wasn’t successful in curbing the disease process. He went in for graft dysfunction and expired after being on dialysisfor few months .

    Reply
  2. Aarthi

    Sir,
    Suppose we are doing plasmapheresis for cast nephropathy , after how many sessions should light chain load be tested.. also if significant fall is noted, how many sessions after that to be given
    Should plasmapheresis be done in the first place

    Reply
  3. plagas

    semantics ! may be

    second hit of knudson is loss of heterozygosity of a tumor suppressor gene

    interestingly apol1 may be behaving as a tsg too with two loss conferring a far greater risk than a single loss or none

    serial hit than second hit ?!

    Reply
  4. Sajan Thomas

    Hi Vivek,
    I have seen a case of collapsing FSGS. The patient was on Sirolimus and had also received a Bisphosphonate in the past.

    Reply

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