Immune cells and type 1 IFN in urine of SLE patients correlate with immunopathology in the kidney.

The immunopathological events in the kidneys of lupus nephritis (LN) patients are poorly understood due in part to the difficulty in acquiring serial biopsies and the inherent limitations in their analysis. To identify a means to circumvent these limitations, we investigated whether immune cells of kidney origin are present in patient urine and whether they correlate with kidney pathology. Flow cytometry analysis was performed on peripheral blood and urine cells of 69 SLE patients, of whom 41 were LN patients. In addition, type I IFN (IFNα/ß) levels were determined in plasma and urine by bioassay. Approximately 60% of non-LN patients had urine lymphocytes. In these patients, T cells were always present and predominantly CD8(+), while B cells were either absent or a mixture of naïve and memory B cells. In contrast, >90% of LN patients had urine lymphocytes. In half, the B and T cells resembled those in non-LN patient urine; however, in the remaining patients, the B cells were exclusively Ig-secreting plasmablasts or plasma cells (PB/PCs) and the T cells were predominantly CD4(+). In addition, pDCs and IFNα/ß frequently accompanied PB/PCs. The majority of patients with urine PB/PCs presented with proliferative nephritis and a significant loss of kidney function, which in some cases had progressed to end stage renal disease (ESRD). In conclusion, urine can provide access to cells of kidney resident populations for phenotypic and functional characterization. Analysis of these cells provides insight into the kidney immunopathology and may serve as biomarkers to identify patients at risk for developing LN and progressing to ESRD.

Urinary excretion of interferon, albumin, and beta 2-microglobulin during interferon treatment.

Serum and urinary levels of albumin, beta 2-microglobulin, and interferon were determined in ten patients undergoing interferon therapy. The pharmacokinetics during a phase I trial of interferon administration intramuscularly is presented. Only trace amounts of interferon activity are found in the urine, even during peak serum interferon activity. Serum beta 2-microglobulin levels increased after interferon treatment, especially at the higher dosing levels. Urinary excretion of beta 2-microglobulin increased due to the relatively low affinity of the transport system. Saturation, competition, or inhibition of the absorption process for beta 2-microglobulin was not attained. Measurement of the urinary albumin/urinary beta 2-microglobulin ratio reveals no glomerular or tubular lesion, and we conclude that interferon therapy does not result in a clinically significant nephrotoxicity.