CVID is a disorder characterized by hypogammaglobulinemia without a known, predisposing cause . Meanwhile, immune complex and complement systems are thought to play an important role on the pathogenesis of nephritis, such as MPGN and MN. Since immunodeficiency diseases, such as CVID and X-linked agammaglobulinemia, cause extremely low levels of immunoglobulin, patients diagnosed with these seem to have low incidence of MPGN or MN. Indeed, as far as we know, there have been only three previous case reports of nephritis associated with hypogammaglobulinemia due to immunodeficiency diseases. Two of these cases were MPGN and one was MN. In each case, nephritis was developed during IVIG treatment [1–3]. On the other hand, there is a paradoxical relationship between immunodeficiency diseases and autoimmune diseases. For example, Barnett et al. has reported that X-linked agammaglobulinemia is associated with polyarticular arthritis and inflammatory bowel diseases. Barnett et al. has also reported that CVID is associated with rheumatoid arthritis, pernicious anemia, and hemolytic anemia [6–8]. The precise mechanism linking CVID with these diseases still remains unclear.
FSGS, clinical-pathologic syndrome of proteinuria associated with focal and segmental sclerotic glomerular lesions, is characterized by podocyte damage. The pathologic classification of FSGS is categorized as primary and secondary, the latter of which is caused by HIV-associated, heroin, familial forms, drug toxicities, but also by structural-functional adaptations to glomerular hyperfiltration such as obesity, hypertension, reflux nephropathy, and so on. A number of morphologic variants of primary and secondary focal sclerosis are now recognized, based on a 2004 Columbia classification system, including FSGS-not otherwise specified (NOS), perihilar, cellular, tip, and collapsing variants. Recently, Changli Wei et al. found that a circulating, soluble form of the urokinase receptor (suPAR) can activate podocyte b3 integrin, leading to FSGS pathology, which provides new insight into this disease and may have important clinical implications .
In our case, differential diagnosis before renal biopsy appeared somewhat difficult because this patient had suffered MPGN in his childhood. In addition, the patient had many complications such as obesity, hypertension, post operative-papillary thyroid carcinoma, and CVID. We considered several possibilities, recurrence of MPGN, CVID-related nephritis, malignancy related nephritis, etc. Renal biopsy finally revealed this patient to have FSGS. According to The Columbia FSGS Classification, this patient was categorized as perihilar variant which was normally due to glomerular hypertension . Namely, it is likely that metabolic disorder, relative to his obesity and hypertension, might have “encouraged” the development of FSGS. Renal biopsy also implied previous MPGN at the same time. There was no clear relationship between our findings and the patient’s chronic, present proteinuria. Since his episode of past MPGN was successfully treated, we could find no link between MGPN and CVID for this case. We started his treatment with diet, exercise, angiotensin receptor blocker (ARB), and statin therapy.
Since hypogammaglobulinemia due to CVID may disturb immune complex and complement system, there is a possibility that current CVID prevents the development of MPGN. In case of recovery of CVID, restoration from hypogammaglobulinemia may cause the recurrence of MPGN through the activation of immune complex and complement system. Therefore, in the present case, we have to pay attention not only to the treatment of obesity and hypertension for FSGS but also to the recurrence of immune-complex related glomerulonephritis such as MPGN.
In conclusion, we report for the first time a case of CVID patient with FSGS. Detection of proteinuria in a CVID patient is rare. In the case of CVID patient with proteinuria, we have to take many possibilities into consideration. Therefore, renal biopsy should be an important tool for a precise and proper diagnosis.