Background: The clinical manifestations of fibrillary-immunotactoid glomerulopathy are still being appreciated. It is unclear whether fibrillary-immunotactoid glomerulopathy actually represents two distinct clinicopathological entities, fibrillary glomerulopathy (FG) and 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<=30nm, ITG>30 nm) or arrangement (FG, random; ITG, focally organized).
Results: Proteinuria (FG approximately 100%, ITG approximately 100%), nephrotic syndrome (FG approximately 71%, ITG approximately 82%), haematuria (FG approximately 71%, ITG approximately 64%), hypertension (FG approximately 67%, ITG approximately 45%), and renal insufficiency (FG approximately 54%, ITG approximately 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 follw-up period 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. 0301+/-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 there is insufficient published data, as yet, to justify subclassification of FG and ITG as distinct clinical entities. Indeed, we argue that it remains to be determined if FG-ITG represents a unique condition or a forme fruste of cryoglobulin- or 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.