Renal replacement therapy in patients on extracorporeal membrane oxygenation support: Who and how.

Patients undergoing extracorporeal membrane oxygenation (ECMO) support frequently develop renal failure requiring renal replacement therapy (RRT). RRT may be performed via a dialysis catheter based approach or via the ECMO circuit. We describe our experience with both techniques. A total of 68 patients undergoing ECMO support at our institution were retrospectively analyzed. Predictors of renal failure requiring RRT were determined. Patients undergoing RRT via a dialysis catheter were compared with those undergoing RRT via the ECMO circuit. 10 of the 68 patients required RRT support prior to ECMO. Of the remaining 58 patients, 25 (43%) required new RRT support on ECMO. Lower albumin levels and postcardiotomy shock were predictive of new renal failure requiring RRT on ECMO. RRT performed via the ECMO circuit demonstrated similar efficacy as via a dialysis catheter. Outcomes were much worse for patients requiring new RRT on ECMO support, with a doubling of the length of ECMO support and less that one-third the survival rate of patients not requiring RRT on ECMO support. New renal failure requiring RRT occurs in nearly one-half of patients on ECMO support, with poor outcomes. RRT may be performed via the ECMO circuit with similar efficacy as via a dialysis catheter.

Acoustic rhinometry in pediatric sleep apnea.

PURPOSE: This prospective study aimed to evaluate the use of acoustic rhinometry (AR) in pediatric obstructive sleep apnea (OSA). METHODS: Children with clinically suspected OSA underwent AR measurements followed by attended overnight polysomnography. RESULTS: Of a total of 20 subjects (13 boys, seven girls), 15 (75%) had OSA, defined as apnea-hypopnea index (AHI) greater than or equal to five events per hour of sleep, and five had primary snoring (PS). The mean AHI was 16.79 vs. 1.96 events/h. Positional changes in airway measurement by AR were present in the OSA group, with an average decrease in nasal cavity volume from upright to supine position of 1.53 cm(3) (p = 0.027). These changes were predictive of sleep apnea (r (2) = 0.65, p = 0.035). CONCLUSIONS: This study demonstrates a marked difference between OSA and PS groups during AR measurements of the nasopharynx. Positional airway changes had been previously reported in adults with OSA and further evaluation of the airway function in pediatric OSA is warranted.

Inhibition of integrin alpha(v)beta6, an activator of latent transforming growth factor-beta, prevents radiation-induced lung fibrosis.

RATIONALE: In experimental models, lung fibrosis is dependent on transforming growth factor (TGF)-beta signaling. TGF-beta is secreted in a latent complex with its propeptide, and TGF-beta activators release TGF-beta from this complex. Because the integrin alpha(v)beta6 is a major TGF-beta activator in the lung, inhibition of alpha(v)beta6-mediated TGF-beta activation is a logical strategy to treat lung fibrosis. OBJECTIVES: To determine, by genetic and pharmacologic approaches, whether murine radiation-induced lung fibrosis is dependent on alpha(v)beta6. METHODS: Wild-type mice, alpha(v)beta6-deficient (Itgb6-/-) mice, and mice heterozygous for a Tgfb1 mutation that eliminates integrin-mediated activation (Tgfb1(+/RGE)) were exposed to 14 Gy thoracic radiation. Some mice were treated with an anti-alpha(v)beta6 monoclonal antibody or a soluble TGF-beta receptor fusion protein. Alpha(v)beta6 expression was determined by immunohistochemistry. Fibrosis, inflammation, and gene expression patterns were assessed 20-32 weeks postirradiation. MEASUREMENTS AND MAIN RESULTS: Beta6 integrin expression increased within the alveolar epithelium 18 weeks postirradiation, just before onset of fibrosis. Itgb6-/- mice were completely protected from fibrosis, but not from late radiation-induced mortality. Anti-alpha(v)beta6 therapy (1-10 mg/kg/wk) prevented fibrosis, but only higher doses (6-10 mg/kg/wk) caused lung inflammation similar to that in Itgb6-/- mice. Tgfb1-haploinsufficient mice were also protected from fibrosis. CONCLUSIONS: Alpha(v)beta6-mediated TGF-beta activation is required for radiation-induced lung fibrosis. Together with previous data, our results demonstrate a robust requirement for alpha(v)beta6 in distinct fibrosis models. Inhibition of alphavbeta6-mediated TGF-beta activation is a promising new approach for antifibrosis therapy.

Propylthiouracil-related diffuse alveolar hemorrhage with negative serologies and without capillaritis.

Propylthiouracil (PTU) has been held responsible for diffuse alveolar hemorrhage (DAH) with positive antineutrophil cytoplasmic antibody (ANCA) and capillaritis. We describe a case of a 23-year-old pregnant female with Grave's disease treated with PTU who presented with flu-like symptoms and progressive dyspnea. Open lung biopsy showed DAH without evidence of capillaritis. All serologies were negative. Five days after PTU withdrawal and intravenous steroid therapy, the patient improved dramatically. She remained symptom free without relapse 9 months after the episode. To the best of our knowledge, this is the first reported case of PTU-related alveolar hemorrhage with negative serologic markers and without capillaritis.

Membrane diffusion in diseases of the pulmonary vasculature.

INTRODUCTION: We examined pulmonary diffusing capacity (D(LCO)) and its partition in pulmonary vascular diseases without evident parenchymal disease to assess the pattern and proportionality of change in membrane diffusion (D(m)) and capillary blood volume (V(c)). Disproportionate reduction in D(m) relative to V(c) (low D(m)/V(c)) in these diseases has been attributed to associated alveolar membrane/parenchymal disease, thus providing a potentially important diagnostic tool. METHODS: Diseases included: idiopathic pulmonary arterial hypertension (n=6), chronic thromboembolic disease (n=5), and intravenous drug use (n=14), providing a spectrum of pulmonary vascular diseases. V(c) and D(m) were determined as described by Roughton and Forster. RESULTS: All diseases showed a reduced V(c) (59+/-10, 69+/-14, 71+/-21 % predicted, respectively) and D(m) (76+/-22, 53+/-19, 63+/-16 % predicted, respectively) with no differences between groups (p>0.05). Disproportionate reduction of D(m) (D(m)/V(c) % predicted <1) was seen in all diseases (range 0.36-1.89). A mathematical analysis is presented to illustrate that changes in vascular geometry may additionally influence the proportionality of changes in D(m) and V(c). The mathematical analysis suggests that when reduction in patency of some vessels co-exits with compensatory dilatation of the remaining vasculature, a disproportionate reduction in D(m) relative to V(c) may result. CONCLUSIONS: The balance between vascular curtailment and compensatory dilatation may contribute to the variability of the D(m)/V(c) relationship seen in pulmonary vascular disease. Disproportionate reduction in D(m) relative to V(c) may result from this imbalance and need not imply subclinical alveolar membrane and/or parenchymal disease.