Predictors of positive immunofixation testing in patients with acute kidney injury.

INTRODUCTION: Acute kidney injury may be the presenting manifestation of multiple myeloma, although optimal use of immunofixation testing in this setting is incompletely defined. The authors attempted to determine clinical and laboratory predictors of positive immunofixation testing in patients with acute kidney injury. PATIENTS AND METHODS: The authors did a retrospective study of hospitalized patients with acute kidney injury who had immunofixation studies done. Various clinical and laboratory variables that may be predictive of the presence of multiple myeloma were evaluated and correlations with immunofixation test results determined. RESULTS: One hundred twenty-eight patients were studied. Thirteen had a monoclonal paraprotein detected by immunofixation testing (positive result). Patients with positive testing had higher total, ionized and corrected calcium levels, although the median total calcium in immunofixation-positive patients was normal at 9.7 mg/dL. Patients with positive testing also had lower hemoglobin and platelet counts. An anion gap of <7 mmol/L and total protein-albumin gap >4 g/dL were also associated with positive results. CONCLUSIONS: In patients with acute kidney injury, relatively higher total, ionized and corrected calcium levels and lower hemoglobin and platelet counts may predict the presence of a monoclonal paraprotein. An anion gap of <7 mmol/L and total protein-albumin gap >4 g/dL may also be predictors. The metabolic consequences of acute kidney injury may attenuate some of these abnormalities as well. These findings may help guide optimal use of immunofixation testing and hence help potentially identify patients who may have multiple myeloma.

Nitric oxide and tubulointerstitial nephritides.

As part of the exponential growth in our understanding of nitric oxide (NO) in health and disease over the past 2 decades, the kidney has become appreciated as a major site where NO may play a number of important roles. Although earlier work on the kidney focused more on effects of NO at the level of larger blood vessels and glomeruli, there has been a rapidly growing body of work showing critical roles for NO in tubulointerstitial disease. In this review we discuss some of the recent contributions to this important field.

Dexamethasone attenuates oxidation of extracellular matrix proteins by human monocytes.

In response to infection or in immune complex-mediated diseases, inflammatory cells may oxidatively damage extracellular matrix (ECM) proteins. In this study we evaluated whether human monocytes could oxidize ECM and whether this could be modulated by exposure to LPS, IgG complexes, and dexamethasone (DEX). Wells in tissue culture plates were coated with the ECM preparation Matrigel. Porous inserts with or without the human monocyte cell line THP-1 were placed into ECM-containing wells and cells were exposed to control conditions or to LPS (10 ng/ml), IgG complexes (200 and 500 microg/ml), or DEX (10(-7) and 10(-6) M). ECM was then subjected to Western blot analysis using an antibody to oxidized protein. In addition, Western blot analysis was carried out on DEX-treated cells to evaluate expression of the NADPH oxidase components p67-phox and gp91-phox. THP-1 cells enhanced ECM oxidation and this effect was augmented by LPS and by IgG aggregates. Preincubation of cells with DEX attenuated ECM oxidation and was also associated with decreased expression of p67-phox and gp91-phox. These findings suggest that human monocytes can oxidize ECM proteins and that this may be modulated by IgG complexes and LPS. Dexamethasone appears to attenuate ECM oxidation and a better understanding of this mechanism might allow for interventions to minimize oxidative damage to ECM proteins by monocytes in infectious and inflammatory states.