Patterns of Noncryoglobulinemic Glomerulonephritis with Monoclonal Ig Deposits

Abstract

SummaryBackground and objectives Several different entities have recently been described among glomerular diseases associated with monoclonal IgG deposits. The aim of this study was to describe the distribution of the different pathologic subtypes of IgG-associated glomerulopathy and to evaluate the IgG isotype involved in these diseases.Design, setting, participants, & measurements This was a retrospective study including all patients with glomerular deposits of monoclonal IgG referred to three nephrology departments between 1980 and 2008.Results Twenty-six patients were included. Nephrotic syndrome was almost constantly associated with a renal dysfunction in 14 of 26 patients. The presence of M-spike was detected in only 30% of the patients, and an overt hematologic malignancy (myeloma, lymphoma) was identified in 9 of 26 patients. Patients were almost equally divided into two distinct histologic patterns: membranous nephropathy (MN) or membranoproliferative glomerulonephritis (MPGN). IgG3 deposits were identified in 80% of patients with MPGN, whereas IgG1 deposits were present in 64% of patients with MN. Ultrastructural study showed that immune deposits were nonorganized in most patients. Seven patients were treated with rituximab with excellent results: five of seven had a complete remission of the nephrotic syndrome and two of seven had a partial response. After a mean 24-month follow-up, only one patient experienced relapse of the nephropathy.Conclusions GN with monoclonal Ig deposits can be associated with MPGN or MN, which are correlated with IgG3 and IgG1 isotypes, respectively. Rituximab appears to have a very favorable benefit-to-risk ratio for patients with no overt hematologic malignancy.

Rituximab–cyclophosphamide‐dexamethasone is highly effective in patients with monoclonal Ig deposit‐related glomerulopathy and indolent non‐Hodgkin lymphomas

“…Less commonly, iNHLs may also promote glomerulonephritis associated with monoclonal deposits [3,12,13], with extremely heterogeneous pathologic pattern as exemplified in our series.…”

“…To date, most published series on glomerulopathy with monoclonal Ig deposits have been based on pathologic patterns [3,6,[12][13][14][15]. Because of the wide heterogeneity of treatments in these series (e.g., no treatment, steroids only, rituximab, or combined chemotherapy), no firm recommendations for iNHL treatment are available.…”

“…Because of the wide heterogeneity of treatments in these series (e.g., no treatment, steroids only, rituximab, or combined chemotherapy), no firm recommendations for iNHL treatment are available. In 2011, Guiard et al suggested that rituximab might have a higher benefit-torisk ratio in a subtype of glomerulopathy with monoclonal Ig deposits (e.g., non-cryoglobulinemic and non-amyloid glomerulonephritis with monoclonal Ig-G deposits) [12]. One of the seven patients receiving rituximab relapsed after a long delay (44 months), a finding close to the rate-of-relapse found in our cohort (3 out of 14 patients, within 5-14 months).…”

“…No patient developed opportunistic complications during the 3-72 months of follow-up. Whether rituximab alone could be proposed to patients with very low burden iNHL [12] to avoid excessive toxicity of alkylating agents or steroids, remains to be determined.…”

Onco-Nephrology

“…At variance with MIDD, in which deposits predominate along tubular basement membranes and cell proliferation is usually mild or absent, PGNMID is a proliferative GN in which deposits are confined to the mesangium and the glomerular basement membrane ( Figure 2); hence, the term non-Randalltype proliferative GN is also used for this entity. Although no case of CLL and related B cell lymphoma was reported in the first series (48,52), 9 of 26 patients with noncryoglobulinemic GN and monoclonal immunoglobulin deposits recently reported by Guiard et al featured an overt hematologic malignancy (53). Among them, one patient had CLL, two had myeloma, and two had non-Hodgkin lymphoma with nonorganized electron-dense deposits fulfilling the definition of PGNMID.…”