Leukocyte analysis of tubulointerstitial nephritis in primary membranoproliferative glomerulonephritis

Abstract

Cellular immune mechanisms may be involved in the pathogenesis of tubulointerstitial nephritis associated with several forms of primary glomerulonephritis. This study aims to characterize the mononuclear leukocytes infiltrating the interstitium in patients with primary membranoproliferative glomerulonephritis (MPGN) and correlates the degree and nature of the infiltrate with renal function. Cellular identification using monoclonal antibodies to leukocyte cell-surface antigens was conducted on renal biopsy specimens from 17 patients with type I primary MPGN (group 1) and 10 controls with various forms of nonproliferative glomerulonephritis (group 2). The majority (14) of the 17 patients in group 1 were black South Africans. Renal function was assessed at the time of renal biopsy. Patients with MPGN had a significant increase in the number of interstitial total leukocytes (LCA), T lymphocytes (T), and B lymphocytes (B) compared with controls. Although the interstitial monocyte (KP(1)) count was also increased in MPGN patients, the difference was not significant. Recorded numbers of cells per square millimeter in group 1 versus group 2 are as follows: LCA, 1306 +/- 1254 versus 138 +/- 91 (P<0.001); T, 638 +/- 547 versus 42 +/- 60 (P.0.01); B, 161 +/- 165 versus 57 +/- 50 (P=0.02); and KP(1), 125 +/- 153 versus 54 +/- 59 (P=0.17). As noted in previous studies, the T lymphocyte was the dominant cell, comprising 48.8% of the total count. However, the combined number of T lymphocytes, B lymphocytes, and monocytes accounted for only 70.6% of the total leukocytic interstitial count, implying that the majority of the remaining 29.4% of the cells were mononuclear leukocytes that did not express the antigens we stained for. There was a moderate correlation between the number of interstitial total leukocytes, and impairment of renal function as measured by both the serum creatinine (r = 0.43) and creatinine clearance (r = -0.41). This correlation also existed for the individual cells comprising the infiltrate and was strongest for T lymphocytes (r = 0.63) followed by monocytes (r =0.46) and B lymphocytes (r = 0.41). In conclusion, we have demonstrated a significant mononuclear leukocytic interstitial infiltrate in our patients with type I MPGN and a correlation between all cells of this infiltrate with impaired renal function. This correlation was strongest for the most frequently observed cell, the T lymphocyte.