Adult-onset idiopathic nephrotic syndrome associated with pure diffuse mesangial hypercellularity

Background. Pure diffuse mesangial hypercellularity (DMH), in its primary form, is a relatively rare histological finding and few data exist in the literature regarding its clinical course and prognosis in nephrotic adults with this diagnosis. Methods. We retrospectively analysed the clinical and histological data of 28 adult nephrotic patients (13 male) with this diagnosis with regard to response to the treatment, outcome and prognostic indicators. Results. Of 25 patients treated with prednisolone (Pred), nine (36%) showed complete remission (CR) of proteinuria, eight (32%) partial remission (PR) and eight (32%) did not respond at all (NR). The combination of cyclosporin treatment with prednisolone of those with PR or NR produced one further complete and two partial remissions. At the end of follow-up (mean 64 months), 10 patients (40%) were in CR, nine (36%) in PR and six (24%) were NR and remained nephrotic. Renal function remained unchanged in patients with CR or PR. In contrast, the six nonresponders progressed to end-stage renal disease (ESRD). Compared with non-responders, patients who responded to Pred were older and had normal renal function at presentation. This group also had less mesangial sclerosis and severe tubulointerstitial fibrosis and none showed synechiae with Bowman's capsule. IgM mesangial deposits were observed in 32% of patients with CR in response to Pred, in 37% of those with PR and in 100% of non-responders, who finally progressed to ESRD. A multivariate analysis of clinical and histological features at biopsy showed persistent nephrotic syndrome (P < 0.001), the severity of DMH (P < 0.03) and the presence of mesangial IgM (P < 0.01) to have independent predictive value for ESRD. This analysis also demonstrated that only mesangial sclerosis (P < 0.03) and the presence of mesangial IgM (P < 0.002) independently predicted the response to therapy. Conclusions. DMH associated with idiopathic nephrotic syndrome is a heterogeneous entity. Patients who respond to therapy (completely or partially) have a benign course similar to that of minimal change nephrotic syndrome. They are usually older and have normal renal function at presentation, whereas 'sclerotic' lesions are less frequent findings in initial biopsies. Non-responders tend to be younger and progress to ESRD. Most of them have impaired renal function at first assessment and more prominent 'sclerotic' lesions on initial biopsies. Mesangial IgM is an independent marker of poorer response to treatment and progression to ESRD but it lacks specificity.