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Thiazolidinediones have been shown to decrease UAE in diabetics and the reduction in UAE has been associated with the thiazolidinediones-induced increase in serum adiponectin levels ( Miyazaki et al . 2007 ). These findings indicate that the beneficial effects of thiazolidinediones on diabetic nephropathy may be mediated by the thiazolidinediones-induced upregulation of circulating adiponectin which is PPARγ-dependent. Consistently, elevated serum adiponectin levels in PPARγ-agonist treated mice appear to increase recovery of injured podocytes ( Rutkowski et al . 2013 ).

Fenofibrate treatment decreases UAE, but the exact underlying mechanism remains unknown ( Keech et al . 2005 ). Moreover, fenofibrate has been reported to increase adiponectin expression in adipose tissue and serum adiponectin levels through PPARα activation and HDL elevation ( Christou Kiortsis 2013 ). Thus, the fenofibrate-induced elevation of serum adiponectin levels may contribute to the concomitant decrease in UAE, because of the renoprotective effects of adiponectin. Consistently, unpublished data from a previous trial performed by our study group showed that the percentage change in circulating HMW adiponectin over 3 months of fenofibrate treatment was negatively correlated with the percentage change in urinary albumin to creatinine ratio (ACR) ( r =−0.648, P =0.043) ( Esprit Chrissy LaceUp Wedge Sandals Womens Shoes hZzFkdqhWW
).

Weight loss can induce a decrease in UAE in overweight or obese subjects ( Kiortsis Christou 2012 ). Long-term diets have been shown to increase serum adiponectin levels ( Christou Kiortsis 2013 ), indicating a possible role of adiponectin on mediating, at least in part, the weight loss-induced changes of UAE. There is a study mentioning that the change in serum adiponectin levels over 1 year of diet was not significantly correlated with the change in ACR ( Nakatsuji et al . 2010 ). Unpublished data from a previous trial performed by our study group showed that circulating HMW adiponectin at baseline was negatively correlated with the percentage change of logACR over 3 months of diet ( r =−0.769, P =0.003) ( Christou et al . 2012 ). Thus, high baseline serum adiponectin levels may predict a more favourable response of UAE during diet, possibly reflecting a higher grade of nephroprotection. Further studies are needed to elucidate the possible role of adiponectin in the weight-loss-induced decrease in UAE.

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Adiponectin is an adipokine that appears to have renoprotective effects through AMPK-activated pathways, resulting in the prevention of albuminuria. The relationship between circulating adiponectin and albuminuria has been reported to show a biphasic pattern. A negative relationship exists in the case of normoalbuminuria, possibly reflecting the increased renal clearance of adiponectin together with the renoprotective effects of adiponectin, and a positive association in more advanced albuminuria, indicating the counteracting upregulation of serum adiponectin levels to mitigate renal injury. Taking into account the fact that the currently believed route of renal biodegradation/excretion of adiponectin is not based on firm evidence, the confirmation of this route and the exploration of the exact related pathways are prerequisites for understanding the role of adiponectin with regard to renal physiology. In addition, the accepted renoprotective role of adiponectin has been based almost exclusively on data from nonhuman experiments, necessitating the performance of studies investigating the relevant issues in human experimental settings. Further clinical studies are needed to translate convincing experimental evidence for the nephroprotective role of adiponectin into clinical practice that could create new therapies for albuminuria, targeting specific pathways of adiponectin action.

Identifying the journeys that matter most can be beneficial even when companies don’t have a nagging customer service problem—the effort can help them find a competitive differentiator. One car rental agency wanted to improve its already good service and distinguish itself from its competitors in light of the increasingly commoditized nature of the industry. Its investigation into what mattered to customers highlighted the airport pickup, a journey that might take less than an hour but that crossed a half-dozen or more touchpoints. The most important aspect was the end-to-end speed of service, from bus to rental counter to car to exit gate—but no one person owned that issue.

By focusing cross-functionally on delivering speed at the airport pickup, the company was able to innovate in ways that helped set it apart: It introduced more flexibility in car selection, developed technology to help customers manage their reservations from mobile devices, and installed virtual customer service kiosks at high-volume locations to give people the option of skipping the line but still working with a live agent. It also pushed hard to shift the emphasis from “cars available” to “the right car for the right customer at the right time.” These efforts provided a real opportunity to differentiate not just the service experience but the brand itself.

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A version of this article appeared in the September 2013 issue of .

Alex Rawson and Ewan Duncan are partners in McKinsey’s Seattle office, and Conor Jones is a partner in its Dublin office.

Alex Rawson and Ewan Duncan are partners in McKinsey’s Seattle office, and Conor Jones is a partner in its Dublin office.

Conor Jones is a partner in its Dublin office.

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