Antibodies to both ICAM-1 and LFA-1 do not protect the kidney against toxic (HgCl2) injury.

BACKGROUND: The role of inflammatory leukocytes in acute renal failure (ARF) remains controversial and appears largely uninvestigated in toxic (in contrast to ischemic) ARF. METHODS: Female Wistar rats were injected with monoclonal antibodies (mAbs) directed to both the leukocyte function-associated antigen 1 (LFA-1) and the intercellular adhesion molecule 1 (ICAM-1). Doses (6 mg/kg of each mAb) were given 24 hours prior to the induction of acute tubular necrosis (ATN) by mercuric chloride administration (2 mg/kg, subcutaneously, day 0) and subsequently every 48 hours. Control rats similarly received either control antibody (12 mg/kg) or vehicle prior to and following the induction of ATN. Renal function was also measured from male Lewis rats that were similarly treated with anti-adhesion antibodies during exposure to 30 minutes of unilateral renal ischemia. RESULTS: Injected antibodies were demonstrated on peripheral blood leukocytes (flow cytometrical detection of mouse anti-LFA-1) and on endothelium (immunohistochemical staining of mouse anti-ICAM-1) and were measured in serum (enzyme-linked immunosorbent assay). Macrophages and T cells were prominent in the kidney of control treatment rats after HgCl2 injection, but anti-adhesion treatment clearly had prevented their infiltration. Notwithstanding, renal tubular injury was equally pronounced in all mercuric chloride treatment groups and so was the decline in renal function (serum creatinine, proteinuria). Tubular epithelial cell proliferation seemed slightly less pronounced and delayed in anti-adhesion treated rats. Kidneys from ischemia exposed rats were, however, functionally protected by identical anti-ICAM-1/anti-LFA-1 treatment. CONCLUSION: Prevention of cellular infiltration by mAbs to LFA-1 and ICAM-1 has no effect on renal morphology, function, or regeneration following mercuric chloride-induced ARF in the rat. This result contrasts with the functional protection of the rat kidney to ischemia/reperfusion injury by virtue of an identical antibody treatment protocol. Resolving that controversy should bring better insight in fundamental processes underlying different types of ARF, and will be the subject of further study.

Empirically treated Pneumocystis carinii pneumonia in London, 1983-1989.

For 227 episodes of Pneumocystis carinii pneumonia (PCP) treated at St Mary's between 1983 and 1989, factors predictive of fatal outcome were age, haemoglobin levels, peripheral lymphocyte count and alveolar-arterial oxygen gradient. Case fatality for the 47 empirically-treated episodes was significantly higher compared with the 180 cytologically proven episodes (55% vs 18%, chi 2 = 25.7, P less than 0.0001). Case fatality for episodes which could not be bronchoscoped was significantly higher compared with bronchoscopy negative cases (66% vs 25%, chi 2 = 4.5, P less than 0.05). Predictive factors for fatal outcome differed significantly for cases which could not be bronchoscoped and cytologically proven cases: haemoglobin level (10.7 g/dl vs 12.0 g/dl, P less than 0.001), lymphocyte count (0.64 x 10(9)/l vs 0.87 x 10(9)/l, P = 0.05) and oxygen gradient (77.7 mmHg vs 58.9 mmHg, P less than 0.02). Such differences were not observed between bronchoscopy negative and cytologically proven cases. Case fatality decreased significantly over time (b = -0.39, SE = 0.14, P less than 0.05). Total and non-fatal first time episodes displayed an inverse relationship between oxygen gradient and time (r = -0.22, P less than 0.006 and r = -0.24, P less than 0.01, respectively). Mean oxygen gradient of fatal episodes for sequential years increased significantly from 73 mmHg in 1983 to 102 mmHg in 1989 (r = 0.92, P less than 0.01). This suggests that medical intervention as well as presentation with less severe disease both contributed to improved case fatality over time.

Improved outcome of Pneumocystis carinii pneumonia in AIDS patients: a multifactorial treatment effect.

Factors determining the outcome of an episode of Pneumocystis carinii pneumonia (PCP) in 149 AIDS patients treated at St Mary's Hospital were identified and their importance on improved survival evaluated between 1984 and 1989. The proportion of fatal episodes of PCP decreased over time. Fatal compared with nonfatal episodes had lower mean alveolar-arterial oxygen gradient (82.5 mmHg vs 53.8 mmHg, P less than 0.001), mean haemoglobin level (11.2 g/dl vs 12.1 g/dl, P = 0.01), mean lymphocyte count (0.68 x 10(9)/l vs 0.92 x 10(9)/l, P = 0.05) and more coinfections (31% vs 5%, P less than 0.001). Over time, the most significant change which occurred was a reduction in alveolar-arterial oxygen gradient at time of first presentation with PCP (r = -0.37, P less than 0.001). Mean alveolar-arterial oxygen gradient declined from 79.9 mmHg in 1984 to 45.3 mmHg in 1989 (r = -0.88, P = 0.02), independently of zidovudine therapy or PCP prophylaxis. Patients were being treated at an earlier stage in their disease course as indicated by their reduced alveolar arterial oxygen gradient. This is due either to earlier patient presentation, earlier medical diagnosis or both. The widespread introduction of zidovudine and PCP prophylaxis may further contribute to improve morbidity and mortality patterns in the future.