IgG4-related disease has attracted wide attention recently. It is characterized by a high level of serum IgG4 and dense infiltration of IgG4-positive plasma cells into multiple organs, with the kidney being one representative target. Although several sets of diagnostic criteria for autoimmune pancreatitis (AIP) are available and renal lesion is recognized as an extra-pancreatic manifestation of AIP, it is difficult to differentiate IgG4-related tubulointerstitial nephritis (TIN) without AIP from other types of TIN. To clarify the entity of IgG4-related kidney disease (IgG4-RKD) and support in-depth studies, the Japanese Society of Nephrology has established a working group to prepare diagnostic criteria for IgG4-RKD. The working group analyzed 41 patients with IgG4-RKD, and collected the following data to devise a diagnostic algorithm and diagnostic criteria for IgG4-RKD: clinical features including extra-renal organ involvement, urinalysis and serological features including serum IgG4 levels, imaging findings demonstrated by computed tomography (CT), renal histology with IgG4 immunostaining, and response to steroid therapy. The conditions for criteria are as follows. (1) Presence of some kidney damage, as manifested by abnormal urinalysis or urine marker(s) and/or decreased kidney function with either elevated serum IgG level, hypocomplementemia, or elevated serum IgE level. (2) Kidney imaging studies showing abnormal renal imaging findings, i.e., multiple low density lesions on enhanced CT, diffuse kidney enlargement, hypovascular solitary mass in the kidney, and hypertrophic lesion of the renal pelvic wall without irregularity of the renal pelvic surface. (3) Serum IgG4 level exceeding 135 mg/dl. (4) Renal histology showing two abnormal findings: (a) dense lymphoplasmacytic infiltration with infiltrating IgG4-positive plasma cells >10/high power field (HPF) and/or ratio of IgG4-positive plasma cells/IgG positive plasma cells >40%. (b) Characteristic ‘storiform’ fibrosis surrounding nests of lymphocytes and/or plasma cells. (5) Extra-renal histology showing dense lymphoplasmacytic infiltration with infiltrating IgG4-positive plasma cells >10/HPF and/or ratio of IgG4-positive plasma cells/IgG-positive plasma cells >40%. The diagnosis is classified into 3 stages of definite, probable and possible according to the combinations of the above conditions. Thirty-nine cases (95.1%) were diagnosed with IgG4-RKD according to the criteria. The provisional criteria and algorithm appear to be useful for clarifying the entity of IgG4-RKD and seeking underlying IgG4-RKD cases; however, further experience is needed to confirm the validity of these criteria.

Proposal for diagnostic criteria for IgG4-related kidney disease