Admission hyperphosphatemia increases the risk of acute kidney injury in hospitalized patients

Acute kidney injury (AKI) is a global public health concern associated with high morbidity, mortality, and healthcare costs. Other than dialysis, no therapeutic interventions reliably improve survival, limit injury, or speed recovery. Despite recognized shortcomings of in vivo animal models, the underlying pathophysiology of AKI and its consequence, chronic kidney disease (CKD), is rich with biological targets. We review recent findings relating to the renal vasculature and cellular stress responses, primarily the intersection of the unfolded protein response, mitochondrial dysfunction, autophagy, and the innate immune response. Maladaptive repair mechanisms that persist following the acute phase promote inflammation and fibrosis in the chronic phase. Here macrophages, growth-arrested tubular epithelial cells, the endothelium, and surrounding pericytes are key players in the progression to chronic disease. Better understanding of these complex interacting pathophysiological mechanisms, their relative importance in humans, and the utility of biomarkers will lead to therapeutic strategies to prevent and treat AKI or impede progression to CKD or end-stage renal disease (ESRD).

Acute kidney injury (AKI) is a common complication of critical illnesses and has a significant impact on outcomes, including mortality and morbidities. Unfortunately, apart from prophylactic measures, no effective treatment for this syndrome is known. Therefore, early recognition of AKI not only can provide better opportunities for preventive interventions, but also opens many gates for research and development of effective therapeutic options. Over the last few years, several new AKI biomarkers have been discovered and validated to improve early detection, differential diagnosis, and differentiation of patients into risk groups for progressive renal failure, need for renal replacement therapy (RRT), or death. These novel AKI biomarkers complement serum creatinine (SCr) and urine output, which are the standard diagnostic tools for AKI detection. In this article, we review the available literature on characteristics of promising AKI biomarkers that are currently the focus of preclinical and clinical investigations. These biomarkers include neutrophil gelatinase-associated lipocalin (NGAL), kidney injury molecule 1 (KIM-1), liver-type fatty acid-binding protein, interleukin 18 (lL-18), insulin-like growth factor-binding protein 7, tissue inhibitor of metalloproteinase 2 (TIMP-2), calprotectin, urine angiotensinogen (AGT), and urine microRNA. We then describe the clinical performance of these biomarkers for diagnosis and prognostication. We also appraise each AKI biomarker's advantages and limitations as a tool for early AKI recognition and prediction of clinical outcomes after AKI. Finally, we review the current and future states of implementation of biomarkers in the clinical practice.

A pre-morbid 'baseline' creatinine is required in order to diagnose and stage acute kidney injury (AKI) using the RIFLE classification. Estimation of baseline creatinine by solving the Modification of Diet in Renal Disease (MDRD) equation assuming a glomerular filtration rate of 75 ml/min/1.73 m(2) has been widely used but never validated. We analysed four cohorts of intensive care unit (ICU) patients from three centres (two from Pittsburgh and one from Mayo and Austin). Three cohorts consisted of preselected patients without AKI (Pittsburgh 1 n = 1048, Mayo n = 737, Austin n = 333), and measured creatinine values in these cohorts were taken to represent baseline creatinine values. The last cohort (Pittsburgh 2 n = 468) consisted of unselected ICU patients with baseline creatinine values recorded within 1 year before ICU admission. Using the Pittsburgh 1 cohort, we derived an equation using the same anthropometric variables as the MDRD equation: baseline creatinine = 0.74 - 0.2 (if female) + 0.08 (if black) + 0.003 × age (in years). We then compared measured creatinine in the Mayo and Austin cohorts and recorded creatinine in the Pittsburgh 2 cohort to the estimated creatinine from: (i) the MDRD equation; (ii) our new equation; (iii) a gender-fixed creatinine of 0.8 mg/dl for females and 1.0 mg/dl for males. Using any of the three methods, the median absolute error of the estimates was of the order of 0.1-0.2 mg/dl, and overall accuracy was similar. When the definition of AKI was limited to the severity grades of Injury and Failure, all three methods were able to generate 78-90% reliable results for preselected normal range cohorts, and 63-70% for the unselected cohort of ICU patients. Estimates of incidence of AKI in the critically ill using RIFLE classification can be affected by the bias and limited accuracy of methods to estimate baseline creatinine. Whenever possible, recorded creatinine values should be used as a reference of baseline. The use of the MDRD equation to estimate baseline creatinine when it is unknown may over- or underestimate some mild (Risk) AKI cases but is unlikely to misclassify patients in Injury and Failure.