Immunoadsorption in anti-glomerular basement membrane glomerulonephritis, a pilot study.

Anti-glomerular basement membrane (anti-GBM) glomerulonephritis is a rare
organ-specific autoimmune disease that is mediated by anti-GBM antibodies. It
is characterized by acute renal failure due to diffuse crescentic
glomerulonephritis, often accompanied by pulmonary hemorrhage. Established
treatment is cyclophosphamide and corticosteroids to suppress anti-GBM
production and daily plasma exchange to remove circulating anti-GBM antibodies.
The vast majority of patients with anti-GBM glomerulonephritis present at
relatively late stages of the disease and develop irreversible end-stage renal
failure despite treatment.

The treatment goal in anti-GBM glomerulonephritis is to achieve undetectable
anti-GBM titres as rapid as possible. Immunoadsorption is an extracorporeal
technique that may lower anti-GBM titres more effectively than plasma exchange.
With this technique the patient*s plasma is passed through an immunoadsorption
column that contains protein A that binds antibodies like anti-GBM antibodies.
However, data on the efficacy of anti-GBM removal by immunoadsorption compared
with plasma exchange are scarce. In the literature, there are only a few case
descriptions of the clinical effect of immunoadsorption in patients with
anti-GBM disease with some cases showing recovery of renal function despite
unfavorable prognosis (serum creatinine >500 µmol/l and/or high percentage of
crescents on renal biopsy).

Immunoadsorption is presently not used in the Netherlands for anti-GBM disease.
Given the dismal renal prognosis of current standard therapy and the
potentially higher efficacy for anti-GBM removal of immunoadsorption, it is
justified to treat a cohort of patients with anti-GBM glomerulonephritis with
immunoadsorption instead of plasma exchange in an open, non-randomized study
using a strict protocol. We will specifically study the efficacy of
immunoadsorption for the dynamics of anti-GBM removal, its tolerability and
side effects, and the logistic feasibility and costs.

To study the efficacy, adverse events, logistic feasibility and costs of
immunoadsorption for the removal of anti-GBM antibodies in patients with acute
renal failure due to anti-GBM glomerulonephritis.

Interventional, open, non-randomized, pilot study. After informed consent,
patients will be treated according to the current treatment protocol with the
exception of daily immunoadsorption instead of daily plasma exchange.

Participating patients will be treated with daily immunoadsorption, instead of
plasma exchange, until anti-GBM titres are undetectable. All other aspects of
the treatment (e.g. immunosuppressive treatment, renal replacement therapy)
will be standard.

From a patient*s perspective, the burden of daily immunoadsorption is
comparable with that of daily plasma exchange with regard to vascular access
(central venous catheter) and blood sampling to monitor treatment response. The
treament time of one immunoadsorption treament is 1 hour longer compared with
the treatment time of plasma exchange. Possible adverse effects of
immunoadsorption are part of the current study proposal but previous studies in
other patient groups suggest that frequency and severity of adverse effects of
immunoadsorption are comparable with plasma exchange. Therefore, it is
justified to treat patients with anti-GBM glomerulonephritis with
immunoadsorption instead of plasma exchange under study conditions because of
the potential of immunoadsorption for a more effective removal of anti-GBM and
the dismal renal prognosis of current treatment. Results of this study will
provide the basis for a larger randomised trial to compare plasma exchange and
immunoadsorption with regard to renal outcome. The results of that study will
potentially benefit future patients with anti-GBM disease.