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By Louis Kuritzky, MD, Clinical Assistant Professor, University of Florida, Gainesville. Dr. Kuritzky is a consultant for Sucampo Pharmaceuticals, Takeda, Boehringer Ingelheim; and is a consultant and on the speaker's bureau for Novo Nordisk, Lilly, Daiichi Sankyo, Forest Pharmaceuticals, Cephalon, Novartis, and Sanofi Aventis.
Kidney function, proteinuria, and adverse outcomes
Source: Hemmelgarn BR, et al. Relations between kidney function, proteinuria, and adverse outcomes. JAMA 2010;303:423-429.
Staging of chronic kidney disease (CKD) is based primarily upon estimated GFR. Proteinuria (PRO) is a strong marker for kidney disease, yet its severity is not included in current risk stratification schemes, which are instead driven by GFR. Indeed, the majority (75%) of proteinuric patients do not have a GFR < 60 mg/min. Intuitively, since either PRO or stage of CKD predicts risk, the combination of the two might be an even better risk predictor.
To study the relationship of CKD, PRO, or the combination with outcomes, data from 920,985 Canadian adults were analyzed. Persons with end-stage renal disease at study inception were excluded.
Over 35 months of follow-up, for each decrement in GFR, all-cause mortality, MI, and end-stage renal disease increased. Within each quartile of GFR, progressively increasing levels of proteinuria (normal, mild, heavy) were associated with increased risk. Persons with the very lowest GFR (i.e., most advanced kidney disease), however, experienced less relative impact per degree of proteinuria; in other words, adverse outcomes are more compounded by proteinuria in CKD 2-4 than by CKD 5.
The recent adoption of a standardized staging system for CKD is a major step forward. These data suggest that future stratification methods would benefit from inclusion of proteinuria as well as GFR.
Inhaled cortico-steroids and COPD exacerbations
Source: Agarwal R, et al. Inhaled corticosteroids vs placebo for preventing COPD exacerbations: A systematic review and metaregression of randomized controlled trials. Chest 2010; 137:318-325.
Acute exacerbations of copd (ae-COPD) are costly to patients. Not only is the symptomatic deterioration and commonplace requirement for hospitalization burdensome, but an AE-COPD is typically followed by loss of pulmonary function that does not return. Additionally, mortality from hospitalized AE-COPD has been reported to be as high as 10%.
We have no known disease-modifying pharmacotherapy for COPD. Although symptom improvement is considerable from bronchodilators and inhaled corticosteroids (ICS), they do not change disease progression. Short of that outcome, reduction in AE-COPD is a worthy goal to seek.
Agarwal et al reviewed data from 11 placebo-controlled COPD trials (n = 8164) employing ICS to examine the impact upon AE-COPD. Overall, ICS use was associated with an 18% relative risk reduction in AE-COPD; this beneficial effect was driven primarily by persons with an FEV1 < 50%.
Recent meta-analyses have shown an increased risk of pneumonia in COPD patients receiving ICS. Because the risk reduction for AE-COPD is modest, careful consideration to the risk-benefit balance of ICS use is appropriate.
Non-alcoholic fatty liver disease in Japanese patients
Source: Hamaguchi E, et al. Histological course of nonalcoholic fatty liver disease in Japanese patients. Tight glycemic control, rather than weight reduction, ameliorates liver fibrosis. Diabetes Care 2010;33:284-286.
In the united states, diabetes and metabolic syndrome are the disorders most commonly associated with non-alcoholic fatty liver diseases (NAFLD). Because obesity, dyslipidemia, hypertension, and insulin resistance are typical operative components of these disorders, it is difficult to make a clear attribution about which is the primary culprit leading to NAFLD.
Japanese subjects do not demonstrate the same degree of obesity as Americans. Study of NAFLD in this population might provide insight about the primary drivers of pathology.
Serial liver biopsies on two occasions were obtained from 39 Japanese NAFLD patients over a mean follow-up of 2.4 years. During this interval, NAFLD improved in 30.7%, worsened in 28.2%, and was unchanged in 41%.
Improvement in glycemic control, as measured by A1C, was the best predictor of NAFLD improvement. Transforming growth factor-beta and plasminogen activator inhibitor type 1 are known regulators of hepatic fibrosis, both of which are stimulated by high glucose levels.