Clinical studies demonstrate that
acute renal failure (ARF) is associated with increased mortality, which may be due to pulmonary complications. ARF may affect the lung via increased renal production or impaired clearance of mediators of
lung injury, such as proinflammatory
cytokines. Bilateral
nephrectomy is a method to examine directly the deleterious systemic effects of absent renal clearance in ARF without the confounding effects that are associated with
ischemia-reperfusion injury (e.g., ischemic ARF) or systemic toxicity (e.g.,
cisplatin-induced ARF). This study contrasts the effects of ischemic ARF and bilateral
nephrectomy on serum
cytokines and
lung injury. It demonstrates that the acute absence of kidney function after both ischemic ARF and bilateral
nephrectomy is associated with an increase in multiple serum
cytokines, including
IL-6 and IL-1beta, and that the
cytokine profiles were distinct.
Lung injury after ischemic ARF and bilateral
nephrectomy was similar and was characterized by pulmonary vascular congestion and neutrophil infiltration. For investigation of the role of proinflammatory
cytokines in
pulmonary injury after ARF, the anti-inflammatory
cytokine IL-10 was administered before bilateral
nephrectomy.
IL-10 treatment improved pulmonary architecture and was associated with a reduction in inflammatory markers, including bronchoalveolar lavage fluid total
protein, pulmonary
myeloperoxidase activity (a
biochemical marker of neutrophils), and the
chemokine macrophage inflammatory protein 2. These data demonstrate for the first time that the acute absence of kidney function results in
pulmonary injury independent of renal
ischemia and highlight the critical role of the kidney in the maintenance of serum
cytokine balance and pulmonary homeostasis.