Contributions to nephrology
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Pathophysiological mechanisms of cardiorenal syndromes (CRS) types 1-5 are still sparsely characterized. In an attempt to address this issue, a consensus conference on CRS was held in Venice, Italy, in November 2012 under the auspices of the Acute Dialysis Quality Initiative (ADQI). ⋯ Pre-conference we performed a systematic search and review of the available literature using a modified Delphi analysis. Hereby identified and in this review discussed questions were: (i) What are the predominant pathophysiologic mechanisms of CRS type 1 in acute decompensated heart failure? (ii) Could biomarker profiling identify pathomechanisms or hemodynamic phenotype of patients with CRS type 1? Could predictive biomarkers improve renal safety of therapy in CRS type 1? (iii) How do the timing, severity and duration relate to the mechanisms and outcomes of CRS type 1? In summary, after discussion and appraisal of the best available evidence, working group 1 makes consensus recommendations for future research on pathologic mechanisms of CRS type 1 and recommendations for clinical practice where treatment is in either proof or disproof of a mechanism.
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Acute kidney injury (AKI) commonly occurs in hospitalized patients and is independently and strongly associates with morbidity and mortality. The clinical benefits of a timely and definitive diagnosis of AKI have not been fully realized due to limitations imposed by the use of serum creatinine and urine output to fulfill diagnostic criteria. These restrictions often lead to diagnostic delays, potential misclassification of actual injury status, and provide little information regarding underlying cause. ⋯ Promising diagnostic injury markers include neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), interleukin 18 (IL-18) and liver-type fatty acid binding protein (L-FABP). However, there are currently insufficient data on damage biomarkers to support their use for AKI staging. Rigorous validation studies measuring the association between the novel damage biomarker(s) and clinically relevant outcomes are needed.
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Sepsis is the most common cause of acute kidney injury (AKI). There has been a growing body of evidence demonstrating the association between worsening of kidney function during sepsis and the risk of short- and long-term mortality. AKI in sepsis is associated with poor outcome and independently predicts increased mortality. ⋯ The expanding population of patients with sepsis and AKI, and the associated excess mortality provide a strong basis for further research aimed at addressing more rigorously all potentially modifiable factors to reduce this burden to patients and health care systems. Better insights into bidirectional and synergistic pathways linking sepsis and AKI might open the window for new therapeutic approaches that interrupt this vicious circle. Here, we discuss the rationale for and the current understanding of the bidirectional relationship between AKI and sepsis.
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Acute kidney injury (AKI) is associated with a heavy burden of morbidity and mortality, despite advances in intensive care and the management of high-risk patients. Numerous clinical trials have failed to ameliorate the outcomes of AKI. ⋯ Similarly, a multidisciplinary dialogue is making progress towards standardization of the clinical trial endpoints to prove efficacy and effectiveness in AKI research. Taken together with the increasing availability of timely, sensitive, and specific novel biomarkers of kidney damage, we are poised to use these tools to conduct successful clinical trials of agents for the prevention and treatment of this devastating clinical syndrome.
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Endothelial cells play a key role in initiating and propagating the inflammatory response seen in ischemia, infections and sepsis. Situated in a key position between the epithelial cells and white blood cells (WBC), they interact and respond to signals from both cell types. ⋯ This last event is in large part responsible for a chronic reduction in regional perfusion, subsequent increased vulnerability to recurrent acute kidney injury, and acceleration of chronic kidney disease progression to end-stage renal disease. Glomerular endothelial dysfunction may lead to preglomerular shunting of blood flow allowing kidney blood flow to remain close to normal while resulting in a reduction in glomerular filtration rate.