Background. The clinical manifestations of fibrillary-immunotactoid glomerulopathy are still being appreciated. It is unclear whether fibrillary-immunotactoid glomerulopathy represents two distinct clinicopathological entities, fibrillary glomerulopathy (FG) immunotactoid glomerulopathy (ITG), or a single disease with different ultrastructural variants. Methods. To address these issues, we analysed the clinical features of 186 patients with fibrillary-immunotactoid glomerulopathy referred to our institutions (25 patients) or reported in the literature (161 patients). In separate analyses, patients were subclassified as having either fibrillary glomerulopathy (FG) or immunotactoid glomerulopathy (ITG) according to fibril diameter (FG less than or equal to 30 nm, ITG>30 nm) or arrangement (FG, random; ITG, focally organized). Results. Proteinuria (FG similar to 100%, ITG similar to 100%), nephrotic syndrome( FG similar to 71%, ITG similar to 82%), haematuria (FG similar to 71%, ITG similar to 64%), hypertension (FG similar to 67%, ITG similar to 45%), and renal insufficiency (FG similar to 54%, ITG similar to 42%) were frequent clinical correlates of both FG and ITG, irrespective of the ultrastructural criteria for diagnosis. Twenty-five patients presenting to our institutions (24 FG, 1 ITG) were divided into three groups based on rate of decline of GFR (mean slope of 1/serum creatinine versus time: group 1 -0.103+/-0.238; group 2 0.121+/-0.040; group 3 0.466+/-0.318) in an attempt to identify clinical predictors of progression at presentation. Rapid progressors (Group 3) had an increased incidence of nephrotic syndrome and tended to have higher blood pressure than patients with milder disease, but did not differ from other groups in age, prevalence of haematuria or degree of renal insufficiency. The number of patients requiring dialysis was 0/10 in group 1, 2/6 in group 2, and 2/4 in group 3 over a follow-up period of 47+/-46, 55+/-32, and 19+/-19 months respectively; two predialysis deaths being recorded in group 3. Four patients received five renal allografts (one patient being transplanted twice) and were followed for 4-11 years. Whereas recurrence of FG was documented in three allografts undergoing post-transplant biopsy, the rate of deterioration of GFR was invariably slower in allografts than native kidneys (mean slope of 1/Cr versus time: 0.036+/-0.01 versus 0.301+/-0.18 respectively). The strength of association between FG-ITG and lymphoproliferative malignancy varied depending on whether patients with monoclonal-gammopathy-associated fibrillary deposits were included or excluded from the analysis. Conclusions. We contend that patients presenting with Congo-red-negative fibrillary deposits on renal biopsy should be evaluated carefully for monoclonal gammopathy and cryoglobulins, but that there is insufficient published data, as yet, to justify subclassification of FG and ITG as distinct clinicopathological entities. Indeed, we argue that it remains to be determined if FG-ITG represents a unique condition or a forme fruste of cryoglobulin- or monoclonal-gammopathy-associated renal disease. Although the optimal treatment for FG-ITG has not been determined, renal transplantation appears an attractive option in patients with end-stage renal failure.
