#3692 Granulomatous interstitial nephritis and immunodeficiency—a link to remember

Abstract Background and Aims Granulomatous interstitial nephritis (GIN) is a rare form of tubulointerstitial nephritis being generally associated to infection, drugs or immune mediated disease. Sarcoidosis is the most frequent disease responsible for GIN, but conversely granulomatous inflammation can also be associated with immunodeficiency. Common variable immunodeficiency (CVID) is an inborn error of immunity characterized by impaired B cell differentiation with defective immunoglobulin production. It is the most prevalent form of significant antibody deficiency affecting both children and adults and can present later in life. Besides recurrent infections, immune dysregulation seen in CVID can lead to autoimmunity, presenting with cytopenia and granulomatous infiltrations of several organs, namely the lungs, liver and lymphoid organs. Kidney involvement is rare in CVID and GIN has been reported in less than 5 cases worldwide to our knowledge. Case report We report the case of a 58-year-old man with a past medical history of type 2 diabetes mellitus, hypertension and of two major skin infections (arm infection with compartment syndrome in childhood and Fournier gangrene at adult age). He presented with anorexia, asthenia, nausea and weight loss (12 Kg in the previous 3 months). Physical examination was unremarkable. Laboratory workup identified leucopenia, lymphopenia, rapidly progressive renal insufficiency (Scr 0.98 mg/dL to 3.5 mg/dL in 2 months), with bland urinary sediment, and urinary protein-to-creatinine ratio of 512.4 mg/g. Additionally, we identified hypercalcemia 11 mg/dL (normal PTH), normal erythrocyte sedimentation rate and increased angiotensin converting enzyme level (ACE 282 U/L). Auto-antibodies screening and complement were normal. Virology (including viral load of EBV and CMV) and tuberculosis quantiferon were also negative. Protein electrophoresis revealed hypoproteinemia with normal albumin and hypogammaglobulinemia and monoclonal gammopathy was excluded. IgG (374 mg/dL) and IgM (17 mg/dL) were below normal range, with normal IgA level. IgG 1 and IgG 2 sub-classes were also markedly decreased as also specific antibodies titters for pneumococcus. Vaccine response was not tested because of the urgent need to begin immunosuppressive treatment. Peripheral blood lymphocyte immunophenotyping showed a slight decrease in B cell proportion (CD19: 4.2%), and analysis of other B and T cell subpopulations in the peripheral blood was not possible due to the urgent need of treatment. Imagiology workup with CT scan revealed multiple adenopathies, lung parenchyma with septal diffuse and irregular thickening and hepatosplenomegaly. Renal biopsy was performed and revealed tubulointerstitial nephritis with noncaseous granulomas. Lung function was normal and broncofibroscopy with biopsy revealed also noncaseous granulomas and excluded infection or neoplasm. There was absence of B cells in the in the bronchoalveolar lavage. Following multidisciplinary discussion with immunoallergology and pneumology, CVID was considered and presented with related complications as granulomatous–lymphocytic infiltration, in the lungs and kidneys, cytopenias, hepatosplenomegaly and persistent diffuse adenopathies, making sarcoidosis diagnosis less probable. Considering immunodeficiency, intravenous immunoglobulin (IVIg) was added to glucocorticoid (GC) therapy (prednisolone 1 mg/kg) with significant pulmonary improvement, decrease in adenopathy size, renal function recovery (Scr 1.2 mg/dL without proteinuria 1 month later) and normalization of ACE and calcium. Conclusion Although GIN is usually associated with sarcoidosis, finding primary hypogammaglobulinemia with defective specific antibody production should raise the suspicion of an underlining immunodeficiency. Although GC are used as first line treatment for both, IVIg replacement treatment is essential to avoid potential severe infections. As such and as our case underlines, evaluation of immunoglobulin serum levels is of paramount importance before considering immunosuppressive treatment, especially in granulomatous disease.