Urinary Biomarkers at the Time of AKI Diagnosis as Predictors of Progression of AKI among Patients with Acute Cardiorenal Syndrome

Abstract

Background and objectives A major challenge in early treatment of acute cardiorenal syndrome (CRS) is the lack of predictors for progression of AKI. We aim to investigate the utility of urinary angiotensinogen and other renal injury biomarkers in predicting AKI progression in CRS.Design, settings, participants, & measurements In this prospective, multicenter study, we screened 732 adults who admitted for acute decompensated heart failure from September 2011 to December 2014, and evaluated whether renal injury biomarkers measured at time of AKI diagnosis can predict worsening of AKI. In 213 patients who developed Kidney Disease Improving Global Outcomes stage 1 or 2 AKI, six renal injury biomarkers, including urinary angiotensinogen (uAGT), urinary neutrophil gelatinase-associated lipocalin (uNGAL), plasma neutrophil gelatinase-associated lipocalin, urinary IL-18 (uIL-18), urinary kidney injury molecule-1, and urinary albumin-to-creatinine ratio, were measured at time of AKI diagnosis. The primary outcome was AKI progression defined by worsening of AKI stage (50 patients). The secondary outcome was AKI progression with subsequent death (18 patients).Results After multivariable adjustment, the highest tertile of three urinary biomarkers remained associated with AKI progression compared with the lowest tertile: uAGT (odds ratio [OR], 10.8; 95% confidence interval [95% CI], 3.4 to 34.7), uNGAL (OR, 4.7; 95% CI, 1.7 to 13.4), and uIL-18 (OR, 3.6; 95% CI, 1.4 to 9.5). uAGT was the best predictor for both primary and secondary outcomes with area under the receiver operating curve of 0.78 and 0.85. These three biomarkers improved risk reclassification compared with the clinical model alone, with uAGT performing the best (category-free net reclassification improvement for primary and secondary outcomes of 0.76 [95% CI, 0.46 to 1.06] and 0.93 [95% CI, 0.50 to 1.36]; P,0.001). Excellent performance of uAGT was further confirmed with bootstrap internal validation.Conclusions uAGT, uNGAL, and uIL-18 measured at time of AKI diagnosis improved risk stratification and identified CRS patients at highest risk of adverse outcomes.

Biomarkers of acute kidney injury: the pathway from discovery to clinical adoption

“…AGT is a 453-amino-acid-long protein with 10 N-terminal amino acids that are cleavable by renin, leading to the formation of angiotensin I [55,149]. Angiotensin I is further converted to angiotensin II by angiotensin-converting enzyme and exerts its robust biologic effects [55,149].…”

“…Angiotensin I is further converted to angiotensin II by angiotensin-converting enzyme and exerts its robust biologic effects [55,149].…”

“…An increase in urine AGT is now considered as one of the most promising biomarkers of AKI progression in patients with acute decompensated heart failure [46,55,154,155].…”

“…Within the past 2 decades, a few novel potential biomarkers ( Table 1) that are measurable in urine or plasma of patients with AKI have been identified [49], including neutrophil gelatinase-associated lipocalin (NGAL) [17,50,51], kidney injury molecule 1 (KIM-1) [27,52], interleukin 18 (lL-18) [53], liver-type fatty acid-binding protein (L-FABP) [54], tissue inhibitor of metalloproteinase 2 (TlMP-2), insulin-like growth factorbinding protein 7 (IGFBP7) [33], calprotectin [42], urine angiotensinogen (AGT) [55], and urine microRNAs [47,56].…”

Clinical diagnostic algorithms of opioid dependence

“…В связи с тем, что биомаркеры отражают повреж-дение различных локусов нефрона, диагностика ОПП, когда его этиология по клинико-лаборатор-ным данным не совсем ясна, предопределила появ-ление исследований, оценивающих значение сразу нескольких биомаркеров [5,16,18,25,26,27,33,35,41]. В проспективном исследовании больных после кардиохирургческих вмешательств было показано, что наибольшей чувствительностью обладает ме-тод, который основывается на одновременном из-мерении концентрации NGAL, NAG и KIM-1 [11].…”