Urinary Calprotectin and the Distinction between Prerenal and Intrinsic Acute Kidney Injury

Abstract

SummaryBackground and objectives To date there is no reliable marker for the differentiation of prerenal and intrinsic acute kidney injury (AKI). We investigated whether urinary calprotectin, a mediator protein of the innate immune system, may serve as a diagnostic marker in AKI.Design, setting, participants, & measurements This was a cross-sectional study with 101 subjects including 86 patients with AKI (34 prerenal, 52 intrinsic including 23 patients with urinary tract infection) and 15 healthy controls. Assessment of urinary calprotectin concentration was by ELISA and immunohistochemistry of kidney biopsy specimens using a calprotectin antibody. Inclusion criteria were: admission to hospital for AKI stage 1 to 3 (Acute Kidney Injury Network); exclusion criteria were: prior renal transplantation and obstructive uropathy.Results Median urinary calprotectin was 60.7 times higher in intrinsic AKI (1692 ng/ml) than in prerenal AKI (28 ng/ml, p Ͻ0.01). Urinary calprotectin in prerenal disease was not significantly different from healthy controls (45 ng/ml, p ϭ 0.25). Receiver operating curve curve analysis revealed a high accuracy of calprotectin (area under the curve, 0.97) in predicting intrinsic AKI. A cutoff level of 300 ng/ml provided a sensitivity of 92.3% and a specificity of 97.1%. Calculating urinary calprotectin/creatinine ratios did not lead to a further increase of accuracy. Immunostainings of kidney biopsies were positive for calprotectin in intrinsic AKI and negative in prerenal AKI.Conclusions Accuracy of urinary calprotectin in the differential diagnosis of AKI is high. Whereas calprotectin levels in prerenal disease are comparable with healthy controls, intrinsic AKI leads to highly increased calprotectin concentrations.

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

“…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].…”

“…Studies investigating the diagnostic accuracy of calprotectin in differentiating prerenal from intrinsic AKI have shown particularly high precision, with an AUC ranging from 0.92 to 0.97 [42,44,45]. A recent multicenter study was conducted to examine the diagnostic accuracy of calprotectin in the differentiation of prerenal and intrinsic acute allograft kidney injury.…”

“…ICU [32] [ ICU [33] May be elevated in the setting of diabetes [34] 0.82 ICU [35] 0.79 ICU [36] 0.84 Cardiac surgery [37] 0.82 Coronary artery bypass surgery [38] 0.71 Coronary artery bypass surgery [39] 0.84 High-risk surgical patients [40] 0.85 Major surgery [41] Calprotectin A 24-kDa heterodimer composed of the 2 monomers S100A8 (10,835 Da) and S100A9 (13,242 Da); promotion of repair after AKI 0.97 Hospitalized patients [42] Hospitalized patients [44] Coronary care units [45] May be elevated in the settings of urinary tract infection, rheumatoid arthritis, inflammatory bowel disease, myocardial infarction, and urothelial cancer [10,42,43] 0.99…”

Acute kidney injury: modern view of problem.

“…Также не существует надежного маркера для диф-ференцировки преренальной и ренальной ОПП. В то же время в исследовании [12] было установле-но, что среднее содержание кальпротектина в моче в 60,7 раз выше при ренальной ОПП (16,92 нг/мл), чем при преренальной ОПП (28 нг/мл), (р<0,01). Уровень кальпротектина мочи 300 нг/мл продемонстрировал чувствительность 92,3% и специфичность 97,1%.…”

Urinary Calprotectin as a Marker to Distinguish Functional and Structural Acute Kidney Injury in Pediatric Population

“…There are few studies conducted in cisplatin induced ischemic kidney in rat and adult that show calprotectin could differentiate between pre-renal and ischemic acute kidney injury (20)(21)(22)(23)(24).…”