Comparative clinical manifestations of IgG4-related and IgG4-negative primary tubulointerstitial nephritis

Aims: To evaluate the prevalence of IgG4-related tubulointerstitial nephritis (TIN) and compare the clinical manifestations of IgG4-related and IgG4-negative primary TIN. Methods: Of 5,174 renal biopsies obtained between January 1996 and February 2010, 46 were positive for primary TIN without other kidney disease. Biopsy tissues were lost for 2 patients. The remaining 44 samples were assayed by immuno-peroxidase staining with monoclonal mouse antibody to human IgG4. Results: Of the 44 patients with primary TIN, 12 (27%) were identified as IgG4+ plasma cells/HPF >= 10 and 32 (73%) as < 10. Estimated glomerular filtration rate (eGFR) was lower and proteinuria was higher in patients with IgG4+ plasma cells/HPF >= 10 (p < 0.05). No other parameter such as age; gender distribution; incidence of hypertension, diabetes mellitus, drug history, pyuria; concentrations of hemoglobin and alkaline phosphatase; or kidney size differed significantly. Of the 44 patients with primary TIN, 25 (57%) were identified as IgG4-positive (IgG4+ plasma cells/HPF >= 1) and 19 (43%) as IgG4-negative. The two groups did not differ in age; gender distribution; incidence of hypertension, diabetes mellitus, drug history, pyuria, or proteinuria; concentrations of hemoglobin and alkaline phosphatase; eGFR; or kidney size. The improvement rate, however, was significantly higher in IgG4-positive than in IgG4-negative patients (p = 0.045). Of the 25 IgG4-positive and 19 IgG4-negative patients, 18 and 13, respectively, were treated, and 18 and 7, respectively, improved (p = 0.002). The median number of IgG4-positive plasma cells/HPF in the former group was 8 (range 1-90). The number of IgG4-positive plasma cells was significantly associated with the degree of proteinuria (r = 0.471, p = 0.018) and age (r = 0.529, p = 0.007). Conclusion: Routine IgG4 staining is necessary in patients with primary TIN. Early treatment is also important in patients with IgG4-related primary TIN.