The characteristic biopsy findings combined with the FN1 gene mutation confirmed the diagnosis of FG. FG can have a variety of histologic patterns, one of which is MPGN on light microscopy, and as a result may be initially mislabeled as MPGN as occurred in this case [7,8,9]. Of note, the FN1 mutation exhibits incomplete penetrance; nevertheless, it is likely the patient's mother, who had been diagnosed with MPGN, almost certainly also had FG [3]. Fibronectin has both a soluble, plasma-derived form and an insoluble, cellular form. In FG, the soluble form deposits in the glomerulus causing kidney injury. This was determined by experiments using antibodies specific to the two forms [8]. FG can recur after transplant because soluble fibronectin still circulates and deposits in the allograft despite the absence of an FN1 genetic mutation in the donor [8]. An MPGN pattern of glomerular injury is almost always secondary to an underlying systemic disease process, related to immune complex deposition, complement dysregulation, or a non-immune complex non-complement mechanism of disease. Patients with an MPGN pattern of injury have been reported to have genetic risks factors [10] and there are reported cases of familial disease with histological findings of MPGN, particularly associated with complement dysregulation [11]. However, most cases with an MPGN pattern of injury are not directly inherited. In contrast, the majority of described cases of FG are hereditary, with a few reports of sporadic cases [12]. Additionally, therapeutic considerations for an MPGN lesion depend directly on the underlying etiology and include a number of immunosuppressive medications [10], which would not be expected to have efficacy in FG, for which there are no specific treatments.

MPGN is reported to recur 20–40% of the time after transplant, although these studies were done before the reclassification of MPGN by immunofluorescence findings and pathogenesis [13, 14].

There is much less data on the recurrence of FG. To our knowledge, only five such cases have been reported previously (Table 2) [1, 2, 8, 15, 16]. In these cases, proteinuria was detected within months to a few years post-transplant, consistent with our findings. In two of these cases the diagnosis of FG was made on the allograft biopsy. One case was misdiagnosed as mesangial proliferative glomerulonephritis on native biopsy [16] and in the other no native biopsy was performed [15]. Further understanding the risk of recurrence after transplant is important for predicting the future clinical course.

In summary, if IF and EM had not been performed on the transplant kidney biopsy, an erroneous diagnosis of recurrent MPGN would have persisted. We emphasize the importance of full histologic evaluation in allograft biopsies for recognition of potentially recurrent glomerular diseases that may have been missed previously on native kidney biopsies or in patients in whom such biopsies were not performed. This may have significant implications for treatment, prognosis, knowing the risk of disease recurrence in future kidney transplants, and providing family members with important information if a genetic disease is identified.