A referral from the haematology ward

You are asked to see a 68 year old woman on the haematology ward of a teaching hospital.  From the notes you learn that she has multiple myeloma with IgG lambda paraprotein.  Serum creatinine at the time of diagnosis was 155μmol/l and there was 13g/24h of proteinuria.  Initial treatment was with bortezomib (Velcade), doxorubicin and dexamethasone, but this was discontinued after 2 cycles due to ‘disease progression’.  You are unable to find an exact description of this ‘progression’ in her notes, but her creatinine had risen to 312μmol/l during this period. 

As a result, therapy was switched to lenalidomide and dexamethasone.  She has been maintained on such therapy for 6 weeks during which time her creatinine fallen to 189μmol/l. 

She has now been admitted following 1 week of lassitude and her creatinine is 427μmol/l, with an albumin of 35g/l.  Dipstick testing shows 4+ protein/no blood with a urinary protein excretion of 4.5g/24h.  She has been self administering low-molecular weight heparin and epo at home and attending for a monthly bisphosphonate infusion.  Other medications are omeprazole and amlodipine.

Examination shows a cushingoid woman with no rash or fever and a BP of 148/83.  There is a trace of oedema but nothing else to find.  Her Hb is 8.9g/dl and her platelet count 123.

  • What further information would you like: either as new investigations or from the course of the illness so far?
  • Would you suggest a kidney biopsy in this case and why?

3 thoughts on “A referral from the haematology ward”

  1. I think there are a few initial issues to consider:

    1) What was the diagnosis of myeloma founded on. Currently the diagnostic criteria require >10% plasma cells on bone marrow, monoclonal protein and target-organ involvement (‘CRAB’) – and one presumes these were met. If renal impairment and proteinuria constituted the only target organ disease, this is clearly a very different clinical entity from advanced skeletal involvement. The latter will doubtless impact on the patient’s performance status, a very important consideration here.

    2) What constituted disease progression with the initial chemo regimen – worsening renal impairment, paraprotein load or bone marrow involvement? We are not given information about the SFLC levels. ‘Progression’ in any of these parameters is worrying given that the initial chemo is bortezomib based.

    The degree of proteinuria at presentation is suggestive of a glomerular lesion as opposed to predominant light chain cast nephropathy (although we do not know how heavy her urinary light chain excretion is). Leading lesions to be considered would hence be AL amyloid or light chain deposition disease. A differential diagnosis exists including, for instance, drug induced lesions (eg collapsing glomerulopathy associated with bisphosphonate use or viral infections such as parvovirus) or a paraneoplastic membranous nephropathy. The recent rise in creatinine may constitute progression of her renal lesion (I note the discordant change in proteinuria, possibly related to the fall in clearance), a super added insult (pre renal hit, drug toxicity) or even renal vein thrombosis given she has been on lenolidamide even through receiving LMWH (reassuring no haematuria). An obstructive lesion clearly needs to be excluded and renal size measured.

    Notwithstanding the above and assuming we will collate a full non invasive dataset of investigations (light chain loads, virology, uimmune screens etc) I think a biopsy will be helpful to characterise the dominant lesion, exclude potential non-paraprotein related disorders as discussed above and establish the degree of chronic damage. If this turns out to be light chain cast nephropathy this will also give us some guidance as to the potential benefit of high cut off dialysis if her renal impairment continues to worsen. Having siad this I would be keen to have some guidance from the haematologists as to what other therapeutic manoeuvres remain for her underlying disease (I assume she will not be a candidate for BMT as she is >65).

  2. I think ‘Mr Peanut’ has covered the important aspects.

    We do need some more background particularly regarding her myeloma history both the extent of disease at diagnosis but also what made the haematologists think that the disease was refractory to the initial induction therapy. It would be helpful to have some more bloods from the early course of disease (FBC, albumin, Ca, urinary light chains) to give us a better idea of things.

    The proteinuria at the start does suggest a more glomerular lesion and LCDD or amyloid are the key differentials (also have cryoglobulinaemia on the list to be thorough). Now things have clearly progressed whether this is progression of the glomerular lesion or cast nephropathy is becomig an issue + other insults be they drug or hypercalciamia or dehydration related. The obvious investigations as listed by Mr Peanut are needed.

    I would do a renal biopsy as we do need to know the extent of the lesion and chronic damage though there is a not insignificant higher risk of bleeding etc. in this case. guidance and collaboration with the haematologists is clearly needed!

  3. Also worth mentioning that although she is moderate risk for a biopsy (significant renal impairment, relative thrombocytopaenia, anaemia needing correction), studies suggest that there is no significant excess risk when biopsying patients with monoclonal gammopathies as compared to the general renal population eg Fish et al cJASN 2011 22:1129-1136

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