Continued hemoptysis after ESRD due to anti-GBM disease


I would like to submit this question about recurrent hemoptysis with Goodpasture syndrome and the need to continue immunosuppression for a patient who remains on chronic hemodialysis after an acute disease.

The story:
30 year old man (smoker) with Goodpasture syndrome (anti GBM positive and ANCA negative), hemoptysis and anti-GBN nephritis went on to develop chronic renal failure despite plasmapheresis, prednisone and cyclophosphamide for 3 weeks.

Cyclophosphamide had been stopped because of severe thrombocytopenia (60,000). Bone marrow smear was normal. Platelets rose to 110,000. While on prednisone therapy (anti-GBM negative) the patient was readmitted with catheter sepsis, thrombocytopenia (70,000) hemoptysis (positive DL CO > 120% and hemorrhagic alveolitis on CT scan. Being now on chronic hemodialysis , should we continue immunosuppresion (prednisone with or without low dose cyclophosphamide) and for how long ?

Richard Turcot, M.D. (Trois-Rivieres, Quebec)

This question was submitted to NEPHROL for a response

David Tiller, M.D., (Royal Prince Alfred Hospital, New South Wales, Australia)
It is a difficult problem when there appears to be continuing activity after renal failure has supervined. There appears to be a poor correlation between the level of anti-GBM in the plasma and clinical activity so you can't rely on that to guide you. If there is continuing evidence of pulmonary haemorrhage (elevated dlCO or haemoptysis) then we would continue with steroids/cyclophosphamide. If you are running into trouble with cyclophosphamide try steroids and cyclosporin A. There are no decent studies that I am aware of to support that combination, but there are some anecdotes. No point in using azathioprine etc. Pheresis is probably also useless. A difficult problem.

C.P. Swainson, M.D., (Royal Infirmary of Edinburgh, Scotland)
If anti-GBM antibodies are still present, and they can persist for a median time of 18 months, recurrent hemoptysis can be triggered by sepsis and smoking. I don't think anyone has demonstrated that recurrences can be prevented by continued immunosuppression, but prudence might suggest that treatment should be continued until antibody levels are very low or absent.

Jeremy Levy, M.D., (Royal Postgraduate Medical School, London, UK
We have seen relapse of isolated pulmonary haemorrhage and/or nephritis, both in patients and animal models, in the setting of sepsis, continued smoking, exposure to hydrocarbons or (importantly in patients on renal replacement therapy) fluid overload with pulmonary oedema.

We routinely immunosuppress with cyclophosphamide for 8-12 weeks, and prednisolone, tailing off over 6 months. Certainly in patients with continuing pulmonary haemorrhage we would use oral prednisolone for several months, even when their kidneys have failed, and continuing well after anti-GBM autoantibodies have become undetectable. In our experience it is rare for pulmonary haemorrhage to relapse in the absence of provoking factors. We would reserve plasma exchange for fulminant pulmonary bleeding.

Norbert Braun MD, (University of Tuebingen, Germany)
We would treat the catheter sepsis by removing all plastic and treatment with antibiotics and iv Igs. If infection is controlled after a week or so, prednisolone and cyclophosphamide po for 3 months could help to control hemotypsis. If the patient is anti-GBM antibody positive then, there is good uncontrolled evidence that immunoadsorption is helpful in stopping pulmonary hemorrhage. A small controlled, unpublished trial in Scandinavia shows that there is a trend of immunoadsorption to be superior to plasmapheresis in RPGN.

(October, 1996)

Helio G. Cardim Silva, M.D.,Faculdade de Ciências Médicas da Santa Casa de Sao Paulo. (Santa Casa School of Medicine) I have been taking care of a patient with Goodpasture syndrome ANCA negative. That patient went on chronic renal failure despite plasmapheresis and imunossupression treatment. He presented severe hemoptysis after acute disease that was reverted after methilprednisolone pulse(1 gr/day for 3 days) He has been on hemodialysis and imunossupression treatment (prednisone and low dose cyclofosfamide) for 5 months. Initial level of anti-GBM was 305 UE/mL, now it is 72 UE/mL.He is well on hemodialysis, prednisone has been tapered and cyclofosfamide was changed for azathioprine. I believe that, in this case, methilprednisolone pulse was effective for hemoptysis remission.
Helio Gomes Cardim Silva (hcardim@mandic.com.br)
Sao Paulo, Sao Paulo Brazil-Saturday, May 24, 1997 at 09:49:54 (PDT)

I would like to submit this question about unresponsiveness to Epoetin therapy in a patient with sever gout. The patient has a Hb of about 6.3g/dl and no intestinal haemorrhage was found on endoscopy. What is the best course of treatment to help raise the level without the need for transfusion. The patient is on the UK transplant list and has cytotoxic antibodies of 65% so further transfusions are to be avoided.
Paul J Murray
Southampton, Hampshire UK-Wednesday, September 17, 1997 at 05:48:18 (PDT)

Erythropoietin unresponsiveness has always been the problem in many ESRD patients. This could be due to several factors the most common of which is iron deficiency. This we can check by knowing the serum ferritin and transferrin saturation. Of course, there are other causes of erythtropoietin resistance like chronic infection or inflamation. In this situation, you have to double the dose of your erythropoietin. It is needless to say that we also have to rule out occult hemolysis.
Ariel B. Tempongko,M.D. (arielbt@skyinet.net)
Quezon City, - Tuesday, November 17, 1998 at 04:27:19 (PST)