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Hematuria is the first manifestation of urinary abnormality in immunoglobulin A nephropathy (IgAN). Hematuria has recently been reported as a risk factor for deterioration of renal function; however, its cause remains unknown.We analyzed the surface marker of peripheral blood mononuclear cells before and immediately after tonsillectomy in IgAN patients and controls (chronic tonsillitis or tonsillar hypertrophy) by flow cytometry and investigated the association with hematuria. To prove our hypothesis that NK cells induce hematuria, we administered IL-12, activator of NK cells, to HIGA mice. In addition, we transferred cultured NK cells to nude rats and transferred the CD16(+)CD56(+) cells, including NK cells, that are derived from the peripheral blood of IgAN patients immediately after tonsillectomy to nude rats to assess the hematuria level and renal histology of the recipients. We also performed cytotoxicity assays against glomerular endothelial cells by NK cells.We found that IgAN patients who showed rapid deterioration of hematuria after tonsillectomy also displayed a significant increase in CD16(+)CD56(+) cells in the peripheral blood immediately after tonsillectomy. Exogenous administration of IL-12 to HIGA mice induced hematuria. Adoptive transfer of either cells of an NK cell line, or of CD16(+)CD56(+) cells derived from IgAN patients, into nude rats induced hematuria in the recipients. In vitro analysis showed that NK cells exert cytotoxic activity toward human glomerular endothelial cells in a dose-dependent manner.CD16(+)CD56(+) cells seem to be responsible for hematuria in IgAN.

We report a case of a 17-year-old boy suffering from severe loin pain and oliguric acute kidney injury after strenuous exercise, with slightly elevated serum myoglobin and creatinine phosphokinase. Exercise-induced acute kidney injury (AKI) was diagnosed. We started intermittent hemodialysis thrice a week from the admission day. Four days later, he temporally lost consciousness, followed by visual agnosia and general clonic seizure. T2-weighted brain magnetic resonance images (MRI) showed multiple areas of increased signal intensity in the subcortical white matter, predominantly in the cerebrum of the posterior and parietal lobes and in the cerebellum. Clinical symptoms improved without sequelae. Follow-up MRI 1 month later showed complete resolution of the signals, and he was diagnosed with reversible posterior leukoencephalopathy syndrome (RPLS). This is the first reported case of exercise-induced AKI associated with RPLS. Vasoconstriction and endothelial dysfunction are considered as the common etiology of these diseases.