Delayed severe pneumonia in mycophenolate mofetil-treated patients with IgA nephropathy

Mycophenolate mofetil (MMF), a relatively new immunosuppressant, is widely used in the field of transplantation and also for autoimmune diseases with good tolerance. It has been reported that MMF possesses potent activity against pneumocystis pneumonia (PCP). This study investigated the effects of this treatment on the occurrence of severe pneumonia (SP) including PCP and its risk factors.

This was a retrospective cohort study. Of 850 IgA nephropathy (IgAN) patients that were followed up in our renal centre, 32 received MMF (1-1.5 g/day) and 47 were treated with cyclophosphamide (CTX; 50-100 mg/day). All the patients also received prednisone. SP was defined as diffuse bilateral lung infiltrate with respiratory failure, and PCP was diagnosed by detecting organisms in sputum and bronchoalveolar lavage.

Patients given MMF or CTX did not differ in their distribution of age, sex, renal function or prednisone dosage. However, 6 of the 32 patients developed SP around the third month after the initiation of MMF administration: 3 were diagnosed with PCP, 2 with suspected PCP and in the other PCP could not be excluded. SP did not occur in patients treated with CTX. Most SP cases (five of six) presented with abrupt onset and rapidly progressed to respiratory failure, from which four died. The deterioration of renal function was strongly associated with the occurrence of SP. Six patients (6 of 16) with chronic renal function impairment (eGFR < 60 ml/min/1.73 m(2)) developed SP while none of the patients with eGFR > 60 ml/min/1.73 m(2) did. Absolute lymphocyte counts decreased significantly in patients with eGFR < 60 ml/min/1.73 m(2) after 3 months of MMF treatment compared to the counts before MMF was initiated (1.71 +/- 0.23 versus 2.43 +/- 0.17 x 10(9)/l, P = 0.04). This effect was more pronounced in patients with SP, which had significantly lower counts than patients without SP (0.22 +/- 0.04 versus 1.91 +/- 0.20 x 10(9)/l, P = 0.001). The occurrence of SP or PCP in patients with chronically impaired renal function was also associated with lymphopenia.

This study is the first report of delayed SP including PCP following MMF plus corticosteroids in patients with IgAN. Chronically impaired renal function might be a risk factor for severe infection, and lymphocyte counts may serve as useful and convenient tools for monitoring the intendance of the occurrence of PCP. This finding and its risk factors need to be further evaluated.