Journal of the American Society of Nephrology : JASN
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An abrupt change in serum creatinine, the most common indicator of acute kidney injury (AKI), is strongly linked to poor outcomes across multiple clinical settings. Despite endless attempts to distill the magnitude and timing of a changing serum creatinine into a standardized metric, singular focus on this traditional functional marker obligates the characterization of AKI to remain, at best, retrospective and causally noninformative. ⋯ Efforts to validate these markers for use in clinical studies now show early promise but face important obstacles including interpretive difficulties inherent in using serum creatinine as a sole comparator for diagnostic performance, a need to better evaluate the incremental performance of new markers above established clinical and biochemical predictors, a relative lack of power to sufficiently examine hard clinical end points, and a potential over-reliance on use alone of receiver operating curves for assessing biomarker utility. Here, we discuss efforts to address these barriers and further ascertain the clinical value of new markers.
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J. Am. Soc. Nephrol. · Apr 2011
Randomized Controlled TrialAddition of atrasentan to renin-angiotensin system blockade reduces albuminuria in diabetic nephropathy.
Although endothelin-receptor antagonists reduce albuminuria in diabetic nephropathy, fluid retention limits their use. Here, we examined the effect of atrasentan, a selective endothelin A receptor (ET(A)R) antagonist, on albuminuria in a randomized, double-blind, placebo-controlled trial of subjects with diabetic nephropathy already receiving stable doses of renin-angiotensin system (RAS) inhibitors. We randomly assigned 89 subjects with eGFR >20 ml/min per 1.73 m(2) and a urinary albumin-to-creatinine ratio (UACR) of 100 to 3000 mg/g to placebo or atrasentan (0.25, 0.75, or 1.75 mg daily) for 8 weeks. ⋯ In the placebo group, 17% of subjects achieved ≥40% reduction in UACR from baseline compared with 30, 50, and 38% in the 0.25-, 0.75-, and 1.75-mg atrasentan groups, respectively (P=0.029 for 0.75 mg versus placebo). Peripheral edema occurred in 9% of subjects receiving placebo and in 14, 18, and 46% of those receiving 0.25, 0.5, and 1.75 mg atrasentan, respectively (P=0.007 for 1.75 mg versus placebo). In summary, atrasentan, at the doses tested, is generally safe and effective in reducing residual albuminuria and may ultimately improve renal outcomes in patients with type 2 diabetic nephropathy.
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J. Am. Soc. Nephrol. · Apr 2011
ReviewRenal dysfunction associated with intra-abdominal hypertension and the abdominal compartment syndrome.
Once considered mostly a postsurgical condition, intra-abdominal hypertension (IAH) and the abdominal compartment syndrome (ACS) are now thought to increase morbidity and mortality in many patients receiving medical or surgical intensive care. Animal data and human observational studies indicate that oliguria and acute kidney injury are early and frequent consequences of IAH/ACS and can be present at relatively low levels of intra-abdominal pressure (IAP). Among medical patients at particular risk are those with septic shock and severe acute pancreatitis, but the adverse effects of IAH may also be seen in cardiorenal and hepatorenal syndromes. ⋯ Transduction of bladder pressure is the gold standard for measuring intra-abdominal pressure, and several nonsurgical methods can help reduce IAP. The role of renal replacement therapy for volume management is not well defined but may be beneficial in some cases. IAH/ACS is an important possible cause of acute renal failure in critically ill patients and screening may benefit those at increased risk.
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Circadian variations in renal function were first described in the 19th century, and GFR, renal blood flow, urine production, and electrolyte excretion exhibit daily oscillations. These clinical observations are well established, but the underlying mechanisms that govern circadian fluctuations in kidney are not fully understood. ⋯ Such studies support a developing model of clock controlled sodium and water transport in renal epithelial cells. Recent advances in identifying novel clock-controlled genes using rodent and cellular models also shed light on the molecular mechanisms by which the circadian clock controls renal function; however, the field is new and much more work remains.